EP1409681A2 - Proteines et acides nucleiques codant ces proteines - Google Patents

Proteines et acides nucleiques codant ces proteines

Info

Publication number
EP1409681A2
EP1409681A2 EP02784815A EP02784815A EP1409681A2 EP 1409681 A2 EP1409681 A2 EP 1409681A2 EP 02784815 A EP02784815 A EP 02784815A EP 02784815 A EP02784815 A EP 02784815A EP 1409681 A2 EP1409681 A2 EP 1409681A2
Authority
EP
European Patent Office
Prior art keywords
amino acid
nucleic acid
polypeptide
protein
seq
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Withdrawn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
EP02784815A
Other languages
German (de)
English (en)
Inventor
Velizar T. Tchernev
Kimberly A. Spytek
Bryan D. Zerhusen
Meera Patturajan
Richard A. Shimkets
Li Li
Esha A. Gangolli
Muralidhara Padigaru
David W. Anderson
Luca Rastelli
Charles E. Miller
Valerie L. Gerlach
Raymond J. Taupier, Jr.
Vladimir Y. Gusev
Steven D. Colman
Adam R. c/o CuraGen Corporation WOLENC
Carol E. A. c/o CuraGen Corporation PENA
Katarzyna Furtak
William M. Grosse
John P. Ii Alsobrook
Denise M. Lepley
Daniel K. Rieger
Catherine E. Burgess
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.)
CuraGen Corp
Original Assignee
CuraGen Corp
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 CuraGen Corp filed Critical CuraGen Corp
Priority claimed from PCT/US2002/002785 external-priority patent/WO2002068649A2/fr
Publication of EP1409681A2 publication Critical patent/EP1409681A2/fr
Withdrawn legal-status Critical Current

Links

Definitions

  • the invention generally relates to nucleic acids and polypeptides encoded thereby.
  • the invention generally relates to nucleic acids and polypeptides encoded therefrom. More specifically, the invention relates to nucleic acids encoding cytoplasmic, nuclear, membrane bound, and secreted polypeptides, as well as vectors, host cells, antibodies, and recombinant methods for producing these nucleic acids and polypeptides.
  • the invention is based in part upon the discovery of nucleic acid sequences encoding novel polypeptides.
  • novel nucleic acids and polypeptides are referred to herein as NONX, or ⁇ ON1-99 nucleic acids and polypeptides.
  • ⁇ ONX nucleic acid or polypeptide sequences.
  • the invention provides an isolated ⁇ OVX nucleic acid molecule encoding a ⁇ ONX polypeptide that includes a nucleic acid sequence that has identity to the nucleic acids disclosed in SEQ ID ⁇ OS:2n-l, wherein n is an integer between 1 and 162, .
  • the NONX nucleic acid molecule will hybridize under stringent conditions to a nucleic acid sequence complementary to a nucleic acid molecule that includes a protein-coding sequence of a ⁇ ONX nucleic acid sequence.
  • the invention also includes an isolated nucleic acid that encodes a ⁇ ONX polypeptide, or a fragment, homolog, analog or derivative thereof.
  • the nucleic acid can encode a polypeptide at least 80% identical to a polypeptide comprising the amino acid sequences of SEQ ID ⁇ OS:2n, wherein n is an integer between 1 and 162.
  • the nucleic acid can be, for example, a genomic DNA fragment or a cDNA molecule that includes the nucleic acid sequence of any of SEQ ID NOS:2n-l, wherein n is an integer between 1 and 162.
  • an oligonucleotide e.g., an oligonucleotide which includes at least 6 contiguous nucleotides of a NONX nucleic acid (e.g., SEQ ID ⁇ OS:2n-l, wherein n is an integer between 1 and 162) or a complement of said oligonucleotide.
  • substantially purified NOVX polypeptides SEQ ID NOS:2n, wherein n is an integer between 1 and 162).
  • the NOVX polypeptides include an amino acid sequence that is substantially identical to the amino acid sequence of a human NOVX polypeptide.
  • the invention also features antibodies that immunoselectively bind to NOVX polypeptides, or fragments, homologs, analogs or derivatives thereof.
  • the invention includes pharmaceutical compositions that include therapeutically- or prophylactically-effective amounts of a therapeutic and a pharmaceutically- acceptable carrier.
  • the therapeutic can be, e.g., a NOVX nucleic acid, a NOVX polypeptide, or an antibody specific for a NOVX polypeptide.
  • the invention includes, in one or more containers, a therapeutically- or prophylactically-effective amount of this pharmaceutical composition.
  • the invention includes a method of producing a polypeptide by culturing a cell that includes a NOVX nucleic acid, under conditions allowing for expression of the NOVX polypeptide encoded by the DNA. If desired, the NOVX polypeptide can then be recovered.
  • the invention includes a method of detecting the presence of a NOVX polypeptide in a sample.
  • a sample is contacted with a compound that selectively binds to the polypeptide under conditions allowing for formation of a complex between the polypeptide and the compound.
  • the complex is detected, if present, thereby identifying the NOVX polypeptide within the sample.
  • the invention also includes methods to identify specific cell or tissue types based on their expression of a NOVX.
  • Also included in the invention is a method of detecting the presence of a NOVX nucleic acid molecule in a sample by contacting the sample with a NOVX nucleic acid probe or primer, and detecting whether the nucleic acid probe or primer bound to a NOVX nucleic acid molecule in the sample.
  • the invention provides a method for modulating the activity of a NOVX polypeptide by contacting a cell sample that includes the NOVX polypeptide with a compound that binds to the NOVX polypeptide in an amount sufficient to modulate the activity of said polypeptide.
  • the compound can be, e.g., a small molecule, such as a nucleic acid, peptide, polypeptide, peptidomimetic, carbohydrate, lipid or other organic (carbon containing) or inorganic molecule, as further described herein.
  • a therapeutic in the manufacture of a medicament for treating or preventing various disorders or syndromes described below.
  • the therapeutic can be, e.g., a NOVX nucleic acid, a NOVX polypeptide, or a NOVX- specific antibody, or biologically-active derivatives or fragments thereof.
  • the compositions of the present invention will have efficacy for treatment of patients suffering from the diseases and disorders disclosed above and/or other pathologies and disorders of the like.
  • the polypeptides can be used as immunogens to produce antibodies specific for the invention, and as vaccines. They can also be used to screen for potential agonist and antagonist compounds.
  • a cDNA encoding NOVX may be useful in gene therapy, and NOVX may be useful when administered to a subject in need thereof.
  • the compositions of the present invention will have efficacy for treatment of patients suffering from the diseases and disorders disclosed above and/or other pathologies and disorders of the like.
  • the invention further includes a method for screening for a modulator of disorders or syndromes including, e.g., the diseases and disorders disclosed above and/or other pathologies and disorders of the like.
  • the method includes contacting a test compound with a NOVX polypeptide and determining if the test compound binds to said NOVX polypeptide. Binding of the test compound to the NOVX polypeptide indicates the test compound is a modulator of activity, or of latency or predisposition to the aforementioned disorders or syndromes.
  • Also within the scope of the invention is a method for screening for a modulator of activity, or of latency or predisposition to disorders or syndromes including, e.g., the diseases and disorders disclosed above and/or other pathologies and disorders of the like by administering a test compound to a test animal at increased risk for the aforementioned disorders or syndromes.
  • the test animal expresses a recombinant polypeptide encoded by a NOVX nucleic acid.
  • Expression or activity of NOVX polypeptide is then measured in the test animal, as is expression or activity of the protein in a control animal which recombinantly- expresses NOVX polypeptide and is not at increased risk for the disorder or syndrome.
  • the expression of NOVX polypeptide in both the test animal and the control animal is compared. A change in the activity of NOVX polypeptide in the test animal relative to the control animal indicates the test compound is a modulator of latency of the disorder or syndrome.
  • the invention includes a method for determining the presence of or predisposition to a disease associated with altered levels of a NOVX polypeptide, a NOVX nucleic acid, or both, in a subject (e.g., a human subject).
  • the method includes measuring the amount of the NOVX polypeptide in a test sample from the subject and comparing the amount of the polypeptide in the test sample to the amount of the NOVX polypeptide present in a control sample.
  • An alteration in the level of the NOVX polypeptide in the test sample as compared to the control sample indicates the presence of or predisposition to a disease in the subject.
  • the predisposition includes, e.g., the diseases and disorders disclosed above and/or other pathologies and disorders of the like.
  • the expression levels of the new polypeptides of the invention can be used in a method to screen for various cancers as well as to determine the stage of cancers.
  • the invention includes a method of treating or preventing a pathological condition associated with a disorder in a mammal by administering to the subject a NOVX polypeptide, a NOVX nucleic acid, or a NOVX-specific antibody to a subject (e.g., a human subject), in an amount sufficient to alleviate or prevent the pathological condition.
  • the disorder includes, e.g., the diseases and disorders disclosed above and/or other pathologies and disorders of the like.
  • the invention can be used in a method to identity the cellular receptors and downstream effectors of the invention by any one of a number of techniques commonly employed in the art.
  • the present invention provides novel nucleotides and polypeptides encoded thereby. Included in the invention are the novel nucleic acid sequences and their encoded polypeptides. The sequences are collectively referred to herein as “NOVX nucleic acids” or “NOVX polynucleotides” and the corresponding encoded polypeptides are referred to as “NOVX polypeptides” or “NOVX proteins.” Unless indicated otherwise, “NOVX” is meant to refer to any of the novel sequences disclosed herein. Table A provides a summary of the NOVX nucleic acids and their encoded polypeptides.
  • NOVX nucleic acids and their encoded polypeptides are useful in a variety of applications and contexts.
  • the various NOVX nucleic acids and polypeptides according to the invention are useful as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins. Additionally, NOVX nucleic acids and polypeptides can also be used to identify proteins that are members of the family to which the NOVX polypeptides belong.
  • NOV1, NOV3, and NOV4 are homologous to a Claudin-like family of proteins.
  • the NOV1, NOV3, and NOV4 nucleic acids, polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions.
  • NOV2 is homologous to the Protein Serine Kinase-like family of proteins.
  • NOV2 nucleic acids, polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions.
  • NOV5 is homologous to a family of Monocarboxylate transporter-like proteins.
  • NOV5 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV6 is homologous to the nitrilase-1-like family of proteins.
  • NOV6 nucleic acids, polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions.
  • NOV7 is homologous to the Cleavage Signal-l -like family of proteins.
  • NOV7 nucleic acids, polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions.
  • NOV8 is homologous to the Matripase-like family of proteins.
  • NOV8 nucleic acids, polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in, various pathologies or conditions.
  • NOV9 is homologous to members of the Neuropeptide Y/Peptide YY receptor-like family of proteins.
  • NOV9 nucleic acids, polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions.
  • NOVsl 0 through 20, , NOV43, NOV44, and NOV83 are homologous to the G-Protein
  • Coupled Receptor-like family of proteins Coupled Receptor-like family of proteins.
  • these nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions.
  • NOV21 and NOV22 are homologous to the Adrenal; secretory serine protease like growth factor binding protein-like family of proteins.
  • NOV21 and NOV22 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions.
  • NOV23 is homologous to the Serine Protease DESC-1-like family of proteins.
  • NOV23 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in various pathologies or conditions.
  • NOV24 is homologous to the Pa chorin-like family of proteins.
  • NOV24 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or disorders.
  • NOV25 is homologous to theProtein Phosphatase-like family of proteins.
  • NOV25 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions.
  • NOV26 is homologous to the GAGE7-like family of proteins.
  • NOV26 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies/disorders.
  • NOV27 is homologous to the Sodium-Glucose Cotransporter-like family of proteins.
  • NOV27 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV28 is homologous to the MYD-1-like family of proteins.
  • NOV28 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV29 is homologous to the CRAL-TRIO-like family of proteins.
  • NOV27 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV30 is homologous to the Ryudocan-like family of proteins.
  • NOV30 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV31 is homologous to the Sulfur-rich Keratin-like family of proteins.
  • NOV31 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV32 is homologous to the DMNT1 associated protein-like family of proteins.
  • NOV32 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV33 is homologous to the Notch 1 -like family of proteins.
  • nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV34, NOV35, NOV51, NOV66, and NOV67 are homologous to the Olfactory Receptor-like family of proteins.
  • NOV34, NOV35, NOV51, NOV66, and NOV67 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV36 is homologous to the Cadherin 11 -like family of proteins.
  • NOV36 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV37 is homologous to the Ten-M2-like family of proteins.
  • NOV33 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV38 and NOV39 are homologous to the Activin/Inhibin-like family of proteins.
  • NOV38 and NOV39 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions NOV40 is homologous to the UDP Glycosyltransferase-like family of proteins.
  • NOV40 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV41 is homologous to the Sodium/Hydrogen Exchanger 4-like family of proteins.
  • NOV41 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV42 is homologous to the Kupffer Cell Receptor-like family of proteins.
  • NOV42 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV45 and NOV46 is homologous to the Mas Proto-Oncogene-like family of proteins.
  • NOV45 and NOV46 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV47 is homologous to the Peptidyl-Prolyl Cis-Trans Isomerase-like family of proteins.
  • NOV47 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV48 is homologous to the Phospholipase C Delta-4-like family of proteins.
  • NOV48 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV49 is homologous to the Leukotriene-B4 Omega Hydroxylase-like family of proteins.
  • NOV49 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV50 is homologous to the Protein Arginine N-Methyltransferase 2-like family of proteins.
  • NOV50 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV52 is homologous to the H326-like family of proteins.
  • NOV52 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV53 is homologous to the Uracil Phosphoribosyltransferase-like family of proteins.
  • NOV53 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV54 is homologous to the Protein Phosphatase 2C-like family of proteins.
  • NOV54 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV55 is homologous to the Heparan Sulfate 6-Sulfotransferase 3-like family of proteins.
  • NOV55 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV56 is homologous to the N-Hydroxyarylamine Sulfotransferase 3-like family of proteins.
  • NOV52 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV57 is homologous to the Testis Specific Serine Kinase-3-like family of proteins.
  • NOV57 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV58 is homologous to the Gap Junction Beta-5-like family of proteins.
  • NOV58 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV59 is homologous to the Translation Initiation Factor 5-like family of proteins.
  • NOV59 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV60 is homologous to the Lynxl-like family of proteins.
  • NOV61 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV61 is homologous to the Adlican-like family of proteins.
  • NOV61 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV62 is homologous to the Neuropsin Precursor-like family of proteins.
  • NOV62 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV63 is homologous to the Wnt-14-like family of proteins.
  • NOV63 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV64 is homologous to the Dipeptidyl peptidase-like family of proteins.
  • NOV64 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV65 is homologous to the Protein phosphatase-like family of proteins.
  • NOV65 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV68 is homologous to the Endoglin (CD105 antigen)-like family of proteins.
  • NOV68 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV69 is homologous to the Interleukin 1 Epsilom-like family of proteins.
  • NOV69 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV70 is homologous to the OS-9-like family of proteins.
  • NOV70 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV71 is homologous to the Sodium/Hydrogen Exchanger 6-like family of proteins.
  • NOV71 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV72 is homologous to the Ubiquitin Specific Protease-like family of proteins.
  • NOV72 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV73 is homologous to the Sulfotransferase-like family of proteins.
  • NOV73 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV74, NOV75, NOV76, NOV77, NOV78, NOV79, and NOV80 are homologous to the Dual Specificity Phosphatase-like family of proteins.
  • NOV74, NOV75, NOV76, NOV77, NOV78, NOV79, and NOV80 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions NOV81 is homologous to the Beta-1, 3-Galactosyltransferase-like family of proteins.
  • NOV81 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV82 is homologous to the Peptide YY-like family of proteins.
  • NOV82 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV84 is homologous to the Phospholipase C delta 1-like family of proteins.
  • NOV84 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV85, NOIV86, and NOV87 are homologous to the GTPase-Activating Protein-like family of proteins.
  • NOV85, NOIV86, and NOV87 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV88 and NOV89 are homologous to the Glyceroil-3-Phosphate Dehydrogenase- like family of proteins.
  • NOV88 and NOV89 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV90 is homologous to the Serine/Threonine-Protein Kinase PAK 2-like family of proteins.
  • NOV90 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV91 is homologous to the D-Dopachrome Tautomerase family of proteins.
  • NOV92 is homologous to the Secreted leucine-rich repeat (LRR)-like family of proteins.
  • LRR Secreted leucine-rich repeat
  • NOV93 is homologous to the Inosine-5'-Monophosphate Dehydrogenase-like family of proteins.
  • NOV93 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV94 is homologous to the Male-Specific Lethal 3-like family of proteins.
  • NOV94 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV95 is homologous to the Cysteine Conjugate Beta Lyase-like family of proteins.
  • NOV95 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV96 is homologous to the Monocarboxylate transporter-like family of proteins.
  • NOV96 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV97 is homologous to the Carboxypeptidase Al-like family of proteins.
  • NOV98 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV98 is homologous to the Agrin-like family of proteins.
  • NOV98 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • NOV99 is homologous to the SNC73-like family of proteins.
  • NOV99 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in various pathologies or conditions
  • the NOVX nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance NOVX activity or function.
  • the nucleic acids and polypeptides according to the invention may be used as targets for the identification of small molecules that modulate or inhibit, e.g., neurogenesis, cell differentiation, cell proliferation, hematopoiesis, wound healing and angiogenesis.
  • NO VI includes three novel human 1 Claudin-like proteins disclosed below. The disclosed sequences have been named NOVla, NOVlb, NOVlc, NOVld, NOVle, NOVlf, andNOVlg.
  • NOVla nucleic acid of 687 nucleotides also referred to as CG56592-02 encoding a novel human Claudin 6-like protein is shown in Table 1 A
  • An open reading frame was identified beginning with an ATG initiation codon at nucleotides 6-8 and ending with a TAG termination codon at nucleotides 678-680.
  • the start and stop codons are in bold letters in Table 1 A, and the 5' and 3' untranslated regions are underlined.
  • Table 1A NOVla nucleotide sequence (SEQ ID NO:l).
  • the NOVla nucleic acid sequence, located on chromsome 12 has 337 of 534 bases (63%) identical to a gb:GENBANK- ID:HSA249735jacc:AJ249735.1 mRNA from Homo sapiens (CLDN6 gene for claudin-6).
  • the "E-value” or "Expect” value is a numeric indication of the probability that the aligned sequences could have achieved their similarity to the BLAST query sequence by chance alone, within the database that was searched.
  • the probability that the subject (“Sbjct”) retrieved from the NOVla BLAST analysis, e.g., Homo sapiens CLDN6 gene for claudin-6, matched the Query NOVla sequence purely by chance is 1.4e "15 .
  • the Expect value (E) is a parameter that describes the number of hits one can "expect” to see just by chance when searching a database of a particular size. It decreases exponentially with the Score (S) that is assigned to a match between two sequences. Essentially, the E value describes the random background noise that exists for matches between sequences.
  • the Expect value is used as a convenient way to create a significance threshold for reporting results. The default value used for blasting is typically set to 0.0001.
  • the Expect value is also used instead of the P value (probability) to report the significance of matches.
  • P value probability
  • an E value of one assigned to a hit can be interpreted as meaning that in a database of the current size one might expect to see one match with a similar score simply by chance.
  • An E value of zero means that one would not expect to see any matches with a similar score simply by chance. See, e.g., http://www.ncbi.nlm.nih.gov/Education/BLASTinfo/.
  • a string of X's or N's will result from a BLAST search. This is a result of automatic filtering of the query for low- complexity sequence that is performed to prevent artifactual hits.
  • the filter substitutes any low-complexity sequence that it finds with the letter "N" in nucleotide sequence (e.g.,
  • the disclosed NOVla polypeptide (SEQ ID NO:2) encoded by SEQ ID NO:l has 229 amino acid residues and is presented in Table IB using the one-letter amino acid code.
  • Signal P, Psort and/or Hydropathy results predict that NONl a has no signal peptide and is likely to be localized the plasma membrane with a certainty of 0.6400.
  • NONl a also may localize to the Golgi body with acertainty of 0.4600, the endoplasmic reticulum (membrane) with a certainty of 0.3700 or in the endoplasmic reticulum (lumen) with a certainty of 0.1000.
  • the most likely cleavage site for a ⁇ ON1 a peptide is between amino acids 24 and 25, at: NCS-CN.
  • Table IB Encoded ⁇ OVla protein sequence (SEQ ID ⁇ O:2).
  • NOVla is predicted to be expressed in Bone Marrow, Brain, Liver, Placenta, and Lung.
  • NOVlb nucleic acid of 687 nucleotides also referred to as CG56586-01 encoding a human Claudin-3-like protein is shown in Table IC.
  • An open reading frame was identified beginning with an ATG initiation codon at nucleotides 6-8 and ending with a TAG codon at nucleotides 678-680. Putative untranslated regions upstream from the initiation codon, and downstream from the termination codon, if any, are underlined in Table IC. The start and stop codons are in bold letters.
  • Table IC NOVlb nucleotide sequence (SEQ ID NO:3).
  • the NOVlb nucleic acid sequence, located on chromsome 11 is 338 of 534 bases (63%) identical to a gb:GENBANK- K>:HSA249735
  • acc:AJ249735.1 mRNA from Homo sapiens (CLDN6 gene for claudin-6) (E 2.8e- 16 ).
  • the disclosed NOVlb polypeptide (SEQ ID NO:4) encoded by SEQ ID NO:3 has 224 amino acid residues and is presented in Table ID using the one-letter amino acid code.
  • Signal P, Psort and/or Hydropathy results predict that NOVlb has a signal peptide and is likely to be localized in the plasma membrane with a certainty of 0.4600.
  • NOVlb may also localize to the microbody (peroxisome) with acertainty of 0.3200, the endoplasmic reticulum (membrane) with a certainty of 0.1000 or in the endoplasmic reticulum (lumen) with a certainty of 0.1000.
  • the most likely cleavage site for a NOVlb peptide is between amino acids 24 and 25, at: VCS-CV.
  • NOVlb is predicted to be expressed in Bone Marrow, Brain, Liver, Placenta, and
  • a disclosed NOVlc nucleic acid of 642 nucleotides (also referred to as CG56592-03) encoding a novel Claudin-6-like protein is shown in Table IE.
  • An open reading frame was identified beginning with a ATG initiation codon at nucleotides 6-8 and ending with a TAG codon at nucleotides 609-611.
  • the start and stop codons are in bold letters, and the 5' and 3' untranslated regions are underlined.
  • the disclosed NOVlc nucleic acid sequence maps to chromosome 12 and has 144 of
  • a disclosed NOVlc protein (SEQ ID NO:6) encoded by SEQ ID NO:5 has 201 amino acid residues, and is presented using the one-letter code in Table IF.
  • Signal P, Psort and/or Hydropathy results predict that NOVlc does have a signal peptide, and is likely to be localized to the plasma membrane with a certainty of 0.4600.
  • NOVlc is also likely to be localized to the microbody (peroxisome) with a certainty of 0.2651, to endoplasmic reticulum (membrane) with a certainty of 0.1000, or to the endoplasmic reticulum (lumen) with a certainty of 0.1000.
  • the most likely cleavage site for NOVlc is between positions 24 and 25, (VCS-CV).
  • NOVlc is predicted to be expressed in Bone Marrow, Brain, Liver, Placenta, and Lung.
  • NOVld A disclosed NOVld nucleic acid of 726 nucleotides (also referred to as CG56592-02) encoding a novel Claudin 6-like protein is shown in Table ⁇ G. An open reading frame was identified beginning with an ATG codon at nucleotides 6-8 and ending with a TAG codon at nucleotides 693-695. The start and stop codons are in bold letters and the 5' and 3' untranslated regions are underlined in Table 1G.
  • Table 1G NOVld nucleotide sequence (SEQ ID NO:7).
  • the NOVld nucleic acid sequence, located on chromsome 12 has 336 of 534 bases (62%) identical to a gb:GENBANK- ID:HSA249735
  • acc:AJ249735.1 mRNA from Homo sapiens (CLDN6 gene for claudin-6) (E 6.5e- 16 ).
  • NOVld polypeptide (SEQ ID NO:8) encoded by SEQ ID NO:7 has 229 amino acid residues and is presented in Table IH using the one-letter amino acid code.
  • Signal P, Psort and/or Hydropathy results predict that NOVld has no signal peptide and is likely to be localized the the plasma membrane with a certainty of 0.6400.
  • NOVld may also localize to the Golgi body with acertainty of 0.4600, the endoplasmic reticulum (membrane) with a certainty of 0.3700 or in the endoplasmic reticulum (lumen) with a certainty of 0.1000.
  • the most likely cleavage site for a NOVld peptide is between amino acids 24 and 25, at: VCS-CV.
  • Expression information was derived from the tissue sources of the sequences that were included in the derivation of NOVld.
  • the sequence is predicted to be expressed in Bone Marrow, Brain, Liver, Placenta, and Lung.
  • NOV1 Homologies to any of the above NOV1 proteins will be shared by the other NOV1 proteins insofar as they are homologous to each other as shown below. Any reference to NOV1 is assumed to refer to all four of the NOV1 proteins in general, unless otherwise noted.
  • the disclosed NOVla polypeptide has homology to the amino acid sequences shown in the BLASTP data listed in Table II.
  • the claudins are a family of integral membrane proteins that are major components of tight junction (TJ) strands.
  • TJ tight junction
  • claudins When claudins are introduced into cells that lack tight junctions, networks of strands and grooves form at cell-cell contact sites that closely resemble native tight junctions. There are at least 17 members of this family in mammals.
  • Claudin family members share -38% amino acid identity, and are predicted to have four transmembrane (TM) domains, which is reminiscent of occludin, although they share no sequence similarity with it. Multiple sequence alignment reveals their sequences to be fairly well conserved in the first and fourth putative TM domains, and in the first and second extracellular loops, but they diverge in the second and third TM domains.
  • the disclosed NOV1 nucleic acid of the invention encoding a Human Claudin -like protein includes the nucleic acid whose sequence is provided in Table 1A ,1C, IE, 1G, or a fragment thereof.
  • the invention also includes a mutant or variant nucleic acid any of whose bases may be changed from the corresponding base shown in Table 1A, IC, IE, or 1G while still encoding a protein that maintains its Human Claudin-like activities and physiological functions, or a fragment of such a nucleic acid.
  • the invention further includes nucleic acids whose sequences are complementary to those just described, including nucleic acid fragments that are complementary to any of the nucleic acids just described.
  • the invention additionally includes nucleic acids or nucleic acid fragments, or complements thereto, whose structures include chemical modifications.
  • modifications include, by way of nonlimiting example, modified bases, and nucleic acids whose sugar phosphate backbones are modified or derivatized. These modifications are carried out at least in part to enhance the chemical stability of the modified nucleic acid, such that they may be used, for example, as antisense binding nucleic acids in therapeutic applications in a subject.
  • up to about 37 percent of the bases may be so changed.
  • the disclosed NOV1 protein of the invention includes the Human Claudin-like protein whose sequence is provided in Table IB, ID, IF, or IH.
  • the invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residue shown in Table IB, ID, IF, or IH while still encoding a protein that maintains its Human Claudin-like activities and physiological functions, or a functional fragment thereof. In the mutant or variant protein, up to about 66 percent of the residues may be so changed.
  • the invention further encompasses antibodies and antibody fragments, such as F ab or (F at> ) 2, that bind immunospecifically to any of the proteins of the invention.
  • NOV1 is a member of a "Human Claudin family”. Therefore, the NOV1 nucleic acids and proteins identified here may be useful in potential therapeutic applications implicated in (but not limited to) various pathologies and disorders as indicated below.
  • the potential therapeutic applications for this invention include, but are not limited to: protein therapeutic, small molecule drug target, antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), diagnostic and/or prognostic marker, gene therapy (gene delivery/gene ablation), research tools, tissue regeneration in vivo and in vitro of all tissues and cell types composing (but not limited to) those defined here.
  • NOV1 nucleic acids and proteins of the invention are useful in potential therapeutic applications implicated in cancer including but not limited to various pathologies and disorders as indicated below.
  • a cDNA encoding the Human Claudin-like protein (NOV1) may be useful in gene therapy, and the Human Claudin -like protein (NOV1) may be useful when administered to a subject in need thereof.
  • compositions of the present invention will have efficacy for treatment of patients suffering from Von Hippel-Lindau (VHL) syndrome, Cirrhosis, Transplantation, Hemophilia, hypercoagulation, Idiopathic thrombocytopenic purpura, autoimmume disease, allergies, immunodeficiencies, transplantation, Graft vesus host, Alzheimer's disease, Stroke, Tuberous sclerosis, hypercalceimia, Parkinson's disease, Huntington's disease, Cerebral palsy, Epilepsy, Lesch-Nyhan syndrome, Multiple sclerosis, Ataxia-telangiectasia, Leukodystrophies, Behavioral disorders, Addiction, Anxiety, Pain, Neuroprotection, Systemic lupus erythematosus , Autoimmune disease, Asthma, Emphysema, Scleroderma, allergy, and Cancer, or other pathologies or conditions.
  • VHL Von Hippel-Lindau
  • Cirrhosis Cirr
  • NOV1 nucleic acids and polypeptides are further useful in the generation of antibodies that bind immuno-specifically to the novel NOV1 substances for use in therapeutic or diagnostic methods.
  • These antibodies may be generated according to methods known in the art, using prediction from hydrophobicity charts, as described in the "Anti-NOVX Antibodies" section below.
  • the disclosed NOV1 proteins have multiple hydrophilic regions, each of which can be used as an immunogen. These novel proteins can be used in assay systems for functional analysis of various human disorders, which will help in understanding of pathology of the disease and development of new drug targets for various disorders.
  • a disclosed NOV2 nucleic acid of 1361 nucleotides (also referred to as CG56596-01) encoding a novel Protein Serine Kinase-like protein is shown in Table 2A.
  • An open reading frame was identified beginning with an ATG initiation codon at nucleotides 20-22 and ending with a TAA codon at nucleotides 1268-1270.
  • a The start and stop codons are in bold letters in Table 2A.
  • Table 2A NOV2 nucleotide sequence (SEQ DD NO:9).
  • the disclosed NOV2 nucleic acid sequence localized to the q21.3-22 region of chromsome 18, has 685 of 997 bases (68%) identical to a gb:GENBANK- ID:HSA272212
  • acc:AJ272212.1 mRNA from Homo sapiens (mRNA for protein serine kinase (PSKHl gene)) (E 6.1e '85 ).
  • a NOV2 polypeptide (SEQ ID NO: 10) encoded by SEQ ID NO:9 has 416 amino acid residues and is presented using the one-letter code in Table 2B.
  • Signal P, Psort and/or Hydropathy results predict that NOV2 contains no signal peptide and is likely to be localized to the endoplasmic reticulum (membrane) with a certainty of 0.5500.
  • NOV2 may also localize to the lysosome (lumen) with a certainty of 0.2403, the plasma membrane with a certainty of 0.1900, or the microbody (peroxisome) with a certainty of 0.1111.
  • Table 2B Encoded NOV2 protein sequence (SEQ ID NO:10).
  • NOV2 is predicted to be expressed in Kidney, Lymph node, Pancreas, Salivary Glands, Brain, and Placenta because of the expression pattern of (GENBANK-ID: gb:GENBANK- ID:HSA272212
  • sequence is predicted to be expressed in keratinocytes because of the expression pattern of (GENBANK-ID: gb:GENBANK-ID:HSPIl 371 l
  • NOV2 also has homology to the amino acid sequences shown in the BLASTP data listed in Table 2C.
  • XM 043047 [Homo sapiens] gi 115963448 I gb IAALl protein 424 254/386 311/386 e-144 1033.1] (AF236367) serine (65%) (79%) kinase Pskhl [Mus musculus]
  • DOMAIN results for NOV2 as disclosed in Tables 2E-2G were collected from the conserveed Domain Database (CDD) with Reverse Position Specific BLAST analyses. This BLAST analysis software samples domains found in the Smart and Pfam collections. For Table 2K and all successive DOMAIN sequence alignments, fully conserved single residues are indicated by black shading or by the sign (
  • the "strong" group of conserved amino acid residues may be any one of the following groups of amino acids: STA, NEQK, NHQK, NDEQ, QHRK, MILV, MILF, HY, FYW.
  • Tables 2E-G lists the domain description from DOMAIN analysis results against NOV2. This indicates that the NOV2 sequence has properties similar to those of other proteins known to contain this domain.
  • CD-Length 256 residues, 100.0% aligned
  • NOV 2 272 SAVDMWALGVITYALLSGFLPFDDESQTRLYRKILKGKYNYTGEPWPSISHLAKDFIDKL 331
  • CD-Length 258 residues, 83.7% aligned
  • NOV 2 100 IGTGSFSRWR VEQKTTKKPFAIKVM-ETREREGREACVSELSVLRRVSHRYIVQLM 155
  • NOV 2 273 AVDMWALGVITYALLS-GFLPFDDESQTRLYRKILKGKY 310
  • Protein phosphorylation is a fundamental process for the regulation of cellular functions. The coordinated action of both protein kinases and phosphatases controls the levels of phosphorylation and, hence, the activity of specific target proteins.
  • One of the predominant roles of protein phosphorylation is in signal transduction, where extracellular signals are amplified and propagated by a cascade of protein phosphorylation and dephosphorylation events.
  • Eukaryotic protein kinases are enzymes that belong to a very extensive family of proteins which share a conserved catalytic core common with both serine/threonine and tyrosine protein kinases. There are a number of conserved regions in the catalytic domain of protein kinases.
  • the disclosed NOV2 nucleic acid of the invention encoding a Protein Serine Kinase- like protein includes the nucleic acid whose sequence is provided in Tables 2A or a fragment thereof.
  • the invention also includes a mutant or variant nucleic acid any of whose bases may be changed from the corresponding base shown in Tables 2A while still encoding a protein that maintains its Protein Serine Kinase -like activities and physiological functions, or a fragment of such a nucleic acid.
  • the invention further includes nucleic acids whose sequences are complementary to those just described, including nucleic acid fragments that are complementary to any of the nucleic acids just described.
  • the invention additionally includes nucleic acids or nucleic acid fragments, or complements thereto, whose structures include chemical modifications. Such modifications include, by way of nonlimiting example, modified bases, and nucleic acids whose sugar phosphate backbones are modified or derivatized.
  • modifications are carried out at least in part to enhance the chemical stability of the modified nucleic acid, such that they may be used, for example, as antisense binding nucleic acids in therapeutic applications in a subject.
  • the mutant or variant nucleic acids, and their complements up to about 32 percent of the bases may be so changed.
  • the disclosed NOV2 protein of the invention includes the Protein Serine Kinase -like protein whose sequence is provided in Tables 2B.
  • the invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residue shown in Table 2B while still encoding a protein that maintains its Protein Serine Kinase-like activities and physiological functions, or a functional fragment thereof. In the mutant or variant protein, up to about 35 percent of the residues may be so changed.
  • the NOV2 nucleic acids and proteins of the invention are useful in potential therapeutic applications implicated in Diabetes, Von Hippel-Lindau (VHL) syndrome , Pancreatitis, Obesity, Lymphedema , Allergies, Alzheimer's disease, Stroke, Tuberous sclerosis, hypercalceimia, Parkinson's disease, Huntington's disease, Cerebral palsy, Epilepsy, Lesch-Nyhan syndrome, Multiple sclerosis, Ataxia-telangiectasia, Leukodystrophies, Behavioral disorders, Addiction, Anxiety, Pain, Neuroprotection, Diabetes, Autoimmune disease, Renal artery stenosis, Interstitial nephritis, Glomerulonephritis, Polycystic kidney disease, Systemic lupus erythematosus, Renal tubular acidosis, IgA nephropathy, and/or other pathologies and disorders.
  • VHL Von Hippel-Lind
  • NOV2 nucleic acids and polypeptides are further useful in the generation of antibodies that bind immunospecif ⁇ cally to the novel substances of the invention for use in therapeutic or diagnostic methods.
  • These antibodies may be generated according to methods known in the art, using prediction from hydrophobicity charts, as described in the "Anti-NOVX Antibodies" section below.
  • the disclosed NOV2 protein has multiple hydrophilic regions, each of which can be used as an immunogen.
  • These novel proteins can be used in assay systems for functional analysis of various human disorders, which are useful in understanding of pathology of the disease and development of new drug targets for various disorders.
  • NOV3 includes three novel human 1 Claudin-like proteins disclosed below. The disclosed sequences have been named NOV3a, NOV3b, and NOV3c. NOV3a
  • a disclosed NOV3a nucleic acid of 695 nucleotides (designated CuraGen Ace. No. CG56594-01) encoding a novel Claudin-19-like protein is shown in Table 3A.
  • An open reading frame was identified beginning with an ATG initiation codon at nucleotides 53-55 and ending with a TGA codon at nucleotides 662-664.
  • a putative untranslated region downstream from the termination codon is underlined in Table 3A, and the start and stop codons are in bold letters.
  • the nucleic acid sequence, localized to chromosome 1, has 402 of 482 bases (83%) identical to a gb:GENBANK-ID:AF249889
  • acc:AF249889.1 mRNA from Mus musculus (claudin-19 mRNA, partial cds) (E l.le "67 ).
  • a NOV3a polypeptide (SEQ ID NO: 12) encoded by SEQ ID NO:l 1 is 203 amino acid residues and is presented using the one letter code in Table 3B.
  • Signal P, Psort and/or Hydropathy results predict that NOV3a has no signal peptide and is likely to be localized at the endoplasmic reticulum (membrane) with a certainty of 0.6850.
  • NOV3a may also localize to the plasma membrane with a certainty of 0.6400, the Golgi body with a certainty of 0.4600, or the endoplasmic reticulum (lumen) with a certainty of 0.1000.
  • the most likely cleavage site for NOV3a is between positions 23 and 24: IIA-ST.
  • a disclosed NOV3b nucleic acid of 695 nucleotides (also referred to as CG56594-01) encoding a novel Claudin-19-like protein is shown in Table 3C.
  • An open reading frame was identified beginning with an ATG initiation codon at nucleotides 53-55 and ending with a TGA termination codon at nucleotides 662-664.
  • the start and stop codons are in bold letters in Table 3C, and the 5' and 3' untranslated regions are underlined.
  • Table 3C NOV3b nucleotide sequence (SEQ ID NO: 13).
  • the NOV3b nucleic acid sequence, located on chromsome 1 has 402 of 482 bases (83%) identical to a gb:GENBANK- ID:AF249889
  • acc:AF249889.1 mRNA from Mus musculus (claudin-19 mRNA, partial cds) (E l.le- 67 ).
  • NOV3b polypeptide (SEQ ID NO: 14) encoded by SEQ ID NO: 13 has 203 amino acid residues and is presented in Table 3D using the one-letter amino acid code.
  • Signal P, Psort and/or Hydropathy results predict that NOV3b has a signal peptide and is likely to be localized the endoplasmic reticulum (membrane) with a certainty of 0.6850.
  • NOV3b may also localize to the plasma membrane with acertainty of 0.6400, the Golgi body with a certainty of 0.4600 or in the endoplasmic reticulum (lumen) with a certainty of 0.1000.
  • the most likely cleavage site for NOV3b is between positions 23 and 24: IIA-ST.
  • Table 3D Encoded NOV3b protein sequence (SEQ ID NO: 14).
  • NOV3b is predicted to be expressed in at least the Spinal cord.
  • NOV3c A disclosed NOV3c nucleic acid of 690 nucleotides (also referred to as CG57576-01) encoding a novel Claudin 19-like protein is shown in Table 3E.
  • An open reading frame was identified beginning with an ATG codon at nucleotides 51-53 and ending with a TGA codon at nucleotides 684-686.
  • the start and stop codons are in bold letters and the 5' and 3' untranslated regions are underlined in Table 31. Because the start codon is not a traditional initiation codon, NOV3c could be a partial reading frame. NOV3c could extend further in the 5' direction.
  • the NOV3c nucleic acid sequence, located on chromsome 1 has 445 of 671 bases (66%) identical to a gb:GENBANK-
  • the disclosed NOV3c polypeptide (SEQ ID NO: 16) encoded by SEQ ID NO: 15 has 211 amino acid residues and is presented in Table 3F using the one-letter amino acid code.
  • Signal P, Psort and/or Hydropathy results predict that NOV3c has no signal peptide and is likely to be localized the the endoplasmic reticulum (membrane) with a certainty of 0.6850.
  • NOV3c may also localize to the plasma membrane with acertainty of 0.6400, the Golgi body with a certainty of 0.4600 or in the endoplasmic reticulum (lumen) with a certainty of 0.1000.
  • the most likely cleavage site for a NOV3c peptide is between amino acids 23 and 24, at: IIA-ST. Table 3F.
  • Encoded NOV3c protein sequence (SEQ ID NO:16).
  • NOV3c is predicted to be expressed in at least Spinal cord.
  • NOV3a also has homology to the amino acid sequences shown in the BLASTP data listed in Table 3G.
  • Table 31 lists the domain description from DOMAIN analysis results against NOV3. This indicates that the NOV3 sequence has properties similar to those of other proteins known to contain this domain.
  • NNOOVV 33 112233 GALFILAGLCTLTAVSWYATLVTQEFFNP EFGPALFVGWASAGLAVLGGSFL 174
  • the claudins are a family of integral membrane proteins that are major components of tight junction (TJ) strands.
  • TJ tight junction
  • claudins When claudins are introduced into cells that lack tight junctions, networks of strands and grooves form at cell-cell contact sites that closely resemble native tight junctions. There are at least 17 members of this family in mammals.
  • Claudin family members share ⁇ 38% amino acid identity, and are predicted to have four transmembrane (TM) domains, which is reminiscent of occludin, although they share no sequence similarity with it. Multiple sequence alignment reveals their sequences to be fairly well conserved in the first and fourth putative TM domains, and in the first and second extracellular loops, but they diverge in the second and third TM domains.
  • the disclosed NOV3 nucleic acid of the invention encoding a Claudin-19 -like protein includes the nucleic acid whose sequence is provided in Table 3A or a fragment thereof.
  • the invention also includes a mutant or variant nucleic acid any of whose bases may be changed from the corresponding base shown in Table 3A while still encoding a protein that maintains its Claudin-19 -like activities and physiological functions, or a fragment of such a nucleic acid.
  • the invention further includes nucleic acids whose sequences are complementary to those just described, including nucleic acid fragments that are complementary to any of the nucleic acids just described.
  • the invention additionally includes nucleic acids or nucleic acid fragments, or complements thereto, whose structures include chemical modifications.
  • modifications include, by way of nonlimiting example, modified bases, and nucleic acids whose sugar phosphate backbones are modified or derivatized. These modifications are carried out at least in part to enhance the chemical stability of the modified nucleic acid, such that they may be used, for example, as antisense binding nucleic acids in therapeutic applications in a subject. In the mutant or variant nucleic acids, and their complements, up to about 17 percent of the bases may be so changed.
  • the disclosed NOV3 protein of the invention includes the Claudin-19 -like protein whose sequence is provided in Table 3B.
  • the invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residue shown in Table 3B while still encoding a protein that maintains its Claudin-19 -like activities and physiological functions, or a functional fragment thereof. In the mutant or variant protein, up to about 48 percent of the residues may be so changed.
  • NOV3 nucleic acid
  • nucleic acid or protein diagnostic and/or prognostic marker serving as a specific or selective nucleic acid or protein diagnostic and/or prognostic marker, wherein the presence or amount of the nucleic acid or the protein are to be assessed, as well as potential therapeutic applications such as the following: (i) a protein therapeutic, (ii) a small molecule drug target, (iii) an antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), (iv) a nucleic acid useful in gene therapy (gene delivery/gene ablation), and (v) a composition promoting tissue regeneration in vitro and in vivo.
  • compositions of the present invention will have efficacy for treatment of patients suffering from Von Hippel-Lindau (VHL) syndrome, Cirrhosis, Transplantation, Hemophilia, hypercoagulation, Idiopathic thrombocytopenic purpura, autoimmume disease, allergies, immunodeficiencies, transplantation, Graft vesus host, Alzheimer's disease, Stroke, Tuberous sclerosis, hypercalceimia, Parkinson's disease, Huntington's disease, Cerebral palsy, Epilepsy, Lesch-Nyhan syndrome, Multiple sclerosis, Ataxia-telangiectasia, Leukodystrophies, Behavioral disorders, Addiction, Anxiety, Pain, Neuroprotection, Systemic lupus erythematosus , Autoimmune disease, Asthma, Emphysema, Scleroderma
  • NOV3 nucleic acids and polypeptides are further useful in the generation of antibodies that bind immunospecifically to the novel substances of the invention for use in therapeutic or diagnostic methods.
  • These antibodies may be generated according to methods known in the art, using prediction from hydrophobicity charts, as described in the "Anti-NOVX Antibodies” section below.
  • These novel proteins can be used in assay systems for functional analysis of various human disorders, which will help in understanding of pathology of the disease and development of new drug targets for various disorders.
  • NOV4 includes three novel human 1 Claudin-like proteins disclosed below. The disclosed sequences have been named NOV4a, NOV4b, and NOV4c. NOVla
  • a disclosed NOV4a nucleic acid of 694 nucleotides (also referred to as CG56589-01) encoding a novel Claudin-6-like protein is shown in Table 4A.
  • An open reading frame was identified beginning with an ATG initiation codon at nucleotides 11-13 and ending with a TAA codon at nucleotides 671-673.
  • Putative untranslated regions upstream from the initiation codon and downstream from the termination codon are underlined in Table 4A, and the start and stop codons are in bold letters.
  • a disclosed NOV4a polypeptide (SEQ ID NO: 18) encoded by SEQ ID NO: 17 is 220 amino acid residues and is presented using the one-letter code in Table 4B.
  • Signal P, Psort and/or Hydropathy results predict that NOV4a has no signal peptide and is likely to be localized in the plasma membrane with a certainty of 0.6400.
  • NOV4a may also localize to the Golgi body with acertainty of 0.4600, the endoplasmic reticulum (membrane) with a certainty of 0.3700, or the enoplasmic reticulum (lumen) with a certainty of 0.1000.
  • the most likely cleavage site for NOV4a is between positions 24 and 25: ILS-II.
  • NOV4a is predicted to be expressed in at least Brain. This information was derived by determining the tissue sources of the sequences that were included in the invention including but not limited to SeqCalling sources, Public EST sources, Literature sources, and/or RACE sources.
  • sequence is predicted to be expressed in Adrenal Gland/Suprarenal gland, Brain, Bronchus, Brown adipose, Cervix, Colon, Coronary Artery, Epidermis, Gall Bladder, Heart, Hippocampus, Islets of Langerhans, Kidney, Liver, Lung, Lung Pleura, Mammary gland/Breast, Oesophagus, Ovary, Oviduct/Uterine Tube/Fallopian tube, Parotid Salivary glands, Peripheral Blood, Placenta, Prostate, Proximal Convoluted Tubule, Respiratory Bronchiole, Skin, Stomach, Substantia Nigra, Thymus, Thyroid, Trachea, Umbilical Vein, Uterus, and Vulva.
  • NOV4b nucleic acid of 694 nucleotides also referred to as CG56589-01
  • Table 4C An open reading frame was identified beginning with an ATG codon at nucleotides 11-13 and ending with a TAA codon at nucleotides 671-67 J. tuc iart and stop codons are in bold letters and the 5' and 3' untranslated regions are underlined in Table 4C. Because the start codon is not a traditional initiation codon, NOV4b could be a partial reading frame. NOV4b could extend further in the 5' direction.
  • Table 4C NOV4b nucleotide sequence (SEQ ID NO:19).
  • the NOV4b nucleic acid sequence, located on chromsome 4 has 330 of 556 bases (59%) identical to a gb:GENBANK- ID:AF134160
  • acc:AF134160.1 mRNA from Homo sapiens (claudin- 1 (CLDNl) mRNA, complete cds) (E 2.9e "09 ).
  • NOV4b polypeptide (SEQ 3D NO:20) encoded by SEQ ID NO: 19 has 220 amino acid residues and is presented in Table 4D using the one-letter amino acid code.
  • Signal P, Psort and/or Hydropathy results predict that NOV4b has no signal peptide and is likely to be localized the the plasma membrane with a certainty of 0.6400.
  • NOV4b may also localize to the Golgi body with acertainty of 0.4600, the endoplasmic reticulum (membrane) with a certainty of 0.3700 or in the endoplasmic reticulum (lumen) with a certainty of 0.1000.
  • the most likely cleavage site for a NOV4b peptide is between amino acids 24 and 25, at: ILS-II.
  • Table 4D Encoded NOV4b protein sequence (SEQ ID NO:20).
  • NOV4b is predicted to be expressed in at least Brain.
  • a disclosed NOV4c nucleic acid of 694 nucleotides (also referred to as CG56589-02) encoding a novel Claudin 6-like protein is shown in Table 4E.
  • An open reading frame was identified beginning with an ATG codon at nucleotides 11-13 and ending with a TAA codon at nucleotides 671-673.
  • the start and stop codons are in bold letters and the 5' and 3' untranslated regions are underlined in Table 4E.
  • the NOV4c nucleic acid sequence, located on chromsome 4 has 331 of 556 bases (59%) identical to a gb:GENBANK-
  • acc:AF134160.1 mRNA from Homo sapiens (claudin- 1 (CLDNl) mRNA, complete cds) (E 3.2e "9 ).
  • the disclosed NOV4c polypeptide (SEQ ID NO:22) encoded by SEQ ID NO:21 has
  • NOV4c has no signal peptide and is likely to be localized the the plasma membrane with a certainty of 0.6400.
  • NOV4c may also localize to the Golgi body with acertainty of 0.4600, the endoplasmic reticulum (membrane) with a certainty of 0.3700 or in the endoplasmic reticulum (lumen) with a certainty of 0.1000.
  • the most likely cleavage site for a NOV4c peptide is between amino acids 24 and 25, at: ILS-II.
  • Table 4F Encoded NOVlc protein sequence (SEQ ID NO:22).
  • the sequence is predicted to be expressed in the following tissues : Adrenal Gland/Suprarenal gland, Brain, Bronchus, Brown adipose, Cervix, Colon, Coronary Artery, Epidermis, Gall Bladder, Heart, Hippocampus, Islets of Langerhans, Kidney, Liver, Lung, Lung Pleura, Mammary gland/Breast, Oesophagus, Ovary, Oviduct/Uterine Tube/Fallopian tube, Parotid Salivary glands, Peripheral Blood, Placenta, Prostate, Proximal Convoluted Tubule, Respiratory Bronchiole, Skin, Stomach, Substantia Nigra, Thymus, Thyroid, Trachea, Umbilical Vein, Uterus, and Vulva.
  • NOV4 also has homology to the amino acid sequences shown in the BLASTP data listed in Table 4G.
  • Table 41 lists the domain description from DOMAIN analysis results against NOV4. This indicates that the NOV4 sequence has properties similar to those of other proteins known to contain this domain.
  • the claudins are a family of integral membrane proteins that are major components of tight junction (TJ) strands.
  • TJ tight junction
  • claudins When claudins are introduced into cells that lack tight junctions, networks of strands and grooves form at cell-cell contact sites that closely resemble native tight junctions. There are at least 17 members of this family in mammals.
  • Claudin family members share -38% amino acid identity, and are predicted to have four transmembrane (TM) domains, which is reminiscent of occludin, although they share no sequence similarity with it. Multiple sequence alignment reveals their sequences to be fairly well conserved in the first and fourth putative TM domains, and in the first and second extracellular loops, but they diverge in the second and third TM domains.
  • the disclosed NOV4 nucleic acid of the invention encoding a Claudin-6 -like protein includes the nucleic acid whose sequence is provided in Table 4A or a fragment thereof.
  • the invention also includes a mutant or variant nucleic acid any of whose bases may be changed from the corresponding base shown in Table 4A while still encoding a protein that maintains its Claudin-6 -like activities and physiological functions, or a fragment of such a nucleic acid.
  • the invention further includes nucleic acids whose sequences are complementary to those just described, including nucleic acid fragments that are complementary to any of the nucleic acids just described.
  • the invention additionally includes nucleic acids or nucleic acid fragments, or complements thereto, whose structures include chemical modifications. Such modifications include, by way of nonlimiting example, modified bases, and nucleic acids whose sugar phosphate backbones are modified or derivatized. These modifications are carried out at least in part to enhance the chemical stability of the modified nucleic acid, such that they may be used, for example, as antisense binding nucleic acids in therapeutic applications in a subject. In the mutant or variant nucleic acids, and their complements, up to about 41 percent of the bases may be so changed.
  • the disclosed NOV4 protein of the invention includes the Claudin-6 -like protein whose sequence is provided in Table 4B.
  • the invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residue shown in Table 4B while still encoding a protein that maintains its Claudin-6-like activities and physiological functions, or a functional fragment thereof. In the mutant or variant protein, up to about 61 percent of the residues may be so changed.
  • the NOV4 nucleic acids and proteins of the invention are useful in potential therapeutic applications implicated in Von Hippel-Lindau (VHL) syndrome, Cirrhosis, Transplantation, Hemophilia, hypercoagulation, Idiopathic thrombocytopenic purpura, autoimmume disease, allergies, immunodeficiencies, transplantation, Graft vesus host, Alzheimer's disease, Stroke, Tuberous sclerosis, hypercalceimia, Parkinson's disease, Huntington's disease, Cerebral palsy, Epilepsy, Lesch-Nyhan syndrome, Multiple sclerosis, Ataxia-telangiectasia, Leukodystrophies, Behavioral disorders, Addiction, Anxiety, Pain,
  • NOV4 nucleic acid, or fragments thereof may further be useful in diagnostic applications, wherein the presence or amount of the nucleic acid or the protein are to be assessed.
  • NOV4 nucleic acids and polypeptides are further useful in the generation of antibodies that bind immunospecifically to the novel substances of the invention for use in therapeutic or diagnostic methods. These antibodies may be generated according to methods known in the art, using prediction from hydrophobicity charts, as described in the "Anti-NOVX Antibodies" section below.
  • NOV4 protein have multiple hydrophilic regions, each of which can be used as an immunogen.
  • This novel protein also has value in development of powerful assay system for functional analysis of various human disorders, which will help in understanding of pathology of the disease and development of new drug targets for various disorders.
  • NOV5 includes three novel Monocarboxylate transporter (MCT3)-like proteins disclosed below.
  • MCT3 Monocarboxylate transporter
  • a disclosed NOV5a nucleic acid of 1502 nucleotides also referred to as CG56635-01 encoding a novel Monocarboxylate transporter (MCT3)-like protein is shown in Table 5a.
  • MCT3 Monocarboxylate transporter
  • the disclosed NOV5a nucleic acid sequence located on chromosome 17, has 672 of 1110 bases (60%) identical to a gb:GENBANK-ID:AFl 32610
  • acc:AF 132610.1 mRNA from Homo sapiens (monocarboxylate transporter MCT3 mRNA, complete cds) (E 1.6e "29 ).
  • a disclosed NOV5a polypeptide (SEQ ID NO:24) encoded by SEQ ID NO:23 is 447 amino acid residues and is presented using the one- letter amino acid code in Table 5B.
  • Signal P, Psort and/or Hydropathy results predict that NOV5a contains no signal peptide and is likely to be localized in the endoplasmic reticulum (membrane) with a certainty of 0.6850.
  • NOV5a is also likely to be localized to the plasma membrane with a certainty of 0.6400, to the Golgi body with a certainty of 0.4600, or to the endoplasmic reticulum (lumen) with a certainty of 0.1000
  • NOV5a is predicted to be expressed in at least Adrenal gland, bone marrow, brain - amygdala, brain - cerebellum, brain - hippocampus, brain - substantia nigra, brain - thalamus, brain -whole, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, lymphoma - Raji, mammary gland, pancreas, pituitary gland, placenta, prostate, retina, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea, uterus.
  • a disclosed NOV5b nucleic acid of 611 nucleotides (also referred to as CG56635-02) encoding a novel Monocarboxylate transporter 3-like protein is shown in Table 5C.
  • An open reading frame was identified beginning with an ATG initiation codon at nucleotides 6-8 and ending with a TGA codon at nucleotides 500-502. The start and stop codons are in bold letters in Table 5B.
  • the disclosed NOV5b nucleic acid sequence located on chromosome 17, has 323 of 520 bases (62%) identical to a gb:GENBANK-ID:AF132610
  • acc:AF132610.1 mRNA from Homo sapiens (monocarboxylate transporter MCT3 mRNA, complete cds) (E 3.2e "18 ).
  • a disclosed NOV5b polypeptide (SEQ ID NO:26) encoded by SEQ ID NO:25 is 191 amino acid residues and is presented using the one-letter amino acid code in Table 5D.
  • NOV5b contains no signal peptide and is likely to be localized in the endoplasmic reticulum (membrane) with a certainty of 0.9325.
  • NOV5b is also likely to be localized to the plasma membrane with a certainty of 0.4960, to the microbody (peroxisome) with a certainty of 0.3200, or to the Golgi body with a certainty of 0.1900
  • the most likely cleavage site for NOV5b is between positions 38 and 39: GLA-FP.
  • Table 5D Encoded NOV5b protein sequence (SEQ ID NO:26).
  • NOV5b is predicted to be expressed in at least the following tissues: adrenal gland, bone marrow, brain - amygdala, brain - cerebellum, brain - hippocampus, brain - substantia nigra, brain - thalamus, brain -whole, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, lymphoma - Raji, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea and uterus.
  • NOV5c is predicted to be expressed in at least the following tissues: adrenal gland, bone marrow, brain - amygdala, brain - cerebellum, brain - hippocampus, brain - substantia nigra, brain - thalamus, brain -whole, fetal brain, fetal kidney
  • a disclosed NOV5c nucleic acid of 704 nucleotides (also referred to as CG56635-03) encoding a novel Monocarboxylate transporter 3-like protein is shown in Table 5E.
  • An open reading frame was identified beginning with an ATG initiation codon at nucleotides 28-30 and ending with a TGA codon at nucleotides 673-675. The start and stop codons are in bold letters in Table 5E.
  • the disclosed NOV5c nucleic acid sequence located on chromosome 17, has 340 of 547 bases (62%) identical to a gb:GENBANK-ID:AF01911 l
  • acc:AF019111.2 mRNA from Mus musculus (monocarboxylate transporter 3 (MCT3) mRNA, complete cds) (E 2.4e "15 ).
  • a disclosed NOV5c polypeptide (SEQ ID NO:28) encoded by SEQ ID NO:27 is 215 amino acid residues and is presented using the one-letter amino acid code in Table 5F.
  • NOV5c contains no signal peptide and is likely to be localized in the endoplasmic reticulum (membrane) with a certainty of 0.8500.
  • NOV5c is also likely to be localized to the microbody (peroxisome) with a certainty of 0.6400, to the plasma membrane with a certainty of 0.4400, or to the nucleus with a certainty of 0.3000
  • Table 5F Encoded NOV5c protein sequence (SEQ ID NO:28).
  • the disclosed NOV5c amino acid sequence has 53 of 110 amino acid residues (48%) identical to, and 72 of 110 amino acid residues (65%) similar to, the 504 amino acid residue ptnr:SPTREMBL-ACC:Q9UBE2 protein from Homo sapiens (Human) (Monocarboxylate
  • NOV5c is predicted to be expressed in at least the following tissues: adrenal gland, bone marrow, brain - amygdala, brain - cerebellum, brain - hippocampus, brain - substantia nigra, brain - thalamus, brain -whole, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, lymphoma - Raji, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea and uterus. .
  • NOV5d A disclosed NOV5d nucleic acid of 1513 nucleotides (also referred to as CG56635-04) encoding a novel Monocarboxylate transporter 3-like protein is shown in Table 5G. An open reading frame was identified beginning with an ATG initiation codon at nucleotides 28-30 and ending with a TGA codon at nucleotides 1444-1446. The start and stop codons are in bold letters in Table 5G. Table 5G. NOV5d Nucleotide Sequence (SEQ ID NO:29)
  • the disclosed NOV5d nucleic acid sequence located on chromosome 17, has 567 of 940 bases (60%) identical to a gb:GENBANK-ID:HSU81800
  • acc:U81800.1 mRNA from Homo sapiens (monocarboxylate transporter (MCT3) mRNA, complete cds) (E 6.5e "30 ).
  • a disclosed NOV5d polypeptide (SEQ ID NO:30) encoded by SEQ ID NO:29 is 472 amino acid residues and is presented using the one-letter amino acid code in Table 5H.
  • Signal P, Psort and/or Hydropathy results predict that NOV5d contains no signal peptide and is likely to be localized in the plasma membrane with a certainty of 0.6000.
  • NOV5d is also likely to be localized to the Golgi body with a certainty of 0.4000, to the endoplasmic reticulum (membrane) with a certainty of 0.3000, or to the microbody (peroxisome) with a certainty of 0.3000
  • NOV5d is predicted to be expressed in at least the following tissues: adrenal gland, bone marrow, brain - amygdala, brain - cerebellum, brain - hippocampus, brain - substantia nigra, brain - thalamus, brain -whole, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, lymphoma - Raji, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea and uterus. .
  • NOV5e A disclosed NOV5e nucleic acid of 465 nucleotides (also referred to as CG56635-05) encoding a novel Monocarboxylate transporter 3-like protein is shown in Table 51.
  • An open reading frame was identified beginning with an ATG initiation codon at nucleotides 7-9 and ending with a TGA codon at nucleotides 436-438.
  • the start and stop codons are in bold letters in Table 51., and the 5' and 3' untranslated regions, if any, are underlined.
  • the disclosed NOV5e nucleic acid sequence located on chromosome 17, has 351 of 434 bases (80%) identical to a gb:GENBANK-ID:AX083362
  • acc:AX083362.1 mRNA from Homo sapiens (Sequence 54 from Patent WOO 112660) (E 1.6e "53 ).
  • a disclosed NOV5e polypeptide (SEQ ID NO:32) encoded by SEQ ID NO:31 is 143 amino acid residues and is presented using the one-letter amino acid code in Table 5J. Signal P, Psort and/or Hydropathy results predict that NOV5e contains no signal peptide and is likely to be localized extracellularly with a certainty of 0.5040.
  • NOV5e is also likely to be localized to the endoplasmic reticulum (membrane) with a certainty of 0.1000, to the endoplasmic reticulum (lumen) with a certainty of 0.1000, or to the lysosome (lumen) with a certainty of 0.1000.
  • the most likely cleavage site for NOV5e is between positions 43 and 44: VLA-EH.
  • Table 5J Encoded NOV5e protein sequence (SEQ ID NO:32).
  • NOV5e is predicted to be expressed in at least Mammalian Tissue, Parathyroid Gland, Mammary gland/Breast, Prostate. .
  • NOV5a also has homology to the amino acid sequences shown in the BLASTP data listed in Table 5K.
  • N0V5a 208 AALGQSLFTRRAFSIFALGTALVGGGYFVPYVHLAPHALDRGLGGYGAALWAVAAMGDA 267 NOVSb 115 115 NOV5C 139 139 N0V5d 232 AALGLSLFTRRAFSIFALGTALVGGGYFVPYVHLAPHALDRGLGGYGAALWAVAAMGDA 291
  • NOV5a 268 GARLVCGWLADQGWVPLPRLLAVFGALTGLGLWWGLVPWGGEESWGGPLLAAAVAYGL 327
  • Monocarboxylates such as lactate and pyruvate play a central role in cellular metabolism and metabolic communication between tissues. Essential to these roles is their rapid transport across the plasma membrane, which is catalysed by a recently identified family of proton-linked monocarboxylate transporters (MCTs).
  • MCTs proton-linked monocarboxylate transporters
  • MCTl is ubiquitously expressed, but is especially prominent in heart and red muscle, where it is up-regulated in response to increased work, suggesting a special role in lactic acid oxidation.
  • MCT4 is most evident in white muscle and other cells with a high glycolytic rate, such as tumour cells and white blood cells, suggesting it is expressed where lactic acid efflux predominates.
  • MCT2 has a ten-fold higher affinity for substrates than MCTl and MCT4 and is found in cells where rapid uptake at low substrate concentrations may be required, including the proximal kidney tubules, neurons and sperm tails.
  • MCT3 is uniquely expressed in the retinal pigment epithelium.
  • MCTl and MCT4 have been shown to interact specifically with OX-47 (CD147), a member of the immunoglobulin superfamily with a single transmembrane helix. This interaction appears to assist MCT expression at the cell surface
  • the disclosed NOV5 nucleic acid of the invention encoding a Monocarboxylate transporter (MCT3)-like protein includes the nucleic acid whose sequence is provided in Table 5A, 5C, 5E, 5G, 51 or a fragment thereof.
  • the invention also includes a mutant or variant nucleic acid any of whose bases may be changed from the corresponding base shown in Table 5A, 5C, 5E, 5G, or 51 while still encoding a protein that maintains its Monocarboxylate transporter (MCT3)-like activities and physiological functions, or a fragment of such a nucleic acid.
  • the invention further includes nucleic acids whose sequences are complementary to those just described, including nucleic acid fragments that are complementary to any of the nucleic acids just described.
  • the invention additionally includes nucleic acids or nucleic acid fragments, or complements thereto, whose structures include chemical modifications.
  • modifications include, by way of nonlimiting example, modified bases, and nucleic acids whose sugar phosphate backbones are modified or derivatized. These modifications are carried out at least in part to enhance the chemical stability of the modified nucleic acid, such that they may be used, for example, as antisense binding nucleic acids in therapeutic applications in a subject. In the mutant or variant nucleic acids, and their complements, up to about 40 percent of the bases may be so changed.
  • the disclosed NOV5 protein of the invention includes the Monocarboxylate transporter (MCT3)-like protein whose sequence is provided in Table 5B, 5D, 5F, 5H, or 5J.
  • the invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residue shown in Table 5B, 5D, 5F, 5H, or 5J while still encoding a protein that maintains its Monocarboxylate transporter (MCT3)-like activities and physiological functions, or a functional fragment thereof. In the mutant or variant protein, up to about 67 percent of the residues may be so changed.
  • NOV5 nucleic acid and polypeptide show homology to the Monocarboxylate transporter (MCT3) familyof proteins. Accordingly, to the NOV5 nucleic acid and polypeptide may function as members of this family.
  • MCT3 Monocarboxylate transporter
  • the NOV5 nucleic acids and proteins identified here may be useful in potential therapeutic applications implicated in (but not limited to) various pathologies and disorders as indicated below.
  • the potential therapeutic applications for this invention include, but are not limited to: protein therapeutic, small molecule drug target, antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), diagnostic and/or prognostic marker, gene therapy (gene delivery/gene ablation), research tools, tissue regeneration in vivo and in vitro of all tissues and cell types composing (but not limited to) those defined here.
  • nucleic acids and proteins of NOV5 are useful in metabolic disorders such as salla disease, infantile sialic acid storage disease, symptomatic deficiency in lactate transport, subnormal erythrocyte lactate transport, muscle injuries, cystinosis, streptozotocin-induced diabetes, hypoxia, cardiac arrest or stroke, neuronal disorders, retinal angiogenesis, and/or other pathologies and disorders.
  • NOV5 nucleic acids and polypeptides are further useful in the generation of antibodies that bind immunospecifically to the novel substances of the invention for use in therapeutic or diagnostic methods.
  • These antibodies may be generated according to methods known in the art, using prediction from hydrophobicity charts, as described in the "Anti-NOVX Antibodies" section below.
  • the disclosed NOV5 protein have multiple hydrophilic regions, each of which can be used as an immunogen.
  • This novel protein also has value in development of powerful assay system for functional analysis of various human disorders, which will help in understanding of pathology of the disease and development of new drug targets for various disorders.
  • NOV6 nucleic acid of 1336 nucleotides also referred to CG56674-01 encoding a novel Nitrilase-1-like protein is shown in Table 6A.
  • An open reading frame was identified beginning with an ATG initiation codon at nucleotides 77-79 and ending with a TAA codon at nucleotides 1058-1060.
  • Table 6A the 5' and 3' untranslated regions are underlined and the start and stop codons are in bold letters.
  • Table 6A NOV6 Nucleotide Sequence (SEQ ID NO:33)
  • the disclosed NOV6 nucleic acid sequence localized to the pi 4.2 region of chromosome 3, has 1319 of 1329 bases (99%) identical to a gb:GENBANK- ID:AF069987
  • acc:AF069987.1 mRNA from Homo sapiens (nitrilase 1 (NIT 1) mRNA, complete cds) (E 3.1 e -290 ).
  • a disclosed NOV6 polypeptide (SEQ ID NO:34) encoded by SEQ ID O:33 is 327 amino acid residues and is presented using the one-letter amino acid code in Table 6B.
  • Signal P, Psort and/or Hydropathy results predict that NOV6 has a signal peptide and is likely to be localized in the cytoplasm with a certainty of 0.4500.
  • NOV6 is also likely to be localized to the microbody (peroxisome) with a certainty of 0.3000, to the lysosome (lumen) with a certainty of 0.2021, or to the mitochondrial matrix space with a certainty of 0.1000.
  • the most likely cleavage site for NOV6 is between positions 27 and 28: LSG-EG
  • Table 6B Encoded NOV6 protein sequence (SEQ ID NO:34).
  • Tables 6E list the domain description from DOMAIN analysis results against NOV6. This indicates that the NOV6 sequence has properties similar to those of other proteins known to contain this domain.
  • Table 6E Domain Analysis of NOV6 gnl I Pfam
  • CD-Length 267 residues, 100.0% aligned
  • the tumor suppressor gene FHIT encompasses the common human chromosomal fragile site at 3pl4.2 and numerous cancer cell biallelic deletions.
  • the nitrilase homologs and Fhit are encoded by two different genes: FHIT and NIT1, localized on chromosomes 3 and 1 in human, and 14 and 1 in mouse, respectively.
  • NIT1 gene Bacterial and plant nitrilases are enzymes that cleave nitriles and organic amides to the corresponding carboxylic acids plus ammonia.
  • the NIT1 gene is expressed as alternatively spliced transcripts.
  • the major NIT1 transcript encodes a deduced 327-amino acid protein that shares 90% amino acid sequence identity with mouse Nitl, 58% identity with the nitrilase domain of C. elegans NitFhit, and 53% identity with the nitrilase domain of Drosophila NitFhit.
  • the NIT1 gene spans approximately 3.2 kb and contains 7 exons.
  • Northern blot analysis detected NIT1 transcripts of approximately 1.4 and 2.4 kb in all adult tissues examined, namely heart, brain, lung, liver, pancreas, kidney, skeletal muscle, and placenta. An approximately 1.2-kb NIT1 transcript was found in skeletal muscle and heart.
  • the disclosed NOV6 nucleic acid of the invention encoding a Nitrilase-1-like protein includes the nucleic acid whose sequence is provided in Table 6A or a fragment thereof.
  • the invention also includes a mutant or variant nucleic acid any of whose bases may be changed from the corresponding base shown in Table 6A while still encoding a protein that maintains its Nitrilase-1-like activities and physiological functions, or a fragment of such a nucleic acid.
  • the invention further includes nucleic acids whose sequences are complementary to those just described, including nucleic acid fragments that are complementary to any of the nucleic acids just described.
  • the invention additionally includes nucleic acids or nucleic acid fragments, or complements thereto, whose structures include chemical modifications.
  • modifications include, by way of nonlimiting example, modified bases, and nucleic acids whose sugar phosphate backbones are modified or derivatized. These modifications are carried out at least in part to enhance the chemical stability of the modified nucleic acid, such that they may be used, for example, as antisense binding nucleic acids in therapeutic applications in a subject. In the mutant or variant nucleic acids, and their complements, up to about 1 percent of the bases may be so changed.
  • the disclosed NOV6 protein of the invention includes the Nitrilase- 1 -like protein whose sequence is provided in Table 6B.
  • the invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residue shown in Table 6B while still encoding a protein that maintains its Nitrilase- 1 -like activities and physiological functions, or a functional fragment thereof. In the mutant or variant protein, up to about 18 percent of the residues may be so changed.
  • NOV6 Nitrilase- 1 -like protein and nucleic acid
  • nucleic acid or protein diagnostic and/or prognostic marker serving as a specific or selective nucleic acid or protein diagnostic and/or prognostic marker, wherein the presence or amount of the nucleic acid or the protein are to be assessed, as well as potential therapeutic applications such as the following: (i) a protein therapeutic, (ii) a small molecule drug target, (iii) an antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), (iv) a nucleic acid useful in gene therapy (gene delivery/gene ablation), and (v) a composition promoting tissue regeneration in vitro and in vivo.
  • the NOV6 nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications implicated in various diseases and disorders described below and/or other pathologies.
  • compositions of the present invention will have efficacy for treatment of patients suffering from cancer, muscle conditions, disorders and diseases, longevity, and/or other pathologies/disorders.
  • the NOV6 nucleic acid, or fragments thereof may further be useful in diagnostic applications, wherein the presence or amount of the nucleic acid or the protein are to be assessed.
  • NOV6 nucleic acids and polypeptides are further useful in the generation of antibodies that bind immunospecifically to the novel substances of the invention for use in therapeutic or diagnostic methods.
  • These antibodies may be generated according to methods known in the art, using prediction from hydrophobicity charts, as described in the "Anti-NOVX Antibodies" section below.
  • the disclosed NOV6 protein have multiple hydrophilic regions, each of which can be used as an immunogen.
  • This novel protein also has value in development of powerful assay system for functional analysis of various human disorders, which will help in understanding of pathology of the disease and development of new drug targets for various disorders.
  • NOV7 includes three novel cleavage signal-l protein-like proteins disclosed below. The disclosed sequences have been named NOV7a, NOV7b, NOV7c, and NOV7d.
  • a disclosed NOV7a nucleic acid of 1822 nucleotides (also referred to as CG56613-01) encoding a novel cleavage signal-l protein-like protein is shown in Table 7A.
  • An open reading frame was identified beginning with an ATG initiation codon at nucleotides 98-100 and ending with a TAA codon at nucleotides 839-841.
  • a putative untranslated region upstream from the initiation codon is underlined in Table 7A. The start and stop codons are in bold letters.
  • Table 7A NOV7a nucleotide sequence (SEQ D3 NO:35).
  • the disclosed NOV7a nucleic acid sequence, localized to chromosome 2, has 1822 of 1828 bases (99%) identical to a gb:GENBANK-ID:HUMCSlPA
  • acc:M61199.1 mRNA from Homo sapiens (Human cleavage signal 1 protein mRNA, complete cds) (E 0.0).
  • the disclosed NOV7a polypeptide (SEQ ID NO:36) encoded by SEQ ID NO:35 has been modified by SEQ ID NO:36.
  • NOV7a has a signal peptide and is likely to be localized to the cytoplasm with a certainty of 0.6500.
  • NOV7A may also localize to the mitochondrial matrix space with a certainty of 0.1000, or the lysosome (lumen) with a certainty of 0.1000.
  • Table 7B Encoded NOV7a protein sequence (SEQ ID NO:36).
  • NOV7a is predicted to be expressed in at least adrenal gland, bone marrow, brain - amygdala, brain - cerebellum, brain - hippocampus, brain - substantia nigra, brain - thalamus, brain -whole, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, lymphoma - Raji, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea, uterus, Aorta, Ascending Colon, Bone, Cervix, Cochlea, Colon, Dermis, Gall Bladder, Hypothalamus, Islets of Langerhans, Liver, Lung, Lymphoid tissue, Ovary, Parathyroid Gland, Parotid Salivary glands, Pineal Gland, Retin
  • the target sequence identified previously, NOV7a was subjected to the exon linking process to confirm the sequence.
  • PCR primers were designed by starting at the most upstream sequence available, for the forward primer, and at the most downstream sequence available for the reverse primer. In each case, the sequence was examined, walking inward from the respective termini toward the coding sequence, until a suitable sequence that is either unique or highly selective was encountered, or, in the case of the reverse primer, until the stop codon was reached.
  • Such primers were designed based on in silico predictions for the full length cDNA, part (one or more exons) of the DNA or protein sequence of the target sequence, or by translated homology of the predicted exons to closely related human sequences sequences from other species.
  • primers were then employed in PCR amplification based on the following pool of human cDNAs: adrenal gland, bone marrow, brain - amygdala, brain - cerebellum, brain - hippocampus, brain - substantia nigra, brain - thalamus, brain -whole, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, lymphoma - Raji, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea, uterus.
  • a disclosed NOV7b nucleic acid of 806 nucleotides (also referred to as CG56613-02) encoding a novel cleavage signal-l protein-like protein is shown in Table 7C.
  • An open reading frame was identified beginning with an ATG initiation codon at nucleotides 21-23 and ending with a TAA codon at nucleotides 762-764.
  • a putative untranslated region upstream from the initiation codon is underlined in Table 7C. The start and stop codons are in bold letters, and the 5' and 3' untranslated regions, if any, are underlined.
  • the disclosed NOV7b nucleic acid sequence, localized to chromosome 2, has 801 of
  • SEQ ID NO:38 The disclosed NOV7b polypeptide (SEQ ID NO:38) encoded by SEQ ID NO:37 has
  • NOV7b has no signal peptide and is likely to be localized to the cytoplasm with a certainty of 0.6500.
  • NOV7b may also localize to the mitochondrial matrix space with a certainty of 0.1000, or the lysosome (lumen) with a certainty of 0.1000.
  • Table 7D Encoded NOV7b protein sequence (SEQ ID NO:38).
  • NOV7b is predicted to be expressed in at least adrenal gland, bone marrow, brain - amygdala, brain - cerebellum, brain - hippocampus, brain - substantia nigra, brain - thalamus, brain -whole, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, lymphoma - Raji, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea, uterus, Aorta, Ascending Colon, Bone, Cervix, Cochlea, Colon, Dermis, Gall Bladder, Hypothalamus, Islets of Langerhans, Liver, Lung, Lymphoid tissue, Ovary, Parathyroid Gland, Parotid Salivary glands, Pineal Gland, Retin
  • a disclosed NOV7c nucleic acid of 806 nucleotides (also referred to as CG56613-03) encoding a novel cleavage signal-l protein-like protein is shown in Table 7E.
  • An open reading frame was identified beginning with an ATG initiation codon at nucleotides 21-23 and ending with a TAA codon at nucleotides 762-764.
  • a putative untranslated region upstream from the initiation codon is underlined in Table 7E. The start and stop codons are in bold letters, and the 5' and 3' untranslated regions, if any, are underlined.
  • Table 7E NOV7c nucleotide sequence (SEQ ID NO:39).
  • the disclosed NOV7c nucleic acid sequence, localized to chromosome 2, has 803 of 812 bases (98%) identical to a gb:GENBANK-ID:HUMCSlPA
  • the disclosed NOV7c polypeptide (SEQ ID NO:40) encoded by SEQ ID NO:39 has 247 amino acid residues and is presented in Table 7F using the one-letter amino acid code.
  • Signal P, Psort and/or Hydropathy results predict that NOV7c has no signal peptide and is likely to be localized to the cytoplasm with a certainty of 0.6500.
  • NOV7f may also localize to the mitochondrial matrix space with a certainty of 0.1000, or the lysosome (lumen) with a certainty of 0.1000.
  • Table 7F Encoded NOV7c protein sequence (SEQ ID NO:40).
  • NOV7c is predicted to be expressed in at least adrenal gland, bone marrow, brain - amygdala, brain - cerebellum, brain - hippocampus, brain - substantia nigra, brain - thalamus, brain -whole, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, lymphoma - Raji, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea, uterus, Aorta, Ascending Colon, Bone, Cervix, Cochlea, Colon, Dermis, Gall Bladder, Hypothalamus, Islets of Langerhans, Liver, Lung, Lymphoid tissue, Ovary, Parathyroid Gland, Parotid Salivary glands, Pineal Gland, Retin
  • NOV7d A disclosed NOV7d nucleic acid of 705 nucleotides (also referred to as 174307820) encoding a novel cleavage signal-l protein-like protein is shown in Table 7G.
  • An open reading frame was identified beginning with an AGA initiation codon at nucleotides 1-3 and ending with nucleotides 703-705.
  • the start codon is in bold letters, and the 5' and 3' untranslated regions, if any, are underlined. Because the start codon is not a traditional initiation codon, and there is no stop codon, NOV7d could be a partial open reading frame extending further in the 5' and 3' directions.
  • the disclosed NOV7d polypeptide (SEQ ID NO:42) encoded by SEQ ID NO:41 has 235 amino acid residues and is presented in Table 7H using the one-letter amino acid code.
  • NOV7e nucleic acid of 759 nucleotides also referred to as 174307820
  • Table 71 An open reading frame was identified beginning with an AGA initiation codon at nucleotides 1-3 and ending with nucleotides 757-759. The start codon is in bold letters, and the 5' and 3' untranslated regions, if any, are underlined. Because the start codon is not a traditional initiation codon, and there is no stop codon, NOV7e could be a partial open reading frame extending further in the 5' and 3' directions. Table 71. NOV7e nucleotide sequence (SEQ ID NO:323).
  • the disclosed NOV7e polypeptide (SEQ ID NO:324) encoded by SEQ ID NO:323 has 253 amino acid residues and is presented in Table 7J using the one-letter amino acid code.
  • NOV7a also has homology to the amino acid sequence shown in the BLASTP data listed in Table 7K.
  • NOV7a 1 1 NOV7b i i NOV7c i i NOV7d i i N0V7e • __ ! 00 55
  • the cleavage signal-l protein (CS-1), a doublet antigen comprised of approximately 14-kDa and 18-kDa proteins has been shown to be present on the surface of sperm of various mammalian species including humans. Polyclonal antibodies to CS-1 inhibit the early cleavage of fertilized eggs without apparently affecting sperm penetration and pronuclear formation.
  • the human CS-1 cDNA has been cloned and expressed in vitro to obtain the recombinant protein (reCS-1) molecule.
  • the CS-1 cDNA clone has been isolated by immunological screening of a human testis lambda gtl 1 cDNA library with mono-specific polyclonal antibody against CS-1.
  • the cDNA is 1828 bp long; the start codon assigned to the first ATG (bp 98-100) encodes a protein with 249 amino acid residues terminating at TAA (bp
  • XCS-1 is a maternally expressed gene product that is the Xenopus homologue of the human cleavage signal protein (CS-1).
  • CS-1 may play an important role in regulating mitosis during early embryogenesis in Xenopus laevis.
  • XCS-1 transcripts have been detected in oocytes.
  • the XCS-1 protein has been detected on the membrane and in the nucleus of blastomeres. It has also been detected on the mitotic spindle in mitotic cells and on the centrosomes in interphase cells.
  • Overexpression of myc-XCS-1 in Xenopus embryos results in abnormal mitoses with increased numbers of centrosomes, " multipolar spindles, and abnormal distribution of chromosomes.
  • the disclosed NOV7 nucleic acid of the invention encoding a Cleavage signal-l protein-like protein includes the nucleic acid whose sequence is provided in Table 7A, or a fragment thereof.
  • the invention also includes a mutant or variant nucleic acid any of whose . bases may be changed from the corresponding base shown in Table 7A while still encoding a protein that maintains its Cleavage signal-l protein-like activities and physiological functions, or a fragment of such a nucleic acid.
  • the invention further includes nucleic acids whose sequences are complementary to those just described, including nucleic acid fragments that are complementary to any of the nucleic acids just described.
  • the invention additionally includes nucleic acids or nucleic acid fragments, or complements thereto, whose structures include chemical modifications.
  • modifications include, by way of nonlimiting example, modified bases, and nucleic acids whose sugar phosphate backbones are modified or derivatized. These modifications are carried out at least in part to enhance the chemical stability of the modified nucleic acid, such that they may be used, for example, as antisense binding nucleic acids in therapeutic applications in a subject. In the mutant or variant nucleic acids, and their complements, up to about 1 percent of the bases may be so changed.
  • the disclosed NOV7 protein of the invention includes the Cleavage signal-l protein- like protein whose sequence is provided in Table 7B.
  • the invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residue shown in Table 2 while still encoding a protein that maintains its Cleavage signal-l protein-like activities and physiological functions, or a functional fragment thereof. In the mutant or variant protein, up to about 21 percent of the residues may be so changed.
  • the invention further encompasses antibodies and antibody fragments, such as F ab or
  • NOV7 Cleavage signal-l protein-like protein
  • the above disclosed information suggests that this Cleavage signal-l protein-like protein (NOV7) is a member of a "Cleavage signal-l protein family". Therefore, the NOV7 nucleic acids and proteins identified here may be useful in potential therapeutic applications implicated in (but not limited to) various pathologies and disorders as indicated below.
  • the potential therapeutic applications for this invention include, but are not limited to: protein therapeutic, small molecule drug target, antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), diagnostic and/or prognostic marker, gene therapy (gene delivery/gene ablation), research tools, tissue regeneration in vivo and in vitro of all tissues and cell types composing (but not limited to) those defined here.
  • the NOV7 nucleic acids and proteins of the invention are useful in potential therapeutic applications implicated in regulation of the cell cycle during early embryogenesis, and therefore may have potential application in the management of embryonic defects. Additionally, this antigen may also be involved in human immunoinfertility and therefore may have application in the treatment of infertility, and/or other diseases or pathologies.
  • NOV7 nucleic acids and polypeptides are further useful in the generation of antibodies that bind immuno-specifically to the novel NOV7 substances for use in therapeutic or diagnostic methods.
  • These antibodies may be generated according to methods known in the art, using prediction from hydrophobicity charts, as described in the "Anti-NOVX Antibodies" section below.
  • the disclosed NOV7 protein has multiple hydrophilic regions, each of which can be used as an immunogen. These novel proteins can be used in assay systems for functional analysis of various human disorders, which will help in understanding of pathology of the disease and development of new drug targets for various disorders.
  • a disclosed NOV8 nucleic acid of 2838 nucleotides (also referred to as 153472451) encoding a novel Matriptase-like protein is shown in Table 8A.
  • An open reading frame was identified beginning with an TAG initiation codon at nucleotides 8-10 and ending with a TGA codon at nucleotides 2279-2281.
  • the start and stop codons are in bold letters in Table 8A, and the 5' and 3' untranslated regions, if any, are underlined.
  • Table 8A NOV8 nucleotide sequence (SEQ ID NO:43).
  • the disclosed NOV8 nucleic acid sequence has 2644 of 2678 bases (98%) identical to a gb:GENBANK-ID:AF118224
  • acc:AFl 18224.2 mRNA from Homo sapiens (matriptase mRNA, complete cds) (E 0.0).
  • NOV8 polypeptide (SEQ ID NO:44) encoded by SEQ ID NO:43 has 757 amino acid residues is presented in Table 8B using the one-letter amino acid code.
  • Signal P, Psort and/or Hydropathy results predict that NOV8 has a signal peptide and is likely to be localized in the plasma membrane with a certainty of 0.8110.
  • NOV8 is predicted to be localized to the Golgi body with a certainty of 0.3000, to the endoplasmic reticulum (membrane) with a certainty of 0.2000, or to the microbody (peroxisome) with a certainty of 0.1527.
  • the most likely ceavage site for NOV8 is between positions 8 and 9, ARK-GG.
  • Table 8B Encoded NOV8 protein sequence (SEQ ID NO:44).
  • NOV8 is predicted to be expressed in at least the following tissues: Adrenal Gland/Suprarenal gland, Aorta, Ascending Colon, Bone Marrow, Brain, Bronchus, Cartilage, Colon, Duodenum, Gall Bladder, Heart, Islets of Langerhans, Kidney, Kidney Cortex, Lung, Mammary gland/Breast, Ovary, Pancreas, Parathyroid Gland, Parotid Salivary glands, Peripheral Blood, Pituitary Gland, Placenta, Prostate, Small Intestine, Stomach, Thymus,Thyroid, Tonsils, Uterus, Vulva, Whole Organism.
  • Adrenal Gland/Suprarenal gland Adrenal Gland/Suprarenal gland, Aorta, Ascending Colon, Bone Marrow, Brain, Bronchus, Cartilage, Colon, Duodenum, Gall Bladder, Heart, Islets of Langerhans, Kidney
  • NOV8 is predicted to be expressed in breast cancer, according to NOV8 nucleic acids, polypeptides, and antibodies. Accordingly to the invention will have diagnostic and therapeutic applications for the detection of breast cancer.
  • the disclosed NOV8 polypeptide has homology to the amino acid sequences shown in the BLASTP data listed in Table 8C.
  • Tables 8E-8R list the domain descriptions from DOMAIN analysis results against NOV8. This indicates that the NOV8 sequence has properties similar to those of other proteins known to contain this domain.
  • Table 8E Domain Analysis of NOV8 gnl]Smart
  • NOV 8 516 RWGGTDADEGEWPWQVSLHALGQGHICGASLISPNWLVSAAHCYIDDRGFRYSDPTQWT 575
  • NOV 8 576 AFLGLHDQSQRSAPGVQERRLKRIISHPFFNDFTFDYDIALLELEKPAEYSSMVRPICLP 635
  • NOV 8 517 WGGTDADEGEWPWQVSLHALGQGHICGASLISPNWLVSAAHCYIDDRGFRYSDPTQWTA 576
  • CD-Length 114 residues, 99.1% aligned
  • NOV 8 302 DYVEI-NGE KYCG-ERSQFWTSNSNKITVRFHSDQSYTDTGFLAEYLS 348
  • Table 8J Domain Analysis of NOV8 gnl I Smart I smart00042, CUB, Domain first found in Clr, Cls, uEGF, and bone morphogenetic protein.,- This domain is found mostly among developmentally-regulated proteins. Spermadhesins contain only this domain. (SEQ ID NO: 807)
  • CD-Length 114 residues, 89.5% aligned
  • NOV 8 129 RFTTPGFPDSPYPAHARCQWALRGDADSVLSLTFRSFDLASCDERGSDLVTVYNTLSPME 188 l+l +1+1 11 + 1 1 + + I I III I I I I +1+ I
  • Table 8K Domain Analysis of NOV8 gnl I Smart I smart00192, LDLa, Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism.
  • LDL low-density lipoprotein
  • the N-terminal type A repeats in LDL receptor bind the lipoproteins .
  • NOV 8 427 CPAQTFRCSNGKCLSKSQQCNGKDDCGDGSDEASCP 462
  • Table 8M Domain Analysis of NOV8 gnl I Smart
  • the N-terminal type A repeats in LDL receptor bind the lipoproteins.
  • Table 8N Domain Analysis of NOV8 gnl I Smart I smart00192, LDLa, Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism.
  • LDL low-density lipoprotein
  • the N-terminal type A repeats in LDL receptor bind the lipoproteins.
  • NOV 8 427 CPAQTFRCSNGKCLSKSQQCNGKDDCGDGSDEASCP 462
  • Table 8P Domain Analysis of NOV8 gnl
  • LRRs Leucine-rich repeats
  • IGFBP insulin like growth factor binding protein
  • RP105 a novel B cell surface molecule. It contains five leucine-rich repeat domains.
  • Leucine-rich repeats (LRRs) are relatively short motifs (22-28 residues in length) found in a variety of cytoplasmic, membrane and extracellular proteins (1) .
  • a common property of this protein family ' involves protein-protein interaction.
  • Other functions of LRR-containing proteins include, for example, binding to enzymes and vascular repair (1) .
  • LRRs form elongated non- globular structures and are often flanked by cysteine rich domains.
  • IGF-I and -II circulating insulin-like growth factors
  • IGF binding protein-3 IGF binding protein-3
  • ALS acid-labile subunit
  • the NOV8 nucleic acid and polypeptide contain structural motifs (i.e. leucine rich repeat domains) that are characteristics of proteins belonging to the leucine-rich repeat protein family. Accordingly, the various NOV8 nucleic acids and polypeptides of the invention are useful, inter alia, as novel members of this protein family.
  • the disclosed NOV8 nucleic acid of the invention encoding a Insulin like growth factor binding protein-like protein includes the nucleic acid whose sequence is provided in Table 8A, or a fragment thereof.
  • the invention also includes a mutant or variant nucleic acid any of whose bases may be changed from the corresponding base shown in Table 8A while still encoding a protein that maintains its Insulin like growth factor binding protein-like activities and physiological functions, or a fragment of such a nucleic acid.
  • the invention further includes nucleic acids whose sequences are complementary to those just described, including nucleic acid fragments that are complementary to any of the nucleic acids just described.
  • the invention additionally includes nucleic acids or nucleic acid fragments, or complements thereto, whose structures include chemical modifications.
  • modifications include, by way of nonlimiting example, modified bases, and nucleic acids whose sugar phosphate backbones are modified or derivatized. These modifications are carried out at least in part to enhance the chemical stability of the modified nucleic acid, such that they may be used, for example, as antisense binding nucleic acids in therapeutic applications in a subject. In the mutant or variant nucleic acid, up to about 2 percent of the bases may be so changed.
  • the disclosed NOV8 protein of the invention includes the Insulin like growth factor binding protein-like protein whose sequence is provided in Table 8B.
  • the invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residue shown in Table 8B while still encoding a protein that maintains its Insulin like growth factor binding protein-like activities and physiological functions, or a functional fragment thereof. In the mutant or variant protein, up to about 18 percent of the residues may be so changed.
  • the invention further encompasses antibodies and antibody fragments, such as F a b or (F ab ) 2, that bind immunospecifically to any of the proteins of the invention.
  • NOV8 Insulin like growth factor binding protein-like protein
  • the above disclosed information suggests that this Insulin like growth factor binding protein-like protein (NOV8) is a member of a "Insulin like growth factor binding protein family". Therefore, the NOV8 nucleic acids and proteins identified here may be useful in potential therapeutic applications implicated in (but not limited to) various pathologies and disorders as indicated below.
  • the potential therapeutic applications for this invention include, but are not limited to: protein therapeutic, small molecule drug target, antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), diagnostic and/or prognostic marker, gene therapy (gene delivery/gene ablation), research tools, tissue regeneration in vivo and in vitro of all tissues and cell types composing (but not limited to) those defined here.
  • the NOV8 nucleic acids and proteins of the invention are useful in potential therapeutic applications implicated in diabetes, obesity, Von Hippel-Lindau (VHL) syndrome, Alzheimer's disease, stroke, tuberous sclerosis, hypercalceimia, Parkinson's disease, Huntington's disease, cerebral palsy, epilepsy, Lesch-Nyhan syndrome, multiple sclerosis, ataxia-telangiectasia, leukodystrophies, behavioral disorders, addiction, anxiety, pain, neuroprotection, cirrhosis, transplantation, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, autoimmume disease, allergies, immunodeficiencies, graft versus host disease (GVHD), lymphaedema, and other diseases, disorders and conditions of the like.
  • VHL Von Hippel-Lindau
  • NOV8 nucleic acids and polypeptides are further useful in the generation of antibodies that bind immuno-specifically to the novel NOV8 substances for use in therapeutic or diagnostic methods.
  • These antibodies may be generated according to methods known in the art, using prediction from hydrophobicity charts, as described in the "Anti-NOVX Antibodies" section below.
  • the disclosed NOV8 protein has multiple hydrophilic regions, each of which can be used as an immunogen.
  • These novel proteins can be used in assay systems for functional analysis of various human disorders, which will help in understanding of pathology of the disease and development of new drug targets for various disorders.
  • NOV9 NOV9 includes three novel Neuropeptide Y/Peptide YY receptor -like proteins disclosed below. The disclosed sequences have been named NOV9a, and NOV9b.
  • NOV9a A disclosed NOV9a nucleic acid of 2276 nucleotides (also referred to as CG56554-01) encoding a novel Neuropeptide Y/Peptide YY receptor -like protein is shown in Table 9A.
  • An open reading frame was identified beginning with an ATG initiation codon at nucleotides 370- 372 and ending with a TAA codon at nucleotides 1549-1551.
  • a putative untranslated region upstream from the initiation codon and downstream from the termination codon is underlined in Table 9A. The start and stop codons are in bold letters.
  • Table 9A NOV9a nucleotide sequence (SEQ ID NO:45).
  • the NOV9a nucleic acid sequence, localized to chromosome 4 has 372 of 434 bases (85%) identical to a gb:GENBANK-
  • NOV9a polypeptide (SEQ ID NO:46) encoded by SEQ ID NO:45 has 393 amino acid residues and is presented in Table 9B using the one-letter amino acid code.
  • Signal P, Psort and/or Hydropathy results predict that NOV9a has no signal peptide and is likely to be localized to the plasma membrane with a certainty of 0.6000.
  • NOV9a may also localize to the Golgi body with a certainty of 0.4000, the endoplasmic reticulum (membrane) with a certainty of 0.3000, or in the microbody (peroxisome) with a certainty of 0.3000.
  • the most likely cleavage site for NOV9a is between positions 64 and 65: GNA-LV.
  • Table 9B Encoded NOV9a protein sequence (SEQ ID NO:46).
  • NOV9a is predicted to be expressed in at least kidney. This information was derived by determining the tissue sources of the sequences that were included in the invention including but not limited to SeqCalling sources, Public EST sources, Literature sources, and/or RACE sources.
  • sequence is predicted to be expressed in lower small intestine, colon, and pancreas, brain, hypothalamus because of SAGE tags identifed for AI308124 and
  • AI307658 ESTs which match to the sequence of the invention: pancreatic cancer, prostate, prostate cancer, brain, glioblastoma, astrocytoma, normal human luminar mammary epithelial cells, breast cancer, ovary, cystadenoma.
  • the SAGE data is reproduced in Example 5.
  • the sequence is also predicted to be expressed in the following tissues because of the expression pattern of related genes in the Neuropeptide Y/Peptide YY/ Orexin/ Galanin/ Cholecystokinin receptor family. NOV9b
  • the target sequence identified previously, NOV9a was subjected to the exon linking process to confirm the sequence.
  • PCR primers were designed by starting at the most upstream sequence available, for the forward primer, and at the most downstream sequence available for the reverse primer. In each case, the sequence was examined, walking inward from the respective termini toward the coding sequence, until a suitable sequence that is either unique or highly selective was encountered, or, in the case of the reverse primer, until the stop codon was reached.
  • Such primers were designed based on in silico predictions for the full length cDNA, part (one or more exons) of the DNA or protein sequence of the target sequence, or by translated homology of the predicted exons to closely related human sequences sequences from other species.
  • primers were then employed in PCR amplification based on the following pool of human cDNAs: adrenal gland, bone marrow, brain - amygdala, brain - cerebellum, brain - hippocampus, brain - substantia nigra, brain - thalamus, brain -whole, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, lymphoma - Raji, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea, uterus.
  • resulting amplicons were gel purified, cloned and sequenced to high redundancy.
  • the resulting sequences from all clones were assembled with themselves, with other fragments in CuraGen Corporation's database and with public ESTs. Fragments and ESTs were included as components for an assembly when the extent of their identity with another component of the assembly was at least 95% over 50 bp.
  • sequence traces were evaluated manually and edited for corrections if appropriate. These procedures provide the sequence reported below, which is designated NOV9b. This differs from the previously identified sequence (NOV9a) in having 38 less amino acids and 3 different ones.
  • a disclosed NOV9b nucleic acid of 1472 nucleotides (also referred to as CG56554-02) encoding a novel Neuropeptide Y/Peptide YY receptor -like protein is shown in Table 9C.
  • An open reading frame was identified beginning with an ATG initiation codon at nucleotides 42- 44 and ending with a TAA codon at nucleotides 1335-1337.
  • a putative untranslated region upstream from the initiation codon and downstream from the termination codon is underlined in Table 9C. The start and stop codons are in bold letters.
  • NOV9b polypeptide (SEQ ID NO:48) encoded by SEQ ID NO:47 has 393 amino acid residues and is presented in Table 9D using the one-letter amino acid code.
  • Signal P, Psort and/or Hydropathy results predict that NOV9b has no signal peptide and is likely to be localized to the plasma membrane with a certainty of 0.6000.
  • NOV9b may also localize to the Golgi body with a certainty of 0.4000, the endoplasmic reticulum (membrane) with a certainty of 0.3000, or in the microbody (peroxisome) with a certainty of 0.3000.
  • the most likely cleavage site for NOV9b is between positions 64 and 65: GNA-LV.
  • Table 9D Encoded NOV9b protein sequence (SEQ DD NO:48).
  • NOV9b is predicted to be expressed in at least the following tissues: lower small intestine, colon, and pancreas, brain, hypothalamus, kidney, pancreatic cancer, prostate, prostate cancer, glioblastoma, astrocytoma, normal human luminar mammary epithelial cells, breast cancer, ovary, cystadenoma. .
  • the disclosed NOV9a polypeptide has homology to the amino acid .sequences shown in the BLASTP data listed in Table 9E.
  • Tables 9G-9H list the domain descriptions from DOMAIN analysis results against NOV9. This indicates that the NOV9 sequence has properties similar to those of other proteins known to contain this domain.
  • CD-Length 254 residues, 100.0% aligned
  • the NOV9 nucleic acids and polypeptides share structure similarity to members to the Neuropeptide Y/Peptide YY/ Orexin Galanin/ Cholecystokinin/pancreatic polypeptide receptor family Neuropeptide Y (NPY) is one of the most abundant neuropeptides in the mammalian nervous system and exhibits a diverse range of important physiologic activities, including effects on psychomotor activity, food intake, regulation of central endocrine secretion, and potent vasoactive effects on the cardiovascular system. It shows sequence homology to peptide YY and over 50% homology in amino acid and nucleotide sequence to pancreatic polypeptide.
  • Neuropeptide Y signals through a family of G protein-coupled receptors present in the brain and sympathetic neurons. At least 3 types of neuropeptide Y receptor have been defined on the basis of pharmacologic criteria, tissue distribution, and structure of the encoding gene.
  • the NPY Yl receptors have been identified in a variety of tissues, including brain, spleen, small intestine, kidney, testis, placenta, and aortic smooth muscle.
  • the Y2 receptor is found mainly in the central nervous system.
  • Orexin A and Orexin B are derived from the same precursor, orexin, or hypocretin
  • OX2R HCRT
  • OX1R OX1R
  • Northern blot analysis revealed that in the rat a 3.5-kb OX2R mRNA is expressed exclusively in the brain. When administered intracerebroventricularly to rats, orexin A and orexin B stimulated food consumption.
  • preproorexin mRNA levels are upregulated upon fasting, thust these peptides are mediators in the central feedback mechanism that regulates feeding behavior.
  • PYY is secreted from endocrine cells in the lower small intestine, colon, and pancreas.
  • pancreatic polypeptide receptors acts through the pancreatic polypeptide receptors in the gastrointestinal tract as an inhibitor of gastric acid secretion, gastric emptying, digestive enzyme secretion by the pancreas, and gut motility.
  • the disclosed NOV9 nucleic acid of the invention encoding a Neuropeptide Y/Peptide YY receptor -like protein includes the nucleic acid whose sequence is provided in Table 9A or a fragment thereof.
  • the invention also includes a mutant or variant nucleic acid any of whose bases may be changed from the corresponding base shown in Table 9A while still encoding a protein that maintains its Neuropeptide Y/Peptide YY receptor -like activities and physiological functions, or a fragment of such a nucleic acid.
  • the invention further includes nucleic acids whose sequences are complementary to those just described, including nucleic acid fragments that are complementary to any of the nucleic acids just described.
  • the invention additionally includes nucleic acids or nucleic acid fragments, or complements thereto, whose structures include chemical modifications.
  • modifications include, by way of nonlimiting example, modified bases, and nucleic acids whose sugar phosphate backbones are modified or derivatized. These modifications are carried out at least in part to enhance the chemical stability of the modified nucleic acid, such that they may be used, for example, as antisense binding nucleic acids in therapeutic applications in a subject. In the mutant or variant nucleic acids, and their complements, up to about 15 percent of the bases may be so changed.
  • the disclosed NOV9 protein of the invention includes the Neuropeptide Y/Peptide YY receptor -like protein whose sequence is provided in Table 9B.
  • the invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residue shown in Table 9B while still encoding a protein that maintains its Neuropeptide Y/Peptide YY receptor -like activities and physiological functions, or a functional fragment thereof.
  • a mutant or variant protein any of whose residues may be changed from the corresponding residue shown in Table 9B while still encoding a protein that maintains its Neuropeptide Y/Peptide YY receptor -like activities and physiological functions, or a functional fragment thereof.
  • up to about 70 percent of the residues may be so changed.
  • the invention further encompasses antibodies and antibody fragments, such as F ab or (F a b) 2 ,that bind immunospecifically to any of the proteins of the invention.
  • This Neuropeptide Y/Peptide YY receptor -like protein (NOV9) is a member of a "Neuropeptide Y/Peptide YY receptor family". Therefore, the NOV9 nucleic acids and proteins identified here may be useful in potential therapeutic applications implicated in (but not limited to) various pathologies and disorders as indicated below.
  • the potential therapeutic applications for this invention include, but are not limited to: protein therapeutic, small molecule drug target, antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), diagnostic and/or prognostic marker, gene therapy (gene delivery/gene ablation), research tools, tissue regeneration in vivo and in vitro of all tissues and cell types composing (but not limited to) those defined here.
  • the NOV9 nucleic acids and proteins of the invention are useful in potential therapeutic applications implicated in obesity, diabetes, kidney disorders, cardiovascular disorders, anorexia, eating disorders, gastrointestinal and digestive diseases, metabolic diseases,CNS disorders, cancer, autoimmune disease, inflammation, and/or other pathologies and disorders.
  • NOV9 nucleic acids and polypeptides are further useful in the generation of antibodies that bind immuno-specifically to the novel NOV9 substances for use in therapeutic or diagnostic methods.
  • These antibodies may be generated according to methods known in the art, using prediction from hydrophobicity charts, as described in the "Anti-NOVX Antibodies" section below.
  • the disclosed NOV9 protein has multiple hydrophilic regions, each of which can be used as an immunogen. These novel proteins can be used in assay systems for functional analysis of various human disorders, which will help in understanding of pathology of the disease and development of new drug targets for various disorders.
  • NOV10 A disclosed NOV 10 nucleic acid of 985 nucleotides (also referred to as CG55964-01) encoding a novel G-Protein Coupled Receptor-like protein is shown in Table 10A. An open reading frame was identified beginning with an ATG initiation codon at nucleotides 33-35 and ending with a TGA codon at nucleotides 981-983.- A putative untranslated region upstream from the initiation codon is underlined in Table 10A. The start and stop codons are in bold letters. Table 10A. NOVIO nucleotide sequence (SEQ ID NO:49).
  • NOV10 polypeptide (SEQ ID NO:50) encoded by SEQ ID NO:49 has 316 amino acid residues and is presented in Table 10B using the one-letter amino acid code.
  • Signal P, Psort and/or Hydropathy results predict that NOV 10b has a signal peptide and is likely to be localized to the endoplasmic reticulum (membrane) with a certainty of 0.6850.
  • NOV10 may also localize to the plasma membrane with a certainty of 0.6400, the Golgi body with a certainty of 0.4600, or in the endoplasmic reticulum (lumen) with a certainty of 0.1000.
  • the most likely cleavage site for NOV10 is between positions 24 and 25: LES-VQ.
  • Table 10B Encoded NOV10 protein sequence (SEQ ID NO:50).
  • NOVIO is predicted to be expressed in at least Apical micro villi of the retinal pigment epithelium, arterial (aortic), basal forebrain, brain, Burkitt lymphoma cell lines, corpus callosum, cardiac (atria and ventricle), caudate nucleus, CNS and peripheral tissue, cerebellum, cerebral cortex, colon, cortical neurogenic cells, endothelial (coronary artery and umbilical vein) cells, palate epithelia, eye, neonatal eye, frontal cortex, fetal hematopoietic cells, heart, hippocampus, hypothalamus, leukocytes, liver, fetal liver, lung, lung lymphoma cell lines, fetal lymphoid tissue, adult lymphoid tissue, Those that express MHC II and III nervous, medulla, subthalamic nucleus, ovary, pancreas, pituitary, placenta, pons, prostate, putamen, serum, skeletal muscle, small
  • the disclosed NOVIO polypeptide has homology to the amino acid sequences shown in the BLASTP data listed in Table IOC.
  • Table 10E lists the domain description from DOMAIN analysis results against NOVIO. This indicates that the NOVIO sequence has properties similar to those of other proteins known to contain this domain.
  • CD-Length 254 residues, 100.0% aligned
  • NOV10 220 SYVQIFITVFQLPQKEARFKAFNTCIAHICVFLQF--YLLAFFSFFTHRFGSHIPPYIHI 277
  • GPCRs G-Protein Coupled Receptor
  • ORs Olfactory receptors
  • ORs Olfactory receptors
  • OR genes cloned in different species were from random locations in the respective genomes.
  • the human OR genes are intron less and belong to four different gene subfamilies, displaying great sequence variability. These genes are dominantly expressed in olfactory epithelium.
  • the disclosed NOVIO nucleic acid of the invention encoding a G-Protein Coupled
  • Receptor -like protein includes the nucleic acid whose sequence is provided in Table lOA or a fragment thereof.
  • the invention also includes a mutant or variant nucleic acid any of whose bases may be changed from the corresponding base shown in Table 10A while still encoding a protein that maintains its G-Protein Coupled Receptor-like activities and physiological functions, or a fragment of such a nucleic acid.
  • the invention further includes nucleic acids whose sequences are complementary to those just described, including nucleic acid fragments that are complementary to any of the nucleic acids just described.
  • the invention additionally includes nucleic acids or nucleic acid fragments, or complements thereto, whose structures include chemical modifications.
  • modifications include, by way of nonlimiting example, modified bases, and nucleic acids whose sugar phosphate backbones are modified or derivatized. These modifications are carried out at least in part to enhance the chemical stability of the modified nucleic acid, such that they may be used, for example, as antisense binding nucleic acids in therapeutic applications in a subject. In the mutant or variant nucleic acids, and their complements, up to about 19 percent of the bases may be so changed.
  • the disclosed NOVIO protein of the invention includes the G-Protein Coupled
  • the invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residue shown in Table 10B while still encoding a protein that maintains its G-Protein Coupled Receptor-like activities and physiological functions, or a functional fragment thereof. In the mutant or variant protein, up to about 25 percent of the residues may be so changed.
  • the invention further encompasses antibodies and antibody fragments, such as F a b or (F ab ) 2 ,that bind immunospecifically to any of the proteins of the invention.
  • NOVIO G-Protein Coupled Receptor-like protein
  • G-Protein Coupled Receptor family a member of a "G-Protein Coupled Receptor family”. Therefore, the NOV10 nucleic acids and proteins identified here may be useful in potential therapeutic applications implicated in (but not limited to) various pathologies and disorders as indicated below.
  • the potential therapeutic applications for this invention include, but are not limited to: protein therapeutic, small molecule drug target, antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), diagnostic and/or prognostic marker, gene therapy (gene delivery/gene ablation), research tools, tissue regeneration in vivo and in vitro of all tissues and cell types composing (but not limited to) those defined here.
  • NOVIO nucleic acids and proteins of the invention are useful in potential therapeutic applications implicated in developmental diseases, MHCII and III diseases (immune diseases), Taste and scent detectability Disorders, Burkitt's lymphoma,
  • Corticoneurogenic disease Signal Transduction pathway disorders, Retinal diseases including those involving photoreception, Cell Growth rate disorders; Cell Shape disorders, Feeding disorders;control of feeding; potential obesity due to over-eating; potential disorders due to starvation (lack of apetite), noninsulin-dependent diabetes mellitus (NIDDM1), bacterial, fungal, protozoal and viral infections (particularly infections caused by HIV-1 or HIV-2), pain, cancer (including but not limited to Neoplasm; adenocarcinoma; lymphoma; prostate cancer; uterus cancer), anorexia, bulimia, asthma, Parkinson's disease, acute heart failure, hypotension, hypertension, urinary retention, osteoporosis, Cr ⁇ hn's disease; multiple sclerosis; and Treatment of Albright Hereditary Ostoeodystrophy, angina pectoris, myocardial infarction, ulcers, asthma, allergies, benign prostatic hypertrophy, and psychotic and neurological disorders, including anxiety, schizophrenia, manic depression, delirium
  • NOV10 nucleic acids and polypeptides are further useful in the generation of antibodies that bind immuno-specifically to the novel NOVIO substances for use in therapeutic or diagnostic methods. These antibodies may be generated according to methods known in the art, using prediction from hydrophobicity charts, as described in the "Anti- NOVX Antibodies" section below.
  • the disclosed NOVIO protein has multiple hydrophilic regions, each of which can be used as an immunogen. These novel proteins can be used in assay systems for functional analysis of various human disorders, which will help in understanding of pathology of the disease and development of new drug targets for various disorders.
  • a disclosed NOV11 nucleic acid of 1014 nucleotides (also referred to as Curagen Accession No. CG55966-01) encoding a novel G-Protein Coupled Receptor -like protein is shown in Table 11 A.
  • An open reading frame was identified beginning with an ATG initiation codon at nucleotides 2-4 and ending with a TGA codon at nucleotides 947-949. Putative untranslated regions upstream from the initiation codon and downstream of the termination codon are underlined in Table 11 A. The start and stop codons are in bold letters.
  • Table 11A NOV11 nucleotide sequence (SEQ ID NO:51).
  • the disclosed NOV11 polypeptide (SEQ ID NO:52) encoded by SEQ ID NO:51 has 315 amino acid residues and is presented in Table 1 IB using the one-letter amino acid code.
  • Table 11B Encoded NOV11 protein sequence (SEQ ID NO:52).
  • the disclosed NOV11 polypeptide has homology to the amino acid sequences shown in the BLASTP data listed in Table 1 IC.
  • Table 1 IE lists the domain description from DOMAIN analysis results against NOVl 1. This indicates that the NOVl 1 sequence has properties similar to those of other proteins known to contain this domain.
  • CD-Length 254 residues, 100.0% aligned
  • NOVll 44 GNCMVLHVIWTEPSLHQPMFYFLSMLALTDLCMGLSTVYTVLGILWRIIREISLDSCIAQ 103
  • NOVll 224 ILKSVLAVA SQEERHKLFQTCISHICAVLVF--YIPIISLTMVHRFGKHLS 272
  • GPCRs G-Protein Coupled Receptor
  • ORs Olfactory receptors
  • OR genes cloned in different species were from random locations in the respective genomes.
  • the human OR genes are intron less and belong to four different gene subfamilies, displaying great sequence variability. These genes are dominantly expressed in olfactory epithelium.
  • the disclosed NOVl 1 nucleic acid of the invention encoding a G-Protein Coupled Receptor -like protein includes the nucleic acid whose sequence is provided in Table 11 A or a fragment thereof.
  • the invention also includes a mutant or variant nucleic acid any. of whose bases may be changed from the corresponding base shown in Table 11A while still encoding a protein that maintains its G-Protein Coupled Receptor-like activities and physiological functions, or a fragment of such a nucleic acid.
  • the invention further includes nucleic acids whose sequences are complementary to those just described, including nucleic acid fragments that are complementary to any of the nucleic acids just described.
  • the invention additionally includes nucleic acids or nucleic acid fragments, or complements thereto, whose structures include chemical modifications.
  • modifications include, by way of nonlimiting example, modified bases, and nucleic acids whose sugar phosphate backbones are modified or derivatized. These modifications are carried out at least in part to enhance the chemical stability of the modified nucleic acid, such that they may be used, for example, as antisense binding nucleic acids in therapeutic applications in a subject.
  • the disclosed NOVl 1 protein of the invention includes the G-Protein Coupled
  • the invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residue shown in Table 1 IB while still encoding a protein that maintains its G-Protein Coupled Receptor -like activities and physiological functions, or a functional fragment thereof. In the mutant or variant protein, up to about 47 percent of the residues may be so changed.
  • the invention further encompasses antibodies and antibody fragments, such as F a b or (F ab ) 2) that bind immunospecifically to any of the proteins of the invention.
  • NOVl 1 G-Protein Coupled Receptor-like protein
  • the above disclosed information suggests that this G-Protein Coupled Receptor-like protein (NOVl 1) is a member of a "G-Protein Coupled Receptor family". Therefore, the NOVl 1 nucleic acids and proteins identified here may be useful in potential therapeutic applications implicated in (but not limited to) various pathologies and disorders.
  • the potential therapeutic applications for this invention include, but are not limited to: protein therapeutic, small molecule drug target, antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), diagnostic and/or prognostic marker, gene therapy (gene delivery/gene ablation), research tools, tissue regeneration in vivo and in vitro of all tissues and cell types composing (but not limited to) those defined here.
  • NOVl 1 nucleic acids and proteins of the invention are useful in potential therapeutic applications implicated in developmental diseases, MHCII and III diseases (immune diseases), Taste and scent detectability Disorders, Burkitt's lymphoma, Corticoneurogenic disease, Signal Transduction pathway disorders, Retinal diseases including those involving photoreception, Cell Growth rate disorders; Cell Shape disorders, Feeding disorders;control of feeding; potential obesity due to over-eating; potential disorders due to starvation (lack of apetite), noninsulin-dependent diabetes mellitus (NIDDM1), bacterial, fungal, protozoal and viral infections (particularly infections caused by HIV-1 or HIV-2), pain, cancer (including but not limited to Neoplasm; adenocarcinoma; lymphoma; prostate cancer; uterus cancer), anorexia, bulimia, asthma, Parkinson's disease, acute heart failure, hypotension, hypertension, urinary retention, osteoporosis, Crohn's disease; multiple sclerosis; and Treatment of Albright Hereditary
  • DPLA Dentatorubro-pallidoluysian atrophy
  • NOVl 1 nucleic acids and polypeptides are further useful in the generation of antibodies that bind immuno-specifically to the novel NOVl 1 substances for use in therapeutic or diagnostic methods.
  • These antibodies may be generated according to methods known in the art, using prediction from hydrophobicity charts, as described in the "Anti- NOVX Antibodies” section below.
  • These novel proteins can be used in assay systems for functional analysis of various human disorders, which will help in understanding of pathology of the disease and development of new drug targets for various disorders.
  • a disclosed NOV 12 nucleic acid of 1067 nucleotides (also referred to as Curagen Accession No. CG56003-01) encoding a novel G-Protein Coupled Receptor -like protein is shown in Table 12A.
  • An open reading frame was identified beginning with an ATG initiation codon at nucleotides 15-17 and ending with a TGA codon at nucleotides 1023-1025.
  • the untranslated regions are underlined and the start and stop codons are in bold letters in Table 12A.
  • Table 12A NOV12 nucleotide sequence (SEQ ID NO:53).
  • the disclosed NOV12 polypeptide (SEQ ID NO 54) encoded by SEQ ID NO:53 has 336 amino acid residues and is presented in Table 12B using the one-letter amino acid code. Table 12B. Encoded NOV12 protein sequence (SEQ ID NO:54).
  • GPCRs G-Protein Coupled Receptor
  • the disclosed NOV12 polypeptide has homology to the amino acid sequences shown in the BLASTP data listed in Table 12C.
  • Table 12E lists the domain description from DOMAIN analysis results against NOV 12. This indicates that the NOV 12 sequence has properties similar to those of other proteins known to contain this domain.
  • CD-Length 254 residues, 99.6% aligned
  • NOV12 152 ARKLCIYIWGWLGIIIPVTVYYSVIEATEGEESLCYNRQMELGAMISQIAGLIGTTFIG 211
  • NOV12 271 IFYVLHQRDNCQQLNYLIETKNILTCLASARSSTDPII 308
  • Olfactory receptors have been identified as extremely large subfamily of G protein-coupled receptors in a number of species. These receptors share a seven transmembrane domain structure with many neurotransmitter and hormone receptors, and are likely to underlie the recognition and G-protein-mediated transduction of odorant signals.
  • OR genes cloned in different species were from random locations in the respective genomes. The human OR genes are intron less and belong to four different gene subfamilies, displaying great sequence variability. These genes are dominantly expressed in olfactory epithelium.
  • the disclosed NOV 12 nucleic acid of the invention encoding a G-Protein Coupled Receptor -like protein includes the nucleic acid whose sequence is provided in Table 12A or a fragment thereof.
  • the invention also includes a mutant or variant nucleic acid any of whose bases may be changed from the corresponding base shown in Table 12A while still encoding a protein that maintains its G-Protein Coupled Receptor-like activities and physiological functions, or a fragment of such a nucleic acid.
  • the invention further includes nucleic acids whose sequences are complementary to those just described, including nucleic acid fragments that are complementary to any of the nucleic acids just described.
  • the invention additionally includes nucleic acids or nucleic acid fragments, or complements thereto, whose structures include chemical modifications.
  • modifications include, by way of nonlimiting example, modified bases, and nucleic acids whose sugar phosphate backbones are modified or derivatized. These modifications are carried out at least in part to enhance the chemical stability of the modified nucleic acid, such that they may be used, for example, as antisense binding nucleic acids in therapeutic applications in a subject.
  • the disclosed NOV 12 protein of the invention includes the G-Protein Coupled Receptor-like protein whose sequence is provided in Table 12B.
  • the invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residue shown in Table 12B while still encoding a protein that maintains its G-Protein Coupled Receptor -like activities and physiological functions, or a functional fragment thereof. In the mutant or variant protein, up to about 77 percent of the residues may be so changed.
  • the invention further encompasses antibodies and antibody fragments, such as F ab or (Fab) 2 , that bind immunospecifically to any of the proteins of the invention.
  • antibodies and antibody fragments such as F ab or (Fab) 2 , that bind immunospecifically to any of the proteins of the invention.
  • NOV12 G-Protein Coupled Receptor-like protein
  • the above disclosed information suggests that this G-Protein Coupled Receptor-like protein (NOV12) is a member of a "G-Protein Coupled Receptor family". Therefore, the NOV 12 nucleic acids and proteins identified here may be useful in potential therapeutic applications implicated in (but not limited to) various pathologies and disorders as indicated below.
  • the potential therapeutic applications for this invention include, but are not limited to: protein therapeutic, small molecule drug target, antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), diagnostic and/or prognostic marker, gene therapy (gene delivery/gene ablation), research tools, tissue regeneration in vivo and in vitro of all tissues and cell types composing (but not limited to) those defined here.
  • the NOV 12 nucleic acids and proteins of the invention are useful in potential therapeutic applications implicated in developmental diseases, MHCII and III diseases (immune diseases), Taste and scent detectability Disorders, Burkitt's lymphoma, Corticoneurogenic disease, Signal Transduction pathway disorders, Retinal diseases including those involving photoreception, Cell Growth rate disorders; Cell Shape disorders, Feeding disorders;control of feeding; potential obesity due to over-eating; potential disorders due to starvation (lack of apetite), noninsulin-dependent diabetes mellitus (NIDDMl), bacterial, fungal, protozoal and viral infections (particularly infections caused by HIV-1 or HIV-2), pain, cancer (including but not limited to Neoplasm; adenocarcinoma; lymphoma; prostate cancer; uterus cancer), anorexia, bulimia, asthma, Parkinson's disease, acute heart failure, hypotension, hypertension, urinary retention, osteoporosis, Crohn's disease; multiple sclerosis; and Treatment of Albright Hereditary
  • DPLA Dentatorubro-pallidoluysian atrophy
  • NOV 12 nucleic acids and polypeptides are further useful in the generation of antibodies that bind immuno-specifically to the novel NOV12 substances for use in therapeutic or diagnostic methods. These antibodies may be generated according to methods known in the art, using prediction from hydrophobicity charts, as described in the "Anti- NOVX Antibodies" section below.
  • the disclosed NOV 12 protein has multiple hydrophilic regions, each of which can be used as an immunogen. These novel proteins can be used in assay systems for functional analysis of various human disorders, which will help in understanding of pathology of the disease and development of new drug targets for various disorders. NOV13
  • NOV 13 includes three novel G-Protein Coupled Receptor -like proteins disclosed below. The disclosed sequences have been named NOV13a and NOV13b.
  • NOV13a A disclosed NOV 13a nucleic acid of 961 nucleotides (also referred to as CG56075-01) encoding a novel G-Protein Coupled Receptor -like protein is shown in Table 13 A.
  • An open reading frame was identified beginning with an ATG initiation codon at nucleotides 12-14 and ending with a TGA codon at nucleotides 936-938. The start and stop codons are shown in bold in Table 13 A, and the 5' and 3' untranslated regions, if any, are underlined.
  • Table 13A NOV13a nucleotide sequence (SEQ DD NO:55).
  • the disclosed NOV 13a polypeptide (SEQ ID NO:56) encoded by SEQ ID NO:55 has 308 amino acid residues and is presented in Table 13B using the one-letter amino acid code.
  • Table 13B Encoded NOV13a protein sequence (SEQ ID NO:56).
  • a disclosed NOV 13b nucleic acid of 961 nucleotides (also referred to as CG56021-02) encoding a novel G-Protein Coupled Receptor -like protein is shown in Table 13C.
  • An open reading frame was identified beginning with an ATG initiation codon at nucleotides 12-14 and ending with a TGA codon at nucleotides 936-938.
  • a putative untranslated region upstream from the initiation codon is underlined in Table 13C. The start and stop codons are in bold letters.
  • Table 13C NOV13b nucleotide sequence (SEQ DD NO:57).
  • the NOV 13b nucleic acid sequence has 648 of 653 bases (99%) identical to a gb:GENBANK-ID:AF065876
  • acc:AF065876.1 mRNA from Homo sapiens (olfactory receptor (OR2D2) gene, partial cds) (E 2.8e " ).
  • NOVl 3b polypeptide (SEQ ID NO:58) encoded by SEQ ID NO:57 has 308 amino acid residues and is presented in Table 13D using the one-letter amino acid code.
  • Signal P, Psort and/or Hydropathy results predict that NOVl 3b has a signal peptide and is likely to be localized to the plasma membrane with a certainty of 0.6000.
  • NOV 13b may also localize to the Golgi body with a certainty of 0.4000, the endoplasmic reticulum (membrane) with a certainty of 0.3000, or in the microbody (peroxisome) with a certainty of 0.3000.
  • the most likely cleavage site for NOVl 3b is between positions 53 and 54: VDS-QL.
  • Table 13D Encoded NOV13b protein sequence (SEQ ID NO:58).
  • NOV 13b is predicted to be expressed in at least Apical microvilli of the retinal pigment epithelium, arterial (aortic), basal forebrain, brain, Burkitt lymphoma cell lines, corpus callosum, cardiac (atria and ventricle), caudate nucleus, CNS and peripheral tissue, cerebellum, cerebral cortex, colon, cortical neurogenic cells, endothelial (coronary artery and umbilical vein) cells, palate epithelia, eye, neonatal eye, frontal cortex, fetal hematopoietic cells, heart, hippocampus, hypothalamus, leukocytes, liver, fetal liver, lung, lung lymphoma cell lines, fetal lymphoid tissue, adult lymphoid tissue, Those that express MHC II and III nervous, medulla, subthalamic nucleus, ovary, pancreas, pituitary, placenta, pons, prostate, putamen, serum, skeletal muscle,
  • the disclosed NOV13a polypeptide has homology to the amino acid sequences shown in the BLASTP data listed in Table 13E.

Abstract

L'invention concerne des séquences nucléotidiques codant de nouveaux polypeptides. L'invention concerne également des polypeptides codés par ces nouvelles séquences nucléotidiques, ainsi que des anticorps se fixant de manière immunospécifique au polypeptide et des dérivés, des variants, des mutants ou des fragments du polypeptide, du polynucléotide ou de l'anticorps précités. L'invention concerne en outre des méthodes thérapeutiques, diagnostiques et de recherche destinées au diagnostic, au traitement ainsi qu'à la prévention de troubles impliquant n'importe lequel de ces nouveaux acides nucléiques humains et de ces nouvelles protéines humaines.
EP02784815A 2001-01-31 2002-01-31 Proteines et acides nucleiques codant ces proteines Withdrawn EP1409681A2 (fr)

Applications Claiming Priority (109)

Application Number Priority Date Filing Date Title
US26551701P 2001-01-31 2001-01-31
US26551401P 2001-01-31 2001-01-31
US26539501P 2001-01-31 2001-01-31
US26541201P 2001-01-31 2001-01-31
US265412P 2001-01-31
US265514P 2001-01-31
US265395P 2001-01-31
US265517P 2001-01-31
US26640601P 2001-02-02 2001-02-02
US266406P 2001-02-02
US26676701P 2001-02-05 2001-02-05
US266767P 2001-02-05
US26697501P 2001-02-07 2001-02-07
US26705701P 2001-02-07 2001-02-07
US266975P 2001-02-07
US267057P 2001-02-07
US26745901P 2001-02-08 2001-02-08
US267459P 2001-02-08
US26782301P 2001-02-09 2001-02-09
US267823P 2001-02-09
US26897401P 2001-02-15 2001-02-15
US268974P 2001-02-15
US27166401P 2001-02-26 2001-02-26
US271664P 2001-02-26
US27183901P 2001-02-27 2001-02-27
US27185501P 2001-02-27 2001-02-27
US271855P 2001-02-27
US271839P 2001-02-27
US27278801P 2001-03-02 2001-03-02
US27304601P 2001-03-02 2001-03-02
US272788P 2001-03-02
US273046P 2001-03-02
US27598901P 2001-03-14 2001-03-14
US27592501P 2001-03-14 2001-03-14
US27594701P 2001-03-14 2001-03-14
US27595001P 2001-03-14 2001-03-14
US275950P 2001-03-14
US275989P 2001-03-14
US275925P 2001-03-14
US275947P 2001-03-14
US27645001P 2001-03-15 2001-03-15
US27644801P 2001-03-15 2001-03-15
US276448P 2001-03-15
US276450P 2001-03-15
US27639701P 2001-03-16 2001-03-16
US27676801P 2001-03-16 2001-03-16
US276397P 2001-03-16
US276768P 2001-03-16
US27865201P 2001-03-20 2001-03-20
US278652P 2001-03-20
US27877801P 2001-03-26 2001-03-26
US27877501P 2001-03-26 2001-03-26
US278778P 2001-03-26
US278775P 2001-03-26
US27988401P 2001-03-29 2001-03-29
US27988201P 2001-03-29 2001-03-29
US279884P 2001-03-29
US279882P 2001-03-29
US28014701P 2001-03-30 2001-03-30
US280147P 2001-03-30
US28308301P 2001-04-11 2001-04-11
US28299201P 2001-04-11 2001-04-11
US283083P 2001-04-11
US282992P 2001-04-11
US28513301P 2001-04-20 2001-04-20
US285133P 2001-04-20
US28574901P 2001-04-23 2001-04-23
US285749P 2001-04-23
US28832701P 2001-05-03 2001-05-03
US28850401P 2001-05-03 2001-05-03
US29404701P 2001-05-29 2001-05-29
US294047P 2001-05-29
US29447301P 2001-05-30 2001-05-30
US294473P 2001-05-30
US29696401P 2001-06-08 2001-06-08
US29895901P 2001-06-18 2001-06-18
US298959P 2001-06-18
US29932401P 2001-06-19 2001-06-19
US299324P 2001-06-19
US31202001P 2001-08-13 2001-08-13
US312020P 2001-08-13
US31290801P 2001-08-16 2001-08-16
US31288901P 2001-08-16 2001-08-16
US312908P 2001-08-16
US312889P 2001-08-16
US31339001P 2001-08-21 2001-08-21
US313390P 2001-08-21
US31547001P 2001-08-28 2001-08-28
US315470P 2001-08-28
US31644701P 2001-08-31 2001-08-31
US316447P 2001-08-31
US31811801P 2001-09-07 2001-09-07
US31811501P 2001-09-07 2001-09-07
US318115P 2001-09-07
US31874001P 2001-09-12 2001-09-12
US318740P 2001-09-12
US32337901P 2001-09-19 2001-09-19
US323379P 2001-09-19
US33024501P 2001-10-18 2001-10-18
US33030801P 2001-10-18 2001-10-18
US330245P 2001-10-18
US330308P 2001-10-18
US33270101P 2001-11-14 2001-11-14
US332701P 2001-11-14
PCT/US2002/002785 WO2002068649A2 (fr) 2001-01-31 2002-01-31 Proteines et acides nucleiques les codant
US288327P 2009-12-20
US288504P 2009-12-21
US296964P 2010-01-21
US318118P 2010-03-26

Publications (1)

Publication Number Publication Date
EP1409681A2 true EP1409681A2 (fr) 2004-04-21

Family

ID=29220168

Family Applications (1)

Application Number Title Priority Date Filing Date
EP02784815A Withdrawn EP1409681A2 (fr) 2001-01-31 2002-01-31 Proteines et acides nucleiques codant ces proteines

Country Status (2)

Country Link
EP (1) EP1409681A2 (fr)
CA (1) CA2437364A1 (fr)

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO02068649A3 *

Also Published As

Publication number Publication date
CA2437364A1 (fr) 2002-09-06

Similar Documents

Publication Publication Date Title
WO2002068649A2 (fr) Proteines et acides nucleiques les codant
US20040067490A1 (en) Therapeutic polypeptides, nucleic acids encoding same, and methods of use
WO2003023008A9 (fr) Polypeptides therapeutiques, acides nucleiques les codant, et modalites d'emploi correspondantes
WO2002064791A2 (fr) Proteines et acides nucleiques codant celles-ci
WO2002050277A2 (fr) Proteines et acides nucleiques codant pour celles-ci
US20040029222A1 (en) Proteins and nucleic acids encoding same
US7033790B2 (en) Proteins and nucleic acids encoding same
US7109000B2 (en) Proteins and nucleic acids encoding same
US20040033493A1 (en) Proteins and nucleic acids encoding same
US20040010119A1 (en) Novel proteins and nucleic acids encoding same
WO2002081517A2 (fr) Nouveaux polypeptides et acides nucleiques codant pour ces derniers
US20040009907A1 (en) Proteins and nucleic acids encoding same
WO2003010327A2 (fr) Nouvelles proteines et acides nucleiques les codant
WO2002081625A2 (fr) Nouveaux anticorps se liant a des polypeptides antigeniques, acides nucleiques codant pour ces antigenes, et procedes d'utilisation de ceux-ci
WO2002072757A2 (fr) Proteines et acides nucleiques codant pour ces proteines
WO2003031571A2 (fr) Nouvelles proteines humaines, polynucleotides les codant et methodes d'utilisation afferentes
US20040038223A1 (en) Novel proteins and nucleic acids encoding same
CA2448540A1 (fr) Polypeptides therapeutiques, acides nucleiques codant ces polypeptides, et leurs procedes d'utilisation
US20040043382A1 (en) Novel proteins and nucleic acids encoding same
WO2002046408A2 (fr) Nouvelles proteines humaines, polynucleotides les codant et procedes d'utilisation
EP1409681A2 (fr) Proteines et acides nucleiques codant ces proteines
AU2002306434A1 (en) Proteins and nucleic acids encoding same
WO2002059313A2 (fr) Nouvelles proteines, et acides nucleiques codant pour elles
EP1390057A2 (fr) Anticorps se liant aux polypeptides antigeniques, acides nucleiques codant les antigenes, et method d'utilisation
EP1686175A2 (fr) Protéines et acides nucléiques les codant

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: 20030827

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 LU MC NL PT SE TR

AX Request for extension of the european patent

Extension state: AL LT LV MK RO SI

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

Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN

18W Application withdrawn

Effective date: 20051104