Neutrokine-alpha
AssigneeHuman Genome Sciences, Inc.
InventorsGuo-Liang Yu, Reinhard Ebner, Jian Ni
Life of this patent
Estimating the term…
Abstract
The present invention relates to a novel Neutrokine-α protein which is a member of the TNF protein family. In particular, isolated nucleic acid molecules are provided encoding the human Neutrokine-α protein including soluble forms of the extracellular domain. Neutrokine-α polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of Neutrokine-α activity. Also provided are diagnostic methods for detecting immune system-related disorders and therapeutic methods for treating immune system-related disorders.
Claims23
An isolated nucleic acid molecule comprising a polynucleotide having a nucleotide sequence at least 95% identical to a sequence selected from the group consisting of:
- (a) a nucleotide sequence encoding the Neutrokine-α polypeptide having the complete amino acid sequence in FIG. 1 (SEQ ID NO:2);
- (b) a nucleotide sequence encoding the Neutrokine-α polypeptide having the complete amino acid sequence encoded by the cDNA clone contained in ATCC No. 97768 deposited on Oct. 22, 1996;
- (c) a nucleotide sequence encoding the Neutrokine-α polypeptide extracellular domain;
- (d) a nucleotide sequence encoding the Neutrokine-α polypeptide transmembrane domain;
- (e) a nucleotide sequence encoding the Neutrokine-α polypeptide intracellular domain;
- (f) a nucleotide sequence encoding a soluble Neutrokine-α polypeptide comprising the extracellular and intracellular domains but lacking the transmembrane domain;
- and
- (g) a nucleotide sequence complementary to any of the nucleotide sequences in (a), (b), (c), (d), (e) or (f) above.
An isolated nucleic acid molecule comprising a polynucleotide having a nucleotide sequence at least 95% identical to a sequence selected from the group consisting of:
- (a) a nucleotide sequence encoding a polypeptide having the amino acid sequence consisting of residues n-285 of SEQ ID NO:2, where n is an integer in the range of 2-190
- (b) a nucleotide sequence encoding a polypeptide having the amino acid sequence consisting of residues 1-m of SEQ ID NO:2, where m is an integer in the range of 274-284;
- (c) a nucleotide sequence encoding a polypeptide having the amino acid sequence consisting of residues n-m of SEQ ID NO:2, where n and m are integers as defined respectively in (a) and (b) above;
- and
- (d) a nucleotide sequence encoding a polypeptide consisting of a portion of the complete Neutrokine-α amino acid sequence encoded by the cDNA clone contained in ATCC No. 97768 deposited on Oct. 22, 1996 wherein said portion excludes from 1 to 190 amino acids from the amino terminus and from 1 to 11 amino acids from the C-terminus of said complete amino acid sequence.
An isolated Neutrokine-α polypeptide comprising an amino acid sequence at least 95% identical to a sequence selected from the group consisting of:
- (a) the amino acid sequence of the Neutrokine-α polypeptide having the complete amino acid sequence in FIG. 1 (SEQ ID NO:2);
- (b) the amino acid sequence of the Neutrokine-α polypeptide having the complete amino acid sequence encoded by the cDNA clone contained in the ATCC No. 97768 deposited on Oct. 22, 1996;
- (c) the amino acid sequence of the Neutrokine-α polypeptide extracellular domain;
- (d) the amino acid sequence of the Neutrokine-α polypeptide transmembrane domain;
- (e) the amino acid sequence of the Neutrokine-α polypeptide intracellular domain;
- (f) the amino acid sequence of a soluble Neutrokine-α polypeptide comprising the domain;
- and
- (g) the amino acid sequence of an epitope-bearing portion of any one of the polypeptides of (a), (b), (c), (d), (e) or (f).
An isolated polynucleotide encoding a modified Neutrokine-α protein, wherein, except for at least one conservative amino acid substitution, said modified peptide has an amino acid sequence that is identical to a member selected from the group consisting of:
- (a) amino acids 1 to 285 of SEQ ID NO:2;
- (b) amino acids 2 to 285 of SEQ ID NO:2;
- (c) amino acids 1 to 46 of SEQ ID NO:2;
- (c) amino acids 47 to 72 of SEQ ID NO:2;
- and
- (c) amino acids 73 to 286 of SEQ ID NO:2.
A modified Neutrokine-α polypeptide molecule, wherein, except for at least one conservative amino acid substitution, said modified peptide has an amino acid sequence that is identical to a member selected from the group consisting of:
- (a) amino acids 1 to 285 of SEQ ID NO:2;
- (b) amino acids 2 to 285 of SEQ ID NO:2;
- (c) amino acids 1 to 46 of SEQ ID NO:2;
- (c) amino acids 47 to 72 of SEQ ID NO:2;
- and
- (c) amino acids 73 to 286 of SEQ ID NO:2.
An isolated nucleic acid molecule comprising a polynucleotide having a sequence at least 95% identical to a sequence selected selected from the group consisting of:
- (a) the nucleotide sequence of SEQ ID NO:7;
- (b) the nucleotide sequence of SEQ ID NO:8;
- (c) the nucleotide sequence of SEQ ID NO:9;
- (d) the nucleotide sequence of a portion of the sequence shown in FIG. 1 (SEQ ID NO:1) wherein said portion comprises at least 30 contiguous nucleotides from nucleotide 1 to nucleotide 2442, excluding the sequence from nucleotide 1387 to 1421, the sequence from nucleotide 9 to 382, the sequence from nucleotide 1674 to 1996, the sequence from nucleotide 1401 to 1784, the sequence from nucleotide 900 to 1237, and any fragments located within these sequences;
- and
- (e) a nucleotide sequence complementary to any of the nucleotide sequences in (a), (b), (c) or (d) above.
Dependencies are inferred from the claim text.