Cytokine that induces apoptosis
AssigneeImmunex Corporation
InventorsSteven R. Wiley, Raymond G. Goodwin
Life of this patent
Estimating the term…
Abstract
A novel cytokine designated TRAIL induces apoptosis of certain target cells, including cancer cells and virally infected cells. Isolated DNA sequences encoding TRAIL are disclosed, along with expression vectors and transformed host cells useful in producing TRAIL polypeptides. Antibodies that specifically bind TRAIL are provided as well.
Claims59
A purified tumor necrosis factor related apoptosis inducing ligand (TRAIL) polypeptide comprising an amino acid sequence that is at least 90% identical to an amino acid sequence selected from the group consisting of amino acids 1 to 281 of SEQ ID NO:2 and amino acids 1 to 291 of SEQ ID NO:6, wherein said TRAIL polypeptide induces apoptosis of Jurkat cells.
A purified TRAIL polypeptide comprising an amino acid sequence selected from the group consisting of amino acids I to 281 of SEQ ID NO:2 and amino acids I to 291 of SEQ ID NO:6.
A purified human TRAIL polypeptide encoded by the cDNA insert of the recombinant vector deposited in strain ATCC 69849.
A purified soluble TRAIL polypeptide comprising an amino acid sequence that is at least 90% identical to a sequence selected from the group consisting of:
- a) the extracellular domain of human TRAIL (amino acids 39 to 281 of SEQ ID NO:2);
- and
- b) a fragment of said extracellular domain;
- wherein said soluble TRAIL polypeptide induces apoptosis of Jurkat cells.
A purified TRAIL polypeptide comprising the sequence of amino acids x to 281 of SEQ ID NO:2, wherein x represents an integer from 39 to 95.
A purified TRAIL polypeptide, wherein said polypeptide is a fragment of the human TRAIL protein of SEQ ID NO:2, wherein said fragment induces apoptosis of Jurkat cells.
A protein expressed by CHO cells transformed with an expression vector comprising the nucleotide sequence presented in SEQ ID NO:10.
A protein expressed by CHO cells transformed with an expression vector comprising the nucleotide sequence presented in SEQ ID NO:12.
A purified soluble TRAIL polypeptide, comprising an amino acid sequence that is at least 90% identical to a sequence selected from the group consisting of:
- a) the extracellular domain of mouse TRAIL (amino acids 39 to 291 of SEQ ID NO:6);
- and
- b) a fragment of said extracellular domain, wherein said fragment induces apoptosis of Jurkat cells.
A purified TRAIL protein, wherein said protein is expressed by E. coli cells transformed with an expression vector comprising a nucleotide sequence selected from the group consisting of:
- a) nucleotides 88 to 933 of the sequence presented as SEQ ID NO:1;
- b) nucleotides 47 to 922 of the sequence presented as SEQ ID NO:5;
- c) a fragment of the nucleotide sequence of (a);
- d) a fragment of the nucleotide sequence of (b);
- and
- e) a nucleotide sequence that is degenerate as a result of the genetic code to a sequence of (a), (b), (c), or (d);
- wherein said protein induces apoptosis of TRAIL-sensitive cancer cells.
A purified polypeptide comprising amino acids 124 to 276 of SEQ ID NO:2.
A purified polypeptide, wherein said polypeptide is a soluble fragment of the TRAIL protein of SEQ ID NO:2, wherein the N-terminal amino acid of said fragment is selected from residues 39 to 124 of SEQ ID NO:2, and the C-terminal amino acid of said fragment is selected from residues 276 to 281 of SEQ ID NO:2.
A purified polypeptide comprising a fragment of the protein of SEQ ID NO:2, wherein said fragment kills TRAIL-sensitive target cells.
A purified TRAIL polypeptide comprising the amino acid sequence presented in SEQ ID NO:2 or SEQ ID NO:6, with the proviso that said polypeptide [lacks the transmembrane region of the protein of SEQ ID NO:2 or SEQ ID NO:6 OR] lacks a transmembrane region, wherein said polypeptide is capable of killing TRAIL-sensitive target cells.
A purified oligomer comprising two or more TRAIL polypeptides, wherein each of said TRAIL polypeptides is a fragment of the protein of SEQ ID NO:2, wherein said oligomer kills TRAIL-sensitive target cells.
Dependencies are inferred from the claim text.