Recombinant soluble CD40 ligand polypeptide and pharmaceutical composition containing the same
AssigneeImmunex Corporation
InventorsRichard J. Armitage, William C. Fanslow, Melanie K. Spriggs, Subhashini Srinivasan, Marylou G. Gibson, Arvia E. Morris, Jeffrey T. McGrew
Life of this patent
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Abstract
There is disclosed a polypeptide (CD40-L) and DNA sequences, vectors and transformed host cells useful in providing CD40-L polypeptides. More particularly, this invention provides isolated human and murine CD40-L polypeptides that bind to the extracellular binding region of a CD40 receptor.
Claims71
A recombinant, soluble CD40L polypeptide that binds CD40, and lacks a CD40L transmembrane region, and that comprises a polypeptide selected from the group consisting of:
- (a) a polypeptide comprising amino acids 47 through 261 of SEQ ID NO:12;
- (b) a polypeptide comprising amino acids 51 through 261 of SEQ ID NO:12;
- (c) a polypeptide comprising amino acids 120 through 261 of SEQ ID NO:12;
- and
- (d) a polypeptide comprising amino acids 113 through 261 of SEQ ID NO:12.
A recombinant, soluble CD40L polypeptide that binds CD40 and that lacks a CD40L transmembrane region, and that is encoded by a DNA molecule selected from the group consisting of:
- (a) a DNA molecule comprising nucleotides 184 through 828 of SEQ ID NO:11;
- (b) a DNA molecule comprising nucleotides 196 through 828 of SEQ ID NO:11;
- (c) a DNA molecule comprising nucleotides 403 through 828 of SEQ ID NO:11;
- (d) a DNA molecule comprising nucleotides 382 through 828 of SEQ ID NO:11;
- and
- (e) a DNA molecule which hybridizes to at least one of the DNA molecules of (a)-(d), under moderately stringent conditions (prewashing solution of 5.times.SSC, 0.5% SDS, 1.0 mM EDTA (pH 8.0) and hybridization conditions of 50.degree. C., 5.times.SSC, overnight).
A recombinant, soluble CD40L polypeptide that binds to CD40 and that is secreted from host cells, which polypeptide is obtained by recombinant expression in the host cells of a DNA molecule selected from the group consisting of:
- (a) a DNA molecule comprising nucleotides 184 through 828 of SEQ ID NO:11;
- (b) a DNA molecule comprising nucleotides 196 through 828 of SEQ ID NO:11;
- (c) a DNA molecule comprising nucleotides 403 through 828 of SEQ ID NO:11;
- (d) a DNA molecule comprising nucleotides 382 through 828 of SEQ ID NO:11;
- and
- (e) a DNA molecule which hybridizes to at least one of the DNA molecules of (a)-(d), under moderately stringent conditions (prewashing solution of 5.times.SSC, 0.5% SDS, 1.0 mM EDTA (pH 8.0) and hybridization conditions of 50.degree. C., 5.times.SSC, overnight).
A recombinant, soluble CD40L polypeptide that binds CD40, and lacks a CD40L transmembrane region, and that comprises a polypeptide comprising amino acids 113 through 261 of SEQ ID NO:12, wherein the cysteine at amino acid 194 of SEQ ID NO:12 is substituted with tryptophan, and which further comprises a leucine zipper as set forth in SEQ ID NO:17.
A recombinant, soluble CD40L polypeptide that binds to CD40 and that lacks a CD40L transmembrane region, and that comprises amino acids 47 through 260 of SEQ ID NO:2 or amino acids 119 through 260 of SEQ ID NO:2.
A recombinant, soluble CD40L polypeptide that binds to CD40 and that lacks a CD40L transmembrane region, which polypeptide is encoded by a DNA molecule selected from the group consisting of:
- (a) a DNA molecule comprising nucleotides 139 through 780, or 355 through 780 of SEQ ID NO:1;
- and
- (b) a DNA molecule which hybridzes to at least one of the DNA molecules of (a) under moderately stringent conditions (prewashing solution of 5.times.SSC, 0.5% SDS, 1.0 mM EDTA (pH 8.0) and hybridization conditions of 50.degree. C., 5.times.SSC, overnight).
A recombinant, soluble CD40L polypeptide that binds to CD40 and that is secreted from host cells, which polypeptide is obtained by recombinant expression in the host cells of a DNA molecule selected from the group consisting of:
- (a) a DNA molecule comprising nucleotides 139 through 780, or 355 through 780 of SEQ ID NO:1;
- and
- (b) a DNA molecule which hybridzes to at least one of the DNA molecules of (a) under moderately stringent conditions (prewashing solution of 5.times.SSC, 0.5% SDS, 1.0 mM EDTA (pH 8.0) and hybridization conditions of 50.degree. C., 5.times.SSC, overnight).
Dependencies are inferred from the claim text.