Human recombinant interleukin-2 muteins
AssigneeCetus Corporation
InventorsDavid F. Mark, Leo S. Lin, Shi-Da Y. Lu
Life of this patent
Estimating the term…
Abstract
Muteins of biologically active proteins such as IFN-.beta. and IL-2 in which cysteine residues that are not essential to biological activity have been deleted or replaced with other amino acids to eliminate sites for intermolecular crosslinking or incorrect intramolecular disulfide bridge formation. These muteins are made via bacterial expression of mutant genes that encode the muteins that have been synthesized from the genes for the parent proteins by oligonucleotide-directed mutagenesis.
Claims10
Recombinant human interleukin-2 mutein. wherein the cysteine at position 125, numbered in accordance with native human interleukin-2, is deleted or replaced by a neutral amino acid and said mutein exhibits the biological activity of native, human interleukin-2.
Human recombinant alanyl-interleukin-2.sub.serine125 mutein.
Human recombinant des-alanyl-interleukin-2.sub.serine125 mutein.
Human recombinant interleukin-2.sub.serine125 mutein which exhibits the biological activity of native human interleukin-2 and which has the deduced amino acid sequence as represented in FIG. 15b with and without N-terminal methionine.
A formulation for the diagnosis or therapeutic treatment (local or systemic) of bacterial, viral, parasitic, protozoan and fungal infections;
- for augmenting cell-mediated cytotoxicity;
- for stimulating lymphokine activated killer cell activity;
- for mediating recovery of immune function of lymphocytes;
- for augmenting alloantigen responsiveness;
- for facilitating recovery of immune function in acquired immune deficient states;
- for reconstitution of normal immunofunction in aged humans and animals;
- in the development of diagnostic assays such as those employing enzyme amplification, radiolabelling, radioimaging;
- for monitoring interleukin-2 levels in the diseased state;
- and for the promotion of T cell growth in vitro for therapeutic and diagnostic purposes for blocking receptor sites for lymphokines;
- comprising:
- (a) an effective amount of a recombinant human interleukin-2 mutein, wherein the cysteine residue at position 125, numbered in accordance with native human interleukin-2, is deleted or replaced by a neutral amino acid and said mutein exhibits the biological activity of native, human interleukin-2;
- and
- (b) an inert, non-allergenic, pharmaceutically compatible carrier medium.
A formulation comprising:
- (a) a recombinant human interleukin-2 mutein, wherein the cysteine residue at position 125, numbered in accordance with native human interleukin-2, is deleted or replaced by a neutral amino acid and said mutein exhibits the biological activity of native, human interleukin-2;
- and
- (b) a polypeptide selected from the group consisting of gamma interferon, B cell growth factor and IL-1.
Dependencies are inferred from the claim text.