Covalently linked polypeptide cell modulators such as interferon-lymphotoxin conjugates
AssigneeG. D. Searle & Co.
InventorsLeslie D. Bell, Keith G. McCullagh, Alan G. Porter
Life of this patent
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Abstract
Described is a new class of polypeptide cell modulators characterized by being composed of two covalently linked cell modulators in a linear polypeptide sequence. Such dual function polypeptides have new and particularly useful activities when the component polypeptide cell modulators are interferons, lymphokines or cytotoxins which act through different and specific cell receptors to initiate complementary biological activities.
Claims30
A composition of the formula
- R.sub.1 --L--R.sub.2
- wherein R.sub.1 is gamma interferon or a biologically active modified gamma interferon which has one of the following activities:
- (a) the ability to protect Vero cells against the cytopathic effect of encephalomyocarditis virus infection;
- or
- (b) antiproliferative activity against HEp-2 cells;
- (c) an immunomodulating activity of native gamma interferon;
- R.sub.2 is human lymphotoxin or a biologically active modified human lymphotoxin which retains a biological activity of native human lymphotoxin;
- and L is a peptide linker segment of from about 1 to about 500 amino acid residues wherein the L retains or potentiates the biological activity of R1 and/or R2.
The protein identified in FIG. 12 and FIG. 13 as IFNX 603 and having the amino acid sequence shown in FIG. 12 and FIG. 13.
The protein identified in FIG. 14 and FIG. 15 as IFNX 604 and having the amino acid sequence shown in FIG. 14 and FIG. 15.
A pharmaceutical composition comprising a therapeutically effective amount of a composition of the formula
- R.sub.1 --L--R.sub.2
- wherein R.sub.1 is gamma interferon or a biologically active modified gamma interferon which has one of the following activities:
- (a) the ability to protect Vero cells against the cytopathic effect of encephalomyocarditis virus infection;
- or
- (b) antiproliferative activity against HEp-2 cells;
- (c) an immunomodulating activity of native gamma interferon;
- R.sub.2 is human lymphotoxin or a biologically active modified human lymphotoxin which retains a biological activity of native human lymphotoxin;
- and L is a peptide linker segment of from about 1 to about 500 amino acid residues wherein the L retains or potentiates the biological activity of R1 and/or R2 admixed with a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.