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US4518584A
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Human recombinant interleukin-2 muteins
Assignee: CENTUS Corp A CORP OF
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Filing: 1983-12-20
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Granted: 1985-05-21
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Expires: 2003-12-20
Abstract
Abstract Muteins of biologically active proteins such as IFN-β 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.
Inventors
- 👤 David F. Mark
- 👤 Leo S. Lin
- 👤 Shi-da Y. Lu
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 14:19
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/52; C07K14/54; C07K14/55; C07K14/555; C07K14/565; C12; C12N; C12N15/00; C12N15/09; C12N15/10; C12N15/102; A; A61; A61K; A61K38/00; Y; Y10; Y10S; Y10S530/00; Y10S530/808; Y10S530/809; Y10S930/00; Y10S930/01; Y10S930/14; Y10S930/141; Y10S930/142
Claims Analysis
Total Claims: 16
Claim 1
Independent Claim
37 words
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.
Claim 2
Dependent Claim
37 words
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.
Claim 3
Dependent Claim
12 words
The mutein of claim 1 wherein said neutral amino acid is serine.
Claim 4
Dependent Claim
5 words
Human recombinant alanyl-interleukin-2 serine125 mutein.
Claim 5
Dependent Claim
5 words
Human recombinant alanyl-interleukin-2 serine125 mutein.
Claim 6
Dependent Claim
5 words
Human recombinant des-alanyl-interleukin-2 serine125 mutein.
Claim 7
Dependent Claim
5 words
Human recombinant des-alanyl-interleukin-2 serine125 mutein.
Claim 8
Dependent Claim
32 words
Human recombinant interleukin-2 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.
Claim 9
Dependent Claim
32 words
Human recombinant interleukin-2 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.
Claim 10
Dependent Claim
15 words
The mutein of claims 1, 2, 3, 4 or 5 wherein the mutein is unglycosylated.
Claim 11
Dependent Claim
160 words
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.
Claim 12
Dependent Claim
160 words
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.
Claim 13
Dependent Claim
33 words
The formulation of claim 7 wherein the mutein is alanyl-interleukin-2 serine125 or des-alanyl-interleukin-2 serine125 and said carrier is selected from the group consisting of distilled water, Ringer's solution, Hank's solution and physiological saline.
Claim 14
Dependent Claim
61 words
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.
Claim 15
Dependent Claim
61 words
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.
Claim 16
Dependent Claim
15 words
The formulation of claim 9 wherein the mutein is alanyl-interleukin-2 serine125 or des-alanyl-interleukin-2 serine125 .
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1988-05-20 | 1988-11-19 | 1989-05-21 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1992-05-20 | 1992-11-19 | 1993-05-21 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1996-05-20 | 1996-11-19 | 1997-05-21 | $7700.00 | Window Closed / Lapsed |