Drug – bio-affecting and body treating compositions – Lymphokine – Interferon
Patent
1993-10-05
1996-04-02
Sayala, Chhaya D.
Drug, bio-affecting and body treating compositions
Lymphokine
Interferon
424 854, 514 2, 514 21, 530351, A61K 3821
Patent
active
055038280
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates generally to alpha interferon compositions. More specifically, the invention relates to an improved alpha interferon composition characterized by high specific activity, a purity of greater than 95% and which upon use in humans is further characterized by a substantial reduction in side effects normally associated with alpha interferon compositions, and a method for large scale production of the composition from human peripheral blood leukocytes.
BACKGROUND OF THE INVENTION
Human alpha interferon comprises a family of more than fifteen proteins with antiviral, antigrowth and immunoregulatory activities Pestka et al., Ann. Rev. Biochem., 56:727 (1987)!. The therapeutic efficacy of human alpha interferons has been established for human cancers and viral diseases. For example, recombinant interferons (IFN alfa-2a, IFN alfa-2b, IFN alfa-2c), cell-line derived interferon (IFN alfa-n1) and interferon derived from leukocytes (IFN alfa-n3) are currently used for the treatment of Condyloma acuminata, hepatitis Weck et al., Am. J. Med., 85(Suppl 2A):159 (1988); Korenman et al., Annal. Intern. Med., 114.:629 (1991); Friedman-Kien et al., JAMA, 259:533 (1988)!, for the regression of some malignancies Baron et al., JAMA, 266:1375 (1991)!, for the treatment of AIDS related Kaposi's sarcoma Physicians Desk Reference, 47th edit., eds. Medical Economics Data, Montvale, N.J., p. 2194 and 2006 (1993)! and are currently being considered for the treatment of human acquired immunodeficiency syndrome (AIDS) either alone or in combination with other antiviral agents Hirsch, Am. J. Med., 85(Suppl 2A):182 (1988)!.
Recombinant interferons can be made by using genetic engineering techniques, for example, in Escherichia coli in large scale Goeddel et al., Nature, 287:411 (1980); Streuli et al., Science, 209:1343 (1980)!. However, genetically engineered interferons are composed of only a single species, which is not post-translationally modified at all or identically to the natural interferons, and which may limit the biological activity of the composition. For example, IFN-.alpha.2 is the sole species in the products Intron.RTM. A (IFN alfa-2b) Schering Plough! and Roferon.RTM. A (IFN alfa-2a) Hoffman-La Roche!.
Interferons derived from natural sources, such as those from human lymphoblastoid, Namalwa, cell line Mizrahi, Meth. Enzymol., 78:54 (1981); Phillips et al., Meth. Enzymol., 119:35 (1986)!, and those from human peripheral blood leukocytes Mogensen et al., Pharmacol. Ther. Part C, 1:369 (1977); Cantell et al., Methods Enzymol., 78:29 (1981); Horowitz, Methods Enzymol., 119:39 (1986)!, are composed of multiple species, each with different structural and biological activity.
Such "natural" interferons are considered by some researchers to provide potentially better therapeutic efficacy than recombinant interferon. For example, natural alpha interferon can be used at a four times lower dosage to treat Condyloma than the recombinant products see, e.g., Physicians Desk Reference, cited above, at pages 1879 and 2194!. The most significant advantage of using natural leukocyte interferon as a therapeutic agent has been its low immunogenecity in patients receiving interferon treatment. It has been documented that patients treated with the recombinant interferons identified above, and lymphoblastoid interferon Wellferon.RTM. IFN alfa-n1 Burroughs Wellcome! have developed neutralizing antibodies to interferon Lok et al., Hepatology, 12:1266 (1990); Jacobs et al., J. Biol. Resp. Mod., 7:447 (1988); Weck et al., J. Interferon Res., 1(Suppl):S37 (1989)!. However, patients treated with leukocyte derived interferon (IFN alfa-n3 or Cantell's partially purified interferon preparation) do not generate detectable serum antibody to interferon Von Wussow et al., Lancet, 2:635 (1987); Liao et al., J. Infect. Dis., 165:757-760 (1992)!. The presence of neutralizing anti-interferon antibodies may potentially block the therapeutic effect of the interferon and therefore may be a significant factor in the c
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Physicians Desk Reference, 47th edit., eds. Medical
DiPaola Mario
Ferencz-Biro Katalin
Liao Mei-June
Padhye Manisha
Rashidbaigi Abbas
Interferon Sciences, Inc.
Sayala Chhaya D.
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