Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing compound containing saccharide radical
Reexamination Certificate
1995-06-07
2004-12-28
Martinell, James (Department: 1631)
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Preparing compound containing saccharide radical
C435S252300, C435S252330, C435S325000, C435S254110, C435S254200, C435S320100, C536S023520
Reexamination Certificate
active
06835557
ABSTRACT:
TECHNICAL FIELD OF INVENTION
This invention relates to DNA sequences, recombinant DNA molecules and processes for producing interferon and interferon-like polypeptides. More particularly, the invention relates to DNA sequences expressed in appropriate host organisms. The recombinant DNA molecules disclosed herein are characterized by DNA sequences that code for polypeptides having an immunological or biological activity of human leukocyte interferon As will be appreciated from the disclosure to follow, the DNA sequences, recambinant DNA molecules and processes of this invention may be used in the production of polypeptides useful in antiviral and antitumor or anticancer agents and methods.
BACKGROUND ART
In this application the interferon nomenclature announced in
Nature
, 286, p. 2421 (Jul. 10, 1980) will be used. This nomenclature replaces that used in our earlier applications from which this application claims priority. E.g., IF is now designated IFN and leukocyte interferon is now designated IFN-&agr;;
Two classes of interferons (“IFN”) are known to exist. Interferons of Class I are small, acid stable (glyco)-proteins that render cells resistant to viral infection (A. Isaacs and J. Lindenmann, “Virus Interference I. The Interferon”,
Proc. Royal Soc. Ser. B
., 147, pp. 258-67 (1957) and W. E. Stewart, II,
The Interferon System
, Springer-Verlag (1979) (hereinafter “
The Interferon System
”)). Although to some extent cell specific (
The Interferon System
, pp. 135-45), IFNs are not virus specific. Instead IFNs protect cells against a wide spectrum of viruses.
Human interferons (“HuIFN”) have been classified into three groups &agr;, &bgr; and &ggr;. HuIFN-&agr; or leukocyte interferon is produced in human leukocyte cells and together with minor amounts of HuIFN-p (fibroblast interferon) in lymphoblastoid cells. HuIFN-&bgr; has been purified to homogeneity and characterized (e.g. M. Rubenstein et al., “Human Leukocyte Interferon: Production, Purification To Homogeneity And Initial Characterization”
Proc. Natl. Acad. Sci. USA
, 76, pp. 640-44 (1979)). It is heterogeneous in regard to size presumably because of the carbohydrate moiety. Two components have been described, one of 21000 to 22000 and the other of 15000-18000 molecular weight. The component of lower molecular weight has been reported to represent a non-glycosylated form. The smaller form of HuIFN-&agr; has also been reported to retain most or all of its HuIFN-&agr; activity (W. E. Stewart, II et al., “Effect Of Glycosylation Inhibitors On The Production And Properties of Human Leukocyte Interferon”,
Virology
, 97, pp. 473-76 (1979)). A portion of the amino acid sequence of HuIFN-&agr; from lymphoblastoid cells and its amino acid composition have been reported (K. C. Zoon et al., “Amino Terminal sequence Of The Major Component Of Human Lymphoblastoid Interferon”,
Science
, 207, pp. 527-28 (1980) and M. Hunkapiller and L. Hood, personal communication (1980))
HuIFN-&agr; has also been reported to exist in several different forms, e.g. British patent application 2,037,296A. These forms appear to differ from each other structurally and physiologically. No accepted nomenclature has been adopted for these forms of HuIFN-&agr;. Therefore, in this application each form will be referred to by a number after the general HuIFN-&agr; designation, i.e., HuIFN-&agr;1 or HuIFN-&agr;3.
HuIFN-&agr; may, like many human proteins, also be polymoiphic. Therefore, cells of particular individuals may produce HuIFN-&agr; species within the more general HuIFN-&agr; group or forms within that group which are physiologically similar but structurally slightly different than the group or form of which it is a part. Therefore, while the protein structure of an HuIFN-&agr; may be generally well-defined, particular individuals may produce a HuIFN-&agr; that is a slight variation thereof, this allelic variation probably being less severe than the difference between the various forms of HuIFN-&agr;.
HuIFN is usually not detectable in normal or healthy cells (
The Interferon System
, pp. 55-57). Instead, the protein is produced as a result of the cell's exposure to an IFN inducer. IFN inducers are usually viruses but may also be non-viral in character, such as natural or synthetic double-stranded RNA, intracellular microbes, microbial products and various chemical agents. Numerous attempts have been made to take advantage of these non-viral inducers to render human cells resistant to viral infection (S. Baron and F. Dianzani (eds.),
Texas Reports On Biology And Medicine
, 35 (“Texas Reports”), pp. 528-40 (1977)). These attempts have not been very successful. Instead, use of exogenous HuIFN itself is now preferred.
Interferon therapy against viruses and tumors or cancers has been conducted at varying dosage regimes and under several modes of administration (The Interferon System, pp. 305-321). For example, interferon has been effectively administered orally, by innoculation—intravenous, intramuscular, intranasal, intradermal and subcutaneous—, and in the form of eye drops, ointments and sprays. It is usually administered one to three times daily in dosages of 10
4
to 10
7
units. The extent of the therapy depends on the patient and the condition being treated. For example, virus infections are usually treated by daily or twice daily doses over several days to two weeks and tumors and cancers are usually treated by daily or multiple daily doses over several months or years. The most effective therapy for a given patient must of course be determined by the attending physician who will consider such well known factors as the course of the disease, previous therapy, and the patient's response to interferon in selecting a mode of administration and dosage regime.
As an antiviral agent, HuIFN has been used to. treat the following: respiratory infections (
Texas Reports
, pp. 486-96); herpes simplex keratitis (
Texas Reports
, pp. 497-500); acute hemorrhagic conjunctivitis (
Texas Reports
, pp. 501-10); varicella zoster (
Texas Reports
, pp. 511-15); cytomegalovirus infection (
Texas Reports
, pp. 523-27); and hepatitis B (
Texas Reports
, pp. 516-22). See also
The Interferon System
, pp. 307-19. However, large scale use of IFN as an antiviral agent requires larger amounts of IFN than heretofore have been available.
HuIFN has other effects in addition to its antiviral action. For example, it antagonizes the effect of colony stimulating factor, inhibits the growth of hemopoietic colony-forming cells and interferes with the normal differentiation of granulocyte and macrophage precursors (
Texas Reoorts
, pp. 343-49). It also inhibits erythroid differentiation in DMSO-treated Friend leukemia cells (
Texas Reports
, pp. 420-28). HuIFN may also play a role in regulation of the immune response. Depending upon the dose and time of application in relation to antigen, HuIFN-&agr; can be both immunopotentiating and immunosuppressive in vivo and in vitro (
Texas Reports
, pp. 357-69). In addition, specifically sensitized lymphocytes have been observed to produce HuIFN-&agr; after contact with antigen. Such antigen-induced HuIFN-&agr; could therefore be a regulator of the immune response, affecting both circulating antigen levels and the expression of cellular immunity (
Texas Reports
, pp. 370-74). HuIFN is also known to enhance the activity of killer lymphocytes and antibody-dependent cell-mediated cytotoxicity (R. R. Herberman et al., “Augmentation By Interferon Of Human Natural And Antibody Dependent Cell-Mediated Cytotoxicity”,
Nature
, 277, pp. 221-23 (1979); P. Beverley and D. Knight, “Killing Comes Naturally”,
Nature
, 278, pp. 119-20 (1979);
Texas Reports
, pp. 375-80). Both of these species are probably involved in the immunological attack on tumor cells.
Therefore, in addition to its use as a human antiviral agent, HuIFN has potential application in antitumor and anticancer therapy (
The Interferon System
, pp. 319-21). It is now known that IFNs affect the growth of many classes of tumors in many animals (
The Interferon System
, pp. 292
Biogen Inc.
Haley Jr. James F.
Martinell James
Weissman Jennifer T.
Wong Connie
LandOfFree
DNA sequences, recombinant DNA molecules and processes for... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with DNA sequences, recombinant DNA molecules and processes for..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and DNA sequences, recombinant DNA molecules and processes for... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3308907