Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
1998-11-05
2001-09-11
Horlick, Kenneth R. (Department: 1656)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C530S350000
Reexamination Certificate
active
06288034
ABSTRACT:
BACKGROUND OF THE INVENTION
This invention relates to methods for treating autoimmune diseases.
Responses of the immune system initiate the destruction and elimination of invading organisms and toxic molecules produced by them. Because these immune reactions are destructive, it is essential that they be made in response only to molecules that are foreign to the host and not to those of the host itself. The ability to distinguish foreign molecules from self molecules is a fundamental feature of the immune system. Occasionally the immune system fails to make this distinction and reacts destructively against the host's own molecules; such autoimmune diseases can be fatal. Thus, tolerance to self antigens breaks down, causing the components of the immune system such as T or B cells (or both) to react against their own tissue antigens. Multiple sclerosis, rheumatoid arthritis, myasthenia gravis, insulin-dependent diabetes mellitus, and systemic lupus erythematosus are a few examples of such autoimmune diseases.
SUMMARY OF THE INVENTION
I have discovered that unglycosylated recombinant human alpha-fetoprotein made in a prokaryote (e.g.,
E. coli
) is useful for inhibiting autoreactive immune cells derived from a mammal. Accordingly, the invention features a method of inhibiting autoreactive immune cell proliferation in a mammal (e.g., a human patient), involving administering to the mammal a therapeutically effective amount of recombinant human alpha-fetoprotein or an immune cell anti-proliferative fragment or analog thereof. Preferably, such immune cells include T cells or B cells; and the recombinant human alpha-fetoprotein used in such methods is produced in a prokaryotic cell (e.g.,
E. coli
) and is unglycosylated.
In another aspect, the invention features a method of treating an autoimmune disease in a mammal (e.g., a human patient), involving administering to the mammal a therapeutically effective amount of recombinant human alpha-fetoprotein or an immune cell anti-proliferative fragment or analog thereof. Such an autoimmune disease is multiple sclerosis; is rheumatoid arthritis; is myasthenia gravis; is insulin-dependent diabetes mellitus; or is systemic lupus erythematosus. In yet other preferred embodiments the autoimmune disease is acquired immune deficiency syndrome or is a rejection of a transplanted organ, tissue or cell. Preferably, the recombinant human alpha-fetoprotein used in such methods is produced in a prokaryotic cell (e.g.,
E. coli
) and is unglycosylated. In other preferred embodiments, such methods further involve administering to the mammal an immunosuppressive agent in an effective dose which is lower than the standard dose when the immunosuppressive agent is used by itself. Preferably, such an immunosuppressive agent is cyclosporine; is a steroid; is azathioprine; is FK-506; or is 15-deoxyspergualin. In yet another preferred embodiment, such a method involves administering to the mammal a tolerizing agent. Preferably, the recombinant human alpha-fetoprotein used in such methods is produced in a prokaryotic cell (e.g.,
E. coli
) and is unglycosylated.
By “immune cell anti-proliferative” is meant capable of inhibiting the growth of an undesirable immune cell e.g., an autoreactive T cell as measured using the assays described herein).
By “therapeutically effective amount” is meant a dose of unglycosylated recombinant human alpha-fetoprotein (or a fragment or analog thereof) capable of inhibiting autoreactive immune cell proliferation.
By “recombinant human alpha-fetoprotein” is meant a polypeptide having substantially the same amino acid sequence as the protein encoded by the human alpha-fetoprotein gene as described by Morinaga et al.,
Proc. Natl. Acad. Sci., USA
80: 4604 (1983). The method of producing recombinant human alpha-fetoprotein in a prokaryotic cell is described in U.S. Ser. No. 08/133,773 issuing as U.S. Pat. No. 5,384,250.
According to the invention, administration of recombinant human alpha-fetoprotein (“rHuAFP”) (or a fragment or analog thereof) can be an effective means of preventing or treating or ameliorating autoimmune diseases in a mammal. To illustrate this, I have shown that recombinant HuAFP produced in a prokaryotic expression system is effective in suppressing T cell proliferation in response to self antigens, despite the fact that such rHuAFP is not modified in the same fashion as naturally occurring HuAFP. The use of natural HuAFP has heretofore been limited by its unavailability, natural HuAFP is obtained by laborious purification from limited supplies of umbilical cords and umbilical cord serum. Because biologically rHuAPP can now be prepared in large quantities using the techniques of recombinant DNA, the use of rHuAFP for treating autoimmune diseases is now possible. The use of rHuAFP is especially advantageous since there are no known adverse side effects related to human alpha-fetoprotein and it is believed that relatively high doses can be safely administered.
Other features ahd advantages of the invention will be apparent from the following detailed description, and from the claims.
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Clark & Elbing LLP
Horlick Kenneth R.
Martinex R & D Inc.
Strzelecka Teresa
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