Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
1999-03-15
2001-11-20
Carlson, Karen Cochrane (Department: 1653)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C530S350000, C530S300000
Reexamination Certificate
active
06319892
ABSTRACT:
This invention relates to the use of recombinant myelin protein for treating T cell-mediated autoimmune diseases of the peripheral nervous system.
Neuropathies of autoimmune genesis have been treated by immunosuppressive or immunomodulating therapy so far. Common treatment methods are the administration of steroids (e.g. cortisone), immunoglobulins and long-term immunosuppressive agents (e.g. azathiopine) or the conduction of plasmapheresis. However, many undesired side-effects accompany these measures as drawbacks, and success is often insufficient.
Therefore, it is the object of the present invention to provide a successful and careful method for treating T cell-mediated autoimmune diseases of the peripheral nervous system.
The inventors have found that autoimmune-B cell and autoimmune-T cell responses, which are directed against peripheral myelin components, play an important part in the pathogenesis of inflammatory demyelinating diseases of the nervous system. These diseases are known as immunoneuropathies of the peripheral nervous system, e.g. chronic inflammatory polyneuritis, Guillain-Barré syndrome, vasculitides of the peripheral nervous system and neuritides in the case of gammopathies.
The presence of neuritic molecules in myelin was proved for the first time by the induction of experimental autoimmune neuritis (EAN) in an animal model where rodents were immunized with homogenates of peripheral nerve tissue (Waksman et al., J. Exp. Med. 102, 213-235 (1955)) or purified P2 protein (Brostoff et al., Nature (New Biol.) 235, 210-217 (1972)). In this animal model for disease of the peripheral nervous system, the immune system is disregulated and autoaggressive T lymphocytes are produced which are specific for structural proteins of the myelin of the peripheral nervous system and result in demyelinization and in inflammation in the peripheral nervous system. This animal model stands in place for the above-mentioned autoimmune diseases of the peripheral nervous system in which an increased T cell number, demyelinization and neuritides occur as well.
The inventors have now found that these T cell-mediated autoimmune diseases of the peripheral nervous system can be eliminated and at least be improved, respectively, by the administration of high doses of the autoantigen, i.e. by the high-dosed administration of myelin protein. This treatment is named high-dosed antigen treatment and results in gentle death of the T cells (T cell apoptosis) which in the final analysis are responsible for the induction and course of the disease. In this connection, it proved to be particularly suitable to carry out the high-dosed antigen treatment in an early disease stage. However, also in the case of an advanced clinical picture considerable success can still be achieved. Thus, it has proved efficient to administer the antigen (myelin protein) in doses of 100 to 500 &mgr;g in rats. For man, higher doses which can easily be determined by a person skilled in the art must be applied in accordance with the greater body weight. For example, a daily dose of from about 5-50 mg, more preferably from about 10 mg-30 mg is exemplary of doses for humans. Intravenous injection is particularly preferred.
All presently known myelin proteins, such as PO, peripheral myelin glycolipids (e.g. GM1), MBP, PLP, MOG, MAG, S-100 protein and particularly P2, are suited as autoantigen to be administered. According to the invention the term “myelin protein” includes mixtures of various proteins, protein fragments and mixtures of protein fragments. It has to be emphasized that these proteins should have been produced recombinantly, since it is very expensive and time-consuming to purify a sufficient amount of proteins from natural myelin. Moreover, when purified protein from bovine nerve myelin is used, BSE can easily be transmitted. In addition, the response in man to purified bovine protein differs very strongly from that to human P2, since some amino acid differences exist between the human sequence and the bovine one. Therefore, natural human P2 has been used for T cell experiments so far, since recombinant protein was not yet available. However, it has been produced meanwhile and it is particularly preferred according to the invention to use recombinant human P2 protein. The sequence and isolation of this protein is described in “Weishaupt et al., J. of Neuroimmunology 63, 149-156 (1995 which is incorporated by reference)”. The sequence shown in this publication is illustrated in FIG.
4
. Further recombinant myelin proteins are described in Oettinger et al., J. of Neuroimmunology 44, 157-163 (1993 which is incorporated by reference).
Gold Ralf
Weishaupt Andreas
Carlson Karen Cochrane
Fulbright & Jaworski LLP
LandOfFree
Use of recombinant myelin protein for treating... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Use of recombinant myelin protein for treating..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Use of recombinant myelin protein for treating... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2571234