DE3915952A1

DE3915952A1 - Medicaments for treating diseases involving intracellular protein - comprising nucleic acid coding for antibody to protein

Info

Publication number: DE3915952A1
Application number: DE19893915952
Authority: DE
Inventors: Peter Werner
Original assignee: Individual
Current assignee: Individual
Priority date: 1989-05-12
Filing date: 1989-05-12
Publication date: 1990-12-06

Abstract

Medicaments for treating diseases involving the intracellular presence of exogenous (e.g. viral) or endogenous (e.g. oncogen) proteins comprises a nucleic acid contg. a promoter region and an associated nucleotide sequence coding for one or more antibodies directed against the active centre of the protein in question, in a non-pathogenic (e.g. (viral) vector. The nucleic acid may contain several operons 'allowing fine regulation in equilibrium with the protein turnover in the cells'. The nucleotide sequence may be code for just the antigen-binding site of the antibody.

Description

Ausgehend von der Erkenntnis, daß viele Erkrankungen des Menschen oder auch anderer Lebewesen wie etwa Pflanzen, Nutztiere etc. sich unter anderem dadurch manifestieren, daß entweder Fremdproteine eingebracht bzw. exprimiert werden, die dann die betroffenen Zellen oftmals in ihren Funktionen schwerwiegend beeinflussen oder aber endogene Proteine, wie z. B. bei den Onkogenen, im extremen, nichtphysiologischen Maße exprimiert werden bzw. aktiv sind, gibt es schon seit längerem den Versuch, Onkogene oder z. B. die Reverse Transkriptase bei den Retroviren zu hemmen, um so den Krankheitsverlauf günstig zu beeinflussen oder aber den Krankheitsausbruch zu verhindern. Die meisten derartigen Ansätze gehen dabei von der enzymatischen Aktivität, die solchen Proteinen meist eigen ist, aus, indem sie durch Einsatz von Substratanaloga oder durch den Einsatz meist durch Trial-and-Error-Verfahren gefundener Inhibitoren diese Aktivität zu behindern suchen.Based on the knowledge that many diseases of the Humans or other living things such as Plants, farm animals etc. manifest themselves, among other things, that either foreign proteins are introduced or expressed, which then often affects the affected cells in their functions seriously affect or endogenous proteins, such as e.g. B. oncogenes, in extreme, non-physiological measure have been expressed or are active for a long time Attempt to oncogenes or z. B. the reverse transcriptase in the Inhibit retroviruses, so that the course of the disease is favorable influence or prevent the onset of the disease. Most of these approaches are based on the enzymatic activity, which is typical of such proteins is, by using substrate analogs or by the Use of inhibitors mostly found by trial-and-error methods seek to hinder this activity.

Diese Verfahren leiden jedoch häufig unter dem Problem mangelnder Wirkung bzw. schwerer Nebenwirkungen.However, these methods often suffer from the problem lack of effectiveness or severe side effects.

Ausgehend von dem wachsenden Fortschritt der Molekularbiologie und der modernen Immunologie ist mittlerweile die aktive Seite/das Aktive Zentrum vieler solcher Proteine bekannt.Based on the growing progress of molecular biology and modern immunology is now the active side / that Active center of many such proteins known.

Ebenso sind vielfach bereits die Sequenzen monoklonaler Antikörper gegen die aktiven Zentren solcher Proteine bekannt. In Kombination mit der modernen Peptidchemie (Epitopvorhersagen) ist daher der Einsatz von intrazellulären Antikörpern, die via ihre Nucleotidsequenz eingeschleust werden, eine ebenso zielgerichtete wie effektive Möglichkeit, solchen Problemen Abhilfe zu verschaffen.Likewise, the sequences are often monoclonal Antibodies against the active sites of such proteins are known. In combination with the modern Peptide chemistry (epitope predictions) is therefore the use of intracellular antibodies, via their nucleotide sequence be smuggled in, as targeted as it is effective Possibility to remedy such problems.

Claims

1. Active ingredient / drug / biotechnological method for the treatment of diseases in which exogenous (generally viral) or pathogenic endogenous proteins are involved intracellularly, particularly characterized in that the active ingredient / the drug from a promoter region with a downstream nucleotide sequence for one or more antibodies against the active center of the protein in question and a z. B. viral, but non-pathogenic vector.

1.1. Active ingredient / drug / biotechnological method according to claim 1, particularly characterized in that instead of one operon, as required, there are several operons, thus allowing fine regulation in equilibrium with the protein turn-over in the cell (= intracellular proteolysis).
1.2. Active substance / drug / biotechnological method according to claims 1 and 1.1, particularly characterized in that instead of a complete antibody, only the "antigen binding site" in the form of the nucleotide sequence of the corresponding epitope of an antibody, ie only the sequence which codes for the Antigen-antibody interaction is responsible.
1.3. Active ingredient / drug / biotechnological method according to claims 1, 1.1, 1.2, particularly characterized in that the nucleotide sequence additionally contains the coding for amino acid sequences which accelerate the proteolytic degradation ("leader sequence for proteases").
1.4. Active substance / drug / biotechnological method according to claims 1, 1.1, 1.2, 1.3, particularly characterized in that the introduction into the cells is carried out by viroid structures, that is to say without protein components.
1.5. Active ingredient / drug / biotechnological method according to claims 1, 1.1, 1.2, 1.3, particularly characterized in that the DNA / RNA is introduced into the target cells by liposomes or vesicles which fuse with the target cells and fuse with the target cells.