DE19904514A1 - Antiviral agent, e.g. vaccine, antibody, agent that inhibits viral replication, transcription or translation, useful for preventing or treating tumors (or conditions which may become tumorous) associated with viral infections - Google Patents

Abstract

Antiviral agent (A) for preventing and/or treating alterations to tissues of mesenchymal origin (or derived tissue alterations), is new. Independent claims are also included for the following: (1) methods for identifying (A) and/or virus against which (A) is directed; (2) apparatus for detecting a virus involved in pathogenesis of tissue alterations comprising a product of a gene of the HMGI(Y) family (undefined), or its fragment or derivative, immobilized on a support; and (3) method for diagnosing tissue alterations by detecting, in a body fluid, antibodies against, or antigens of, a virus implicated in the alterations.

Description

The invention relates to agents for the prevention and / or treatment of leiomyomas, Ver the same, method of determining for the preparation of the agent essential Components as well as a device for determining a pathogenesis of Leiomyomas involved agent and its use.

Leiomyomas of the uterus, even if they are benign, are a health policy nice problem. Thus, studies have shown that in western European countries every third Woman has uterine leiomyomas and, for example, in the US every fifth visit to the gynecologist fibroids (Morton, C.C., Am. J. Pathol., 1998; 153 (4): 1050-20).  

If these leiomyomas manifest themselves symptomatically, this can be, for. B. with significant Blutun and health risks, pain and urinary incontinence. In addition, these leiomyomas can result in infertility in the affected women to have.

Currently there is no causal myoma therapy available. A causal therapy is missing too for endometrial polyps and endometriosis. Currently there are two therapies for fibroids the surgical removal of the uterus (hysterectomy), so alone in the US about 200,000 hysterectomies each year (Morton, loc. cit.), or the fibroids nucleation, d. H. the "peeling" of the tumors, at uterus-preservation. In the case of Myo Menucleation can cause a medical reduction of the myoma preoperatively Use of hormone antagonists, however, in this respect with unwanted Nebenwir diseases that cause menopausal symptoms.

It thus exists for leiomyomas, in particular those of the uterus, as well as endometrium poly penis and endometriosis an urgent need for preventive therapy concepts and the here for suitable means.

It is thus an object of the present invention to provide a means for prevention and / or Treatment of leiomyomas, especially those of the uterus, as well as Endometriumpo lypen or endometriosis.

Furthermore, it is an object of the present invention to provide a method with which can be determined those essential components which are used to produce the inventions The agents are suitable or required.

Finally, it is an object of the invention to provide a device for determining a involved in the pathogenesis of leiomyomas, endometrial polyps or endometriosis Agent and to provide a for the production of the inventive agents we essential component to provide.  

According to the invention, the object is achieved by a means for prevention and / or treatment of leiomyomas comprising a vaccine against a virus whose nucleic acid min at least one binding site for a gene product of genes of the HMGI (Y) family or their Derivatives includes.

Furthermore, the object is achieved by a means for the prevention and / or treatment of Leiomyomas comprising a vaccine against a virus whose nucleic acid JUr Gene product encoded, said gene product with at least one gene product of genes the HMGI (Y) family or its derivatives interacts.

Furthermore, the object is achieved by the use of the agent according to the invention Prevention and / or treatment of endometrial polyps.

The object is also achieved by the use of the agent according to the invention Prevention and / or treatment of endometriosis.

Finally, the object is achieved by using the agent according to the invention is used for Immunization against the viruses involved in the pathogenesis and / or etiology of Leiomyo men, endometrial polyps and / or endometriosis.

The object is further solved by the inventive composition for the production a pharmaceutical composition comprising the agent according to the invention and egg a pharmaceutically acceptable carrier for the prevention and / or treatment of Leiomyo endometrial polyps and endometriosis or for immunization against the viruses that with the pathogenesis and / or etiology of leiomyomas, endometrial polyps and endo metriose are used.

In a further aspect, the object is achieved by a method for determining viruses suitable for the preparation of an agent for the prevention and / or treatment of leiomyomas, endometrial polyposis or endometriosis, the agent comprising a vaccine against a virus whose nucleic acid binds at least one binding site a gene product of genes of the HMGI (Y) family or their derivatives, or whose nucleic acid codes for a gene product, wherein the gene product comprises at least one binding site for a gene product of genes of the HMGI (Y) family or their derivatives, in particular Inventive means comprising the steps:

• a) transfection of a normal karyotype cell culture derived from one Leiomyoma, endometrial polyps or endometrial tissue, with an expression vector for a gene of the HGMI (Y) family or its derivative,
• b) Comparison of the RNA pattern of the transfected cells with that of control cultures and,
• c) checking that expressed in the transfected cultures against control cultures or amplified expressed RNA (s) by sequence homology to the presence of viral Elements.

In a further aspect, the object is achieved by a method for determining Preparation of an agent for the prevention and / or treatment of leiomyomas, endometri umpolypen or endometriosis of suitable viruses, wherein the agent is a vaccine against Virus whose nucleic acid has at least one binding site for a gene product of Genes of the HMGI (Y) family or derivatives thereof, or its nucleic acid for a Gene product encoded, wherein the gene product at least one binding site for a Genpro comprising genes of the HMGI (Y) family or their derivatives, in particular an invention means according to the invention, which comprises carrying out a PCR test, wherein the for the PCR used primer (pairs) correspond to the sequence of viral nucleic acid.

Finally, in a further aspect, the object is achieved according to the invention by a method for determining viruses suitable for the preparation of an agent for the prevention and / or treatment of leiomyomas, endometrial polyps or endometriosis, the agent comprising a vaccine against a virus whose nucleic acid contains at least one Binding site for a gene product of genes of the HMGI (Y) family and their derivatives comprises, or encodes the nucleic acid for a gene product, wherein the gene product comprises at least one binding site for a gene product of genes of the HMGI (Y) family or derivatives thereof in particular an agent according to the invention, comprising the steps:

• a) Creating a cDNA library of a leiomyoma, endometrial polyps or endo metriotics that activate the gene of the HGMI (Y) family or a gene Having derivative, and
• b) screening the cDNA library with a virus-specific probe or
• c) Analysis of the cDNA clones for viral sequences or
• d) Comparison with a normal myometrium cDNA library.

Furthermore, the object is achieved by a device for Bestim One of the pathogenesis of leiomyomas, endometrial polyps or endometriosis involved virus, which is a gene product of genes of the HMGI (Y) family or part thereof or its derivative bound to a carrier.

The object is also achieved by the use of the device according to the invention Provision of one for the preparation of an agent for the prevention and / or treatment of Leiomyomas, endometrial polyps or endometriosis essential component.

The object is also achieved by the use of the invention A method for detecting viruses against which for the prevention and / or treatment of Leiomyomas, endometrial polyps or endometriosis can be immunized.

In the inventive agents for the prevention and / or treatment of Leiomen, En dometrium polyps or endometriosis as well as in the active immunizing agent the viruses involved in the pathogenesis and / or etiology of leiomyomas, endometrium  polyps or endometriosis are connected, is provided in one embodiment that the Vaccine comprises a virus particle or parts of a virus particle.

Furthermore, it can be provided that the binding site on the nucleic acid of the virus Structural and sequence feature of a first AT-rich sequence.

Furthermore, it can be provided that the binding site on the nucleic acid of the virus in addition to the first sequence still includes the structural and sequence features that

• A second AT-rich sequence is present, and
• - The first and second sequence are arranged at a spatial distance from each other.

Furthermore, the invention proposes that the spatial distance is selected so that the first sequence and the second sequence relative to each other in a plane on the nucleic acid are arranged.

In the compositions of the invention it is provided that the genes of the HMGI (Y) family MAG genes, HMGIC, HMGIY, aberrant transcripts of genes of the HMGI (Y) family and Derivatives thereof include.

In an alternative embodiment of the inventive means it is provided that the Vaccine is an antibody directed against the virus.

It can be provided that the antibody is selected from the group which monoklo nale antibodies, polyclonal antibodies, polyvalent antibodies, antibody fragments and Derivatives thereof.

In the inventive compositions may be provided in both alternatives that the Virus is selected from the group comprising polyoma viruses.  

In a particularly preferred embodiment, it is provided that the virus out is selected from the group comprising BK virus and JVC virus.

In one embodiment of the agent according to the invention, it can furthermore be provided that that the leiomyomas are uterine leiomyomas.

In the inventive method for determining for the preparation of an agent for Prevention and / or treatment of leiomyomas, endometrial polyps or endometriosis suitable virus, said agent comprising a vaccine against a virus whose nucleic acid acid at least one binding site for a gene product of genes of the HMGI (Y) family and their derivatives, or whose nucleic acid codes for a gene product, wherein the Gene product at least one binding site for a gene product of genes of HMGI (Y) - Family or derivatives thereof, in particular an agent according to the invention, is in one Embodiment The gene of the HMGI (Y) family selected from the group comprising HMGIC, HMGIY, MAG, aberrant transcripts of the genes of the HMGI (Y) family and derivatives thereof includes.

In the method according to the invention it can be provided that the virus, the viral Ele or the virus-specific probe is selected from the group of viruses, the polyoma Viruses included.

In a further embodiment of the method according to the invention, it can be provided that that the hybridization, in particular in the context of screening, under conditions niedri ger stringency is made.

In the device according to the invention for determining a pathogenesis of Leiomyomas, endometrial polyps or endometriosis involved virus, which is a gene product of genes of the HMGI (Y) family or a part thereof or its derivatives taken as well as its use to provide a for the production of an inventions Composition according to the invention for the prevention and / or treatment of leiomyomas, endometri  Umpolypen or endometriosis essential component, it can be provided that the Carrier is selected from the group of materials that are required for binding of peptides and / or proteins.

In one embodiment of the device according to the invention can be provided that the Gene product or a part thereof or its derivative comprises at least that part which is a Binding of viral nucleic acid to the gene product allowed.

In the apparatus according to the invention may further be provided that the viral Nu at least the structural and sequence feature of a first AT-rich sequence includes.

In a further embodiment it can be provided that the viral nucleic acid in addition to the first AT-rich sequence, the structural and sequence features include that a second AT-rich sequence is present and the first sequence and the second sequence are arranged in a spatial distance from each other.

In a particularly preferred embodiment, it is provided that the spatially Di is selected so that the first sequence and the second sequence relative to each other in a level are arranged on the nucleic acid.

In an alternative embodiment of the device according to the invention, it is provided that the gene product of genes of the HMGI (Y) family or a part thereof or its Deri vat comprises at least that portion that encodes a binding of a viral nucleic acid allowed gene product.

In the uses according to the invention of the immunizing agents according to the invention tion against the viruses involved in the pathogenesis and / or etiology of leiomyomas, Endo metriumpolypen or endometriosis are connected, and for the production of erfindungsge According to the pharmaceutical composition it can be provided that the immunization is an active immunization.  

Before the invention is explained in more detail below, Be used herein Be In addition to the general understanding of the skilled person on the Ge be defined.

In particular, benign tumors of smooth muscle should be described herein as leiomyomas (Definition according to Baltzer, J. et al .; Gynecology - A Short Textbook, 5th ed., 1994, Thieme Verlag).

Among endometrial polyps herein are particularly hyperplasia and polypous wax Forms of endometrium with stromal and glandular (epithelial) or exclusively stromal component understood.

By endometriosis, it is intended in particular to include endometrial foci elsewhere than in the uterine cavity (definition according to Baltzer loc. cit.).

In particular, fibroids are to be understood here as meaning leiomyomas (definition according to Baltzer, loc. Cit.).

The invention is based on the following surprising discovery.

Despite many efforts, the aetiology / pathogenesis of uterine leiomyomas has been so far unclear (Morton loc. cit.). Various possible causes of uterine leiomyomas will be for example, by Cramer, S.F. et al. (Cramer S.F., J. Reprod. Med. 1995, 40 (8): 595-600), for example, injury and repair of the endometrium. Also, the involvement of estrogen and estrogen receptors in the development of smooth muscle neoplasms Uterus were discussed in the literature, such. Tiltman A.J. (Tiltman A.J., Curr. Opin. Obstet. Gynecol., 1997; 9 (1): 48-51. Due to various investigations has become however, the notion develops that mutations of the genes of the HMGI (Y) family are involved (See Schoenmakers E.F. et al., Nat. Genet. 1995, 10 (4): 436-44), wherein as yet unclear whether the said mutations are primary or secondary events.  

Quite unexpectedly, the inventors found that the pathogenesis of Leiomyomas just not only on mutations, especially chormosome aberrations in Be rich of loci of members of the HMGI (Y) gene family, but it is a Consequence of the interaction of mutational events of the members of the HMGI (Y) - Gene family and a virus, in particular a weakly transforming virus, or In infection with such, whereby the viral infection itself is already sufficient to one Myomentstehung trigger, whose growth potential by a - possibly subsequent - Mutation of genes of the HMGI (Y) family is enhanced.

Without being limited in the following by these assumptions, in particular not in the Detail, it seems currently to be so that, as a result of infection with a weak transform virus and its subsequent persistence, presumed to be integrated into the cellular Genome, in cells without further mutation of genes of the HMGI (Y) family the transform Therefore, viral proteins are only weakly expressed and the resulting tumors therefore grow very slowly and stay small. As a result of a mutation-induced re-activation of genes of the HMGI (Y) family, e.g. B. by displacement of enhancers in Juxta position to the genes, there is an increased activation of the genes of the transforming Proteins and an overall increased expression thereof. Those in the cell are more common harldenen transforming proteins lead to a significantly higher growth activity the corresponding tumors and thus to increased tumor growth.

Specifically, it has been found that the gene products of the members of the genes of HMGI (Y) - Family that can typically bind to nucleic acids, such as described by French, S.W. et al. (French, S.W., et al., Mol. Cell Biol., 1996; 16 (10): 5393-99; Yie, J. et al .; Mol. Cell Biol., 1997, 17 (7): 3649-62), also on nucleic acid of transforming viruses when binding in the region of the regulatory regions of the nucleic acid (eg. Promoters and enhancers) the gene products of the genes of the HMGI (Y) family on the Tran scripting rate of the viral transforming proteins influence.  

Furthermore, it has been found that the gene products of the members of the genes of HMGI (Y) - Family can also interact with a gene product of a viral nucleic acid.

This interaction may occur in a direct interaction of the two gene products, i. H. the gene product of the viral nucleic acid and that of a gene of the HMGI (Y) family, consist. Another form of interaction may be that these by a further component is mediated, d. H. no direct interaction between the two gene pro is present. This mediating further component can, for example, a nucleic acid and, in particular, such a nucleic acid which is a binding site for a gene product of genes of the HMGI (Y) family as described above.

As a result of this interaction of gene products of the genes of the HMGI (Y) family with Nucleic acid of transforming viruses, in particular the regulatory regions of Nucleic acid (eg, promoters and enhancers) of these viruses may prevent the development of Leiomyomas, endometrial polyps and endometriosis are counteracted by a vaccine against the corresponding viruses, d. H. those viruses whose nucleic acid is at at least one binding site for a gene product of genes of the HMGI (Y) family or their Derivatives which prevents the corresponding tissues, i. H. the myometrium and the endometrium, as well as other mesenchymal tissues, become virally infected and thus the formation of the complex of viral nucleic acid and gene products the genes of the HMGI (Y) family prevents what subsequently leads to the formation of leiomyomas, endometrial polyps and endometriosis.

In the pathogenesis of leiomyomas, endometrial polyps and endometriosis white seems a binding of gene products of viral nucleic acid with gene products of genes of HMGI (Y) family and their derivatives, and consequently the influence of the increase viral transforming proteins. On the basis of this interaction can according to vaccines and thus the agents of the invention available ge which are directed against a virus, the said interaction zwi  protein encoded by its nucleic acid, on the one hand, and gene products of genes of the HMGI (Y) family or derivatives thereof.

Herein, binding of a gene product of genes of the HMGI (Y) family or their deriva to viral nucleic acid or to the gene product of viral nucleic acid, in particular a include any interaction of the molecular species involved, which results in the components forming the complex no longer serve as individual components but the complex is the only perceptible component. One of the like binding includes, for example. Interaction by electrostatic forces of attraction, of the Wals forces, hydrophobic interaction, hydrogen bonds and disulfide bridges and combinations thereof. Such a complex comprises at least the two Gene product species, d. H. a gene product of the viral nucleic acid and a gene product of However, genes of the HMGI (Y) family, which can interact directly with each other, can also additionally comprise a nucleic acid, wherein also in this case a direct Wechselwir kung of the two gene product species can take place, but not necessarily take place got to.

In that regard, one aspect of the invention also relates to a vaccine against transforming Vi used for the prevention and / or treatment of leiomyomas, in particular of the uterus, Endometrial polyps and endometriosis is suitable.

With the agents according to the invention is thus a prevention for and causal therapy of Leiomyomas, endometrial polyps and endometriosis possible and the previous unsprayed therapy concepts with their not inconsiderable risk potential become obsolete. there It is especially noteworthy that the use of vaccines for the body especially Gentle, as usually associated with relatively fewer side effects.

The production of vaccines against viruses is well known in the art and, for example. described in Modrow, S .; Falcon, D .; Molecular Virology, Spectrum, Akad. Verl., 1997.  

For vaccines, there are basically several types known, namely live vaccines, the virus capable of replication contain inactivated virus vaccines, where the viruses are in no longer reproducible form, split vaccines, which only from those for the Im munition important components of the virus exist, even as a subunit vaccine or An termed vaccines, and so-called "synthetic antigen vaccines". All vorer Such vaccine forms may be used in the context of the present invention.

Live vaccines contain replicable virus strains that have specific protection but cause no disease in healthy animals. A live vaccine can either from homologous (similar) or heterologous (alien) virus strains herge be presented. As homologous vaccines can be naturally derived or artificially herge strains of a virus were used.

Naturally obtained vaccine virus strains originate from field strains that only have one have weak or no virulence more, so in healthy animals no disease cause more, but increase in the host and promote the formation of immunity ken.

A subgroup of live vaccines concerns the artificially attenuated, attenuated Tribes. They are derived from well immunizing, fully virulent field viruses, that after a more or less large number of passages, preferably in cell cultures, artificially cultivated, thereby losing their virulence to the natural host. The Virulence loss in such a passing virus population does not occur at all at the same time Virus particles. By certain selection methods but you can attenuated Viru spiegelgut isolated (eg plaque method, final dilution method, etc.).

Attenuation is a targeted weakening or abolition of virulence a replicable virus for a given host while preserving the Vermeh viability, antigenicity and immunogenicity, over a given generation The result remains constant.  

Attenuation may be a modification or a mutation in terms of loss of the ill making properties, here in this case in particular with regard to the transfor mating properties. It is correspondingly more or less stable. While you are in the past for artificial attenuation of virulence mainly passages in animals or hatching eggs, attenuated strains are mainly obtained from cell cultures over permanent passages.

Live vaccines from heterologous virus strains can then provide immune protection, if there are very close immunological relationships between species-different viruses exist. You can then as a vaccine strain the related heterologous and therefore not use pathogenic virus strain.

Live vaccines have advantages and disadvantages. On average, a better and better will be with them achieved longer-lasting immunity. A well-attenuated vaccine virus can reduce immunity stimulation only if administered in sufficient concentration. The determination of a corresponding sufficient concentration can be achieved by simple routine tests are carried out within the skill of the average person skilled in the art lie. The vaccine protection usually starts after a few days after vaccination. Responsible for this are several processes: interference, interferon formation, fast Ent development of cellular immunity. Another advantage of live vaccines is that they can be applied very easily locally, z. B. orally or by aerosol. This is special In view of the comparatively easy accessibility of the affected tissues or Organs in the case of leiomyomas, endometrial polyps and endometriosis beneficial because in In such a case, the end user can apply an appropriate remedy himself.

Furthermore, according to the present invention ver vaccines from inactivated viruses be used. Virus inactivation is generally the abrogation of the infectiousness of a Virus particle called. In Impfstoftherstellung specifically meant by inactivity tion that viruses are artificial, with chemical-physical processes, the ability to multiply is taken without the other activities, in particular the antigenic and  immunogenic ability to be adversely affected. For vaccines from inactivated viruses the term "antigenic vaccine" is sometimes found in the literature.

The starting material for these vaccines are virus-containing organs or tissues, but today primarily from cell cultures, purified and highly concentrated Virus suspensions of fully virulent well-immunized virus strains. These are concentrated trated virus suspensions are then inactivated gently by suitable methods. operating room Timal are chemical or physical treatments that use the virus nucleic acid as a carrier proliferation and infectivity, but destroy the protein components of the virus effective components for antigenicity and immunogenicity are as little harm as possible, denature or change. Well-proven means are z. As formaldehyde and certain Deter genzien. The physical components are heat and radiation.

Furthermore, in connection with the present invention, split vaccines can be used used, the antigenic and immunogenic by splitting of viruses Virus components contained in, usually, purified form.

In the enveloped viruses, these are the virus-specific glycoproteins of the lipid-containing envelope len. Specific antibodies against these antigens bind in vivo to the glycoproteins of the Virus, thereby blocking their adhesion function to the cells and thus the infectivity.

The immunizing glycoproteins of enveloped viruses can be detected by the chemical Aufspal Release the virus envelope (certain lipid-dissolving detergents). The virus is losing by spontaneously and completely its infectious properties and then the ge wanted glycoprotein from unwanted components like nucleoprotein, capsid enzyme, Lipids etc. of the decomposed virus material by physico-chemical methods gerei nished, concentrated and processed into a vaccine.

For non-enveloped, nude viruses, split vaccines are important for immunization co-capsid proteins can be developed by those skilled in the art.  

Finally, synthetic antigenic vaccines can also be used by genetically engineered processes. About isolation and identification of relevant genes of the virus genome, for example, the capsid protein of the corre sponding viruses are produced by genetic engineering. It is within the capabilities the expert, the corresponding nucleic acid or resulting proteins so far to shorten that only the antigenic determinant or the corresponding epitope as Vaccine component remains. In this sense, the device according to the invention is also to use. The tRNA attached to the gene product of genes of the HMGI (Y) family Germaterial-bound viral nucleic acid can be used, usually after elution be determined to determine which virus, or its nucleic acid, in the training of for responsible for the development of leiomyomas, endometrial polyps and endometriosis Complex of viral nucleic acid and gene product of a gene of the HMGI (Y) family be is part.

After this identification, the inventive device but also for the ready one for the preparation of a composition of the invention for prevention and / or Treatment of leiomyomas, especially of the uterus, endometrial polyps and endomes triose essential component can be used. This is a viral nucleic acid or a pool of viral nucleic acids is added to the device according to the invention, whereupon that viral nucleic acid to the device or to this in a carrier material bound gene product of a gene of the HMGI (Y) family which contains at least one Bin site for the gene product of a gene of the HMGI (Y) family. Unbound or unspecifically bound viral nucleic acid is removed, for example by Wa rule the support material with a suitable washing solution. Subsequently, the speci fish-bound viral nucleic acid from the carrier eluted. The thus obtained Nucleic acid can then be used to form a viral component that can be incorporated into the inventive agent is used. For example, the viral nucleic acid in an expression vector is cloned and the expressed viral peptide or protein as Vaccine can be used. Alternatively, for example, the thus expressed viral peptide or protein, possibly after further intermediate steps involving the subject  People are known to be used for the production of antibodies, which in turn can be used as a vaccine in the agents according to the invention. Together hang with it is the expressed viral peptide or protein or the anti-directed against it body used for the manufacture of a remedy for the prevention and / or treatment of Leiomyomas, endometrial polyps or endometriosis essential component.

The same applies to the case of the binding of a gene product of the viral nucleic acid a gene product of a gene of the HMGI (Y) family. In this case, instead of the viral Nucleic acid The gene products of viral nucleic acid, in particular nucleic acid of Kandi data viruses, d. H. such viruses, which are suspected of the - causal - origin of Leiomyo men, endometrial polyps or endometriosis. The according to specifi shear binding and subsequent elution obtained from viral nucleic acid encoded Gene products can then be used directly as a vaccine or other modifiers tion or further processing steps are subjected. It can also be provided be that the vaccines are further purified or ver with appropriate adjuvants or suitably treated or prepared for the intended use to become.

The vaccines can be added to adjuvants, such as complete or incomplete Constant Freund's adjuvant. Further additives are the experts in this field known.

The agent according to the invention for the prevention and / or treatment of leiomyomas, wel a vaccine against a virus, wherein the nucleic acid of the virus at least a binding site for a gene product of genes of the HMGI (Y) family and their derivatives may also be used for the prevention and / or treatment of the following diseases or Disease states are used: endometrial polyps and endometriosis. The reason for this possible use is due to the fact that all three mentioned diseases or disease conditions, described above are comparable.  

The same applies to the use of the also disclosed means for prevention and / or Treatment of Leiomyomas, which comprises a vaccine against a virus, wherein the Nucleic acid of the virus encoded for a gene product, said gene product at least with a gene product of genes of the HMGI (Y) family or their derivatives interacts, to Prevention and / or treatment of endometrial polyps and endometriosis.

In the case of the agents according to the invention, the prevention of the treatment is in the Foreground.

In general, the agents according to the invention can be present as a pharmaceutical preparation, that in addition to a vaccine against a virus, wherein the nucleic acid of the virus at least a binding site for a gene product of genes of the HMGI (Y) family and their derivatives also includes pharmaceutically acceptable carriers useful to those of skill in the art are known.

The agents according to the invention can be used in addition to those exemplified above Vaccine other additives, such as the stabilization of the vaccine, the preservation, the modification of the properties of the vaccine itself, as well as substances that the egg properties of the agents according to the invention.

Agents that modify the properties of the vaccine itself can be adjuvants, such as for example, incomplete or complete Freund's adjuvant.

The compositions of the invention may further comprise components which they in a for convert the respective desired application form preferred form. So z. In the Case of the formation of the agents according to the invention as aerosols in addition to the vaccine ent speaking be provided for the aerosol formation required carrier material.

The agent according to the invention can, for example, in the form of a solution or emulsion for intraderm oral, intravenous or subcutaneous injection. Liquid solutions of the invention appropriate means may also be present in infusible form.  

Furthermore, the agents according to the invention can be present in lyophilized form.

Moreover, the agents according to the invention can in principle be used in any phar in pharmaceutically suitable form, including, for example, tablets, dragees, supposito rien, gels, powders.

The vaccine itself can be a complete virus particle, live or attenuated, as well as inactivated or parts thereof, the parts of which are typically the antigenic and carry immunological properties of the respective virus. It can be provided that the vaccine a variety of different virus particles or antigenic or immunogenic includes effective parts. The virus particles as well as the parts can be modified even in Form present. Such modifications may be made by, as generally fizr peptides, proteins that may be glycosylated, is known.

The virus particles or parts thereof may be produced by genetic engineering. It is not him necessary that the virus particles or parts thereof with the for the emergence of the leiomyomas, Endometrial polyps or endometriosis responsible or at least associated with it Virus is identical. It is crucial that those used in the vaccine or the Her virus, including parts thereof, are suitable for combating Disease causal agent, d. H. Virus to generate directed immune response and thus the transforming properties of the agent or virus involved in the pathogenesis prevent.

It has been found that the binding site on the nucleic acid of the virus has a number of Includes structural and sequence features. Basically, fizr seems to be the binding of gene products of the HMGI (Y) family, parts and derivatives thereof, the presence of ei ner - first - AT-rich sequence of importance. AT-rich sequence is not to understand that this forms an exclusive sequence consisting of AT dimers. Rather, this sequence may include any order of the two bases that may be interrupted by single or multiple nucleotides. Next to this first struk  tur- and sequence feature have the said binding sites of the gene products of HMGI (Y) family still a second AT-rich sequence, which may be similar like the first AT-rich sequence. Both AT-rich sequences are in a spatial di punch arranged relative to each other. This spatial distance results from the spatial Dimensions and thus from the secondary and tertiary structure of the HMGI (Y) proteins, d. H. the gene products of the genes of the HMGI (Y) family. As a result of this secondary and tertiary structure For a binding of the HMGI (Y) gene product, it is necessary for the first sequence and the second sequence arranged relative to each other in a plane on the viral nucleic acid are. Looking at the DNA as a three-dimensional model, so are the signs th arrangement acting as binding sites AT-rich sequences on the Be each facing side. This arrangement is also referred to as "acid face". If these three structural or sequence features of the viral nucleic acid are present, it occurs to a particularly sustainable binding of the gene product to the viral sequence, esp in regulatory regions of the nucleic acid (eg, promoters and enhancers) since before zugt this has the said structure and sequence characteristics. Missing one or more of these sequence or structural features, the binding of a gene product of the genes of HMGI (Y) family weak or absent.

Conversely, if one looks at the secondary or tertiary structure of the gene products of the gene HMGI (Y) family, there exist three regions, or domains, in a defined Distance apart, the AT-rich sequences have a high affinity have. Successful binding to a nucleic acid thus requires that the AT-rich sequences are arranged at a distance corresponding thereto. These Removal results from the pitch of the nucleic acid, which is usually about 10 base pairs is, with the result that the distance of the AT-rich sequences is usually 10 bases pairs as well as integer multiples up to ≦ 3 of them.

According to the present invention, such vaccines are for the agents according to the invention which are directed against a virus whose nucleic acid is at least one binding represent at least one gene product of genes of the HMGI (Y) family or their derivatives  having. Genes of the HMGI (Y) family are well known in the art. The genes of HMGI (Y) family represent a family of genes including, but not limited to, HMGIC, HMGIY and MAG genes. As an example, let us refer to the international patent application PCT / EP96 / 00716 and PCT / DE96 / 02494, the disclosure of which is herein incorporated by reference Reference is made. It is noteworthy that the binding site on the viral Nu small acid suitable for any of the above genes or its gene product is net. Herein the term gene product is intended to refer to parts thereof as long as these parts are still suitable to bind a viral nucleic acid. Likewise, the term Genpro comprising the respective derivatives of the gene product which have a modification, as is customary for peptides and proteins, and, for example, Dele tions and exchanges of carboxy-terminal portions of the proteins. In particular The term derivatives of the genes of the HMGI (Y) family also includes those in PCT / DE 96 10 2494 described aberrant transcripts and their translation products, as long as these as before are able to bind to the viral nucleic acid, especially in regulatory region Nucleic acid (eg., Promoters and enhancers) thereof. The characteri sation of such aberrant transcripts is described, for example, by Kazmierczak, B. et al .; At the. J. Pathol., 1998; 153 (2): 431-5 and their structure, for example, by Schoenmakers, E.F. et al., op.

In an alternative embodiment of the inventive means can be provided that the vaccine is an antibody directed against the virus. It is exhausted if the antibody is not primarily against the virus or a corresponding part directed thereof, but by means of a corresponding cross-reactivity its effect satisfied and accordingly ensures that there is no interaction between the vira len nucleic acid with the gene product of the genes of the HMGI (Y) family comes. It can be provided that the antibody ge against any component of the virus is directed, d. H. it may be directed against or interacting with proteins or protein fragments of the viral capsid, the optionally present glycopeptide or else with the corresponding viral nucleic acid or fragments thereof.  

The antibody as used in the invention may be a monoclonal antibody or polyclonal antibody. The term antibody herein may include a mixture of different monoclonal antibodies. Further, as used herein, the term antibody is intended to encompass any peptide or protein which has at least one antibody property, in particular, binds to a suitable epitope and causes the complex of antibody plus epitope or antigen to be involved in a pathogenesis of leiomyomas, endometrial polyps, and the like Endometriosis is no longer accessible form over leads or is removed from the pathogenesis process. This can be done, for example, by an interaction of a gene product of a gene of the HMGI (Y) family with the viral nucleic acid or with a gene product of a viral nucleic acid (the corresponding virus being causally involved in the development of leiomyomas, endometrial polyps or endometriosis is involved) the latter is avoided, and this prevention can be caused both directly and indirectly, indirectly, for example, by removing the ent speaking viruses or virus particles. The term antibody also includes antibody fragments and their derivatives, in particular (Fab) 'or F (ab) ₂ fragments as well as single-chain antibodies and the like. Derivatives of these antibodies are also known to those skilled in the art and include, in particular.

The above applies mutatis mutandis in the event that a vaccine against a virus is intended, whose nucleic acid codes for a gene product, said gene product at least one gene product of genes of the HMGI (Y) family or their derivatives interacts.

The viruses against which a vaccine or an antibody in the compositions of the invention ent preferably belong to the group of polyoma viruses. Polyoma viruses belong to Family of Papovaviridae, which include the papilloma virus and simian vacuolating virus 40 (SV 40) belong. The family is characterized by extreme heat stability. Papovaviri dae are envelopeless cubic DNA viruses with a diameter of 45 to 55 nm, covers send 72 capsomers as well as a cyclic double-stranded DNA.  

In the inventive use of the immunizing agent according to the invention, and in particular active immunization, against the viruses involved in the pathogenesis and / or Atiology of leiomyomas, endometrial polyps or endometriosis are associated For example, viruses prefer those causally related to the pathogenesis / etiology of leiomyomas, endo metrium polyps or endometriosis are connected or associated.

In the methods of the invention cell cultures are used which are derived from a leiomyoma, endometrial polyp or endometriotic tissue. The manufacturer Such cell cultures are known to those skilled in the art and are described for example in Stern, C. et al .; Geburtsh. u. Frauenheilk. 52 (1992), 767-772.

Under normal karyotype is to be understood here the set of chromosomes, as he after Application of routine techniques, provided that it is shown in a representation of ≧ 500 gangs per haploid set no identifiable anomalies especially of the areas 12q14-15 and 6p21.

An expression vector for a gene of the HMGI (Y) family is characterized in that it belongs to its entirety leads to the expression of a gene of the HMGI (Y) family and thus to Her position of corresponding gene products. Typically, such an expression vector comprises an origin of replication that is responsible for a gene product of the HMGI (Y) gene family or Frag ment encoding nucleic acid, and appropriate transcriptional and translational regulation rende sequences. Such constructs are known in the art and described, for example, in US Pat Winnacker, E.-L .; From Genes to Clones; Weinheim; New York: VCH, 1987.

In principle, any transfection method is within the scope of the present invention applicable, which leads to a transfection of the corresponding cell cultures.

The production of cDNA is known to those skilled in the art. For the comparison of the RNA or cDNA pattern of the transfected cells or cultures with those of non Transfected cells or cultures are typically used as under the Me  method of the so-called "differential display" (Diatchenko, L .; Proc. Natl. Acad. Sci. USA, Vol. 93, pp. 6025-6030, 1996).

When checking in the transfected cultures over control cultures expri mated or amplified expressed RNA (s) by sequence homology to the presence Viral elements is typically operated so that the sequence with the aid of from relevant databases, eg. B. BLAST, a database service of the National Center for Biotechnology Information (NCBI), reviewed or identified where appropriate.

It is within the scope of the process of the invention that also by the primary transcript Nucleic acids derived for the comparison of the RNA pattern of transfi ornamented cultures can be used with that of control cultures. Ent speaking, it is possible to make this comparison on the basis of the cDNA pattern, wherein the cDNA is derived from the transcription products, i. H. the RNA species using known methods.

The control cultures are usually those with normal karyotype derived from a leiomyoma, endometrial polyp or endometriotic tissue, and which with a Expression vector transfected, however, the gene of the HMGI (Y) family or its Derivative, d. H. the insert encoding a gene product is missing. But control cultures can also be those that are transfected with no expression vector.

In a further method according to the invention, in which the execution of a PCR Assays are provided, with the probe used for the PCR being a viral probe the PCR test according to the methods known in the art. Under PCR test, a poly merase chain reaction test understood in which at least one sequence-specific primer is used for selective amplification of the desired nucleic acid (fragments). (please refer Newton, C.R .; Graham, A .; "PCR"; 1994, Spektrum Akadem. Publisher, Heidelberg, Berlin, Oxford.  

By primer or viral probe herein are meant oligonucleotides and / or nucleic acid fragments understood to be directed to a detection of nucleic acids containing a Homology to the primer / probe. The preparation of such viral probes may be done in any way known to those skilled in the art, such as by organic chemical Synthesis or using PCR or cloning techniques.

Is in the context of a method according to the invention a cDNA library of a Leiomyoma, endometrial polyps or endometrial tissue applied, the / of an activity has a gene of the HMGI (Y) family or a derivative, so the activity be identified by a corresponding chromosome aberration.

In the methods of the invention, screening is typically under conditions low stringency. Under conditions of low stringency should be understood be that by lowering, for example, the hybridization temperature or modification the washing conditions (eg increasing the salt concentration) also bind to such Nucleic acids are made whose homology to the sequence of the probe is markedly reduced where at first, a detection of false-positive nucleic acid sequences accepted will, as a final clarification whether it is a positive signal or result, by sequencing and sequence analysis of the identified sequences, and thus permits excretion of the false-positive sequences.

In the method according to the invention, by comparison of the RNA or cDNA pattern of transfected cell cultures with that of control cultures, or by a positive signal in a PCR test using primer (pairs), the Sequen viral nucleic acids, or by a positive signal when screening a cDNA library with a virus-specific probe, or by analysis of the cDNA clones on viral sequences or comparison with a normal myometrium cDNA library, It has been found that viral elements in the leiomyomas, endometrial polyps or En dometriosis tissue or the cell cultures imaged therefrom  be seen that the viral elements are identified and / or classified and exclusive used for Impfstoftherstellung.

The device according to the invention for the determination of a pathogenesis of Leiomyomas, endometrial polyps or endometriosis virus involved includes a gene pro of genes of the HMGI (Y) family linked to a carrier. In connection with the device according to the invention and its possible uses includes the Term gene product also includes parts of the gene products or derivatives of the gene products. It lies the definition of gene products also the above given definition of genes of the Based on HMGI (Y) family.

The gene product is coupled to a support material, which is known to those skilled in the Ge area is selected accordingly. Suitable carrier materials are all those materials which allow binding of proteins or derivatives, either directly or indirectly. suitable Support materials are typically found in the field of chromatography materials. Such a bond may also be an adsorption or a reversible bond. Because it When the gene products of the HMGI (Y) family are proteins, those described in Im mobilization of proteins used in processes and compounds.

With regard to the design of the gene products bound to the carrier material is in we to make sure that the area is bound to the carrier material or is available for binding viral nucleic acid that binds to the viral Nu is responsible. In that regard, the corresponding gene product may be shortened or For example, be made available as a fusion protein. Any construct is included conceivable, provided that the nucleic acid-binding part of the gene product or that part of the Gene product of the genes of the HMGI (Y) family, which is responsible for the binding of the gene product of vi ral nucleic acid is still available for binding of a nucleic acid is available.  

In the specific case, such a device may be designed so that it is at an affinity chromatographic column, corresponding to the column material Gene product of genes of the HIVIGI (Y) family, be it from a gene product or ver different gene products, is immobilized and different approaches or mixtures viral nucleic acid or gene product encoded by viral nucleic acid to Trä germatrix are added. As a result of the interaction between the gene product and the viral nucleic acid or the gene product of the viral nucleic acid comes to an end formation of a stable complex. Non-specifically bound viral nucleic acid or un bound nucleic acid or non-specifically bound or unbound gene product of viral nucleic acid and other components of the applied sample are used by the Washed column. Through a suitable elution buffer are then - possibly specific - the interactions between the gene product and that bound to the gene product reduced viral nucleic acid or the bound gene product of the viral nucleic acid, such that the corresponding viral nucleic acids or the gene products encoded by them eluted and further analyzed.

The invention will be elucidated by the following examples, experimental findings and figures further explained. It shows

Fig. 1 shows the size distribution of fibroids with normal karyotype (gray columns) as well as 12q14-15 aberrations (black columns) and

Fig. 2 is an overview of the vectors used in Example 4.

example 1

The results of previous cytogenetic studies on uterine fibroids are contradictory regarding possible correlations between tumor size and the occurrence of clonal Chromosomal aberrations. The problem of these studies, however, is that the investigated Tumors possibly z. B. are selected by size. Since the question of a possible Kor  relation but also depends on whether the chromosome aberrations secondary on and increase the growth potential of the affected tumors, was a study unselected fibroids performed. Only fibroids according to Hysterek were examined tomie, where all tumors were examined, which by palpation of the surgically ent distant uterus were detectable.

A total of 155 fibroids from 96 patients were cytogenetically examined. Showed 28% of myomas clonal karyotype changes. On the three main karyotype groups with normal karyotype, aberrations of the chromosomal region 12q14-15 and deletion of the lan Genes of chromosome 7 accounted for 72%, 12%, and 8%. The average tumor size Table 1 shows the groups.

Table 1 Average fibroid size in the three major karyotype groups with 12q14-15 aberrations, deletions of the long arm of chromosomes 7 and normal karyotype

Karyotype group average size [cm] ± standard deviation [cm] normal karyotype 3, 4 ± 2.1 12q14-15 aberrations 8, 9 ± 5, 6 Deletion of chromosome 7 3.5 ± 2.0

The results clearly show that the occurrence of 12q14-15 aberrations, which correlate molecularly with mutations in or in the region of the HMGIC gene, is accompanied by a highly significant increase in the size of the corresponding fibroids when compared either with normal karyotype fibroids or with Deletions on the long arm of chromosome 7 are compared. The differences become clear not only when comparing the mean values, but also the distributions of the tumor sizes of the individual tumor groups, as shown in FIG. 1.

In summary, the appearance of chromosome aberrations of the chro 12q14-15, associated with enhanced expression of HMGIC gene or ex associated with altered transcripts of this gene, to an enhanced tumor wax tum.

Example 2

Mutations in the region of the HMGIC or HMGIY gene manifest themselves cytogenetically by chromosome aberrations of the region 12q14-15 and 6p21, respectively. At least theoretically but it is quite conceivable that the cytogenetically recognizable aberrations are only "the tip of the Iceberg "and represent a much larger part of the mutations of the two Gene is associated with cytogenetically unrepresentable chromosomal modifications. Would this In the case, it could be a key role of the said aberrations in the tumorent overall as a primary mutation. A method for after One of the "hidden" rearrangements is fluorescence in situ hybridization (FISH). It was tested on a series of 40 fibroids with an apparently normal karyotype FISH- Carried out experiments using cosmid and PAC probes carrying the Lo coverage of the HMGIC or HMGIY gene. The probes were so ge selects a range of about 150 kb 5 'to 40 kb 3' from the HMGIC gene and from 30 kb 5 'to 40 kb 3 'from the HMGIY gene. All myomas were using the probes for both Genes studied; at least 20 metaphases were analyzed. In no case erga there is evidence of conventional cytogenetics unrecognizable, ver revealed chromosomal rearrangements of the examined areas.

Considering the frequency of fibroids without apparent cytogenetic changes conditions (see Example 1) and the results of the studies presented in this example, It is likely that the mutations of the genes of the HMGI (Y) family in the majority the uterine fibroids plays no key role.  

Example 3

Regardless of whether these changes are primary or secondary, being considered molecular assumed genetic basis of 12q14-15 and 6p21 aberrations in uterine fibroids, that it is due to the chromosomal rearrangements to an expression / enhanced expression or an expression of aberrant transcripts of the HMGIC gene or HGMIY gene, which is absent in normal uterine tissue. For the HMGIC gene is by means of an RT-PCR in nor Malignant uterine tissue usually no HMGIC gene expression detectable. There were investigated with this method 40 myoma tissue with apparently normal karyotype. aim The investigation was again to determine whether in these fibroids, as in those with 12q14-15 changes, evidence of HMGIC gene expression.

In none of these fibroids were indications of expression found, so that out From these results it can be concluded that in the formation of these fibroids HMGIC gene expression is not the primary event.

Example 4

To study the effect of HMGIC on the SV 40 promoter, two vector systems are transfected into a cell. These are the expression vector H3HX for HMGIC and the "pGL3 luciferase reporter vector" from Promega. The complete "pGL3 Luciferase Reporter Vector" system from Promega comprises 4 different vectors that allow DNA sections to be examined for promoter or enhancer regions. These vectors are shown in FIG . To study promoter sections, the vector "pGL3 enhancer" is needed. The vector "pGL3 promoter" is intended for the study of enhancer elements. Furthermore, the vector "pGL3 promoter" is used in this experiment to test the mode of action of HMGIC on an SV40 promoter or promoters of other polyomaviruses. For this purpose, the vector H ₃ H _{x is} cotransfected with the vector "pGL3 promoter".

The vector "pGL3-Control" serves as a positive control for the system, a transfection finally with the vector "pGL3 promoter" as a negative control.

The individual vectors have the same except for promoter and enhancer elements Basic structure. They have a modified coding region for fireflies Luciferase (Photinus pyralis) (luc +), which is used to study transcriptional activity in transfected eukaryotic cells. Furthermore, they contain a pro karyotic origin of replication for propagation in E. coli, an ampicillin resistance gene for the selection, an origin of replication of filamentous phage (f1 ori) for the products single-stranded DNA (ssDNA) and a multi-cloning site (MCS) 3 'and 5' of Lucife rase gene.

The "pGL3 promoter" vector is 5010 base pairs in size and contains in contrast to "pGL3 enhancer" an SV40 promoter and no enhancer. DNA fragments ver contain apparent enhancer sequences, 3 'or 5' of the luciferase gene can be used and thus lead to reinforcement. Furthermore, the SV40 promoter can by replaced by the polyomavirus promoters.

The vector "pGL3-Control" (5256 base pairs) contains an SV40 promoter and an En hancer sequence, which leads to a high expression of luc + in most mammalian cells. This vector is used to control transfection efficiency and sets the internal standard for the promoter and enhancer activity of the other vectors.

HeLa cells have been found to be suitable for the study as they are very easy to handle ben, the process of transfection withstand almost no damage and no expressi on HMGIC (the absence of HMGIC expression was confirmed by Detected "Northern Blot"). The cells are transfected into 6-well plates used.  

For the process of transfection, 2 μg DNA with cell medium (TC 199), excluding calves serum and antibiotics, mixed (both can interfere with complex formation), final volume 100 μl.

10 μl of "SuperFect" are added to the DNA mixture. After mixing, incubate for 10 min at room temperature, with complexes of the DNA and the "SuperFect" form.

During the incubation the old medium is aspirated from the cells and the cells are rinsed with 1 × PBS. The mixture of "SuperFect" and DNA is mixed with 888 μl of cell medium containing 20% calf serum, which is then added to the cells. After incubation (in the incubator at 37 ° C. and 6% CO ₂ ) for 16-18 hours, fresh medium (20%) is added and the mixture is incubated for a further 8-32 hours.

The evaluation of the experiment is carried out with the "Luciferase Assay Kit" by Stratagene (s.u.).

Luciferase extraction and determination of luciferase concentration

After incubation of the transfected cells, the medium is aspirated and 500 μl 1 × Cell lysis buffer added. After 15 minutes incubation, at room temperature on a Shakers, lysing the cells. The cell lysate is transferred to Eppendorf cups. This is for for a short time at 4 ° C storable. For a long time it can be stored at -80 ° C, this however, up to 50% of the luciferase activity is lost.

For the determination of the luciferase concentration, 20 μl of cell lysate are mixed with 1000 μl of "luciferase assay reagent" (LSA) (both should be at room temperature). The luciferin in the reaction mixture is reacted under ATP consumption to produce light quanta.

Luciferase substrate (luciferin) + ATP + O ₂ → light (560 nm) + oxyluciferin + AMP + PP _i

The emitted light quanta can be measured with a photocell of a luminometer become. The determined values are calculated in relative light units (RLL) given and convey in relation to other values information about the educated Amount of luciferase.

Results

So far, two separate series of measurements were performed. Further measurements, before all things with promoter regions of the BK and JCV viruses can be made easily be in the present test system by cloning the corresponding promoter regions into the test vectors.

The results of the first 2 series of measurements are summarized in Table 2.

Table 2 Results of transfection attempt

The measurement results are above those of the negative control and among those of the positive con troll with a very strong promoter, indicating a slight regulation of the viral promoter region occupied by HMGIC.

This demonstrates the involvement of viruses in the genesis of Leiomyomas, endometrial polyps and endometriosis.

The features disclosed in the foregoing description and in the claims Invention can be used individually as well as in any combination for the realization be essential to the invention in its various embodiments. The Offenba content of the claims is hereby incorporated by reference.

Claims (32)

1. A means for the prevention and / or treatment of leiomyomas comprising a vaccine against a virus whose nucleic acid has at least one binding site for a gene product of Genes of the HMGI (Y) family or their derivatives. 2. Means for the prevention and / or treatment of leiomyomas comprising a vaccine against a virus whose nucleic acid encodes a gene product, this gene product at least one gene product of genes of the HMGI (Y) family or their derivatives interacts.   3. Composition according to claim 1 or 2, characterized in that the vaccine is a virus particle or parts thereof. 4. Composition according to claim 1 or 3, characterized in that the binding site on the Nucleic acid of the virus, the structural and sequence feature of a first AT-rich sequence includes. 5. Composition according to claim 4, characterized in that the binding site on the nucleic acid of the virus in addition to the first sequence nor the structural and sequence features comprises that

• a second AT-rich sequence is present, and
• - The first and second sequence are arranged at a spatial distance from each other.

6. Means according to claim 5, characterized in that the spatial distance is selected is that the first sequence and the second sequence relative to each other in a plane on the Nucleic acid are arranged. 7. Composition according to one of claims 1-6, characterized in that the genes of HMGI (Y) family MAG genes, HMGIC, HMGIY, aberrant transcripts of genes of HMGI (Y) family and derivatives thereof. 8. Composition according to claim 1 or 2, characterized in that the vaccine is an antibody which is directed against the virus or a part thereof.   9. Composition according to claim 8, characterized in that the antibody is selected from the group containing monoclonal antibodies, polyclonal antibodies, polyvalent antibodies, Antibody fragments and derivatives thereof. 10. Composition according to one of claims 1-9, characterized in that the virus is selected is from the group comprising polyoma viruses. 11. Composition according to claim 10, characterized in that the virus is selected from the Group comprising BK virus and JVC virus. 12. Composition according to one of claims 1-11, characterized in that the leiomyomas sol of the uterus. 13. Use of the agent according to any one of claims 1-12 for the prevention and / or loading treatment of endometrial polyps. 14. Use of the agent according to any one of claims 1-12 for the prevention and / or loading treatment of endometriosis. 15. Use of the agent according to any one of claims 1-12 for immunization against the Viruses associated with the pathogenesis and / or etiology of leiomyomas, endometrial polyps or endometriosis are connected. 16. Use of the agent according to any one of claims 1-12 for the preparation of a pharma ceutical composition comprising the agent according to any one of claims 1-12 and ei a pharmaceutically acceptable carrier for the prevention and / or treatment of Leiomyo endometrial polyps and endometriosis or for immunization against the viruses that with the pathogenesis and / or etiology of leiomyomas, endometrial polyps or endo metriose are connected.   17. Use according to claim 15 or 16, characterized in that the immunization is an active immunization. 18. A method for detecting viruses suitable for the preparation of a means for the prevention and / or treatment of leiomyomas, endometrial polyps or endometriosis, where the agent comprises a vaccine against a virus whose nucleic acid has at least one binding site for a gene product of genes of HGMI ( Y) family or derivatives thereof, or whose nucleic acid codes for a gene product, wherein the gene product comprises at least one binding site for a gene product of genes of the HMGI (Y) family or derivatives thereof, in particular an agent according to one of the preceding claims, which includes the steps:

• a) transfection of a normal karyotype cell culture derived from a leiomyoma, endometrial polyp or endometrial tissue, with an expression vector for a gene of the HMGI (Y) family or its derivative,
• b) comparison of the RNA pattern of the transfected cells with that of control cultures, and
• c) Examination of RNA (s) expressed or amplified in the transfected cultures relative to control cultures by sequence homology to the presence of viral elements.

19. A method for determining for the production of an agent for prevention and / or loading treatment of leiomyomas, endometrial polyps or endometriosis of suitable viruses, where wherein the agent comprises a vaccine against a virus whose nucleic acid has at least one Binding site for a gene product of genes of the HGMI (Y) family or their derivatives or whose nucleic acid codes for a gene product, wherein the gene product minde at least one binding site for a gene product of genes of the HMGI (Y) family or their  Derivatives, in particular an agent according to one of the preceding claims, which performing a PCR test, the primers used for the PCR (pairs) correspond to the sequence of viral nucleic acid. 20. A method for detecting viruses suitable for the preparation of a composition for the prevention and / or treatment of leiomyomas, endometrial polyps or endometriosis, where the agent comprises a vaccine against a virus whose nucleic acid has at least one binding site for a gene product of genes of HMGI ( Y) family or derivatives thereof, or whose nucleic acid codes for a gene product, wherein the gene product comprises at least one binding site for a gene product of genes of the HMGI (Y) family or their derivatives, in particular an agent according to one of the preceding claims, which includes the steps:

• a) creating a cDNA library of a leiomyoma, endometrial polyps or endometriotic tissue which has an activation of a gene of the HGMI (Y) family or a derivative, and
• b) screening the cDNA library with a virus-specific probe or
• c) Analysis of the cDNA clones for viral sequences or
• d) Comparison with a normal myometrium cDNA library.

21. The method according to any one of claims 18-20, characterized in that the gene of HMGI (Y) family is selected from the group consisting of HMGIC, HMGIY, MAG, aberrant Transcripts of the genes of the HMGI (Y) family and derivatives thereof.   22. The method according to any one of claims 18-21, characterized in that the virus, the viral element or the virus-specific probe is selected from the group of viruses that Includes polyoma viruses. 23. The method according to any one of claims 18-22, characterized in that the Hybridisie especially under screening, under conditions of low stringency is taken. 24. Use of a method according to any one of claims 18-23 for detecting viruses, against for the prevention and / or treatment of leiomyomas, endometrial polyps or Endometriosis can be immunized. 25. Device for determining a pathogenesis of leiomyomas, endometrium polyp or endometriosis virus, which is a gene product of genes of HGMI (Y) family or a part thereof or its derivatives which binds to a Trä ger is bound. 26. The device according to claim 25, characterized in that the carrier is selected from the group of materials that bind to peptides and / or proteins suitable materials. 27. The device according to claim 25 or 26, characterized in that the gene product or a part thereof or its derivative at least that part which binds viral nucleic acid to the gene product allowed. 28. The device according to claim 27, characterized in that the viral nucleic acid to comprises at least the structural and sequence feature of a first AT-rich sequence.   29. The device according to claim 28, characterized in that the viral nucleic acid ne ben of the first sequence nor the structural and sequence features comprises that

• a second AT-rich sequence is present and
• - The first sequence and second sequence are arranged in a spatial distance from each other.

30. The apparatus according to claim 29, characterized in that the spatial distance so is selected such that the first sequence and the second sequence relative to each other in an Ebe ne are arranged on the nucleic acid. 31. The device according to claim 25 or 26, characterized in that the gene product of Genes of the HMGI (Y) family or part thereof or its derivative at least that part which allows binding of a gene product encoded by a viral nucleic acid. 32. Use of the device according to one of claims 25-31 for providing a for the preparation of an agent for the prevention and / or treatment of leiomyomas, En dometrium polyps or endometriosis essential component.