CA2239682A1

CA2239682A1 - Nucleic acid sequences of genes of the high mobility group proteins and uses thereof

Info

Publication number: CA2239682A1
Application number: CA002239682A
Authority: CA
Inventors: Jorn Bullerdiek
Original assignee: Individual
Current assignee: Individual
Priority date: 1995-12-21
Filing date: 1996-12-20
Publication date: 1997-07-03
Also published as: JP2000504933A; AU1870597A; NZ504445A; EP0870024A2; JP2010029207A; WO1997023611A3; WO1997023611A2; DE19548122A1; JP2007312778A

Abstract

The invention relates to DNA sequences, the use thereof and the use of DNA
sequences of the MAG genes or high mobility group protein genes, agents for treating various disorders including tumour disorders, for influencing vascular development and for contraception and tissue regeneration, and to suitable kits and procedures. The specified sequences, agents, applications, kits and procedures allow a specific action on molecular mechanisms common to various disorders, vascular development, contraception and tissue regeneration. This reduces the drawbacks normally observed with agents and procedures of this type.

Description

Professor Jorn Bullerdiek Nucleic Acid Sequences of Genes of the High Mobility Group Proteins and Their Use The object of this invention is DNA sequences, their use, and the use of DNA sequences of MAG genes or of genes of the high mobility group proteins, substances for the purpose of treating different diseases as well as for the purposes of contraception and tissue generation and corresponding kits and methods.

When studying the molecular basis of aberrant cell growth that accompanies the growth of benign and m~lign~nt tumors, so-called MAG genes (multiple-tumor aberration growth genes) were identified as belonging to the group to which high mobility group protein (HMG genes) genes belong.

The genes of the high mobility group proteins, such as the HMGI-C gene located on the human chromosome 12 and the HMGI-Y gene on chromosome 6, which, among the known HMG genes, has the relative highest homologous degree compa~ed to HMGI-C, usually have components that code for DNA-bonding protein parts and components that code for protein-bonding components.

Schoenm~kers' (Schoenmakers et al., Nature Genet 10: 436 - 444 (1995)) studies show that mutations of the HMGI-C gene are the most likely cause of the development of many benign human tumors, some groups of which are: uterus leiomyoma, lipoma, pleomorphic adenoma of the salivary gland, endometrium polyps, hamarto chondroma of the lung, aggressive angiomyxoma, and fibroadenoma of the m~mm~

With the exception of the pleomorphic adenoma, all of the above tumors are of mesenchymal origin or contain mesenchymal components that are considered to be monoclonal. Today the pleomorphic adenoma is mostly considered to be an epithelial tumor, although its histogenesis still has not been completely det~rmined and there are discussions concerning the participation of mesenchymalic cells in the development of tumors. Many of the tumors sometimes or even regularly show mesenchymalic metaplasia. Also striking is the appearance of myxoid cartilage in many of the tumors, which is characteristic of hamarto chondroma of the lung and the pleomorphic adenoma, for example.

Ashar (Ashar et al., Cell 82: 57 - 65 (1995)) has conf~rmed Schoenmakers' (SchoPnm~k~xs et al., Nature Genet 10: 436 - 444 (1995)) fin(lin~s for the lipoma group.
The mutations that can manifest themselves cytogenetically as structural chromosome aberrations of region ql4-15 of chromosome 12, can be proven with the help ofthemethods of the polymerase chain reaction for the rapid amplification of 3' cDNA ends (3' RACE PCR) and/or for fluorescence in situ-hybridization. It is found that often breaks occur in the third and more rarely in the fourth intron of the HMGI-C gene. The 3 ' located component of the gene is separated from its original sequence due to breaks and is substituted by a so-called ectopic DNA sequence. Such ectopic sequences appalelllly ori~n~te in other genes. The fusion gene of the ectopic sequence with parts of the HMGI-C that codes for the DNA-bonding components remains on the resulting derivative of chromosome 12 and is expressed as a fusion transcript in the cells, together with the original transcript. It is not known whether only an expression of the gene, e.g. caused by the shift of an enhancer in the area of the gene, can result in the growth of a turnor.

It is r~n~rk~ble that many of the above turnors have sub-groups for which the chromosome changes of band 6p21 are characteri~tic. The gene for HMGI-Y is located in this band, which, as already indicated above, has the highest homologous degree of all known HMG genes compared to the HMGI-C gene, so that mutations of this gene may also play a role in many of the above tumors.

The agents described in the state of the art that are used for the purpose of influencing angioneoplasm, i.e. (neo-)angiogenesis, (neo-)vascul~ri7~tion and tumor angiogenesis, and for the purpose of preventing blindness due to neo-vasc~ ri7~tion as often occurs in connection with diabetes mellitus, for example, and for the purpose of treating endometriosis, for the purpose of contraception and tissue regeneration, are charact~ri7ed in that they use an indirect mech~ni.~m to arrive at their final effect.

Indirect merh~ni~m means that the respective agent itself, or effector molecules formed or activated by this agent, act on the target cells, possibly while using receptors or more or less specific receptor-like structures, and intelrere in the cellular activity without carrying any specificity inherent in their own structure which would make it possible to influence the translation and/or the transcription of the gene or the sequences that are responsible for the respective phenomenon or clinical picture.

A number of basic disadvantages can be deducted from this mech~ni~m Due to non-specific receptor mech~ni.em~ or cross-reactivities of the receptors or receptor-like structures, said agents often are accepted into other tissues as target tissue or target cells.
This is why there are no specific effective locations and therefore significant side-effects must be anticipated. In addition, the influence of said agents on the reactions within the cell results in a considerable disturbance which may or may not result in the desired effect in the target cell.

Especially problematic is influencing angioneoplasm with state of the art agents. Apart from the hope of spontaneous healing, the only other common option in clinical scenarios is to transplant vessels. The availability of suitable vessels is a very basic problem.

Influ~ncin~ angioneoplasm in order to prevent tumor angiogenesis seems to be a promising prospect for an effective cancer therapy that is being examined using suitable, but typically systemic agents. The use of such systemic agents, however, is accompanied by corresponding negative effects, as described above and as they result from simil~rly non-specific radiation therapy.

There are numerous causes for the loss of vision and an equal number of different tre~tmPnt.c are available today. It is a known fact that the vision of patients that suffer from diabetes mellitus is impaired due to neo-vascularization that can result in total blin(1ne~s. It is possible to slow vision loss by treating the diabetes mellitus; however, there is an urgent need for an agent that specifically makes it possible to treat or prevent blindness due to neo-vasc~ ri7~tion, independent of the therapy for diabetes mellitus.

The side-effects of hormonal agents used for contraceptive purposes are sufficiently known and, despite intensive efforts on the part of the drug companies, still exist. A
central problem in the development of oral contraceptives certainly is the fact that there still is a need for a well tolerable and reliable agent that interrupts a pregnancy following the nidation of the fertilized egg.

Finally, tissue regeneration still is a largely unsolved problem despite successes, above all in the area of skin culture. Typically, complex nutrient solutions are used in order to regenerate at least some tissues. However, the ability to reproduce the process is not always certain, due to the complex media or complex media a-lmix~lres that are used whereby complex media or media admixtures are necessary because a targeted admixture of individual factors is rarely successful. Even if individual compositions are known that would allow for the regeneration of the respective tissue in the desired manner, side-effects have to be anticipated as well, due to the indirect action of such compositions. In addition, the person responsible for regenerating the tissue, as well as the patient who is to receive the regenerated tissue, might be at great risk due to the biological sources required for the regeneration process.

The treatment of tumors still poses one of the greatest challenges to medicine. Despite complehensive efforts, there are few specific therapies. Often chemotherapy and radiation therapy offer the only alternatives, but they have inherent side-effects that often question the use of the therapies as such.

The invention is charged with describing and making available DNA sequences that are suitable, for example, for providing agents for the purpose of treating diseases or for the purpose of influencing biological systems while reducing the side-effects that are usually associated with such treatments.

Another object of the invention is to show new uses of sequences of the MAG genes or the genes of the high mobility group proteins, and to provide agents for the specific treatment of diseases or for influencing biological systems, while reducing the side-effects that are usually associated with thern.

The object of the invention is attained through a DNA sequence that is characteri7:ed by at least one sequence as shown in figures 1 through 19.

In one of the embodiments the DNA sequence corresponds partially or completely to the sequence of the HMGI-C gene.

In another embodiment of the invention, parts of the sequences shown in figures 1 through 19 make up a part of the DNA sequence of the HMGI-C gene.

It is possible for the DNA sequence to be mutant as compared to the DNA sequenceshown in figures 1 through 19.

The invention proposes that the DNA sequence primarily has the same sequence as the one shown in figures 1 through 19, including the respective complementary strand and modified versions of both strands.

An alternative is that the DNA sequence has a primarily functionally identical nucleic acid sequence to the sequences shown in figures 1 through 19.

In one embodiment, the DNA sequence in accordance with the invention has at least one sequence that codes for a DNA-bonding part of the corresponding translation product(s).

An ~ltern~tive is that the sequence in accordance with the invention does not have a sequence that codes for the protein-bonding part of the corresponding translation product(s).

In a pre~lled embodiment, the sequence in accordance with the invention has one or several sequences Sr which replace(s) or supplement(s) the sequence(s) that code(s) for the protein-bonding part of the corresponding translation product(s).

In an especially plefelled embo~iment sequence, Sr is selected from the group that comprises other sequences of the human genome, sequences of other (donor) org~ni~m~
and artificial sequences and combinations thereo~

In an alternative embodiment, the sequences shown in figures 1 through 19 are aberrant transcripts of the HMGI-C gene.

In the following paragraphs the above sequences will be called SAT.

The invention also describes an expression vector that comprises at least one transcription promoter that is followed by at least one of the SAT sequences further down. - -In addition, the invention comprises a host cell that transfers or transforms with an expression vector in accordance with the invention.

In a plefe"ed embodiment the host cell is a prokaryotic cell.

In yet another embodiment the host cell is an eukaryotic cell.

In a plefelled embodiment the eukaryotic cell is a yeast cell.

In an especially plefelled embodiment, the eukaryotic cell is a m~mm~l cell.

In addition, the invention describes a protein that is a translation product of one or several of the SAT sequences and/or the corresponding transcript(s) in native or mutant form and/or in a complete or fragmented form whereby the translation product glycosylates, is native or mutant and/or is in a complete or fragmented state, glycosylates partially or not at all and/or phosphorylates or does not phosphorylate and/or is chemically modified or not chemically modified.

In yet another aspect the object of the invention is attained through the use of at least one of the SAT sequences in accordance with the invention for the purpose of influencing angloneoplasm.

The invention also describes another aspect that attains the object of the invention through the use of a MAG gene for the purpose of influencing angioneoplasm.

Another aspect that attains the object of the invention is the use of at least one high mobility group protein gene for the purpose of influencing angioneoplasm.

In a plerelled embodiment, the high mobility group protein gene is selected from the group that comprises the HMGI-C gene and the HMGI-Y gene.

In the following paragraphs the above genes or groups of genes will be referred to as GG.

_ It is possible to use sequences that have fundamentally the same nucleic acid sequence as the GG genes.

An alternative is the use of sequences that have essentially the same functional nucleic acid sequence as that of the GG genes.

In the following paragraphs, the above defined sequences together with the above defined GG genes will be referred to as SG sequences.

In another embodiment, the SG sequences have at least one sequence that codes for a DNA-bonding component of the corresponding translation product(s).

In another alternative of the invention the SG sequences and their derivatives in accordance with the invention do not have any of the sequences that code for the protein-bonding component of the corresponding translation product(s).

In addition, the SG sequences or derivatives in accordance with the invention have one or several Sr sequences that replace(s) or supplement(s) the sequence(s) that code(s) for the protein-bonding component of the corresponding translation product(s).

It is possible for the Sr sequence to be selected from the group that comprises other sequences ofthe human genome, sequences of other (donor) org~ni.~m~, and artificial sequences and combinations thereo~

In one embodiment the SAT and SG sequences and their derivatives in accordance with the invention are double-strands and/or a coding and/or non-coding single strand and/or cDNA.

The SAT and SG sequences and their derivatives in accordance with the invention can be native and/or mutant and/or in a fragmented or non-fragmented state.

In an embodiment of the invention the SAT and SG sequences and their derivatives in accordance with the invention can have at least one promoter and/or at least one enhancer element and/or at least one transcription t~orrnin~tion element andlor at least one resistance gene and/or at least one additional m~rking gene.

In one embodiment at least one of the SAT or SG sequences or their derivatives in accordance with the invention can be cloned in a host system.

In this case the SAT and SG sequences and their derivatives in accordance with the invention are copied at least once.

In the following paragraphs the above GG genes, the SG sequences and their derived sequences or the different embodiments will be referred to as ST sequences.

In accordance with the invention the object of the invention is attained with the help of an agent used for the purpose of influencing angioneoplasm and that is comprised of at least one agent Ms that is selected from the group that comprises sense DNA, sense RNA, sense cDNA, antisense DNA, antisense RNA and antisense cDNA and combinations thereof as a single strand and/or double strand.

It may be possible for the sequence(s) of the agent(s) Ms to be native or mutant and/or in a complete or a fragmented state and/or chemically modified or not chemically modified.

In a plere~,ed embodiment of the invention the sequence of the Ms agent(s) correspond(s) to a or several ST or SAT sequence(s) andlor the corresponding transcript(s) that is(are) native or mutant and in a complete or fragmented state.

In the subsequent paragraphs the agents selected from the group that comprises the nucleic acid will be referred to as MMAKS agents.

In addition, the object of the invention is attained with the help of an agent used for the purpose of influencing angioneoplasm that comprises at least one agent Mp that is selected from the group that comprises poly-clonal antibodies, mono-clonal antibodies, and fragments and derivatives thereof.

In this case it is especially ~ler~ d if the Mp agent acts against a ST or SAT sequence(s) and/or the corresponding transcription product(s) that is(are) native or mutant and/or in a complete or fragmented state.

In an especially prerelled embodiment the Mp agent acts against one or several translation products of a ST or SAT sequence or several sequences andlor the corresponding transcript(s) that is(are) native or mutant and/or in a complete or fragmented state and whereby said translation product(s) is(are) native or mutant andlor in a complete or fragmented state andlor is(are) glycosylated, partially glycosylated or not glycosylated and/or is(are) phosphorylated or not phosphorylated.

In addition, within the framework of the invention, agent Mp in accordance with the invention acts against an antibody or a fragment of an antibody which in turn acts against one or several ST or SAT sequences andlor the translation product(s) and/or the corresponding transcription product(s) that is(are) native or mutant and/or in a complete or fragmented state.

In addition, it is possible for agent Mp in accordance with the invention to act against an antibody or a fragment of the antibody which in turn acts against one or severaltranslation products of one or several of the ST or SAT sequences and/or the corresponding transcript(s) that is(are) native or mutant and/or in a complete or fragmented state and whereby said translation product(s) is(are) native or mutant and/or in a complete or fragmented state and/or is(are) glycosylated, partially glycosylated or not glycosylated and/or is(are) phosphorylated or not phosphorylated.

In the subsequent paragraphs the above agents selected from the group of antibodies and fragments and their derivatives will be referred to as MMAKP agents.

In accordance with the invention the object is also attained with the help of an agent used for the purpose of influencing angioneoplasm that is comprised of at least one translation product of one or several ST or SAT sequences and/or the corresponding transcript(s) that is(are) native or mutant and/or in a complete or fragmented state and whereby said translation product(s) is(are) native or mutant and/or in a complete or fragmented state and/or is(are) glycosylated, partially glycosylated or not glycosylated and/or is(are) phosphorylated or not phosphorylated andlor is(are) chemically modified or not chemically modified.

In the subsequent paragraphs the above translation product will be referred to as translation product TP.

Finally the object of the invention is attained with the help of an agent in accordance with the invention that is used for the purpose of influencing angioneoplasm and that is comprised of at least one ~r~ssion inhibitor and/or at least an agent that stimulates the t;~ression.

Especially plerelLed in this case is when the expression inhibitor and/or the agent that stim~ tes the expression has a higher degree of specificity for one or several of the ST or SAT sequences compared to other genes of the respective genetic system.

Especially prerelled is a scenario in which the expression inhibitor and/or the agent that stirnulates the expression is specific for one or several ST or SAT sequences.

The above described expression inhibitor will be referred to as expression inhibitor I and the above described agent that stimulates the ~ression will be referred to as agent ES.

One use of the agent in accordance with the invention for the purpose of influencing angioneoplasm concerns angiogenesis.

Especially plcÇellcd is an effect which reduces and/or prevents angiogenesis.

In an alternative, angiogenesis can be stimul~te~

Especially plc~lcd is an embodiment in which the influence on the angioneoplasm affects tumor angiogenesis.

In addition, one use of the agents in accordance with the invention for the purpose of influencing angioneoplasm concerns vascularization.

Especially prcrel,cd in this case is an embodiment in which vascularization is stimulated.

As altern~tive is for vascularization to be reduced or prevented.

Another aspect of the invention concerns the treatment and/or prevention of blindness due to neo-v~cul~ri7~tion while using at least one of the agents in accordance with the invention for the purpose of influencing angioneoplasm.

Finally another aspect of the invention is to improve the vessel supply of heart muscle tissue with cardiac infarction damage while using at least one agent in accordance with the invention for the purpose of influencing angioneoplasm.

It is possible to use the agent in accordance with the invention in hllm~n~ and/or ~nim~

In addition, it is possible to use the agent for therapeutic and/or diagnostic applications in hllm~n.~ and/or ~nim,ql.~.

In addition, it is possible to use it in vitro.

Another use in accordance with the invention of at least one of the agents in accordance with the invention is its/their use in the production of a drug for therapeutic and/or diagnostic applications for the purpose of influencing angioneoplasm.

Another aspect of the invention describes a kit for the purpose of influencing angioneoplasm that contains at lest one MMAKS and/or one MMA~CP agent.

It is possible for the kit to contain at least one translation product of one or several of the ST or SAT sequences and/or the corresponding transcript(s) that is(are) native or mutant and/or in a complete or fragmented state and whereby said translation product(s) is(are) native or mutant and/or in a complete or fragrnented state and/or is(are) glycosylated, partially glycosylated or not glycosylated and/or is(are) phosphorylated or not phosphorylated and/or is(are) chemically modified or not chemically modified.

At least one expression inhibitor I and/or at least one agent ES that stimulates the expression is contained in one embodiment of the kit.

In an especially pler~lled embodiment of the invention the kit contains at least one MMAKS and/or at least one MMAKP agent and/or one translation product TP and/or at least one e~ression inhibitor I and/or at least an agent ES that stim~ tes the ~Aplession.

In an especially prefelled embo~iment the kit can be used for the purpose of influencing tumor angiogenesis.

In another embodiment the kit is used for the purpose of influencing angiogenesis;

It also is possible to use the kit for the purpose of influencing vascularization.

An alternative is to use the kit for the purpose of inhibiting angioneoplasm.

An alternative is to use the kit for the purpose of stimulating angioneoplasm.

Finally, it is possible to use the kit for the purpose of treating and/or preventing blindness due to neo-vascul~ri7~tion.

In addition, it is possible to use the kit in accordance with the invention for the purpose of improving the vessel supply of heart muscle tissue daInaged by cardiac infarction.

The kit may be used for therapeutic treatrnent and/or for diagnosis purposes.

It is possible to use the kit in humans and/or ~nim~l~

Finally it is possible to use the kit in in vitro systems.

The object is attained in accordance with the invention through the use of at least one of the sequences SATin accordance with the invention for the treatment of endometriosis.

In a broader aspect in which the object is attained, the invention concerns the use of a MAG gene for the treatment of endometriosis.

A further aspect of the invention in which the object is attained concerns the use of at least one high mobility group protein gene for the treatment of endometriosis.

In a plefelled embodiment, it is provided that the high mobility group protein gene is selected from the group which comprises the HMGI-C gene and the HMGI-Y gene.

The above genes and/or groups of genes are designated below as genes GG.

It can be provided that sequences are used with essentially the same sequence of nucleic acid as the gene GG-In an alternative, sequences can be used with a nucleic sequence which is essentially thesame functionally as that of the gene GG.

The above-def~ned sequences together with the above-defined genes GG will be clesi~ted below as sequences SG.

In a further embodiment, it is provided that the sequences SG have at least one sequence which codes for a DNA binding portion of the corresponding translation product(s).

In a further alternative of the invention, it is provided that the sequences SG and derivatives thereof do not have any sequence which codes for the protein-binding portion of the corresponding translation product(s).

It can further be provided that the sequences SG or derivatives thereof in accordance with the invention have one or several sequences Sr which replace the sequence(s) which code for the protein-binding portion of the corresponding translation product(s).

It is possible in this case for the sequence Sr to be selected from the group which comprises other sequences of the human genome, sequences of other (donor) org~ni~m~, and artificial sequences and combinations thereof.

In one embodiment, it is provided that the sequences SAT or SG~ as well as derivatives thereof in accordance with the invention are present as double-strand and/or coding and/or non-coding single strand and/or cDNA.

It can further be provided that the sequences SAT or SG as well as derivatives thereof in accordance with the invention are present in native and~or mutant and/or fragmented or unfragmented forms.

In one embodiment of the invention, the sequences SAT or SG as well as derivatives thereof in accordance with the invention have at least one enhancer element and/or at least one transcription termin~tion element and/or at least one resistance gene and/or at least one other m~king gene.

In one embodiment, at least one of the sequences SAT or SG or derivatives thereof in accordance with the invention are present as clones in a host system.

It is provided In this case that the sequences SAT or SG or derivatives thereof in accordance with the invention are present in at least one copy.

The aforernentioned gene GG, the sequences SG~ and the sequences derived theleLo", or the various embodiments are designated below as sequences ST.

The object is attained in accordance with the invention through an agent for the treatment of endometriosis which comprises at least one agent Ms, which is selected from the group which comprises sense DNA, sense RNA, sense cDNA, antisense DNA, ~nti~en~e RNA, and ~nti~en~e cDNA, and combinations thereof as individual strands and/or doublestrands.

It can be provided that the sequence(s) of the agent(s) Ms are present in native or mutant form and/or complete or fragmented and/or chemically modified or not chemically modified.

In a plefel,ed embodiment, the sequence of the agent(s) Ms correspond to sequence(s) ST
or the corresponding transcript(s) which are present in native or mutant form, complete or fragmented.

The above agents selected from the group comprising the nucleic acids shall be referred to below as agents MMAKS-The object is further attained through an agent for the treatment of endometriosis which comprises at least one agent Mp which is selected from the group which comprisespolyclonal antibodies, monoclonal antibodies, and fragments and derivatives of the same.

It is especially pr~r~lled In this case that the agent Mp be directed against a sequence(s) ST or SAT and/or the corresponding transcription product(s) which are present in native or mutant form and/or complete or fragmented.

In a particularly pl~relled embodiment, the agent Mp acts against one or severaltranslation products of a sequence or several sequences ST or SAT and/or of the corresponding transcript(s) which are present in native or mutant form and/or complete or fragmented and whereby said translation product(s) are present in native or mutant form and/or complete or fragmented and/or glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated.

In addition, it is within the frarnework of the present invention that the agent Mp in accordance with the invention acts against an antibody or a fragment thereof which in turn acts against one or more sequences ST or SAT and/or the corresponding transcription product(s) which are present in native or mutant form and/or complete or fragmented.

In addition, it can be provided that the agent in accordance with the invention act against an antibody or a fragment of the same which in turn acts against one or several translation products of one or several sequences ST or SAT and/or corresponding transcript(s) which are present in native or mutant form and/or complete or fragmented and whereby said translation product(s) are present in native or mutant form and/or complete or fragmented and/or glycosylated, partially glycosylated or not glycosylated and/or phosphorylated or not phosphorylated.

The aforementioned agent selected from the group comprised of antibodies and fragments and derivatives of the same will be designated below as agent MMA~P-The object is attained in accordance with the invention through an agent which comprisesat least one translation product of one or several sequences ST or SAT and/or the corresponding transcript(s) which are present in native or mutant form and/or complete or fragmented and whereby said translation product(s) are present in native or mutant form and/or complete or fragmented and/or glycosylated, partially glycosylated or notglycosylated and/or phosphorylated or not phosphorylated and/or chemically modified or not chemically modified.

The translation product described above shall be designated below as translation product TP.

Finally, the object is attained by means of an agent in accordance with the invention for the treatment of endometriosis which comprises at least one expression inhibitor and/or at least one agent which stimulates the expression.

It is particularly plerelled In this case that the expression inhibitor and/or the expression stim~ tin~ agent have an elevated specificity for one or more of the sequences ST or SAT
compared with other genes of the genetic system in question.

It is quite particularly pl~r~lr~d In this case that the expression inhibitor and/or the eA~lession-stimulating agent be specific for one or more sequences ST or SAT.

One application in accordance with the invention provides that at least one of the agents in accordance with the invention is used for the treatment of endometriosis in humans or in ~nim~

In one embodiment, use is indicated for therapeutic and/or diagnostic application in humans and/or in ~nim~

A further application in accordance with the invention provides the in vitro application of at least one of the agents in accordance with the invention.

Finally, an application in accordance with the invention can provide for the application of at least one of the agents in accordance with the invention for the manufacture of a drug for the therapeutic and/or diagnostic application in the treatment of endometriosis.

In a fur~er aspect, the invention concerns a kit for the treatment of endometriosis which contains at least an agent MM~RS and/or an agent MMAKP.

It is possible for a kit to contain a translation product of one or more of sequences ST or SAT and/or of the corresponding transcript(s) which are present in native or mutant form and/or complete or fragmented and whereby said translation product(s) are present in native or mutant form and/or complete or fragmented and/or glycosylated, partially glycosylated or not glycosylated and/or phosphorylated or not phosphorylated and/or chemically modified or not chemically modified.

In one embodiment of the kit, at least one expression inhibitor I and/or one expression-stimulating agent ES are contained.

In a particularly pl~relled embodiment, it is provided that at least one agent MMA~CS and/or at least one agent MMAKP and/or at least one translation product TP and/or at least one expression inhibitor I and/or at least one expression-stimulating agent ES is contained.

The kit can be used for therapeutic treatment and/or for diagnosis.

It is provided that the kit will be used with humans and/or ~nim~

Finally, the kit can also be used in in vitro systems.

The object can be attained in accordance with the invention through the use of at least one of the sequences SAT for contraception.

In a broader aspect in which the object is attained, the invention concerns the use of a MAG gene for contraception.

Another aspect of the invention in which the object is attained concems the use of at least one high mobility group protein gene for contraception.

In a p,efelled embodiment, it is provided that the high mobility group protein gene is selected from the group which comprises the HMGI-C gene and the HMGI-Y gene.

The above gene or group of genes are designated below as genes GG

It can be provided that sequences are used with essentially the same nucleic acid sequence as the genes GG

In an altemative, sequences can be used with nucleic acid sequence which is, in essence, functionally the same as that of genes GG

The sequences defined above, together with genes GG, which are likewise defined above, shall be design~ted from this point forward as sequences SG.

In a further embodiment, it is provided that the sequences SG have at least one sequence which code for a DNA-binding portion of the corresponding translation product(s).

In a further alternative of the invention, it is provided that the sequences SG and derivatives thereof have no sequence which codes for the protein-binding portion of the collespol-ding translation product(s).

_ Furthermore, it can be provided that the sequences SG or derivatives thereof in accordance with the invention have one or more sequences Sr which replace or supplement that sequence or those sequences which code for the protein-binding portion of the corresponding translation product(s).

It is possible In this case for the sequences Sr to be selected from the group which comprises the other sequences of the human genome, sequences of other (host) org~ni~m~, and artificial sequences and combinations thereof.

In one embodiment, it is provided that the sequences SAT and SG as well as derivatives thereof in accordance with the invention are present as double strand and/or coding and/or non-coding single strand and/or cDNA.

Furthermore, it can be provided that the sequences SAT and SG as well as derivatives thereof in accordance with the invention are present as natives and/or mutants and/or fragmented or not fragmented.

In one embodiment of the invention, the sequences SAT and SG as well as derivatives thereof have at least one promoter and/or at least one enhancer element and/or at least one transcription termin~tion element and/or at least one resistance gene and/or at least one other m~rking gene.

In one embodiment, at least one of the sequences SAT or SG or derivatives in accordance with the invention are present as clones in a host system.

It is provided In this case that the sequences SAT and SG as well as derivatives thereof in accordance with the invention are present in at least one copy.

The aforementioned genes GG the sequences SG~ and the sequences derived thereL."" or from the various embodiments are designated below as sequences ST.

The object is attained in accordance with the invention through an agent for contraception which comprises at least one agent Ms which is selected from the group which comprises sense DNA, sense RNA, sense cDNA, antisense DNA, antisense RNA, and antisense cDNA and combinations thereof as single strand andlor as double strand.

It can be provided that the sequence(s) of the agent(s) Ms are present in native or mutant form and/or complete or fragrnented andlor chemically modified or not chemicallymodified.

In a preferred embodiment, the sequence of the agent(s) Ms correspond to a sequence(s) ST or SAT andlor to the corresponding transcript(s) which is present in native or mutant form, complete or fragmented.

The aforementioned agents derived from the ~roup comprising nucleic acids shall be design~ted below as agent MMAICS-The object can also be attained through an agent for contraception which comprises atleast one Ms which is selected from the group which comprises polyclonal antibodies, monoclonal antibodies, and fragments and derivatives of the same.

It is particularly ~er~ d In this case that the agent Mp act against the sequence(s) ST or SAT andlor the corresponding transcription product(s) which are present in native or mutant form and/or complete or fragmented.

In a particularly pref~ d embodiment, the agent Mp acts against one or more translation products of one or more sequences ST or SAT and/or of the corresponding transcript(s) which are present in native or mutant form and/or complete or fragmented and whereby said translation product(s) are present in native or mutant form and/or compete or fragmented and/or glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated.

Furthermore, it is within the framework of the present invention that the agent Mp in accordance with the invention acts against an antibody or a fragment of the same which in turn acts against a sequence(s) ST or SAT and/or the corresponding transcription product(s) are present in native or mutant form and/or complete or fragmented.

Furthermore, it can be provided that the agent Mp in accordance with the invention acts against an antibody or a fragment of the same which in turn acts against one or several translation products of one or more sequences ST or SAT and/or of the corresponding transcript(s) which are present in native or mutant form and/or complete or fragrnented, and whereby said translation product(s) are present in native or mutant form and/or complete or fragmented and/or glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated.

The above-indicated agents selected from the group comprising the antibodies andfragments and derivatives of the same will be design~ted below as agents MMAECP

The object is attained in accordance with the invention through an agent for contraception which comprises at least one translation product(s) or one or more sequences ST or SAT
and/or of the corresponding transcript(s) which are present in native or mutant form and/or complete or fragmented and whereby said translation product(s) are present in native or mutant form and/or complete or fragmented and/or glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated and/or chemically modified or not chemically modified.

The above described translation product is designated below as translation product TP.

Finally, the object is attained through an agent in accordance with the invention for contraception which comprises at least one expression inhibitor and/or at least one agent which stimulates the expression.

It is particularly pref~l,ed in this case that the expression inhibitor and/or the agent which ~tim~ tes the expression have an elevated specificity for one or more of the sequences ST
or SAT col~aled with other genes of the particular genetic system.

It is particularly pler~;lled in this case that the expression inhibitor and/or the agent which stimulates the t;,.~ression be specific for one or more sequenceS ST or SAT-The above described expression inhibitor will be desi~n~ted below as ~ression inhibitor I and the above described expression-stimulating agent will be design~te(l below as ES.

An application in accordance with the invention provides the application of at least one of the agents in accordance with the invention for oral contraception.

A further application in accordance with the invention provides the use of at least one of the agents in accordance with the invention for local contraception.

It can be provided that the application is for humans and/or for ~nim~

In an alternative, the application concerns the therapeutic application for hllm~n~ andlor for ~nim~

A further application in accordance with the invention of at least one of the agents in accordance with the invention concerns the m~nuf~cture of a drug for therapeuticapplication.

In an additional application in accordance with the invention, the aspect through which the object is attained concerns the invention of a kit for contraception which contains at least one agent MMA~CS and/or at least one agent MMAKP.

It is possible for a kit to contain at least one translation product of one or more of the sequences ST or SAT and/or of the corresponding transcript(s) which are present in native or mutant form and/or complete or fragmented and whereby said translation product(s) in native or mutant form and/or complete or fragmented and/or glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated and/or chemically modified or not chemically modified.

In one embodiment of the kit, at least one expression ir~ibitor I and/or at least one expressing-stim~ ting agent ES is contained.

In a particularly plefelled embodiment, it is provided that at least one agent MMA~CS and/or at least one agent MMAKP and/or at least one translation product TP and/or at least one e~lession inhibitor I and/or at least one expression-stimul~tin~ agent ES be contained in the kit.

In a quite particularly plerelled embodiment, the kit can be used for oral contraception.

Furthermore, it is possible for the kit to be used for local contraception.

The kit can be used for therapeutic treatment and/or for diagnosis.

It is provided that the kit is used for hum~n~ and/or animals.

~inally, the kit can also be used in in vitro systems.

In a fur~er aspect, the invention concerns a process of contraception which provides that at least one agent is ~imini~tered which is selected from the group which contains sense DNA, sense RNA, sense cDNA, ~nti.~,o.n~e DNA, antisense RNA, and ~nt1~n~e cDNA and combinations thereof as a single strand and/or as a double strand and whereby the sequence of the agent selected from the group corresponds to the sequence(s) ST and/or SAT and/or the corresponding transcript(s) which is(are) present in native or mutant form and/or complete or fr.agmented.

In addition, the invention represents a process for contraception which provides for the ~lmini.~tration of at least one agent which is selected from the group which contains polyclonal antibodies, monoclonal antibodies, and fragments and derivatives of the same and whereby the agent selected from the group acts against the sequence(s) ST and/or SAT
and/or in the direction opposite to the corresponding transcript(s) which are present in native or mutant form and/or complete or fragmented.

Ln a further aspect of the invention, a process for contraception is suggested which provides that at least one agent be ~lmini~tered which is selected from the group which contains polyclonal antibodies, monoclonal antibodies, and fragments and derivatives of the same and whereby the agent selected from the group acts against one or more of sequences ST and/or SAT and/or of the corresponding transcript(s) which is(are) present in native or mutant form and/or complete or fragmented and whereby said translation product(s) is(are) present in native or mutant form and/or complete or fragmented and/or glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated.

In addition, the invention suggests a procedure for contraception which is characteri~ed by the fact that at least one agent is a-lmini~t~.red which is a translation product of one or more sequences ST and/or SAT and/or of the corresponding transcript(s) which is(are) present in native or mutant forrn and/or complete or fragrnented and whereby said translation product(s) is(are) present in native or mutant form and/or complete or fragmented and/or glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated and/or chemically modified or not chemically modified.

In plefelled embodiments of the process in accordance with the invention for contraception, said agent is ~(imini~tered orally.

In a further prefelled embodiment, it is provided that said agent is a-lmini~tered periodically.

An additional alternative of the procedure in accordance with the invention provides that said agent is a~lmini~tered following conception.

The object is attained in accordance with the invention through the use of at least one of sequences SAT for tissue regeneration.

In a further aspect through which the object is attained, the invention concerns the use of a MAG gene for tissue regeneration.

Another aspect of the invention in which the object is attanined concerns the use of at least one high mobility group protein gene for tissue regeneration.

In a prerel~ed embodiment, it is provided that the high mobility group protein gene is selected from the group which compnses the HMGI-~ gene and the HMGI-Y gene.

The above genes or groups of genes are design~ted below as gene GG

It can be provided that sequences are used with essentially the same nucleic acid sequence as genes GG

In an alternative, sequences are used with a nucleic acid sequence which is essentially the same functionally as that of the genes GG

The above-defined sequences together with the above-defined genes GG shall be designated below as sequences SG.

In a further embodiment, it is provided that the sequences SG have at least one sequence which codes for a DNA-binding portion of the corresponding translation product(s).

In a further alternative of the invention, it is provided that the sequences SG and derivatives thereof do not have any sequence which codes for the protein-binding portion of the corresponding translation product(s).

Furthermore, it can be provided that the sequences SG or derivatives thereof in accordance with the invention have one or more sequences Sr which replace or supplement that sequence or those sequences which code for the protein-binding portion of the corresponding translation product(s).

It is possible In this case for the sequence Sr to be selected from the group which comprises other sequences of the human genome, sequences of other (host) org~ni.~m.
and artificial sequences and combinations thereof.

In one embodiment, it is provided that the sequences SAT or SG and derivatives in accordance with the invention thereof are present as double strand and/or coding and/or non-coding single strand and/or cDNA.

Further nore, it can be provided that the sequences SAT of SG and the derivatives thereof in accordance with the invention are present as native and/or mutant and/or fragmented or not fragmented.

In one embodiment of the invention, the sequences SAT or SG and derivatives thereof in accordance with the invention can have at least one promoter and/or at least one enhancer element and/or at least one transcription termin~tion element and/or at least one resistance gene and/or at least one other m~rking gene.

In one embodiment, at least one of the sequences SAT or SG or derivatives thereof in accordance with the invention are present as clones in a host system.

It is provided In this case that the sequences SAT or SG and derivatives thereof in accordance with the invention are present in at least one copy.

The above genes GG the sequences SG~ and the sequences derived theleLulll or thevarious embodiments will be designated below as sequences ST.

The object is attained in accordance with the invention through an agent for tissue regeneration which comprises at least one agent Ms which is selected from the group which compri.~çs sense DNA, sense RNA, sense cDNA, ~nti~.n~e DNA, antisense RNA,and antisense cDNA and combinations thereof as single strand or double strand.

It can be provided that the sequence(s) of agent(s) Ms are present in native or mutant form and/or complete or fragmented and/or chemically modified or not chemically modified.

In a pLefelled embodiment, the sequence of agent(s) Ms correspond to a sequence(s) ST or SAT and/or to the corresponding transcript(s) which are present in native or mutant form, complete or fragmented.

The above agents selected ~om the group comprised on nucleic acids are designated below as agents MMA~CS-Furthermore, the object is attained in accordance with the invention through an agent forregeneration of tissue which comprises at least one agent Mp which is selected from the group which comprises polyclonal antibodies, monoclonal antibodies, and fragments and derivatives of the same.

It is particularly ~refelled In this case that the agent Mp be directed against a sequence(s) ST or SAT and/or the corresponding transcription product(s) which are present in native or mutant form and/or complete or fragmented.

In a particularly prefelled embodiment, the agent Mp acts against one or more translation products of a sequence or several sequences ST or SAT and/or of the colles~onding transcripts which are present in native or mutant form and/or complete or fragmented and whereby said translation product(s) are present in native or mutant form andlor complete or fragmented and/or glycosylated, partially glycosylated, or not glycosylated andlor phosphorylated or not phosphorylated.

Fur~ermore, it is within the framework of the invention for the agent Mp in accordance with the invention to be directed against an antibody or a fragment thereof which in turn acts against a sequence(s) ST or SAT andlor the corresponding transcription product(s) which are present in native or mutant form and/or complete or fragmented.

Furthermore, it can be provided that the agent Mp in accordance with the invention acts against an antibody or a fragment thereof which in turn acts against one or moretranslation product(s) of a sequence(s) ST or SAT and/or of the corresponding transcript(s) which are present native or mutated andlor complete or fragmented and whereby said translation product(s) are present in native or mutant form and/or complete or fragmented andlor glycosylated, partially glycosylated, or not glycosylated andlor phosphorylated or not phosphorylated.

The above agents selected from the group comprising the antibodies and fragments and derivatives of the same are designated below as agents MMAKP.

The object is attained in accordance with the invention through an agent for theregeneration of tissue which comprises at least one translation product of a sequence(s) ST
or SAT and/or of the corresponding transcript(s) which is(are) present in native or mutant form and/or complete or fragmented and whereby said translation product(s) is(are) present in native or mutant form and/or complete or fragmented and/or glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated and/or chemically modified or not chemically modified.

The above-described translation product is designated below as translation product TP.

Finally, the object is attained through an agent in accordance with the invention for regeneration of tissue which comprises at least one agent which stimulates the expression.

It is particularly preferred In this case that compared with other genes of the particular .
genetic system, the agent which stimulates the expression have an elevated specificity for one or more sequences ST or SAT-It is quite particularly preferred In this case that the agent which stimulates the expressionbe specific for a sequence or several sequences ST or SAT.

The above-described agent which stim~ tes the expression will be designated below as the ~plession stimlll~ting agent ES.

An application in accordance with the invention of at least one of the agents inaccordance with the invention for regeneration of tissue provides that the tissue to be regenerated is selected from the group which comprises degenerative tissue, traumatically damaged tissue, and tissue damaged by other means.

An application of at least one of the agents in accordance with the invention for the regeneration of tissue is particularly ~l~relled if the tissue to be regenerated is mesenchymal tissue.

It is quite particularly plefell~d that the mesenchymal tissue be selected from the group which comprises cartilage, muscle, fat, and connective and support tissue.

A further application in accordance with the invention concerns the application of at least one of the agents in accordance with the invention for the regeneration of tissue _ vivo.

The invention suggests that the use take place in humans andlor in ~nim~l.c, Furthermore, the use for therapeutic application in humans and/or in ~nim~l~ is provided.

A further aspect of the invention concerns the use of at least one of the agents in accordance with the invention for regeneration of tissue _ vitro.

It is particularly preferred that the application take place in or on cultures which are selected from the group which comprises cell cultures, tissue cultures, organ cultures, and combinations thereof.

In a further application in accordance with the invention, the agent in accordance with the invention is provided for the m~n~lf~cture of a drug for therapeutic application in the regeneration of tissue.

In a further aspect, the invention concerns a kit for the regeneration of tissue which contains at least an agent MMA}CS and/or an agent MMAKP

It is possible for a kit to contain at least one translation product of one or several of the sequences ST or SAT and/or of the corresponding transcript(s) which is present in native or mutant form and/or complete or fragrnented and whereby said translation product(s) are present in native or mutant form and/or complete or fragmented and/or glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated and/or chemically modified or not chemically modified.

In one embodiment at least one expression-stim~ ting agent ES is contained.

In a particularly preferred embodiment, it is provided that at least one agent MMAICS and/or at least one agent MMAKP and/or at least one translation product TP and/or at least one expression-stim~ tion agent ES is contained in the kit in accordance with the invention.

The kit can be used for therapeutic treatment andlor for diagnosis.

Furthermore, it can be provided that the kit is used _ vivo.

It is provided that the kit is used for humans and/or for animals.

Finally, the kit can also be used in in vitro systerns.

It is particularly plefelled In this case if the kit is used in or on cultures which are selected from the group which comprises cell cultures, tissue cultures, organ cultures, and combinations of the same.

In a further aspect, the invention concerns a process for the regeneration of tissue in which at least one of the sequences ST or SAT is expressed in the tissue which is to be regenerated.

In a further aspect through which the object is attained, the invention concerns a procedure which comprises the following steps:
a) Pl~al~lion of cells which are de~ ted target cells;
b) Introduction of at least one of the sequences ST or SAT into the target cells;
c) Induction of the expression by at least one of the sequences ST or SAT into the target cells; and optionally d) Cultivation of the target cells.

It can be provided that in the cultivation of the target cells at least one of the sequence ST
or SAT is expressed.

In a pl~relled embodiment, at least one of the sequences ST or SAT is introduced _ vitro into the target cells by means of a procedure which is selected from the group which comprises transfection, microinjection, electroporation, gene transfer by means of liposomes, and transformation brought about through agents.

In addition, it can be provided that the expression and/or induction of the expression is influenced by at least one agent MMA~CS and/or at least one agent MMA~P and/or at least one translation TP and/or at least one t;Aplessillg-stimulating agent ES.

In one embodiment, the target cells can originate from an animal organism including from a human.

In another embodiment, it is provided that the target cells originate from an animal organism but not from a human.

It can be provided that the target cells represent a different cell type than the cell types contained in the tissue which is to be regenerated.

Alternatively, it can be provided that the cell types represent a cell type such as is contained in the tissue which is to be regenerated.

It is prefe.led that the target cells (de-)differentiate into pluripotent stem cells under the influence of at least one of the sequences ST or SAT.

In a plerelled embodiment of the procedure, the target cells are co-cultured with other cells and/or cell types.

It is particularly piefelled In this case that the cells and/or cell types used for co-cultivation influence the differentiation state of the target cells.

In a further embodiment, the target cells are prepared through the withdrawal of material from an organism whereby the m~teri~l is selected from the group which comprisesbiological fluids cont~ining cells, individual cells, tissue, and organs.

It is furthermore provided that following introduction of at least one of the sequences ST
or SAT in the target cells, these target cells are introduced into an animal org~ni~m It is further provided that following introduction of at least one of the sequences ST or SAT
into the target cells, expression be induced in the target cells before the target cells are introduced into an animal org~ni.cm.

In an alternative, following the introduction of at least one of the sequences ST or SAT into the target cells their expression is induced in the target cells after which the target cells were introduced into an animal org~ni~m.

In a plerelled embodiment, the target cells which were introduced into an animalorganism are in a differentiated and/or differentiation-competent condition.

In a quite particularly plerelled embodiment, the animal organism is a human organi~m.

It is provided that the organism in which the target cells are introduced is identical with the organism from which the target cells were taken.

Alternatively, it is provided that the organism in which the target cells are introduced are di~c;ll~ from the organism from which the target cells originate.

It can be provided that at least one of the sequences ST or SAT is introduced into the tissue in the organism which is to be regenerated and/or the corresponding cells.

In a particularly prefelled embodiment, it is provided that at least one of the sequences ST
or SAT is introduced into the tissue to be regenerated and/or the corresponding cells with the use of gene-therapeutic procedures.

In one embodiment of the procedure in accordance with the invention, the introduced sequence ST or SAT is expressed.

It is particularly pr~r~lled that the expression of the introduced sequence ST or SAT be influenced by at least one agent MMAKS and/or at least one agent MMA cP and/or at least one translation product TP and/or one eXpression-stim~ ting agent ES.

A particularly prefelled embodirnent in accordance with the invention provides that the tissue to be regenerated is selected from the group which comprises mesenchymal tissue.

A further quite particularly preferred embodiment of the procedure in accordance with the invention provides that the mesenchymal tissue is selected from the group which comprises cartilage, muscle, fat, and connective and support tissue.

In an additional aspect, the invention while achieving the object concerns the use of at least one of the sequences SAT in accordance with the invention for the treatment of tumor diseases.

In a further aspect in which the object is attained, the invention concerns the use of a MAG gene for the treatment of tumor diseases.

Another aspect of the invention in which the object is attained concerns the use of at least one high mobility group protein gene for the treatment of tumor diseases.

In a plerelled embodiment, it is provided that the high mobility group protein gene is selected from the group which comprises the HMGI-C gene and the HMGI-Y gene.

The above genes or groups of genes are design~ted below as GG.

It can be provided that sequences are used with essentially the same sequence of nucleic acids as the genes GG.

In an altçrn~tive, sequences can be used with a sequence of nucleic acids which is, in essence, functionally the same as that of the genes GG.

The above-defined sequences together with the above-defined genes GG will be designated below as sequences SG.

In an additional embodiment, it is provided that the sequences SG have at least one sequence which codes for a DNA-binding portion of the corresponding translation product(s).

In an additional alternative of the invention, it is provided that the sequences SG in accordance with the invention and derivatives thereof have no sequence which codes for the protein-binding portion of the corresponding translation product(s).

Furthermore, it can be provided that the sequences SG or derivatives in accordance with the invention thereof have one or more sequences Srwhich replace or supplement that sequence or those sequences which code for the protein-binding portion of the corresponding translation product _ or products.

It is possible In this case for the sequence Sr to be selected from the group which compri~es other sequences of the human genome, sequences of other (donor) orgAni~ms, and artificial sequences and combinations thereof.

In one embodiment, it is provided that the sequences SAT and SG, as well as derivatives thereof in accordance with the invention are present as a double strand and/or a coding and/or non-coding single strand and/or cDNA.

Purtherrmore, it can be provided that the sequences SAT and SG as well as derivatives thereof in accordance with the invention are present as natives and/or mutants and/or are fragmented or not fragmented.

In one embodiment of the invention, the sequences SAT and SG as well as derivatives thereof in accordance with the invention have at least one promoter and/or at least one enhancer element and/or at least one transcription terrnin~tion element and/or at least one resistance gene and/or at least one other m~rking gene.

In one ernbodiment, at least one of the sequences SAT or SG or derivatives thereof in accordance with the invention are present as clones in a host system.

It is provided in this case that the sequences SAT and SG as well as derivatives thereof in accordance with the invention are present in at least one copy.

The above genes GG~ the sequences SG~ and the sequences or different embodiment forms derived therefrom will be designated below as sequences ST.

According to the invention, the object is attained by an agent for treating tumor diseases that includes at least one MSAT agent selected from the group that includes sense DNA, sense RNA, sense cDNA, antisense DNA,antisenseRNA and antisense cDNA, and combinations thereof, as a single strand and/or as a double strand, whereby the sequence of the MSAT agent corresponds to one or more of the SAT or ST sequences or to the corresponding transcript(s).

In a plerelled form of embodirnent it is provided that the sequence of the SAT or ST
sequences or of the corresponding transcripts is present in native or mutant form and/or complete or as a fragment.

In a further form of embodiment it can be provided that the sequence of the MSAT agent is present in native or mutant form and/or complete or as a fragment and/or chemically modified or not chemically modified.

Furthermore the invention suggests an agent for treating tumor diseases that includes at least one MPAT agent selected from the group that includes polyclonal antibodies, monoclonal antibodies, and fTagments and derivatives thereof, whereby the MPAT agent is acting against the SAT or ST se~uence(s) and/or the corresponding transcript(s), which is(are) present in native or mutant form and/or complete or a fragment.

In the framework of the present invention, an agent for treating tumor diseases is moreover suggested that contains at least one MPAT agent selected from the group that includes polyclonal antibodies, monoclonal antibodies, and firagments and derivatives thereof, and whereby the MPAT agent is acting against one or more translation products of one or more of the SAT or ST sequences and/or of the corresponding transcript(s), which is(are) present in native or mutant form and/or complete or a fragment and whereby the said translation product or said translation products is(are) present in native or mutant form and/or complete or as a fragment and/or glycosylated or partially glycosylated or not glycosylated and/or phosphorylated or not phosphorylated.

The invention suggests a further agent for treating tumor diseases that is charact~ri7ed by at least one translation product of one or more SAT or ST sequences and/or of the corresponding transcript(s), which is(are) present in native or mutant form and/or complete or as a fragment and whereby the said translation product(s) is(are) present in native or mutant form and/or complete or as a fragment and/or glycosylated or partially glycosylated or not glycosylated and/or phosphorylated or not phosphorylated and/or chemically modified or not chemically modified.

Finally the invention provides another agent for treating tumor diseases that includes at least one MJAT agent that is an expression inhibitor that has greater specificity for one or more of the SAT or ST sequences than for other tissues of the corresponding genetic system.

Furthermore the invention provides an agent for treating tumor diseases that includes at least one MIAT agent that is an expression inhibitor specific for at least one of the SAT or ST sequences.

In a plefelled form of embodiment it is provided that the tumor to be treated expresses a gene selected from the group that includes MAG genes, high mobility group protein genes, HMGI-C genes, HMGI-Y genes, and their derivatives.

It can furthermore be provided that one of the agents of the invention is used to produce a drug for treating tumor diseases.

In a pref~lled form of embodiment it is provided that the drug is used for treating types of tumors that express a gene selected from the group that includes MAG genes, highmobility group protein genes, HMGI-C genes, HMGI-Y genes, and their derivatives.
In a further form of embodiment it can be provided that at least one agent of the invention is used for treating types of tumor that express a gene selected from the group that includes MAG genes, high mobility group protein genes, HMGI-C genes, HMGI-Y
genes, and their derivatives.

A DNA sequence according to the invention, which is characterized by a sequence as shown in Figures 1 to 19, is advantageous for developing novel agents based on this sequence and its corresponding transcripts and translation products, whereby the nucleic acids must be conf~rmed to be molecules carrying information in their structures. Such agents can be drug products, as well as agents used in diagnostics, but are not limited to these. These agents can also be used advantageously in various processes and also for the therapy of various illnesses or for producing appropriate drugs for treating these illnesses. Thus with the description of the sequences of the invention, a versatile agent is made available. It must be noted thereby that the advantages reslllting from the sequences of the invention are not limited to an exact char~ct~ri7~tion of a specific site of action, which can therefore be affected by the use of suitable agents, including those of the invention, but the corresponding sequences themselves serve to cause effects based on the presence of the sequences of the invention or sequences derived there~iolll and/or their transcripts and/or their translation products.
These sequences can also be affected advantageously if they are biologically active as such in an org~ni~m, whether as a result of basic biological processes or as a result of the introduction of these sequences by means of a technical measure, or in an _ vitro system.

These general advantages are also furnished if parts of the sequences shown in Figures 1 to 19 are a part of the DNA sequence of the HMGI-C gene.

The term "genes" in connection with this Application is intended to include the sequence of the exons and introns and also the corresponding cDNA of the respective gene.
Compared with the sequences shown in Figures 1 to 19, mutations of the DNA sequence of the invention offer a further advantage in that they enable a sequence-specific agent, e.g. in the form of an antisense DNA acting against the sequences of the invention, to be distinguished from other sites of action if necessary, and thus the stringency occurring when nol~mu~lt sequences are used would not guarantee the required specificity of interaction between the respective complementary strands.

Mutation in the sense of the present invention also includes a fragmentation of the sequences, whereby fragmentation includes shortening of the sequences at the 5'-end and/or at the 3'-end up to an oligomer, as well as loss of a sequence(s) of at least one nucleotide arranged within the sequence. Moreover the term "fragmented sequence or gene" herein is intentled to include a sequence/gene that has one or more introns that can be respectively deleted partially or completely.

Furthermore, such mutant sequences allow translation products to be obtained whose biological activity is essPnti~lly identical to that of the translation products of native sequences. On the level of the amino acid sequence of the translation products, such mutations can manifest themselves in a variety of ways, including insertions, deletions, or silent mutations, among others. On the DNA level, such mutations allow the sequence to be matched to the use of certain tRNA anticodons and thus make it possible to match the translation rate of the corresponding sequences to the respective requirements or the respective host system.

On the other hand, applications are conceivable in which essPnti~lly the same sequence as the DNA sequence shown in Figures 1 to 19 is advantageous and e.g. delivers the necessary stringency. A modified version of the DNA sequences of the invention also offers the possibility of including suitable signals recognized by the biological background. The presence of such signals can lead to a changed transcription and/or translation rate, e.g. as a result of an increased half-life of the transcripts, but is not limited to this.

The aforementioned advantages can also exist when nucleic acid sequences are used that are only functionally the same. It must be taken into consideration thereby that the term "functionally the same nucleic acids" takes into account the functional principle on which the HMGI-C gene, but also in general the MAG genes or the high mobility group protein genes, is based.

Without predjudice, there exists in the literature the perception that the corresponding gene products essentially consist of a DNA-binding portion and a protein-bindingportion. As a result, this term "functionally the same nucleic acid sequence" is also intt~n~1ed to include those sequences that code for translation products with a similar function to the translation products of the sequences of the invention or of the MAG
genes or of the high mobility group protein genes. The advantageous effects described above must also be taken into account for such translation products. The term is also inttonfle~ to include those nucleic acid sequences that lead to a translation product that is functionally the same, i.e. those that lead to a functionally still active translation product in the above sense as a result of the degeneration of the genetic code. The fact that the sequences of the invention have a (nucleic acid) sequence that codes for a DNA-binding portion of the corresponding translation product(s), ensures that the sequences of the invention yield a translation product that is capable of binding to DNA. Vice versa, the nucleic acid sequence as such gives a precisely defined target for agents in which the ~e.luired sequence specificity is inherent in their molecular structure, such as e.g.
~ntie~nee DNA or antibodies acting against the DNA-binding portion of the sequence and/or of the corresponding translation products.

Because sequences of the invention sometimes lack a sequence that codes for the protein-binding moiety of the translation product(s) corresponding to the DNA sequences of the invention, there exists the possibility of influ- .ncing in a desired manner the effect on the chromatin structure that would otherwise be mediated via the protein-binding portion.

If on the other hand one or more Sr sequences is(are) present that replace(s) orcomplete(s) the sequence(s) that code(s) for the protein-binding portion of the translation product(s) corresponding to the sequences of the invention, this opens up the advantageous possibility of a specific interaction with cellular (protein) components. As a result, other cellular factors can interact with the additional or new portions of the translation product. Vice versa, at the DNA level another region can thus be introduced that allows a response to the sequences of the invention.

Depending on the respective question under consideration, the sequence Sr, which is selected from the group that includes other sequences of the human genome, sequences of other (donor) org~ni~m~ and artificial sequences and combinations thereof, also offers many possibilities for influencing cellular events.

The fact that the sequences shown in Figures 1 to 19 are aberrant transcripts of the HMGI-C gene, makes it possible to distinguish between aberrant transcripts on the one hand, and non-aberrant transcripts on the other hand, and also between the respective translation products. For those skilled in the art, this results in a wealth of advantages in both the therapeutic and diagnostic fields.

Thus it is e.g. conceivable that the translation products of the aberrant transcripts stimulate or hlt~llu~t certain reaction chains in the cellular events, for example by acting as competitive inhibitors.

With an expression vector of the type according to the invention, which includes at least one transcription promoter followed downstream by at least one DNA sequence of the invention, there exists the possibility of obtaining corresponding transcripts and translation products of the DNA sequences of the invention in a simple and rapid manner.

Using a further form of embodiment of the expression vector, there is also the possibility of transforming or transfecting various host systems. Depending on the respective host system used, various promoters can be provided, both eukaryotic and prokaryotic, as well as optionally enhancer elements and/or suitable t~rmin~tion elements, as are sufficientIy well-known in the state of the art.

Whether a prokaryotic or a eukaryotic cell is used as the host cell depends on the purpose for which the ~Lession vector is being used. Owing to their nutrient requirements and comparatively greater ease of cultivation, prokaryotic cells are to be plefelled when the inherent disadvantages of host systerns of this type, such as e.g. lack of glycosylation or possibly the formation of inclusion bodies, are not important for the purpose of the cultivation.

On the other hand eukaryotic cells, especially yeast cells and m~mm~ n cells, offer an advantage, e.g. when post-translational modifications are important for the further intended use.

Advantages are also gained from a protein or peptide that is a translation products[sic] of one or more SAT sequences and/or of the corresponding transcript(s) that is(are) present in native or mutant form and/or complete or as a fragment, and whereby the said translation product(s) is(are) present in native or mutant form and/or complete or as a fragment and/or glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated and/or chemically modified or not chemically modified. Thus there exists the possibility of preparing effector molecules coded by the ST and/or SAT
sequences, without c~nging the genetic background of the system under observation. In addition to direct substitution or completion of the cellular level with respect to the translation product(s) TP, e.g. in the form of "flooding," the possibility is also offered of encin~ cellular events by using derivatives present in native or mutant form and/or complete or as a fragment, including the various possible glycosylation forms and the physiologically particularly important phosphorylation forms and other modified forms, whereby the said molecules can assist the effect of the native translation product if necessary, or else e.g. can also initiate this or can respond to the corresponding chment sites of cellular mech~ni~m~ in the sense of a competitive inhibition.

The use of at least one sequence of the invention and/or of an MAG gene or at least a high mobility group protein gene and particularly the use of the HMGI-C gene or the HMGI-Y gene to influence vessel development is advantageous in that it gives a specific site of action as well as specificity of the agent to be used in principle to influence vessel development. This ensures that the expression of the corresponding genes or sequences is influenced by a suitable agent, which can include the corresponding genes or sequences themselves. Based on this very direct mech~ni~m of action, all those disadvantages that occur with indirect meçh~ni~m~ of action are avoided to a very great extent. This leads to less disturbance of the cellular processes in the sense of a nonspecific disturbance and thus in the end also to reduced seçondary effects on the systemic level.

The explanations given above in cormection with the advantageous effects of mutations and other forms of the SAT sequences of the invention also apply to the ST sequences of course, and are included herein for reference.

The advantageous effects are also furnished when the ST and/or SAT sequences are present as a double strand and/or a coding andlor noncoding single strand and/or cDNA. It lies within the framework of the present invention if the said sequences are present as DNA or as RNA. The use of such constructs according to the invention enables somatic and/or transitional gene therapy for influencing vessel development.

Furthermore it is advantageous if the corresponding sequences are also present as a single strand, whether coding or noncoding, whereby agents can then be used that act specifically on the single strand, in order to ensure that vessel development is influenced.
It is possible for those sWlled in the art to utilize the said sequences in both their native or mutant form and/or their fragmented form, without having to forego the advantage of the directly mediated action. Here too, the previous explanation conc~rning mutation and fragmentation applies.

Vessel development can also be influenced advantageously if the ST and SG sequences have at least one eukaryotic promoter and/or at least one enhancer element and/or at least one transcription tç~nin~tion element andlor at least one resistance gene and/or at least one other marker gene. The transcription and/or translation can be influenced by these elements in a way that is more advantageous for influencing vessel development. Thus a suitable eukaryotic promoter can be controlled, e.g. via the presence of specific factors and thus a pre~et~rrnined expression can be in~ ce~ by endogenous and/or exogenous factors. Resistance genes would allow further distinguishing of the cell populations to be influenced and could also be used as selection markers. A marker gene would be advantageous in this connection in so far as an indication of the processes proceeding at the molecular or molecular-genetic level could be ensured thereby.

Because the ST and/or SAT sequences are present as clones in a host system, there exists the possibility of achieving vessel development both _ vivo and in vitro via the effects of the level of expression caused by the natural presence of the ST and/or SAT sequences.
This can lead, for example, to particularly rapid vessel growth.

The fact that at least one copy, i.e. an ST and/or SAT sequence of the invention, is present in the respective biological system, makes it possible to achieve further advantageous effects in the sense of the above explanations, via gene dosage effects.

An agent of the invention for influencing vessel development selected from the group that includes sense DNA, sense RNA, sense cDNA, ~nti~n~e DNA, ~nti~n~e RNA, and antisense cDNA, and combinations thereof, as a single strand and/or a double strand, whereby this agent is(are)[sic] present in native or mutant form and/or complete or as a fragment and/or chemically modified or not chemically modified, is particularly advantageous.

If the sequence of the agent(s) corresponds to an ST or SAT sequence(s) or to the corresponding transcript(s), which is(are) present in native or mutant form and/or complete or as a fragment, it is possible to exert an influence via a corresponding interaction between the respective nucleic acids [text mi.~sing in original] the expression, i.e. the transcription and/or translation on the influencing of vessel development advantageously. Thus it is e.g. conceivable to raise the level of expression of the corresponding sequences by using a suitable sense DNA or sense RNA. Vice versa, it is conceivable, e.g. in the case of reducing tumor angiogenesis, to use corresponding antisense DNAlantisense RNA and thus to reduce the expression. As a result of the reduced c;~iession of the ST and/or SAT sequences, tumor angiogenesis is red~lcecl, which leads to a reduction in the volume of the tumor until it disappears. Corresponding mech~ni.cm.~ are also obtained when cDNA or antisense cDNA are used. The advantageous effect can also be observed when the corresponding agent is present in non-native form, i.e. mutant and/or fragmented. Such mutations are advantageous in so far as the interaction of the sequence-specific agents with the ST and/or SAT sequences and/or cellular factors can be distinguished against the genetic background. Vice versa, a possibly advantageous response of original target sequences is possible with a sequence that is largely native. The corresponding sequences of the agents used do not necessarily have to be present in complete form, i.e. in complete length; favorable effects can also be achieved when they are present as a fragment, as defined above.

It is also conceivable for the agent of the invention to be introduced into the cell or be present there and itself serve as a matrix, and for it to have biological effects. Such effects can be caused by DNA and/or RNA and/or corresponding translation products.
Thus the possibility of somatic gene therapy andlor transitional gene therapy is opened up by the agents of the invention.

Although the use of both DNA and RNA is possible in principle within the framework of the agents of the invention, owing to the reduced stability of RNA in biological systems, the use of DNA may be appropriate when a longer-term effect is desired, and vice versa the use of RNA may be appropriate when only a short-term influence on the corresponding sequences is desired.

Chemical modification of the agents of the invention may be advantageous among other things in so far as e.g. the biological half-life of the agent can be influenced thereby and thus the duration of the action of the agent of the invention can be influenced precisely.

There are quite particular advantages when the corresponding agent is acting against the ST and/or SAT transcripts. Thus the accessibility of the transcripts relative to the sequences typically present as a double strand can be important for the effectiveness of the inhibition, but also for the effectiveness of the stimlll~tion. In addition to the native form, the mutant form of the transcript also offers the possibility of a fur~er influencing of the specificity of the interaction, whereby the corresponding transcripts can optionally be present complete or as a fragment, whereby the various splice forms are to be understood as a fragment in addition to the forms defined above.

With an agent of the invention for influencing vessel development selected from the group that includes polyclonal antibodies, monoclonal antibodies, and fragments and deli~ati~/es of the same, a specific tool is made available for advantageous use. The specificity of said agent is acting against the ST andlor SAT sequences and/or the collespollding transcript(s), which is(are) present in native or mutant form and/or complete or as a fragment. Thus the aforementioned specificity of the agent causes a highly specific interaction with said sequences. In addition to the epitopes established by the native sequences, including those yielded by the respective transcription products, the mutant transcription products of the optionally mutant sequences are also tissue- and organ-specific compared with the r~m~ining cellular antigenic background, or that of other cells, so that the target cell specificity of optionally systemically applied agents required for influencing vessel development--associated with the fewest possible side effects--is ensured. The same also applies to the presence of fragmen~.c of the transcription products.

In addition to the use of polyclonal and monoclonal antibodies, the use of fragments and derivatives thereof can also be particularly advantageous in the sense of the present invention. Fragments include all those forms of molecules derived from antibodies that continue to allow more or less specific binding to an antigen or epitope. Derivatives are understood to mean antibodies or fragments derived from the original structure of the antibodies. These include, among others, antibodies comprising only one protein chain, as well as marked antibodies. ~rkin~ include all those described in the literature and include among others m~rking with enzymes, luminescence, complex-formers, biotin and biotin derivatives, digoxigenin, and radioactive markers.

It is furthermore provided that the antibodies, fragments, and derivatives of these are modified so that uptake into the cell is possible ~ltili~ing biological and/or chemical and/or physical merh~ni.cm~. Such a modification can consist for example in that the molecule has at its disposal an additional structure (e.g. a corresponding domain or attached compound) that enables receptor-mediated or other, possibly nonspecific, uptake.

What has been explained above with respect to the specificity of the said agent opposite to ST and/or SAT sequences or the corresponding transcripts also applies to their translation products. Here too, in addition to the [text mi~sing in original] by the native form of the translation products of the sequences or their transcripts, those translation products are particularly important that are tr~ncl~ted from mutant sequences. In addition to the numerous epitopes of the native translation products present, the aberrant translation products are of particular interest for a selective response by defined cell populations, whereby in addition to the disappearance of epitopes previously present, the new appearance of epitopes is also of importance. Such epitopes can in principle be caused both by the primary sequence and also by the secondary, tertiary, or qu~tern~ry structure, and can also affect the glycosylation and phosphorylation sites.

The specificity of an agent for inflll~ncing vessel development can also be influenced by an agent that is itself selected ~om the group, including polyclonal antibodies,monoclonal antibodies, and fragments and derivatives of these, in that this agent is acting against the antibodies or fragme-nts or derivatives, which for their part are acting against the ST and/or SAT sequences and/or the corresponding transcript(s) in their various forms, as defined above, or opposite to the corresponding translation product(s) in their various forms.

An advantageous influencing of vessel development is also allowed by an agent of the invention for influencing vessel development that [word mi.c.~ing in original] at least one translation products[sic] of one or more ST and/or SAT sequences and/or of the col,esponding transcript(s) that is(are) present in native or mutant form and/or complete or as a fragment, and whereby the said translation product(s) is(are) present in native or mutant form and/or complete or as a fragment and/or glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated and/or chemically modified or not chemically modified.

The said advantages of a protein or peptide that is a translation product of one or more S[sub]AT sequences and/or of the corresponding transcript(s), which is present in native or mutant form and/or complete or as a fragrnent, also apply of course to the agent of the invention and are herewith included for reference.

Other advantages result from the use of at least one t;~ ssion inhibitor and/or at least one expression-stim~ t1n~ agent in the framework of an agent for influencing vessel development. The aforementioned MMAKS and MMAKP agents of the invention can alsorepresent such e~lession inhibitors or ~ ssion-stimlll~ting agents. Expression inhibitors and expression-stimulating agents different from these are also included, however. It is within the me~ing of this invention that the genetic background is modulated relative to the expression of ST and/or SAT sequences by correspondinginhibitors or stim~ ting agents. The desired influencing of vessel development can result from this relative relationship of the e~ression of the genetic background on the one hand and of the ST and/or SAT sequences on the other hand. It is also entirely possible to use said MMAKS and MMAKP agents in addition to the - nonspecific, since they influence the total genetic background of the cellular system - inhibitors and/or stimulating agents.

The selectivity of the influencing of vessel development can be increased in an advantageous manner with an increased specificity of the expression inhibitor or the e~lession-stimulating agent for one or more of the ST and/or SAT sequences, compared with other genes of the genetic systern concerned.

The said advantages concerning the influencing of vessel development also extend to angiogenesis, whereby this can if necessary be reduced and/or intellu~ted in an advantageous manner. Vice versa, stimulation of angiogenesis is also possible and can be carried out advantageously using the ST and/or SAT sequences in the broadest sense, including the corresponding translation products and the agents of the invention.

The agent of the invention is of central importance for influencing vessel development when this relates to tumor angiogenesis. As already explained, the presence of a vascular system is essential for the growth of a tumor. With the sequences and agents of the invention or the use of the invention of the ST sequences in the broadest sense and including the translation products and the agents derived therefrom, it is now possible to control tumor angiogenesis and thus a novel method is set forth for the treatment of various tumors. Thus comparatively nonspecific therapies such as chemo- and radiation therapy with their widely known side effects become obsolete, and instead a highly specific form of therapy is made possible. A further impairment of systemic angiogenesis can also be avoided by suitable measures, such as e.g. a~mini~tration of the agent explicitly at the site of the tumor angiogenesis.

Said specificity is based among other things on the fact that stronger expression of HMGI-C has not been found hitherto in any tissue of the adult org~ni~m, with thèexception of the endometrium, so that in fact the development of blood vessels in the environment of the tumor can be interrupted selectively.

The explanations given in connection with angiogenesis also apply when the agents or their use relate to influencing vessel development in the sense of vasc~ ri7~tion.

Just as in other diseases, processes of (neo-)angiogenesis, (neo-)vascul~ri7~tion, and disturbancesofvasc~ ri7~tionalsoplayalargepartinvisioni~pAil.llentssuchase.g.in diabetes mellitus. Thus an advantageous specific treatment is possible here too, using the agents or sequences of the invention, as is surmounting the initially explained disadvantages of existing therapies. The preventive aspect of such a treatment is of considerable importance when the agents or sequences of the invention are used according to the invention, so that further impairment of the health and well-being of the patient by a vision impai,ll,ent is avoided.

The use according to the invention of the agents of the invention for influencing vessel development can be used advantageously in improving the blood supply of infarct-damaged heart muscle tissue. (Neo-)angiogenesis and (neo-)vasc~ ri7~tion enable the heart muscle tissue to be better supplied with vessels thereby. In addition to achieving~ a fundamentally improved state of health of infarct patients, either bypass operations can be omitted completely or the healing process can be successfully reinforced. Moreover the use according to the invention relates to improved blood supply to the heart muscle tissue in general and to that of high-risk patients specifically.

The advantages with respect to influencing vessel development extend to both the human and animal org~ni~m, whereby a therapeutic and/or diagnostic use is advantageous in hllm~n~ and/or ~nim~l~

In addition to the direct benefit that a human experiences by the influencing of vessel development, whether for regeneration purposes or for the treatment of tumor diseases or effects of diabetes mellitus (impairment of vision), the benefit can also be of an indirect nature, e.g. when applopliate vessel m~teri~l is produced for transplantation purposes, under the influence of the sequences and/or agents of the invention or uses in ~nim~

Use in the sense of veterinary medical use is also included, of course.
In addition to this very broad therapeutic use, an advantageous diagnostic use is also possible in principle in both hllm~n~ and animals. It is particularly advantageous thereby to use the MMA1CS and MMAICP agents, above all when they carry markers that can be detected by means of non-invasive test methods. Thus, for example, it can be checked whether a therapeutic measure has the desired success at the genetic level. Inflllençing~
vessel development according to the invention is also advantageous when an agent of the invention and/or one of the ST and/or SAT sequences or their uses is(are) used _ vitro.
This includes use in cell, tissue, and organ cultures, among others.

Finally, the agent of the invention or its use can also be used to produce a drug for therapeutic and/or diagnostic use, so that a drug is available that is clearly superior to agents of the state of the art used for the purpose of influencing vessel development or for the purpose of tre~tm~nt of diabetes mellitus and tumor diseases, as far as side effects associated wi~ these are concerned.

The aforementioned advantages also apply of course to the kit of the invention in its various forms of embodiment and are included herein for reference. The same applies to the advantages resulting from the individual components of the kit.

The advantages of a kit are generally considered to be in that, among other things, the respective agent is ready prepared in the optimal manner for its use. This also includes a suitable spatial arrangement. Advantageous effects can result thereby precisely from the combination of the various agents.

In addition to its therapeutic use for influencing vessel development, including reduction of tumor angiogenesis for treating effects of diabetes mellitus and for improving vessel provision of infarct-damaged heart muscle tissue, the kit of the invention can also be used for diagnostic and test purposes; e.g. information can be gained advantageously as to how far certain therapeutic measures are char~cten7ed by success or whether certain substances produce the effects ascribed to them.

The explanations given in connection with the use of the ST and/or SAT sequences of the invention in the broadest sense, including the corresponding transcripts and translation products, as well as in connection with the agents of the invention for influencing vessel development, of course apply also to their use for treating endometriosis and tocorresponding agents and kits of the invention for treating endometriosis and are included herein for reference.

Without predjudice, it is assumed that the stnlchlring of the endometrium takes place under the influence of the expression of the HMGI-C gene, even when endometriosis is present, as a result of which influencing the e~l~es~ion of this gene or functionally similar genes by using the said sequences or agents and kits leads to a specific treatment for endometriosis that is virtually free of side effects.

The explanations given in connection with the use of the ST and/or SAT sequences of the invention in the broadest sense, including the corresponding transcripts and translation products, as well as in connection with the agents of the invention for influencing vessel development, of course apply also to their use for contraception and to corresponding agents and kits of the invention and are included herein for reference.

Here too the invention is based on the surprising finding that the HMGI-C gene participates in the structl-nng of the endometrium. When the sequences or agents of the invention are used, contraception or pregnancy is achieved by specifically influencing the endometrium receiving the fertilized ovum, for example in the sense of suppressing its stmctllring Since the HMGI-C gene is expressed almost exclusively in the endometrium in the healthy adult human org~ni~m, this ensures that even when an ~plop-iate agent is applied systemically, only the desired target site, i.e. the endometrium, is exposed to the infl~lçnce of the corresponding agents of the invention and thus the side effects observed when hormonal agents are ~-imini.~tered for contraception are virtually absent.

The uses according to the invention or agents and methods for contraception provide for local contraception as well as oral contraception. In addition to the significant advantage of decidedly simple and reliable oral ~dmini~tration in the framework of oral contraception, local contraception also offers advantages. Thus the formulation of the a~plopliate ple~alations can be simple, since gastrointestin~l passage is not necessary.
Tn~te~11, it can be ensured by means of e.g. aerosols that the agents of the invention reach their site of action, i.e. the endometrium, directly.

Further advantages resulting from the individual forms of embodiment of the use of the invention, like those resulting from the agents of the invention for contraception and the methods of the invention for contraception, have of course already been stated in connection with the influencing of vessel development and are included herein for reference.

As far as advantageous effects are concerned, it can also be stated that by periodic ~mini.~tration of the agent of the invention or by means of the processes of the invention, a cyclicity becomes possible with respect to the strllct lring of the endometrium that may be useful from the point of view of basic medical or biological considerations and represents a therapeutic use of the agents of the invention, for example in cases of menstrual problems.

An advantage of the process of the invention that should be particularly emphasized is that the agents of the invention can be a-1mini~tered after conception. Without prejudice as to the mecll~ni~m of action, it can be stated that according to our present understanding, the structuring of the endome~ium can be influenced before, during, and after nidation by influencing the ~ ression of the HMGI-C gene or analogous genes, so that the endometrium degenerates and the pregnancy is inte,l,lyted.

The explanations given in connection with the use of the sequences of the invention and ST sequences in the broadest sense, including the corresponding transcripts and translation products, as well as in connection with the agents, kits, and optionally processes of the invention for influencing vessel development and for contraception, of course apply to their use for tissue regeneration and to corresponding agents, kits, and methods of the invention, and are included herein for reference.

Tissue regeneration is understood herein to mean both regeneration of tissue with recourse to exactly the type of tissue to be regenerated, in the sense of an increase in the mass of the tissue, as well as the production of new tissue starting from a difrerenl type of tissue or cell than that to be produced.

Furthermore the uses, agents, kits, and processes of the invention for tissue regeneration allow the regeneration of tissue that hitherto could not be regenerated or only with difficulty, or makes corresponding regeneration processes safer overall both for the personnel entrusted with the task of tissue regeneration and for the final recipient of the tissue regenerated in this manner; through the use of the invention and the kit of the invention and the process of the invention, however, defined conditions are created tha allow a specific intervention in the sequence of events of tissue regeneration, while avoiding the involvement of m~tçri~l from biological sources that pose a risk, at least latent, in the form of possible viral ~hepatitis C, HIV) and bacterial cont~min~tion~ as well as factors not tolerated immunologically (anaphylactic shock).

CA 02239682 1998-06-19 -.

The use of at least one of the agents of the invention _ vivo is associated withconsiderable advantages for a number of reasons. Thus for example no collection of m~terial is required from any tissue or organism whatsoever. Thus rejection reactions resulting from tissue incompatibility and problems that might result from the use of m~teri~l from biological sources do not occur.

Vice versa, the use of at least one of the agents of the invention in vitro can likewise be advantageous, namely when a corresponding use is not possible under the conditions lly prevailing in the or~ni~m This may be the case e.g. when no tissue is available in principle that is suitable to serve as starting m~t~ri~l for the regeneration process of the invention. The use in or on cultures selected from the group that includes cell cultures, tissue cultures, organ cultures, and combinations thereof, facilitates controlled tissue regeneration to a not inconsiderable extent, while the uses of the invention or agents and processes used for this purpose can be used and carried out under defined conditions. Moreover there exists the possibility in such _ vitro systems of producing corresponding material beyond the respective current need and thus of being in a position to satisfy an unforeseen need.

In connection with this Application, a therapeutic treatment is also int~.n~eA to include such a treatment for cosmetic purposes.

It is moreover held that the use of an agent of the invention is quite particularly advantageous in the process of the invention.

For the process of tissue regeneration, a variant can also be advantageous from the point of view of cost-effectiveness of the process or safety, in which the prepared or cultivated target cells already express at least one of the ST and/or SAT sequences, whereby the process step of the invention would omit the introduction of at least one of said sequences. The subsequent steps of the process remain llnch~nged.

Depending on the tissue to be regenerated, various processes can be selected to introduce the ST and/or SAT sequences. Those skilled in the art can ascertain the optimal transformation- or tranfection protocol in each case by applopliate routine tests.

Target cells origin~ting from a human are quite particularly advantageous. The human concerned can be the person who is to receive the tissue regenerated according to the invention, or else another person who is a suitable donor. In principle, target cells from a dead person can also be used. The latter may be the case, e.g. if no suitable living donor is available, or if a suitable donor is already dead and his tissue, for example because of age, is no longer suitable for direct transplantation purposes.

It can also be advantageous, however, if target cells originate from an animal organism other than a human. Thus, e.g., the use of target cells that origin~te for example from a transgenic ~nimal may make sense under certain conditions, particularly if the transgenic animal yields target cells that are histocompatible with those of the recipient organism or have other advantageous properties.

. CA 02239682 1998-06-19 The use of target cells that represent a dir~elenl type of cell from the cell types contained in the tissue to be regenerated is advantageous when target cells taken from the tissue to be regenerated are not suitable for regeneration purposes. Using the process of the invention, corresponding agents, and kits, such target cells can be caused to regenerate in the sense of a proliferation and differentiation.

Vice versa, the use of target cells that belong to the same cell type as that contained in the tissue to be regenerated can increase the success of the process, above all when the tissue to be regenerated is still sufficiently intact, but the extent of the tissue still present is not enough to fulfill the respective biological function to its full extent.

The (de-)difr~le"lalion of the target cells under the influence of at least one of the ST
and/or SAT sequences of the invention in the broadest sense, including of the corresponding transcripts and translation products, as well as agents of the invention acting against these, to produce pluripotent stem cells, allows cells to be changed into a condition that allows development of the respective cell into each mesenchymal cell type and thus allows the regeneration of almost any desired mesenchymal tissue. This also includes a case in which the direction in which the regeneration of the invention finally proceeds, is detennined by the influence of additional factors, if necessary of the cellular ellvilolllllent in which the cell is situated or into which the cell is introduced.

Advantageous effects occur when target cells of the process of the invention are co-cultivated with other cells and/or cell types. As already indicated in the above section, co-cultivation can have a determinative influence on the direction of the (re-)differentiation of the target cells in the sense of a tissue regeneration. Without prejudice, it can be assumed that influences apparelltly ~m~n~te from the cells used for the co-cultivation that influence the dirrelellliation state of the target cells. Such an influence can be mediated by more or less soluble factors, but also cellularly, with the latter also including interactions of cell membrane structures or components in the broader sense as well as other physical or chemical phenomena such as e.g. mernbrane pot~nti~l~

Depending on the type of tissue to be regenerated, as well as on the sources available in principle, the m~teri~l collected from an organism can be selected from the group that includes cell-cont~ining biological fluids, cells, single cells, tissue, and organs. With the collection of cell-cont~ il-g biological fluids or single cells, it is ensured that further steps to recover single cells from tissues or organs are avoided to a great extent. This ensures that cells are utilized for regeneration purposes that actually appear to be best suited for the respective case. It can also be advantageous, however, to collect tissue or even complete organs. Thus it is conceivable that with the collection of tissue or organs, several cell types are available whose suitability can be tested during a routine test proc. s~ing Moreover when tissues or organs are collected, an advantage can result in that otherwise the collection of suitable cell m~teri~l would be impossible.

After introduction of at least one of the ST and/or SAT sequences of the invention, the introduction of target cells into an animal organism offers advantages in that the respective animal or~ni~m, including the human, thus contains biologically active tissue in order to elimin~te defects or deficiencies relating to this. The target cells can be introduced thereby when the target cells are either in the form of single cells, or, after cultivation, are already in the form of cell aggregates, tissue, or the like. Finally it is also conceivable in principle for the target cells to be introduced into an animal organism in order to develop there further under the influence of the biological system. Later collection of the target cells further modified and/or increased and/or differenti~ted in the biological system, i.e. the animal org~ni.~m, is likewise to be included thereby.

After introduction of at least one of the ST and/or SAT sequences of the invention into the target cells, it can be advantageous to induce their eApression in the target cells before the target cells are introduced into an animal organism. The advantage is that thus the possible influence of the biological system on the di~elellLiation is limited. This can be particularly advantageous when differentiation of the target cells in the desired direction would not be guaranteed in a cellular environment owing to the differentiation factors or signals there.

Vice versa, it is also advantageous, after introduction of at least one of the sequences of the invention or ST sequences, to induce their ~A~,ession in the target cells after the target cells have been introduced into an animal organism. This subsequent induction can be advantageous if the proliferation and/or di~elellliation of the target cells is only to take place under the influence of the target region or the target . .... .. . .. . . .. .

tissue with its specific di~elellliation signals and factors, in order to exclude premature di~e~ Liation in a direction other than the desired one.

Of course, the said advantages also result with respect to whether the target cells introduced into an animal organism are in a differ~nti~tecl and/or di~ere lliation-competent state.

If the animal organism into which the target cells are introduced is a human org~ni~m, particular advantages result thel~ionl, among others with respect to the treatment of degenerative diseases, such as e.g. ar~rotic diseases or muscular dystrophy. Similar to the advantages discussed in connection with the recovery of suitable target cells, these also result from the fact that the target cells are introduced into an organism that is identical with the organism from which the target cells were collected.

Vice versa, it can also be advisable for the organism into which the target cells are introduced to be different from the organism from which the target cells originate, e.g.
when the organism into which the target cells are introduced no longer has any of its own starting m~tPri~l available.

Quite particular advantages result in the processes of the invention when at least one of ~e SAT sequences of the invention or the ST sequence is introduced into the tissue in the organism that is to be regenerated and/or the corresponding cells. Such a measure ensures that no surgical operations are required, either for collection or reintroduction of corresponding m~teri~l, which is of central importance when the regions from which the material is collected or into which the m~teri~l is introduced are only accessible by invasive means. Moreover the work required is reduced, . CA 02239682 1998-06-19 as is the risk that the tissue to be regenerated is col~t~",in~ted or else that a non-optimal regenerative development occurs under the conditions of in vitro cultivation.

Introduction of the constructs concerned as such into the tissue to be regenerated and/or the corresponding cells using gene therapy processes presents a quite particularly advantageous possibility, with particular advantages resulting from the use of suitable viral systems. Using routine tests for the application concerned, those skilled in the art can ascertain the process required for introduction of the sequences.

Finally, other advantages also result from the fact that expression of the introduced sequences of the invention and the ST sequences is influenced by at least one MMA~CS agent and/or at least one MMA~P agent and/or at least one translation product TP and/or at least one expression-stimulating agent ES. Thus there exists the possibility of controlling the extent of the regeneration both with respect to its spatial pattern and also with respect to its time course.

The uses and agents of the invention for treating tumor diseases are generally advantageous in so far as a specific therapy for tumor diseases thus becomes possible, without the occurrence of systemic side effects as is the case with other therapies for treating tumor diseases such as e.g. chemotherapy or radiation therapy. As already stated, only a few tissues in the healthy organism express the SAT or ST sequences of the invention, whereas they are expressed strongly in a number of tumor diseases. As a result the agents, kits, and processes of the invention, which are specific for said sequences, allow a specific therapy for cancer, which moreover is free of side effects as a result of the mech~ni.~m of action on which it is based.

Although not limited to these, quite particular advantages with respect to specificity and reduction of side effects, as well as efficacy of the agent of the invention, result when the tumor to be treated expresses a gene selected from the group that includes MAG genes, high mobility group protein genes, HMGI-C proteins, HMGI-Y genes, and their derivatives. The same applies to the use of at least one of the agents of the invention for producing a drug for treating tumor diseases.

Further advantages of the various forms of embodiment of the agents of the invention and kits that contain these individually or in any combination for treating tumor diseases, as well as of the uses of the invention, result of course from the explanations in association with the uses of the invention of the ST and SAT sequences of the invention in the broadest sense, including the corresponding transcripts and translation products, agents and kits and optionally processes for influencing vessel development, for contraception, and for tissue regeneration, and are included herewith for reference.

The DNA sequences clairned in the invention are shown in Figures 1 to 19. Moreover the sequences are s--mm~ e~ together with further general data in the sequence protocol, whereby Fig. 1 correspondsto SEQIDNO: l;
Fig. 2 corresponds to SEQ ID NO: 2;
Fig. 3 corresponds to SEQ ID NO: 3;

Fig. 4 corresponds to SEQ ID NO: 4;
Fig.5 collc;~ondstoSEQIDNO: 5;
Fig. 6 corresponds to SEQ ID NO: 6;
Fig.7 correspondstoSEQIDNO: 7;
Fig. 8 corresponds to SEQ ID NO: 8;
Fig. 9 corresponds to SEQ ID NO: 9;
Fig. 10 collcs~onds to SEQ ID NO: 10;
Fig. 11 colle~onds to SEQ ID NO: 11;
Fig. 12 corresponds to SEQ ID NO: 12;
Fig. 13 colles~onds to SEQ ID NO: 13;
Fig. 14 corresponds to SEQ ID NO: 14;
Fig. 15 corresponds to SEQ ID NO: 15;
Fig. 16 colle~onds to SEQ ID NO: 16;
Fig. 17 corresponds to SEQ ID NO: 17;
Fig. 18 corresponds to SEQ ID NO: 18; and Fig. 19 corresponds to SEQ ID NO: 19.

When the bases given in Figures 1 to 19 are other than A, C, G, and T, the following nom~t-clAtllre applies:

R can be A or G, Y can be C or T, K can be G or T, McanbeAorC, S can be G or C, and WcanbeAorT.

For fi~rther illustration of the invention, eight Examples are also given below, chosen at random from the wealth of material available.

The techniques used in the following Examples are surnmarized below. When changes are required for the individual Example, they are stated at the a~propliate points.

Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) The reverse transcriptase polymerase chain reaction (RT-PCR) includes the transcription of RNA into cDNA which is then subjected to a regular polymerase chain reaction using a suitable primer.

In the examples described herein, the RNA was isolated with the TRIzol reagent (Life Technologies, Gaithersburg, U.S.A.). The tissues, healthy tissue as well as tumor tissue, were stored under liquid nitrogen for the time between removaVoperation and start of the RNA isolation.

The RNA was transcribed into cDNA using the M-MLV Reverse Transcriptase (Life Technologies, Gaithersburg, U.S.A.), and then used for the RT-PCR.

The RT-PCR was conducted as a so-called nested PCR, that is, as a sequence of two polymerase chain reactions with the primers used being nested into each other. As a special case, in the polymerase chain reaction employed herein the primers were nested on one side only, on the other side the same primers were used for both polymerase chain reactions. Fig. 1 shows details and the position of the primers within the exon of the HMGI-C.

3 ~ @1 ~A, ¦ RNAmolecule Es5 Es4 Es3 E~2Esl fragment length,:
l.PCR: -- 250bp 2.PCR: -- 220bp ¦Primer: ¦¦ReYex4 ¦ ¦ P1 SE1 ¦

[figure captions]

RNA-Molekul = RNA molecule Fragmentlange = fragment length [All others as per source]

Fig. 1: Genome structure of the HMGI-C gene, RNA and cDNA and position of the primers used for the RT-PCR.

The PCR shown in Fig.l does not cover shortened or aberrant transcripts mi~.~in~ the exons 4 and 5. Therefore, in addition to the PCR with the primers shown above, in some cases a PCR was used where the primer Revex 4 (see Fig. 1 ) was replaced by a primer from the 3rd exon. The sequences of all used primers are summ~ri7ed in Table 1.

Table l: Primers used for the RT-PCR of the HMGI-C, their sequences (each from S' to 3') and their positions within the gene (see also Fig. 1).

Primer name Sequence Position SEl CTTCAGCCCAGGGACAAC Exon 1 Pl CGCCTCAGAAGAGAGGAC Exon 1 Revex 3 TTCCTAGGCCTGCCTCTT Exon 3 Revex 4 TCCTCCTGAGCAGGCTTC Exon 4/Exon 5 Polymerase chain reaction for the rapid amplification of 3 ' cDNA ends (3 ' RACE PCR, rapid amplification of cDNA ends).

The procedure was used as described by Schoenrnakers (Scho~nm~ker.~ et al., Nature Genet 10:436-444 (1995)).

Cytogenetic and molecular cytogenetic procedures The cytogenetic and molecular cytogenetic procedures (fluorescence in-situ hybridization) were performed according to published standard methods (Bullerdiek et al., Cytogenet Cell Genet 45:187-190 (1987); Kievits et al., Cytogenet Cell Genet 53:134-136 (1990)). The following probes were used: cRM133, cRM76, cRM99, cRM53 (Scho~nm~kç~s et al., Nature Genet 10:436-444 (1995)) Example 1: Expression of the HMGI-C gene in normal tissue Di~e~nt tissue types were investigated with RT-PCR with regard to the expression of the HMGI-C gene; only tissues of non-tumor source were tested.

The results are summarized in Table 2.

Table 2: Tissues tested for expression ofthe HMGI-C gene, its origin (epithelial/mesenchymal) and extent of the expression of the HMGI-C gene.

Tissue Origin Expression of the HMGI-C gene Myometrium, smooth muscles mesenchymal Adipose tissue, hypodermis and mesenchymal m~mm~
Endometrium epitheliaVmesenchymal ++
Umbilical cord mesenchymal Blood vessels (adult) mesenchymal (+) Blood vessels (fetal) mesenchymal ++
Skin (fetal, gestation week 11 ) epitheliaVmesenchymal ++
Cartilage - mesenchymal Cartilage (fetal, gestation week 11) mesenchymal ++
++: strong t;~res~ion + : weak e~res~ion (+): very weak expression - : no detectable expression From among the tested normal tissues, adult blood vessels showed a very weak and fetal blood vessels (arteria and vena umbilicalis) a significantly stronger expression of the HMGI-C gene. Endometrial tissue of the proliferation phase and the fetal tissues also showed a marked expression. All other tissues showed no ~Lession.

The tests were conducted with the gene of the HMGI-C as a model; based on the extensive sequence homology and the similar e~lession patterns in the embryonal and fetal development of the mouse, similar results can be expected with the HMGI-Y gene.

Example 2: Aberrant transcripts of the HMGI-C gene cDNA was isolated from established cell lines and primary tumor material from human benign mesenchymal tumors (uterus leiomyoma, pulmonary hamartochondromas, aggressive angiomyxoma) as well as from tumors of the head salivary glands; it was then amplified by RACE-PCR and sequenced.

The obtained sequences are compared to sequence of the native HMGI-C gene.

Based on the results of this sequencing, a transcript or its cDNA was labeled as an aberrant transcript when, as a minimum, the sequence of the exons 1-3 (of a total of 5 exons) is present, and the sequence of exon 3 is followed by a sequence other than that of exon 4 or the sequence of exon 4 iS followed by a sequence other than that of exon 5. The sequences fused to the HMGI-C gene were regarded as ectopic when their origin from a region of the chromosome 12 other than that of the HMGI-C or from another chromosome could be verified.

The tests performed as described yielded various aberrant transcripts detailed in Figures 1-19. The sequence of the transcripts always starts with the 15' nucleotide of exon 1 of the HMGI-C gene; the region of the sequence between the first nucleotide of the first exon and the first nucleotide of the primer was added from a databank. The sequence contains either the complete sequence to the poly-A tail or a part thereof. In any case, the sequence goes far beyond the 3rd exon or 4th exon and therefore characterizes the aberrant transcript.

Example 3: Rearrangement of the HMGI-C gene in h~m~n iopericytomas Tumor m~ttori~l from two tumors, fixed in a paraffin matrix, was subjected to a fluorescence in-situ hybridization. Cosmid clones obtained from the region of the HMGI-C or the sequences directly fl~nking on 3' and 5' were used as probes. The tests were performed on interface nuclei isolated from the tumor material and showed the breaking points to be within the cosmid covered regions of the tumors tested; this allowed for the conclusion that this is the same type of mutation as with the other mesenchymal tumors.

Example 4: Dirrerelltiation of cells with mutant HMGI-C gene Cells of tumors with verified rearrangement of the HMGI-C gene (3 lipomas, 5 pulmonary hamartomas, 2 uterus leiomyomas) were co-cultured with normal cartilage cells. The cell culture conditions (Bullerdiek et al., Cytogenet Cell Genet 45:187-190 (1987)) for the co-cultivation were adjusted such that in the culture the differenti~te~
status of the cartilage cells was m~int~ined (no addition of fetal calf serum). The tumor cells oligin~te~ from primary cultures with additional fetal calf serum. In the cell culture the tumor cells differenti~te~ into cartilage cells, independent of whether they were tumors co~ g cartilage or not.

Example 5: Inhibition of neoangiogenesis and neovasc~ ri~tion Events related to neoangiogenesis, neovascularisation and vascularisation defects are important factors not only in the development of tumors but also in the pathogenesis of many other diseases such as diabetes mellitus (Battegay et al., J.Mol. Med. 1995 (73), 333-346). The example described herein ~Y~mined the role of the HMGI-C gene withregard to neoangiogenesis and neovascul~ri~hon using the techniques described at the beginning and including clonality tests (Noguchi et al., Cancer Res. 52: 6594-6597 (1992)). The techniques mentioned at the beginning and the clonality tests showed that the observed vasc~ ri~tion originated from the tumor cells themselves. Because of the role of HMGI-C in the proliferation and differentiation of pericytes, the neov~clll~ri~tion of myomas, lipomas, leiomyomas and aggressive angiomyxomas ori in~ting from the tumor cells, and based on the data to the gene expression, the (neo)angiogenesis and the (neo)v~cul~ri~tion can be affected as desired by the sequences shown in Figures 1-19, the sequences ST~ the claimed means and materials, kits and possibly methods, or by their use.

Example 6: Treatment of endometriosis The term endometriosis refers to ectopic endometrium that participates "in the normal cyclical and the pathological changes of the endometrium corporis" (Psychrembel, 1982).
The histologic structure conforms to the normal endometrium in so far as epithelial and mesenchymal components are present. It could be shown, using the techniques described at the beginning, that the or~ni7~tion of the ectopic endometrium is based on the expression of the HMGI-C gene, similar to physiologically normal endometrium.
Therefore, treatment of endometriosis can be based on the sequences shown in Figures 1-19, the sequences ST, the claimed means and materials, or their use.

Example 7: Contraception Using the techniques described at the beginning it could be shown that the expression of the HMGI-C gene is involved in the org~ni7~tion of the endometrium. Thus, the sequences shown in Figures 1-19, the sequences ST~ the claimed means and materials or their use provide means and methods for contraception.

Example 8:

Using the techniques described at the beginnin~, three pulmonary hamartochondromas were investigated, all of which showed a translocation between chromosome 12 and 14 with presence oftwo normal chromosomes 12 and one derivative 14, with the corresponding derivative 12 missing. The chromosomal breaking point on chromosome 12 was situated 5' from HMGI-C, the e~reSSiOn of which was also shown in all tumors.

This proves that incorporating one of the sequences ST or SAT leads to a proliferation of normal tissue which can be used for purposes of tissue regeneration or stimulation of angiogenesis or vascul~ris~tion.

Exarnple 9: Expression of the HMGI-C gene upon cartilage formation during embryonal development of the mouse A cDNA fragment of the HMGI-C gene of the mouse (approx. 1.8 kb length, approx. 800 bp 5' UTR to 200 bp 3' UTR) was cloned into an in-vitro translation vector. The presence of T7 or Sp6 RNA polymerase promoters was exploited to synthesize a RNA probe suitable for in-situ RNA-RNA hybridization. This probe was then used for hybridizing in tissue slices of mouse embryos in different stages of development. The results show that, arnong others, a very strong expression of the gene occurs during cartilage formation from mesenchymal progenitor cells.

.. .. . ... . .... ..... ,, . .. . . ~ . . . .

This e~ression is not only detected with mesenchyma of mesodermal but also of ectodermal origin (head area).

Example 10: Transfection studies with expression constructs and antisense constructs of HMGI-C and its derivatives The above-mentioned cDNA fragment of the mouse or a corresponding antisense sequence was cloned into an eukaryotic expression vector. In this construct it is controlled by the LTR sequence of Moloney's virus of mouse sarcoma. The construct was then used for the lipofectin-mediated transfection in various primary and established cells. Stable tran~Çe~ were selected by means of ampicillin. It could be shown that upon transfection into primary human fetal fibroblasts the number of cumulative doublings of the transfectant population increased significantly over controls that were only transfected with the vector. A reverse effect was observed on transfection with the antisense construct. The same vector system was then used for cloning the described aberrant transcripts of the human HMGIC; in this case as well, an increase in the number of cl-mnl~tive doublings of the population was also obtained. Depending on the cDNA
sequence used this increase was 10-35% higher than with the cDNA sequence of themouse.

Example 11: DNA-relaxant effect of the proteins derived from the aberrant transcripts Using the DNA sequences SEQ ID Nr. 1-19, consisting of parts of the cDNA sequence of the HMGI-C gene and other DNA sequences mostly appendixed to the 3rd exon of this gene, recombinant proteins were synthesized in the expression vector pET7C and purified.

The proteins purified in this way were then tested for the formation of the so-called negative super coils, in the topoisomerase-mediated relaxation assay described by Nissen and Reeves (J. Biol. Chem. 270, 4355-4360, 1995). This investigations showed that the capacity to induce such negative super coils was in all derivatives higher than in the unmodified recombinant HMGI-C protein used as a control. The allowable conclusion that, arnong others, the interaction of the proteins with the DNA affects the therapeutic efficacy, leads to the deduction that all sequences shown possess an increased effficacy with regard to the applications mentioned.

The features of the invention revealed in the preceding description and in the claims can, both alone and in any combination, be of significance for the realization of the invention in its various forms of implementation.

CA 02239682 l998-06-l9 SEQUENCE LISTING

(1) GENERAL INFORMATION:
(i) APPLICANT:
(A) NAME: Joern Bullerdiek (B) STREET: Weissdornpfad 14 (C) CITY: Bremen (E) COUNTRY: Germany (F) POSTAL CODE (ZIP): 28355 (ii) TITLE OF INVENTION: Nucleic acid sequences of genes of the high mobility group proteins and their use (iii) NUMBER OF SEQUENCES: 19 (iv) COMPUTER READABLE FORM:
(A) MEDIUM TYPE: Floppy disk (B) COMPUTER: IBM PC compatible (C) OPERATING SYSTEM: PC-DOS/MS-DOS
(D) SOFTWARE: PatentIn Release #1.0, Version #1.30 (EPO) (2) INFORMATION FOR SEQ ID NO: 1:
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(A) LENGTH: 566 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 1:

GGTGAGCCCT CTCCTAAGAG ACCCAGGGGA AGACCCAAAG GCAGCA~AAA CAAGAGTCCC 180 TCTA~AGCAG CTCAAAAGAA AGCAGAAGCC ACTGGAGAAA AACGGCCAAG AGGCAGACCT 240 CCCTGTGGAA TAGATAACAT CATCATCCCC ~ AcTG AGGTGTGGGG AAGTTACCTC 480 ATGAATGAAA AP~ AAA A~AAAA 566 CA 02239682 l998-06-l9 (2) INFORMATION FOR SEQ ID NO: 2:
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AAGGAAGAGT CC~YYl~lCC AGTAACAAAA GTATGCCTGA CAAGAGGCTC TAAGCTGTCC 360 TGGATGCCAA T~lLL~lGCC GACTACTTTA CAGTGATTGA TTGCTCATAC CTCACGGSAA 420 CTATTGCCCA TGATCATAGT TTAGCTGGCG CTGCTTTATA A~AGAATGWA TGWAGAAATT 540 AATGWATGAA APU~U~VAAA APU~UUAAAA AP~ ~AAAA AAA~V~AAAA AP}~ULAAGA 600 CA 02239682 l998-06-l9 (2) INFORMATION FOR SEQ ID NO: 3:
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TCTA~AGCAG CTCAA~AGAA AGCAGAAGCC ACTGGAGA~A AACGGCCAAG AGGCAGACCT 240 AGGA~ATGGA AGAAGACAGG AATGTCAGGC CTCTGAGCTC AAGCTAAGCC ATCATATCCC 300 TTGAGAAGGT ACTTTGTGAT ATTCCCCCAC CCTTGA~AAG GTACTTTGTA ATACTCTCCC 660 A~ACCTATAA GAACTAACGA TAATCCCACC ACACTTTGCT CACTCTCTTT TCAGACTCAG 780 CCCACCTGCA CCCAGGTGAT TAAAAAGCTT TATTGCTCAC ACAAAAAAAA A~AAGATGTC 840 CA 02239682 l998-06-l9 (2) INFORMATION FOR SEQ ID NO: 4:
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GGTGAGCCCT CTCCTAAGAG ACTCAGGGGA AGACCCA~AG GCAGCAAAAA CAAGAGTCCC 180 TCTA~AGCAG CTCAAAAGAA AGCAGAAGCC ACTGGAGA~A AACGGCCAAG AGGCAGACCT 240 AGGA~ATGGC CACAACAAGT TGTTCAGAAG AAGCCTGCTC AGGTTCATGC TGGAGGATGA 300 TACCCTATCC TTAATATTAT TACAGGAGCA AGCCTCCATT GACTTTCTGT TCCCTA~ACA 420 CCCAATGCCA AATATATA~A ATTGGCATAT TAATTGCACT GCATCTACTA CGTGTAGCTA 540 AGATTCA~AT TTCTCAGCAA GGTCTTCATT ATCCAGCCTA ACCTAACTTT CACCAATCTC 600 CTCAAAATTT GTATTCCAGC CTTGATGAAT TTATCTTCCT GCAATA~AGA ATATTTGCTG 660 TC~AAAAAAA APP~U~A~G ATGTCGACGG ATCCTTTAGT AGTAGTAGGC GGCCGCTCTA 720 CA 02239682 l998-06-l9 (2) INFORMATION FOR SEQ ID NO: 5:
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AGCAAGAGAA GACAGGAAGG AA~AATCAGA GTAAGGTTTC AATGAGTTTC TGCAAATTCT 360 TACTAAACAA AA~ AAA GATGTCGACG GATCCTTTAG TAGTAGTAGG CGGCCGCTCT 480 (2) INFORMATION FOR SEQ ID NO: 6:
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CAATAAAACA GAAGCAWATT TGTTCTAAAA PA~ AAA AAAAAAAAA 349 CA 02239682 l998-06-l9 (2) INFORMATION FOR SEQ ID NO: 7:
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GGTGAGCCCT CTCCTAAGAG ACCCAGGGGA AGACCCAAAG GCAGCA~AAA CAAGAGTCCC 180 TCTA~AGCAG CTCAAAGGAA AGCAGAAGCC ACTGGAGA~A AACGGCCAAG AGGCAGACCT 240 AGGA~ATGGG ACAATCTACT ACCAAGAACC AGCTCCAAGA AGAAAACATC TCTGGGAAAC 300 TAAA~ AAA AP~U~AA 739 CA 02239682 l998-06-l9 (2) INFORMATION FOR SEQ ID NO: 8:
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AGGA~ATGGG TGGACAGGAA GTAGAATTTA TTGCTGTAGT AATGGCTTCT GGAGAAATGG 300 AAACATCTTA AGGCACTCCA ATAAACAATC TT~lllllGC AAA~U~AAA AAA 533 (2) INFORMATION FOR SEQ ID NO: 9:
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(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 9:
ATGAGCGCAC GCGGTGAGGG CGCGGGGCAG CCGTCCACTT CAGCCCAGGG ACA~CCTGCC 60 CCTCTA~AGC AGCTCAAAAG AAAGCAGAAG CCACTGGAGA A~AACGGCCA AGAGGCAGAC 240 CTAGGA~ATG GCCTACTATT GCACTTTGCA CACACTGGAT A~ACATCTGC TGAATGAGTG 300 GACAATAAAA CAGAAGCAAA lll~llCTAA AAAAAAAAAA AAAAAAGCWT GTCGACGG 358 (2) INFORMATION FOR SEQ ID NO: 10:
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TCTAAAGCAG CTCAAAAGAA AGCAGAAGCC ACTGGAGA~A AACGGCCAAG AGGCAGACCT 240 TTGAGAAGGT A~lll~lGAT ATTCCCCCAC CCTTGAAAAG GTACTTTGTA ATACTCTCCC 660 CCCACCTGCA CCCAGGTGAT TAAAAAGCTT TATTGCTCAC ACA~AAAAAA AAAAGATGTC 840 CA 02239682 l998-06-l9 (2) INFORMATION FOR SEQ ID NO~
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TCTA~AGCAG CTCAAAAGAA AGCAGGAGCC ACTGGAGAAA AACGGCCAAG AGGCAGACCT 240 AP~ ~AAA AAAAAGATGT CGACGGATCC TTTAGTAGTA GGCGGCCGCT CTAGAGGATC 480 CA 02239682 l998-06-l9 (2) INFORMATION FOR SEQ ID NO: 12:
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TCTA~AGCAG CTCAAAAGAA AGCAGAAGCC ACTGGAGAAA AACGGCCAAG AGGCAGACCT 240 APUV~U~AAA APU~V~AAA AP~U~V~AAA AGATGTCGAC GGATCCTT 528 (2) INFORMATION FOR SEQ ID NO: 13:
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ATGAGCTTTA AGTGGAATAA AAACAGAGTT ACCATGAAAA AP~ ~AAA AAP~ AAG 480 CA 02239682 l998-06-l9 (2) INFORMATION FOR SEQ ID NO: 14:
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TCTA~AGCAG CTCAAAAGAA AGCAGAAGCC ACTGGAGAAA AACGGCCAAG AGGCAGACCT 240 AACAGAGCGA GACTCCATCT AACAATAATA ACAATA~AGC TATTGRCCAA AAA~4U~AAA 660 AP}U~U~AAA AAGATGTCGA CGGATCCTT 689 CA 02239682 l998-06-l9 (2) INFORMATION FOR SEQ ID NO: 15:
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TCTA~AGCGG CTCA~AAGAA AGCAGAAGCC ACTGGAGAAA AACGGCCAAG AGGCAGACCT 240 CA 02239682 l998-06-l9 (2) INFORMATION FOR SEQ ID NO: 16:
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AGGAAATGGA ATA~ACAGGA TTCCCAGGAG TGACTTGGTT CTGAATGACT TGGAAGTCAA 300 TGGATGCCAA T~lll~lGCC GTWCTACTTT ACAGGTGATT GATTGCTCAT ACTTCACGGC 420 CA 02239682 l998-06-l9 (2) INFORMATION FOR SEQ ID NO: 17:
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GGTGTCATGT GGTGTTCATC AGTTTGAAAA GAAGTATTTC TG~L~lllGC CTCAAGATGT 360 CA 02239682 l998-06-l9 l07 (2) INFORMATION FOR SEQ ID NO: 18:
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(2) INFORMATION FOR SEQ ID NO: 19:
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(A) LENGTH: 797 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 19:

CCCTCAGCCA TTGATGGAAA GTTCAGCAAG ATCAGCAACA A~ACCAAGAA A~ATGATCCT 360 GATTCATTRA AARCTAGCTG CTCTTAAAAA AAPI~ A~ A~AAAAGATG TCGACGGATC 720

Claims

1. DNA sequence, characterized by at least one sequence as shown in Figures 1 to 19.

2. DNA sequence according to claim 1 characterized by the fact that the DNA sequence corresponds in whole or in parts to that of the HMGI-C gene.

3. DNA sequence according to claims 1 or 2 characterized by the fact that parts of the sequences shown in Figures 1-19 constitute a part of the DNA sequence of the HMGI-C gene.

4. DNA sequence according to one of the claims 1 to 3 characterized by the fact that the DNA sequence is mutant relative to the sequences shown in Figures 1 to 19.

5. DNA sequence according to one of the claims 1 to 4 characterized by the fact that the DNA sequence shows essentially the same sequence as the sequences shown in Figures 1 to 19, including in each case the complementary strand and modified versions of both strands.

6. DNA sequence according to one of the claims 1 to 5, characterized by a nucleic acid sequence that is essentially and functionally identical to the sequences shown in Figures 1 to 19.

7. DNA sequence according to one of the claims 1 to 6 characterized by the fact that it possesses at least one sequence which codes for the DNA-binding component of thecorresponding translation product or the corresponding translation products.

8. DNA sequence according to claim 7 characterized by the fact that the sequencepossesses no sequence which codes for the protein-binding component of the corresponding translation product or the corresponding translation products.

9. DNA sequence according to claim 7 characterized by the fact that it possesses one or more sequences Sr which substitute(s) for the sequence(s) or which supplement(s) the sequence(s) that code(s) for the protein-binding component of the corresponding translation product or corresponding translation products.

10. DNA sequence according to claim 9 characterized by the fact that the sequence Sr is selected from that group which contains other sequences of the human genome, sequences of other (donor) organisms and artificial sequences and their combinations.

11. DNA sequence characterized by the fact that the sequences shown in Figures 1 to 19 are aberrant transcripts of the HMGI-C gene.

12. Expression vector that includes at least one transcription promoter with at least one downstream DNA sequence according to claims 1 to 11.

13. Host cell that is transfected or transformed with an expression vector according to claim 12.

14. Host cell according to claim 13 characterized by the fact that the host cell is a prokaryotic cell.

15. Host cell according to claim 13 characterized by the fact that the host cell is a eukaryotic cell.

16. Host cell according to claim 15 characterized by the fact that the eukaryotic cell is a yeast cell.

17. Host cell according to claim 15 characterized by the fact that the eukaryotic cell is a mammalian cell.

18. Protein characterized by the fact that it is a translation product of one gene or several of the genes/one sequence or several of the sequences as defined in one of the claims 1 to 11 and/or the corresponding transcript or the corresponding transcripts which is(are) native or mutant and/or is(are) present as complete entity or as fragments, and where the translation product is native or mutant and/or is completely or fragmentally glycosylated, partially glycosylated or not glycosylated and/or phosphorylated or not phosphorylated and/or chemically modified or not chemically modified.

19. Use of at least one of the sequences according to claims 1 to 11 for affecting the vascular development.

20. Use of at least one MAG gene for affecting vascular development.

21. Use of at least one high mobility group protein gene for affecting vascular development.

22. Use according to claim 21 characterized by the fact that the high mobility group protein gene is selected from that group which consists of the HMGI-C gene and the HMGI-Y gene.

23. Use according to one of the claims 20 to 22 characterized by the fact that sequences with essentially the same nucleic acid sequence as that of the genes defined in claims 20 to 22 are used.

24. Use according to one of the claims 20 to 22 characterized by the fact that sequences are used which have a nucleic acid sequence functionally the same as that of the genes defined in claims 20 to 22.

25. Use according to one of the claims 20 to 24 characterized by the fact that the genes or sequences defined in claims 20 to 24 have at least one sequence that codes for aDNA-binding portion of the corresponding translation product(s).

26. Use according to claim 25 characterized by the fact that the genes or sequences defined in claims 20 to 25 have no sequence that codes for the protein-binding portion of the corresponding translation product(s).

27. Use according to claim 25 characterized by the fact that the genes or sequences defined in claims 20 to 25 have one or more sequences Sr that replace or extend the sequence(s) that code(s) for the protein-binding portion of the corresponding translation product(s).

28. Use according to claim 27 characterized by the fact that the sequences Sr are selected from the group that includes other sequences of the human genome, sequences of other (donor) organisms, and artificial sequences and combinations thereof.

29. Use according to one of the claims 19 to 28 characterized by the fact that the genes or sequences are present in the form of double strand and/or coding and/or noncoding single strand and/or cDNA.

30. Use according to one of the claims 19 to 29 characterized by the fact that the genes or sequences are present in native and/or mutant and/or fragmented or nonfragmented form.

31. Use according to claim 30 characterized by the fact that the genes or sequences have at least one promoter and/or at least one enhancer element and/or at least one transcription termination element and/or at least one resistance gene and/or at least one other marker gene.

32. Use according to one of the claims 19 to 31 characterized by the fact that at least one of the genes or sequences is present in a form cloned in a host system.

33. Use according to one of the claims 19 to 32 characterized by the fact that the genes or sequences are present in at least one copy.

34. Agents for influencing vascular development characterized by at least one agent MS
that is selected from the group that includes sense DNA, sense RNA, sense cDNA, antisense DNA, antisense RNA, and antisense cDNA and combinations thereof as a single strand and/or double strand.

35. Agents according to claim 34 characterized by the fact that the sequence(s) of the agent Ms is(are) present in native or mutant form and/or complete or as a fragment and/or in a chemically modified or not chemically modified form.

36. Agent according to claim 34 or 35 characterized by the fact that the sequence of the agent MS corresponds to the sequence(s) or the gene(s) as defined in one of the claims 1 to 11 and 20 to 33 and/or to the corresponding transcript(s) that is(are) present in native or mutant form, complete or as a fragment.

37. Agent for influencing vascular development characterized by at least one agent Mp that is selected from the group that includes polyclonal antibodies, monoclonal antibodies, and fragments and derivatives of the same.

38. Agent according to claim 37 characterized by the fact that the agent Mp acts against the sequence(s) or the gene(s) as defined in one of the claims 1 to 11 and 20 to 33 and/or the corresponding transcription product(s) that is(are) present in native or mutant form and/or complete or as a fragment.

39. Agent according to claim 37 characterized by the fact that the agent Mp acts against one or more translation products of one or more genes or one or more sequences as defined in one of the claims 1 to 11 and 20 to 33 and/or the corresponding transcript(s) that is(are) present in native or mutant form and/or complete or as a fragment, and wherein said translation product(s) is(are) present in native or mutant form and/or complete or as a fragment and/or in a form glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated.

40. Agent according to claim 37 characterized by the fact that the agent Mp acts against an antibody or a fragment of the same that for its part acts against the sequence(s) or the gene(s) as defined in one of the claims 1 to 11 and 20 to 33 and/or the corresponding transcription product(s) that is(are) present in native or mutant form and/or complete or as a fragment.

41. Agent according to claim 37 characterized by the fact that the agent Mp acts against an antibody or a fragment of the same that for its part acts against one or more translation products of one or more genes or one or more sequences as defined in one of the claims 1 to 11 and 20 to 33 and/or the corresponding transcript(s) that is(are) present in native or mutant form and/or complete or as a fragment, and wherein said translation product(s) is(are) present in native or mutant form and/or complete or as a fragment and/or in a form glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated.

42. Agent for influencing vascular development characterized by at least one translation product of one or more genes or one or more sequences as defined in one of the claims 1 to 11 and 20 to 33 and/or the corresponding transcript(s) that is(are) present in native or mutant form and/or complete or as a fragment, and wherein said translation product(s) is(are) present in native or mutant form and/or complete or as a fragment and/or in a form glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated and/or chemically modified or not chemically modified.

43. Agent for influencing vascular development characterized by at least one expression inhibitor and/or at least one agent stimulating expression.

44. Agent according to claim 43 characterized by the fact that the expression inhibitor and/or the agent stimulating expression has increased specificity for one or more genes or one or more sequences as defined in claims 1 to 11 and 20 to 33 in comparison to other genes of the genetic system in question.

45. Agent according to claim 43 characterized by the fact that the expression inhibitor and/or the agent stimulating expression is specific for the gene(s) or the sequence(s) as defined in claims 1 to 11 and 20 to 33.

46. Use of at least one of the agent according to one of the claims 34 to 45 to influence vascular development characterized by the fact that the influence on vascular development relates to angiogenesis.

47. Use according to claim 46 characterized by the fact that angiogenesis is reduced and/or cut off.

48. Use according to claim 46 characterized by the fact that angiogenesis is stimulated.

49. Use according to claim 46 characterized by the fact that the influence on vascular development relates to tumor angiogenesis.

50. Use of at least one of the agents according to one of the claims 34 to 45 to influence vascular development characterized by the fact that the influence on vascular development relates to vascularization.

51. Use according to claim 50 characterized by the fact that vascularization is stimulated.

52. Use according to claim 50 characterized by the fact that vascularization is reduced or cut off.

53. Use of at least one of the agents according to one of the claims 34 to 45 for the treatment and/or prevention of loss of sight as a consequence of neovascularization.

54. Use of at least one of the agents according to one of the claims 34 to 45 for the improvement of vascular supply to myocardial tissue damaged by infarct.

55. Use according to one of the claims 19 to 33 and 45 to 54 characterized by the fact that the use occurs in humans and/or in animals.

56. Use according to claim 55 for therapeutic and/or diagnostic application in humans and/or in animals.

57. Use according to one of the claims 19 to 33 and 45 to 54 characterized by the fact that it is applied in vitro.

58. Use of at least one of the agents according to one of the claims 34 to 45 for the production of a drug for therapeutic and/or diagnostic application in influencing vascular development.

59. Kit for influencing vascular development characterized by the fact that the kit contains at least one agent according to claims 34 to 36 and/or according to claims 37 to 41.

60. Kit for influencing vascular development characterized by the fact that at least one translation product of one or more genes or one or more sequences as defined in one of the claims 1 to 11 and 20 to 33, and/or the corresponding transcript(s) that is(are) present in native or mutant form and/or complete or as a fragment, is contained therein, and wherein said translation product(s) is(are) present in native or mutant form and/or complete or as a fragment and/or in a form glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated and/or chemically modified or not chemically modified.

61. Kit for influencing vascular development characterized by the fact that at least one expression inhibitor and/or at least one agent stimulating expression according to claims 43 to 45 is contained therein.

62. Kit for influencing vascular development characterized by the fact that at least one agent as defined in claims 34 to 36 and/or 37 to 41 and/or at least one translation product as defined in claim 42 and/or at least one expression inhibitor and/or at least one agent stimulating expression as defined in claims 43 to 45 is contained therein.

63. Kit according to one of the claims 59 to 62 characterized by the fact that it is used for influencing tumor angiogenesis.

64. Kit according to one of the claims 59 to 62 characterized by the fact that it is used for influencing angiogenesis.

65. Kit according to one of the claims 59 to 62 characterized by the fact that it is used for influencing vascularization.

66. Kit according to one of the claims 59 to 65 characterized by the fact that it has an inhibiting effect on vascular development.

67. Kit according to one of the claims 59 to 65 characterized by the fact that it has a stimulating effect on vascular development.

68. Kit according to one of the claims 59 to 62 as well as 64 to 66 characterized by the fact that it is used for the treatment and/or prevention of loss of sight as a consequence of neovascularization.

69. Kit according to one of the claims 59 to 69 as well as 64, 65, and 67 characterized by the fact that it is used for the improvement of vascular supply to myocardial tissue damaged by infarct.

70. Kit according to one of claims 59 to 69 characterized by the fact that it is used for therapeutic treatment and/or for diagnosis.

71. Kit according to claims 59 to 70 characterized by the fact that it is used in humans and/or animals.

72. Kit according to claims 59 to 70 characterized by the fact that it is used in in-vitro systems.

73. Use of at least one of the sequences according to claims 1 to 11 for the treatment of endometriosis.

74. Use of at least one MAG gene for the treatment of endometriosis.

75. Use of at least one high mobility group protein gene for the treatment of endometriosis.

76. Use according to claim 75 characterized by the fact that the high mobility group protein gene is selected from the group that includes the HMGI-C gene and the HMGI-Y
gene.

77. Use according to one of the claims 74 to 76 characterized by the fact that sequences are used with essentially the same nucleic acid sequence as that of the genes defined in claims 74 to 76.

78. Use according to one of the claims 74 to 76 characterized by the fact that sequences are used having a nucleic acid sequence in essence functionally the same as that of the genes defined in claims 74 to 76.

79. Use according to one of the claims 74 to 78 characterized by the fact that the genes or sequences defined in claims 74 to 78 have at least one sequence that codes for aDNA-binding portion of the corresponding translation product(s).

80. Use according to claim 79 characterized by the fact that the genes or sequences defined in claims 74 to 79 have no sequence that codes for the protein-binding portion of the corresponding translation product(s).

81. Use according to claim 79 characterized by the fact that the genes or sequences defined in claims 74 to 79 have one or more sequences Sr that replace or extend that sequence(s) that code(s) for the protein-binding portion of the corresponding translation product(s).

82. Use according to claim 81 characterized by the fact that the sequence Sr is selected from the group that includes other sequences of the human genome, sequences of other (donor) organisms, and artificial sequences and combinations thereof.

83. Use according to one of the claims 73 to 82 characterized by the fact that the genes or sequences are present in the form of double strand and/or coding and/or noncoding single strand and/or cDNA.

84. Use according to one of the claims 73 to 83 characterized by the fact that the genes or sequences are present in native and/or mutant and/or fragmented or nonfragmented form.

85. Use according to one of the claims 73 to 84 characterized by the fact that the genes or sequences have at least one promoter and/or at least one enhancer element and/or at least one transcription termination element and/or at least one resistance gene and/or at least one other marker gene.

86. Use according to one of the claims 73 to 85 characterized by the fact that at least one of the genes or at least one of the sequences is present in a form cloned in a host system.

87. Use according to one of the claims 73 to 86 characterized by the fact that the genes or sequences are present in at least one copy.

88. Agent for influencing vascular development characterized by at least one agent MS
that is selected from the group that includes sense DNA, sense RNA, sense cDNA, antisense DNA, antisense RNA, and antisense cDNA and combinations thereof as a single strand and/or double strand.

89. Agent according to claim 88 characterized by the fact that the sequence(s) of the agent MS is(are) present in native or mutant form and/or complete or as a fragment and/or in a chemically modified or not chemically modified form.

90. Agent according to claim 88 or 89 characterized by the fact that the sequence of the agent corresponds to the sequence(s) or the gene(s) as defined in one of the claims 1 to 11 and 71 to 84 and/or to the corresponding transcript(s) that is(are) present in native or mutant form, complete or as a fragment.

91. Agent for the treatment of endometriosis characterized by at least one agent Mp that is selected from the group that includes polyclonal antibodies, monoclonal antibodies, and fragments and derivatives of the same.

92. Agent according to claim 91 characterized by the fact that the agent Mp acts against the sequence(s) or the gene(s) as defined in one of the claims 1 to 11 and 74 to 87 and/or the corresponding transcription product(s) that is(are) present in native or mutant form and/or complete or as a fragment.

93. Agent according to claim 91 characterized by the fact that the agent Mp acts against one or more translation products of one or more genes or one or more sequences as defined in one of the claims 1 to 11 and 74 to 87 and/or the corresponding transcript(s) that is(are) present in native or mutant form and/or complete or as a fragment, and wherein said translation product(s) is(are) present in native or mutant form and/or complete or as a fragment and/or in a form glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated.

94. Agent according to claim 91 characterized by the fact that the agent Mp acts against an antibody or a fragment of the same that for its part acts against the sequence(s) or the gene(s) as defined in one of the claims 1 to 11 and 74 to 87 and/or the corresponding transcription product(s) that is(are) present in native or mutant form and/or complete or as a fragment.

95. Agent according to claim 91 characterized by the fact that the agent Mp acts against an antibody or a fragment of the same that for its part acts against one or more translation products of one or more genes or one or more sequences as defined in one of the claims 1 to 11 and 74 to 87 and/or the corresponding transcript(s) that is(are) present in native or mutant form and/or complete or as a fragment, and wherein said translation product(s) is(are) present in native or mutant form and/or complete or as a fragment and/or in a form glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated.

96. Agent for the treatment of endometriosis characterized by at least one translation product of one or more genes or one or more sequences as defined in claims 1 to 11 and 74 to 87 and/or the corresponding transcript(s) that is(are) present in native or mutant form and/or complete or as a fragment, and wherein said translation product(s) is(are) present in native or mutant form and/or complete or as a fragment and/or in a form glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated and/or chemically modified or not chemically modified.

97. Agent for the treatment of endometriosis characterized by at least one expression inhibitor and/or at least one agent stimulating expression.

98. Agent according to claim 97 characterized by the fact that the expression inhibitor and/or the agent stimulating expression has increased specificity for one or more genes or one or more sequences as defined in claims 1 to 11 and 74 to 87 in comparison to other genes of the genetic system in question.

99. Agent according to claim 97 characterized by the fact that the expression inhibitor and/or the agent stimulating expression is specific for the gene or several of the genes or the sequence or several of the sequences as defined in claims 1 to 11 and 74 to 87.

100. Use of at least one of the agents according to one of the claims 88 to 99 for the treatment of endometriosis characterized by the fact that the use occurs in humans and/or in animals.

101. Use according to claim 100 for therapeutic and/or diagnostic application in humans and/or in animals.

102. Use of at least one of the agents according to one of the claims 88 to 99 for the treatment of endometriosis characterized by the fact that it is applied in vitro.

103. Use of at least one of the agents according to one of the claims 88 to 99 for the production of a drug for therapeutic and/or diagnostic application in the treatment of endometriosis.

104. Kit for the treatment of endometriosis characterized by the fact that the kit contains at least one agent according to claims 88 to 90 and/or according to claims 91 to 95.

105. Kit for the treatment of endometriosis characterized by the fact that at least one translation product of one or more genes or one or more sequences as defined in one of the claims 1 to 11 and 74 to 87, and/or the corresponding transcript(s) that is(are) present in native or mutant form and/or complete or as a fragment, is contained therein, and wherein said translation product(s) is(are) present in native or mutant form and/or complete or as a fragment and/or in a form glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated and/or chemically modified or not chemically modified.

106. Kit for the treatment of endometriosis characterized by the fact that at least one expression inhibitor and/or at least one agent stimulating expression according to claims 97 to 99 is contained therein.

107. Kit for the treatment of endometriosis characterized by the fact that at least one agent as defined in claims 88 to 90 and/or claims 91 to 95 and/or at least one translation product as defined in claim 96 and/or at least one expression inhibitor and/or at least one agent stimulating expression as defined in claims 97 to 99 is contained therein.

108. Kit according to one of the claims 104 to 107 characterized by the fact that it is used for therapeutic treatment and/or for diagnosis.

109. Kit according to claims 104 to 108 characterized by the fact that it is used in humans and/or animals.

110. Kit according to claims 104 to 108 characterized by the fact that it is used in in-vitro systems.

111. Use of at least one of the sequences according to claims 1 to 11 for contraception.

112. Use of at least one MAG gene for contraception.

113. Use of at least one high mobility group protein gene for contraception.

114. Use according to claim 113 characterized by the fact that the high mobility group protein gene is selected from the group that includes the HMGI-C gene and the HMGI-Y
gene.

115. Use according to one of the claims 112 to 114 characterized by the fact that sequences are used with essentially the same nucleic acid sequence as that of the genes defined in claims 112 to 114.

116. Use according to one of the claims 112 to 114 characterized by the fact that sequences are used having a nucleic acid sequence in essence functionally the same as that of the genes defined in claims 112 to 114.

117. Use according to one of the claims 112 to 116 characterized by the fact that the genes or sequences defined in claims 112 to 116 have at least one sequence that codes for a DNA-binding portion of the corresponding translation product(s).

118. Use according to claim 117 characterized by the fact that the genes or sequences defined in claims 112 to 117 have no sequence that codes for the protein-binding portion of the corresponding translation product(s).

119. Use according to claim 117 characterized by the fact that the genes or sequences defined in claims 112 to 117 have one or more sequences Sr that replace or extend that sequence that codes for, or those sequences that code for, the protein-binding portion of the corresponding translation product(s).

120. Use according to claim 119 characterized by the fact that the sequence Sr is selected from the group that includes other sequences of the human genome, sequences of other (donor) organisms, and artificial sequences and combinations thereof.

121. Use according to one of the claims 111 to 120 characterized by the fact that the genes or sequences are present in the form of double strand and/or coding and/ornoncoding single strand and/or cDNA.

122. Use according to one of the claims 111 to 121 characterized by the fact that the genes or sequences are present in native and/or mutant and/or fragmented or nonfragmented form.

123. Use according to one of the claims 111 to 122 characterized by the fact that the genes or sequences have at least one promoter and/or at least one enhancer element and/or at least one transcription termination element and/or at least one resistance gene and/or at least one other marker gene.

124. Use according to one of the claims 111 to 123 characterized by the fact that at least one of the genes or one of the sequences is present in a form cloned in a host system.

125. Use according to one of the claims 111 to 124 characterized by the fact that the genes or sequences are present in at least one copy.

126. Agent for contraception characterized by at least one agent Ms that is selected from the group that includes sense DNA, sense RNA, sense cDNA, antisense DNA, antisense RNA, and antisense cDNA and combinations thereof as a single strand and/or double strand.

127. Agent according to claim 126 characterized by the fact that the sequence(s) of the agent MS is(are) present in native or mutant form and/or complete or as a fragment and/or in a chemically modified or not chemically modified form.

128. Agent according to claims 126 or 127 characterized by the fact that the sequence of the agent MS corresponds to the sequence(s) or the gene(s) as defined in one of the claims 1 to 11 and 112 to 125 and/or to the corresponding transcript(s) that is(are) present in native or mutant form, complete or as a fragment.

129. Agent for contraception characterized by at least one agent Mp that is selected from the group that includes polyclonal antibodies, monoclonal antibodies, and fragments and derivatives of the same.

130. Agent according to claim 129 characterized by the fact that the agent Mp acts against the sequence(s) or the gene(s) as defined in one of the claims 1 to 11 and 112 to 125 and/or the corresponding transcription product(s) that is(are) present in native or mutant form and/or complete or as a fragment.

131. Agent according to claim 129 characterized by the fact that the agent Mp acts against one or more translation products of one or more genes or one or more sequences as defined in one of the claims 1 to 11 and 112 to 125 and/or the corresponding transcript(s) that is(are) present in native or mutant form and/or complete or as a fragment, and wherein said translation product(s) is(are) present in native or mutant form and/or complete or as a fragment and/or in a form glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated.

132. Agent according to claim 129 characterized by the fact that the agent Mp acts against an antibody or a fragment of the same that for its part acts against the sequence(s) or the gene(s) as defined in one of the claims 1 to 11 and 112 to 125 and/or thecorresponding transcription product(s) that is(are) present in native or mutant form and/or complete or as a fragment.

133. Agent according to claim 129 characterized by the fact that the agent Mp acts against an antibody or a fragment of the same that for its part acts against one or more translation products of one or more genes or one or more sequences as defined in one of the claims 1 to 11 and 112 to 125 and/or the corresponding transcript(s) that is(are) present in native or mutant form and/or complete or as a fragment, and wherein said translation product(s) is(are) present in native or mutant form and/or complete or as a fragment and/or in a form glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated.

134. Agent for contraception characterized by at least one translation product of one or more genes or one or more sequences as defined in one of the claims 1 to 11 and 112 to 125 and/or the corresponding transcript(s) that is(are) present in native or mutant form and/or complete or as a fragment, and wherein said translation product(s) is(are) present in native or mutant form and/or complete or as a fragment and/or in a form glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated and/or chemically modified or not chemically modified.

135. Agent for contraception characterized by at least one expression inhibitor and/or at least one agent stimulating expression.

136. Agent according to claim 135 characterized by the fact that the expression inhibitor and/or the agent stimulating expression has increased specificity for one or more genes or one or more sequences as defined in claims 1 to 11 and 112 to 125 in comparison to other genes of the genetic system in question.

137. Agent according to claim 135 characterized by the fact that the expression inhibitor and/or the agent stimulating expression is specific for the gene or several of the genes or the sequence or several of the sequences as defined in claims 1 to 11 and 112 to 125.

138. Use of at least one of the agent according to claims 126 to 137 for oral contraception.

139. Use of at least one of the agent according to claims 126 to 137 for local contraception.

140. Use according to one of the claims 138 or 139 characterized by the fact that the use occurs in humans and/or in animals.

141. Use according to claim 140 for therapeutic application in humans and/or in animals.

142. Use of at least one of the agents according to one of the claims 126 to 137 for the production of a drug for therapeutic application.

143. Kit for contraception characterized by the fact that the kit contains at least one agent according to claims 126 to 128 and/or according to claims 129 to 133.

144. Kit for contraception characterized by the fact that at least one translation product of one or more genes or one or more sequences as defined in one of the claims 1 to 11 and 112 to 125, and/or the corresponding transcript(s) that is(are) present in native or mutant form and/or complete or as a fragment, is contained therein, and wherein said translation product(s) is(are) present in native or mutant form and/or complete or as a fragment and/or in a form glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated and/or chemically modified or not chemically modified.

145. Kit for contraception characterized by the fact that at least one expression inhibitor and/or at least one agent stimulating expression according to claims 135 to 137 is contained therein.

146. Kit for contraception characterized by the fact that at least one agent as defined in claims 126 to 128 and/or 129 to 133 and/or at least one translation product as defined in claim 134 and/or at least one expression inhibitor and/or at least one agent stimulating expression as defined in claims 135 to 137 is contained therein.

147. Kit according to one of the claims 143 to 146 characterized by the fact that it is used for oral contraception.

148. Kit according to one of the claims 143 to 146 characterized by the fact that it is used for local contraception.

149. Kit according to one of the claims 143 to 148 characterized by the fact that it is used for therapeutic treatment and/or for diagnosis.

150. Kit according to one of the claims 143 to 149 characterized by the fact that it is used in humans and/or animals.

151. Kit according to one of the claims 143 to 149 characterized by the fact that it is used in in-vitro systems.

152. Process for contraception characterized by the fact that at least one agent is furnished that is selected from the group that includes sense DNA, sense RNA, sense cDNA, antisense DNA, antisense RNA, and antisense cDNA and combinations thereof as a single strand and/or double strand, and wherein the sequence of the agent selected from the group corresponds to the sequence(s) or the gene(s) as defined in one of the claims 1 to 11 and 112 to 125 and/or to the corresponding transcript(s) that is(are) present in native or mutant form, complete or as a fragment.

153. Process for contraception characterized by the fact that at least one agent is furnished that is selected from the group that includes polyclonal antibodies, monoclonal antibodies, and fragments and derivatives of the same, and wherein the agent selected from the group acts against the sequence(s) or the gene(s) as defined in one of the claims 1 to 11 and 112 to 125 and/or the corresponding transcript(s) that is(are) present in native or mutant form, complete or as a fragment.

154. Process for contraception characterized by the fact that at least one agent is furnished that is selected from the group that includes polyclonal antibodies, monoclonal antibodies, and fragments and derivatives of the same, and wherein the agent selected from the group acts against one or more translation products of one or more genes or one or more sequences as defined in one of the claims 1 to 11 and 112 to 125 and/or the corresponding transcript(s) that is(are) present in native or mutant form and/or complete or as a fragment, and wherein said translation product(s) is(are) present in native or mutant form and/or complete or as a fragment and/or in a form glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated.

155. Process for contraception characterized by the fact that at least one agent is furnished that is a translation product of one or more genes or one or more sequences as defined in one of the claims 1 to 11 and 112 to 125 and/or the corresponding transcript(s) that is(are) present in native or mutant form and/or complete or as a fragment, and wherein said translation product(s) is(are) present in native or mutant form and/or complete or as a fragment and/or in a form glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated and/or chemically modified or not chemically modified.

156. Process according to one of the claims 152 to 155 characterized by the fact that said agent is delivered orally.

157. Process according to one of the claims 152 to 156 characterized by the fact that said agent is delivered periodically.

158. Process according to one of the claims 152 to 157 characterized by the fact that said agent is delivered after conception.

159. Use of at least one of the sequences according to claims 1 to 11 for the regeneration of tissue.

160. Use of at least one MAG gene for the regeneration of tissue.

161. Use of at least one high mobility group protein gene for the regeneration of tissue.

162. Use according to claim 161 characterized by the fact that the high mobility group protein gene is selected from the group that includes the HMGI-C gene and the HMGI-Y
gene.

163. Use according to one of the claims 160 to 162 characterized by the fact that sequences are used with essentially the same nucleic acid sequence as that of the genes defined in claims 160 to 162.

164. Use according to one of the claims 160 to 162 characterized by the fact that sequences are used having a nucleic acid sequence in essence functionally the same as that of the genes defined in claims 160 to 162.

165. Use according to one of the claims 160 to 164 characterized by the fact that the genes or sequences defined in claims 160 to 164 have at least one sequence that codes for a DNA-binding portion of the corresponding translation product(s).

166. Use according to claim 165 characterized by the fact that the genes or sequences defined in claims 160 to 164 have no sequence that codes for the protein-binding portion of the corresponding translation product(s).

167. Use according to claim 165 characterized by the fact that the genes or sequences defined in claims 160 to 164 have one or more sequences Sr that replace or extend that sequence that codes for, or those sequences that code for, the protein-binding portion of the corresponding translation product(s).

168. Use according to claim 167 characterized by the fact that the sequence Sr is selected from the group that includes other sequences of the human genome, sequences of other (donor) organisms, and artificial sequences and combinations thereof.

169. Use according to one of the claims 159 to 168 characterized by the fact that the genes or sequences are present in the form of double strand and/or coding and/ornoncoding single strand and/or cDNA.

170. Use according to one of the claims 159 to 169 characterized by the fact that the genes or sequences are present in native and/or mutant and/or fragmented or nonfragmented form.

171. Use according to claims 159 to 170 characterized by the fact that the genes or sequences have at least one promoter and/or at least one enhancer element and/or at least one transcription termination element and/or at least one resistance gene and/or at least one other marker gene.

172. Use according to one of the claims 159 to 171 characterized by the fact that at least one of the genes or one of the sequences is present in a form cloned in a host system.

173. Use according to one of the claims 159 to 172 characterized by the fact that the genes or sequences are present in at least one copy.

174. Agent for the regeneration of tissue characterized by at least one agent MS that is selected from the group that includes sense DNA, sense RNA, sense cDNA, antisense DNA, antisense RNA, and antisense cDNA and combinations thereof as a single strand and/or double strand.

175. Agent according to claim 174 characterized by the fact that the sequence(s) of the agent MS is(are) present in native or mutant form and/or complete or as a fragment and/or in a chemically modified or not chemically modified form.

176. Use according to one of the claims 174 or 175 characterized by the fact that the sequence of the agent MS corresponds to the sequence(s) or the gene(s) as defined in one of the claims 1 to 11 and 160 to 173 and/or to the corresponding transcript(s) that is(are) present in native or mutant form, complete or as a fragment.

177. Agent for the regeneration of tissue characterized by at least one agent Mp that is selected from the group that includes polyclonal antibodies, monoclonal antibodies, and fragments and derivatives of the same.

178. Agent according to claim 177 characterized by the fact that the agent Mp acts against the sequence(s) or the gene(s) as defined in one of the claims 1 to 11 and 160 to 173 and/or the corresponding translation product(s) that is(are) present in native or mutant form and/or complete or as a fragment.

179. Agent according to claim 177 characterized by the fact that the agent Mp acts against one or more translation products of one or more genes or one or more sequences as defined in one of the claims 1 to 11 and 160 to 173 and/or the corresponding transcript(s) that is(are) present in native or mutant form and/or complete or as a fragment, and wherein said translation product(s) is(are) present in native or mutant form and/or complete or as a fragment and/or in a form glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated.

180. Agent according to claim 177 characterized by the fact that the agent Mp acts against an antibody or a fragment of the same that for its part acts against the sequence(s) or the gene(s) as defined in one of the claims 1 to 11 and 160 to 173 and/or thecorresponding transcription product(s) that is(are) present in native or mutant form and/or complete or as a fragment.

181. Agent according to claim 177 characterized by the fact that the agent Mp acts against an antibody or a fragment of the same that for its part acts against one or more translation products of one or more genes or one or more sequences as defined in one of the claims 1 to 11 and 160 to 173 and/or the corresponding transcript(s) that is(are) present in native or mutant form and/or complete or as a fragment, and wherein said translation product(s) is(are) present in native or mutant form and/or complete or as a fragment and/or in a form glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated.

182. Agent for the regeneration of tissue characterized by at least one translation product of one or more genes or one or more sequences as defined in one of the claims 1 to 11 and 160 to 173 and/or the corresponding transcript(s) that is(are) present in native or mutant form and/or complete or as a fragment, and wherein said translation product(s) is(are) present in native or mutant form and/or complete or as a fragment and/or in a form glycosylated, partially glycosylated, or not glycosylated and/or phosphorylated or not phosphorylated and/or chemically modified or not chemically modified.

183. Agent for the regeneration of tissue characterized by at least one agent stimulating expression.

184. Agent according to claim 183, characterized in that the specificity of the agent that stimulates the expression is increased for the genes or sequences defined in claims 1 to 11 and 160 to 173, compared to the other genes of the respective genetic system.

185. Agent according to claim 183, characterized in that the agent that stimulates the expression is specific for the gene or several of the genes/the sequence or several of the sequences defined in claims 1 to 11 and 160 to 173.

186. Use of at least one agent according to one of the claims 174 to 185 for theregeneration of tissue, characterized in that the tissue to be regenerated is selected from the group that comprises degenerated tissue, traumatically damaged tissue, and tissue that was damaged in other ways.

187. Use of at least one agent according to one of the claims 174 to 185 for theregeneration of tissue, characterized in that the tissue to be regenerated is mesenchymal tissue.

188. Use according to claim 187, characterized in that the mesenchymal tissue is selected from the group that comprises cartilage tissue, muscle tissue, fatty tissue, connective tissue and supportive tissue.

189. Use of at least one of the agent according to one of the claims 174 to 185 for the regeneration of tissue, characterized in that it is used in vivo.

190. Use according to at least one of the claims 186 to 189, characterized in that it is used on humans and/or animals.

191. Use according to claim 190, characterized in that it is used for therapeutic application in humans and/or animals.

192. Use of at least one of the agent according to one of the claims 174 to 185 for the regeneration of tissue, characterized in that it is used in vitro.

193. Use according to one of the claims 159 to 173 and 192, characterized in that it is used in or on cultures selected from the group that comprises cell cultures, tissue cultures, organ cultures and combinations thereof.

194. Use of at least one of the agents according to one of the claims 174 to 185 for the production of a medical drug for therapeutic application in the regeneration of tissue.

195. Kit for the regeneration of tissue, characterized in that the kit contains at least one agent according to the claims 174 to 176 and/or according to the claims 177 to 181.

196. Kit for the regeneration of tissue, characterized in that it contains at least one translation product of a gene or several genes/a sequence or several of the sequences defined in one of claims 1 to 11 and 160 to 173 and/or the corresponding transcript or the corresponding transcripts, which are present in native or mutant form either completely or as fragments, and whereby said translation product or said translation products are present either in native or mutant form, and/or completely or as fragments, and/or in glycosylated, partially glycosylated or non-glycosylated form and/or in phosphorylated or non-phosphorylated form and/or in chemically modified form.

197. Kit for the regeneration of tissue, characterized in that at least one agent that stimulates the expression according to the claims 183 to 185 is present.

198. Kit for the regeneration of tissue, characterized in that it comprises at least one agent as defined in the claims 174 to 176 and/or the claims 177 to 181 and/or at least one translation product as defined in claim 182 and/or at least one agent that stimulates the expression, as defined in claims 183 to 185.

199. Kit according to one of the claims 195 to 198, characterized in that it is used for therapeutic treatment and/or diagnosis.

200. Kit according to one of the claims 195 to 199, characterized in that it is applied in vivo.

201. Kit according to claim 200, characterized in that it is used for humans and/or animals.

202. Kit according to one of the claims 195 to 199, characterized in that it is used in in vitro-systems.

203. Kit according to one of the claims 195 to 199 and 202, characterized in that it is used in or on cultures selected from the group that comprises cell cultures, tissue cultures, organ cultures and combinations thereof.

204. Process for the regeneration of tissue, characterized in that at least one of the genes/sequences defined in the claims 1 to 11 and 160 to 173 are expressed in the tissue to be regenerated.

205. Process for the regeneration of tissue, characterized by the following steps:
a) the provision of cells that are labeled as target cells;
b) the introduction of at least one of the genes/sequences defined in claims 1 to 11 and 160 to 175 into the target cells;
c) the induction and expression of at least one of the genes/sequences defined in claims 1 to 11 and 160 to 173 into the target cells; and optionally d) the cultivation of the target cells.

206. Process according to claim 205, characterized in that at least one of the genes/sequences defined in claims 1 to 11 and 160 to 173 is expressed in the cultivation of the target cells.

207. Process according to claim 205 or 206, characterized that at least one of the genes/sequences defined in the claims 1 to 11 and 160 to 173 is introduced in vitro into the target cells by means of a process that is selected from the group that comprises transfection, microinjection, electroporation, and gene transfer by means of liposomes and transformation by means of agents.

208. Process according to one of the claims 205 to 207, characterized in that the induction of the expression and/or the expression are influenced by at least one agent as defined in the claims 174 to 176 and/or 177 to 181 and/or at least one translation product as defined in claim 182 and/or at least one agent that stimulates the expression, as defined in the claims 183 to 185.

209. Process according to one of the claims 205 to 208, characterized in that the target cells are from an animal organism, including that of a human.

210. Process according to one of the claims 205 to 208, characterized in that the target cells are from a non-human animal organism.

211. Process according to one of the claims 205 to 210, characterized in that the target cells represent a different cell type than the cell types contained in the tissue to be regenerated.

212. Process according to one of the claims 205 to 210, characterized in that the target cells represent a cell type that is contained in the cell types of the tissue to be regenerated.

213. Process according to one of the claims 205 to 212, characterized in that the target cells (de-)differentiate to pluripotent stem cells under the influence of at least one of the genes/sequences defined in claims 1 to 11 and 160 to 173.

214. Process according to one of the claims 205 to 213, characterized that the target cells are co-cultivated with other cells and/or cell types.

215. Process according to claim 214, characterized in that the cells and/or cell types used for co-cultivation influence the differentiating condition of the target cells.

216. Process according to one of the claims 205 to 215, characterized in that the cell lines are provided by removing material from an organism, whereby the material is selected from the group that comprises biological fluids containing cells, cells, individual cells, tissue, and organs.

217. Process according to one of the claims 205 to 216, characterized in that the target cells are introduced into an animal organism after at least one of the genes/sequences defined in claims 1 to 11 and 160 to 173 were introduced into said target cells.

218. Process according to claim 127, characterized in that at least one of the genes/sequences defined in claims 1 to 11 and 160 to 173 are introduced into the target cells, and their expression is induced into the target cells before the target cells are introduced into an animal organism.

219. Process according to claim 217, characterized in that at least one of the genes/sequences defined in the claims 1 to 11 and 160 to 173 are introduced into the target cells, and their expression is induced into the target cells after the target cells were introduced into an animal organism.

220. Process according to one of the claims 217 to 219, characterized in that the target cells introduced into an animal organism are in a differentiated and/or a differentiation-competent condition.

221. Process according to one of the claims 217 to 220, characterized in that the animal organism is a human organism.

222. Process according to one of the claims 217 to 221, characterized in that the organism into which the target cells are introduced is identical to the organism from which the target cells were taken.

223. Process according to one of the claims 217 to 221, characterized in that the organism into which the target cells are introduced is different from the organism from which the target cells originated.

224. Process according to claim 204, characterized in that at least one gene/sequence as defined in claims 1 to 11 and 160 to 173 is introduced into the tissue to be regenerated, which is in the organism, and/or into the appropriate cells.

225. Process according to claim 224, characterized in that at least one gene/sequence as defined in claims 1 to 11 and 160 to 173 is introduced into the tissue to be regenerated and/or the corresponding cells using gene-therapeutic processes.

226. Process according to one of the claims 224 and 225, characterized in that the introduced gene or the introduced sequence is expressed.

227. Process according to one of the claims 224 to 226, characterized in that the expression of the introduced gene or the introduced sequence is influenced by at least one agent as defined in claims 174 to 176 and/or 177 to 181 and/or at least one translation product as defined in claim 182 and/or at least one agent that stimulates the expression as defined in the claims 183 to 185.

228. Process according to one of the claims 204 to 227, characterized in that the tissue to be regenerated was selected from the group that comprises mesenchymal tissue.

229. Process according to claim 228, characterized in that the mesenchymal tissue is selected from the group that comprises cartilage tissue, muscle tissue, fatty tissue, connective tissue and supporting tissue.

230. Use of at least one of the sequences according to claims 1 to 11 for the treatment of tumors.

231. Use of at least one MAG gene for the treatment of tumors.

232. Use of at least one high mobility group protein-gene for the treatment of tumors.

233. Use according to claim 232, characterized that the high mobility group protein-gene is selected from the group that comprises the HMGI-C gene and the HMGI-Y gene.

234. Use according to one of the claims 231 to 233, characterized in that sequences having essentially the same nucleic acid sequence as those of the genes defined in claims 231 to 233 are used.

235. Use according to one of the claims 231 to 235, characterized in that sequences with a nucleic acid sequence that is, in essence, functionally the same as that of the genes defined in the claims 231 to 233, are used.

236. Use according to one of the claims 231 to 235, characterized in that the genes or sequences defined in claims 231 to 235 have at least one sequence that codes for a DNA-binding portion of the corresponding translation product or the corresponding translation products.

237. Use according to claim 236, characterized in that the genes or sequences defined in the claims 231 to 236 have no sequences that code for the protein-binding portion of the corresponding translation product or the corresponding translation products.

238. Use according to claim 236, characterized in that the genes/sequences defined in claims 231 to 236 have one or more sequences Sr that replace(s) or supplement(s) the respective sequence(s) that code(s) for the protein-binding portion of the corresponding translation product or the corresponding translation products.

239. Use according to claim 238, characterized in that the sequence Sr is selected from the group that comprises other sequences of the human genome, sequences of other(donor) organisms and artificial sequences and combinations thereof.

240. Use according to one of the claims 230 to 239, characterized in that the genes or sequences are present as a double strand and/or coding and/or non-coding single strand and/or cDNA.

241. Use according to one of the claims 230 to 240, characterized in that the genes or sequences are present in native and/or mutant and/or fragmented or non-fragmented form.

242. Use according to claim 241, characterized in that the genes or sequences have at least one promoter and/or at least one enhancer element and/or at least one transcription termination element and/or at least one R-determinant and/or at least one other marker gene.

243. Use according to one of the claims 230 to 242, characterized in that at least one of the genes/one of the sequences is present as a clone in a host system.

244. Use according to one of the claims 230 to 243, characterized in that the genes or sequences are present in at least one copy.

245. Agent for the treatment of tumors, characterized by at least one MSAT agent selected from the group that comprises the sense DNA, sense RNA, sense cDNA, antisense DNA, antisense RNA and antisense cDNA and combinations thereof, as a single and/or as a double strand, whereby the sequence of the MSAT agent corresponds to a sequence or several of the sequences as defined in claims 1 to 11 and 231 to 244 and/or the corresponding transcript/the corresponding transcripts.

246. Agent according to claim 245, characterized in that the sequence of the sequences or the corresponding transcripts defined in the claims 1 to 11 and 231 to 244 is present in native or mutant form and/or complete or as a fragment.

247. Agent according to claim 245 and 246, characterized in that the sequence of the MSAT agent is present in native or mutant form, and/or complete or as fragment and/or chemically modified or non-chemically modified.

248. Agent for the treatment of tumors, characterized by at least one MPAT agent that is selected from the group that comprises polyclonal antibodies, monoclonal antibodies and fragments and derivatives of the same, whereby the MPAT agent acts against a sequence or several of the sequences as defined in the claims 1 to 11 and 231 to 244 and/or the corresponding transcript/transcripts are present in native or mutant form, and/or complete or as a fragment.

249. Agent for the treatment of tumors, characterized by at least one MPAT agent that is selected from the group that comprises polyclonal antibodies, monoclonal antibodies and fragments and deviates thereof, and whereby the MPAT agent acts against one or several translation products of one or several of the sequences as defined in the claims 1 to 11 and 231 to 244 and/or the corresponding transcript/transcripts, which are present in native or mutant form and/or complete or as fragment, and whereby said translation product(s) are present in native or mutant form, and/or complete or as a fragment and/or glycosylated, partially glycosylated, or non-glycosylated and/or phosphorylated or non-phosphorylated.

250. Agent for the treatment of tumors, characterized by at least one translation product of a sequence or several sequences as defined in one of the claims 1 to 11 and 231 to 244 and/or the corresponding transcript/transcripts which is(are) present in native or mutant form, and/or complete or as fragment, and whereby said translation product(s) are present in native or mutant form and/or complete or as a fragment and/or glycosylated, partially glycosylated and/or phosphorylated or non-phosphorylated and/or chemically modified or non-chemically modified.

251. Agent for the treatment of tumors, characterized by at least one MJAT agent, which is an expression inhibitor that has an increased specificity for one or several sequences as defined in claims 1 to 11 and 231 to 244, compared to other genes of the corresponding genetic system.

252. Agent for the treatment of tumors, characterized by at least one MJAT agent, which is an expression inhibitor that is specific for at least one of the sequences as defined in claims 1 to 11 and 231 to 244.

253. Agent for the treatment of tumors according to one of the claims 245 to 252, characterized in that the tumor to be treated has an expression of a gene that is selected from the group comprising the MAG genes, high mobility protein-genes, HMGI-C genes, HMGI-Y genes and their derivatives.

254. Use of at least one agent according to one of the claims 245 to 253 for theproduction of a medical drug for the treatment of tumors.

255. Use according to claim 254, characterized in that the medical drug is used for the treatment of tumors that have an expression of a gene that is selected from the group comprising the MAG genes, high mobility group protein-genes, HMGI-C genes, HMGI-Y genes and their derivatives.

256. Use of at least one of the agent according to one of the claims 245 to 253 for the treatment of types of tumors that have expressions of a gene selected from the group that comprises the MAG genes, high mobility group protein-genes, HMGI-C genes, HMGI-Ygenes and their derivatives.