Abstract: Method for producing a modified oligonucleotide, wherein at least one polymer, preferably polyalkylene oxide, and/or a compound is covalently bound to the 5?-end or the 3?-end of the oligonucleotide via native ligation forming a native ligation site, with the proviso that the polymer and/or the compound is not a protein or peptide, if only the 5?-end of the oligonucleotide is modified by binding of the polymer or compound via native ligation. The invention is further directed to a modified oligonucleotide obtainable by the inventive method as well as the use of such modified oligonucleotide for the preparation of a medicament for preventing and/or treating a tumor, formation of metastasis, an immune disease or disorder, a cardiovascular disease or disorder, and/or a viral disease or disorder.

Abstract: A method for preventing and/or treating a tumor, the method comprising: intravenously administering an antisense oligonucleotide in an amount of between about 400 to about 800 mg/m2/treatment cycle, the antisense oligonucleotide comprises 8 to 30 nucleotide building blocks, which hybridizes with mRNA of TGF-beta-2, -1 and/or -3 for the preparation of a pharmaceutical composition.

Abstract: A mixture comprising at least one inhibitor or suppressor of the expression of a gene and at least one molecule binding to an expression product of said gene.

Abstract: Medicament comprising a combination of at least one inhibitor of the effect of a substance negatively effecting an immune response, the substance selected from the group consisting of TGF-? and its receptors, VEGF and its receptors, interleukin 10 (IL-10) and its receptors, PGE2 and its receptors, wherein the inhibitor has a molecular weight of less than 100 kDa and at least one stimulator positively effecting an immune response.

Abstract: Method for producing a modified oligonucleotide, wherein at least one polymer, preferably polyalkylene oxide, and/or a compound is covalently bound to the 5?-end or the 3?-end of the oligonucleotide via native ligation forming a native ligation site, with the proviso that the polymer and/or the compound is not a protein or peptide, if only the 5?-end of the oligonucleotide is modified by binding of the polymer or compound via native ligation. The invention is further directed to a modified oligonucleotide obtainable by the inventive method as well as the use of such modified oligonucleotide for the preparation of a medicament for preventing and/or treating a tumor, formation of metastasis, an immune disease or disorder, a cardiovascular disease or disorder, and/or a viral disease or disorder.

Abstract: Pharmaceutical composition comprising a chemotherapeutic agent and a TGF-beta antisense oligonucleotide, wherein the antisense oligonucleotide reduces the sensitivity and IC50, respectively, of the cytotoxicity of the chemotherapeutic agent. Preferably, the antisense oligonucleotide is a TGF-beta 1, 2, and/or 3 antisense oligonucleotide and the chemotherapeutic agent is preferably gemcitabine, 5-fluorouracil, temozolomide, dacarbacine, docetaxel, cisplatin, oxaliplatin, tamoxifen, or irinotecan.

Abstract: The present invention is directed to peptides, antibodies and antibody fragments inhibiting activity of “Melanoma Inhibitory Activity” (MIA).

Abstract: The present invention is directed to peptides, antibodies and antibody fragments inhibiting activity of “Melanoma Inhibitory Activity” (MIA).

Abstract: Pharmaceutical composition comprising a chemotherapeutic agent and a TGF-beta antisense oligonucleotide, wherein the antisense oligonucleotide reduces the sensitivity and IC50, respectively, of the cytotoxicity of the chemotherapeutic agent. Preferably, the antisense oligonucleotide is a TGF-beta 1, 2, and/or 3 antisense oligonucleotide and the chemotherapeutic agent is preferably gemcitabine, 5-fluorouracil, temozolomide, dacarbacine, docetaxel, cisplatin, oxaliplatin, tamoxifen, or irinotecan.

Abstract: This invention is related to the use of at least one oligonucleotide with a length of from about 8 to about 30 nucleotide building blocks for manufacturing a pharmaceutical preparation for the prophylaxis and/or the treatment of diseases, that are modulated by TGF-beta2, TGF-beta1, TGF-beta3, VEGF, interleukin-10, c-jun, c-fos, and/or prostaglandin E2 in a mammal, wherein said oligonucleotide hybridizes with a messenger RNA of a TGF-beta2, TGF-beta1, TGF-beta3, VEGF, interleukin-10, c-jun, c-fos and/or prostaglandin E2 gene and wherein said preparation comprises said oligonucleotide in a concentration of about 1 microM to about 25 microM.

Abstract: A conjugate or compound comprising polyethyleneglycol and an oligonucleotide, wherein at least one polyethyleneglycol is linked to the 5?-end of the oligonucleotide and at least one polyethyleneglycol is linked to the 3?-end of the oligonucleotide, wherein the molecular weight of the polyethyleneglycol linked to the 5?- and 3?-end of the oligonucleotide is identical and is <5000 Da, or wherein the molecular weight of the polyethyleneglycol linked to the 5?- and 3?-end of the oligonucleotide is different.

Abstract: An antisense oligonucleotide selected from the group of the sequence 5?-TTG CAT AAA CCC AAG GAG-3? (SEQ ID NO: 1) and modifications thereof a fragment having at least 8 nucleotides of the sequence 5?-TTG CAT AAA CCC AAG GAG-3? (SEQ ID NO: 1) and modifications thereof.

Abstract: A method for preventing and/or treating a tumor, the method comprising: intravenously administering an antisense oligonucleotide in an amount of between about 400 to about 800 mg/m2/treatment cycle, the antisense oligonucleotide comprises 8 to 30 nucleotide building blocks, which hybridizes with mRNA of TGF-beta-2, -1 and/or -3 for the preparation of a pharmaceutical composition.

Abstract: The present invention is directed to peptides, antibodies and antibody fragments inhibiting activity of “Melanoma Inhibitory Activity” (MIA).

Abstract: The invention concerns a pharmaceutical composition comprising at least one stimulator of the immune cell functions and at least one substance inhibiting the cell proliferation and/or inducing cell death. In a preferred embodiment the stimulator of the function of the immune system and/or the immune cells are antagonists of TGF-beta selected from the group of oligonucleotides hybridizing with an area of the messenger RNA and or DNA encoding TGF-beta and the at least one substance inhibiting cell proliferation and/or inducing cell death is selected from the group of temozolomide, nitrosoureas, Vinca alkaloids, antagonists of the purine and pyrimidines bases, cytoststatic active antibiotics, caphthotecine derivatives, anti estrogens, anti-androgens and analogs of gonadotropin releasing hormone.

Abstract: Antisense-oligonucleotides or effective derivatives thereof hybridizing with an area of a gene coding for transforming growth factor-? (TGF-?) comprising the following nucleic acid sequences identified in the sequence listing under SEQ ID NO. 1-56 and 137 or comprising the following nucleic acid sequences identified in the sequence listing under SEQ ID NO. 57 to 136 each of the nucleic acids having a DNA- or RNA-type structure.

Abstract: This invention is related to the use of at least one oligonucleotide with a length of from about 8 to about 30 nucleotide building blocks for manufacturing a pharmaceutical preparation for the prophylaxis and/or the treatment of diseases, that are modulated by TGF-beta2, TGF-beta1, TGF-beta3, VEGF, interleukin-10, c-jun, c-fos, and/or prostaglandin E2 in a mammal, wherein said oligonucleotide hybridizes with a messenger RNA of a TGF-beta2, TGF-beta1, TGF-beta3, VEGF, interleukin-10, c-jun, c-fos and/or prostaglandin E2 gene and wherein said preparation comprises said oligonucleotide in a concentration of about 1 microM to about 25 microM.

Abstract: A method for the preparation of an antisense oligonucleotide or derivative thereof comprising the steps of: selecting a target nucleic acid, if necessary elucidating its sequence; generating the antisense oligonucleotide with the proviso that: the oligonucleotide comprises at least 8 residues; the oligonucleotide comprises at maximum twelve elements, which are capable of forming three hydrogen bonds each to cytosine bases; the oligonucleotide does not contain four or more consecutive elements, capable of forming three hydrogen bonds each with four consecutive cytosine bases (CCCC) within the target molecule or alternatively four or more consecutive elements of GGGG; the oligonucleotide does also not contain 2 or more series of three consecutive elements, capable of forming three hydrogen bonds each with three consecutive cytosine bases (CCC) within the target molecule, or alternatively 2 or more series of three consecutive elements of GGG; and the ratio between residues forming two hydrogen bonds per residue

Abstract: Antisense-oligonucleotides or effective derivatives thereof hybridizing with an area of a gene coding for transforming growth factor-? (TGF-?) comprising the following nucleic acid sequences identified in the sequence listing under SEQ ID NO. 1-56 and 137 or comprising the following nucleic acid sequences identified in the sequence listing under SEQ ID NO. 57 to 136 each of the nucleic acids having a DNA- or RNA-type structure.

Abstract: Medicament comprising a combination of at least one inhibitor of the effect of a substance negatively effecting an immune response, the substance selected from the group consisting of TGF-? and its receptors, VEGF and its receptors, interleukin 10 (IL-10) and its receptors, PGE2 and its receptors, wherein the inhibitor has a molecular weight of less than 100 kDa and at least one stimulator positively effecting an immune response.