Antisense Pharma Gmbh

Biognostik Gesellschaft Fur Biomolekulare Diagnostik Mbh

Other

Biognostik Ges. Fur Biomolekulare Diagnostik Mbh

Isarna Therapeutics Gmbh

Autotelic, LLC

Karl-Hermann Schlingensiepen

Reimar Schlingensiepen

Wolfgang Brysch

Georg-Ferdinand Schlingensiepen

Frank Jaschinski

Ulrich Bogdahn

Anneliese Schneider

Anja-Katrin Bosserhoff

Guenter Auerbach

Georg-F Schlingensiepen

Piotr Jachimczak

Mara Szyrach

Reinhard Buettner

Tanja Rothammer-Hampl

Susanne Schmaus

Hubert Heinrichs

Bernd Betzler

Andreas Mitsch

Michael Hafner

Astrid Bischof

Tamara Bauer

Tanja Rothammer

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&#x2032;-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&#x2032;-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.

Method for selective oligonucleotide modification

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/m/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.

Dosage of oligonucleotides suitable for the treatment of tumors

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.

Mixture comprising an inhibitor or suppressor of a gene and a molecule binding to an expression product of that gene

Method for stimulating the immune system

Pharmaceutical composition comprising a chemotherapeutic agent and a TGF-beta antisense oligonucleotide, wherein the antisense oligonucleotide reduces the sensitivity and IC, 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.

Combination of a chemotherapeutic agent and an inhibitor of the TGF-beta system

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

Method for inhibiting 'melanoma inhibitory activity' MIA

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.

Use of low doses of oligonucleotides antisense to TGF-&#x3b2; genes in the treatment of brain tumors

An antisense oligonucleotide selected from the group of

Antisense oligonucleotide to inhibit melanoma inhibitory activity, MIA

Antisense-oligonucleotides or effective derivatives thereof hybridizing with an area of a gene coding for transforming growth factor-&#x3b2; (TGF-&#x3b2;) 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.

Antisense-oligonucleotides for the treatment of immuno-suppressive effects of transforming growth factor-&#x3b2; (TGF-&#x3b2;)

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 (2H-bond-R) with the target molecule and those residues forming three hydrogen bonds per residue (3H-bond-R) with the target molecule, is ruled by the following specifications: 3H-bond-R/3H-bond-R+2H-bond-R&#x2267;0.29; and synthesizing the oligonucleotide thus generated in a per se known manner.

Antisense oligonucleotide preparation method

A pharmaceutical composition comprising an effective amount of a compound which is capable from preventing and treating neuronal injury, degeneration, cell death and/or neoplasms in which expression of c-jun, c-fos or jun-B plays a causal role which compound being an antisense nucleic acid or effective derivative thereof, said antisense nucleic acid hybridizing with an area of the messenger RNA (mRNA) and/or DNA encoding c-jun, c-fos or jun-B.

Pharmaceutical composition comprising antisense-nucleic acid for prevention and/or treatment of neuronal injury, degeneration and cell death and for the treatment of neoplasms

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 (2H-bond-R) with the target molecule and those residues forming three hydrogen bonds per residue (3H-bond-R) with the target molecule, is ruled by the following specifications: 3H-bond-R/3H-bond-R+2H-bond-R&#x2267;0.29, and synthesizing the oligonucleotide thus generated in a per se known manner.

Antisense-oligonucleotides or effective derivatives thereof hybridizing with an area of a gene coding for transforming growth factor-&bgr; (TGF-&bgr;) 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.

Antisense-oligonucleotides for transforming growth factor-&bgr; (TGF-&bgr;)

The present invention is related to an antisense-nucleic acid or effective derivatives thereof hybridizing with an area of the messenger RNA (mRNA) or the DNA, encoding the p185 receptor (also termed c-erbB-2, HER2 or neu), a pharmaceutical composition, comprising an antisense nucleic acid or effective derivatives thereof hybridizing with an area of the messenger RNA (mRNA) or the DNA, encoding the c-erbB-2 receptor as well as the use of said antisense nucleic acids and derivatives thereof for the manufacturing of a pharmaceutical composition for the treatment of neoplasms and/or immune diseases and/or diseases involving pathological angiogenesis.

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Donaustauf, Germany

Karl-Hermann Schlingensiepen