Abstract: The present invention refers to immunosuppression-reverting oligonucleotides comprising 12 to 18 nucleotides, wherein at least one of the nucleotides is modified, and the oligonucleotide hybridizes with a nucleic acid sequence of an ectonucleotidase (NTPdase; CD73) of SEQ ID NO.1 (human), wherein the oligonucleotide inhibits at least 50% of the CD39 expression. The invention is further directed to a pharmaceutical composition comprising such oligonucleotide.

Abstract: The present invention refers to immunosuppression-reverting oligonucleotides comprising 12 to 18 nucleotides, wherein at least one of the nucleotides is modified, and the oligonucleotide hybridizes with an hybridizing active region of the nucleic acid sequence of an ectoenzyme (CD73) of SEQ ID NO.1 (human) and/or SEQ ID NO.2 (human). The invention is further directed to a pharmaceutical composition comprising such oligonucleotide. The oligonucleotide and the pharmaceutical composition are used in a method of preventing and/or treating a disorder, where a CD73 imbalance is involved.

Abstract: The present invention refers to oligonucleotides comprising 10 to 25 nucleotides, wherein at least one of the nucleotides is modified, and the oligonucleotide hybridizes with mRNA of angiotensin-converting enzyme 2 (ACE2) of SEQ ID NO.1 and/or with pre-mRNA of ACE2 of SEQ ID NO.2 resulting in a reduction of the level of ACE2, ACE2 mRNA, ACE2 pre-mRNA or a combination thereof of 30 to 99% compared to an untreated control. The invention is further directed to a pharmaceutical composition comprising such oligonucleotide. The oligonucleotide and the pharmaceutical composition are used in a method of preventing and/or treating a viral disease.

Abstract: An ANGPTL4 inhibitor consists of an oligonucleotide has 12 to 22 nucleotides. At least one of the nucleotides is modified, and the oligonucleotide hybridizes with a nucleic acid sequence of human and/or muse ANGPTL4 and inhibits the expression of ANGPTL4. A pharmaceutical composition can include the ANGPTL4 inhibitor and a pharmaceutically acceptable carrier, excipient diluent, or a combination of these.

Abstract: The present invention refers to an inhibitor consisting of oligonucleotides comprising 10 to 25 nucleotides, wherein at least one of the nucleotides is modified, and the oligonucleotide hybridizes with a nucleic acid sequence of C/EBP-homologous protein (Chop) of SEQ ID NO.1 (human) and/or SEQ ID NO. 48 (human) but also with mouse and rat sequences, wherein the oligonucleotide N inhibits at least 50% of the Chop expression. The invention is further directed to a pharmaceutical composition comprising such oligonucleotide.

Abstract: The present invention refers to an antisense oligonucleotide comprising 10 to 25 nucleotides, wherein at least one of the nucleotides is modified, and the antisense oligonucleotide hybridizes with a nucleic acid sequence of Programmed Cell Death 1 (PD-5 1) of SEQ ID NO.1, wherein the antisense oligonucleotide inhibits at least 30% of the PDl expression in a cell compared to an untreated cell. The invention further refers to a pharmaceutical composition comprising such antisense oligonucleotide as well as the use of the antisense oligonucleotide or the pharmaceutical composition in a method of preventing and/or treating a malignant tumor, a benign tumor and/or an infectious disease. The antisense oligonucleotide or the pharmaceutical composition is alternatively used for reducing expression of PD-1 in an isolated immune cell in preparation for cell therapy.

Abstract: The present invention relates to a novel approach for treating cancer, which is based on targeting PD-L1 mRNA. The invention is directed to oligonucleotides comprising 10 to 20 modified or unmodified nucleotides complementary to specifically selected regions of the PD-L1.

Abstract: The present invention refers to an inhibitor consisting of an oligonucleotide comprising 12 to 25 nucleotides, wherein at least one of the nucleotides is modified, and the oligonucleotide hybridizes with a nucleic acid sequence of MTDH of SEQ ID NO.1 (human mRNA), SEQ ID NO.2 (human pre-mRNA), SEQ ID NO.223 (mouse mRNA) and/or SEQ ID NO.224 (mouse pre-mRNA), wherein the oligonucleotide inhibits at least 50% of the MTDH expression. The invention is further directed to a pharmaceutical composition comprising such oligonucleotide.

Abstract: The present invention refers to a method for reducing expression of a target RNA in an isolated cell in preparation for cell therapy, comprising incubating the isolated cell comprising the target RNA with an antisense oligonucleotide without use of a transfection means, wherein the antisense oligonucleotide is administered to the isolated cell at least once in a time period of day 0 to day 21, the antisense oligonucleotide hybridizes with the target RNA and reduces the transcription of the target RNA, reduces the expression of the protein encoded by the target RNA or a combination thereof up to 8 weeks from day 0 of the incubation with the antisense oligonucleotide. The invention further relates to an isolated cell obtainable by the method of the present invention and a pharmaceutical composition comprising the isolated cell. The isolated cell and the pharmaceutical composition are used in a method of preventing and/or treating a disease.

Abstract: The present invention refers to an oligonucleotide comprising 12 to 25 nucleotides, wherein at least one of the nucleotides comprises a modification selected from the group consisting of a bridged nucleic acid such as LNA, ENA, a 2?Fluoro modified nucleotide, a 2 O-Methyl modified nucleotide, a 2 O-Methoxy modified nucleotide, a FANA and a combination thereof. The oligonucleotide hybridizes with a nucleic acid sequence of Foxp3 of SEQ ID NO.1 and/or of SEQ ID NO.2 resulting in a reduction of the expression of FoxP3 mRNA, FoxP3 pre-mRNA or a combination thereof. The invention is further directed to a pharmaceutical composition comprising an oligonucleotide of the present invention and to the oligonucleotide and pharmaceutical composition, respectively for use in a method of preventing and/or treating a disorder, where FoxP3 imbalance is involved.

Abstract: The present invention refers to an oligonucleotide consisting of 10 to 20 nucleotides hybridizing with SEQ ID NO.1 encoding PD-L1, wherein the oligonucleotide has a fundamentally reduced number of potential off-target binding sites resulting in a markedly reduced risk for off-target effects. Further, the present invention is directed to a pharmaceutically composition comprising such oligonucleotide and a pharmaceutically acceptable excipient.

Abstract: An ANGPTL4 inhibitor consists of an oligonucleotide has 12 to 22 nucleotides. At least one of the nucleotides is modified, and the oligonucleotide hybridizes with a nucleic acid sequence of human and/or muse ANGPTL4 and inhibits the expression of ANGPTL4. A pharmaceutical composition can include the ANGPTL4 inhibitor and a pharmaceutically acceptable carrier, excipient diluent, or a combination of these.

Abstract: An ANGPTL4 inhibitor consisting of an oligonucleotide has 12 to 22 nucleotides. At least one of the nucleotides is modified, and the oligonucleotide hybridizes with a nucleic acid sequence of human and/or mouse ANGPTL4 and inhibits the expression of ANGPTL4. Also disclosed herein is a pharmaceutical composition of the ANGPTL4 inhibitor and a pharmaceutically acceptable carrier, excipient, diluent, or a combination thereof.

Abstract: The present invention refers to an inhibitor consisting of oligonucleotides comprising 10 to 25 nucleotides, wherein at least one of the nucleotides is modified, and the oligonucleotide hybridizes with a nucleic acid sequence of C/EBP-homologous protein (Chop) of SEQ ID NO.1 (human) and/or SEQ ID NO. 48 (human) but also with mouse and rat sequences, wherein the oligonucleotide N inhibits at least 50% of the Chop expression. The invention is further directed to a pharmaceutical composition comprising such oligonucleotide.

Abstract: The present invention refers to immunosuppression-reverting oligonucleotides comprising 12 to 18 nucleotides, wherein at least one of the nucleotides is modified, and the oligonucleotide hybridizes with a nucleic acid sequence of an ectonucleotidase (NTPdase; CD73) of SEQ ID NO.1 (human), wherein the oligonucleotide inhibits at least 50% of the CD39 expression. The invention is further directed to a pharmaceutical composition comprising such oligonucleotide.

Abstract: The present invention refers to immunosuppression-reverting oligonucleotides comprising 12 to 18 nucleotides, wherein at least one of the nucleotides is modified, and the oligonucleotide hybridizes with a nucleic acid sequence of indoleamine-2,3-dioxygenase (IDO-1) of SEQ ID NO.1 (human) in a hybridizing active area, wherein the oligonucleotide inhibits at least 50% of the IDO-1 expression. The invention is further directed to a pharmaceutical composition comprising such oligonucleotide.

Abstract: The present invention relates to a novel approach for treating inflammatory disorders and other diseases, which is based on targeting ROR gamma t mRNA. The invention is directed to oligonucleotides comprising 10 to 22 modified or unmodified nucleotides complementary to specifically selected regions of the RORC, transcript variant 2 mRNA (RORC2), which codes for the ROR gamma t protein.

Abstract: The invention refers to an oligonucleotide consisting of 10 to 20 nucleotides of selected regions of the TGF-beta1, TGF-beta2 or TGF-beta3 nucleic acid sequence, which comprises modified nucleotides such as LNA, ENA, polyalkylene oxide-, 2?-fluoro, 2?-O-methoxy and/or 2?-O-methyl modified nucleotides. The selected regions are preferably the region of nucleic acid no. 1380 to 1510, no. 1660 to 1680, no. 2390 to 2410, or no. 2740 to 2810 of the TGF-beta2 nucleic acid sequence of SEQ ID NO. 1, specific regions of the TGF-beta1 nucleic acid sequence of SEQ ID NO. 149, or specific regions of the TGF-beta3 nucleic acid sequence of SEQ ID No. 267. The invention further relates to pharmaceutical compositions comprising such oligonucleotide, wherein the composition or the oligonucleotide is used in the prevention and/or treatment of a malignant and/or benign tumor, an immunologic disease, fibrosis, glaucoma, etc.

Abstract: The present invention relates to a novel approach for treating cancer, which is based on targeting PD-L1 mRNA. The invention is directed to oligonucleotides comprising 10 to 20 modified or unmodified nucleotides complementary to specifically selected regions of the PD-L1.

Abstract: The present invention refers to an oligonucleotides comprising 12 to 18 nucleotides, wherein at least one of the nucleotides is modified, and the oligonucleotide hybridizes with a nucleic acid sequence of neuropilin 1 (NRP1, CD304) of SEQ ID NO.1 (NM_003873.5), wherein the oligonucleotide inhibits at least 50% of the NRP1 expression. The invention is further directed to a pharmaceutical composition comprising such oligonucleotide.