The invention relates to fusion constructs and checkpoint inhibitors, methods of using fusion constructs and checkpoint inhibitors, and methods of treating undesirable or aberrant cell proliferation or hyperproliferative disorders, such as tumors, cancers, neoplasia and malignancies.

The present invention relates to the construction of a new class of Targeted Secretion Inhibitors (TSIs), which comprise a non-cytotoxic protease, translocation peptide and a targeting moiety peptide, wherein the targeting moiety peptide has a free N-terminal domain and a free C-terminal domain; to a single-chain fusion protein precursor thereof, and to a method of activating said single-chain fusion protein precursor.

The present invention relates to the construction of a new class of Targeted Secretion Inhibitors (TSIs), which comprise a non-cytotoxic protease, translocation peptide and a targeting moiety peptide, wherein the targeting moiety peptide has a free N-terminal domain and a free C-terminal domain; to a single-chain fusion protein precursor thereof, and to a method of activating said single-chain fusion protein precursor.

The present invention provides a manufacturing process for preparing a peptide, preferably a decapeptide, such as degarelix, by incorporating p-nitro-phenylalanin in the amino acid sequence preferably during stepwise solid phase synthesis, and converting these into the required amino acids Aph(Hor) and/or D-Aph(Cbm), preferably while attached to a solid phase. The invention further provides intermediates useful in the manufacturing process.

The present invention provides a manufacturing process for preparing a peptide, preferably a decapeptide, such as degarelix, by incorporating p-nitro-phenylalanin in the amino acid sequence preferably during stepwise solid phase synthesis, and converting these into the required amino acids Aph(Hor) and/or D-Aph(Cbm), preferably while attached to a solid phase. The invention further provides intermediates useful in the manufacturing process.

Disclosed are compositions and methods related to improving pharmacological properties of bioactive compounds targeting nervous system.

Disclosed are compositions and methods related to improving pharmacological properties of bioactive compounds targeting nervous system.

The conjugation of luteinizing hormone-releasing hormone (LHRH) with activated cisplatin using a malonate linker gives rise to a new Platinum-LHRH conjugate that effectively targets tumor cells that express the LHRH receptor. The Pt-LHRH conjugate may be used in a method for killing or inhibiting the growth of a tumor cell, especially in late state, highly invasive and aggressive stage IV tumors and in reoccurring tumors.

The conjugation of luteinizing hormone-releasing hormone (LHRH) with activated cisplatin using a malonate linker gives rise to a new Platinum-LHRH conjugate that effectively targets tumor cells that express the LHRH receptor. The Pt-LHRH conjugate may be used in a method for killing or inhibiting the growth of a tumor cell, especially in late state, highly invasive and aggressive stage IV tumors and in reoccurring tumors.

The present invention provides a manufacturing process for preparing a peptide, preferably a decapeptide, such as degarelix, by incorporating p-nitro-phenylalanin in the amino acid sequence preferably during stepwise solid phase synthesis, and converting these into the required amino acids Aph(Hor) and/or D-Aph(Cbm), preferably while attached to a solid phase. The invention further provides intermediates useful in the manufacturing process.