The present invention provides methods for producing a lyophilized degarelix product which, upon reconstitution with water for injection in an amount of 20 mg/ml, shows a viscosity of up to 15 mPas. The present invention also provides a lyophilized degarelix drug substance which shows, upon dissolution in water in an amount of 20 mg/ml, a viscosity of up to 3.2 mPas, and processes for providing this lyophilized degarelix drug substance.

The present invention provides methods for producing a lyophilized degarelix product which, upon reconstitution with water for injection in an amount of 20 mg/ml, shows a viscosity of up to 15 mPas. The present invention also provides a lyophilized degarelix drug substance which shows, upon dissolution in water in an amount of 20 mg/ml, a viscosity of up to 3.2 mPas, and processes for providing this lyophilized degarelix drug substance.

Methods for ex vivo expansion of very small embryonic like stem cells in the absence of feeder cells are provided. In some embodiments the methods include providing a plurality of VSELs; and growing the VSELs in a culture medium that includes a histone deacetylase inhibitor, luteinizing hormone, follicle-stimulating hormone, and optionally transforming growth factor beta in an amount that is sufficient to overcome quiescence of the VSELs. Also provided are feeder cell-free cell cultures, ex vivo expanded VSELs, pharmaceutical compositions that include the disclosed ex vivo expanded VSELs, methods for overcoming quiescence in VSELs, methods for re-establishing imprinting in VSELs, method for treating injuries to tissues in subjects, methods for repopulating cell types in subjects, methods for bone marrow transplantation, methods for treating radiation exposure in subjects, and methods that relate to regenerative medicine.

Methods for ex vivo expansion of very small embryonic like stem cells in the absence of feeder cells are provided. In some embodiments the methods include providing a plurality of VSELs; and growing the VSELs in a culture medium that includes a histone deacetylase inhibitor, luteinizing hormone, follicle-stimulating hormone, and optionally transforming growth factor beta in an amount that is sufficient to overcome quiescence of the VSELs. Also provided are feeder cell-free cell cultures, ex vivo expanded VSELs, pharmaceutical compositions that include the disclosed ex vivo expanded VSELs, methods for overcoming quiescence in VSELs, methods for re-establishing imprinting in VSELs, method for treating injuries to tissues in subjects, methods for repopulating cell types in subjects, methods for bone marrow transplantation, methods for treating radiation exposure in subjects, and methods that relate to regenerative medicine.

A pharmaceutical combination comprising: (a) a phosphatidylinositol-3-kinase inhibitor selected from 5-(2,6-di-morpholin-4-yl-pyrimidin-4-yl)-4-trifluoromethyl-pyridin-2-ylamine, (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide) or any pharmaceutically acceptable salt thereof and (b) a gonadorelin agonist and, optionally, (c) an antiestrogen agent, particularly for use in the treatment or prevention of a cancer; uses of such a combination in the preparation of a medicament for the treatment or prevention of a cancer; pharmaceutical compositions of the combination of said therapeutic agents and methods of treating a cancer in a subject comprising administering to said subject a therapeutically effective amount of such a combination.

A pharmaceutical combination comprising: (a) a phosphatidylinositol-3-kinase inhibitor selected from 5-(2,6-di-morpholin-4-yl-pyrimidin-4-yl)-4-trifluoromethyl-pyridin-2-ylamine, (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide) or any pharmaceutically acceptable salt thereof and (b) a gonadorelin agonist and, optionally, (c) an antiestrogen agent, particularly for use in the treatment or prevention of a cancer; uses of such a combination in the preparation of a medicament for the treatment or prevention of a cancer; pharmaceutical compositions of the combination of said therapeutic agents and methods of treating a cancer in a subject comprising administering to said subject a therapeutically effective amount of such a combination.

A pharmaceutical combination comprising: (a) a phosphatidylinositol-3-kinase inhibitor selected from 5-(2,6-di-morpholin-4-yl-pyrimidin-4-yl)-4-trifluoromethyl-pyridin-2-ylamine, (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide) or any pharmaceutically acceptable salt thereof and (b) a gonadorelin agonist and, optionally, (c) an antiestrogen agent, particularly for use in the treatment or prevention of a cancer; uses of such a combination in the preparation of a medicament for the treatment or prevention of a cancer; pharmaceutical compositions of the combination of said therapeutic agents and methods of treating a cancer in a subject comprising administering to said subject a therapeutically effective amount of such a combination.

The present invention relates to improved pharmaceutical formulations, uses and methods for the oral delivery of peptide or protein drugs with advantageously high bioavailability, safety and cost-effectiveness. In particular, the invention provides a peptide or protein drug having a molecular weight of equal to or less than about 50 kDa for use as a medicament, wherein said peptide or protein drug is to be administered orally in combination with a pharmaceutically acceptable copper salt/complex and/or a pharmaceutically acceptable zinc salt/complex, and with a pharmaceutically acceptable reducing agent. The invention also provides a pharmaceutical composition comprising: a peptide or protein drug having a molecular weight of equal to or less than about 50 kDa; a pharmaceutically acceptable copper salt/complex and/or a pharmaceutically acceptable zinc salt/complex; and a pharmaceutically acceptable reducing agent.

This disclosure is directed to compositions and methods for treating cancer using combination therapies of NK-92 cells with cancer drugs (e.g. thalidomide, cisplatin, and paclitaxel).

This disclosure is directed to compositions and methods for treating cancer using combination therapies of NK-92 cells with cancer drugs (e.g. thalidomide, cisplatin, and paclitaxel).