Abstract: The present invention relates to a method for the isolation of proteins that comprise disulfide-bonds in their native conformation. Essentially, a method of the present makes the use of reducing agents such as ?-mercaptoethanol or dithiothreitol in protein isolation methods obsolete. A method of the present invention is particularly suitable for the isolation of precursor proteins such as proinsulin from recombinant cells.

Abstract: The present invention relates to a method for the isolation of proteins that comprise disulfide bonds in their native conformation. Essentially, a method of the present invention makes use of reducing agents such as ?-mercaptoethanol or dithiothreitol in protein isolation methods obsolete. A method of the present invention is particularly suitable for the isolation of precursor proteins such as proinsulin from recombinant cells.

Abstract: The present invention relates to a antisolvent solidification process wherein a liquid medium comprising at least one organic or inorganic compound which is to be solidified is forced through a membrane into one or more antisolvents, or wherein one or more antisolvents are forced through a membrane into a liquid medium comprising at least one organic or inorganic compound which is to be solidified, yielding a composition comprising solid particles comprising said organic and/or inorganic compound(s).

Abstract: The subject invention provides a drug delivery system comprising at least one compartment consisting of (i) a drug-loaded thermoplastic polymer core, (ii) a drug-loaded thermoplastic polymer intermediate layer and (iii) a non-medicated thermoplastic polymer skin covering the intermediate layer, wherein said intermediate layer is loaded with (a) crystals of a first pharmaceutically active compound and with (b) a second pharmaceutically active compound in dissolved form and wherein said core is loaded with said second compound in dissolved form.

Abstract: Antibodies which block binding of hPD-1 to hPD-L1 or hPD-L2 and their variable region sequences are disclosed. A method of increasing the activity (or reducing downmodulation) of an immune cell through the PD-1 pathway is also disclosed.

Abstract: The subject invention provides a drug delivery system comprising at least one compartment consisting of (i) a drug-loaded thermoplastic polymer core, (ii) a drug-loaded thermoplastic polymer intermediate layer and (iii) a non-medicated thermoplastic polymer skin covering the intermediate layer, wherein said intermediate layer is loaded with (a) crystals of a first pharmaceutically active compound and with (b) a second pharmaceutically active compound in dissolved form and wherein said core is loaded with said second compound in dissolved form.

Abstract: The invention relates to 5,6-dihydropyrrolo[2,1-?]isoquinoline and pyrrolo[2,1-?]isoquinoline derivatives according to general formula (I) or a pharmaceutically acceptable salt thereof. The compounds can be used for the treatment of infertility.

Abstract: The present invention relates to substituted steroid compounds having the formula Wherein R1 is H or halogen; R2 is H, (1C-4C)alkyl, (1C-4C)acyl, glucuronyl or sulfamoyl; R3 is H or halogen; R4 is H, (1C-4C)alkyl, (2C-4C)alkenyl or (2C-4C)alkynyl; R5 is methyl or ethyl; R6 is H or methyl; R7 is H or methyl; R8 is H or acyl for use in the treatment and prevention of endometriosis, for contraception, for hormonal therapy in perimenopausal and post-menopausal women, for the treatment of osteoporosis and for the treatment uterine fibroids and other menstrual-related disorders, such as dysfunctional uterine bleeding.

Abstract: The present invention relates to hexafluoroisopropanol derivatives having the general formula I to pharmaceutical compositions comprising the same and to the use of these hexafluoroisopropanol derivatives in the treatment of atherosclerosis.

Abstract: An intrauterine system for the retention of a biologically active compound within the uterus of a female mammal is formed by a frame defining an interior space for receipt of a deposit of the compound. The frame has an open structure allowing access to a substantial part of an outer surface of the deposit and the deposit has a rate controlling structure that controls a rate of release of the compound within the uterus. Retention elements are provided on the frame for retaining the frame within the uterus.

Abstract: Antibodies which block the binding of human Programmed Death Receptor 1 (hPD-1) to its ligands (hPD-L1 or hPD-L2) and their variable region sequences are disclosed. A method of increasing the activity (or reducing downmodulation) of an immune response through the PD-I pathway is also disclosed.

Abstract: The subject invention provides a drug delivery system comprising at least one compartment consisting of (i) a drug-loaded thermoplastic polymer core, (ii) a drug-loaded thermoplastic polymer intermediate layer and (iii) a non-medicated thermoplastic polymer skin covering the intermediate layer, wherein said intermediate layer is loaded with (a) crystals of a first pharmaceutically active compound and with (b) a second pharmaceutically active compound in dissolved form and wherein said core is loaded with said second compound in dissolved form.

Abstract: The present invention relates to N-benzyl,N?-arylcarbonylpiperazine derivatives having the general formula I to pharmaceutical compositions comprising the same, and to the use of a these N-benzyl,N?-arylcarbonylpiperazine derivatives for the manufacture of a medicament for treating or preventing atherosclerosis and related disorders associated with cholesterol and bile acids transport and metabolism.

Abstract: The invention relates to 1H-[1,2,3]triazolo[4,5-c]pyridine-4-carbonitrile derived Cathepsin S inhibitors of Formula (I), wherein R1 is H or (C1-3)alkyl; R2 is halogen or (C1-4)alkyl, optionally substituted with one or more halogens; n is 1-3; X is O or CH2; U, V and W are CH; or one of U, V and W is N; Y is a group capable of interacting with the Sn . . . S2 substites of the active site of Cathepsin S; or a pharmaceutically acceptable salt thereof, to pharmaceutical compositions comprising the same as well as to the use of these derivatives for the preparation of a medicament for the treatment of cathepsin S related diseases such as atherosclerosis, obesity, inflammation and immune disorders, such as rheumatoid arthritis, psoriasis, cancer, and chronic pain, such as neuropathic pain.

Abstract: The invention relates to the compound N-(2-oxo-2-propoxyethyl)-?-phenyl-D-phenyl-alanyl-N-[(1-amino-6-iso-quinolinyl)methyl]-L-prolinamide or a pharmaceutically acceptable salt thereof, to a pharmaceutical composition comprising said compound, as well as to the use of the compound for the manufacture of a medicament for treating or for preventing thrombin mediated diseases.

Abstract: An intrauterine system (1) for the retention of a biologically active compound within the uterus of a female mammal is formed by a frame (16) defining an interior space (20) for receipt of a deposit of the compound (22). The frame has an open structure (18) allowing access to a substantial part of an outer surface of the deposit and the deposit has a rate controlling structure that controls a rate of release of the compound within the Uterus. Retention elements (6) are provided on the frame for retaining the frame within the uterus.

Abstract: The present invention relates compounds of the formula (I) oligosaccharide-spacer-A ??(I), wherein the oligosaccharide is a negatively charged oligosaccharide residue comprising two to twenty five monosaccharide units, the charge being compensated by positively charged counterions, and wherein the oligosaccharide residue is derived from an oligosaccharide which has (AT-III mediated) anti-Xa activity per se; the spacer is an essentially pharmacologically inactive flexible linking residue having a chain length of 10 to 70 atoms; A is the residue —CH[NH—SO2—R1][CO—NR2—CH(4-benzamidine)-CO—NR3R4], wherein R1 is phenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, (iso)quinolinyl, tetrahydro(iso)quinolinyl, 3,4-dihydro-1H-isoquinolinyl, chromanyl or the camphor group, which groups may optionally be substituted with one or more substituents selected from (1-8C)alkyl or (1-8C)alkoxy; and wherein R2 and R3 are independently H or (1-8C)alkyl; R4 is (1-8C)alkyl or (3-8C)cycloalkyl; or R3 and R4 together with the nitroge

Abstract: Process for the preparation of a compound of general formula (II) wherein R1 and R2 independently are hydrogen or a hydroxy- or hydrocarbyl group; or wherein R1 and R2 together are a double bonded oxygen; R3 is hydrogen; R?4 is a nitrobenzophenone group; and R5 and R6 independently are hydrogen or a hydroxy- or hydrocarbyl group; from a compound of general formula (I) wherein, R1, R2 R3, R5 and R6 are as defined above and R4 is hydrogen; wherein the compound of formula (I) is reacted under alkaline conditions with 2-chloro-5-nitrobenzophenone in the presence of an alkanolic solvent and the compound of formula (II) is directly crystallized from this alkanolic solvent. Complex of an alkanol and a compound of general formula (II) obtainable from the above process and processes wherein the above process or complex are used.

Abstract: The present invention relates compounds of the formula (I) oligosaccharide-spacer-A (I), wherein the oligosaccharide is a negatively charged oligosaccharide residue comprising two to twenty five monosaccharide units, the charge being compensated by positively charged counterions, and wherein the oligosaccharide residue is derived from an oligosaccharide which has (AT-III mediated) anti-Xa activity per se; the spacer is an essentially pharmacologically inactive flexible linking residue having a chain length of 10 to 70 atoms; A is the residue —CH[NH—SO2—R1] [CO—NR2—CH(4-benzamidine)-CO—NR3R4], wherein R1 is phenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, (iso)quinolinyl, tetrahydro(iso)quinolinyl, 3,4-dihydro-1H-isoquinolinyl, chromanyl or the camphor group, which groups may optionally be substituted with one or more substituents selected from (1-8C)alkyl or (1-8C)alkoxy; and wherein R2 and R3 are independently H or (1-8C)alkyl; R4 is (-8C)alkyl or (3-8C)cycloalkyl; or R3 and R4 together with the nitrogen atom t

Abstract: The present invention relates to tetrahydroquinoline derivatives having general formula I: or a pharmaceutically acceptable salt thereof, wherein R1 is formyl, (1-6C)alkylcarbonyl or (1-6C)alkylsulfonyl; R2 and R3 are H or (1-4C)alkyl; R4 is phenyl; R5 is (1-4C)alkyl; Y—X is C(O)—O, S(O)2-O, NHC(O)—O, NHC(S)—O, OC(O)—O, bond-O, C(O)—NH, S(O)2-NH, NHC(O)—NH, NHC(S)—NH, OC(O)—NH, bond-NH, NH—C(O), O—C(O), NH—S(O)2, or O—S(O)2 or Y—X is a bond; R6 is H, trifluoromethyl, (1-6C)alkyl, 1- or 2-adamantyl(1-4C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (3-9C)heteroaryl, (3-6C)cycloalkyl, (2-6C)heterocycloalkyl, (1-4C)alkylthio(1-4C)alkyl, (6-10C)aryl(1-4C)alkyl, (3-9C)heteroaryl(1-4C)alkyl, (3-6C)cycloalkyl(1-4C)alkyl, (2-6C)heterocycloalkyl(1-4C)alkyl, R8,R9-aminocarbonyl(1-4C)alkyl, R8,R9-amino(1-4C)alkyl, R8-oxycarbonyl(1-4C)alkyl, R8-oxy(1-4C)alkyl, R8-carbonyl(1-4C)alkyl or (6-10C)aryl; R7 is H, (1-4C)alkyl, (1-4C)alkoxy, halogen, trifluoromethyl, cyano, nitro, hydroxyl; and R8 and/or R9 is H, (1-4C)alkyl, (2-4C