Abstract: The present disclosure relates to a class of engineered polypeptides having a binding affinity for interleukin-1 receptor type-I (IL-1R-I) which comprise the binding motif (BM) EX2X3X4X5X6X7EIX10X11LPNLX16RX18QYX21A FIX25X26LX28D. The present disclosure also relates to the use of such an IL-1R-I binding polypeptide as a therapeutic, prognostic and/or diagnostic agent.

Abstract: The present disclosure relates to a class of engineered polypeptides having a binding affinity for interleukin-1 receptor type-I (IL-1R-I) which comprise the binding motif (BM) EX2X3X4X5X6X7EIX10X11LPNLX16RX18QYX21AFIX25X26LX28D. The present disclosure also relates to the use of such an IL-1R-I binding polypeptide as a therapeutic, prognostic and/or diagnostic agent.

Abstract: A fusion protein is provided, comprising i) a biologically active polypeptide; and ii) a half-life extending polypeptide moiety comprising 2-80 units independently selected the amino acid sequences according to SEQ ID NO: 1: X1-X2-X3-X4-X5-X6-D-X8-X9-X10-X11 (SEQ ID NO: 1) in which, independently: X1 is P or absent; X2 is V or absent; X3 is P or T; X4 is P or T; X5 is T or V; X6 is D, G or T; X8 is A, Q or S; X9 is E, G or K; X10 is A, E P or T; and X11 is A, P or T. The half-life extending polypeptide moiety has a generally unfolded conformation and provides a fusion protein with a large hydrodynamic radius that may avoid renal clearance. As a result, the biological half-life of the fusion protein is increased and the biological effect of the biologically active polypeptide may thus be prolonged.

Abstract: The present disclosure relates to a class of engineered polypeptides having a binding affinity for interleukin-1 receptor type-I (IL-1R-I) which comprise the binding motif (BM) EX2X3X4X5X6X7EIX10X11LPNLX16RX18QYX21AFIX25X26LX28D. The present disclosure also relates to the use of such an IL-1R-I binding polypeptide as a therapeutic, prognostic and/or diagnostic agent.

Abstract: A fusion protein is provided, comprising i) a biologically active polypeptide; and ii) a half-life extending polypeptide moiety comprising 2-80 units independently selected the amino acid sequences according to SEQ ID NO: 1: X1-X2-X3-X4-X5-X6-D-X8-X9-X10-X11 (SEQ ID NO: 1) in which, independently: X1 is P or absent; X2 is V or absent; X3 is P or T; X4 is P or T; X5 is T or V; X6 is D, G or T; X8 is A, Q or S; X9 is E, G or K; X10 is A, E P or T; and X11 is A, P or T. The half-life extending polypeptide moiety has a generally unfolded conformation and provides a fusion protein with a large hydrodynamic radius that may avoid renal clearance. As a result, the biological half-life of the fusion protein is increased and the biological effect of the biologically active polypeptide may thus be prolonged.

Abstract: Disclosed herein are a modified sulfamidase, a composition comprising a modified sulfamidase, as well as methods for preparing a modified sulfamidase and therapeutic use of such a sulfamidase. In particular, the present disclosure relates to a modified sulfamidase comprising substantially no epitopes for glycan recognition receptors, thereby enabling transportation of said sulfamidase across the blood brain barrier of a mammal, wherein said sulfamidase has catalytic activity in the brain of said mammal.

Abstract: Disclosed herein are a modified iduronate 2-sulfatase, a composition comprising a modified iduronate 2-sulfatase, as well as methods for preparing a modified iduronate 2-sulfatase and therapeutic use of such a iduronate 2-sulfatase. In particular, the present disclosure relates to a modified iduronate 2-sulfatase sulfatase comprising substantially no epitopes for glycan recognition receptors, wherein said iduronate 2-sulfatase has a catalytic activity of at least 50% of that of unmodified iduronate 2-sulfatase in vitro.

Abstract: Disclosed herein are a modified lysosomal protein, methods for preparing a modified lysosomal protein and therapeutic use of such a modified protein. Further disclosed herein is a method of treating a mammal afflicted with a lysosomal storage disease. In particular, the present disclosure relates to a method of preparing a modified lysosomal protein, said method comprising reacting a glycosylated lysosomal protein with an alkali metal periodate and reacting said lysosomal protein with an alkali metal borohydride for a time period of no more than 2 h, thereby modifying glycan moieties of the lysosomal protein and reducing the activity of the lysosomal protein with respect to glycan recognition receptors.

Abstract: The invention relates to a polypeptide capable of binding human complement component 5 (C5), said polypeptide comprising the amino acid sequence (SEQ ID NO: 296) [BM]-[L2]-QSX42X43LLX46EAKKLX52X53X54Q wherein [BM] is a C5 binding motif; [L2] is an interconnecting loop; X42 is selected from A and S; X43 is selected from N and E; X46 is selected from A, S and C; X52 is selected from E, N and S; X53 is selected from D, E and S, provided that X53 is not D when X52 is N; and X54 is selected from A and S.

Abstract: The present disclosure relates to a class of engineered polypeptides and provides a polypeptide comprising the sequence EX2X3X4AX6X7EIX10 X11LPNLX16X17X18QX20 X21AFIX25X26LX28X29X30 PX32QSX35X36LLX39E AKKLX45X46X47Q (SEQ ID NO: 55). The present disclosure also relates to populations of polypeptide variants based on a common scaffold, each polypeptide in the population comprising the amino acid sequence EX2X3X4AX6X7EIX10 X11LPNLX16X17X18QX20 X21AFIX25X26LX28X29X30 PX32QSX35X36LLX39E AKKLX45X46X47Q (SEQ ID NO: 55), and methods for selecting a desired polypeptide having an affinity for a predetermined target from said population.

Abstract: Disclosed herein are a modified sulfamidase, a composition comprising a modified sulfamidase, as well as methods for preparing a modified sulfamidase and therapeutic use of such a sulfamidase. In particular, the present disclosure relates to a modified sulfamidase comprising substantially no epitopes for glycan recognition receptors, thereby enabling transportation of said sulfamidase across the blood brain barrier of a mammal, wherein said sulfamidase has catalytic activity in the brain of said mammal.

Abstract: The invention relates to a polypeptide capable of binding human complement component 5 (C5), said polypeptide comprising the amino acid sequence (SEQ ID NO: 296) [BM]-[L2]-QSX42X43LLX46EAKKLX52X53X54Q wherein [BM] is a C5 binding motif; [L2] is an interconnecting loop; X42 is selected from A and S; X43 is selected from N and E; X46 is selected from A, S and C; X52 is selected from E, N and S; X53 is selected from D, E and S, provided that X53 is not D when X52 is N; and X54 is selected from A and S.

Abstract: Disclosed herein are a modified sulfamidase, a composition comprising a modified sulfamidase, as well as methods for preparing a modified sulfamidase and therapeutic use of such a sulfamidase. In particular, the present disclosure relates to a modified sulfamidase comprising substantially no epitopes for glycan recognition receptors, thereby enabling transportation of said sulfamidase across the blood brain barrier of a mammal, wherein said sulfamidase has catalytic activity in the brain of said mammal.

Abstract: The present disclosure relates to a class of engineered polypeptides and provides a polypeptide comprising the sequence EX2X3X4AX6X7EIX10 X11LPNLX16X17X18QX20 X21 AFIX25X26LX28X29X30 PX32QSX35X36LLX39E AKKLX45X46X47Q (SEQ ID NO: 55). The present disclosure also relates to populations of polypeptide variants based on a common scaffold, each polypeptide in the population comprising the amino acid sequence EX2X3X4AX6X7EIX10 X11 LPNLX16X17X18QX20 X21 AFIX25X26LX28X29X30 PX32QSX35X36LLX39E AKKLX45X46X47Q (SEQ ID NO: 55), and methods for selecting a desired polypeptide having an affinity for a predetermined target from said population.

Abstract: Disclosed are compounds which inhibit SSAO enzyme activity. Also disclosed are pharmaceutical compositions comprising these compounds and the use of these compounds in the treatment or prevention of medical conditions wherein inhibition of SSAO activity is beneficial, such as inflammatory diseases, immune disorders and the inhibition of tumor growth.

Abstract: 2-{4-[1-(4-chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl}ethan-1-amine; 3-aminopropyl 4-[1-(4-chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]piperidine-1-carboxylate; 1-{4-[1-(4-chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl}-4-(dimethylamino)butan-1-one; 5-amino-1-{4-[1-(4-chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl}pentan-1-one; N-(2-aminoethyl)-4-[1-(4-chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]piperidine-1-carboxamide; N-(3-aminopropyl)-4-[1-(4-chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]piperidine-1-carboxamide; 4-[1-(4-chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-N-[3-(dimethylamino)propyl]piperidine-1-carboxamide; 1-({4-[1-(4-chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl}carbonyl)piperazine; 4-({4-[1-(4-chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl}carbonyl)morpholine; 1-({4-[1-(4-chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl}carbonyl)-1,4-diazepane; ethyl 1-[1-(4-chlorophenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl]piperidine-4-carbo

Abstract: 2-{4-[1-(4-chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl}ethan-1-amine; 3-aminopropyl 4-[1-(4-chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]piperidine-1-carboxylate; 1-{4-[1-(4-chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl}-4-(dimethylamino)butan-1-one; 5-amino-1-{4-[1-(4-chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl}pentan-1-one; N-(2-aminoethyl)-4-[1-(4-chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]piperidine-1-carboxamide; N-(3-aminopropyl)-4-[1-(4-chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]piperidine-1-carboxamide; 4-[1-(4-chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-N-[3-(dimethylamino)propyl]piperidine-1-carboxamide; 1-({4-[1-(4-chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl}carbonyl)piperazine; 4-({4-[1-(4-chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl}carbonyl)morpholine; 1-({4-[1-(4-chlorophenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl}carbonyl)-1,4-diazepane; ethyl 1-[1-(4-chlorophenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl]piperidine-4-carbo

Abstract: The present invention relates to compounds of the general formula (I) wherein R1, R2 and R3 are as defined herein, which can act as inhibitors of protein kinases, specially the Fms-like tyrosine kinase 3 (FLT3). A species illustrative of members of the general formula is The invention also relates to the use of the compounds in therapy, pharmaceutical compositions comprising the compounds and the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of hematological malignancies, such as AML, MLL, T-ALL, B-ALL and CMML, myeloproliferative disorders, other proliferative disorders like cancer, autoimmune disorders and skin disorders like psoriasis and atopic dermatitis.

Abstract: Disclosed are compounds which inhibit SSAO enzyme activity. Also disclosed are pharmaceutical compositions comprising these compounds and the use of these compounds in the treatment or prevention of medical conditions wherein inhibition of SSAO activity is beneficial, such as inflammatory diseases, immune disorders and the inhibition of tumour growth.

Abstract: The present disclosure relates to a class of engineered polypeptides and provides a polypeptide comprising the sequence EX2X3X4AX6X7EIX10 X11LPNLX16X17X18QX20 X21AFIX25X26LX28X29X30 PX32QSX35X36LLX39E AKKLX45X46X47Q (SEQ ID NO: 55). The present disclosure also relates to populations of polypeptide variants based on a common scaffold, each polypeptide in the population comprising the amino acid sequence EX2X3X4AX6X7EIX10 X11LPNLX16X17X18QX20 X21AFIX25X26LX28X29X30 PX32QSX35X36LLX39E AKKLX45X46X47Q (SEQ ID NO: 55), and methods for selecting a desired polypeptide having an affinity for a predetermined target from said population.