The invention provides FGFR fusion proteins, methods of making them, and methods of using them to treat proliferative disorders, including cancers and disorders of angiogenesis. The FGFR fusion molecules can be made in CHO cells and may comprise deletion mutations in the extracellular domains of the FGFRs which improve their stability. These fusion proteins inhibit the growth and viability of cancer cells in vitro and in vivo. The combination of the relatively high affinity of these receptors for their ligand FGFs and the demonstrated ability of these decoy receptors to inhibit tumor growth is an indication of the clinical value of the compositions and methods provided herein.

The invention provides FGFR fusion proteins, methods of making them, and methods of using them to treat proliferative disorders, including cancers and disorders of angiogenesis. The FGFR fusion molecules can be made in CHO cells and may comprise deletion mutations in the extracellular domains of the FGFRs which improve their stability. These fusion proteins inhibit the growth and viability of cancer cells in vitro and in vivo. The combination of the relatively high affinity of these receptors for their ligand FGFs and the demonstrated ability of these decoy receptors to inhibit tumor growth is an indication of the clinical value of the compositions and methods provided herein.

The present invention provides to a bispecific single chain antibody construct binding to a target cell surface antigen via a first binding domain and to the T cell surface antigen CD3 via a second binding domain, wherein serum albumin is fused to the C-terminus of the antibody construct. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

The present invention provides to a bispecific single chain antibody construct binding to a target cell surface antigen via a first binding domain and to the T cell surface antigen CD3 via a second binding domain, wherein serum albumin is fused to the C-terminus of the antibody construct. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

The present invention describes a simple purification process for recombinant human serum albumin. The process results in highly purified protein with limited number of purification steps. The broth containing human albumin is clarified by centrifugation and microfiltration, diafiltered and captured by cation exchange chromatography by a process that allows 140-230 mg of albumin to be captured per mi of resin. Product related impurities are removed by hydrophobic interaction chromatography, optimised to allow 87-97% recovery in flow through mode. The final series of processes are so combined that there is easy transition from one step to the next with minimal interventions and adjustments. The entire process of purification is completed within two days from harvest to final product. Thus a cost-effective process with improved recovery of protein at each step is developed. The purified human serum albumin is analyzed for purity and shows physicochemical characteristics that are similar to standard albumin.

The present invention describes a simple purification process for recombinant human serum albumin. The process results in highly purified protein with limited number of purification steps. The broth containing human albumin is clarified by centrifugation and microfiltration, diafiltered and captured by cation exchange chromatography by a process that allows 140-230 mg of albumin to be captured per mi of resin. Product related impurities are removed by hydrophobic interaction chromatography, optimised to allow 87-97% recovery in flow through mode. The final series of processes are so combined that there is easy transition from one step to the next with minimal interventions and adjustments. The entire process of purification is completed within two days from harvest to final product. Thus a cost-effective process with improved recovery of protein at each step is developed. The purified human serum albumin is analyzed for purity and shows physicochemical characteristics that are similar to standard albumin.

A chromatography device for removing a solute from a fluid is provided. The device has a first plate having an inlet and a first channel. The first channel directs the fluid from the inlet towards chromatographic media housed in a chamber coupled to the first plate. The chamber has a leading edge for receiving the fluid from the first channel and a trailing edge for delivering the fluid to a second channel. The chromatographic media is configured to remove the solute from the fluid as the fluid passes through the chamber. The device also has a second plate coupled to the chamber having the second channel and an outlet. The second channel directs the fluid from the chamber to the outlet. The direction of flow of fluid through the first channel and the second channel is transverse to a direction of flow of the fluid through the chromatographic media. A method of removing a solute from a fluid is also provided.

A chromatography device for removing a solute from a fluid is provided. The device has a first plate having an inlet and a first channel. The first channel directs the fluid from the inlet towards chromatographic media housed in a chamber coupled to the first plate. The chamber has a leading edge for receiving the fluid from the first channel and a trailing edge for delivering the fluid to a second channel. The chromatographic media is configured to remove the solute from the fluid as the fluid passes through the chamber. The device also has a second plate coupled to the chamber having the second channel and an outlet. The second channel directs the fluid from the chamber to the outlet. The direction of flow of fluid through the first channel and the second channel is transverse to a direction of flow of the fluid through the chromatographic media. A method of removing a solute from a fluid is also provided.

This application provides the first observation of methylmalonylation/malonylation in organic acidemias (OAs), such as methylmalonic acidemia (MMA) and propionic acidemia (PA), which results in modification of enzymes in key pathways dysregulated in OAs, including sirtuin 5 (SIRT5). Hyperacylation of SIRT5 prevents it from de-acylating CPS1 (including removing methymalonyllation), which prevents activation of CPS1 and likewise, inhibits a key component of the glycine cleavage system, GCSH. Based on these observations, provided herein is a mutant form of SIRT5 containing four mutated lysines that cannot accept acyl groups, methods of its use for treating OA patients, and kits.

This application provides the first observation of methylmalonylation/malonylation in organic acidemias (OAs), such as methylmalonic acidemia (MMA) and propionic acidemia (PA), which results in modification of enzymes in key pathways dysregulated in OAs, including sirtuin 5 (SIRT5). Hyperacylation of SIRT5 prevents it from de-acylating CPS1 (including removing methymalonyllation), which prevents activation of CPS1 and likewise, inhibits a key component of the glycine cleavage system, GCSH. Based on these observations, provided herein is a mutant form of SIRT5 containing four mutated lysines that cannot accept acyl groups, methods of its use for treating OA patients, and kits.