Quality similarity-driven development of biosimilar monoclonal antibodies.

The number of approved and marketed biosimilar monoclonal antibodies has been increasing steeply in recent years in regulated markets. In contrast to small molecular generic drugs, structure and variant profile of biosimilar mAbs are not identical with those of the reference medicinal product. Biosimilarity is proven by using the "totality of evidence" approach, and it forms the basis of the approval process of biosimilars in regulated markets.

Comparative Physicochemical and Biological Characterisation of the Similar Biological Medicinal Product Teriparatide and Its Reference Medicinal Product.

Background: In January 2017, the European Commission approved Terrosa (company code RGB-10) as one of the first biosimilar medicinal products of teriparatide for the same indications as for the reference medicinal product Forsteo (Lilly France S.A.S.

Method development and qualification of capillary zone electrophoresis for investigation of therapeutic monoclonal antibody quality.

Capillary electrophoresis techniques are widely used in the analytical biotechnology. Different electrophoretic techniques are very adequate tools to monitor size-and charge heterogenities of protein drugs. Method descriptions and development studies of capillary zone electrophoresis (CZE) have been described in literature.

Capillary isoelectric focusing method development and validation for investigation of recombinant therapeutic monoclonal antibody.

Capillary isoelectric focusing (cIEF) is a basic and highly accurate routine analytical tool to prove identity of protein drugs in quality control (QC) and release tests in biopharmaceutical industries. However there are some "out-of-the-box" applications commercially available which provide easy and rapid isoelectric focusing solutions for investigating monoclonal antibody drug proteins. However use of these kits in routine testings requires high costs.

Efflux transport of serum amyloid P component at the blood-brain barrier.

Serum amyloid P component (SAP), a member of the innate immune system, does not penetrate the brain in physiological conditions; however, SAP is a stabilizing component of the amyloid plaques in neurodegenerative diseases. We investigated the cerebrovascular transport of human SAP in animal experiments and in culture blood-brain barrier (BBB) models. After intravenous injection, no SAP could be detected by immunohistochemistry or ELISA in healthy rat brains.

Serum amyloid P component induces TUNEL-positive nuclei in rat brain after intrahippocampal administration.

Serum amyloid P component (SAP)-induced neuronal apoptosis has been demonstrated on the primary culture of embryonic rat cerebral cortex in vitro. Here we present pieces of evidence that cell death is also induced by serum amyloid P component in living rat brain similarly to that in cell culture. Intrahippocampally administered SAP diffuses from the site of injection to the cortical and subcortical area of the rat brain and enters the cells of brain tissue in 1 week.

Evidence for an extended interacting surface between beta-amyloid and serum amyloid P component.

Studying the interaction between serum amyloid P component (SAP) and beta-amyloid (Abeta) a new Abeta binding site was identified on the SAP near the known binding site at the two bound calcium ions. SAP stabilizes deposits in neurodegenerative diseases, which is manifested via Abeta-binding. Because the inhibition of this interaction is a potential therapeutic target in neurodegeneration, the structural basis of SAP-Abeta binding was studied.

Flow cytometry-based method to analyze the change in Tau phosphorylation in a hGSK-3beta and hTau over-expressing EcR-293 cell line.

Neurofibrillary tangles are composed of insoluble aggregates of microtubule-associated protein Tau. In the pathology of Alzheimer's disease (AD), accumulation of hyperphosphorylated Tau results in formation of paired helical filaments. One of the main candidate to hyperphosphorylate Tau in AD is glycogen synthase kinase 3beta (GSK-3beta).

Glycosaminoglycans inhibit neurodegenerative effects of serum amyloid P component in vitro.

Serum amyloid P component, a member of pentraxin serum protein family, has been suggested to contribute to the progression of neurodegeneration including Alzheimer's disease by binding to beta-amyloid fibrils leading to an increased stability of the deposits against proteolytic degradation and by inducing neuronal apoptosis. Here, we show that glycosaminoglycans inhibit both the serum amyloid P component-beta-amyloid interaction and the neurotoxic effect of serum amyloid P component. These effects correlate with the structure of glycosaminoglycans and show different structure-activity relationship in the case of the two different effects.

Human serum amyloid P component attenuates the bacterial lipopolysaccharide-induced increase in blood-brain barrier permeability in mice.

Endotoxin challenge leads to septic shock, multi-organ failure and death in mice. Permeability of the blood-brain barrier (BBB) is increased by endotoxemia. Serum amyloid P component (SAP) is a lipopolysaccharide (LPS)-binding protein that can modulate the host reactions during infections.

Serum amyloid P component induces neuronal apoptosis and beta-amyloid immunoreactivity.

Previously we have reported serum amyloid P component (SAP) induced cell death in cerebro-cortical cultures of rat brain. In this paper we studied the types of target cells and the molecular mechanism of SAP-induced cell death. Immuno-electron and light microscopy revealed that SAP penetrates the plasma membrane and translocates selectively into the nuclei of neurons.