Preclinical immunogenicity testing using anti-drug antibody analysis of GX-G3, Fc-fused recombinant human granulocyte colony-stimulating factor, in rat and monkey models.

Human granulocyte colony-stimulating factor (G-CSF, this study used Fc-fused recombinant G-CSF; GX-G3) is an important glycoprotein that stimulates the proliferation of granulocytes and white blood cells. Thus, G-CSF treatment has been considered as a crucial regimen to accelerate recovery from chemotherapy-induced neutropenia in cancer patients suffering from non-myeloid malignancy or acute myeloid leukemia. Despite the therapeutic advantages of G-CSF treatment, an assessment of its immunogenicity must be performed to determine whether the production of anti-G-CSF antibodies causes immune-related disorders.

A glycosylated Fc-fused glucagon-like peptide-1 receptor agonist exhibits equivalent glucose lowering to but fewer gastrointestinal side effects than dulaglutide.

Aim: To evaluate the pharmacokinetic and pharmacodynamic properties of a novel glycosylated Fc-fused glucagon-like peptide-1(GLP-1-gFc) receptor agonist with distinctive receptor binding affinity, designed to improve in vivo stability and safety relative to the commercial GLP-1 analogue dulaglutide, and assess its safety profile and pharmacokinetics in healthy humans.

Materials And Methods: We constructed GLP-1-gFc and determined its binding affinity and potency using in vitro instrumental and cell-based analyses followed by in vivo comparison of the glucose-lowering and gastrointestinal side effects between GLP-1-gFc and dulaglutide. A phase 1 clinical trial was conducted to confirm the efficacy and safety profile of GLP-1-gFc.

Preclinical evaluation of a biobetter candidate: Pharmacokinetics and pharmacodynamics of GX-G3 in healthy and neutropenia-induced rats.

Neutropenia is a condition of an abnormally low number of neutrophils which render patients more susceptible to infections, especially to bacterial infections, as the condition may become life threatening and deadly without prompt medical attention. Various factors such as, anticancer drugs, radiotherapy, infectious diseases, congenital defects, or vitamin B12/B9 deficiency can trigger neutropenia. GX-G3, a human hybrid (hy) Fc-fused granulocyte colony stimulating factor (G-CSF), was developed as next-generation G-CSF for the treatment of cancer therapy-induced neutropenia.

Biophysical evaluation of hybrid Fc fusion protein of hGH to achieve basal buffer system.

A newly developed hybrid Fc (hyFc) is a non-immunogenic and non-cytolytic Fc with intact Ig structure derived from human IgD and IgG4. It is fused with the human growth hormone (GXD-9) and was evaluated by various biophysical techniques. Two thermal transitions were evident by DSC, reflecting the unfolding of IgG4 and the conjugated protein.

A long-acting erythropoietin fused with noncytolytic human Fc for the treatment of anemia.

The Fc fusion technology has been introduced to generate long-acting antagonistic drugs such as Enbrel, Orencia and Amevive. Here, Genexine created a novel noncytolytic hybrid Fc (hyFc) as a carrier of agonistic protein drugs using naturally existing IgD and IgG4 Fcs without any mutation in the hyFc region. The erythropoietin (EPO) fused with hyFc exhibited little binding activity to FcγR and C1q molecules that are main mediators for death of target cells.

Natural form of noncytolytic flexible human Fc as a long-acting carrier of agonistic ligand, erythropoietin.

Human IgG1 Fc has been widely used as a bioconjugate, but exhibits shortcomings, such as antibody- and complement-mediated cytotoxicity as well as decreased bioactivity, when applied to agonistic proteins. Here, we constructed a nonimmunogenic, noncytolytic and flexible hybrid Fc (hyFc) consisting of IgD and IgG4, and tested its function using erythropoietin (EPO) conjugate, EPO-hyFc. Despite low amino acid homology (20.

Allele and genotype frequencies of CYP2C9 in a Korean population.

Aims: To determine the frequencies of the variant alleles and the genotypes of CYP2C9 in a Korean population.

Methods: Three hundred and fifty-eight healthy Korean subjects were studied. CYP2C9 alleles were detected by polymerase chain reaction-restriction fragment length polymorphism assays and direct sequencing assays.

Transdermal eperisone elicits more potent and longer-lasting muscle relaxation than oral eperisone.

Eperisone hydrochloride is widely used for the treatment of plasticity to relieve muscle stiffness and back pain. However, oral eperisone has a very low bioavailability and short muscle relaxant activity, because of the profound intestinal first-pass metabolism. To improve the efficacy and compliance of eperisone, we designed a new dosage form, a transdermal patch, and evaluated the efficacy of the eperisone patch with the muscle relaxant activity of rats.

Carbon monoxide as a novel central pyrogenic mediator.

Carbon monoxide (CO) are produced by heme oxygenase (HO), and HO was detected in hypothalamus. However, the roles of CO produced in hypothalamus was not fully elucidated. So, we tested the effects of CO on body temperature because preoptic-anterior hypothalamus was known as the presumptive primary fever-producing site.