CT-P39 Compared With Reference Omalizumab in Chronic Spontaneous Urticaria: Results From a Double-Blind, Randomized, Active-Controlled, Phase 3 Study.

Background: This study compared the therapeutic equivalence of CT-P39 (an omalizumab biosimilar) and EU-approved reference omalizumab (ref-OMA) in patients with chronic spontaneous urticaria.

Methods: This double-blind, randomized, active-controlled Phase 3 study (NCT04426890) included two 12-week treatment periods (TPs). In TP1, patients received CT-P39 300 mg, ref-OMA 300 mg, CT-P39 150 mg, or ref-OMA 150 mg.

Biosimilar Candidate CT-P42 in Diabetic Macular Edema: 24-Week Results from a Randomized, Active-Controlled, Phase III Study.

Objective: To demonstrate the therapeutic similarity of CT-P42 compared with reference aflibercept (Eylea) in adult patients with diabetic macular edema (DME).

Design: Randomized, active-controlled, double-masked, phase III clinical trial PARTICIPANTS: Patients with a diagnosis of either type 1 or 2 diabetes mellitus with DME involving the center of the macula.

Methods: Patients were randomized (1:1) to receive either CT-P42 or reference aflibercept (2 mg/0.

Safety and Effectiveness of Regdanvimab for COVID-19 Treatment: A Phase 4 Post-marketing Surveillance Study Conducted in South Korea.

Introduction: Regdanvimab, a neutralising monoclonal antibody (mAb) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), received approval for the treatment of coronavirus disease 2019 (COVID-19) in South Korea in 2021. The Ministry of Food and Drug Safety in South Korea mandate that new medications be re-examined for safety and effectiveness post-approval in at least 3000 individuals. This post-marketing surveillance (PMS) study was used to evaluate the safety and effectiveness of regdanvimab in real-world clinical care.

Safety and effectiveness of intravenous CT-P13 in inflammatory arthritis: post-marketing surveillance study in Thailand.

The infliximab biosimilar CT-P13 was approved in Thailand in 2015. This open-label, multicenter, post-marketing surveillance study evaluated the safety (events of special interest [ESIs]; primary end point) and effectiveness of 46 weeks of CT-P13 treatment according to routine practice in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA), with 1 year follow-up post-treatment. 30 patients were enrolled (16 RA, 8 AS and 6 PsA).

Six-Year Survival Outcomes for Patients with HER2-Positive Early Breast Cancer Treated with CT-P6 or Reference Trastuzumab: Observational Follow-Up Study of a Phase 3 Randomised Controlled Trial.

Background: The Phase 3 CT-P6 3.2 study demonstrated equivalent efficacy and comparable safety between CT-P6 and reference trastuzumab in patients with human epidermal growth factor receptor-2 (HER2)-positive early breast cancer after up to 3 years' follow-up.

Objective: To investigate long-term survival with CT-P6 and reference trastuzumab.

A non-interventional, post-marketing surveillance study evaluating the safety and effectiveness of biosimilar rituximab (CT-P10) during routine clinical practice in the Republic of Korea.

Background: CT-P10 was the first licensed rituximab biosimilar. This Korean post-marketing surveillance study evaluated CT-P10 safety and effectiveness in approved indications.

Research Design And Methods: This prospective, open-label, observational, phase 4 study collected routine clinical practice data across 27 centers in the Republic of Korea.

Pharmacokinetic equivalence of CT-P39 and reference omalizumab in healthy individuals: A randomised, double-blind, parallel-group, Phase 1 trial.

Background: CT-P39 is being developed as a biosimilar of reference omalizumab. This study aimed to assess the pharmacokinetic equivalence of CT-P39 to European Union-approved and United States-licensed reference omalizumab (EU- and US-omalizumab, respectively).

Methods: This two-part, randomised, parallel-group, double-blind Phase 1 trial (NCT04018313) was conducted in healthy individuals with a total immunoglobulin E (IgE) level ≤100  international units (IU)/ml at screening.

Candidate Bevacizumab Biosimilar CT-P16 versus European Union Reference Bevacizumab in Patients with Metastatic or Recurrent Non-Small Cell Lung Cancer: A Randomized Controlled Trial.

Background: CT-P16 is a candidate bevacizumab biosimilar.

Objective: This double-blind, multicenter, parallel-group, phase III study aimed to establish equivalent efficacy between CT-P16 and European Union-approved reference bevacizumab (EU-bevacizumab) in patients with metastatic or recurrent non-squamous non-small cell lung cancer (nsNSCLC).

Patients And Methods: Patients with stage IV or recurrent nsNSCLC were randomized (1:1) to receive CT-P16 or EU-bevacizumab (15 mg/kg every 3 weeks; ≤ 6 cycles) with paclitaxel (200 mg/m) and carboplatin (area under the curve 6.

Long-term efficacy and safety of CT-P10 or rituximab in untreated advanced follicular lymphoma: a randomized phase 3 study.

Rituximab biosimilars are a cornerstone of treatment of advanced-stage follicular lymphoma (FL). This double-blind, parallel-group, phase 3 trial randomized (1:1) adults (≥18 years) with stage III to IV indolent B-cell lymphoma, including grades 1 to 3a FL, to receive CT-P10 or rituximab (375 mg/m2 IV), with cyclophosphamide, vincristine, and prednisone, every 3 weeks for 8 cycles (induction period). Patients achieving complete response (CR), unconfirmed CR, or partial response (PR) received CT-P10 or rituximab maintenance for 2 years (375 mg/m2, every 8 weeks).

Adjuvant effect of B domain of staphyloccocal protein A displayed on the surface of hepatitis B virus capsid.

The hepatitis B virus (HBV) capsid-based recombinant particles, which display both major hydrophilic region of HBV surface antigen (HBV-MHR) and B domain of Staphylococcal protein A (SPAB ), were produced using Escherichia coli as expression host. SPAB was used as an adjuvant to elicit the immune response to HBV-MHR, and its adjuvant effect in the immunized mice was estimated with varying the position and amount of SPAB on the HBV capsid particles. Compared to the emulsified aluminum gel (alum gel) that is a currently commercialized vaccine adjuvant, SPAB caused the significantly higher level of anti-HBV immunoglobulin G (IgG) titer and seroconversion rate, and notably SPAB at the most surface-exposed position on the recombinant particle led to the highest immune response.

Self-assembled proteinticle nanostructures for 3-dimensional display of antibodies.

"Proteinticle" is a nano-scale protein particle that is self-assembled inside cells with constant 3D structure and surface topology. The binding of IgG to the B domain of Staphylococcal protein A (SPA(B)) molecules that are genetically inserted on the surface of proteinticle enables the variable domains of bound IgG to be well oriented to effectively capture antigens, accordingly forming a highly sensitive 3D IgG probe. The five different proteinticles that originate from humans, bacteria, and virus and totally differ in size, shape, and surface structure were used for the surface display of SPA(B).

Synthesis of Mycoplasma arginine deiminase in E. coli using stress-responsive proteins.

We found Escherichia coli proteins, elongation factor Ts (Tsf), and malate dehydrogenase (Mdh) that can exist in the form of native and soluble proteins even under stress situation such as heat shock and protein denaturing condition. To examine their property as solubility enhancers, aggregation-prone Mycoplasma arginine deiminase (mADI), which has been suggested as anti-cancer agent, was fused to the C-terminal of each of them and cloned into pET28a to be expressed in the E. coli cytoplasm.

Engineered protein nanoparticles for in vivo tumor detection.

Two different protein nanoparticles that are totally different in shape and surface structure, i.e. Escherichia coli DNA-binding protein (eDPS) (spherical, 10 nm) and Thermoplasma acidophilum proteasome (tPTS) (cylindrical, 12 × 15 nm) were engineered for in vivo optical tumor detection: arginine-glycine-aspartic acid (RGD) peptide (CDCRGDCFC) was genetically inserted to the surface of each protein nanoparticle, and also near-infrared fluorescence dye was chemically linked to the surface lysine residues.

A simple one-step assay platform based on fluorescence quenching of macroporous silicon.

We synthesized 3D macroporous silicon through a simple electrochemical dissolution process and systematically estimated its protein adsorption and effect on fluorescence emission. Compared with conventional 2D polystyrene plate, the macroporous silicon showed a superior protein adsorption capacity and significant fluorescence quenching effect. We developed a 3D macroporous silicon-based adenosine assay system through the following fabrication process: streptavidin molecules that have been immobilized on the surface of macroporous silicon are attached with biotin-linked and adenosine-specific DNA aptamer, followed by hybridization between the attached aptamer and fluorescent chemical (carboxytetramethylrhodamine/CTMR) that is conjugated with a short complementary DNA sequence.

YrhB is a highly stable small protein with unique chaperone-like activity in Escherichia coli BL21(DE3).

Escherichia coli YrhB (10.6 kDa) from strain BL21(DE3) that is commonly used for protein overexpression is a stable chaperone-like protein and indispensable for supporting the growth of BL21(DE3) at 48 °C but not defined as conventional heat shock protein (HSP). YrhB effectively prevented heat-induced aggregation of ribonucleotide synthetase (PurK).

A sensitive diagnostic assay of rheumatoid arthritis using three-dimensional ZnO nanorod structure.

We synthesized a three-dimensional nanorod structure of zinc oxide (ZnO) using a simple sol-gel process and systematically investigated properties of the ZnO nanorods regarding protein adsorption and effect on fluorescence emission. As compared to conventional polystyrene plate that has been widely used for strong protein adsorption, the ZnO nanorods had a superior protein adsorption capacity and significantly amplified fluorescence emission, suggesting the ZnO nanorods are attractive for fluorescence-based biomolecular detection assays. When applied to diagnostic assay of rheumatoid arthritis (RA) using cyclic citrullinated peptide (CCP) probe with a RCGRS motif that reportedly has a strong affinity for ZnO, the ZnO nanorods gave apparently high positive signals for all the RA-positive standards and patient sera, whereas upon the detection using conventional polystyrene plate, all the detection signals were relatively negligible.

Fluorescent ferritin nanoparticles and application to the aptamer sensor.

We synthesized fluorescent ferritin nanoparticles (FFNPs) through bacterial expression of the hybrid gene consisting of human ferritin heavy chain (hFTN-H), spacer (glycine-rich peptide), and enhanced green (or red) fluorescent protein [eGFP (or DsRed)] genes. The self-assembly activity of hFTN-H that leads to the formation of nanoparticles (12 nm in diameter), the conformational flexibility of the C-terminus of hFTN-H, and the glycine-rich spacer enabled eGFPs (or DsReds) to be well displayed on the surface of each ferritin nanoparticle, resulting in the construction of green (or red) FFNPs [gFFNPs (or rFFNPs)]. As compared to eGFP (or DsRed) alone, it is notable that the developed FFNPs showed significantly amplified fluorescence intensity and also enhanced stability.

Lyophilization and enhanced stability of fluorescent protein nanoparticles.

Protein nanoparticles (PNPs) that are nanostructured biomaterials with intrinsic biological function have been widely employed as three-dimensional nanobiomaterials for sensitive bioassays, MRI contrast, semiconductor devices, template for hybrid materials, etc., and stable and long-term maintenance of PNPs seems to be of crucial importance. We evaluated the stability of PNPs and the efficacy of lyophilization for the long-term stability of PNPs, especially using green fluorescent protein nanoparticles (gFPNPs) as a model PNP.

Human G-CSF synthesis using stress-responsive bacterial proteins.

We previously reported that under the stress condition caused by the addition of 2-hydroxyethyl disulfide, a thiol-specific oxidant, to growing cultures of Escherichia coli BL21(DE3), a population of stress-responsive proteins [peptidyl-prolyl cis-trans isomerase B (PpiB), bacterioferritin (Bfr), putative HTH-type transcriptional regulator yjdC (YjdC), dihydrofolate reductase (FolA), chemotaxis protein cheZ (CheZ), and glutathione synthetase (GshB)] were significantly upregulated when compared with the nonstress condition. When those stress-responsive proteins were used as fusion partners for the expression of human granulocyte colony-stimulating factor (hG-CSF), the solubility of hG-CSF was dramatically enhanced in E. coli cytoplasm, whereas almost all of the directly expressed hG-CSF were aggregated to inclusion bodies.

A highly sensitive and selective diagnostic assay based on virus nanoparticles.

Early detection of the protein marker troponin I in patients with a higher risk of acute myocardial infarction can reduce the risk of death from heart attacks. Most troponin assays are currently based on the conventional enzyme linked immunosorbent assay and have detection limits in the nano- and picomolar range. Here, we show that by combining viral nanoparticles, which are engineered to have dual affinity for troponin antibodies and nickel, with three-dimensional nanostructures including nickel nanohairs, we can detect troponin levels in human serum samples that are six to seven orders of magnitude lower than those detectable using conventional enzyme linked immunosorbent assays.

Multiple stressor-induced proteome responses of Escherichia coli BL21(DE3).

Through 2-DE based quantitative proteomics, the dynamic characteristics of overall proteome profiles of Escherichia coli BL21(DE3) were systematically analyzed in the presence of four different stressors. Dithiothreitol and 2-hydroxyethyl disulfide are a reducing and an oxidizing agent, respectively, which disturb the redox balance in cytoplasm, while guanidine hydrochloride and heat shock are protein denaturants influencing protein folding. Heat shock proteins/foldases, transcription/translation-related proteins, various metabolic enzymes, and other stress regulatory proteins were found to be significantly up-regulated in response to the stressors.

Solubility enhancement of aggregation-prone heterologous proteins by fusion expression using stress-responsive Escherichia coli protein, RpoS.

Background: The most efficient method for enhancing solubility of recombinant proteins appears to use the fusion expression partners. Although commercial fusion partners including maltose binding protein and glutathione-S-transferase have shown good performance in enhancing the solubility, they cannot be used for the proprietory production of commercially value-added proteins and likely cannot serve as universal helpers to solve all protein solubility and folding issues. Thus, novel fusion partners will continue to be developed through systematic investigations including proteome mining presented in this study.

Transport proteins PotD and Crr of Escherichia coli, novel fusion partners for heterologous protein expression.

The Escherichia coli proteome response to the stressor GdnHCl was analyzed through 2-dimensional gel electrophoresis (2-DE). We identified PotD (spermidine/putrescine-binding periplasmic protein) and Crr [glucose-specific phosphotransferase (PTS) enzyme IIA component] as a stress-responsive protein. Even under a stress situation where the total number of soluble proteins decreased by about 10%, 3.