A5054887519- HER2/EGFR in Cancer Research
- Cancer Treatment and Pharmacology
- Angiogenesis and VEGF in Cancer
- Monoclonal and Polyclonal Antibodies Research
- Biosimilars and Bioanalytical Methods
- Protein purification and stability
- Advanced Biosensing Techniques and Applications
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- GDF15 and Related Biomarkers
- Nutrition and Health in Aging
- Glycosylation and Glycoproteins Research
- Immune Cell Function and Interaction
- Psoriasis: Treatment and Pathogenesis
- Nuclear Receptors and Signaling
- SARS-CoV-2 and COVID-19 Research
- Respiratory viral infections research
- Microscopic Colitis
- Inflammatory Bowel Disease
- COVID-19 Clinical Research Studies
- Peptidase Inhibition and Analysis
- Cell Adhesion Molecules Research
- Integrated Circuits and Semiconductor Failure Analysis
- Computational Drug Discovery Methods
- Heparin-Induced Thrombocytopenia and Thrombosis
Johnson & Johnson (United States)
2012-2025
Springhouse
2022-2024
Janssen (United States)
2013-2024
University at Buffalo, State University of New York
2018
Janssen (Belgium)
2013
Therapeutics Clinical Research
2013
The near impermeability of the blood-brain barrier (BBB) and unique neuroimmune environment CNS prevents effective use antibodies in neurological diseases. Delivery biotherapeutics to brain can be enabled through receptor-mediated transcytosis via proteins such as transferrin receptor, although limitations ability Fc-mediated effector function clear pathogenic targets introduce safety liabilities. Hence, novel delivery approaches with alternative clearance mechanisms are warranted.Binders...
T cell-redirecting bispecific antibodies (bsAbs) to treat advanced stage solid tumors are gaining interest after recent clinical successes. The immune checkpoint human leukocyte antigen G (HLA-G) is expressed in several tumor types while normal tissues expression limited. Here, we describe JNJ-78306358, a antibody (bsAb) tumors. JNJ-78306358 binds with high affinity the α3 subunit of HLA-G on cancer cells and purposely engineered weaker CD3ε cells. induced potent cell-mediated cytotoxicity...
Abstract The analysis of Non-Liquid Matrices (NLMs) can provide key information on many aspects in drug discovery and development. These include but are not limited to uptake distribution, engagement modulation, target exposure. A thorough understanding these is fundamental the progression In cases, such an only be achieved through quantitative NLMs. Such dependence lead bottlenecks development process—as practices regulations that govern bioanalysis conventional liquid matrices typically...
The effective management of validated ligand-binding assays used for PK, PD and immunogenicity assessments biotherapeutics is vital to ensuring robust consistent assay performance throughout the lifetime method. structural integrity functional quality critical reagents often linked performance; therefore, physicochemical biophysical characterization coupled with assessment can enable highest degree reagent quality. implementation a systematic process monitoring attributes, utilizing detailed...
The interleukin (IL)-23/T<sub>h</sub>17/IL-17 immune pathway has been identified to play an important role in the pathogenesis of psoriasis. Many therapeutic proteins targeting IL-23 or IL-17 are currently under development for treatment In present study, a mechanistic pharmacokinetics (PK)/pharmacodynamics (PD) study was conducted assess target-binding and disposition kinetics monoclonal antibody (mAb), CNTO 3723, its soluble target, mouse IL-23, IL-23-induced psoriasis-like model. A...
Abstract Growth Differentiation Factor‐15 (GDF15) is a circulating polypeptide linked to cellular stress and metabolic adaptation. GDF15's half‐life ~3 h activates the glial cell line‐derived neurotrophic factor family receptor alpha‐like (GFRAL) expressed in area postrema. To characterize sustained GFRAL agonism on food intake (FI) body weight (BW), we tested extended analog of GDF15 (Compound H [CpdH]) suitable for reduced dosing frequency obese cynomolgus monkeys. Animals were chronically...
Tumor necrosis factor (TNF) and interleukin (IL)-17A are pleiotropic cytokines implicated in the pathogenesis of several autoimmune diseases including rheumatoid arthritis (RA) psoriatic (PsA). JNJ-61178104 is a novel human anti-TNF anti-IL-17A monovalent, bispecific antibody that binds to both TNF IL-17A with high affinities blocks binding their receptors vitro. also potently neutralizes IL-17A-mediated downstream effects multiple cell-based assays. In vivo, treatment resulted...
Antibody-drug conjugates (ADC) have shown impressive clinical activity with approval of many agents in hematologic and solid tumors. However, challenges remain both efficacy safety ADCs. This study describes novel trastuzumab-auristatin the hydrophilic monomethylauristatin E (MMAE) prodrug MMAU, optimization a glycopeptide linker leading to wider therapeutic window. Trastuzumab was conjugated auristatin payloads via series linkers using stabilized maleimide handle. The ADCs were...
Mucosal immunity is dominated by secretory IgA and IgM, although these are less favorable compared to IgG molecules for therapeutic development. Polymeric IgM actively transported across the epithelial barrier via engagement of polymeric Ig receptor (pIgR), but lack a lumen-targeted active transport mechanism, resulting in poor biodistribution therapeutics mucosal tissues. In this work, we describe discovery characterization single-domain antibodies (VHH) that engage pIgR undergo...
The global health crisis and economic tolls of COVID-19 necessitate a panoply strategies to treat SARS-CoV-2 infection. To date, few treatment options exist, although neutralizing antibodies against the spike glycoprotein have proven be effective. Because infection is initiated at mucosa propagates mainly this site throughout course disease, blocking virus mucosal milieu should However, administration biologics presents substantial challenge. Here, we describe bifunctional molecules...
ABSTRACT Biotherapeutic drugs against tumor necrosis factor (TNF) are effective treatments for moderate to severe inflammatory bowel disease (IBD). Here, we evaluated CNTO 5048, an antimurine TNF surrogate monoclonal antibody (mAb), in a CD45RBhigh adoptive T cell transfer mouse colitis model, which allows examination of the early immunological events associated with gut inflammation and therapeutic effects. The study was designed quantitatively understand effects IBD on 5048 disposition,...
Therapeutic monoclonal antibodies (mAbs) possess a high degree of heterogeneity associated with the cell expression system employed in manufacturing, most notably glycosylation. Traditional immunoassay formats used to quantify therapeutic mAbs are unable discriminate between different glycosylation patterns that may exist on same protein amino acid sequence. Mass spectrometry provides technique distinguish specific antibody within sample, thereby allowing for simultaneous quantification mAb...
Abstract JNJ-78306358 is a first-in-class bispecific antibody (bsAb), engineered using the Zymeworks Azymetric™ platform, to treat advanced stage solid tumors. Human leukocyte antigen G (HLA-G) non-classical major histocompatibility class I molecule with an immune tolerance role at maternal-fetal interface. HLA-G has limited normal tissue expression, mainly detected in placenta and pituitary gland. However, expressed multiple human cancers, potential cancer evasion. Comprehensive...
Aim: Meso Scale Discovery U-PLEX® provides an opportunity to develop multiplexed pharmacokinetic (PK) immunoassays. Two case studies demonstrate the utility of PK methods. Materials & methods: Development ligand-binding assays quantify nonclinical plasma concentrations a biotherapeutic that has degraded due in vivo biotransformation, and clinical serum from two biotherapeutics spiked into single sample. Results: Data U-PLEX methods are comparable results single-readout streptavidin gold...
Background and Purpose Antigen‐binding fragment (F ab ) reversal agents were developed to reverse, in bleeding emergency, the long‐acting anticoagulant effect of JNJ‐64179375 (JNJ‐9375), a monoclonal antibody that binds exosite‐1 on thrombin. Experimental Approach The pharmacokinetic pharmacodynamic (PK/PD) activities three varying vitro binding affinities JNJ‐9375 characterised cynomolgus monkeys. time course activity effects each agent evaluated. A mechanism‐based PK/PD model, which...
<div>Abstract<p>Antibody–drug conjugates (ADC) have shown impressive clinical activity with approval of many agents in hematologic and solid tumors. However, challenges remain both efficacy safety ADCs. This study describes novel trastuzumab–auristatin the hydrophilic monomethylauristatin E (MMAE) prodrug MMAU, optimization a glycopeptide linker leading to wider therapeutic window. Trastuzumab was conjugated auristatin payloads via series linkers using stabilized maleimide...
<p>Digestion of lintuzumab-mavg-MMAU DAR8 by cynomolgus monkey liver microsomes at pH 4.5.</p>
<p>Characterization of DAR4 ADCs.</p>
<p>ADC in vitro activity against cancer cell lines with different HER2 expression levels.</p>
<p>Lysosomal degradation of T-mcvc-MMAE DAR4 and T-mavg-MMAU DAR8.</p>