Developability studies before initiation of process development: improving manufacturability of monoclonal antibodies.

abstract：:The development of antibody therapeutics relies on animal models that accurately recapitulate disease biology. Syngeneic mouse models are increasingly used with new molecules to capture the biology of complex cancers and disease states, and to provide insight into the role of the immune system. The establishment of sy...

journal_title：mAbs

authors： Wang F,Tsai JC,Davis JH,Chau B,Dong J,West SM,Hogan JM,Wheeler ML,Bee C,Morishige W,Cayton T,David-Brown D,Zhang C,Kozhich A,Sproul T,Dollinger G,Rajpal A,Strop P

更新日期：2020-01-01 00:00:00

abstract：:Monoclonal antibodies are widely used for the treatment of cancer, inflammatory and infectious diseases and other disorders. Most of the marketed antibodies are monospecific and therefore capable of interacting and interfering with a single target. However, complex diseases are often multifactorial in nature, and invo...

journal_title：mAbs

authors： Kontermann RE

更新日期：2012-03-01 00:00:00

abstract：:Despite availability of biologic therapies, limited patient access to many of the most-effective cancer treatments affects overall health outcomes. To address this issue, many governments have enacted legislation for the approval of biosimilars. The term "biosimilar" refers to a biologic product that is developed to b...

journal_title：mAbs

authors： Socinski MA,Curigliano G,Jacobs I,Gumbiner B,MacDonald J,Thomas D

更新日期：2015-01-01 00:00:00

abstract：:Bispecific antibody therapeutics can expand the functionality of a conventional monoclonal antibody drug because they can bind multiple antigens. However, their great potential is counterbalanced by the challenges faced in their production. The classic asymmetric bispecific containing an Fc requires the expression of ...

journal_title：mAbs

authors： Cooke HA,Arndt J,Quan C,Shapiro RI,Wen D,Foley S,Vecchi MM,Preyer M

更新日期：2018-11-01 00:00:00

abstract：:Given the increasing use of combination therapy with multiple monoclonal antibodies (mAbs), there is a clinical need for multiplexing assays. For the frequently co-administered anti-human epidermal growth factor receptor 2 (HER2) mAbs trastuzumab and pertuzumab, we developed a high-throughput and robust hybrid ligand-...

journal_title：mAbs

authors： Schokker S,Fusetti F,Bonardi F,Molenaar RJ,Mathôt RAA,van Laarhoven HWM

更新日期：2020-01-01 00:00:00

abstract：:The cervical mucosa of women who are highly exposed to HIV-1, yet remain persistently seronegative (HEPS), presents a unique opportunity to study the dynamics of an immune compartment potentially capable of preventing HIV-1 infection. Herein, we provide a detailed characterization of the immunoglobulin repertoire of c...

journal_title：mAbs

authors： Gaudet RG,Breden F,Plummer F,Berry JD

更新日期：2011-03-01 00:00:00

abstract：:One aspiration for the formulation of human monoclonal antibodies (mAb) is to reach high solution concentrations without compromising stability. Protein surface activity leading to instability is well known, but our understanding of mAb adsorption to the solid-liquid interface in relevant pH and surfactant conditions ...

journal_title：mAbs

authors： Couston RG,Skoda MW,Uddin S,van der Walle CF

更新日期：2013-01-01 00:00:00

abstract：:Certolizumab pegol (Cimzia(®)) is currently the only PEGylated anti-TNFα biologic approved for the treatment of rheumatoid arthritis and Crohn disease. The product, developed by UCB, is a humanized antigen-binding fragment (Fab') of a monoclonal antibody that has been conjugated to polyethylene glycol. Certolizumab pe...

journal_title：mAbs

authors： Goel N,Stephens S

更新日期：2010-03-01 00:00:00

abstract：:Antibody engineering must be accompanied by mapping strategies focused on identifying the epitope recognized by each antibody to define its unique functional identity. High throughput fine specificity determination remains technically challenging. We review recent experiences aimed at revisiting the oldest and most ex...

journal_title：mAbs

authors： Rojas G,Tundidor Y,Infante YC

更新日期：2014-01-01 00:00:00

abstract：:Monoclonal antibodies are used with great success in many different therapeutic domains. In order to satisfy the growing demand and to lower the production cost of these molecules, many alternative systems have been explored. Among them, the baculovirus/insect cells system is a good candidate. This system is very safe...

journal_title：mAbs

authors： Cérutti M,Golay J

更新日期：2012-05-01 00:00:00

abstract：:Process intensification has shown great potential to increase productivity and reduce costs in biomanufacturing. This case study describes the evolution of a manufacturing process from a conventional processing scheme at 1000-L scale (Process A, n = 5) to intensified processing schemes at both 1000-L (Process B, n = 8...

journal_title：mAbs

authors： Xu J,Xu X,Huang C,Angelo J,Oliveira CL,Xu M,Xu X,Temel D,Ding J,Ghose S,Borys MC,Li ZJ

更新日期：2020-01-01 00:00:00

abstract：:Glycosylation is an important post-translational modification during protein production in eukaryotic cells, and it is essential for protein structure, stability, half-life, and biological functions. In this study, we produced various monoclonal antibody (mAb) glycoforms from Chinese hamster ovary (CHO) cells, includi...

journal_title：mAbs

authors： Zheng K,Yarmarkovich M,Bantog C,Bayer R,Patapoff TW

更新日期：2014-05-01 00:00:00

abstract：:Blockade of immune checkpoint pathways by programmed cell death protein 1 (PD-1) antibodies has demonstrated broad clinical efficacy against a variety of malignancies. Sintilimab, a highly selective, fully human monoclonal antibody (mAb), blocks the interaction of PD-1 and its ligands and has demonstrated clinical ben...

journal_title：mAbs

authors： Wang J,Fei K,Jing H,Wu Z,Wu W,Zhou S,Ni H,Chen B,Xiong Y,Liu Y,Peng B,Yu D,Jiang H,Liu J

更新日期：2019-11-01 00:00:00

abstract：:There are currently ~25 recombinant full-length IgGs (rIgGs) in the market that have been approved by regulatory agencies as biotherapeutics to treat various human diseases. Most of these are based on IgG1k framework and are either chimeric, humanized or human antibodies manufactured using either Chinese hamster ovary...

journal_title：mAbs

authors： Raju TS,Jordan RE

更新日期：2012-05-01 00:00:00

abstract：:CD4(+) CD25(+) regulatory T cells are expanded in solid and hematological malignancies including chronic lymphocytic leukemia (CLL). Several cytokines and co-stimulatory molecules are required for generation, survival and maintenance of their suppressive effect. We and others have shown direct cytotoxic effect of the ...

journal_title：mAbs

authors： Gowda A,Ramanunni A,Cheney C,Rozewski D,Kindsvogel W,Lehman A,Jarjoura D,Caligiuri M,Byrd JC,Muthusamy N

更新日期：2010-01-01 00:00:00

abstract：:High titer (>10 g/L) monoclonal antibody (mAb) cell culture processes are typically achieved by maintaining high viable cell densities over longer culture durations. A corresponding increase in the solids and sub-micron cellular debris particle levels are also observed. This higher burden of solids (≥15%) and sub-micr...

journal_title：mAbs

authors： McNerney T,Thomas A,Senczuk A,Petty K,Zhao X,Piper R,Carvalho J,Hammond M,Sawant S,Bussiere J

更新日期：2015-01-01 00:00:00

abstract：:Immunotherapy approaches for Alzheimer disease currently are among the leading therapeutic directions for the disease. Active and passive immunotherapy against the beta-amyloid peptides that aggregate and accumulate in the brain of those afflicted by the disease have been shown by numerous groups to reduce plaque path...

journal_title：mAbs

authors： Gouras GK

更新日期：2009-03-01 00:00:00

abstract：:Glycosylation is a critical attribute for development and manufacturing of therapeutic monoclonal antibodies (mAbs) in the pharmaceutical industry. Conventional antibody glycan analysis is usually achieved by the 2-aminobenzamide (2-AB) hydrophilic interaction liquid chromatography (HILIC) method following the release...

journal_title：mAbs

authors： Yang X,Kim SM,Ruzanski R,Chen Y,Moses S,Ling WL,Li X,Wang SC,Li H,Ambrogelly A,Richardson D,Shameem M

更新日期：2016-05-01 00:00:00

abstract：:Complex cellular targets such as G protein-coupled receptors (GPCRs), ion channels, and other multi-transmembrane proteins represent a significant challenge for therapeutic antibody discovery, primarily because of poor stability of the target protein upon extraction from cell membranes. To assess whether a limited set...

journal_title：mAbs

authors： Scott MJ,Jowett A,Orecchia M,Ertl P,Ouro-Gnao L,Ticehurst J,Gower D,Yates J,Poulton K,Harris C,Mullin MJ,Smith KJ,Lewis AP,Barton N,Washburn ML,de Wildt R

更新日期：2020-01-01 00:00:00

abstract：:The advantages of site-specific over stochastic bioconjugation technologies include homogeneity of product, minimal perturbation of protein structure/function, and - increasingly - the ability to perform structure activity relationship studies at the conjugate level. When selecting the optimal location for site-specif...

journal_title：mAbs

authors： Huang BCB,Kim YC,Bañas S,Barfield RM,Drake PM,Rupniewski I,Haskins WE,Rabuka D

更新日期：2018-11-01 00:00:00

abstract：:Tandem single-chain variable fragment (scFv) bispecific antibodies (bsAb) are one of the most promising bsAb formats reported thus far. Yet, because of their increased aggregation propensity, high impurity content due to low expression level, smaller size and lack of the Fc region, it is challenging to isolate these p...

journal_title：mAbs

authors： Chen SW,Tan D,Yang YS,Zhang W

更新日期：2020-01-01 00:00:00

abstract：:Genomic studies have been revolutionized by the use of next generation sequencing (NGS) that delivers huge amounts of sequence information in a short span of time. The number of applications for NGS is rapidly expanding and significantly transforming many areas of life sciences. The field of antibody research and disc...

journal_title：mAbs

authors： Fischer N

更新日期：2011-01-01 00:00:00

abstract：:During the past two decades we have seen a phenomenal evolution of bispecific antibodies for therapeutic applications. The 'zoo' of bispecific antibodies is populated by many different species, comprising around 100 different formats, including small molecules composed solely of the antigen-binding sites of two antibo...

journal_title：mAbs

authors： Brinkmann U,Kontermann RE

更新日期：2017-02-01 00:00:00

abstract：:Currently, almost all FDA approved therapeutic antibodies (except ReoPro, Lucentis and Cimzia which are Fabs), and the vast majority of those in clinical trials are full-size antibodies mostly in IgG1 format of about 150 kDa size. A fundamental problem for such large molecules is their poor penetration into tissues (e...

journal_title：mAbs

authors： Dimitrov DS

更新日期：2009-01-01 00:00:00

abstract：:An immunotoxin (IT) constructed with RFB4, a murine anti-CD22 monoclonal antibody, and the "deglycosylated" A chain of ricin has shown activity at safe doses in patients with non-Hodgkin lymphoma and in children with acute lymphoblastic leukemia. The dose limiting toxicity is vascular leak syndrome (VLS), which appear...

journal_title：mAbs

authors： Liu XY,Pop LM,Schindler J,Vitetta ES

更新日期：2012-01-01 00:00:00

abstract：:Optimization of biophysical properties is a critical success factor for the developability of monoclonal antibodies with potential therapeutic applications. The inter-domain disulfide bond between light chain (Lc) and heavy chain (Hc) in human IgG1 lends structural support for antibody scaffold stability, optimal anti...

journal_title：mAbs

authors： Shen Y,Zeng L,Zhu A,Blanc T,Patel D,Pennello A,Bari A,Ng S,Persaud K,Kang YK,Balderes P,Surguladze D,Hindi S,Zhou Q,Ludwig DL,Snavely M

更新日期：2013-05-01 00:00:00

abstract：:The importance of antibodies in activating immune responses against tumors is now better appreciated with the emergence of checkpoint blockade antibodies and with engineered antibody Fc domains featuring enhanced capacity to focus potent effector cells against cancer cells. Antibodies designed with Fc regions of the I...

journal_title：mAbs

authors： Josephs DH,Spicer JF,Karagiannis P,Gould HJ,Karagiannis SN

更新日期：2014-01-01 00:00:00

abstract：:A mono-specific antibody may recruit a second antigen binding specificity, thus converting to a dual-specific Two-in-One antibody through mutation at the light chain complementarity-determining regions (CDRs). It is, however, unknown whether mutation at the heavy chain CDRs may evolve such dual specificity. Herein, we...

journal_title：mAbs

authors： Lee CV,Koenig P,Fuh G

更新日期：2014-05-01 00:00:00

abstract：:Although extensively studied, protein-protein interactions remain highly elusive and are of increasing interest in drug development. We show the assembly of a monoclonal antibody, using multivalent carboxylate ions, into highly-ordered structures. While the presence and function of similar structures in vivo are not k...

journal_title：mAbs

authors： Esue O,Xie AX,Kamerzell TJ,Patapoff TW

更新日期：2013-03-01 00:00:00

abstract：:Therapeutic antibodies continue to develop as an emerging drug class, with a need for preclinical tools to better predict in vivo characteristics. Transgenic mice expressing human neonatal Fc receptor (hFcRn) have potential as a preclinical pharmacokinetic (PK) model to project human PK of monoclonal antibodies (mAbs)...

journal_title：mAbs

authors： Avery LB,Wang M,Kavosi MS,Joyce A,Kurz JC,Fan YY,Dowty ME,Zhang M,Zhang Y,Cheng A,Hua F,Jones HM,Neubert H,Polzer RJ,O'Hara DM

更新日期：2016-08-01 00:00:00