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#33080112   2020/10/20 To Up

A multicenter study on effectiveness and safety of risankizumab in psoriasis: an Italian 16-week real-life experience during the COVID-19 pandemic.

Risankizumab is a humanized IgG monoclonal antibody that binds with high affinity and specificity to the p19 subunit and selectively inhibits IL-23, critical for psoriatic inflammation. In phase-3 trials (UltIMMa-1, UltIMMa-2, and IMMvent) risankizumab demonstrated early and sustained efficacy at 12-week dosing in patients with moderate-to-severe psoriasis. To date, limited real-life data are available on its effectiveness and safety.
K Hansel, A Zangrilli, L Bianchi, K Peris, A Chiricozzi, A Offidani, F Diotallevi, M C Fargnoli, M Esposito, P Amerio, G Gualdi, L Bianchi, L Stingeni

1147 related Products with: A multicenter study on effectiveness and safety of risankizumab in psoriasis: an Italian 16-week real-life experience during the COVID-19 pandemic.

100ug100ug100ug Lyophilized100 μg100 μg

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#33080002   2020/10/20 To Up

Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19.

Therapies that improve survival in critically ill patients with coronavirus disease 2019 (COVID-19) are needed. Tocilizumab, a monoclonal antibody against the interleukin 6 receptor, may counteract the inflammatory cytokine release syndrome in patients with severe COVID-19 illness.
Shruti Gupta, Wei Wang, Salim S Hayek, Lili Chan, Kusum S Mathews, Michal L Melamed, Samantha K Brenner, Amanda Leonberg-Yoo, Edward J Schenck, Jared Radbel, Jochen Reiser, Anip Bansal, Anand Srivastava, Yan Zhou, Diana Finkel, Adam Green, Mary Mallappallil, Anthony J Faugno, Jingjing Zhang, Juan Carlos Q Velez, Shahzad Shaefi, Chirag R Parikh, David M Charytan, Ambarish M Athavale, Allon N Friedman, Roberta E Redfern, Samuel A P Short, Simon Correa, Kapil K Pokharel, Andrew J Admon, John P Donnelly, Hayley B Gershengorn, David J Douin, Matthew W Semler, Miguel A Hernán, David E Leaf,

2053 related Products with: Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19.

96T 5 Geach2.5 mg100ul10 mg1 mg1000 1,000 tests100ug

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#33079696   2020/10/20 To Up

Development of novel methods for non-canonical myeloma protein analysis with an innovative adaptation of immunofixation electrophoresis, native top-down mass spectrometry, and middle-down de novo sequencing.

Objectives Multiple myeloma (MM) is a malignant plasma cell neoplasm, requiring the integration of clinical examination, laboratory and radiological investigations for diagnosis. Detection and isotypic identification of the monoclonal protein(s) and measurement of other relevant biomarkers in serum and urine are pivotal analyses. However, occasionally this approach fails to characterize complex protein signatures. Here we describe the development and application of next generation mass spectrometry (MS) techniques, and a novel adaptation of immunofixation, to interrogate non-canonical monoclonal immunoproteins. Methods Immunoprecipitation immunofixation (IP-IFE) was performed on a Sebia Hydrasys Scan2. Middle-down de novo sequencing and native MS were performed with multiple instruments (21T FT-ICR, Q Exactive HF, Orbitrap Fusion Lumos, and Orbitrap Eclipse). Post-acquisition data analysis was performed using Xcalibur Qual Browser, ProSight Lite, and TDValidator. Results We adapted a novel variation of immunofixation electrophoresis (IFE) with an antibody-specific immunosubtraction step, providing insight into the clonal signature of gamma-zone monoclonal immunoglobulin (M-protein) species. We developed and applied advanced mass spectrometric techniques such as middle-down de novo sequencing to attain in-depth characterization of the primary sequence of an M-protein. Quaternary structures of M-proteins were elucidated by native MS, revealing a previously unprecedented non-covalently associated hetero-tetrameric immunoglobulin. Conclusions Next generation proteomic solutions offer great potential for characterizing complex protein structures and may eventually replace current electrophoretic approaches for the identification and quantification of M-proteins. They can also contribute to greater understanding of MM pathogenesis, enabling classification of patients into new subtypes, improved risk stratification and the potential to inform decisions on future personalized treatment modalities.
W Ian Deighan, Valerie J Winton, Rafael D Melani, Lissa C Anderson, John P McGee, Luis F Schachner, David Barnidge, David Murray, H Denis Alexander, David S Gibson, Michael J Deery, Feargal P McNicholl, Joseph McLaughlin, Neil L Kelleher, Paul M Thomas

1516 related Products with: Development of novel methods for non-canonical myeloma protein analysis with an innovative adaptation of immunofixation electrophoresis, native top-down mass spectrometry, and middle-down de novo sequencing.

100ug Lyophilized1mg100ug Lyophilized100ug100ug Lyophilized200 1000 Units100ug Lyophilized 50 UG

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#33079615   // To Up

Pharmacokinetics of novel Fc-engineered monoclonal and multispecific antibodies in cynomolgus monkeys and humanized FcRn transgenic mouse models.

Monoclonal antibodies (mAbs) are among the fastest growing and most effective therapies for myriad diseases. Multispecific antibodies are an emerging class of novel therapeutics that can target more than one tumor- or immune-associated modulators per molecule. The combination of different binding affinities and target classes, such as soluble or membrane-bound antigens, within multispecific antibodies confers unique pharmacokinetic (PK) properties. Numerous factors affect an antibody's PK, with affinity to the neonatal Fc receptor (FcRn) a key determinant of half-life. Recent work has demonstrated the potential for humanized FcRn transgenic mice to predict the PK of mAbs in humans. However, such work has not been extended to multispecific antibodies. We engineered mAbs and multispecific antibodies with various Fc modifications to enhance antibody performance. PK analyses in humanized FcRn transgenic mouse (homozygous Tg32 and Tg276) and non-human primate (NHP) models showed that FcRn-binding mutations improved the plasma half-lives of the engineered mAbs and multispecific antibodies, while glycan engineering to eliminate effector function did not affect the PK compared with wild-type controls. Furthermore, results suggest that the homozygous Tg32 mouse model can replace NHP models to differentiate PK of variants during lead optimization, not only for wild-type mAbs but also for Fc-engineered mAbs and multispecific antibodies. This Tg32-mouse model would enable prediction of half-life and linear clearance of mAbs and multispecific antibodies in NHPs to guide the design of further pharmacology/safety studies in this species. The allometric exponent for clearance scaling from Tg32 mice to NHPs was estimated to be 0.91 for all antibodies.
Delphine Valente, Christine Mauriac, Thorsten Schmidt, Ingo Focken, Jochen Beninga, Brian Mackness, Huawei Qiu, Pascale Vicat, Abdullah Kandira, Katarina Radošević, Srini Rao, John Darbyshire, Mostafa Kabiri

1100 related Products with: Pharmacokinetics of novel Fc-engineered monoclonal and multispecific antibodies in cynomolgus monkeys and humanized FcRn transgenic mouse models.

100.00 ug100.00 ug100.00 ug100.00 ug100.00 ug100.00 ug100.00 ug100.00 ug100.00 ug100.00 ug100.00 ug100.00 ug

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#33079613   2020/10/20 To Up

Tocilizumab prescribing criteria for COVID-19 patients.


Ayman M Al-Qaaneh, Fuad H Al-Ghamdi

1516 related Products with: Tocilizumab prescribing criteria for COVID-19 patients.

1 G96 Well 100 G1 g50 ug 100ul100μg 5 G250 mg0.1ml (1mg/ml)

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#33079180   2020/10/20 To Up

Clinical Characteristics and Outcomes of COVID-19 Patients Receiving Compassionate Use Leronlimab.

Leronlimab, a monoclonal antibody blocker of CCR5 originally developed to treat HIV-1 infection, was administered as an open label compassionate use therapeutic for COVID-19.
Bryant Yang, Jennifer A Fulcher, Jenny Ahn, Marlene Berro, David Goodman-Meza, Kush Dhody, Jonah B Sacha, Arash Naeim, Otto O Yang

1332 related Products with: Clinical Characteristics and Outcomes of COVID-19 Patients Receiving Compassionate Use Leronlimab.

ML0.5 mg5 mg1 mg1000 tests

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#33078980   // To Up

A T-cell-dependent antibody response study using a murine surrogate anti-PD-1 monoclonal antibody as an alternative to a non-human primate model.

The programmed cell death 1 (PD-1) pathway represents a major immune checkpoint which may be engaged by cells in a tumor microenvironment to overcome active T-cell immune surveillance. Pembrolizumab (Keytruda) is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG/κ isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. The current work was focused on developing a mouse T-Dependent Antibody Response (TDAR) model using a murinized rat anti-mouse PD-1 antibody (muDX400; a rodent surrogate for pembrolizumab) to evaluate the potential impact of treatment with a PD-1 inhibitor on immune responses to an antigen challenge (e.g. HBsAg in Hepatitis B vaccine). Despite the lower binding affinity and T compared to pembrolizumab, ligand blocking data indicated muDX400 had appropriate pharmacological activity and demonstrated efficacy in mouse tumor models, thus was suitable for pharmacodynamic and vaccination studies in mice. In a vaccination study in which mice were concomitantly administered muDX400 and the Hepatitis B vaccine, muDX400 was well-tolerated and did not result in any immune-mediated adverse effects. The treatment with muDX400 was associated with a shift in the ratio between naive and memory cells in both CD4 and CD8 T-lymphocytes in the spleen but did not affect anti-HBsAg antibody response profile. The mouse TDAR model using the Hepatitis B vaccine and the surrogate anti-PD1 monoclonal antibody was a useful tool in the evaluation of the potential immune-mediated effects of pembrolizumab following vaccination and appears to be a suitable alternative for the nonhuman primate TDAR models utilized for other checkpoint inhibitors.
Lisa M Plitnick, Beth Hutchins, Sheri Dubey, Nianyu Li, Rupesh P Amin, Stephanie Born, Ruban Mangadu, Joseph H Phillips, Venkataraman Sriram, Danuta J Herzyk

1200 related Products with: A T-cell-dependent antibody response study using a murine surrogate anti-PD-1 monoclonal antibody as an alternative to a non-human primate model.

0.1 mg100ug Lyophilized100μl100ug Lyophilized100μl100ug Lyophilized100ul100μl100ul100μl100μl100μl

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#33078896   2020/10/20 To Up

Humanization of Chicken-derived scFv Using Yeast Surface Display and NGS Data Mining.

Generation of high-affinity monoclonal antibodies by immunization of chickens is a valuable strategy, particularly for obtaining antibodies directed against epitopes that are conserved in mammals. We established a generic procedure for the humanization of chicken-derived antibodies. To this end, high-affinity binders of the epidermal growth factor receptor extracellular domain were isolated from immunized chickens using yeast surface display. Complementarity determining regions (CDRs) of two high-affinity binders were grafted onto a human acceptor framework. Simultaneously, Vernier zone residues, responsible for spatial CDR arrangement were partially randomized. A yeast surface display library comprising approximately 300,000 variants was screened for high-affinity binders in the scFv and Fab format. Next-generation sequencing disclosed humanized antibody variants with restored affinity and improved protein characteristics compared to the parental chicken antibodies. Furthermore, our sequencing data give new insights into the importance of antibody format, used during the humanization process. Starting from the antibody repertoire of immunized chickens, this work features an effective and fast high-throughput approach for the generation of multiple humanized antibodies with potential therapeutic relevance. This article is protected by copyright. All rights reserved.
Adrian Elter, Jan P Bogen, Steffen C Hinz, David Fiebig, Arturo Macarrón Palacios, Julius Grzeschik, Björn Hock, Harald Kolmar

1916 related Products with: Humanization of Chicken-derived scFv Using Yeast Surface Display and NGS Data Mining.

100 µg100ug Lyophilized100ug2.5 mg1.0 mg50 100 Tests1 mg96 wells (1 kit)2ug

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#33078867   2020/10/20 To Up

PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease.

Despite the availability of effective drug therapies that reduce low-density lipoprotein (LDL)-cholesterol (LDL-C), cardiovascular disease (CVD) remains an important cause of mortality and morbidity. Therefore, additional LDL-C reduction may be warranted, especially for people who are unresponsive to, or unable to take, existing LDL-C-reducing therapies. By inhibiting the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme, monoclonal antibodies (PCSK9 inhibitors) reduce LDL-C and CVD risk.
Amand F Schmidt, John-Paul L Carter, Lucy S Pearce, John T Wilkins, John P Overington, Aroon D Hingorani, J P Casas

2208 related Products with: PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease.

100 100 100 100 100 100.00 ug100.00 ug100 ug100 ug200ug0.1 mg200 ug

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