6 research outputs found
Discovery of a Chemical Modification by Citric Acid in a Recombinant Monoclonal Antibody
Recombinant therapeutic monoclonal
antibodies exhibit a high degree
of heterogeneity that can arise from various post-translational modifications.
The formulation for a protein product is to maintain a specific pH
and to minimize further modifications. Generally Recognized as Safe
(GRAS), citric acid is commonly used for formulation to maintain a
pH at a range between 3 and 6 and is generally considered chemically
inert. However, as we reported herein, citric acid covalently modified
a recombinant monoclonal antibody (IgG1) in a phosphate/citrate-buffered
formulation at pH 5.2 and led to the formation of so-called “acidic
species” that showed mass increases of 174 and 156 Da, respectively.
Peptide mapping revealed that the modification occurred at the N-terminus
of the light chain. Three additional antibodies also showed the same
modification but displayed different susceptibilities of the N-termini
of the light chain, heavy chain, or both. Thus, ostensibly unreactive
excipients under certain conditions may increase heterogeneity and
acidic species in formulated recombinant monoclonal antibodies. By
analogy, other molecules (e.g., succinic acid) with two or more carboxylic
acid groups and capable of forming an anhydride may exhibit similar
reactivities. Altogether, our findings again reminded us that it is
prudent to consider formulations as a potential source for chemical
modifications and product heterogeneity
An Industry Perspective on Forced Degradation Studies of Biopharmaceuticals: Survey Outcome and Recommendations
Discovery of a Chemical Modification by Citric Acid in a Recombinant Monoclonal Antibody
CEPC Conceptual Design Report: Volume 2 - Physics & Detector
The Circular Electron Positron Collider (CEPC) is a large international scientific facility proposed by the Chinese particle physics community to explore the Higgs boson and provide critical tests of the underlying fundamental physics principles of the Standard Model that might reveal new physics. The CEPC, to be hosted in China in a circular underground tunnel of approximately 100 km in circumference, is designed to operate as a Higgs factory producing electron-positron collisions with a center-of-mass energy of 240 GeV. The collider will also operate at around 91.2 GeV, as a Z factory, and at the WW production threshold (around 160 GeV). The CEPC will produce close to one trillion Z bosons, 100 million W bosons and over one million Higgs bosons. The vast amount of bottom quarks, charm quarks and tau-leptons produced in the decays of the Z bosons also makes the CEPC an effective B-factory and tau-charm factory. The CEPC will have two interaction points where two large detectors will be located. This document is the second volume of the CEPC Conceptual Design Report (CDR). It presents the physics case for the CEPC, describes conceptual designs of possible detectors and their technological options, highlights the expected detector and physics performance, and discusses future plans for detector R&D and physics investigations. The final CEPC detectors will be proposed and built by international collaborations but they are likely to be composed of the detector technologies included in the conceptual designs described in this document. A separate volume, Volume I, recently released, describes the design of the CEPC accelerator complex, its associated civil engineering, and strategic alternative scenarios
CEPC Conceptual Design Report: Volume 2 - Physics & Detector
The Circular Electron Positron Collider (CEPC) is a large international scientific facility proposed by the Chinese particle physics community to explore the Higgs boson and provide critical tests of the underlying fundamental physics principles of the Standard Model that might reveal new physics. The CEPC, to be hosted in China in a circular underground tunnel of approximately 100 km in circumference, is designed to operate as a Higgs factory producing electron-positron collisions with a center-of-mass energy of 240 GeV. The collider will also operate at around 91.2 GeV, as a Z factory, and at the WW production threshold (around 160 GeV). The CEPC will produce close to one trillion Z bosons, 100 million W bosons and over one million Higgs bosons. The vast amount of bottom quarks, charm quarks and tau-leptons produced in the decays of the Z bosons also makes the CEPC an effective B-factory and tau-charm factory. The CEPC will have two interaction points where two large detectors will be located. This document is the second volume of the CEPC Conceptual Design Report (CDR). It presents the physics case for the CEPC, describes conceptual designs of possible detectors and their technological options, highlights the expected detector and physics performance, and discusses future plans for detector R&D and physics investigations. The final CEPC detectors will be proposed and built by international collaborations but they are likely to be composed of the detector technologies included in the conceptual designs described in this document. A separate volume, Volume I, recently released, describes the design of the CEPC accelerator complex, its associated civil engineering, and strategic alternative scenarios
CEPC Conceptual Design Report: Volume 2 - Physics & Detector
The Circular Electron Positron Collider (CEPC) is a large international scientific facility proposed by the Chinese particle physics community to explore the Higgs boson and provide critical tests of the underlying fundamental physics principles of the Standard Model that might reveal new physics. The CEPC, to be hosted in China in a circular underground tunnel of approximately 100 km in circumference, is designed to operate as a Higgs factory producing electron-positron collisions with a center-of-mass energy of 240 GeV. The collider will also operate at around 91.2 GeV, as a Z factory, and at the WW production threshold (around 160 GeV). The CEPC will produce close to one trillion Z bosons, 100 million W bosons and over one million Higgs bosons. The vast amount of bottom quarks, charm quarks and tau-leptons produced in the decays of the Z bosons also makes the CEPC an effective B-factory and tau-charm factory. The CEPC will have two interaction points where two large detectors will be located. This document is the second volume of the CEPC Conceptual Design Report (CDR). It presents the physics case for the CEPC, describes conceptual designs of possible detectors and their technological options, highlights the expected detector and physics performance, and discusses future plans for detector R&D and physics investigations. The final CEPC detectors will be proposed and built by international collaborations but they are likely to be composed of the detector technologies included in the conceptual designs described in this document. A separate volume, Volume I, recently released, describes the design of the CEPC accelerator complex, its associated civil engineering, and strategic alternative scenarios