Poster: A Novel LC-MS/MS Assay for Quantifying Dermatan Sulfate as a Cerebrospinal Fluid Biomarker for Mucopolysaccharidosis II Disease
Accumulation of dermatan sulfate (DS) in tissue and body fluid leads to mucopolysaccharidosis II (MPS II) disorder. The study aims to develop an LC-MS/MS assay to measure DS in human cerebrospinal fluid (CSF) as a biomarker.
White Paper: Host Cell Protein Testing: Perspective of Current and Future Techniques
Biologics are produced using living cells or organisms. The living cells can be derived from prokaryotic, eukaryotic, and mammalian cells that are genetically engineered to encode the protein of therapeutic use. During the protein expression process, thousands of endogenous proteins, or host-cell proteins (HCPs), are produced and needed to maintain cellular function and regulation, as well as the protein of interest. In cells, the HCPs have a wide range of functions such as growth, proliferation, survival, gene transcription, and protein synthesis, but they are unwanted impurities in the biologics product. Due to their highly diverse physicochemical characteristics, these HCPs can co-purify with the drug substance, and—despite purification steps meant to remove them from the therapeutic protein of interest—low levels can remain in the final drug product, contaminating it. Good Manufacturing Practices (GMP) require that manufacturers demonstrate that they have cleared drug substances
of residual HCPs to the lowest level possible prior to releasing their drug products. The methodologies for meeting this
challenge are changing rapidly as new instrumentation and techniques are becoming available to laboratories. The following paper outlines the latest developments, focusing on emerging best practices.
White Paper: Outsourcing Analytical Testing For Biologics – A CRO’S Perspective
Biologics are complex large molecules derived from living organisms or manufactured from cells, and they have inherent structural heterogeneity. Indeed, proteins, given their chemistry, are the “most structurally complex and functionally sophisticated molecules known.”1
Thus, the analytical testing required to support Chemical, Manufacturing, and Controls (CMC) activities of biologics is highly sophisticated, and is becoming more so as the modalities of biologics grow more complex (with antibody drug conjugates, conjugate vaccines, PEGylated proteins, fusion proteins, gene therapies, and cell-based therapies).
Case Study: Clinical Study of Abuse-Deterrent Formulation to Suppress Release of Hydrocodone
Chronic pain affects millions of Americans, with a prevalence higher than heart disease, cancer, and diabetes combined. Chronic pain resulting in osteoarthritis and cancer is often treated with opioid medications. Opioid medications can provide short-, intermediate-, or long-acting analgesia. Hydrocodone is one of the currently approved formulations available in IR and ER forms. Extended-release forms are formulated as both combination products with acetaminophen or non-steroidal anti-inflammatory drugs or single-entity drug. All currently approved oral opioids have limitations, including continued concern about abuse and misuse in the intended patient population. Like other opioids used in analgesia, hydrocodone can be abused and is subject to criminal diversion. A number of the abuse-deterrent formulations in development and available on the market utilize hard-to-crush tablet technologies.
Video: Dr. Song Li, Frontage’s Founder, Ringing The Bell Of The Hong Kong Stock Exchange
Frontage Holdings Corporation, the
parent company of Frontage Laboratories, Inc., a fast-growing
contract research organization, specializing in R&D product
development services, with operations in both the United
States and China, announced on May 30 that the Company's Shares have initiated trading on the
Main Board of The Stock Exchange of Hong Kong.
Poster: Characterization of Interchain Cysteine Linked Antibody Drug Conjugates in Mouse Plasma by LC/MS
Antibody drug conjugates (ADCs) has become promising therapy for the treatment of cancers. Among all the ADCs under developing, 2/3 of them are interchain cysteine linked ADCs. The ADCs are manufactured by partially reduce the 4 pairs of interchain disulfide bond followed by conjugate cytotoxic payloads to the thiols, as a consequence, the antibodies are linked with 0, 2, 4, 6, 8 drugs. The drug to antibody ratio (DAR) and the drug linking position are important parameters that affect the therapeutic effects and need to be well characterized.
The ADCs in the mouse plasma were purified by affinity capture with anti-human IgG beads followed wash with PBS supplied with 0.1% tween-20. The ADC was eluted with 0.1% TFA and neutralized with 1M tris (PH=8).
1. Heavy chain positional isomers separation and Identification.
2. Heavy chain positional isomers abundance determination.
1. Reduced ADC HRMS analysis. The Purified ADC was deglycosylated and reduced and then analyzed with HRMS.
2. Bottom up analysis. Purified ADC was treated with IdeS to remove Fc part followed by denaturation, reduction, alkylation, chymotrpsin digestion and then subject to LC/MS analysis.
3. LC-MS/MS analysis. Isomer fraction were collected and digested with trypsin, the digest was analyzed by LC/MS/MS for drug linking position identification.