An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein produced mainly by plasma cells that is used by the immune system to neutralize pathogens such as pathogenic bacteria and viruses.
Monoclonal antibodies are important reagents used in biomedical research, in diagnosis of diseases, and in treatment of such diseases as infections and cancer.
These antibodies are produced by cell lines or clones obtained from animals that have been immunized with the substance that is the subject of study.
How Molecular Structure Influences Potency of a Therapeutic BiologicMerck Life Sciences
This review will give the listener an understanding of how the molecular structure, and the different ways they can be measured, influences binding and affects potency of a therapeutic biologic.
Product characterization is key to successful biological drug development. Comprehensive characterization of new therapeutic monoclonal antibodies requires a deep understanding of their structural and functional critical quality attributes (CQAs) which may impact product potency, stability and safety. Various analytical approaches can be used to characterize the effects of changes during the process of generating a biological drug.
This webinar will review some of the approaches to N-glycan profiling of monoclonal antibodies using Mass Spectrometry (MS), including Hydrogen Deuterium Exchange (HDX-MS) analytics. Using the Humira monoclonal antibody, the effect of glycosylation on the Fc-region mediated effector function was assessed with binding and CDC and ADCC activity assays. This review will give the listener an understanding of how the molecular structure, and the different ways they can be measured, influences binding and affects potency of a therapeutic biologic.
In this webinar you will learn:
- HDX-MS - when and why to use
- Glycosylation effects assessment by activity assays
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein produced mainly by plasma cells that is used by the immune system to neutralize pathogens such as pathogenic bacteria and viruses.
Monoclonal antibodies are important reagents used in biomedical research, in diagnosis of diseases, and in treatment of such diseases as infections and cancer.
These antibodies are produced by cell lines or clones obtained from animals that have been immunized with the substance that is the subject of study.
How Molecular Structure Influences Potency of a Therapeutic BiologicMerck Life Sciences
This review will give the listener an understanding of how the molecular structure, and the different ways they can be measured, influences binding and affects potency of a therapeutic biologic.
Product characterization is key to successful biological drug development. Comprehensive characterization of new therapeutic monoclonal antibodies requires a deep understanding of their structural and functional critical quality attributes (CQAs) which may impact product potency, stability and safety. Various analytical approaches can be used to characterize the effects of changes during the process of generating a biological drug.
This webinar will review some of the approaches to N-glycan profiling of monoclonal antibodies using Mass Spectrometry (MS), including Hydrogen Deuterium Exchange (HDX-MS) analytics. Using the Humira monoclonal antibody, the effect of glycosylation on the Fc-region mediated effector function was assessed with binding and CDC and ADCC activity assays. This review will give the listener an understanding of how the molecular structure, and the different ways they can be measured, influences binding and affects potency of a therapeutic biologic.
In this webinar you will learn:
- HDX-MS - when and why to use
- Glycosylation effects assessment by activity assays
Combinatorial chemistry by Sunil Yadav SD Bihani College sri gangangar sunilkamal1045
The Combinatorial Chemistry is a scientific method in which a very large number of chemical entities are synthesized by condensing a small number of chemical compounds together in all combinations defined by a small set of chemical reactions.
PEPTIDOMIMETICS , HERE WE HAVE INCLUDED THE INTRODUCTION, CLASSIFICATION, ADVANTAGES , DISADVANTAGES, ITS METHODS PREPARATION, PRINCIPLES OD DRUG DESIGN, ITS CHEMISTRY. STEREOCHEMISTRY, SYNTHESIS AND APPLICATIONS
Pharmacogenetics is the study of influences of a gene on therapeutic and adverse effects of drugs.
Pharmacogenetics plays an important role in drug development and drug safety.
Combinatorial chemistry by Sunil Yadav SD Bihani College sri gangangar sunilkamal1045
The Combinatorial Chemistry is a scientific method in which a very large number of chemical entities are synthesized by condensing a small number of chemical compounds together in all combinations defined by a small set of chemical reactions.
PEPTIDOMIMETICS , HERE WE HAVE INCLUDED THE INTRODUCTION, CLASSIFICATION, ADVANTAGES , DISADVANTAGES, ITS METHODS PREPARATION, PRINCIPLES OD DRUG DESIGN, ITS CHEMISTRY. STEREOCHEMISTRY, SYNTHESIS AND APPLICATIONS
Pharmacogenetics is the study of influences of a gene on therapeutic and adverse effects of drugs.
Pharmacogenetics plays an important role in drug development and drug safety.
I Contratti di Sperimentazione Clinica - Studio Legale Pandolfini Assistenza ...Studio Legale Pandolfini
Servizi di Assistenza Legale alle Imprese dello Studio Legale Pandolfini: I Contratti di Sperimentazione Clinica.
Sperimentazioni Cliniche Profit e No Profit
Responsabilità nelle Sperimentazioni Cliniche
Contratto di Sperimentazione Clinica: Il Soggetto e le Clausole
Franciscan Alliance Blazes New Trails in Healthcare DeliveryAvaya Inc.
Franciscan Alliance operates 13 hospitals and more than 170 medical practices across Indiana, Illinois and Michigan. Avaya Fabric Networking gave them the bandwidth they need to support future technologies and the flexibility to grow. Learn more: http://bit.ly/1ICcUww
How To Build A Change Control System with SharePointDux Raymond Sy
Presented by Dux Raymond Sy
meetdux.com
SharePoint Technology Conference
June 24, 2009
Cambridge, MA
Watch Recorded Screencast: http://vimeo.com/5358854
As the markets for real estate usually remain stable in many areas of in the world, opportunities continue to exist for the development of real estate projects. This lecture is designed to analyze the real estate development process primarily from the perspective of the developer. The lecture concentrates on the development of a real estate project from its conceptual ideas until the operational start-up, and from the initiation of the concept designs until the project is defined.
The lecture examines most of the phases of the development process, from idea inception through studying the various available options for the use of the lands and estimating the projects' costs and income to determine the best and optimum commercial use of the lands. This includes an overview about the development of the project's financial feasibility of real estate development, which involves the identification and evaluation of critical assumptions related to the creation, construction, and operation of economically viable commercial real estate projects.
The lecture is introductory in scope and assumes attendants have little or no experience with the development process.
An understanding of the real estate development process benefits not only potential developers, but investors, lenders, builders, public sector participants, and end-users of the products as well.
12 steps to achieve excellence in debt collection and recoveryEXUS
The challenges Collection & Recovery departments face nowadays have forced them to become more inventive and efficient.
The 12 steps to achieve excellence in C&R embed business knowledge that EXUS has accumulated all these years through the cooperation with field experts.
Go through this presentation and evaluate how these “best practices” employed by top financial institutions in the world can be adopted by your organisation.
A simplified presentation of the complex and crucial process of protein folding which takes place after an amino acid chain is translated by ribosomes from mRNA.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
2. Introduction
Some of the questions I started with two years ago:
• How do mAbs differ from traditional molecules?
• How do they degrade?
• What factors affect mAb stability?
• How safe are the degradation products?
• What is an acceptable degradation limit?
• How can we detect degradation products?
3. Overview
• What are mAbs?
• How are they constructed?
• How do they breakdown?
• What is it that drives degradation?
• Examples of degradation?
• Assessing mAb stability
5. How do mAbs differ from traditional chemical molecules?
Size
Aspirin Growth hormone IgG Antibody
21 atoms 3,000 atoms 25,000 atoms
Complexity
150 parts 14,000 parts 6,000,000 parts
9. Structure of Monoclonal Antibody!
Antigen specific • Therapeutic mAbs
binding predominantly of IgG1 class
and subtype
• IgG consist of 2 heavy and
light chains
• Around 150kDa in size
• Chains held together by
disulfide bond between
conserved cysteine residues
at the hinge region
• Fc region binding cell
surface Ig receptors
• Antigen binding variable
Cell receptor region
specific binding
10. Structure of Monoclonal Antibody!
Antigen specific • Therapeutic mAbs
binding predominantly of IgG1 class
and subtype
• IgG consist of 2 heavy and
light chains
• Around 150kDa in size
• Chains held together by
disulfide bond between
conserved cysteine residues
at the hinge region
• Fc region binding cell surface
Ig receptors
• Antigen binding variable
Cell receptor region
specific binding
11. The importance of structure on the mechanism of action!
An#body
dependant
cellular
cytotoxicity
Mechanism of action
include:
• Cell death via ADCC
• Cell death CDCC
• Inducing apoptosis
• Neutralization of
soluble molecules
• Mediating cellular
activity
12. The importance of structure on the mechanism of action!
ELISA studies are not sufficient as they:
• only tell you they are binding
• do not demonstrate biological activity
Cell based studies
• demonstrate biological activity
• may require multiple functional studies to assess various modes
of action
13. Specificity is derived from protein structure (shape)!
Primary Structure
– the amino acid sequence linked via covalent peptide bonds
Secondary Structure
– linking of sequences of amino acids by non covalent interactions
(Alpha helices, Beta sheets)
14. Specificity is derived from protein structure (shape)!
Primary Structure
– the amino acid sequence
Secondary Structure
– linking of sequences of amino
acids by hydrogen bonding (beta
sheets, alpha helices)
Tertiary Structure
– attractions between beta sheets and alpha
helices to give 3-D structures
Quaternary Structures
– protein consisting of more than one amino
acid chain (complex of protein molecules)
15. Monoclonal antibody quaternary structure!
• Y shaped Quaternary
structure.
• Functionality relies on
quaternary structure
• Interchain disulfide bonds at
the hinge region and non
covalent interactions between
CH3 domains stabilise the
structure
• CH2 domain is overlaid by an
oligosaccharide covalently
attached at Asn297
16. Glycans influence Monoclonal antibody function!
Glycosylation is a critical quality
attribute
• CH2 domain is overlaid by an
oligosaccharide covalently attached
at Asn297
• Small contribution to mAb size
• Influence t ½
• Stability to degradation
• Influence protein folding
• Solubility
• Changes can alter functional
activity
• Immunogenicity
23. Processes contributing to degradation mAbs
Chemical degradation - Deamidation
- Change in conformation
- Change in bonding
- Change in bonding - Change in conformation
- Change in pH - Change in bonding
- Change in pH
24. Processes contributing to degradation mAbs
Physical instabilities
Fragmentation - Dissociation or cleavage of chains
Loss of activity
Denaturation - Change of shape/structure – alteration of bonds
necessary for native conformation
25. Processes contributing to degradation mAbs
Aggregation - Can form dimers, tetramers or larger
aggregates/particles
• Decreased bioactivity
• Increased immunogenicity
aggregated protein
• Affect fluid dynamics in organ systems
30. Processes contributing to degradation mAbs
Surface interactions
• Adsorption - interact with all types of surfaces. Can potentially
interact with devices during production and storage
• Leaching – presence of solubilising agents in the formulation
increases likelihood of leaching.
• Silicon – act as nucleation sites in certain circumstances
silicone oil
36. Stability references
International Conference for
Harmonization (ICH)
• ICH Q2 R1 Analytical validation
• ICH Q5C Stability Testing of
Biotechnological/Biological
products
• ICH Q6B Specifications Test
Procedures and Acceptance
Criteria for Biotechnological/
Biological Products
37. Stability references
NHS guidelines (draft) require:
• Physical
• Chemical
• Functional
• Needs to be adopted, yellow cover
39. Processes contributing to degradation of mAbs
Native protein
Chemical Stability Physical stability/Aggregation
Oxidation Conformational Stability Colloidal Stability
(2ry, 3ry, 4ry structure) (multimers, sub-visible/visible particles)
Deamidation
Free energy change Intermolecular
Hydrolysis interactions
Proteolysis
Unfolded states
Aggregates
Biologics specific techniques Traditional assay techniques
40. Conclusion!
• Remember ICH guidance requires
chemical, physical & functional activity for a reason!
• Many physical and chemical factors can affect
product quality, efficacy & safety issues
• It is important to understand the chemistry of mAbs in order to:
design stability studies which can effectively identify degradation
products
evaluate the impact on product quality and safety
41. Conclusion
The less we know about a mAb the more stable we think it is!
42. Follow us at - mabstalk.com
26th September 2012
Maria Connolly!
Director of Quality & Compliance!
