Factors impacting the SC bioavailability of therapeutic antibodies
|
|
|
- Marion Howard
- 6 years ago
- Views:
Transcription
1 Factors impacting the SC bioavailability of therapeutic antibodies How can we improve it? Saileta Prabhu 19 May 2014
2 SC bioavailability (%) of therapeutic antibodies in humans varies to a large extent 2 mab-a mab-b Adalimumab mab-c mab-d mab-e Isotype? FcRn? CL? Formulation? Charge? Zheng, 2012
3 Objectives for today 3 Physical, chemical, and biological factors influence SC PK and bioavailability of therapeutic mabs? Leverage our knowledge to improve SC PK/F
4 Outline: Factors impacting SC PK/ bioavailability 4 Site Molecule Patient Product
5 Outline: Factors impacting SC PK/ Site: SC space bioavailability 5 Properties of SC tissue Capillary & lymph permeability and flow Sites of administration Volume Tissue response to needle injection Site Patient Molecule Product
6 Site of administration: SC space 6
7 Chemical and physiological features of SC tissue 7 Hyaluronic acid Chondroitin sulfate Collagen fibers Kinnunen and Mrsny, 2014
8 Vascular and lymphatic system involved in transport of antibodies in SC tissue 8 McLennan, 2005
9 mab solubility, stability and/or function may be impacted prior to SC absorption 9 Kinnunen and Mrsny, 2014
10 Does site of administration impact bioavailability? 10 Limited data to draw conclusions Golimumab SC profile in humans Serum Golimumab Concentration (u g/ml)" 1 0" SC: Upper Arm (N=18) 8" SC: Abdomen (N=18) SC: Thigh (N=18) 6" 4" 2" 0" 0" 7" 14" 21" 28" 35" 42" 49" 56" 63" 70" Xu, 2010 Rituximab SC PK parameters in rats Foot Ab Back Bioavailability, % Tmax, days Fig. 4 Pharmacokinetic parameters calculated for rituximab administered by SC injection to rats by noncompartmental analysis. (a) T max and (b) bioavailability (grey bars) and dose normalized C max (black bars). * significantly different from injection at the back (p<0.05). # significantly different from injection of 10 and 40 mg/kg (p<0.05). a b Kagan, 2012 C max /Dose
11 Outline: Factors impacting SC PK/ bioavailability Properties of SC tissue Capillary/lymph permeability Sites of administration Volume Tissue response to needle injection Site Patient Molecule Product Size, weight Isotype FcRn binding Charge Hydrophobicity Solubility Aggregates Immunogenicity 11
12 Antibodies are a heterogeneous product with complex 3Dstructures Fab: CDR Antigen Binding Fc: Effector functions FcRn-Recycling Possible variants due to process or product changes Pyro- Glu (2) Deamida3on (3 x 2) Methionine oxida3on (2 x 2) Glyca3on (2 x 2) Glycosyla3on variants (5) Sialyla3on (5) C- term Lys (2) 2 x 6 x 4 x 4 x 5 x 5 x 2 = million Fab/CDR = specificity, MOA and antigen-mediated clearance Fc= FcγR and complement binding, effector function and recycling Adapted from Kozlowski and Swann,
13 FcRn appears to impact SC bioavailability in mouse 13 I253A.H435A IV WT N434Y N434H FcRn binding; BA (70%) compared to wild type (50%); whereas FcRn; BA (5%) as compared to wild type (50%) FcRn++ WT SC I253A.H435A WT N434Y N434H FcRn-- Balthasar et al. unpublished Deng, 2012
14 No impact of FcRn affinity on SC bioavailability in Cyno IV PK profiles SC PK profiles 14 Datta-Mannan, 2014
15 Changes in amino acid residues can impact the charge of IgG1 antibodies 15 WT (pi ~7) mutate Lysà Ala (pi ~ 3) mutate Asp,Gluà Ala (pi ~10) Main peak Poten?al sources of charge variants: C- terminal lysine N- terminal glutamine Methionine oxida3on Sialyla3on D. McDonald, J. Wang, V. Ling Boswell et al, 2010
16 Variants differing by 2 AA show 2-fold difference in clearance in cyno following IV administration 16 mab A WT V1 Seq changes in red XXSNXXX XXRKXXX Antibody Concentration ( µ g/ml) Cyno WT WT mg/kg mg/kg WT 3.0 mg/kg mg/kg v1 0.3 mg/kg v1 3.0 mg/kg Time (days) Dongwei Li
17 Impact of charge on PK and distribution 17 PK and tissue distribution profile in rats following single IV administration of 5B3 variants 1000 Concentration ( µ g/ml) h5b serum pi6.1 h5b plasma h5b serum pi8.6 h5b plasma 5B3-pI B3 variant-pi 8.61 Time (days ) Tissue concentrations on day 3-post dose Andy Boswell, Rong Deng, Bob Kelley
18 pi changes > 1 reported to influence PK of IgG4 mab following administration in mice 18 pi pi Igawa et al, 2010
19 Can we leverage our limited knowledge to improve SC PK/F? Properties of SC tissue Capillary/lymph permeability Sites of administration Volume Tissue response to needle injection Size/wt FcRn binding Charge, hydrophobicity Solubility Aggregates Immunogenicity 19 Site Molecule Tolerability Inter-individual variability Device-related factors Patient Product Formulation ph Volume Viscosity Excipients Dose/regimen
20 Acknowledgements 20 Le Dao Yanan Zheng Daniela Bumbaca Sean Joseph Wendy Putnam Andy Boswell Wolfgang Richter Amita Joshi Paul Fielder
21 Appendix Subtitle Goes Here
22 Kinetic Approach for Lymphatic Trafficking by Combining Visual and Quantitative Assessment Visual Assessment Quantitative Assessment gred Axial LN Inguinal LN 75µL anti-gd-alexa680 infused ID at 5µl/min Real time evaluation by Near-IR optical lymphatic imaging in a healthy mouse obtained seconds after anti-gd-alexa infusion Peripheral lymph flow of anti-gd-alexa is used to quantify the lymphatic transport kinetics based on its rate of appearance in two regional (Inguinal and axial) lymph nodes 10 9 Study interactions between molecular properties/formulation components/injection factors and physiological processes df/f Intensity Inguinal Node Time-course of the fluorescence intensity PMB and Bio-Medical Imaging groups Time (s) m1-anti-gd Alexa-Free Dye m2-anti-gd m3-anti-gd 22
on Non-Consensus Protein Motifs Analytical & Formulation Sciences, Amgen. Seattle, WA
N-Linked Glycosylation on Non-Consensus Protein Motifs Alain Balland Analytical & Formulation Sciences, Amgen. Seattle, WA CASSS - Mass Spec 2010 Marina Del Rey, CA. September 8 th, 2010 Outline 2 Consensus
Delivery of proteins (Routes of administration and absorption enhancement) The parenteral route of administration:
Delivery of proteins (Routes of administration and absorption enhancement) 1 The parenteral route of administration: Parenteral administration is here defined as administration via those routes where a
Antigen Receptor Structures October 14, Ram Savan
Antigen Receptor Structures October 14, 2016 Ram Savan savanram@uw.edu 441 Lecture #8 Slide 1 of 28 Three lectures on antigen receptors Part 1 (Today): Structural features of the BCR and TCR Janeway Chapter
Nature Medicine: doi: /nm.4322
1 2 3 4 5 6 7 8 9 10 11 Supplementary Figure 1. Predicted RNA structure of 3 UTR and sequence alignment of deleted nucleotides. (a) Predicted RNA secondary structure of ZIKV 3 UTR. The stem-loop structure
Endogenous TNFα orchestrates the trafficking of neutrophils into and within lymphatic vessels during acute inflammation
SUPPLEMENTARY INFORMATION Endogenous TNFα orchestrates the trafficking of neutrophils into and within lymphatic vessels during acute inflammation Samantha Arokiasamy 1,2, Christian Zakian 1, Jessica Dilliway
Drug Penetration to Sanctuary Sites Oral vs. IV Administration
Drug Penetration to Sanctuary Sites Oral vs. IV Administration Courtney V. Fletcher, Pharm.D. Dean, College of Pharmacy Professor, Department of Pharmacy Practice and Division of Infectious Diseases University
Biomolecules: amino acids
Biomolecules: amino acids Amino acids Amino acids are the building blocks of proteins They are also part of hormones, neurotransmitters and metabolic intermediates There are 20 different amino acids in
Supplementary Figure 1. Characterization of basophils after reconstitution of SCID mice
Supplementary figure legends Supplementary Figure 1. Characterization of after reconstitution of SCID mice with CD4 + CD62L + T cells. (A-C) SCID mice (n = 6 / group) were reconstituted with 2 x 1 6 CD4
Dual-targeting anti- CD47 bispecific antibodies: Safely provoking macrophages to feast NALM-6 tumor cells (B-ALL) Human macrophages
Dual-targeting anti- CD47 bispecific antibodies: Safely provoking macrophages to feast Krzysztof Masternak, PhD, Head of Biology 1 2 nd Biologics & BOARD Biosimilars MEETING Congress MARCH 2012 NALM-6
STRATEGIES FOR SUSTAINING EXPOSURE OF PEPTIDE THERAPEUTICS: CASE STUDIES
STRATEGIES FR SUSTAINING EXPSURE F PEPTIDE THERAPEUTICS: CASE STUDIES ASIA TIDES KYT JAPAN 23 FEBRUARY 2017 CHRISTPHER A. RHDES, PH.D. PRESENTATIN UTLINE Delivery Technologies for Sustained Exposure of
B cell activation and antibody production. Abul K. Abbas UCSF
1 B cell activation and antibody production Abul K. Abbas UCSF 2 Lecture outline B cell activation; the role of helper T cells in antibody production Therapeutic targeting of B cells 3 Principles of humoral
EMERGING STRATEGIES FOR ENGINEERING MONOCLONAL ANTIBODIES WITH IMPROVED PK/PD. Douglas Sheridan, PhD Alexion Pharmaceuticals June 29 th, 2017
EMERGING STRATEGIES FOR ENGINEERING MONOCLONAL ANTIBODIES WITH IMPROVED PK/PD Douglas Sheridan, PhD Alexion Pharmaceuticals June 29 th, 2017 DISCLOSURE Douglas Sheridan, Ph.D. Senior Director, Research
Nuevas vías de administración de Trastuzumab MIQUEL ÀNGEL SEGUÍ PALMER
Nuevas vías de administración de Trastuzumab MIQUEL ÀNGEL SEGUÍ PALMER Trastuzumab, a humanized monoclonal antibody against the extracellular domain of the HER2 receptor, is the standard-of-care treatment
ndln NK Cells (x10 3 ) Days post-infection (A/PR/8) *** *** *** Liver NK Cells (x10 4 ) Days post-infection (MCMV)
A mln NK Cells(x ) 6 1 * ndln NK Cells (x ) ns C Lung NK Cells(x ) 1 1 7 * D LN NK Cells (x ) 1 7 1 7 Days post-infection (A/PR/8) * * E Liver NK Cells (x ) 1 7 Days post-infection (A/PR/8) * * * 1 7 Days
Supplementary Figure 1. Properties of various IZUMO1 monoclonal antibodies and behavior of SPACA6. (a) (b) (c) (d) (e) (f) (g) .
Supplementary Figure 1. Properties of various IZUMO1 monoclonal antibodies and behavior of SPACA6. (a) The inhibitory effects of new antibodies (Mab17 and Mab18). They were investigated in in vitro fertilization
Proteins are sometimes only produced in one cell type or cell compartment (brain has 15,000 expressed proteins, gut has 2,000).
Lecture 2: Principles of Protein Structure: Amino Acids Why study proteins? Proteins underpin every aspect of biological activity and therefore are targets for drug design and medicinal therapy, and in
Principles of Adaptive Immunity
Principles of Adaptive Immunity Chapter 3 Parham Hans de Haard 17 th of May 2010 Agenda Recognition molecules of adaptive immune system Features adaptive immune system Immunoglobulins and T-cell receptors
Anti-Simponi Antibodies
Anti-Simponi Antibodies AbD Serotec offers you recombinant monoclonal antibodies to the antibody drug golimumab (Simponi). Our ready-made anti-golimumab antibodies are ideal for preclinical research and
Supplementary Figures
Supplementary Figures Supplementary Fig. 1. Surface thiol groups and reduction of activated T cells. (a) Activated CD8 + T-cells have high expression levels of free thiol groups on cell surface proteins.
Multiple-Choice Questions Answer ALL 20 multiple-choice questions on the Scantron Card in PENCIL
Multiple-Choice Questions Answer ALL 20 multiple-choice questions on the Scantron Card in PENCIL For Questions 1-10 choose ONE INCORRECT answer. 1. Which ONE of the following statements concerning the
Genentech Research & Early Development
Genentech Research & Early Development Founders Research Centers 1 & 2 Founders Research Centers 1 & 2 Andrew Chan, M.D., Ph.D. Senior Vice President, Research Biology September 2017 gred focus areas Discovering
NKTR-255: Accessing IL-15 Therapeutic Potential through Robust and Sustained Engagement of Innate and Adaptive Immunity
NKTR-255: Accessing IL-15 Therapeutic Potential through Robust and Sustained Engagement of Innate and Adaptive Immunity Peiwen Kuo Scientist, Research Biology Nektar Therapeutics August 31 st, 2018 Emerging
ANTIBODIES Jiri Mestecky, M.D., Ph.D. - Lecturer
ANTIBODIES Jiri Mestecky, M.D., Ph.D. - Lecturer Distribution in body fluids: secretions plasma (serum), tears, saliva, milk, genitourinary, and intestinal Cells producing antibodies and their tissue distribution:
NKTR-255: Accessing The Immunotherapeutic Potential Of IL-15 for NK Cell Therapies
NKTR-255: Accessing The Immunotherapeutic Potential Of IL-15 for NK Cell Therapies Saul Kivimäe Senior Scientist, Research Biology Nektar Therapeutics NK Cell-Based Cancer Immunotherapy, September 26-27,
Aug 28 th, 2017 Pierre Daublain
Analyzing the Potential Root Causes of Variability of Pharmacokinetics in Preclinical Species to Inform Derisking Strategies in Discovery and Early Development Aug 28 th, 2017 Pierre Daublain Outline Problem
Gentilucci, Amino Acids, Peptides, and Proteins. Peptides and proteins are polymers of amino acids linked together by amide bonds CH 3
Amino Acids Peptides and proteins are polymers of amino acids linked together by amide bonds Aliphatic Side-Chain Amino Acids - - H CH glycine alanine 3 proline valine CH CH 3 - leucine - isoleucine CH
Supplemental Figure 1. Cell-bound Cetuximab reduces EGFR staining intensity. Blood
Antibody-mediated depletion of CD19-CAR T cells Supplemental 1 Supplemental Materials Supplemental Figure 1. Supplemental Figure 1. Cell-bound Cetuximab reduces EGFR staining intensity. Blood cells were
The MOLECULES of LIFE
The MOLECULES of LIFE Physical and Chemical Principles Solutions Manual Prepared by James Fraser and Samuel Leachman Chapter 16 Principles of Enzyme Catalysis Problems True/False and Multiple Choice 1.
Live cell imaging of trafficking of the chaperone complex vaccine to the ER. BMDCs were incubated with ER-Tracker Red (1 M) in staining solution for
Live cell imaging of trafficking of the chaperone complex vaccine to the ER. BMDCs were incubated with ER-Tracker Red (1 M) in staining solution for 15 min at 37 C and replaced with fresh complete medium.
TTI-2341: A Novel Brain-Penetrant, Orally Available, Covalent EGFR Inhibitor for the Treatment of Brain Cancers
TTI-2341: A Novel Brain-Penetrant, Orally Available, Covalent EGFR Inhibitor for the Treatment of Brain Cancers November 2017 2 EGFR is a Drug Target in Brain Cancer Epidermal growth factor receptor (EGFR)
PHAR3316 Pharmacy biochemistry Exam #2 Fall 2010 KEY
1. How many protons is(are) lost when the amino acid Asparagine is titrated from its fully protonated state to a fully deprotonated state? A. 0 B. 1 * C. 2 D. 3 E. none Correct Answer: C (this question
The toll-like receptor 4 ligands Mrp8 and Mrp14 play a critical role in the development of autoreactive CD8 + T cells
1 SUPPLEMENTARY INFORMATION The toll-like receptor 4 ligands Mrp8 and Mrp14 play a critical role in the development of autoreactive CD8 + T cells Karin Loser 1,2,6, Thomas Vogl 2,3, Maik Voskort 1, Aloys
Supplementary Figure 1. ALVAC-protein vaccines and macaque immunization. (A) Maximum likelihood
Supplementary Figure 1. ALVAC-protein vaccines and macaque immunization. (A) Maximum likelihood tree illustrating CRF01_AE gp120 protein sequence relationships between 107 Envs sampled in the RV144 trial
2. Which of the following amino acids is most likely to be found on the outer surface of a properly folded protein?
Name: WHITE Student Number: Answer the following questions on the computer scoring sheet. 1 mark each 1. Which of the following amino acids would have the highest relative mobility R f in normal thin layer
BASIC PHARMACOKINETICS
BASIC PHARMACOKINETICS MOHSEN A. HEDAYA CRC Press Taylor & Francis Croup Boca Raton London New York CRC Press is an imprint of the Taylor & Francis Group, an informa business Table of Contents Chapter
Clinical Trials A Practical Guide to Design, Analysis, and Reporting
Clinical Trials A Practical Guide to Design, Analysis, and Reporting Duolao Wang, PhD Ameet Bakhai, MBBS, MRCP Statistician Cardiologist Clinical Trials A Practical Guide to Design, Analysis, and Reporting
Biochemistry - I. Prof. S. Dasgupta Department of Chemistry Indian Institute of Technology, Kharagpur Lecture 1 Amino Acids I
Biochemistry - I Prof. S. Dasgupta Department of Chemistry Indian Institute of Technology, Kharagpur Lecture 1 Amino Acids I Hello, welcome to the course Biochemistry 1 conducted by me Dr. S Dasgupta,
Introduction. A system of soluble enzymes and proteins. Complement components: C1 to C9, B, D and P
Complement Introduction A system of soluble enzymes and proteins Complement components: C1 to C9, B, D and P When activated, each component is split into small and large (major) fragments a b *A horizontal
Immunology - Lecture 2 Adaptive Immune System 1
Immunology - Lecture 2 Adaptive Immune System 1 Book chapters: Molecules of the Adaptive Immunity 6 Adaptive Cells and Organs 7 Generation of Immune Diversity Lymphocyte Antigen Receptors - 8 CD markers
Chemistry 121 Winter 17
Chemistry 121 Winter 17 Introduction to Organic Chemistry and Biochemistry Instructor Dr. Upali Siriwardane (Ph.D. Ohio State) E-mail: upali@latech.edu Office: 311 Carson Taylor Hall ; Phone: 318-257-4941;
Anti-HIV Activity of Modified Milk Proteins and Fragments Thereof Dr. René Floris, NIZO Food Research, The Netherlands
Anti-HIV Activity of Modified Milk Proteins and Fragments Thereof Dr. René Floris, NIZ Food Research, The Netherlands René Floris has studied chemistry at Leiden University and obtained his PhD degree
Supplementary Figure 1 (previous page). EM analysis of full-length GCGR. (a) Exemplary tilt pair images of the GCGR mab23 complex acquired for Random
S1 Supplementary Figure 1 (previous page). EM analysis of full-length GCGR. (a) Exemplary tilt pair images of the GCGR mab23 complex acquired for Random Conical Tilt (RCT) reconstruction (left: -50,right:
Amino acids. Dr. Mamoun Ahram Summer semester,
Amino acids Dr. Mamoun Ahram Summer semester, 2017-2018 Resources This lecture Campbell and Farrell s Biochemistry, Chapters 3 (pp.66-76) General structure (Chiral carbon) The amino acids that occur in
Basic Pharmacokinetics and Pharmacodynamics: An Integrated Textbook with Computer Simulations
Basic Pharmacokinetics and Pharmacodynamics: An Integrated Textbook with Computer Simulations Rosenbaum, Sara E. ISBN-13: 9780470569061 Table of Contents 1 Introduction to Pharmacokinetics and Pharmacodynamics.
Page 8/6: The cell. Where to start: Proteins (control a cell) (start/end products)
Page 8/6: The cell Where to start: Proteins (control a cell) (start/end products) Page 11/10: Structural hierarchy Proteins Phenotype of organism 3 Dimensional structure Function by interaction THE PROTEIN
Topics. Humoral Immune Response Part II Accessory cells Fc Receptors Opsonization and killing mechanisms of phagocytes NK, mast, eosynophils
Topics Humoral Immune Response Part II Accessory cells Fc Receptors Opsonization and killing mechanisms of phagocytes NK, mast, eosynophils Immune regulation Idiotypic network 2/15/2005 MICR 415 / 515
all of the above the ability to impart long term memory adaptive immunity all of the above bone marrow none of the above
1. (3 points) Immediately after a pathogen enters the body, it faces the cells and soluble proteins of the innate immune system. Which of the following are characteristics of innate immunity? a. inflammation
Crystallization-grade After D After V3 cocktail. Time (s) Time (s) Time (s) Time (s) Time (s) Time (s)
Ligand Type Name 6 Crystallization-grade After 447-52D After V3 cocktail Receptor CD4 Resonance Units 5 1 5 1 5 1 Broadly neutralizing antibodies 2G12 VRC26.9 Resonance Units Resonance Units 3 1 15 1 5
11 november 2014 University of Twente. Ir. Nol Brouwers Luuk Jansen Bsc
11 november 2014 University of Twente Ir. Nol Brouwers Luuk Jansen Bsc What do we do? We develop and deliver DermalDose, a patented alternative for syringes, to pharmaceutical industries Our mission, is
Pharmacokinetic and absolute bioavailability studies in early clinical development using microdose and microtracer approaches.
Pharmacokinetic and absolute bioavailability studies in early clinical development using microdose and microtracer approaches. Lloyd Stevens PhD Senior Research Fellow Pharmaceutical Profiles Nottingham,
Biogen Idec Oncology Pipeline. Greg Reyes, MD, PhD SVP, Oncology Research & Development
Biogen Idec Oncology Pipeline Greg Reyes, MD, PhD SVP, Oncology Research & Development March 25, 2009 Biogen Idec Strategy in Lymphoma / Leukemia CLL RITUXAN NHL FC-RITUXAN GA101 RITUXAN-CVP RITUXAN-CHOP
File name: Supplementary Information Description: Supplementary figures and supplementary tables. File name: Peer review file Description:
File name: Supplementary Information Description: Supplementary figures and supplementary tables. File name: Peer review file Description: Supplementary Figure 1. Schematic of Ras biochemical coupled assay.
CS612 - Algorithms in Bioinformatics
Spring 2016 Protein Structure February 7, 2016 Introduction to Protein Structure A protein is a linear chain of organic molecular building blocks called amino acids. Introduction to Protein Structure Amine
Reactions and amino acids structure & properties
Lecture 2: Reactions and amino acids structure & properties Dr. Sameh Sarray Hlaoui Common Functional Groups Common Biochemical Reactions AH + B A + BH Oxidation-Reduction A-H + B-OH + energy ª A-B + H
Absolute bioavailability and pharmacokinetic studies in early clinical development using microdose and microtracer approaches.
Absolute bioavailability and pharmacokinetic studies in early clinical development using microdose and microtracer approaches. Dr Lloyd Stevens Senior Research Fellow Pharmaceutical Profiles Nottingham,
Supplementary Appendix
Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Nair S, Branagan AR, Liu J, Boddupalli CS, Mistry PK, Dhodapkar
Amino acids. (Foundation Block) Dr. Essa Sabi
Amino acids (Foundation Block) Dr. Essa Sabi Learning outcomes What are the amino acids? General structure. Classification of amino acids. Optical properties. Amino acid configuration. Non-standard amino
Cellular Neurobiology BIPN140. 1st Midterm Exam October 18 th, Tuesday Material covered: Lectures 1-6 & Reading
Cellular Neurobiology BIPN140 1st Midterm Exam October 18 th, Tuesday Material covered: Lectures 1-6 & Reading Review session October 17 th 3500 Pacitic Hall, 6-8 pm (access code is 127895) Come with questions!
Tissue Distribution/Penetration and Pharmacokinetics of CD101
Tissue Distribution/Penetration and Pharmacokinetics of CD0 Yanan Zhao, Brendan Prideaux, Pei-Yu Chen, Yoji Nagasaki, Min Hee Lee, Grayson Hough, Voon Ong, Veronique Dartois, David S. Perlin Public Health
NK cell flow cytometric assay In vivo DC viability and migration assay
NK cell flow cytometric assay 6 NK cells were purified, by negative selection with the NK Cell Isolation Kit (Miltenyi iotec), from spleen and lymph nodes of 6 RAG1KO mice, injected the day before with
BIOPHARMACEUTICS and CLINICAL PHARMACY
11 years papers covered BIOPHARMACEUTICS and CLINICAL PHARMACY IV B.Pharm II Semester, Andhra University Topics: Absorption Distribution Protein binding Metabolism Excretion Bioavailability Drug Interactions
1. If the MTC is 100 ng/ml and the MEC is 0.12 ng/ml, which of the following dosing regimen(s) are in the therapeutic window?
Page 1 PHAR 750: Biopharmaceutics/Pharmacokinetics October 23, 2009 - Form 1 Name: Total 100 points Please choose the BEST answer of those provided. For numerical answers, choose none of the above if your
Objective: You will be able to explain how the subcomponents of
Objective: You will be able to explain how the subcomponents of nucleic acids determine the properties of that polymer. Do Now: Read the first two paragraphs from enduring understanding 4.A Essential knowledge:
Afferent lymph-derived T cells and dendritic cells use different CCR7-dependent routes for lymph node entry and intranodal migration
Braun et al. Supplementary Information 1 Supplementary Information Afferent lymph-derived T cells and dendritic cells use different CCR7-dependent routes for lymph node entry and intranodal migration Asolina
PHA Final Exam Fall 2006
PHA 5127 Final Exam Fall 2006 On my honor, I have neither given nor received unauthorized aid in doing this assignment. Name Please transfer the answers onto the bubble sheet. The question number refers
1. Measurement of the rate constants for simple enzymatic reaction obeying Michaelis- Menten kinetics gave the following results: =3x10-5 = 30μM
1. Measurement of the rate constants for simple enzymatic reaction obeying Michaelis- Menten kinetics gave the following results: k 1 = 2 x 10 8 M -1 s -1, k 2 = 1 x 10 3 s -1, k 3 = 5 x 10 3 s -1 a) What
Dendritic cells in cancer immunotherapy Aimin Jiang
Dendritic cells in cancer immunotherapy Aimin Jiang Feb. 11, 2014 Dendritic cells at the interface of innate and adaptive immune responses Dendritic cells: initiators of adaptive immune responses Dendritic
PHA Final Exam. Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment.
PHA 5127 Final Exam Fall 2012 On my honor, I have neither given nor received unauthorized aid in doing this assignment. Name Please transfer the answers onto the bubble sheet. The question number refers
Integrin v 3 targeted therapy for Kaposi s sarcoma with an in vitro evolved antibody 1
Integrin v 3 targeted therapy for Kaposi s sarcoma with an in vitro evolved antibody 1 CHRISTOPH RADER, 2 MIKHAIL POPKOV, JOHN A. NEVES, AND CARLOS F. BARBAS III 2 Department of Molecular Biology and The
FDB FOOD AND DRUGS BOARD G H A N A GUIDELINES FOR CONDUCTING BIOEQUIVALENCE STUDIES
FDB FOOD AND DRUGS BOARD G H A N A GUIDELINES FOR CONDUCTING BIOEQUIVALENCE STUDIES 1 SCOPE In pursuance of section 47 of the Food and Drugs Law 1992, P.N.D.C.L 305B, as amended by Act 523, 1996, these
Lecture 3: 8/24. CHAPTER 3 Amino Acids
Lecture 3: 8/24 CHAPTER 3 Amino Acids 1 Chapter 3 Outline 2 Amino Acid Are Biomolecules and their Atoms Can Be Visualized by Two Different Ways 1) Fischer projections: Two dimensional representation of
Practical application of analytical tools for characterization of an impurity-related particle formation mechanism
Practical application of analytical tools for characterization of an impurity-related particle formation mechanism Jared S. Bee, Ph.D. Protein aggregation measurement in biotherapeutics Maryland Center
B220 CD4 CD8. Figure 1. Confocal Image of Sensitized HLN. Representative image of a sensitized HLN
B220 CD4 CD8 Natarajan et al., unpublished data Figure 1. Confocal Image of Sensitized HLN. Representative image of a sensitized HLN showing B cell follicles and T cell areas. 20 µm thick. Image of magnification
Charges on amino acids and proteins. ph 1. ph 7. Acidic side chains: glutamate and aspartate
harges on amino acids and proteins Acidic side chains: glutamate and aspartate A A- + + + - + Basic side chains: arginine, lysine & histidine Glycine @ p 1 B+ B + + + The amino group, pka 9.6 3 N+ The
DEVELOPMENT OF CELLULAR IMMUNOLOGY
DEVELOPMENT OF CELLULAR IMMUNOLOGY 1880 s: Antibodies described (dominated studies of immunology until 1960 s) 1958: Journal of Immunology (137 papers) lymphocyte not listed in index Two papers on transfer
An#body structure & func#on
An#body structure & func#on Objec&ves You should be able to: ü Define an&body ü Describe an&body structure ü Compare between different types or classes of an&body and their func&on An#bodies = Immunoglobulin
IMMUNOBIOLOGY, BIOL 537 Exam # 2 Spring 1997
Name I. TRUE-FALSE (1 point each) IMMUNOBIOLOGY, BIOL 537 Exam # 2 Spring 1997 Which of the following is TRUE or FALSE relating to immunogenicity of an antigen and T and B cell responsiveness to antigen?
Practice Problems 3. a. What is the name of the bond formed between two amino acids? Are these bonds free to rotate?
Life Sciences 1a Practice Problems 3 1. Draw the oligopeptide for Ala-Phe-Gly-Thr-Asp. You do not need to indicate the stereochemistry of the sidechains. Denote with arrows the bonds formed between the
Chapter 5. Generation of lymphocyte antigen receptors
Chapter 5 Generation of lymphocyte antigen receptors Structural variation in Ig constant regions Isotype: different class of Ig Heavy-chain C regions are encoded in separate genes Initially, only two of
Mechanisms of Drug Action
10/31/05 Page 1 20.201 Mechanisms of Drug Action Lecture #18: Pharmacokinetics October 31, 2005 Review Dose-response Protein binding, drug transport(ers) Metabolism NOW: PHARMACOKINETICS Circulatory System
T Cell Activation, Costimulation and Regulation
1 T Cell Activation, Costimulation and Regulation Abul K. Abbas, MD University of California San Francisco 2 Lecture outline T cell antigen recognition and activation Costimulation, the B7:CD28 family
Biological systems interact, and these systems and their interactions possess complex properties. STOP at enduring understanding 4A
Biological systems interact, and these systems and their interactions possess complex properties. STOP at enduring understanding 4A Homework Watch the Bozeman video called, Biological Molecules Objective:
TITLE: A Role of Plasminogen in Promoting the Immune Escape in Small Cell Lung Cancer. PRINCIPAL INVESTIGATOR: Vera Levina, PhD. Pittsburgh, PA 15213
AWARD NUMBER: W81XWH-15-1-0295 TITLE: A Role of Plasminogen in Promoting the Immune Escape in Small Cell Lung Cancer PRINCIPAL INVESTIGATOR: Vera Levina, PhD CONTRACTING ORGANIZATION: University of Pittsburgh
Significance and Functions of Carbohydrates. Bacterial Cell Walls
Biochemistry 462a - Carbohydrate Function Reading - Chapter 9 Practice problems - Chapter 9: 2, 4a, 4b, 6, 9, 10, 13, 14, 15, 16a, 17; Carbohydrate extra problems Significance and Functions of Carbohydrates
Ionization of amino acids
Amino Acids 20 common amino acids there are others found naturally but much less frequently Common structure for amino acid COOH, -NH 2, H and R functional groups all attached to the a carbon Ionization
Dissecting T cell activation and function at the single cell level
Dissecting T cell activation and function at the single cell level Regulation and outcome of immune cell interactions in vivo Lymph node In vivo imaging of immune responses with two-photon microscopy
Varun Goel 1, Nathalie H Gosselin 2, Claudia Jomphe 2, Husain Attarwala 1, Xiaoping (Amy) Zhang 1, JF Marier 2, Gabriel Robbie 1
Population Pharmacokinetic (PK) / Pharmacodynamic (PD) Model of Serum Transthyretin (TTR) Following Patisiran Administration in Healthy Volunteers and Patients with Hereditary TTR-Mediated (hattr) Amyloidosis
Supporting Information
Supporting Information Horwitz et al. 73/pnas.35295 A Copies ml - C 3NC7 7 697 698 7 7 73 76-2 2 Days Gp2 residue G458D G459D T278A 7/36 N28 K D 28 459 A28T ID# 697 ID# 698 ID# 7 ID# 7 ID# 73 ID# 76 ID#
Practical Application of PBPK in Neonates and Infants, Including Case Studies
Practical Application of PBPK in Neonates and Infants, Including Case Studies Presented at the conference : Innovative Approaches to Pediatric Drug Development and Pediatric Medical Countermeasures: A
The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not
The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product.
This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data.
abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis which is part of the
AP Bio. Protiens Chapter 5 1
Concept.4: Proteins have many structures, resulting in a wide range of functions Proteins account for more than 0% of the dry mass of most cells Protein functions include structural support, storage, transport,
Phosphoserine Detection Kit
Kit 0701/PSER-KIT 02/080507 Background and Specificity extracellular signals to the nucleus. Phosphorylated epitopes may serve as docking sites for the assembley of protein complexes or may alter the 3-dimensional
Biochemistry 15 Doctor /7/2012
Heme The Heme is a chemical structure that diffracts by light to give a red color. This chemical structure is introduced to more than one protein. So, a protein containing this heme will appear red in
Fundamentals of Organic Chemistry CHEM 109 For Students of Health Colleges
Fundamentals of Organic Chemistry CHEM 109 For Students of Health Colleges Credit hrs.: (2+1) King Saud University College of Science, Chemistry Department CHEM 109 CHAPTER 9. AMINO ACIDS, PEPTIDES AND
Midterm 1 Last, First
Midterm 1 BIS 105 Prof. T. Murphy April 23, 2014 There should be 6 pages in this exam. Exam instructions (1) Please write your name on the top of every page of the exam (2) Show all work for full credit
Electron Microscopy Imaging Reveals Unique Higher Order Structures of Adalimumab-TNFα and Infliximab-TNFα Complexes
Electron Microscopy Imaging Reveals Unique Higher Order Structures of Adalimumab-TNFα and Infliximab-TNFα Complexes Siew Leong Chan Protein Analytics, AbbVie Bioresearch Center Worcester MA Acknowledgement
Amino acids. Dr. Mamoun Ahram and Dr. Diala Abu-Hassan Summer semester,
Amino acids Dr. Mamoun Ahram and Dr. Diala Abu-Hassan Summer semester, 2017-2018 dr.abuhassand@gmail.com Resources This lecture Campbell and Farrell s Biochemistry, Chapters 3 (pp.66-76) General structure
effect on the upregulation of these cell surface markers. The mean peak fluorescence intensity
SUPPLEMENTARY FIGURE 1 Supplementary Figure 1 ASIC1 disruption or blockade does not effect in vitro and in vivo antigen-presenting cell activation. (a) Flow cytometric analysis of cell surface molecules
The Comet Assay Tails of the (Un)expected
The Comet Assay Tails of the (Un)expected Use of the in vivo comet assay in pharmaceutical development Bas-jan van der Leede Janssen R&D Johnson & Johnson Pharmaceutical Companies Discovery Sciences Genetic