DOCSLIB.ORG

Boosting Anti-Infective Antibody and Vaccine Development

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Boosting Anti-Infective Antibody and Vaccine Development ADVERTISEMENT FEATURE YUMAB GmbH www.yumab.com YUMAB: boosting anti-infective antibody and vaccine development YUMAB, a global provider of fully human monoclonal antibody discovery and development, has relocated its headquarters to Germany’s hotspot of infectious research and is advancing new opportunities for the expedited development of prophylactic and therapeutic antibodies and vaccines to fight infectious diseases. Biotechnology company YUMAB, a global provider The combination of deep expertise in infectious of fully human monoclonal antibody (mAb) dis- Therapeutics disease and an advanced fully human mAb discov- covery and development, has recently relocated its ery and development platform makes YUMAB an profile headquarters and research and development labs to ideal partner to drive infectious disease programs Science Campus Braunschweig-South, Germany’s Pathogens YUMAB® PLATFORM Vaccines from basic research to clinical translation. The fully infectious disease research hotspot. YUMAB is now human mAbs developed at YUMAB can be tailored colocated with the Helmholtz Centre of Infection to the specific needs of any kind of mAb develop- Diagnostics Research (HZI), the Leibniz Institute-German ment program, at any stage, and with the properties Collection of Microorganisms and Cell Cultures needed for novel prophylactic or therapeutic strate- (DSMZ) and the German Centre for Infection Research gies against infectious diseases. (DZIF): three world leaders in the fight against infec- Fig. 1| Driving anti-infective mAbs with YUMAB’s tious diseases that provide an ideal environment for fully human mAb and target discovery and Partnering to fight infectious diseases YUMAB to expand its global collaboration network development platform. YUMAB is committed to accelerating the develop- in this space. ment of its customers’ anti-infective mAb pipelines YUMAB’s antibody platform enables the develop- The YUMAB edge in infectious disease with its antibody discovery and lead optimization ment of fully human antibodies, from the company’s In the fight against pathogens, the adaptive immune platform, which has already generated fully human universal libraries (1011) and from patient-derived system generates T cells and antibody-producing therapeutic mAb lead candidates in other areas. libraries, against any type of antigen, even against B cells that can provide lifelong immunity as a sec- YUMAB’s flexible and broad collaboration strategy full virus particles, bacterial and fungal cells. This ond line of defense if innate immune mechanisms maximizes the impact of its antibody technology and approach delivers fully human mAbs with broad fail. Prophylactic vaccination mimics an infection and is well suited for the development of novel mAb- ranges of specificities and minimal immunogenic- achieves similar protection. However, immunization based solutions in the infectious disease space. ity that are ideal for the development of diagnostics can fail owing to immunosuppression, lack of previ- According to YUMAB’s CEO, Thomas Schirrmann, and therapeutics. ous immunity, outbreaks of emerging pathogens or “YUMAB’s platform provides access to biological “Recent conceptual and technological advances imperfect vaccine design, requiring other strategies drug candidates that have evolved over millions in mAb development could have an enormous to stop or prevent an infection. of years of exposure to pathogens. We can rapidly impact on the field of infectious diseases, par- mAbs offer the possibility to fight infections pro- develop advanced antibodies from patient libraries ticularly in the context of emerging infectious phylactically and therapeutically, but pathogen and identify novel immunogenic targets for vaccine disease (EID) outbreaks, in which the process of variability, mutational resistance, multiple entry development. With our relocation to one of the vaccine development for new pathogens may be and pathogenic mechanisms challenge efficacy. world’s hotspots for infectious disease research, we difficult and prolonged,” argued Anthony Fauci, Emerging strategies include the use of mAbs that tar- can take these developments to the next level.” director of the National Institute of Allergy and get crucial pathogen epitopes, oligoclonal antibodies 1. Marston, H. D., Paules, C. I. & Fauci, A. S. N. Engl. J. Med. 378, Infectious Diseases, in a recent perspective in and antibody–drug conjugates, all of which require 1469–1472 (2018). the New England Journal of Medicine1. “The rapid robust and rapid antibody development platforms. 2. GBI Research. Industry Pipeline for Monoclonal Antibodies Encompasses Over 2,800 Programs, says GBI Research. development and strategic deployment of effec- YUMAB uses either its universal antibody libraries, http://gbiresearch.com/media-center/press-releases/industry- tive, highly specific preventive and therapeutic which represent the entire natural human antibody pipeline-for-monoclonal-antibodies-encompasses-over-2800- interventions have the potential to alter the course repertoire, or immune libraries generated from programs-says-gbi-research (2017). of an epidemic.” infected or vaccinated patients for initial in vitro dis- Since the US Food and Drug Administration’s 1998 covery. Bypassing animal immunization eliminates approval of MedImmune’s Synagis (palivizumab) for potential epitope preference by the host immune the prevention of respiratory syncytial virus infection response, which can misguide antibody responses in newborns, only four other anti-infective neutral- to non-neutralizing epitopes. Moreover, in vitro selec- izing mAbs have been approved: GlaxoSmithKline’s tion results in high success rates and can identify Abthrax (raxibacumab) and Elusys’ Anthim (obiltox- antibodies of broad specificity for better diagnostics, aximab), both for inhalational anthrax, in 2012 and vaccines and drugs (Fig. 1). 2016, respectively; Merck’s Zinplava (bezlotoxumab) Two YUMAB founders, Stefan Dübel and Michael for Clostridium difficile infection in 2016; and TaiMed Hust, have long track records in the development of Biologics’ Trogarzo (ibalizumab-uiyk) for HIV in 2018. neutralizing antibodies against HIV, Ebola, Venezuelan Thomas Schirrmann, CEO But with the anti-infective mAb development pipe- and Western equine encephalitis viruses, and bacterial YUMAB GmbH line now representing one of the most active areas toxins from Clostridium botulinum and Bacillus anthra- Braunschweig, Germany 2 in mAb development , YUMAB is poised to join the cis; protective antibodies against wild-type Marburg contact Tel: +49 531 4811 700 race to develop next-generation mAbs to fight infec- virus; and super-humanized antibodies against Email: [email protected] tious diseases. Aspergillus fumigatus and Clostridium diphtheria toxins. B24 | June 2018 | biopharmadealmakers.nature.com ADVERTISER RETAINS SOLE RESPONSIBILITY FOR CONTENT ©2018 Mac millan Publishers Li mited. All ri ghts reserved. .
Load more

Recommended publications
  • AHFS Pharmacologic-Therapeutic Classification System
    AHFS Pharmacologic-Therapeutic Classification System Abacavir 48:24 - Mucolytic Agents - 382638 8:18.08.20 - HIV Nucleoside and Nucleotide Reverse Acitretin 84:92 - Skin and Mucous Membrane Agents, Abaloparatide 68:24.08 - Parathyroid Agents - 317036 Aclidinium Abatacept 12:08.08 - Antimuscarinics/Antispasmodics - 313022 92:36 - Disease-modifying Antirheumatic Drugs - Acrivastine 92:20 - Immunomodulatory Agents - 306003 4:08 - Second Generation Antihistamines - 394040 Abciximab 48:04.08 - Second Generation Antihistamines - 394040 20:12.18 - Platelet-aggregation Inhibitors - 395014 Acyclovir Abemaciclib 8:18.32 - Nucleosides and Nucleotides - 381045 10:00 - Antineoplastic Agents - 317058 84:04.06 - Antivirals - 381036 Abiraterone Adalimumab; -adaz 10:00 - Antineoplastic Agents - 311027 92:36 - Disease-modifying Antirheumatic Drugs - AbobotulinumtoxinA 56:92 - GI Drugs, Miscellaneous - 302046 92:20 - Immunomodulatory Agents - 302046 92:92 - Other Miscellaneous Therapeutic Agents - 12:20.92 - Skeletal Muscle Relaxants, Miscellaneous - Adapalene 84:92 - Skin and Mucous Membrane Agents, Acalabrutinib 10:00 - Antineoplastic Agents - 317059 Adefovir Acamprosate 8:18.32 - Nucleosides and Nucleotides - 302036 28:92 - Central Nervous System Agents, Adenosine 24:04.04.24 - Class IV Antiarrhythmics - 304010 Acarbose Adenovirus Vaccine Live Oral 68:20.02 - alpha-Glucosidase Inhibitors - 396015 80:12 - Vaccines - 315016 Acebutolol Ado-Trastuzumab 24:24 - beta-Adrenergic Blocking Agents - 387003 10:00 - Antineoplastic Agents - 313041 12:16.08.08 - Selective
    [Show full text]
  • Phage Display-Based Strategies for Cloning and Optimization of Monoclonal Antibodies Directed Against Human Pathogens
    Int. J. Mol. Sci. 2012, 13, 8273-8292; doi:10.3390/ijms13078273 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms Review Phage Display-based Strategies for Cloning and Optimization of Monoclonal Antibodies Directed against Human Pathogens Nicola Clementi *,†, Nicasio Mancini †, Laura Solforosi, Matteo Castelli, Massimo Clementi and Roberto Burioni Microbiology and Virology Unit, “Vita-Salute” San Raffaele University, Milan 20132, Italy; E-Mails: [email protected] (N.M.); [email protected] (L.S.); [email protected] (M.C.); [email protected] (M.C.); [email protected] (R.B.) † These authors contributed equally to this work. * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +39-2-2643-5082; Fax: +39-2-2643-4288. Received: 16 March 2012; in revised form: 25 June 2012 / Accepted: 27 June 2012 / Published: 4 July 2012 Abstract: In the last two decades, several phage display-selected monoclonal antibodies (mAbs) have been described in the literature and a few of them have managed to reach the clinics. Among these, the anti-respiratory syncytial virus (RSV) Palivizumab, a phage-display optimized mAb, is the only marketed mAb directed against microbial pathogens. Palivizumab is a clear example of the importance of choosing the most appropriate strategy when selecting or optimizing an anti-infectious mAb. From this perspective, the extreme versatility of phage-display technology makes it a useful tool when setting up different strategies for the selection of mAbs directed against human pathogens, especially when their possible clinical use is considered.
    [Show full text]
  • The Effect of Raxibacumab on the Immunogenicity of Anthrax Vaccine Adsorbed: a Phase
    The effect of raxibacumab on the immunogenicity of anthrax vaccine adsorbed: a Phase IV, randomised, open-label, parallel-group, non-inferiority study Nancy Skoura, PhD1, Jie Wang-Jairaj, MD2, Oscar Della Pasqua MD2, Vijayalakshmi Chandrasekaran, MS1, Julia Billiard, PhD1, Anne Yeakey, MD3, William Smith, MD4, Helen Steel, MD2, Lionel K Tan, FRCP2 1GlaxoSmithKline, Inc. Collegeville, PA, USA 2GlaxoSmithKline. Stockley Park West, Middlesex, UK 3GlaxoSmithKline, Inc. Rockville, MD, USA 4AMR, at University of TN Medical Center, Knoxville, TN; New Orleans Center for Clinical Research (NOCCR), USA Author for Correspondence: Dr Lionel K Tan GlaxoSmithKline Stockley Park West 1–3 Ironbridge Road Uxbridge Middlesex UB11 1BT UK Email: [email protected] Tel: +44 (0)7341 079 683 1 Abstract: 340/350 Body text: 4321/4500 words including Research in Context Table/Figures: 2/4 References: 30 2 Abstract Background Raxibacumab is a monoclonal antibody (Ab) which binds protective antigen (PA) of Bacillus anthracis and is approved for treatment and post-exposure prophylaxis (PEP) of inhalational anthrax. Anthrax vaccine adsorbed (AVA), for anthrax prophylaxis, consists primarily of adsorbed PA. This post-approval study evaluated the effect of raxibacumab on immunogenicity of AVA. Methods In this open-label, parallel-group, non-inferiority study in three centres in the USA, healthy volunteers (aged 18–65 years) with no evidence of PA pre-exposure were randomised 1:1 to receive either subcutaneous 0·5 mL AVA on Days 1, 15, and 29 or raxibacumab intravenous infusion (40 mg/kg) immediately before AVA on Day 1, followed by AVA only on Days 15 and 29.
    [Show full text]
  • A Review of the Efficacy of FDA-Approved B. Anthracis Anti
    toxins Review A Review of the Efficacy of FDA-Approved B. anthracis Anti-Toxin Agents When Combined with Antibiotic or Hemodynamic Support in Infection- or Toxin-Challenged Preclinical Models Zoe Couse 1, Xizhong Cui 1, Yan Li 1, Mahtab Moayeri 2, Stephen Leppla 2 and Peter Q. Eichacker 1,* 1 Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA; [email protected] (Z.C.); [email protected] (X.C.); [email protected] (Y.L.) 2 National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; [email protected] (M.M.); [email protected] (S.L.) * Correspondence: [email protected] Abstract: Anti-toxin agents for severe B. anthracis infection will only be effective if they add to the benefit of the two mainstays of septic shock management, antibiotic therapy and titrated hemody- namic support. Both of these standard therapies could negate benefits related to anti-toxin treatment. At present, three anthrax anti-toxin antibody preparations have received US Food and Drug Adminis- tration (FDA) approval: Raxibacumab, Anthrax Immune Globulin Intravenous (AIGIV) and ETI-204. Each agent is directed at the protective antigen component of lethal and edema toxin. All three agents were compared to placebo in antibiotic-treated animal models of live B. anthracis infection, and Raxibacumab and AIGIV were compared to placebo when combined with standard hemodynamic support in a 96 h canine model of anthrax toxin-associated shock. However, only AIG has actually Citation: Couse, Z.; Cui, X.; Li, Y.; been administered to a group of infected patients, and this experience was not controlled and offers Moayeri, M.; Leppla, S.; Eichacker, P.Q.
    [Show full text]
  • RAXIBACUMAB Safely and Effectively
    HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all of the information needed to use RAXIBACUMAB safely and effectively. See full prescribing information --------------------DOSAGE FORMS AND STRENGTHS---------------- for RAXIBACUMAB. Single-use vial contains 1700 mg/34 mL (50 mg/mL) raxibacumab solution. (3) RAXIBACUMAB injection, for intravenous use Initial U.S. Approval: 2012 ----------------------------- CONTRAINDICATIONS--- ---------------------- None. (4) -------------------------- INDICATIONS AND USAGE--- ------------------- Raxibacumab is indicated for the treatment of adult and pediatric patients with ----------------------WARNINGS AND PRECAUTIONS--- --------------- inhalational anthrax due to Bacillus anthracis in combination with appropriate Infusion reactions may occur. Premedicate with diphenhydramine. Slow or antibacterial drugs, and for prophylaxis of inhalational anthrax when interrupt infusion and administer treatment based on severity of the reaction. alternative therapies are not available or are not appropriate. (1) (5.1) Limitations of Use: The effectiveness of raxibacumab is based solely on efficacy studies in -----------------------------ADVERSE REACTIONS--- ---------------------- animal models of inhalational anthrax. (1.2, 14.1) Common adverse reactions in healthy adult subjects (≥1.5%) were: rash, pain There have been no studies of raxibacumab in the pediatric population. in extremity, pruritus, and somnolence. (6.1) Dosing in pediatric patients was derived using a population PK approach.
    [Show full text]
  • Studies on Antitoxin Use for Postexposure Prophylaxis (PEP)
    ACIP Anthrax Vaccine Work Group William Bower, MD, FIDSA Epidemiology Team Lead Bacterial Special Pathogens October 23, 2018 National Center for Emerging and Zoonotic Disease Division of High-Consequence Pathogens and Pathology Outline Overview of anthrax antitoxins Studies on antitoxin use for postexposure prophylaxis (PEP) . Anthrax antitoxin for PEP and survival in animal models . Anthrax antitoxin effect on acquired immunity . Anthrax antitoxin use with anthrax vaccine adsorbed (AVA) Work group discussions Guidance on anthrax antitoxin use for PEP 2 Anthrax Pathogenesis 3 Background – Anthrax Antitoxins There are currently three FDA approved anthrax antitoxins RAXIBACUMAB . Initial U.S. Approval: 2012 . Human IgG1λ monoclonal antibody that binds the protective antigen (PA) component of Bacillus anthracis toxin ANTHRASIL (Anthrax Immune Globulin Intravenous (AIGIV)) . Initial U.S. Approval: 2015 . Purified human IgG containing polyclonal antibodies that bind the protective antigen (PA) component of B. anthracis lethal and edema toxins collected from individuals immunized with AVA ANTHIM (obiltoxaximab) . Initial U.S. Approval: 2016 . Chimeric IgG1 kappa monoclonal antibody that binds the PA component of B. anthracis toxin 4 Background – Anthrax Antitoxins Indications Anthrax antitoxins all have an indication for the treatment of adult and pediatric patients with inhalation anthrax due to B. anthracis in combination with appropriate antimicrobials The monoclonal antitoxins, raxibacumab and obiltoxaximab, are also indicated for
    [Show full text]
  • 1 Supplementary Materials 1 2 Data Sources 3 in Total, 60 Antibodies
    1 Supplementary Materials 2 3 Data Sources 4 In total, 60 antibodies and antibody-based biologics that were approved 5 by the EMA or FDA between 1995 and 2019 were included in our analyses. 6 The excluded antibodies were: (1) the withdrawn or marketing discontinued antibodies 7 or fusion proteins (e.g., muromonab-CD3, efalizumab, tositumomab- 8 I131, daclizumab, catumaxomab, edrecolomab, Nebacumab, and alefacept); (2) 9 antibody-drug conjugates (e.g., brentuximab vedotin, ado-trastuzumab 10 emtansine, inotuzumab ozogamicin, gemtuzumab ozogamicin, 11 and polatuzumab vedotin); (3) bi-specific antibodies (e.g., emicizumab and 12 blinatumomab); (4) antibodies with neither F CL, nor KD information available 13 (e.g., Ibritumomab tiuxetan, efmoroctocog-α, eftrenonacog-α, mogamulizumab, 14 and ustekinumab); (5) single-dosed antibodies that cannot support Css calculation, 15 including abciximab, 16 alemtuzumab, basiliximmab, bezlotoxumab, idarucizumab, obiloxaximab, and 17 raxibacumab; and (6) local dosing and acting antibodies (e.g., aflibercept, ranibizumab, 18 and brolucizumab). 19 We obtained the labeled TDs and dosing regimens from 20 the Drugs@FDA website and the literature. The following information was also 21 collected: (1) molecular weight, (2) administration route, (3) bioavailability (F), (4) in 22 vitro antigen-binding dissociation constant (KD), (5) the antibody systemic clearance 23 (CL), (6) target abundance and half-life, (7) the approved indications, 24 and (8) the mechanism of action. More specifications for these parameters were 25 provided in the Supplementary Table 1. 26 1 27 Supplementary Figure 1 28 29 30 Supplementary Figure 1. Target turnovers are not relevant to TEARs in four 31 disease-target scenarios. Dots represent the mean values.
    [Show full text]
  • Monoclonal Antibodies for Infectious Diseases
    Monoclonal antibodies for infectious diseases Martin Friede 1890: Emil von Behring and Shibasaburo Kitasato From anti-toxin to the serotherapy of diptheria, tetanus Nobel prize for von Behring in 1901 2 | The birth of anti-infectives 3 | A century of trials and success Diptheria Influenza (pandemic) Tetanus Haemophilus influenza Rabies Pseudomonas Hepatitis A & B Malaria Varicella Polio RSV Hemorhagic fever Pneumococcus Ebola (?) Meningococcus …. And others 4 | And still a strong demand Procurement by PAHO revolving fund (doses) 2009 2010 2011 2012 Tetanus 14000 5000 17000 32000 Rabies 15000 16000 31000 40000 Hepatitis B 47000 48000 5000 72000 Varicella 12000 15000 23000 21000 5 | The Birth of Monoclonal antibodies 1975 Cesar Milstein and Georges Köhler develop technique for making monoclonal antibodies Nobel prize: 1982 "Developed as a "research tool…" Currently $140,000,000,000 / year market 6 | The pros and cons of monoclonal antibodies for infectious diseases Safety theoretically easy to predict (but not always…) Functions rapidly (unlike vaccines) Quicker to develop than vaccines Supply: limited ! Cost: !!!!! Especially when grams of product needed ! Time to development !! 7 | mAbs in infectious disease Palivizumab: anti-RSV mAb (Medimmune 1998) – First monoclonal approved for prophylaxis of infectious disease (RSV). – For premature infants (<29 weeks), CHF, bronchopulmonary dysplasia. – $7000-10,000 per treatment course (4-5 months). Raxibacumab: anti-anthrax mAb (GSK 2012) – Approved using animal rule – For treatment of inhalation anthrax. 8 | Improved production systems Murine myeloma NS0 cells Variable glycosylation CHO cells patterns -> immunogenicity, function PerC6 Tobacco plants Yield 0.1g/l 10g/l Technical skills barrier, Technology access barrier, Cost of goods: $10,000/g $100g CAPEX barrier.
    [Show full text]
  • Raxibacumab: a Panacea for Anthrax Disease?
    Comment Raxibacumab: a panacea for anthrax disease? When anthrax exposure is suspected, recommended isolates is unclear.5 Raxibacumab treatment of anthrax post-exposure prophylaxis is 60 days of antibiotics in animal models has focused on using the B anthracis (ciprofloxacin or doxycycline) combined with anthrax type strain Ames. However, diversity of the B anthracis vaccination. Anthrax Vaccine Adsorbed (AVA) is pathogen does exist,6 and new anthrax-like diseases are approved for human use in the USA, and Anthrax evolving in nature.7,8 Future work investigating the ability Vaccine Precipitated (AVP) is approved in the UK. The of AVA and raxibacumab to prevent anthrax from a major antigen in these vaccines is the Bacillus anthracis B anthracis diversity panel consisting of wildlife-outbreak protective antigen; this molecule is secreted by isolates and genetically unique vaccine-resistant strains B anthracis and creates a pore in the host membrane using an animal model would be of considerable that binds then separately translocates lethal factor value. Demonstration of anti-toxin efficacy against Flickr/Navy Medicine and oedema factor into the cell.1 Even with prompt the Bacillus cereus biovar anthracis, an anthrax-causing Lancet Infect Dis 2020 antibiotic treatment, the toxins released can still B cereus variant, would also be an important milestone Published Online April 22, 2020 overwhelm the host, leading to toxaemia and death; for raxibacumab. Although currently isolated to areas in https://doi.org/10.1016/ thus, development and testing of anti-toxin treatments west and central Africa, B cereus biovar anthracis infects S1473-3099(20)30164-X is needed.
    [Show full text]
  • (INN) for Biological and Biotechnological Substances
    WHO/EMP/RHT/TSN/2019.1 International Nonproprietary Names (INN) for biological and biotechnological substances (a review) 2019 WHO/EMP/RHT/TSN/2019.1 International Nonproprietary Names (INN) for biological and biotechnological substances (a review) 2019 International Nonproprietary Names (INN) Programme Technologies Standards and Norms (TSN) Regulation of Medicines and other Health Technologies (RHT) Essential Medicines and Health Products (EMP) International Nonproprietary Names (INN) for biological and biotechnological substances (a review) FORMER DOCUMENT NUMBER: INN Working Document 05.179 © World Health Organization 2019 All rights reserved. Publications of the World Health Organization are available on the WHO website (www.who.int) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: [email protected]). Requests for permission to reproduce or translate WHO publications –whether for sale or for non-commercial distribution– should be addressed to WHO Press through the WHO website (www.who.int/about/licensing/copyright_form/en/index.html). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted and dashed lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned.
    [Show full text]
  • Pharmacology and Anti-Infective Role of Raxibacumab: a Novel Monoclonal Antibody for the Treatment of Anthrax H Singh1, S Ratol2, P Thangaraju3, S Kumar1, a Goel4
    358 Pharmacology and Anti-infective Role of Raxibacumab: A Novel Monoclonal Antibody for the Treatment of Anthrax H Singh1, S Ratol2, P Thangaraju3, S Kumar1, A Goel4 ABSTRACT Anthrax, caused by Bacillus anthracis (B anthracis), poses a potential threat as a bioterror agent because after inhalation, the spores rapidly cause bacteraemia and toxaemia. It produces a toxin consisting of three proteins ie protective antigen (PA), oedema factor (EF) and lethal factor (LF). Protective antigen plays a central role in the pathophysiology of anthrax and offers an excellent therapeutic target for treatment of anthrax. Raxibacumab is a recombinant, fully human, IgG1λ monoclonal antibody directed against PA of B anthracis. It inhibits PA binding to the anthrax toxin receptor and inhibits toxin-mediated cell death. It has been approved under animal rule or animal efficacy rule by the United States Food and Drug Administration which comes into play when it is not feasible or ethical to perform controlled clinical trials in humans. It has shown promising results in various animal studies which includes significantly improved survival rates in the raxi- bacumab group than non-raxibacumab group. Keywords: Anthrax, Bacillus anthracis, raxibacumab Farmacología y papel antiinfeccioso del raxibacumab: un novedoso anticuerpo mono- clonal para el tratamiento del ántrax H Singh1, S Ratol2, P Thangaraju3, S Kumar1, A Goel4 RESUMEN El ántrax, causado por el Bacillus anthracis, representa una amenaza potencial como agente bio- terrorista, porque tras su inhalación, las esporas rápidamente causan bacteriemia y toxemia. Pro- duce una toxina que consta de tres proteínas, a saber, el antígeno protector (AP), el factor edema (FE), y el factor letal (FL).
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 9,446,134 B2 Maggio (45) Date of Patent: *Sep
    USOO9446.134B2 (12) United States Patent (10) Patent No.: US 9,446,134 B2 Maggio (45) Date of Patent: *Sep. 20, 2016 (54) STABILIZING ALKYLGLYCOSIDE 5, 198420 A 3, 1993 Donahoe et al. COMPOSITIONS AND METHODS THEREOF 5,369,095 A 11/1994 Kee 5,556,757 A 9/1996 Alstyne et al. (71) Applicant: Aegis Therapeutics, LLC, San Diego, 5,556,940 A 9, 1996 Willick et al. 5,661,130 A 8, 1997 Meezan CA (US) 6,524,557 B1 2/2003 Backstrom et al. (72) Inventor: Edward T. Maggio, San Diego, CA 6,551,578 B2 4/2003 Adjei et al. (US) 7,425,542 B2 9/2008 Maggio 7.998,927 B2 8/2011 Maggio (73) Assignee: Aegis Therapeutics, LLC, San Diego, 8,133,863 B2 * 3/2012 Maggio ........................ 514,111 CA (US) 8,226,949 B2 7/2012 Maggio 2002/0110524 A1 8, 2002 Cowan et al. (*) Notice: Subject to any disclaimer, the term of this 2004/0209814 A1 10/2004 Nauck patent is extended or adjusted under 35 2005/0215475 A1 9/2005 Ong et al. U.S.C. 154(b) by 0 days. 2005/0276843 A1 12/2005 Quay et al. 2006, 0046962 A1 3/2006 Meezan et al. This patent is Subject to a terminal dis 2006, OO74025 A1 4/2006 Quay et al. claimer. 2006/00846.04 A1 4/2006 Kitaura et al. 2006,0183674 A1 8, 2006 Brand (21) Appl. No.: 14/494,990 2007/011 1938 A1 5/2007 Pert 2008. O194461 A1 8/2008 Maggio (22) Filed: Sep.
    [Show full text]