Immunome | Date: 2016-05-31
Monoclonal antibodies for medical and scientific research; antibodies and immunoconjugates for medical and scientific research; proteins and components of proteins for medical and scientific research; cells, cell extracts and components of cells for medical and scientific research. Monoclonal antibodies and immunoconjugates for medical or clinical use; pharmaceutical compositions comprising monoclonal antibodies; pharmaceutical compositions comprising immunoconjugates; cells, cell extracts and components of cells for medical or clinical use; pharmaceutical preparations for use in the diagnosis, prevention, management and treatment of oncological, neurological, infectious disease, metabolic, viral, endocrine, musculoskeletal, cardiovascular, cardiopulmonary, genitourinary, sexual dysfunction, hepatological, opthalmic, respiratory, gastrointestinal, hormonal, dermatological, psychiatric and immune system related conditions, diseases and disorders; diagnostic preparations for medical use; diagnostic kits comprising reagents for medical and clinical use. Biotechnology services, namely, development of monoclonal antibodies; pharmaceutical, medical, scientific, biopharmaceutical and biotechnology research and development; drug discovery services; providing medical and scientific research information in the field of medicine and pharmaceuticals.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 270.02K | Year: 2008
DESCRIPTION (provided by applicant): Botulinum neurotoxin (BoNT) is an extremely potent neuromuscular blocker that is the cause of the food-borne illness, botulism, and a Category A Select Bioterror agent. Patients exposed to the toxin experience a respira tory paralysis that can be fatal. At present, the only available countermeasures for BoNT exposure are immune sera from either human or equine sources. Unfortunately, the human sera are in very limited supply and the equine sera can cause serious immune si de effects. The long-term goal of this research is to create a panel of antibody therapeutics for BoNT exposure that are able to counteract in exposed individuals any of the 7 known BoNT serotypes. A major impediment to this objective is that studies have shown that significant neutralization of BoNT cannot be achieved with a single antibody. Rather, oligoclonal combinations of three or more antibodies are required, most likely because they can induce rapid clearance of BoNT from the systemic circulation be fore it can poison its target neurons. This proposal builds on a novel human antibody cloning method, which has produced a human IgG antibody that binds serotype B BoNT (BoNT/B) with extremely high affinity. We will modify this antibody such that it will b e able to rapidly clear BoNT/B from the blood circulation, conjugating it to a monoclonal antibody specific for the human complement receptor 1 (CR1). This will create a new product, a heteropolymer antibody (HP). The BoNT/B specific HP will bind to CR1 on the surface of red blood cells and delivers the toxin to hepatic macrophages for destruction. Engaging this immune clearance mechanism of BoNT will enable the HP to neutralize BoNT/B with potency comparable to BoNT antisera. The result of this project wil l be a single HP that is a safe and effective replacement for human and equine BoNT antisera for the treatment of BoNT/B exposure. PUBLIC HEALTH RELEVANCE: At present, there are insufficient quantities of human antisera capable of treating a large-scale ty pe B botulinum neurotoxin (BoNT/B) exposure, such as may occur in a bioterror attack (1). We have cloned a human antibody that binds BoNT/B with extremely high affinity and has partial neutralizing activity. We will modify this antibody using heteropolymer technology (2) to increase its neutralization potency so that it will be an effective countermeasure for BoNT/B exposure.
Immunome | Entity website
Immunome | Entity website
Puligedda R.D.,Lankenau Institute for Medical Research |
Kouiavskaia D.,U.S. Food and Drug Administration |
Adekar S.P.,Lankenau Institute for Medical Research |
Adekar S.P.,Immunome |
And 7 more authors.
Antiviral Research | Year: 2014
An essential requirement for eradication of poliomyelitis is the elimination of circulating vaccine derived polioviruses (cVDPV) and polioviruses excreted by chronically infected individuals with immunodeficiencies (iVDPV). As part of a post-eradication risk management strategy, a human monoclonal antibody (mAb) therapeutic could play a role in halting excretion in asymptomatic carriers and could be used, in combination with vaccines and antiviral drugs, to protect polio-exposed individuals. Cross-neutralizing mAbs may be particularly useful, as they would reduce the number of mAbs needed to create a comprehensive PV therapeutic. We cloned a panel of IgG mAbs from OPV-vaccinated, IPV-boosted healthy subjects. Many of the mAbs had potent neutralizing activities against PV wild-type (WT) and Sabin strains, and two of the mAbs, 12F8 and 1E4, were significantly cross-reactive against types 1 and 2 and types 1 and 3, respectively. Mapping the binding epitopes using strains resistant to neutralization (escape mutants) suggested that cross-specific PV binding epitopes may primarily reside within the canyon region, which interacts with the cellular receptor molecule CD155 and the cross-neutralizing chimpanzee/human mAb, A12. Despite their close proximity, the epitopes for the 12F8 and 1E4 mAbs on Sabin 1 were not functionally identical to the A12 epitope. When tested together, 12F8 and 1E4 neutralized a diverse panel of clinically relevant PV strains and did not exhibit interference. Virus mutants resistant to the anti-poliovirus drug V-073 were also neutralized by the mAbs. The 12F8 and 1E4 mAbs may suitable for use as anti-PV therapeutics. © 2014 Published by Elsevier B.V.