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Pharmacokinetics of Human Recombinant Anti-Botulinum Toxin Antibodies in Rats

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Ology Bioservices Inc., 630 Bancroft Way, Suite D, Berkeley, CA 94710, USA
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Fiveprime Therapeutics Inc., 111 Oyster Point Blvd, South San Francisco, CA 94080, USA
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Portola Pharmaceuticals Inc., 270 E Grand Ave, South San Francisco, CA 94080, USA
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OncoMed Inc., 800 Chesapeake Dr, Redwood City, CA 94063, USA
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Ology Bioservices Inc., 13200 NW Nano Ct, Alachua, FL 32615, USA
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Department of Anesthesia and Perioperative Care, University of California, San Francisco, 1001 Potrero Ave, San Francisco, CA 94110, USA
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Author to whom correspondence should be addressed.
Received: 30 April 2019 / Revised: 2 June 2019 / Accepted: 3 June 2019 / Published: 17 June 2019
(This article belongs to the Section Bacterial Toxins)
Botulinum neurotoxins (BoNT) are potential biothreat agents due to their high lethality, potency, and ease of distribution, thus the development of antitoxins is a high priority to the US government. This study examined pre-clinical pharmacokinetic studies in rats of four oligoclonal anti-BoNT mAb-based therapeutics (NTM-1631, NTM-1632, NTM-1633, NTM-1634) for five BoNT serotypes (A, B, E, C, and D). NTM-1631, NTM-1632, and NTM-1633 each consist of three IgG1 mAbs, each with a distinct human or humanized variable region which bind to distinct epitopes on BoNT serotype A, B, or E respectively. NTM-1634 consists of four human immunoglobulin G1 (IgG1) mAbs binding BoNT C/D mosaic toxins. The mechanism of these antitoxins requires that three antibodies simultaneously bind toxin to achieve rapid clearance. Rats (total 378) displayed no adverse clinical signs attributed to antibody treatment from any of the antitoxins. Pharmacokinetic evaluation demonstrated that the individual mAbs are slowly eliminated, exhibiting dose-dependent exposure and long elimination half-lives ranging from 6.5 days to 10 days. There were no consistent differences observed between males and females or among the individual antibodies in each formulation in half-life. Anti-drug antibodies (ADA) were observed, as expected for human antibodies administered to rats. The results presented were used to support the clinical investigation of antibody-based botulism antitoxins. View Full-Text
Keywords: botulinum neurotoxin; pharmacokinetics; recombinant antibody; rat; oligoclonal antibody; anti-botulinum neurotoxin antibody botulinum neurotoxin; pharmacokinetics; recombinant antibody; rat; oligoclonal antibody; anti-botulinum neurotoxin antibody
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MDPI and ACS Style

Espinoza, Y.; Wong, D.; Ahene, A.; Der, K.; Martinez, Z.; Pham, J.; Cobb, R.R.; Farr-Jones, S.; Marks, J.D.; Tomic, M.T. Pharmacokinetics of Human Recombinant Anti-Botulinum Toxin Antibodies in Rats. Toxins 2019, 11, 345. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11060345

AMA Style

Espinoza Y, Wong D, Ahene A, Der K, Martinez Z, Pham J, Cobb RR, Farr-Jones S, Marks JD, Tomic MT. Pharmacokinetics of Human Recombinant Anti-Botulinum Toxin Antibodies in Rats. Toxins. 2019; 11(6):345. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11060345

Chicago/Turabian Style

Espinoza, Yero, David Wong, Ago Ahene, Kenneth Der, Zachary Martinez, John Pham, Ronald R. Cobb, Shauna Farr-Jones, James. D. Marks, and Milan T. Tomic 2019. "Pharmacokinetics of Human Recombinant Anti-Botulinum Toxin Antibodies in Rats" Toxins 11, no. 6: 345. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11060345

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