Evidence map›Paper›PMID 31212950›Full record

ArticleToxins2019

Pharmacokinetics of Human Recombinant Anti-Botulinum Toxin Antibodies in Rats.

Yero Espinoza, David Wong, Ago Ahene, Kenneth Der, Zachary Martinez, John Pham, Ronald R Cobb, Shauna Farr-Jones, James D Marks, Milan T Tomic

Abstract read
In one paragraph

Article in Toxins, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Trial
  2. Trial
  3. Article
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  8. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Yero EspinozaOlogy Bioservices Inc., 630 Bancroft Way, Suite D, Berkeley, CA 94710, USA. yero.espinoza@ologybio.com.
David WongOlogy Bioservices Inc., 630 Bancroft Way, Suite D, Berkeley, CA 94710, USA. david.wong@ologybio.com.
Ago AheneFiveprime Therapeutics Inc., 111 Oyster Point Blvd, South San Francisco, CA 94080, USA. ago.ahene@fiveprime.com.
Kenneth DerPortola Pharmaceuticals Inc., 270 E Grand Ave, South San Francisco, CA 94080, USA. kder@portola.com.
Zachary MartinezOlogy Bioservices Inc., 630 Bancroft Way, Suite D, Berkeley, CA 94710, USA. zach.martinez@ologybio.com.
John PhamOncoMed Inc., 800 Chesapeake Dr, Redwood City, CA 94063, USA. Jtpham2015@yahoo.com.
Ronald R CobbOlogy Bioservices Inc., 13200 NW Nano Ct, Alachua, FL 32615, USA. ron.cobb@ologybio.com.ORCID 0000-0002-6199-1931
Shauna Farr-JonesDepartment of Anesthesia and Perioperative Care, University of California, San Francisco, 1001 Potrero Ave, San Francisco, CA 94110, USA. shauna.farr-jones@ucsf.edu.ORCID 0000-0003-4130-6332
James D MarksDepartment of Anesthesia and Perioperative Care, University of California, San Francisco, 1001 Potrero Ave, San Francisco, CA 94110, USA. jim.marks@ucsf.edu.
Milan T TomicOlogy Bioservices Inc., 630 Bancroft Way, Suite D, Berkeley, CA 94710, USA. milan.tomic@ologybio.com.

Funding

NIAID NIH HHS HHSN272200800028CNIAID NIH HHS HHSN272201100031C
6 · The paper itself

Abstract

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.

Indexed as

AnimalsAntibodies, MonoclonalBotulinum ToxinsFemaleHumansImmunoglobulin GMaleRats, Sprague-DawleyRecombinant ProteinsAntibodies, MonoclonalBotulinum ToxinsImmunoglobulin GRecombinant Proteinsanti-botulinum neurotoxin antibodybotulinum neurotoxinoligoclonal antibodypharmacokineticsratrecombinant antibody

Identifiers

PMID31212950
PMCPMC6628388

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.