Evidence map›Paper›PMID 21700771›Full record

ArticleBlood2011

Prolonged half-life and preserved enzymatic properties of factor IX selectively PEGylated on native N-glycans in the activation peptide.

Henrik Østergaard, Jais R Bjelke, Lene Hansen, Lars Christian Petersen, Anette A Pedersen, Torben Elm, Flemming Møller, Mette B Hermit, Pernille K Holm, Thomas N Krogh and 12 more

Abstract read
In one paragraph

Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
8.1field-weighted citation impact, top 2% of its field
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

41 citing papers in PubMed, 136 citations in OpenAlex.

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  14. Review
  15. Advances and innovations in haemophilia treatment.Nature reviews. Drug discovery · 2018
    Review
  16. GlycoPEGylated recombinant factor IX for hemophilia B in context.Drug design, development and therapy · 2018
    Review
  17. Review
  18. Article
  19. Recent advances in hemophilia B therapy.Drug delivery and translational research · 2017
    Review
  20. Article
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

22 authors at 3 institutions in 3 countries.

Henrik ØstergaardHaemostasis Biology, Novo Nordisk A/S, Maaloev, Denmark. hqsg@novonordisk.com
Jais R Bjelke
Lene Hansen
Lars Christian Petersen
Anette A Pedersen
Torben Elm
Flemming Møller
Mette B Hermit
Pernille K Holm
Thomas N Krogh
Jørn M Petersen
Mirella Ezban
Brit B Sørensen
Mette D Andersen
Henrik Agersø
Haleh Ahmadian
Kristoffer W Balling
Marie Louise S Christiansen
Karin Knobe
Timothy C Nichols
Søren E Bjørn
Mikael Tranholm
Novo Nordisk (Denmark) · DKLund University · SEUniversity of North Carolina at Chapel Hill · US

Funding

Maintenance of Models of Human Hemophilia and VWDR24HL063098 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI NICHOLS, TIMOTHY CHARLES · 1999 to 2019
$15.1M
NHLBI NIH HHS R24 HL063098
6 · The paper itself

Abstract

Current management of hemophilia B entails multiple weekly infusions of factor IX (FIX) to prevent bleeding episodes. In an attempt to make a longer acting recombinant FIX (rFIX), we have explored a new releasable protraction concept using the native N-glycans in the activation peptide as sites for attachment of polyethylene glycol (PEG). Release of the activation peptide by physiologic activators converted glycoPEGylated rFIX (N9-GP) to native rFIXa and proceeded with normal kinetics for FXIa, while the K(m) for activation by FVIIa-tissue factor (TF) was increased by 2-fold. Consistent with minimal perturbation of rFIX by the attached PEG, N9-GP retained 73%-100% specific activity in plasma and whole-blood-based assays and showed efficacy comparable with rFIX in stopping acute bleeds in hemophilia B mice. In animal models N9-GP exhibited up to 2-fold increased in vivo recovery and a markedly prolonged half-life in mini-pig (76 hours) and hemophilia B dog (113 hours) compared with rFIX (16 hours). The extended circulation time of N9-GP was reflected in prolonged correction of coagulation parameters in hemophilia B dog and duration of effect in hemophilia B mice. Collectively, these results suggest that N9-GP has the potential to offer efficacious prophylactic and acute treatment of hemophilia B patients at a reduced dosing frequency.

Indexed as

AnimalsBinding SitesDisease Models, AnimalDogsFactor IXFemaleHalf-LifeHemophilia BHemostaticsHumansIn Vitro TechniquesKineticsMaleMiceMice, Mutant StrainsPolyethylene GlycolsFactor IXHemostaticsPolyethylene GlycolsPolysaccharidesRecombinant Proteins

Identifiers

PMID21700771
PMCPMC3952454
OpenAlexW2069900144

What OpenQuestion holds

Textmetadata
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.