Safety and PK/PD correlation of TV-1106, a recombinant fused human albumin-growth hormone, following repeat dose administration to monkeys

Ashkenazi, Nurit; Rosenstock, Moti; Hallak, Hussein; Bassan, Merav; Rasamoelisolo, Michele; Leuschner, J; Shinar, Doron

doi:10.1016/j.ghir.2016.08.001

Cited by 2 publications

(2 citation statements)

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“…30 This rescue concept has been utilized in the hGH-albumin conjugate albutropin. 31,32 In the attempt to identify a long-acting hGH molecule, hGHalbumin fusions were deselected because of the risk of immunogenicity from the connecting regions of such molecules and chose to pursue half-life prolongation of hGH molecules to which noncovalent albumin binding moieties were conjugated.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Although hGH has been reported to escape lysosomal degradation to some degree, the amount of receptor-mediated degradation can be lessened further by reducing receptor affinity, which might result in loss of efficacy or by conjugation to molecules that are capable of rescuing internalized molecules from lysosomal degradation by binding to the neonatal Fc receptor . This rescue concept has been utilized in the hGH-albumin conjugate albutropin. , …”

Section: Resultsmentioning

confidence: 99%

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Long-Acting Human Growth Hormone Analogue by Noncovalent Albumin Binding

et al. 2018

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The present work describes a series of human growth hormone (hGH) albumin binder conjugates with an extended in vivo half-life. A broad range of different conjugates were studied by varying the albumin binder structure and conjugation site. Conjugates were conveniently obtained by reductive alkylation or by alkylation to introduced cysteines using functionalized albumin-binding side chains. In vitro and in vivo profiling provided the basis for identification of position L101C in human growth hormone as the most optimal position for conjugation, where both a sufficient level of receptor binding and a suitably long half-life could yield a molecule with potential for a once-weekly dosing regimen.

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Section: ■ Results and Discussionmentioning

confidence: 99%