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D. Victor Perlroth, Joel Naor, Wayne To, hong liang; A novel biologics platform extends half-life and improves tissue penetration of intravitreally injected biological agents. Invest. Ophthalmol. Vis. Sci. 2018;59(9):209.
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© ARVO (1962-2015); The Authors (2016-present)
Therapeutics for retinal diseases often require administration by intravitreal injections, and the ocular half-lives of biologic agents such as aflibercept and ranibizumab are relatively short. Thus, patients are subject to frequent injections in order to keep disease activity under control. We have developed a novel, highly branched phosphorylcholine based biopolymer that is water soluble, optically clear and can be conjugated to biologic molecules such as antibodies to form antibody biopolymer bioconjugates with extended ocular half-life and enhanced tissue penetration.
Ocular tissue distribution and pharmacokinetics of 125I labeled protein moieties conjugated to custom phosphorylcholine-based biopolymers were evaluated in male rabbits after intravitreal injection. Plasma and ocular tissue samples were collected from 2 animals per time point at various intervals up to 56 days and analyzed for radioactivity to determine the presence of the bioconjugate. Clinical observations and ocular examinations were performed on animals throughout the studies.
Radioactivity measurements indicated that the vitreal half-life of the bioconjugates ranged from 10 to 16 days, depending on the size of the bioconjugate. The elimination profile from both the retina and the choroid approximated that of the vitreous. Importantly, penetration of the bioconjugates into retina and choroid was superior to what has been observed for other large biologics such as antibodies and FC-fusions.
Conjugation of biologic therapeutic molecules with novel, phosphorylcholine-based biopolymers extended the typical ocular half-life of biological agents three to five fold. In addition, the bioconjugates showed markedly increased penetration into the retina and choroid, indicating that the bioconjugate improves ocular tissue distribution. Together, these data suggest this novel antibody biopolymer conjugate approach may ease patient burden by increasing ocular durability of effect for biologics, therefore requiring fewer treatment administrations in order to keep disease activity under control.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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