Long-acting protein drugs for the treatment of ocular diseases

Joy G. Ghosh (), Andrew A. Nguyen, Chad E. Bigelow, Stephen Poor, Yubin Qiu, Nalini Rangaswamy, Richard Ornberg, Brittany Jackson, Howard Mak, Tucker Ezell, Vania Kenanova, Elisa de la Cruz, Ana Carrion, Bijan Etemad-Gilbertson, Roxana Garcia Caro, Kan Zhu, Vinney George, Jirong Bai, Radhika Sharma-Nahar, Siyuan Shen, Yiqin Wang, Kulandayan K. Subramanian, Elizabeth Fassbender, Michael Maker, Shawn Hanks, Joanna Vrouvlianis, Barrett Leehy, Debby Long, Melissa Prentiss, Viral Kansara, Bruce Jaffee, Thaddeus P. Dryja and Michael Roguska
Additional contact information
Joy G. Ghosh: Novartis Institutes for BioMedical Research
Andrew A. Nguyen: Novartis Institutes for BioMedical Research
Chad E. Bigelow: Novartis Institutes for BioMedical Research
Stephen Poor: Novartis Institutes for BioMedical Research
Yubin Qiu: Novartis Institutes for BioMedical Research
Nalini Rangaswamy: Novartis Institutes for BioMedical Research
Richard Ornberg: Novartis Institutes for BioMedical Research
Brittany Jackson: Novartis Institutes for BioMedical Research
Howard Mak: Novartis Institutes for BioMedical Research
Tucker Ezell: Novartis Institutes for BioMedical Research
Vania Kenanova: Novartis Institutes for BioMedical Research
Elisa de la Cruz: Novartis Institutes for BioMedical Research
Ana Carrion: Novartis Institutes for BioMedical Research
Bijan Etemad-Gilbertson: Novartis Institutes for BioMedical Research
Roxana Garcia Caro: Novartis Institutes for BioMedical Research
Kan Zhu: Novartis Institutes for BioMedical Research
Vinney George: Novartis Institutes for BioMedical Research
Jirong Bai: Novartis Institutes for BioMedical Research
Radhika Sharma-Nahar: Novartis Institutes for BioMedical Research
Siyuan Shen: Novartis Institutes for BioMedical Research
Yiqin Wang: Novartis Institutes for BioMedical Research
Kulandayan K. Subramanian: Novartis Institutes for BioMedical Research
Elizabeth Fassbender: Novartis Institutes for BioMedical Research
Michael Maker: Novartis Institutes for BioMedical Research
Shawn Hanks: Novartis Institutes for BioMedical Research
Joanna Vrouvlianis: Novartis Institutes for BioMedical Research
Barrett Leehy: Novartis Institutes for BioMedical Research
Debby Long: Novartis Institutes for BioMedical Research
Melissa Prentiss: Novartis Institutes for BioMedical Research
Viral Kansara: Novartis Institutes for BioMedical Research
Bruce Jaffee: Novartis Institutes for BioMedical Research
Thaddeus P. Dryja: Novartis Institutes for BioMedical Research
Michael Roguska: Novartis Institutes for BioMedical Research

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: Abstract Protein drugs that neutralize vascular endothelial growth factor (VEGF), such as aflibercept or ranibizumab, rescue vision in patients with retinal vascular diseases. Nonetheless, optimal visual outcomes require intraocular injections as frequently as every month. Here we report a method to extend the intravitreal half-life of protein drugs as an alternative to either encapsulation or chemical modifications with polymers. We combine a 97-amino-acid peptide of human origin that binds hyaluronan, a major macromolecular component of the eye’s vitreous, with therapeutic antibodies and proteins. When administered to rabbit and monkey eyes, the half-life of the modified proteins is increased ∼3–4-fold relative to unmodified proteins. We further show that prototype long-acting anti-VEGF drugs (LAVAs) that include this peptide attenuate VEGF-induced retinal changes in animal models of neovascular retinal disease ∼3–4-fold longer than unmodified drugs. This approach has the potential to reduce the dosing frequency associated with retinal disease treatments.

Date: 2017
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DOI: 10.1038/ncomms14837

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