Methods and pharmaceuticals for treatment of viral infections of the eye
Inventors
Squiquera, Luis • Sulley, Jamie
Assignees
Publication Number
US-10293032-B2
Publication Date
2019-05-21
Expiration Date
2036-06-13
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Abstract
Viral infections of the eye, and particularly viral infections in the Herpesviridae and Adenoviridae families, can be treated by administration of a pharmaceutical made up of an enzymatically active ribonuclease and a vehicle. Advantageously, the enzymatically active ribonuclease is ranpirnase, the '805 variant, rAmphinase 2, and Amphinase 2, and the vehicle is an aqueous solution.
Core Innovation
The invention provides methods and pharmaceuticals for treating viral infections of the eye caused by viruses from the Herpesviridae and Adenoviridae families through administration of enzymatically active ribonucleases combined with a vehicle. The enzymatically active ribonucleases include ranpirnase, the '805 variant, Amphinase 2, and rAmphinase 2, with preferred administration as an aqueous solution. These ribonucleases belong to the ribonuclease A superfamily and demonstrate antiviral activity against herpes simplex virus types and adenoviruses.
The problem addressed by the invention is the inadequate efficacy and safety of existing treatments for viral eye infections. Known antiviral treatments like topical acyclovir cause frequent application requirements and irritation, while oral options can have serious systemic side effects. Other antivirals such as gancyclovir require intravenous administration and have limited outpatient use. Therefore, there is a need for a better pharmaceutical and method that effectively treat viral eye infections while minimizing adverse effects and irritation.
Contrary to expectations that proteinaceous ribonucleases would irritate the eye, experimental Draize tests demonstrated that ranpirnase applied topically in an aqueous solution is non-irritating as measured by international ocular irritation criteria. Given the high homology and similar antiviral activity of the '805 variant, Amphinase 2, and rAmphinase 2 to ranpirnase, these ribonucleases are also expected to be safe and effective for treating viral infections of the human eye.
Claims Coverage
The patent contains multiple independent claims focusing on methods of treating adenoviral infections of the eye using enzymatically active ribonucleases from the ribonuclease A superfamily, particularly ranpirnase and its variants, with pharmaceutical compositions including specified vehicles and modes of administration.
Using ribonuclease A superfamily enzymes for treating adenoviral eye infections
A method of treating adenoviral infection of the eye by administering a therapeutically effective dose of a ribonuclease that is a member of the ribonuclease A superfamily.
Selection of specific ribonucleases for treatment
The ribonuclease used is selected from ranpirnase, the '805 variant, Amphinase 2, and rAmphinase 2, including their functional equivalents.
Non-irritancy of ribonucleases to the eye
The ribonuclease is non-irritating to the eye as determined by the Globally Harmonized System of Classification Evaluation Criteria and the European Economic Community Ocular Evaluation Criteria.
Administration of ribonucleases in ophthalmic pharmaceutical compositions
Administering an ophthalmic composition comprising a therapeutically effective dose of a ribonuclease (from the ribonuclease A superfamily) that is non-irritating to the eye and a vehicle, where the vehicle may be an aqueous solution.
Topical administration of ranpirnase for adenoviral eye infections
Topically administering to the eye a therapeutically effective amount of ranpirnase, including recombinant ranpirnase, formulated as various ophthalmic pharmaceutical compositions such as solutions, suspensions, gels, ointments, and nanoparticles.
Treatment targeting specific adenoviral strains and diseases
Treatment is directed toward adenoviral infections causing viral conjunctivitis, epidemic keratoconjunctivitis, or pharyngoconjunctival fever caused by adenovirus types 3, 4, 7, 8, 19, 29, or 37.
The claims cover methods and compositions using ribonuclease A superfamily enzymes, especially ranpirnase and its variants, that are non-irritating and formulated for ophthalmic use to treat adenoviral infections of the eye, including topical administration targeting specific adenoviral diseases.
Stated Advantages
Ranpirnase and similar ribonucleases provide effective treatment of viral infections of the eye with antiviral activity against Herpesviridae and Adenoviridae families.
The ribonucleases are non-irritating to the eye, avoiding the inflammation and irritation commonly caused by protein therapeutics.
Topical administration allows direct delivery to the eye, enabling outpatient treatment unlike some existing intravenous antivirals.
The treatment avoids the frequent dosing and significant adverse systemic effects associated with current antiviral medications.
Documented Applications
Treatment of human viral eye infections such as conjunctivitis, keratitis, retinitis, keratoconjunctivitis, chorioretinitis, pharyngoconjunctival fever, and CMV retinitis.
Treatment of infections caused by Herpesviridae family viruses including herpes simplex virus types 1 and 2, human cytomegalovirus, herpes zoster virus, and varicella zoster virus.
Treatment of infections caused by Adenoviridae family viruses consisting of adenovirus types 3, 4, 7, 8, 19, 29, and 37.
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