Methods of treating ocular inflammatory diseases
Inventors
Jeffords, Elizabeth W. • Gukasyan, Hovhannes John • Verhoeven, Rozemarijn • Hemmati, Houman David • Estes, Daniel J. • Graham, Richard
Assignees
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Publication Number
US-12263160-B2
Publication Date
2025-04-01
Expiration Date
Abstract
The present invention relates to methods of treating ocular inflammatory diseases by administering ophthalmic pharmaceutical compositions of roflumilast. Administration of ophthalmic pharmaceutical compositions of roflumilast can provide significant immunomodulatory and anti-inflammatory activity relative to existing immunomodulatory, immunosuppressant, or non-steroidal anti-inflammatory therapies, including corticosteroids and antihistamines, while also providing an improved safety and convenience profile relative to one or both agents.
Core Innovation
The disclosed invention provides methods for treating a patient having an ocular inflammatory or immune-mediated disorder by administering a stable ophthalmic pharmaceutical suspension comprising a therapeutically effective amount of roflumilast or a pharmaceutically acceptable salt or metabolite thereof. The suspension is administered to an ocular surface and ocular tissues involved in inflammatory and immune-mediated processes, and is formulated with a viscosity agent, a surfactant, and a buffer.
The stable ophthalmic pharmaceutical suspension has a pH between 6.0 and 6.7, with the pH maintained to reduce hydrolysis. The disclosure associates the suspension with tolerability and safety assessments in documented studies, including ocular parameters such as intraocular pressure and central corneal thickness.
Related embodiments state that administration results in reduction of at least one side effect relative to administration of an immunosuppressant, immunomodulatory, or a non-steroidal anti-inflammatory agent. Other embodiments downregulate cytokine activity driven by inflammatory stress in at least one ocular tissue selected from corneal and conjunctival tissue, and in one claim set the cytokine downregulation is superior to that achieved by comparator agents.
Claims Coverage
The consolidated content provides three independent claim sets that collectively cover treatment of ocular inflammatory or immune-mediated disorders using a stable ophthalmic pharmaceutical suspension of roflumilast or a pharmaceutically acceptable salt or metabolite thereof with defined viscosity-agent, surfactant, buffer amounts and a suspension pH between 6.0 and 6.7. The inventive features center on side-effect reduction versus comparator agents, cytokine downregulation in specified ocular tissues, and a superiority requirement for cytokine downregulation.
Stable ophthalmic suspension with defined excipient amounts and pH
A stable ophthalmic pharmaceutical suspension comprising a therapeutically effective amount of roflumilast or a pharmaceutically acceptable salt or metabolite thereof, an amount of a viscosity agent, an amount of a surfactant, and an amount of a buffer, wherein the pH is between 6.0 and 6.7.
Reduction of at least one side effect versus comparator agents
Administration results in a reduction of at least one side effect relative to administration of an immunosuppressant, immunomodulatory, or a non-steroidal anti-inflammatory agent.
Downregulates stress-driven cytokine activity in corneal or conjunctival tissue
Administration downregulates cytokine activity driven by inflammatory stress in at least one ocular tissue selected from corneal and conjunctival tissue.
Superior cytokine downregulation versus comparator agents
Administration downregulates cytokine activity in a manner that is superior to the downregulation of cytokines by administration of an immunosuppressant, immunomodulatory, or a non-steroidal anti-inflammatory agent.
Overall claim coverage centers on administering a stable ophthalmic pharmaceutical suspension containing roflumilast or a pharmaceutically acceptable salt or metabolite with specified excipient concentration ranges and a pH of 6.0 to 6.7, and then demonstrating either reduction of at least one side effect versus comparator agent classes and/or downregulation of stress-driven cytokine activity in ocular tissues, including a superiority cytokine downregulation requirement in one independent claim.
Stated Advantages
Reduction of at least one side effect relative to administration of an immunosuppressant, immunomodulatory, or a non-steroidal anti-inflammatory agent.
Downregulation of cytokine activity driven by inflammatory stress in at least one ocular tissue selected from corneal and conjunctival tissue.
Superior downregulation of cytokines compared to immunosuppressant, immunomodulatory, or non-steroidal anti-inflammatory agent treatments.
Documented Applications
Treating a patient having an ocular inflammatory or immune-mediated disorder by administering the described stable ophthalmic pharmaceutical suspension to the ocular surface.
Ocular surface diseases and related steroid-typically treated conditions, including allergic conjunctivitis or keratoconjunctivitis and Meibomian gland dysfunction.
Anterior or posterior ocular inflammatory or immune-mediated disorders selected from enumerated eye diseases such as uveitis, including juvenile idiopathic arthritis-associated uveitis, and diabetic retinopathy.
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