Sustained release formulations for delivery of proteins to the eye and methods of preparing same
Inventors
Wong, Vernon G. • Wood, Louis L. • Huang, Glenn T.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9814773-B2
Publication Date
2017-11-14
Expiration Date
Abstract
The present invention provides for injectable pharmaceutical sustained release formulations for delivery of active agents, particularly therapeutic proteins, to the eye. The formulations are biocompatible, biodegradable sustained release formulations comprising low-solubility liquid excipients and relatively small amounts (less than about 10%) of biocompatible, biodegradable polymer such as PLA or PLGA polymers. A unit dose of 5 μL to 100 μL of the formulation provides for sustained release of the agent for at least 14 days.
Core Innovation
The invention describes a liquid pharmaceutical formulation for injection into the eye for the sustained release of a therapeutic protein. The formulation includes a liquid, biodegradable, biocompatible non-polymeric excipient in the form of benzyl benzoate and a biodegradable, biocompatible poly(d,l-lactide-co-glycolide) (PLGA) polymer having a lactide:glycolide ratio of 50:50, a molecular weight range of 7,000-17,000, and an alkyl ester end group.
The formulation defines a wt % ratio of non-polymeric excipient to polymer of about 90:10 to 99:1, inclusive. After injection of about 5 µL to about 100 µL, inclusive, using a 25, 27, 28, 30 gauge, or smaller needle, the formulation maintains monolithic integrity and liquid state.
The invention also describes a syringeable liquid ophthalmic formulation in which a pharmaceutically active protein is present in a therapeutically effective amount for a subject in need thereof. In this syringeable formulation, benzyl benzoate is combined with the specified PLGA polymer in a benzyl benzoate:polymer wt % ratio of 90:10 to 99:1, inclusive, and the pharmaceutically active protein is solubilized or dispersed in the liquid ophthalmic formulation.
Claims Coverage
The independent claims cover two closely related inventive features, with additional refinements for syringeability and post-injection behavior. The main features are the specific benzyl benzoate/PLGA liquid composition, the PLGA property constraints, the defined excipient-to-polymer wt % ratio, and the requirement that the formulation remains monolithic or a liquid bolus state after injection while sustaining release for at least about 14 days.
Monolithic benzyl benzoate/PLGA liquid for ocular sustained protein release
A liquid pharmaceutical formulation for injection into the eye for the sustained release of a therapeutic protein comprising benzyl benzoate and a biodegradable, biocompatible PLGA polymer having a lactide:glycolide ratio of 50:50, MW range 7,000-17,000, and an alkyl ester end group, with a wt % ratio of non-polymeric excipient to polymer of about 90:10 to 99:1 inclusive.
Needle-deliverable monolithic integrity after small-volume injection
Upon and following injection of about 5 µL to about 100 µL inclusive of the formulation using a 25, 27, 28, 30 gauge, or smaller needle, the formulation maintains its monolithic integrity and liquid state.
Sustained release for at least about 14 days
The formulation releases the therapeutic protein from the liquid formulation for a period of at least about 14 days.
Syringeable ophthalmic benzyl benzoate/PLGA liquid with protein solubilized or dispersed
A syringeable liquid ophthalmic formulation comprising a pharmaceutically active protein in a therapeutically effective amount, benzyl benzoate, and a biodegradable, biocompatible PLGA polymer having a lactide:glycolide ratio of 50:50, MW range 7,000-17,000, and an alkyl ester end group, with a benzyl benzoate:polymer wt % ratio of 90:10 to 99:1 inclusive, wherein the pharmaceutically active protein is solubilized or dispersed in the liquid ophthalmic formulation.
Small-gauge syringeability enabling post-injection liquid bolus release
A volume of about 5 µL to about 100 µL inclusive of the liquid ophthalmic formulation is syringeable through a 25, 27, 28, 30 gauge, or smaller needle, and upon injection and thereafter the liquid ophthalmic formulation maintains a liquid bolus state.
The independent claims cover a benzyl benzoate/PLGA liquid ophthalmic formulation with defined PLGA composition and a specified excipient-to-polymer wt % ratio. They require that after small-volume injection through small-gauge needles the formulation remains monolithic or in a liquid bolus state and sustains release of a therapeutic protein for at least about 14 days.
Stated Advantages
Maintains monolithic integrity and liquid state upon and following injection.
Maintains a liquid bolus state upon injection and thereafter.
Releases the therapeutic protein for at least about 14 days.
Is syringeable through a 25, 27, 28, 30 gauge, or smaller needle while preserving the post-injection liquid state.
Documented Applications
Injection into the eye for sustained release of a therapeutic protein.
Syringeable liquid ophthalmic formulation for a subject in need of a therapeutically effective amount of a pharmaceutically active protein, delivered by injection to the subject’s eye.
Interested in licensing this patent?