JP-7857231-B2 - Heterodimer compositions and methods for treating eye disorders

Inventors

• パッラグ，イアン，チャールズ
• ナイマーク，ウェンディ，アリソン
• ステイハム，マシュー アレクサンダー ジョン
• リージース，ゲオルギウス
• バチストン，カイル

Assignees

• リップル セラピューティクス コーポレーション

Dates

Publication Date

20260512

Application Date

20210429

Priority Date

20200501

Claims (14)

1. Equation (I): A compound, or a pharmaceutically acceptable salt thereof, represented by the structure of [the compound].
2. Equation (I): A compound represented by its structure.
3. Equation (I): A pharmaceutical implant comprising a compound represented by the structure of formula (I), or a pharmaceutically acceptable salt thereof, comprising at least 50% by weight of the compound of formula (I) .
4. Equation (I): A pharmaceutical implant comprising a compound represented by the structure of formula (I), and containing at least 50% by weight of the compound of formula (I) .
5. A pharmaceutical implant according to claim 3 or 4 , comprising at least about 70% by weight of the compound of formula (I) .
6. A pharmaceutical implant according to claim 3 or 4, comprising at least about 80% by weight of the compound of formula (I).
7. A pharmaceutical implant according to claim 3 or 4 , comprising at least about 90% by weight of the compound of formula (I) .
8. A pharmaceutical implant according to claim 3 or 4 , comprising at least about 95% by weight of the compound of formula (I) .
9. A pharmaceutical implant according to claim 3 or 4 , comprising at least about 98% by weight of the compound of formula (I) .
10. The pharmaceutical implant according to claim 3 or 4, wherein the pharmaceutical implant is an implant inside the eyeball.
11. The pharmaceutical implant according to claim 10 , wherein the pharmaceutical implant is an implant located inside the eye cavity.
12. The pharmaceutical implant according to claim 10, wherein the pharmaceutical implant is an implant in the vitreous humor.
13. The pharmaceutical implant according to claim 3 or 4 , wherein the pharmaceutical implant is an intraocular implant.
14. The pharmaceutical implant according to claim 3 or 4, wherein the pharmaceutical implant is an implant in the vitreous body.

Description

Cross-reference to related applications This application claims the benefits of U.S. Provisional Patent Application No. 63/019,182, filed 1 May 2020, which is incorporated herein by reference in its entirety. Prostaglandins (prostaglandin analogs) are state-of-the-art medications in the treatment of glaucoma and can be used to treat other eye disorders. In some cases, prostaglandins are useful in lowering intraocular pressure (IOP), a major risk factor for glaucoma. Typically, prostaglandins are formulated for ophthalmic use and delivered in the form of eye drops. However, frequent ocular administration of prostaglandins is often required to achieve efficacy. For example, it has been reported that once-daily administration of latanoprost reduces IOP by an average of approximately 35%. In some embodiments herein, a compound comprising a first radical (D1) and a second radical (D2) (e.g., having the formula D1-L-D2) is disclosed. In some examples, D1 is a treatable group (also referred herein as a treatable radical), L is a linker, and D2 is a drug (also referred herein as a drug radical). In some embodiments, L is a hydrolyzable linker or bond such that when the compound of formula D1-L-D2 is administered (e.g., for ophthalmic use) (or is present in or otherwise exposed to an aqueous environment such as a buffer, tears, serum), D1 and D2 are released (e.g., in their free, non-radical forms). In some examples, group D1 is bonded to an activator D2 (e.g., an untreatable activator) via linker L (e.g., covalently) (e.g., D1-L-D2), thereby obtaining a compound containing other untreatable drugs (e.g., D2-L-D2 (e.g., D2-D2)) in a treatable form. In some cases, a drug (such as a prostaglandin) binds to a processable group (such as a steroid or other radical of a formula described herein, such as formula (I)). In some cases, the processable group D1 may or may not be processable on its own when in free form, but when combined with D2 (e.g., via a linker L), it yields a processable solid (e.g., at physiological temperature) (e.g., at temperatures above physiological temperature). In one example herein, a platform is provided for providing compounds and implants (e.g., those with high drug content, low excipient content (e.g., those that typically require removal), and other benefits as described herein) that result in the long-term release of therapeutic agents (e.g., prostaglandins, steroids, beta-blockers, etc.) in biological and therapeutic applications, such as ocular (e.g., implant) administration. In some examples, the compounds provided herein (e.g., unprocessable drugs such as prostaglandins, conjugated to processable radicals such as steroids, radicals, etc., via a linker, etc.) can be processed into forms (e.g., implants, coatings, or other bodies) that can be administered to an individual requiring administration (e.g., the individual's eye). In some examples, such compounds can be processed without the need for additional excipients or materials (e.g., controlled-release polymers, extracellular matrix, or other components). In some examples, the absence or minimal amount of additional excipients or materials limits the impact on drug delivery while promoting high levels of drug delivery (e.g., small implants can contain high amounts of drug). In some cases, such compounds (or implants containing such compounds) are administered to an individual (e.g., implanted) so that sustained and/or otherwise controlled (e.g., topical) delivery of the drug is achieved. In some cases, the delivery of compounds (e.g., in the form of implants or coatings) facilitates the delivery of drug components or their radicals over long periods, such as weeks, months, or longer. In some cases, the compounds, formulations, and implants provided herein facilitate long-term drug delivery to individuals requiring delivery without requiring frequent dosing. For example, as discussed herein, prostaglandins are often formulated and administered as eye drops, such as those administered daily. In some cases, administration is required to maintain (e.g., optimize) therapeutic efficacy without requiring strict adherence to frequent dosing. However, in the case of the compounds provided herein, long-term delivery of such drugs can be achieved over periods of weeks, months, or longer with infrequent dosing (e.g., once or twice a year). In some embodiments, group D1 is also an activator or active drug (e.g., its radical). In some embodiments, both D1 and D2 are effective in the treatment of a single indication such that the administration of the compound herein produces a combined therapeutic effect. For example, in some embodiments, D1 is a steroid and D2 is a prostaglandin. In some embodiments, such as in the treatment of glaucoma, the anti-inflammatory effect of the steroid and the intraocular pressure-lowering effect of the prostaglandin both exert a therapeutic effect. In some embodiments, when the compound is formulated as an implant or fo