Methods for treating symptoms of dry eye disease

Patent metadata

Field	Value
Publication number	US-12053501-B2
Application number	US-202117521366-A
Country	US
Kind code	B2
Filing date	Nov 8, 2021
Priority date	Jan 22, 2016
Publication date	Aug 6, 2024
Grant date	Aug 6, 2024

Abstract

The present disclosure relates to, among other things, compositions and methods for treating an inflammatory condition including, but not limited to, ocular inflammation, dry eye disease, and ocular neuropathic pain. One aspect of the present disclosure relates to a composition comprising (a) chemerin or a fragment or analog thereof and (b) a lipid entity linked to the chemerin or fragment or analog thereof.

First claim

What is claimed is:

1. A method of reducing irritated or burning eyes in a human subject having dry eye disease, the method comprising topically administering to an eye of the human subject a therapeutically effective amount of a composition, wherein the composition comprises:
a chemerin fragment consisting of the sequence of Y-F-P-G-Q-F-A-F-S(SEQ ID NO.: 2) or a chemerin analog consisting of the sequence of Y*-F-L-P-S*-Q-F-A*-Tic-S(SEQ ID NO.: 3), wherein * denotes D amino acids and Tic represents 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid;
a lipid entity selected from the group consisting of α-linolenic acid, γ-linolenic acid, palmitic acid, vaccenic acid, oleic acid, and elaidic acid; and
a linker connecting the lipid entity to the chemerin fragment or chemerin analog, wherein the linker comprises polyethylene glycol, KGG, or a combination thereof.

2. The method of claim 1 , wherein the composition is administered once a day, twice a day, or thrice a day.

3. The method of claim 1 , wherein the lipid entity is linked at or near the N-terminus of the chemerin fragment or chemerin analog.

4. The method of claim 1 , wherein a combination of the lipid entity and the linker is palmitate-PEG 8 KGG.

5. The method of claim 1 , wherein the composition is formulated for topical administration as eye drops.

6. A method of reducing irritated or burning eyes in a human subject having dry eye disease, the method comprising topically administering to an eye of the human subject a therapeutically effective amount of a composition, thereby increasing tear film stability, wherein the composition comprises:
a chemerin fragment consisting of the sequence of Y-F-P-G-Q-F-A-F-S(SEQ ID NO.: 2) or a chemerin analog consisting of the sequence of Y-F-L-P-S-Q-F-A-Tic-S(SEQ ID NO.: 3), wherein Tic represents 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid;
a lipid entity selected from the group consisting of α-linolenic acid, γ-linolenic acid, palmitic acid, vaccenic acid, oleic acid, and elaidic acid; and
a linker connecting the lipid entity to the chemerin fragment or chemerin analog, wherein the linker comprises polyethylene glycol, KGG, or a combination thereof.

7. A method of reducing blurred vision in a human subject having dry eye disease, the method comprising topically administering to an eye of the human subject a therapeutically effective amount of a composition, wherein the composition comprises:
a chemerin fragment consisting of the sequence of Y-F-P-G-Q-F-A-F-S(SEQ ID NO.: 2) or a chemerin analog consisting of the sequence of Y*-F-L-P-S*-Q-F-A*-Tic-S(SEQ ID NO.: 3), wherein * denotes D amino acids and Tic represents 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid;
a lipid entity selected from the group consisting of α-linolenic acid, γ-linolenic acid, palmitic acid, vaccenic acid, oleic acid, and elaidic acid; and
a linker connecting the lipid entity to the chemerin fragment or chemerin analog, wherein the linker comprises polyethylene glycol, KGG, or a combination thereof.

8. A method of reducing blurred vision in a human subject having dry eye disease, the method comprising topically administering to an eye of the human subject a therapeutically effective amount of a composition, wherein the composition comprises:
a chemerin fragment consisting of the sequence of Y-F-P-G-Q-F-A-F-S(SEQ ID NO.: 2) or a chemerin analog consisting of the sequence of Y-F-L-P-S-Q-F-A-Tic-S(SEQ ID NO.: 3), wherein Tic represents 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid;
a lipid entity selected from the group consisting of α-linolenic acid, γ-linolenic acid, palmitic acid, vaccenic acid, oleic acid, and elaidic acid; and
a linker connecting the lipid entity to the chemerin fragment or chemerin analog, wherein the linker comprises polyethylene glycol, KGG, or a combination thereof.

Assignees

• Tufts Medical Center
• Tufts College
• On Target Therapeutics Llc

Inventors

• Cohen Charles
• Kumar Krishna
• Kopin Alan S
• Harwood Benjamin N
• Raman Venkata S
• Hamrah Pedram

Classifications

• A61K9/0048

  Eye, e.g. artificial tears · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61K47/60

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title

• A61K47/65

  Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers · CPC title