Compositions and methods for treating age-related macular degeneration

Patent metadata

Field	Value
Publication number	US-2022184102-A1
Application number	US-202017598660-A
Country	US
Kind code	A1
Filing date	Mar 27, 2020
Priority date	Mar 27, 2019
Publication date	Jun 16, 2022
Grant date	—

Abstract

Provided are chemically modified tetracycline (CMT) derivatives for the treatment of non-exudative macular degeneration. The CMT derivatives lack antimicrobial activity, include a phenol ring, and a chemical structure sufficient to chelate Zn2+. Methods of inhibiting and/or minimizing inflammation in a subject, including administering to the subject a dose of a CMT derivative, are also provided. Methods of treating non-exudative age-related macular degeneration (AMD) are provided.

First claim

What is claimed is:

1 . A chemically modified tetracycline (CMT) derivative for the treatment of non-exudative macular degeneration, wherein the CMT derivative:
lacks anti-microbial activity; comprises a phenol ring; and comprises a chemical structure sufficient to chelate Zn2+.

2 . The CMT derivative of claim 1 , wherein the CMT derivative lacks antimicrobial activity due to deletion of a C4 dimethylamino.

3 . The CMT derivative of any of the above claims, wherein the CMT derivative lacks antimicrobial activity due to dosing below a minimum inhibitory concentration.

4 . The CMT derivative of any of the above claims, wherein the phenol ring comprises a diethylamino group to enhance scavenging of reactive oxygen species.

5 . The CMT derivative of any of the above claims, wherein the chemical structure comprises the following structure:

6 . The CMT derivative of any of the above claims, wherein the CMT derivative is doxycycline.

7 . The CMT derivative of claim 6 , wherein the CMT derivative is given at a dose of 40 mg per day.

8 . The CMT derivative of claim 6 , wherein the CMT derivative is ORACEA® tetracycline derivative.

9 . The CMT derivative of claim 6 , wherein the dose of the doxycycline is given at a concentration less than 100 mg per day.

10 . A method of inhibiting and/or minimizing inflammation in a subject, the method comprising administering to a subject in need a dose of a CMT derivative of any of the above claims, wherein the dose of the CMT derivative is sufficient to inhibit activation of gut microbiome inflammatory cells, wherein the dose of the CMT derivative is below a minimum inhibitory concentration for antimicrobial activity.

11 . The method of claim 10 , wherein the CMT derivative is administered at a dose of about 100 mg per day, optionally at a dose of about 40 mg per day.

12 . The method of claim 10 or 11 , wherein the subject is a human subject, optionally wherein the human subject is suffering from non-exudative age-related macular degeneration.

13 . A method of treating non-exudative age-related macular degeneration (AMD) in a subject, the method comprising:
providing a subject susceptible to and/or suffering from non-exudative AMD; and administering to the subject a CMT derivative of any of claims 1 - 9 .

14 . The method of claim 13 , wherein the CMT derivative is administered at a dose of about 100 mg per day, optionally at a dose of about 40 mg per day, optionally at a dose of less than about 40 mg per day.

15 . The method of any of claims 13 to 14 , wherein the dose of the CMT derivative is sufficient to inhibit activation of gut microbiome inflammatory cells.

16 . The method of any of claims 13 to 15 , wherein the dose of the CMT derivative is sufficient to decrease gut leakage of inflammatory cytokines.

17 . The method of any of claims 13 to 16 , wherein the dose of the CMT derivative is below a minimum inhibitory concentration for antimicrobial activity.

18 . The method of any of claims 13 to 17 , wherein the dose of the CMT derivative is sufficient to prevent activation of inflammatory cells that can transit to a retina of the subject.

19 . The method of any of claims 13 to 18 , wherein the dose of the CMT derivative is sufficient to inhibit pro-inflammatory pathways to an eye of the subject.

20 . A composition for administration to a subject, the composition comprising a chemically modified tetracycline (CMT) derivative, wherein the CMT derivative lacks anti-microbial activity, comprises a phenol ring, and comprises a chemical structure sufficient to chelate Zn 2+ , and wherein the CMT derivative is included in the composition at a concentration sufficient to provide a dose of about 40 mg per day when administered to a subject.

21 . The composition of claim 20 , wherein the composition is configured to treatment non-exudative macular degeneration when administered to a subject.

22 . The composition of any of claims 20 to 21 , wherein the CMT derivative lacks antimicrobial activity due to deletion of a C4 dimethylamino.

23 . The composition of any of claims 20 to 22 , wherein the CMT derivative lacks antimicrobial activity due to dosing below a minimum inhibitory concentration.

24 . The composition of any of claims 20 to 23 , wherein the CMT derivative is doxycycline.

25 . The composition of any of claims 20 to 24 , further comprising an excipient or a pharmaceutically acceptable carrier.

Assignees

• Yates Paul Andrew
• Reichel Elias
• Leone Ashton
• Univ Virginia Patent Foundation

Inventors

• Yates Paul Andrew
• Reichel Elias
• Leone Ashton

Classifications

• A61P27/02 Primary

  Ophthalmic agents · CPC title

• A61K31/65 Primary

  Tetracyclines · CPC title