Treatment of ocular neovascularization and related diseases

• US 6,696,415 B2
• Filed: 04/17/2001
• Issued: 02/24/2004
• Est. Priority Date: 04/17/2000
• Status: Active Grant

• Current Assignee: Children'S Hospital Research Foundation
• Original Assignee: Children'S Hospital Research Foundation
• Inventors: Paradis, Helene, Gendron, Robert L.
• Primary Examiner(s): Caputa, Anthony C.
• Assistant Examiner(s): YAEN, CHRISTOPHER H
• Application Number:
  US09/836,503
• Publication Number:
  US 20020137678A1
• Time in Patent Office: 1,043 Days
• Field of Search: 435/183, 435/188.5, 514/12
• US Class Current: 514/13.3
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C12N 2799/021 for the expression of a heterologous nucleic acid
• CPC Class Codes: C12N 9/10 Transferases (2.) ribonucleases C12N9/22

Abstract

Tubedown-1 (tbdn-1), a protein associated with acetyltransferase activity has been characterized and its cDNA isolated. Tbdn-1 regulates endothelial differentiation through protein acetylation, DNA-binding or by interacting with and/or acetylating other protein targets important for endothelial differentiation. In normal adult eyes, tbdn-1 is expressed highly in the corneal endothelium proper and in the vascular endothelium of the limbus and retina. Tbdn-1 is absent or downregulated in the vascular endothelia of diseased and injured eyes, including eyes from patients with proliferative retinopathies involving neovascularization. Inhibition of tbdn-1 expression in endothelial cells in vitro indicates tbdn-1 acts as an inhibitor of angiogenesis. Thus, high levels of tbdn-1 expression present in normal ocular endothelial cells is associated with suppression of abnormal neovascularization in the eye demonstrating the therapeutic usefulness of tbdn-1 as a regulator of retinal angiogenesis.

Claims

1. An isolated amino acid molecule consisting of the sequence shown in SEQ ID No. 2.

5. A pharmaceutical formulation comprising (a) the isolated amino acid molecule of claim 1, wherein said molecule is biologically active and (b) a pharmaceutically acceptable carrier adapted for administration by either intraocular injection, subretinal injection, subconjunctival injection or by topical administration to an ocular surface.

9. The pharmaceutical formulation of claim 5, wherein the formulation is adapted for administration to treat ocular neovascularization in mammals.

2. An isolated amino acid molecule consisting of the sequence shown in SEQ ID No. 3.

6. A pharmaceutical formulation comprising (a) the isolated amino acid molecule of claim 2, wherein said molecule is biologically active and (b) a pharmaceutically acceptable carrier adapted for administration by either intraocular injection, subretinal injection, subconjunctival injection or by topical administration to an ocular surface.

10. The pharmaceutical formulation of claim 6, wherein the formulation is adapted for administration to treat ocular neovascularization in mammals.

3. An isolated amino acid molecule consisting of the sequence shown in SEQ ID No. 4.

7. A pharmaceutical formulation comprising (a) the isolated amino acid molecule of claim 3, wherein said molecule is biologically active and (b) a pharmaceutically acceptable carrier adapted for administration by either intraocular injection, subretinal injection, subconjunctival injection or by topical administration to an ocular surface.

11. The pharmaceutical formulation of claim 7, wherein the formulation is adapted for administration to treat ocular neovascularization in mammals.

4. An isolated amino acid molecule consisting of the sequence shown in SEQ ID No. 5.

8. A pharmaceutical formulation comprising (a) the isolated amino acid molecule of claim 4, wherein said molecule is biologically active and (b) a pharmaceutically acceptable carrier adapted for administration by either intraocular injection, subretinal injection, subconjunctival injection or by topical administration to an ocular surface.

12. The pharmaceutical formulation of claim 8, wherein the formulation is adapted for administration to treat ocular neovascularization in mammals.