Aav variants for the treatment of dry AMD
The recombinant adeno-associated virus (rAAV) vector delivers therapeutic genes via intravitreal injection to treat dry AMD by targeting specific genes in the retina, improving symptoms and preventing progression.
Patent Information
- Authority / Receiving Office
- HK · HK
- Patent Type
- Applications
- Current Assignee / Owner
- ADVERUM BIOTECHNOLOGIES INC
- Filing Date
- 2026-04-01
- Publication Date
- 2026-07-17
AI Technical Summary
Current treatments for dry age-related macular degeneration (AMD) are inadequate in effectively addressing the symptoms and progression of the disease, particularly dry AMD, which affects a significant portion of patients.
A recombinant adeno-associated virus (rAAV) vector is administered via intravitreal injection to deliver therapeutic genes directly to the retina, targeting specific genes associated with dry AMD.
The rAAV vector effectively improves symptoms and potentially prevents the progression of dry AMD by delivering therapeutic genes directly to the retina, providing a targeted and effective treatment approach.
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Abstract
Description
TRANSLATION OF ABSTRACT AND TITLE Request to Record Designated Patent Application No. EP23898681.4 (Publication No. EP4626485) in Hong Kong Our Ref.: P4785HK00 54) Title: AAV Variant for the Treatment of Dry Age-Related Macular Degeneration 57) Abstract: This invention provides a gene therapy based on recombinant adeno-associated virus (rAAV) that can be administered via intravitreal injection to improve symptoms associated with dry AMD, prevent dry AMD, and treat dry AMD. Abstract
Claims
THAT WHICH IS CLAIMED:
1. A polynucleotide cassette for increasing the concentration of human CFI in the vitreous humor and / or retinal extracellular space of a mammalian eye, comprising: a. an enhancer and promoter region; b. a chimeric intron; c. a Kozak sequence d. a unique coding sequence optimized for increased expression and low CpG, operatively linked to the promoter region wherein the coding sequence is a human CFI gene, e. a human scaffold attachment region; and f. a polyadenylation site.
2. The polynucleotide cassette of claim 1, wherein the promoter region further comprises an enhancer element.
3. The polynucleotide cassette of claim 1, wherein the chimeric intron comprises at least one element selected from the group comprising: (a) an adenovirus tripartite leader sequence (TPL), (b) an enhancer element, and (c) an intron from mouse IgH.
4. The polynucleotide cassette of claim 1, further comprising AAV2 inverted terminal repeats (ITRs).
5. The polynucleotide cassette of claim 1, wherein the polyadenylation site is the human growth hormone polyadenylation site.
6. The polynucleotide cassette of claim 1, wherein the coding sequence has a nucleotide sequence having at least 90% identity to the nucleotide sequence set forth in SEQ ID NO1 7. The polynucleotide cassette of claim 1, wherein the coding sequence of the human CFI gene is selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:
6.
8. A method of increasing the concentration of human CFI in the vitreous humor and / or retinal extracellular space of a mammalian eye, comprising administering to a subject a recombinant adeno‐associated virus (rAAV) vector at a dosage ranging from about 1E9 to about 4E12 vector genomes (vg) / eye, wherein the rAAV vector comprises an AAV2 capsid variant and wherein the rAAV vector comprises a polynucleotide cassette comprising: a. An enhancer and promoter region; b. a chimeric intron; c. a Kozak sequence d. a unique coding sequence optimized for increased expression and low CpG, operatively linked to the promoter region wherein the coding sequence is a human CFI gene, e. a human scaffold attachment region; and f. a polyadenylation site.
9. The method of claim 8 wherein the polynucleotide cassette further comprises an enhancer element.
10. The method of claim 8, wherein the chimeric intron of the polynucleotide cassette comprises at least one element selected from the group comprising: (a) an adenovirus tripartite leader sequence (TPL), (b) an enhancer element, and (c) an intron from mouse IgH.
11. The method of claim 8, wherein the polynucleotide cassette further comprises AAV2 inverted terminal repeats (ITRs).
12. The method of claim 8, wherein the polyadenylation site of the polynucleotide cassette is the human growth hormone polyadenylation site.
13. The method of claim 8, wherein the polynucleotide cassette has a nucleotide sequence having at least 90% identity to the nucleotide sequence set forth in SEQ ID NO:
1.
14. The method of claim 8, wherein the coding sequence of a human CFI gene is selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:
6.
15. The method of claim 8, wherein rAAV vector is administered intravitreally.
16. The method of claim 8, wherein the AAV2 capsid variant is selected from the group comprising AAV2.7m8 and AAV2.5T‐LSV1.
17. The method of claim 8, wherein the rAAV vector is administered at a dosing range selected from the group of ranges consisting of from about 1E9 to about 4E12 vg / eye, from about 10E10 to about 4E11 vg / eye, from about 2E10 to about 3E11 vg / eye, from about 2E10 to about 2E11 vg / eye, from about 2.5E10 to about 2E11 vg / eye, from about 2E10 to about 1E11 vg / eye, from about 2E10 to about 9E10 vg / eye, from about 2E10 to about 8E10 vg / eye, and from about 3E10 to about 7E10 vg / eye.
18. The method of claim 8, wherein human CFI is detectable in the vitreous humor at least 4 weeks after intravitreal injection of said rAAV vector.
19. The method of claim 8, wherein the level of C3b‐inactivating activity in an eye of said subject is increased.
20. The method of claim 8, wherein the level of iC3b‐degradation activity in an eye of the subject is increased.
21. The method of claim 8, wherein the rAAV vector is administered as an intravitreal injection.
22. The method of claim 8, wherein the human CFI expressed from the rAAV vector is capable of degrading C3b into iC3b.
23. A polynucleotide cassette for increasing the concentration of human CFI in a mammalian eye, comprising: a. an enhancer and promoter region; b. a chimeric intron; c. a Kozak sequence d. a unique coding sequence optimized for increased expression and low CpG, operatively linked to the promoter region wherein the coding sequence is a human CFI gene, e. a human scaffold attachment region; and f. a polyadenylation site.
24. The polynucleotide cassette of claim 24, wherein said polynucleotide cassette is for increasing the concentration of human CFI in the vitreous humor and / or retinal extracellular space of a mammalian eye.
25. A method of treating dry acute macular degeneration (dry‐AMD) in a human subject, comprising administering to a subject in need thereof a therapeutically effective amount of recombinant adeno‐associated virus (rAAV) vector, wherein the rAAV vector comprises an AAV2 capsid variant and a polynucleotide cassette comprising: a. An enhancer and promoter region; b. a chimeric intron; c. a Kozak sequence d. a unique coding sequence optimized for increased expression and low CpG, operatively linked to the promoter region wherein the coding sequence is a human CFI gene, e. a human scaffold attachment region; and f. a polyadenylation site.
26. The method of claim 26, wherein the rAAV vector is administered intravitreally.
27. The method of claim 26, wherein the therapeutically effective amount is a dosage ranging from about 1E9 to about 4E12 vector genomes (vg) / eye.
28. The method of claim 26, wherein there is a reduction in the geographic atrophy area and / or in the rate of growth of the geographic atrophy area after administration of the rAAV vector.
29. The method of claim 26, wherein the therapeutically effective amount is a dosage ranging from about 2E10 to about 9E10 vector genomes (vg) / eye.
30. An intravitreal dosage form, comprising a recombinant adeno‐associated virus (rAAV) vector at a dosage ranging from about 1E9 to about 4E12 vg / eye, wherein the rAAV vector comprises a polynucleotide cassette according to claim 1, and wherein the rAAV vector comprises an AAV2 capsid variant.
31. The intravitreal dosage form of claim 30, wherein rAAV vector comprises an AAV2_7m8 capsid variant and a dosage ranging from about 9E9 to about 9E10 vg / eye.