Granted Patent
B1
US 12,233,157 · App. 18/783,305 · Granted Feb 25, 2025
Hydrogel formulations and methods and devices for administration of the same
Inventors:
Tomasz Pawel Stryjewski (Somerville, MA); James Anthony Stefater, III (Boston, MA); Laurence A. Roth (Windham, NH); Kelsey-Ann Leslie (Cambridge, MA)
Assignee:
PYKUS THERAPEUTICS, INC.
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Abstract
The invention provides methods and polymer compositions for treating ocular disorders, where the methods and compositions comprise polymer that can form a hydrogel in the eye of a subject. The hydrogel is formed by reaction of (i) a nucleo-functional polymer that is a biocompatible polymer, such as a thiolated hyaluronic acid polymer, containing a plurality of thio-functional groups —R 1 —SH wherein R 1 is hydrolyzable and (ii) an electro-functional polymer that is a biocompatible polymer, such as a poly(ethylene glycol) polymer, containing at least one thiol-reactive group.
Claims (21)
1. A method of contacting retinal tissue in an eye of a subject, the method comprising:
injecting into the vitreous cavity of the eye of the subject an effective amount of a nucleo-functional polymer and an electro-functional polymer; and
allowing the nucleo-functional polymer and the electro-functional polymer to react to form a hydrogel in the vitreous cavity, which hydrogel contacts the retinal tissue in the eye, thereby providing a retinal tamponade;
wherein the nucleo-functional polymer is a biocompatible polymer comprising hyaluronic acid containing a plurality of thio-functional —R 1 —SH, wherein R 1 is hydrolyzable, and the electro-functional polymer is a biocompatible polymer comprising poly(ethylene glycol) containing at least one thiol-reactive group.
2. The method of claim 1 , wherein —R 1 —SH is
and n=1-3 or n=2.
3. The method of claim 1 , wherein —R 1 —SH is
4. The method of claim 1 , wherein up to about 200 μL of the nucleo-functional polymer, the electro-functional polymer, or a combination thereof is administered.
5. The method of claim 1 , wherein the nucleo-functional polymer and the electro-functional polymer are focally applied in the vitreous cavity.
6. The method of claim 1 , wherein the subject is having undergone a vitrectomy for repair of a retinal detachment or macular hole.
7. The method of claim 1 , wherein the subject has a physical discontinuity in the retinal tissue, a tear in the retinal tissue, a break in the retinal tissue, or a hole in the retinal tissue.
8. The method of claim 1 , wherein the nucleo-functional polymer and the electro-functional polymer are injected separately as liquid aqueous pharmaceutical compositions or together as a single, liquid aqueous pharmaceutical composition to the vitreous cavity of the eye of the subject.
9. The method of claim 8 , wherein the separate liquid aqueous pharmaceutical compositions or single liquid aqueous pharmaceutical composition has a pH in the range of about 6.9 to about 7.2 or about 6.8 to about 7.6.
10. The method of claim 1 , wherein the hydrogel has a transparency of at least 95% for light in the visible spectrum when measured through the hydrogel having a thickness of 1 cm.
11. The method of claim 1 , wherein the hydrogel has a gelation time of less than about 10 minutes.
12. The method of claim 1 , wherein the hydrogel undergoes complete biodegradation from the eye of the subject within about 3 days to about 7 days, about 2 weeks to about 8 weeks, or about 4 months to about 6 months, or within 12 months or 24 months.
13. The method of claim 1 , wherein the hydrogel has a biodegradation half-life in the range of from about 1 week to about 3 weeks or from about 8 weeks to about 15 weeks when disposed within the vitreous cavity of an eye.
14. The method of claim 1 , wherein the hydrogel generates a pressure within the eye of less than 25 mmHg.
15. The method of claim 1 , wherein the nucleo-functional polymer has a weight-average molecular weight in the range of from about 75 kDa to about 300 kDa; and the electro-functional polymer has a weight-average molecular weight in the range of from about 500 g/mol to about 1,000,000 g/mol.
16. The method of claim 1 , wherein the mole ratio of (i) thio-functional groups —R 1 —SH to (ii) thiol-reactive groups is about 0.5:1 to about 1.2:1, about 0.6:1 to about 1.2:1, or about 0.67:1.
17. The method of claim 1 , wherein the poly(ethylene glycol) is linear, branched, a dendrimer, or multi-armed.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 31, 2024
From: STRYJEWSKI, TOMASZ PAWEL; STEFATER, JAMES ANTHONY, III; ROTH, LAURENCE A; LESLIE, KELSEY-ANN
To: PYKUS THERAPEUTICS, INC.
Reel/Frame 068139/0105 →
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