Polymeric leuprolide acetate formulations

HK40138731APending Publication Date: 2026-10-09TOLMAR INT LTD
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Patent Information

Application Number
HK62026127200
Authority / Receiving Office
HK · HK
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-07-05
Filing Date
2026-08-07
Publication Date
2026-10-09
Estimated Expiration
2044-07-02

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Abstract

Liquid-liquid polymer leuprolide acetate (LA) formulations comprising a biodegradable polymer and biocompatible solvent, and methods of using the formulations.
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Description

Abstract: A liquid-liquid polymeric leuprolide acetate (LA) formulation comprising a biodegradable polymer and a biocompatible solvent, and a method of using the formulation.

Claims

Attorney Docket No.38368.0020P1 CLAIMS What is claimed is:

1. A pharmaceutical product comprising: a first container comprising a polymer solution of a biodegradable polymer dissolved in a biocompatible solvent; and a second container comprising a drug solution of leuprolide acetate dissolved in the biocompatible solvent at a concentration of 20% to 45% (w / w) leuprolide acetate; wherein the polymer and drug solutions of the first and second containers are not mixed prior to use.

2. The pharmaceutical product of claim 1, wherein the concentration remains at 20% to 45% (w / w) leuprolide acetate over the entire shelf life of the pharmaceutical product.

3. The pharmaceutical product of claim 1 or 2, wherein the concentration remains at 20% to 45% (w / w) leuprolide acetate at 24 months or longer storage at 2 to 8°C.

4. The pharmaceutical product of claim 1, 2, or 3, wherein the concentration remains at 20% to 45% (w / w) leuprolide acetate at 6 months or longer storage at 25°C.

5. The pharmaceutical product of any one of the preceding claims, wherein when contents of the first and second containers are mixed, the resulting composition is an extended-release composition for subcutaneous injection into a subject that upon injection into the subject, forms an in situ depot that releases the leuprolide acetate over a time period from about 1 month to about 6 months.

6. The pharmaceutical product of any one of the preceding claims, comprising a drug solution of leuprolide acetate dissolved in the biocompatible solvent at a concentration of 22% to 36% (w / w) leuprolide acetate.

7. The pharmaceutical product of any one of the preceding claims, wherein theAttorney Docket No.38368.0020P1 biodegradable polymer comprises one or more of the following monomers: lactide, glycolide, caprolactone, p-dioxanone, trimethylene carbonate, ethylene oxide, propylene oxide, sebacic anhydride, diketene acetals / diols, thylene oxide, 1,5- dioxepan-2-one, 1,4-dioxepan-2-one, lactic acid, or any combination thereof.

8. The pharmaceutical product of claim 7, wherein the biodegradable polymer is poly(D,L-lactide-co-glycolide) (PLG), poly(D,L-lactide) (PLA), poly(lactic-glycolic acid), poly-lactic acid, or poly(D,L-lactide-co- ^-caprolactone) (PLC).

9. The pharmaceutical product of claim 7, wherein the biodegradable polymer is poly(D,L-lactide-co-glycolide) (PLG).

10. The pharmaceutical product of claim 9, wherein the molar ratio of lactide to glycolide monomers in the polymer is 50:50 to 95:

5.

11. The pharmaceutical product of claim 9, wherein the molar ratio of lactide to glycolide monomers in the polymer is 50:50, 75:25, or 85:

15.

12. The pharmaceutical product of any one of the preceding claims, wherein the polymer solution has a viscosity of 3,000 cP to 50,000 cP at 25°C.

13. The pharmaceutical product of any one of the preceding claims, wherein the biocompatible solvent is N-methyl-2-pyrrolidone (NMP), dimethyl sulfoxide (DMSO), 2-pyrrolidon, N,N-dimethylformamide, propylene carbonate (PC), caprolactam, triacetin, dimethylacetamide (DMA), benzyl benzoate (BnBzO), methyl ethyl ketone, methyl lactate, benzyl alcohol, tributyl citrate, acetyl tributyl citrate, acetyl triethyl citrate, triethyl citrate, diethylene glycol monomethyl ether, ethyl acetate, N-ethyl-2- pyrrolidone, glycofurol, or any combination thereof.

14. The pharmaceutical product of any one of the preceding claims, wherein the biodegradable polymer is a PLG polymer having a 50:50 molar ratio of lactide to glycolide; the biocompatible solvent is NMP; the first container is formulated to deliver 125 mg to 155 mg NMP and 75 mg to 90 mg of the PLG polymer, and the second container is formulated to deliver 7.5 mg leuprolide acetate and 5 mg to 40 mg NMP.

15. The pharmaceutical product of any one of claims 1-13, wherein theAttorney Docket No.38368.0020P1 biodegradable polymer is a PLG polymer having a 75:25 molar ratio of lactide to glycolide, the biocompatible solvent is NMP; the first container is formulated to deliver 90 mg to 170 mg NMP and 155 mg to 165 mg of the PLG polymer, and the second container is formulated to deliver 22.5 mg leuprolide acetate and 35 mg to 105 mg NMP.

16. The pharmaceutical product of any one of claims 1-13, wherein the biodegradable polymer is a PLG polymer having a 75:25 molar ratio of lactide to glycolide, the biocompatible solvent is NMP; the first container is formulated to deliver 80 mg to 178 mg NMP and 145 mg to 185 mg of the PLG polymer, and the second container is formulated to deliver 30 mg leuprolide acetate and 35 mg to 135 mg NMP.

17. The pharmaceutical product of any one of claims 1-13, wherein the biodegradable polymer is a PLG polymer having a 75:25 molar ratio of lactide to glycolide, the biocompatible solvent is NMP; the first container is formulated to deliver 120 mg to 225 mg NMP and 185 mg to 235 mg of the PLG polymer, and the second container is formulated to deliver 30 mg leuprolide acetate and 35 mg to 135 mg NMP.

18. The pharmaceutical product of any one of claims 1-13, wherein the biodegradable polymer is a PLG polymer having an 85:15 molar ratio of lactide to glycolide, the biocompatible solvent is NMP; the first container is formulated to deliver 100 mg to 170 mg NMP and 145 mg to 185 mg of the PLG polymer, and the second container is formulated to deliver 45 mg leuprolide acetate and 50 mg to 95 mg NMP.

19. A method of reducing luteinizing hormone (LH) levels in a subject in need of LHRH reduction, the method comprising subcutaneously administering an extended release composition prepared by mixing the polymer and drug solutions of the first and second containers of any one of the preceding claims.

20. The method of claim 19, wherein the extended release composition is prepared by mixing the polymer and drug solutions of the first and second containers using 30 or fewer mixing cycles.Attorney Docket No.38368.0020P1 21. The method of claim 19 or 20, wherein the extended release composition is prepared by mixing the polymer and drug solutions of the first and second containers using 20 or fewer mixing cycles.

22. The method of any one of claims 19-21, wherein administering the extended release composition treats one or more of the following diseases or conditions: hormone-related prostate cancer, hormone-related mammary (breast) cancer, hormone-related endometrial cancer, hormone-related ovarian cancer, hormone- related cervical cancer, endometriosis, fibroids, or central precocious puberty (CPP).

23. The method of claim 22, wherein the hormone-related prostate cancer is advanced prostate cancer.

24. The method of any one of claims 19-21, wherein administering the extended release composition: (a) reduces serum testosterone levels in a male subject, or (b) reduces estrogen or estradiol levels, or follicle stimulating hormone (FSH) levels, in a female subject.

25. The method of any one of claims 19-21, wherein administering the extended release composition suppresses ovarian function in a subject with HR+ breast cancer.

26. The method of any one of claims 19-21, wherein administering the extended release composition blocks or suppresses hormones to prevent or delay puberty in a transgender individual.

27. The method of any one of claims 19-26, wherein the extended release composition is administered once per every one month, once per every three months, once per every four months, or once per every six months.

28. A prefilled syringe system for administration of the pharmaceutical product of any one of claims 1-18, wherein the first container is a first syringe comprising the polymer solution and the second container is a second syringe comprising the drug solution.

29. The prefilled syringe system of claim 28, wherein the first syringe and the second syringe are coupled together.Attorney Docket No.38368.0020P1 30. A kit comprising the prefilled syringe system of claim 28 or 29 together with instructions for mixing and administration.

31. The pharmaceutical product of any one of claims 1-18, for use in a method of reducing luteinizing hormone (LH) levels in a subject in need of LHRH reduction.

32. The pharmaceutical product of claim 31, wherein reducing luteinizing hormone (LH) levels treats prostate cancer, treats central precocious puberty (CPP), or suppresses ovarian function in a subject with HR+ breast cancer.

33. The use of the pharmaceutical product of any one of claims 1-18 in the manufacture of a medicament for use in a method of reducing luteinizing hormone (LH) levels in a subject in need of LHRH reduction.

34. The use of claim 30, wherein reducing luteinizing hormone (LH) levels treats prostate cancer, treats central precocious puberty (CPP), or suppresses ovarian function in a subject with HR+ breast cancer.