Granted Patent B2

US 12,310,983 · App. 18/331,875 · Granted May 27, 2025

Inventor: Ryan Beal (Camarillo, CA)

Assignee: DYVE BIOSCIENCES, INC.

A61K33/00A61K9/0014A61K9/06A61K9/16A61K9/7023A61K31/045A61K31/133A61K31/198A61K31/4172A61K31/661A61K31/685A61K31/704A61K33/30A61K33/42A61K35/00A61K39/3955A61K47/02A61K47/10A61K47/12A61K47/14A61K47/183A61K47/22A61K47/24A61P35/04C07K16/2818A61K2039/505C07K2317/76

Abstract

Claims (28)

1. A method for inhibiting metastasis of a solid tumor in a subject, the method comprising transdermally administering to a subject in need thereof an effective amount of a transdermal formulation comprising a buffer selected from sodium bicarbonate and sodium carbonate as an anti-metastatic agent and in an amount sufficient to raise the pH in the microenvironment of the solid tumor, wherein the transdermally administering provides systemic delivery of the buffer; wherein the formulation excludes another antimetastatic agent.

2. The method of claim 1 , wherein the transdermally administering is performed by contacting intact skin of the subject with the transdermal formulation containing the buffer.

3. The method of claim 1 , wherein the transdermal formulation further contains a penetrant that encourages transmission across the dermis and that effects skin-penetrating properties to the buffer.

4. The method of claim 3 , wherein the penetrant comprises:

an alcohol in an amount to provide 0.5-20% w/w of the transdermal formulation; and

a zwitterion in an amount to provide 25-70% w/w of the transdermal formulation.

5. The method of claim 3 , wherein the penetrant comprises:

an alcohol in an amount to provide 0.5-20% w/w of the transdermal formulation; and

a zwitterion in an amount to provide 1-50% w/w of the transdermal formulation.

6. The method of claim 5 , wherein the transdermal formulation further comprises a nonionic surfactant which is in an amount of 1-25% w/w of the transdermal formulation and a polar solvent in an amount of 1-25% w/w of the transdermal formulation;

wherein the amount of the polar solvent is a greater amount than the amount of the nonionic surfactant.

7. The method of claim 6 , wherein the nonionic surfactant is a poloxamer and the polar solvent is water.

8. The method of claim 3 , wherein the penetrant is in an amount such that the resulting transdermal formulation comprises:

i) one or more electrolytes selected from sodium chloride and sodium citrate and in an amount sufficient to impart viscosity and viscoelasticity to the formulation;

ii) one or more surfactants; and

iii) benzyl alcohol or an analog thereof.

9. The method of claim 3 ,

wherein the penetrant further comprises a keratinolytic agent effective to reduce thiol linkages, disrupt hydrogen bonding, and/or effect keratin lysis;

wherein the penetrant further comprises at least one skin penetrating peptide (SPP);

wherein the penetrant further comprises a chemical permeation enhancer (CPE); and/or

wherein the transdermal formulation comprises micelles.

10. The method of claim 1 , wherein the concentration of the buffer in the transdermal formulation is in the range of 1-40% wt/wt.

11. The method of claim 1 , wherein the buffer is sodium bicarbonate, sodium carbonate, or both and the concentration of buffer in the transdermal formulation is in the range of 5-35% by wt/wt.

12. The method of claim 1 , wherein the buffer further comprises a carbonate buffer, a phosphate buffer, a tris buffer, a lysine buffer, a chloroacetate buffer, or a buffer employing non-natural amino acids with similar pKa values to lysine.

13. The method of claim 1 , wherein the method further includes testing the solid tumor for sensitivity or resistance to pH adjustment.

14. The method of claim 13 , wherein the testing comprises evaluating biopsied cells of the solid tumor in culture.

15. The method of claim 1 , wherein the subject is human, a veterinary subject, or an animal model.

16. The method of claim 1 , wherein the transdermal formulation is applied under an occlusive patch.

Assignments (1)

Continuity (15)

References Cited (268)