Claims for Patent: 10,231,976

Summary for Patent: 10,231,976

Title:	Methods for the use of progestogen as a glucocorticoid sensitizer
Abstract:	Provided are methods and kits for administering progestogen as a glucocorticoid sensitizer to restore corticosteroid sensitivity or reverse the glucocorticoid insensitivity or enhance glucocorticoid sensitivity, in order to treat one or more glucocorticoid insensitivity related diseases or conditions. For example, these include methods for reversing the glucocorticoid insensitivity in a subject having no history of menstrual cycle-related exacerbation or allergy to self-hormones, particularly progesterone, such as premenstrual or perimenstrual deterioration in the symptoms, e.g., premenstrual worsening of atopic dermatitis or premenstrual exacerbations of asthma, and exhibiting relatively or totally refractory responses to glucocorticoid therapy, e.g., glucocorticoid resistance. The methods and kits provide for the administration of a sex hormone to the subject who is corticosteroid dependent or corticoid resistant or unresponsive or intolerant to corticosteroids.
Inventor(s):	Du; Tao Tom (North Potomac, MD)
Assignee:	PRAIRIE PHARMACEUTICALS LLC (Bethesda, MD)
Application Number:	13/021,950
Patent Claims:	1. A method for the treatment of either an asthma with glucocorticoid insensitivity condition or a chronic obstructive pulmonary disorder with glucocorticoid insensitivity condition in a patient, said method comprising a step of administering to said patient a pharmaceutical composition comprising 17 alpha-hydroxyprogesterone caproate in an amount effective in alleviating said glucocorticoid insensitivity condition and a pharmaceutically acceptable carrier; wherein the patient has no history of menstrual cycle-related exacerbation; wherein the effective amount of the pharmaceutical composition is from about 0.001 to about 100 mg/kg of body weight of 17 alpha-hydroxyprogesterone caproate given orally per day. 2. The method of claim 1, wherein the effects of the administration of the pharmaceutical composition comprise steroid-sparing in a corticosteroid-dependent patient, responding to or tolerating of corticosteroids, achieving efficacy by using a low dose of corticosteroid, preventing a patient from developing uncontrollable conditions or resistance or exacerbations in response to antigen exposures, infections, exercise, or irritants, achieving optimal immune-functions, easy administration of steroids that can be tapered or withdrawn, reducing intolerance to prolonged administration of corticosteroids, decreasing risks for developing a corticosteroid-related adverse event, wherein the corticosteroid-related adverse event comprises opportunistic infections or bone loss, or combinations thereof. 3. The method of claim 1, wherein the pharmaceutical composition is administered daily. 4. The method of claim 1, wherein the pharmaceutical composition is administered according to a dosing regimen selected from the group consisting of an administration interval less than one week, once weekly or exceeding once per week. 5. The method of claim 4, wherein the administration interval is selected from the group consisting of once per day, twice per day, three times per day, and up to 24 times per day. 6. The method of claim 4, wherein the administration interval is selected from the group consisting of once every other week, once monthly, once every two months, and once every three months. 7. The method of claim 1, wherein the pharmaceutical composition is administered once monthly. 8. The method of claim 1, wherein the pharmaceutical composition is administered by a formulation selected from the group consisting of solution, emulsion, elixir, tincture, paste, aerosol, capsule, tablet, powder, and a sustained release formulation. 9. The method of claim 1, wherein the 17 alpha-hydroxyprogesterone caproate is administered prior to, simultaneously with, or following glucocorticoid therapy. 10. The method of claim 9, wherein the glucocorticoid is selected from the group consisting of hydrocortisone, cortisone acetate, dexamethasone, prednisone, prednisolone, methylprednisolone, betamethasone, triamcinolone, beclometasone, Paramethasone, fluticasone, fludrocortisone acetate, deoxycorticosterone acetate, Fluprednisolone, fluticasone propionate, budesonide, beclomethasone dipropionate, flunisolide, and triamcinolone acetonide. 11. The method of claim 1, further comprising administering to the patient one or more additional treatments for restoring corticosteroid sensitivity or reversing the glucocorticoid insensitivity or enhancing glucocorticoid sensitivity to treat the asthma with glucocorticoid insensitivity condition or the chronic obstructive pulmonary disorder with glucocorticoid insensitivity condition. 12. The method of claim 11, wherein the one or more additional treatments are administering agents selected from the group consisting of an androgen, an estrogen, an immunosuppressive or immunomodulator agent, a calcineurin inhibitor, a p38 MAP kinase inhibitor, a JNK inhibitor, a vitamin D, an MIF inhibitor, a histone deacetylate-2 activator, a theophylline, a phosphoinositide-3-kinase-.delta. inhibitor, an antioxidant, an iNOS inhibitor, a p-glycoprotein inhibitor, and combinations thereof. 13. The method of claim 11, wherein the 17 alpha-hydroxyprogesterone caproate is administered prior to, simultaneously with, or following the administration of the one or more additional treatments which are selected from the group consisting of dehydroepiandrosterone, estradiol, cyclosporine, methotrexate, gold, 6-mercaptopurine, infliximab, etanercept, adalimumab, intravenous immunoglobulin, Mepolizumab, cyclosporin, tacrolimus, a p38 MAP kinase inhibitor, a JNK inhibitor, a vitamin D, an MIF inhibitor, a histone deacetylate-2 activator, a theophylline, a phosphoinositide-3-kinase-.delta. inhibitor, an antioxidant, an iNOS inhibitor, a p-glycoprotein inhibitor, and combinations thereof. 14. A method of treating a smoking-induced glucocorticoid insensitivity condition in a patient, said method comprising a step of administering to said patient a pharmaceutical composition comprising 17 alpha-hydroxyprogesterone caproate in an amount effective in alleviating said glucocorticoid insensitivity condition and a pharmaceutically acceptable carrier; wherein the patient has no history of menstrual cycle-related exacerbation; wherein the effective amount of the pharmaceutical composition is from about 0.001 to about 100 mg/kg of body weight of 17 alpha-hydroxyprogesterone caproate given orally per day. 15. A method of treating a glucocorticoid insensitivity condition in a patient with an increased IL-2 production, said method comprising a step of administering to said patient a pharmaceutical composition comprising 17 alpha-hydroxyprogesterone caproate in an amount effective in reducing interleukin-2 levels and a pharmaceutically acceptable carrier; wherein the effective amount of the pharmaceutical composition is from about 0.001 to about 100 mg/kg of body weight of 17 alpha-hydroxyprogesterone caproate given orally per day. 16. The method of 1, wherein the effective amount is selected such that the glucocorticoid insensitivity condition is improved by more than 10%.

Details for Patent 10,231,976

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Janssen Biotech, Inc.	REMICADE	infliximab	For Injection	103772	08/24/1998		2030-02-08
Immunex Corporation	ENBREL	etanercept	For Injection	103795	11/02/1998		2030-02-08
Immunex Corporation	ENBREL	etanercept	For Injection	103795	05/27/1999		2030-02-08
Immunex Corporation	ENBREL	etanercept	Injection	103795	09/27/2004		2030-02-08
Immunex Corporation	ENBREL	etanercept	Injection	103795	02/01/2007		2030-02-08
Immunex Corporation	ENBREL MINI	etanercept	Injection	103795	09/14/2017		2030-02-08