Claims for Patent: 9,873,667

Summary for Patent: 9,873,667

Title:	Arylsulfanyl compounds and compositions for delivering active agents
Abstract:	Compounds and compositions for the delivery of active agents are provided. Methods of administration and preparation are also provided.
Inventor(s):	Pusztay; Stephen (Ansonia, CT), Saraf; Sushma (Wappingers Falls, NY), Wang; Nai Fang (Scarsdale, NY)
Assignee:	EMISPHERE TECHNOLOGIES INC. (Roseland, NJ)
Application Number:	12/375,369
Patent Claims:	1. A compound selected from: ##STR00023## ##STR00024## ##STR00025## ##STR00026## ##STR00027## ##STR00028## and pharmaceutically acceptable salts thereof. 2. A pharmaceutical composition comprising: (A) a biologically active agent; and (B) a delivery agent compound of Formula I, or a pharmaceutically acceptable salt thereof ##STR00029## wherein A is a branched or unbranched C.sub.1-C.sub.13 alkylene, C.sub.3-C.sub.13 arylene group, or a C.sub.3-C.sub.13 alkyl(arylene) group, and R.sub.1-R.sub.5 are independently hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 alkoxy, C.sub.2-C.sub.4 alkenyl, halogen or hydroxy, in which at least one of R.sub.1-R.sub.5 is methoxy. 3. A pharmaceutical composition comprising: (A) a biologically active agent; and (B) a delivery agent compound selected from ##STR00030## ##STR00031## ##STR00032## ##STR00033## ##STR00034## ##STR00035## and pharmaceutically acceptable salts thereof. 4. The pharmaceutical composition of claim 2 or claim 3, wherein the biologically active agent is a protein, polypeptide, peptide, hormone, polysaccharide, mucopolysaccharide, carbohydrate, or lipid. 5. The pharmaceutical composition of claim 4, wherein the biologically active agent is selected from: BIBN-4096BS, growth hormones, human growth hormones, recombinant human growth hormones (rhGH), bovine growth hormones, porcine growth hormones, growth hormone releasing hormones, growth hormone releasing factor, glucagon, interferons, .alpha.-interferon, .beta.-interferon, .gamma.-interferon, interleukin-1, interleukin-2, insulin, porcine insulin, bovine insulin, human insulin, human recombinant insulin, insulin-like growth factor (IGF), IGF-1, heparin, unfractionated heparin, heparinoids, dermatans, chondroitins, low molecular weight heparin, very low molecular weight heparin, ultra low molecular weight heparin, calcitonin, salmon calcitonin, eel calcitonin, human calcitonin; erythropoietin (EPO), atrial naturetic factor, antigens, monoclonal antibodies, somatostatin, protease inhibitors, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, leutinizing-hormone-releasing-hormone, follicle stimulating hormone, glucocerebrosidase, thrombopoietin, filgrastim, prostaglandins, cyclosporin, vasopressin, cromolyn sodium, sodium chromoglycate, disodium chromoglycate, vancomycin, desferrioxamine (DFO), parathyroid hormone (PTH), fragments of PTH, glucagon-like peptide 1 (GLP-1), antimicrobials, anti-fungal agents, vitamins; analogs, fragments, mimetics and polyethylene glycol (PEG)-modified derivatives of these compounds; gallium or gallium salts; glucagons; zanamivir, sumatriptan, almotriptan, naratriptan, rizatriptan, frovatriptan, eletriptan, caspofungin acetate, CPHPC, RNAi and any combination thereof. 6. The pharmaceutical composition of claim 5, wherein the biologically active agent is selected from insulin, leutinizing-hormone releasing hormone, heparin, recombinant human growth hormone, glucagon, caspofungin acetate, calcitonin, PTH, zanamivir, erythropoietin, analogs, fragments, mimetics and polyethylene glycol (PEG)-modified derivatives of these compounds; and any combination thereof. 7. The pharmaceutical composition of claim 5, wherein the biologically active agent comprises insulin. 8. A dosage unit form comprising: (A) a pharmaceutical composition of claim 2 or claim 3; (B) a biologically active agent; and (C) (a) an excipient, (b) a diluents, (c) a disintegrant, (d) a lubricant, (e) a plasticizer, (f) a colorant, (g) a dosing vehicle, or (h) any combination thereof. 9. The dosage unit form of claim 8, wherein the biologically active agent is a protein, polypeptide, peptide, hormone, polysaccharide, mucopolysaccharide, carbohydrate, or lipid. 10. The dosage unit form of claim 9, wherein the biologically active agent is selected from: argatroban, BIBN-4096BS, growth hormones, human growth hormones (hGH), recombinant human growth hormones (rhGH), bovine growth hormones, porcine growth hormones, growth hormone releasing hormones, growth hormone releasing factor, interferons, glucagon, .alpha.-interferon, .beta.-interferon, .gamma.-interferon, interleukin-1, interleukin-2, insulin, porcine insulin, bovine insulin, human insulin, human recombinant insulin, insulin-like growth factor, insulin-like growth factor-1, heparin, un fractionated heparin, heparinoids, dermatans, chondroitins, low molecular weight heparin, very low molecular weight heparin, ultra low molecular weight heparin, calcitonin, salmon calcitonin, eel calcitonin, human calcitonin; erythropoietin, atrial naturetic factor, antigens, monoclonal antibodies, somatostatin, protease inhibitors, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, leutinizing-hormone-releasing-hormone, follicle stimulating hormone, glucocerebrosidase, thrombopoietin, filgrastim, prostaglandins, cyclosporin, vasopressin, cromolyn sodium, sodium chromoglycate, disodium chromoglycate, vancomycin, desferrioxamine, parathyroid hormone, fragments of PTH, glucagon-like peptide 1 (GLP-1), antimicrobials, anti-fungal agents, vitamins; analogs, fragments, mimetics and polyethylene glycol-modified derivatives of these compounds; gallium or gallium salts; glucagons, zanamivir, sumatriptan, almotriptan, naratriptan, rizatriptan, frovatriptan, eletriptan, capsofungin acetate, CPHPC, RNAi and any combination thereof. 11. The dosage unit form of claim 10, wherein the biologically active agent is insulin, Leutenizing-hormone releasing hormone, heparin, Recombinant Human Growth Hormone, glucagon, caspofungin acetate, calcitonin, PTH, zanamivir, erythropoietin or a combination thereof. 12. The dosage unit form of claim 9, wherein the active agent is insulin. 13. The dosage unit form of claim 9, wherein the active agent is glucagon. 14. The dosage unit form of claim 8, wherein the dosage unit form is a tablet, a capsule, a powder, or a liquid. 15. The dosage unit form of claim 8, wherein the dosing vehicle is a liquid selected from water, 1,2-propane diol, ethanol, and any combination thereof. 16. A method for administering a biologically-active agent to an animal in need of the agent, the method comprising administering orally to the animal a pharmaceutical composition of any one of claims 2-3. 17. A method for preparing a pharmaceutical composition comprising mixing: (A) a biologically active agent; (B) at least one compound of claim 1; and (C) optionally, a dosing vehicle wherein the ratio of compound (B) to biologically active agent (A) ranges from about 400:1 to about 25:1. 18. A pharmaceutical composition comprising: (A) a biologically active agent; and (B) a compound of Formula I, or a pharmaceutically acceptable salt thereof ##STR00036## wherein A is a branched or unbranched C.sub.1-C.sub.13 alkylene, C.sub.3-C.sub.13 arylene group, or a C.sub.3-C.sub.13 alkyl(arylene) group, R.sub.1-R.sub.5 are independently hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 alkoxy, C.sub.2-C.sub.4 alkenyl, halogen or hydroxy, in which at least one of R.sub.1-R.sub.5 is methoxy, wherein the ratio of compound of Formula (I) to biologically active agent ranges from about 400:1 to about 25:1. 19. The pharmaceutical composition of claim 2, wherein the ratio of delivery agent to biologically active agent is about 2:1, about 2.5:1, about 8:1, about 50:1, about 66.7:1, about 100:1, about 200:1, or about 500:1. 20. The method of claim 16, wherein the ratio of delivery agent to biologically active agent is about 2:1, about 2.5:1, about 8:1, about 50:1, about 66.7:1, about 100:1, about 200:1, or about 500:1. 21. The pharmaceutical composition of claim 2, wherein the ratio of delivery agent compound to biologically active agent ranges from about 400:1 to about 25:1. 22. The pharmaceutical composition of claim 3, wherein the ratio of delivery agent compound to biologically active agent ranges from about 400:1 to about 25:1. 23. The pharmaceutical composition of claim 3, wherein the ratio of delivery agent to biologically active agent is about 2:1, about 2.5:1, about 8:1, about 50:1, about 66.7:1, about 100:1, about 200:1, or about 500:1.

Details for Patent 9,873,667

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	HUMULIN R U-100	insulin human	Injection	018780	10/28/1982		2026-07-27
Eli Lilly And Company	HUMULIN R U-500	insulin human	Injection	018780	12/29/2015		2026-07-27
Eli Lilly And Company	HUMULIN R U-100	insulin human	Injection	018780	08/06/1998		2026-07-27
Eli Lilly And Company	HUMULIN R U-500	insulin human	Injection	018780	03/31/1994		2026-07-27
Eli Lilly And Company	HUMULIN R U-100	insulin human	Injection	018780	05/25/2018		2026-07-27