Claims for Patent: 8,703,821

Summary for Patent: 8,703,821

Title:	Dialkyl ether delivery agents
Abstract:	The present invention provides dialkyl ether compounds and pharmaceutically acceptable salts thereof, compositions containing the same and one or more active agents, and methods of administering active agents with the same.
Inventor(s):	Song; Jianfeng (West Windsor, NJ)
Assignee:	Emisphere Technologies Inc. (Roseland, NJ)
Application Number:	12/295,853
Patent Claims:	1. A pharmaceutical composition comprising: (A) a biologically active agent; and (B) at least one delivery agent compound having the formula ##STR00060## or a pharmaceutically acceptable salt thereof, wherein A is a C.sub.1-C.sub.6 alkylene group; B is a C.sub.1-C.sub.2 alkylene group; R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are independently H, halogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkoxyl, un substituted or substituted haloalkoxyl, hydroxyl, --C(O)R.sup.8, --NO.sub.2, --NR.sup.9R.sup.10, --N.sup.+R.sup.9R.sup.10R.sup.11 (R.sup.12), carbonate, ureido, --CX.sub.3, or --CN, optionally interrupted by a O, N, S, or --C(O)-- group, wherein A and R.sub.1 may together form a cycloalkyl group, wherein R.sup.8 is independently H, C.sub.1-C.sub.4 alkyl, C.sub.2-C.sub.4 alkenyl, or --NH.sub.2; R.sup.9, R.sup.10, R.sup.11, and R.sup.12 are independently H or C.sub.1-C.sub.10 alkyl; and X is a halogen, and wherein said biologically active agent is selected from: amylin and amylin agonists; adrenocorticotropin; antigens; antimicrobials, antibiotics, anti-bacterials and anti-fungal agents; anti-migraine agents; BIBM-4096BS, sumatriptan succinate; antivirals, acyclovir, valacyclovir; atrial naturetic factor; argatroban; bisphosphonates, alendronate, clodronate, etidronate, ibandronate, incadronate, minodronate, neridronate, olpadronate, pamidronate, risedronate, tiludronate, zoledronate, EB1053, AND YH529; BIBN4096BS-(1-piperidinecarboxamide. n-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl)carbonyl]pentyl]amino]-1- -[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4(1,4-dih ydro-2-oxo-3(2HO-quinazolinyl)-. [R--(R*,S*)])--); calcitonin, salmon calcitonin, eel calcitonin, porcine calcitonin, human calcitonin; cholecystokinin (CCK) and CCK agonists, CCK-8; cromolyn sodium (sodium or disodium chromoglycate); CPHPC; cyclosporine; desferrioxamine (DFO); erythropoietin; exedin and exedin agonists, exendin-3, exendin-4; filgrastim; follicle stimulating hormone (recombinant and natural); gallium nitrate; glucagon; glucagon-like peptide 1 (GLP-1), glucagon, glucagon-like peptide 2 (GLP-2); glucocerebrosidase; gonadotropin releasing hormone; growth hormone releasing factor; growth hormone releasing hormones; growth hormone, human growth hormone (hGH), recombinant human growth hormone (rhGH), bovine growth hormone, porcine growth hormone; heparin, unfractionated heparin, heparinoids, dermatans, chondroitins, low molecular weight heparin, very low molecular weight heparin, ultra low molecular weight heparin, synthetic heparin, fondiparinux; insulin, porcine insulin, bovine insulin, human insulin, human recombinant insulin, optionally having counter ions selected from the group consisting of zinc, sodium, calcium and ammonium; insulin-like growth factor, IGF-1; interferons, .alpha.-interferon, .beta.-interferon, omega interferon, .gamma. interferon; interleukin-1; interleukin-2; interleukin-11; interleukin-21; leutinizing hormone and leutinizing hormone releasing hormone; leptin (OB protein); methyphenidate salt; monoclonal antibodies, retuxin, tnf-alpha soluble receptors; oxytocin; parathyroid hormone (PTH), PTH 1-34 and PTH 1-38; peptide YY (PYY), PYY agonists, PYY3-36; dipeptidyl peptidase IV (DPP-4) inhibitors; prostaglandins; protease inhibitors; somatostatin; thrombopoietin; vancomycin; vasopressin; vitamins; vaccines, anthrax vaccines, y. pestis vaccines, influenza vaccines, herpes vaccines; analogs, mimetics and polyethylene glycol-modified derivatives of any of the above compounds, and any combination thereof. 2. The composition of claim 1, wherein said delivery agent compound is selected from: ##STR00061## ##STR00062## ##STR00063## ##STR00064## ##STR00065## ##STR00066## ##STR00067## ##STR00068## ##STR00069## ##STR00070## ##STR00071## ##STR00072## and pharmaceutically acceptable salts thereof. 3. The pharmaceutical composition of claim 1, wherein A is an unbranched and unsubstituted C.sub.1-C.sub.6 alkylene group. 4. The pharmaceutical composition of claim 1 wherein B is an unbranched and unsubstituted C.sub.1-C.sub.2 alkylene group. 5. The pharmaceutical composition of claim 1 wherein B is a methylene group. 6. The pharmaceutical composition of claim 1 wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are independently selected from H, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy or hydroxyl. 7. The pharmaceutical composition of claim 1 wherein at least one of R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 is a methyl, chlorine, fluorine, methoxy, bromine, 1-methylethyl, butyl, ethyl, --OC.sub.4H.sub.9, or phenyl. 8. The pharmaceutical composition of claim 1 wherein at least one of R.sub.1, R.sub.2, R.sub.3, R and R.sub.5 is methyl. 9. The pharmaceutical composition of claim 1 wherein at least one of R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 is chlorine. 10. The pharmaceutical composition of claim 1 wherein at least one of R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 is fluorine. 11. The pharmaceutical composition of claim 1 wherein at least one of R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 is methoxy. 12. The pharmaceutical composition of claim 1 wherein at least one of R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 is bromine. 13. The pharmaceutical composition of claim 1 wherein at least one of R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 is 1-methylethyl. 14. The pharmaceutical composition of claim 1 wherein at least one of R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 is butyl. 15. A compound selected from: ##STR00073## ##STR00074## ##STR00075## ##STR00076## ##STR00077## ##STR00078## ##STR00079## ##STR00080## ##STR00081## ##STR00082## ##STR00083## and pharmaceutically acceptable salts thereof. 16. The pharmaceutical composition of claim 1, wherein said biologically active agent comprises insulin, unfractionated heparin, low molecular weight heparin, very low molecular weight heparin, ultra low molecular weight heparin, calcitonin, parathyroid hormone, erythropoietin, daptomycin, human growth hormones, analogs, mimetics or polyethylene glycol-modified derivatives of these compounds, or any combination thereof. 17. A method for administering a biologically active agent to an animal in need of the agent, the method comprising administering orally to the animal the pharmaceutical composition of claim 1. 18. A method for preparing a pharmaceutical composition of claim 1, comprising mixing: (A) at least one biologically active agent; (B) at least one delivery agent compound of Formula I; and (C) optionally, a dosing vehicle.

Details for Patent 8,703,821

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		2026-04-18
Eli Lilly And Company	HUMULIN R U-500	insulin human	Injection	018780	12/29/2015		2026-04-18
Eli Lilly And Company	HUMULIN R U-100	insulin human	Injection	018780	08/06/1998		2026-04-18
Eli Lilly And Company	HUMULIN R U-500	insulin human	Injection	018780	03/31/1994		2026-04-18
Eli Lilly And Company	HUMULIN R U-100	insulin human	Injection	018780	05/25/2018		2026-04-18
Amgen, Inc.	NEUPOGEN	filgrastim	Injection	103353	02/20/1991		2026-04-18
Amgen, Inc.	NEUPOGEN	filgrastim	Injection	103353	06/28/2000		2026-04-18