Claims for Patent: 6,440,929

Summary for Patent: 6,440,929

Title:	Pulmonary delivery of active agents
Abstract:	The present invention relates to pulmonary delivery of active agents. Acylated or sufonated amino acids are used as carriers to facilitate pulmonary delivery of active agents to a target.
Inventor(s):	Milstein; Sam J. (Larchmont, NY), Smart; John E. (Katonah, NY), Sarubbi; Donald J. (Carmel, NY), Leipold; Monica (Thornwood, NY), Flanders; Elizabeth (Ridgefield, CT), O\'Toole; Doris (Carmel, NY), Leone-Bay; Andrea (Ridgefield, CT), Gschneidner; David (Stamford, CT)
Assignee:	Emisphere Technologies, Inc. (Tarrytown, NY)
Application Number:	09/744,777
Patent Claims:	1. A method for administering a biologically-active agent to an animal in need of said agent, said method comprising administering via the pulmonary route to said animal a composition comprising (A) an active agent and (B) a carrier comprising an acylated amino acid, a sulfonated amino acid, a polyamino acid which includes an acylated amino acid, a polyamino acid which include a sulfonated amino acid, or any combination of any of the foregoing. 2. A method as defined in claim 1 wherein said active agent is selected from the group consisting of a biologically active agent, a chemically active agent, or a combination thereof. 3. A method as defined in claim 2, wherein said biologically active agent comprises at least one peptide, mucopolysaccharides, carbohydrate, or lipid. 4. A method as defined in claim 3, wherein said biologically active agent is selected from the group consisting of growth hormones, human growth hormones (hGH), recombinant human growth hormones (rhGH), bovine growth hormone, porcine growth hormones, growth hormone-releasing hormones, interferons, .alpha.-interferon, .beta.-interferon, .gamma.-interferon, interleukin-1, interleukin-II, 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, sodium chromoglycate, disodium chromoglycate, vancomycin, desferrioxamine (DFO), parathyroid hormone (PTH), fragments of PTH, antimicrobials, anti-fungal agents, analogs, fragments, mimetics and polyethylene glycol (PEG)-modified derivatives of these compounds; and any combination thereof. 5. A method as defined in claim 3, wherein said biologically active agent is selected from the group consisting of human growth hormones (hGH), recombinant human growth hormones (rhGH), bovine growth hormone, growth hormone-releasing hormones, interferons, .alpha.-interferon, .beta.-interferon, .gamma.-interferon, interleukin-1, interleukin-II, insulin, insulin-like growth factor (IGF), IGF-1, heparin, unfractionated heparin, heparinoids, 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, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, leutinizing-hormone-releasing-hormone, follicle stimulating hormone, glucocerebrosidase, thrombopoietin, filgrastim, prostaglandins, cyclosporin, vasopressin, sodium chromoglycate, disodium chromoglycate, vancomycin, desferrioxamine (DFO), parathyroid hormone (PTH), fragments of PTH, antimicrobials, anti-fungal agents, analogs, fragments, mimetics and polyethylene glycol (PEG)-modified derivatives of these compounds; and any combination thereof. 6. A method as defined in claim 3, wherein said biologically active agent comprises an interferon, interleukin-II, insulin, insulin-like growth factor (IGF), JGF-1, heparin, low molecular weight heparin, low molecular weight heparin, calcitonin, oxytocin, vasopressin, vancomycin, desferrioxamine, parathyroid hormone, and combinations thereof. 7. A method as defined in claim 2, wherein said biologically active agent selected from the group consisting of insulin, insulin-like growth factor (IGF), IGF-1, or combinations thereof. 8. The method of claim 1, wherein the carrier comprises a compound having the formula ##STR7## wherein R.sup.1 is C.sub.1 -C.sub.7 alkyl, C.sub.3 -C.sub.10 cycloalkyl, cycloalkenyl, aryl, thienyl, phenyl, naphthyl, pyrrolo, or pyridyl; R.sup.1 is optionally substituted with one or more C.sub.1 -C.sub.7 alkyl, C.sub.2 -C.sub.7 alkenyl, C.sub.2 -C.sub.7 alkynl, C.sub.6 -C.sub.10 cycloalkyl, phenyl, phenoxy, F, Cl, Br, --OH, --SO.sub.2, --SO.sub.3 H, --NO.sub.2, --SH, --PO.sub.3 H, oxazolo, isoxazolo, alkoxy having the formula --OR.sup.6, --COOR.sup.7, --N(R.sup.5).sub.2, --N.sup.+ (R.sup.5).sub.3 X.sup.-, or any combination thereof; Y is ##STR8## or --SO.sub.2 --; X is halogen, hydroxide, sulfate, tetrafluoroborate, or phosphate; R.sup.2 is hydrogen, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, or --(CH.sub.2).sub.n --COOH, where n is 1 to 10; R.sup.3 is C.sub.1 C.sub.24 alkyl, C.sub.2 -C.sub.24 alkenyl, C.sub.2 -C.sub.24 alkyne, C.sub.3 -C.sub.10 cycloalkyl, C.sub.3 -C.sub.10 cycloalkenyl, phenyl, naphthyl, (C.sub.1 -C.sub.10 alkyl) phenyl, (C.sub.2 -C.sub.10 alkenyl) phenyl, (C.sub.1 -C.sub.10 alkyl) naphthyl, (C.sub.2 -C.sub.10 alkenyl) naphthyl, phenyl (C.sub.1 -C.sub.10 alkyl), phenyl (C.sub.2 -C.sub.10 alkenyl), naphthyl (C.sub.1 -C.sub.10 alkyl) or naphthyl (C.sub.2 -C.sub.10 alkenyl); R.sup.3 being optionally substituted with C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.1 -C.sub.4 alkoxy, --OH, --SH, halogen, --NH.sub.2, --CO.sub.2 R.sup.4, C.sub.3 -C.sub.10 cycloalkyl, C.sub.3 -C.sub.10 cycloalkenyl, heterocyclic having 3-10 ring atoms wherein the hetero atom is one or more of N, O, S or any combination thereof, aryl, (C.sub.1 -C.sub.10 alk)aryl, ar(C.sub.1 -C.sub.10 alkyl), or any combination thereof; R.sup.4 is hydrogen, C.sub.1 -C.sub.4 alkyl, or C.sub.2 -C.sub.4 alkenyl; R.sup.5 is hydrogen or C.sub.1 -C.sub.10 alkyl; R.sup.6 is C.sub.1 -C.sub.10 alkyl, alkenyl, alkynyl, aryl or cycloalkyl; and R.sup.7 is hydrogen, C.sub.1 -C.sub.10 alkyl, alkenyl, alkynl, aryl or cycloalkyl. 9. The method of claim 8, wherein the active agent is selected from the group consisting of insulin, insulin-like growth factor (IGF), IGF-1, or combinations thereof. 10. The method of claim 1, wherein the carrier comprises a compound having the formula Ar--Y--(R.sup.8).sub.n --OH, wherein Ar is a substituted or unsubstituted phenyl or naphthyl, preferably Ar is substituted or unsubstituted 2-OH-phenyl; Y is ##STR9## or --SO.sub.2 --; R.sup.8 has the formula ##STR10## R.sup.9 is C.sub.1 to C.sub.24 alkyl, C.sub.1 to C.sub.24 alkenyl, phenyl, naphthyl, (C.sub.1 to C.sub.10 alkyl) phenyl, (C.sub.1 -C.sub.10 alkenyl) phenyl, (C.sub.1 to C.sub.10 alkyl) naphthyl, (C.sub.1 to C.sub.10 alkenyl) naphthyl, phenyl (C.sub.1 to C.sub.10 alkyl), phenyl (C.sub.1 to C.sub.10 alkenyl), naphthyl (C.sub.1 to C.sub.10 alkyl) and naphthyl (C.sub.1 to C.sub.10 alkenyl); R.sup.9 is optionally substituted with C.sub.1 to C.sub.4, alkyl, C.sub.1 to C.sub.4 alkenyl, C.sub.1 to C.sub.4 alkoxy, --OH, --SH, --CO.sub.2 R.sup.11, cycloalkyl, cycloalkenyl, heterocyclic alkyl, alkaryl, heteroaryl, heteroalkaryl, or any combination thereof; R.sup.9 is optionally interrupted by oxygen, nitrogen, sulfur or any combination thereof; R.sup.10 is hydrogen, C.sub.1 to C.sub.4 alkyl or C.sub.1 to C.sub.4 alkenyl; and R.sup.11 is hydrogen, C.sub.1 to C.sub.4 alkyl or C.sub.1 to C.sub.4 alkenyl. 11. The method of claim 10, wherein the active agent is selected from the group consisting of insulin, insulin-like growth factor (IGF), IGF-1, or combinations thereof. 12. The method of claim 1, wherein the carrier comprises a compound having the formula ##STR11## and salts thereof. 13. The method of claim 12, wherein the active agent is selected from the group consisting of insulin, insulin-like growth factor (IGF), IGF-1, or combinations thereof. 14. The method of claim 1, wherein the carrier comprises a compound having the formula ##STR12## or a salt thereof. 15. The method of claim 14, wherein the active agent is selected from the group consisting of insulin, insulin-like growth factor (IGF), IGF-1, or combinations thereof. 16. The method of claim 1, wherein the carrier comprises a compound having the formula ##STR13## or a salt thereof. 17. The method of claim 16, wherein the active agent is selected from the group consisting of insulin, insulin-like growth factor (IGF), IGF-1, or combinations thereof.

Details for Patent 6,440,929

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Amgen, Inc.	NEUPOGEN	filgrastim	Injection	103353	02/20/1991		2018-07-27
Amgen, Inc.	NEUPOGEN	filgrastim	Injection	103353	06/28/2000		2018-07-27
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2018-07-27