(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 17 September 2009 (17.09.2009) WO 2009/114650 Al (51) International Patent Classification: (US). GOSWAMY, Amit [US/US]; 130 Knowles Drive, A61K 31/10 (2006.01) A61K 45/06 (2006.01) Suite A, Los Gatos, CA 95032 (US). A61K 31/195 (2006.01) A61P 29/00 (2006.01) (74) Agents: NOLAN, James S. @ et al.; Mintz Levin Cohn (21) International Application Number: Ferris Glovsky And Popeo, P.C , One Financial Center, PCT/US2009/036867 Boston, MA 021 11 (US). (22) International Filing Date: (81) Designated States (unless otherwise indicated, for every 11 March 2009 ( 11.03.2009) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, English (25) Filing Language: CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, (26) Publication Language: English EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, (30) Priority Data: KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, 61/035,706 11 March 2008 ( 11.03.2008) US MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, (71) Applicant (for all designated States except US): CHAK- NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SHU RESEARCH, INC. [US/US]; 130 Knowles Drive, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, Suite A, Los Gatos, CA 95032 (US). UG, US, UZ, VC, VN, ZA, ZM, ZW. (72) Inventors; and (84) Designated States (unless otherwise indicated, for every (75) Inventors/Applicants (for US only): BHUSHAN, Rajiv kind of regional protection available): ARIPO (BW, GH, [IN/US]; 3838 Mumford Place, Palo Alto, CA 94306 GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, (US). DUFFIELD, Christopher [US/US]; 130 Knowles ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, Drive, Suite A, Los Gatos, CA 95032 (US). GIN, Jerry, TM), European (AT, BE, BG, CH, CY, CZ, DE, DK, EE, B. [US/US]; 1206 Sargent Drive, Sunnyvale, CA 94807 ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, [Continued on next page] (54) Title: METHODS AND COMPOSITIONS FOR TREATING INFLAMMATION AND INFLAMMATION-RELATED PATHOLOGIES (57) Abstract: Methods and compositions are provided for the treatment of inflammation and disorders, diseases, and adverse conditions, i.e., pathologies, caused by or other wise associated with inflammatory processes. A metal ion sequestering agent that directly or indirectly exerts an anti inflammatory effect is administered to a subject in combi nation with a sequestration inactivating moiety that facili tates transport of the metal ion sequestering agent through biological membranes. The sequestration inactivating m oi ety also inactivates the metal ion sequestering agent until association between the two components is cleaved in vivo to release the active sequestering agent. Compositions con taining a metal ion sequestering agent and a sequestration inactivating moiety are also provided; the compositions op tionally contain an added anti-inflammatory agent. MCP FIG. 1D 200 inflammation MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, TR), before the expiration of the time limit for amending the OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, claims and to be republished in the event of receipt of MR, NE, SN, TD, TG). amendments (Rule 48.2(h)) Published: METHODS AND COMPOSITIONS FOR TREATING INFLAMMATION AND INFLAMMATION-RELATED PATHOLOGIES CROSS-REFERENCE TO RELATED APPLICATION [0001] This application claims priority under 35 U.S.C. § 119(e)(l) to provisional U.S. Patent Application Serial No. 61/035,706, filed March 11, 2008, the disclosure of which is incorporated by reference herein. TECHNICAL FIELD [0002] This disclosure relates generally to the field of pharmacotherapy, and more particularly relates to methods and compositions for the prevention and treatment of inflammation and conditions associated with inflammation. The disclosure finds utility in the fields of medicine, pharmacology, and drug delivery. BACKGROUND [0003] Inflammation is a complex biological response of vascular tissue to harmful stimuli, such as oxidative stress, irritants, pathogens, and damaged cells. It is a protective attempt by the organism to remove an injurious stimulus and initiate the healing process for injured tissue. The inflammatory response involves the production and release of inflammatory modulators that function to both destroy damaged cells and heal injured tissue. In order to perform this function, however, various inflammatory modulators either directly produce and/or signal the release of agents that produce reactive oxygen species for the purpose of destroying invading agents and/or injured cells. The inflammatory response, therefore, involves a balance between the destruction of damaged cells and the healing of injured tissue, since an imbalance can lead to oxidative stress and the onset of various inflammatory disease pathologies. [0004] More specifically, oxidative stress in a biological system is caused by the imbalance between the system's production of reactive oxygen species and the system's actual ability to detoxify and repair the damage resulting from such species. Typical formulations for the prevention and/or treatment of oxidative stress involve the administration of antioxidants, i.e., agents that primarily function by reducing the rate at which oxidation occurs or otherwise inhibiting the oxidation of other compounds. Many antioxidants involve a post-oxidation mechanism in which free radical chain reactions initiated by free radicals produced during oxidation are terminated. Other antioxidants work by undergoing direct oxidation by free radicals, thus reducing the fraction of other compounds that are oxidized. [0005] The use of such antioxidants to reduce oxidative stress and/or prevent or treat disease is, however, controversial. Further, although the administration of antioxidants may function to slow or prevent the oxidation of various compounds in the body, they typically do not function to treat and/or prevent the underlying mechanisms that lead to oxidative stress. More specifically, with respect to the present disclosure, typical antioxidants do not function to prevent and/or treat inflammation, which often involves or leads to oxidative stress. [0006] Accordingly, there is a need in the art for methods and compositions that not only prevent and/or treat inflammation but also reduce oxidative stress and/or prevent and/or treat inflammation-related pathologies. The subject methods and compositions presented herein meet these and other needs in the art. SUMMARY OF THE DISCLOSURE [0007] In one aspect of the disclosure, a method is provided for treating an inflammatory condition in a subject. The method involves administering to the subject an effective amount of an inactivated metal ion sequestering agent that is readily transported through biological membranes and which is activated in vivo to sequester metal ions that are directly causing, indirectly causing, or otherwise associated with the inflammatory condition. The metal ion sequestering agent is in inactivated form prior to administration . For instance, the metal ion sequestering agent may be in inactivated form by virtue of being associated with an effective amount of a sequestration inactivating moiety that inactivates the ability of the metal ion sequestering agent to sequester metal ions. The sequestration inactivating moiety may also facilitate transport of the metal ion sequestering agent through biological membranes. The inactivated metal ion sequestering agent is sometimes referred to herein as a "prochelator," although sequestration of metal ions can involve sequestration and complexation processes beyond the scope of chelation per se. The term "prochelator" is analogous to the term "prodrug" insofar as a prodrug is a therapeutically inactive agent until activated in vivo, and the prochelator, as well, is incapable of sequestering metal ions until activated in vivo. The use of prochelator components and compositions in the treatment of inflammatory conditions, as described herein, is believed to be a completely novel and unprecedented discovery. [0008] The metal ion sequestering agent and the sequestration inactivating moiety are generally, although not necessarily, administered in a single composition in which the two components are combined. In such a case, there may be some fraction of each component that is not associated with the other, but the majority of each component will be associated with the other as explained herein. The method may also involve separate administration of the metal ion sequestering agent and the sequestration inactivating moiety, or, in some cases, the two components may be incorporated in separate and discrete sections of a dosage form. Accordingly, in another embodiment, a method of the disclosure involves co-administration of a therapeutically effective amount of the metal ion sequestering agent and an amount of a sequestration inactivating moiety effective to inactivate the sequestering agent and facilitate transport thereof through biological membranes. [0009] In another aspect of the disclosure, a composition is provided for the treatment of inflammatory conditions. The composition contains a therapeutically effective amount of an anti-inflammatory agent, a therapeutically effective amount of a metal ion sequestering agent, and, in association with the metal ion sequestering agent,