COMPOSITIONS, KITS, AND METHODS TO INDUCE ACQUIRED CYTORESISTANCEUSING STRESS PROTEIN INDUCERS

• US 20160271164A1
• Filed: 09/28/2015
• Published: 09/22/2016
• Est. Priority Date: 09/29/2014
• Status: Active Grant

• Current Assignee: Fred Hutchinson Cancer Center
• Original Assignee: Fred Hutchinson Cancer Research Center (Fred Hutchinson Cancer Research Center|Argus Genetics|Mars)
• Inventors: Zager, Richard, Johnson, Ali CM
• Granted Patent: US 10,639,321 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A01N 1/0226 Physiologically active agents, i.e. substances affecting physiological processes of cells and tissue to be preserved, e.g. anti-oxidants or nutrients
• CPC Class Codes: A61K 31/194 having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
• CPC Class Codes: A61K 31/555 containing heavy metals, e.g. hemin, hematin, melarsoprol
• CPC Class Codes: A61K 31/714 Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
• CPC Class Codes: A61K 33/26 Iron; Compounds thereof
• CPC Class Codes: A61K 38/42 Haemoglobins; Myoglobins
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07H 23/00 Compounds containing boron, silicon, or a metal, e.g. chelates, vitamin B12 esters with inorganic acids C07H11/00; metal salts, see parent compounds

Abstract

The present disclosure provides compositions, kits, and methods to protect organs by inducing acquired cytoresistance without causing injury to the organ. The compositions, kits, and methods utilize heme proteins, iron and/or vitamin B12 and, optionally, agents that impact heme protein metabolism.

Claims

1-244. -244. (canceled)

245. A composition comprising:

246. A kit comprising:

a therapeutically effective amount of;

(i) iron sucrose and (ii) tin protoporphyrin, wherein administration of the therapeutically effective amount of the iron sucrose and the tin protoporphyrin to an organ at least one of;

protects the organ without causing injury to the organ;

generates acquired cytoresistance in the organ in the absence of causing injury to the organ;

or up-regulates expression of protective stress proteins in the organ without causing injury to the organ.

247. A kit of claim 246, further comprising administration instructions.

248. A kit of claim 246, wherein the organ is protected from an injury based on an insult.

249. A kit of claim 246, wherein the administration occurs at least 8 hours before a scheduled insult.

250. A kit of claim 249, wherein the scheduled insult is surgery, chemotherapy, or radiocontrast toxicity.

251. A kit of claim 250, wherein the surgery is an organ transplant surgery.

252. A kit of claim 246, wherein the organ is a transplanted organ.

253. A kit of claim 246, wherein the organ is a kidney and protection against injury is evidenced by prevention or reduction in blood urea nitrogen (BUN) or serum creatinine increases as compared to a reference level.

254. A kit of claim 246, wherein the kit includes a therapeutically effective amount of vitamin B12 or a derivative of vitamin B12.

255. A kit of claim 246, wherein the kit includes a therapeutically effective amount of myoglobin or a nitrited myoglobin.

256. A method comprising administering to an organ a composition comprising a therapeutically effective amount of:

(i) iron sucrose and (ii) tin protoporphyrin, before an injury to the organ occurs, wherein administering to the organ the therapeutically effective amount of the composition at least one of;

protects the organ from the injury without causing injury to the organ;

generates acquired cytoresistance in the organ in the absence of causing injury to the organ;

or up-regulates expression of protective stress proteins in the organ without causing injury to the organ.

257. A method of claim 256, wherein the injury is an injury based on an insult.

258. A method of claim 256, wherein administering to the organ the therapeutically effective amount of the composition occurs at least 8 hours before a scheduled insult.

259. A method of claim 258, wherein the scheduled insult is surgery, chemotherapy, or radiocontrast toxicity.

260. A method of claim 259, wherein the surgery is an organ transplant surgery.

261. A method of claim 256, wherein the organ is a transplanted organ.

262. A method of claim 256, wherein the organ is a kidney and protection is evidenced by prevention or reduction in BUN or serum creatinine increases as compared to a reference level.

263. A method of claim 256, wherein the composition includes a therapeutically effective amount of vitamin B12 or a derivative of vitamin B12.

264. A method of claim 256, wherein the composition includes a therapeutically effective amount of myoglobin or nitrited myoglobin.