# US 8,772,237 B2 · Compositions and methods for counteracting effects of reactive oxygen species and free radicals > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,772,237 B2 - Document ID: US8772237B2 - Status: Granted - Kind: B2 - Application number: 13/218,685 - Filed: 2011-08-26 - Published: 2012-03-08 - Granted: 2014-07-08 - Earliest claimed: 1999-11-18 - Assignees: Ischemix LLC - Applicants: Victor E. Shashoua - Inventors: Victor E. Shashoua - Web page: https://patentgrep.com/patent/US8772237B2 ## CPC - C07K 7/06: having 5 to 11 amino acids - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - A61P 39/06: Free radical scavengers or antioxidants - C07K 5/1021: {with the first amino acid being acidic} - C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract Peptide compounds and methods for upregulating expression of a gene encoding an antioxidative enzyme, such as superoxide dismutase or catalase, to counteract harmful oxidative effects of reactive oxygen species and other free radicals are described. The peptide compounds may be used to treat or prevent diseases and conditions characterized by undesirable elevation of reactive oxygen species and other free radicals, to upregulate AP-1 gene expression, and to treat pain. The peptide compounds may be used as components of pharmaceuticals and dietary supplements. ## Claims ### Claim 1 A method of treating an ischemic injury in a subject, the method comprising administering to the subject a peptide compound, wherein the amino acid sequence of the peptide compound is Asp Gly Asp, Asp Gly, Thr Val Ser, or Glu Ala, wherein the peptide compound is administered in an amount effective to treat the ischemic injury, wherein the peptide compound comprises an amino terminal capping group and/or a carboxy terminal capping group. ### Claim 2 (depends on 1) The method of claim 1, wherein the amino terminal capping group is a lipoic acid moiety (Lip). ### Claim 3 (depends on 1) The method of claim 1, wherein the ischemic injury is a reperfusion injury. ### Claim 4 (depends on 1) The method of claim 1 wherein the ischemic injury results from a stroke. ### Claim 5 (depends on 1) The method of claim 1, wherein the ischemic injury is a myocardial infarction. ### Claim 6 (depends on 1) The method of claim 1, wherein the ischemic injury results from an occlusion. ### Claim 7 (depends on 1) The method of claim 1, wherein the ischemic injury results from a heart attack. ### Claim 8 (depends on 1) The method of claim 1, wherein the ischemic injury is a drug-induced injury. ### Claim 9 (depends on 2) The method of claim 2, wherein the peptide compound is [Lip]-Asp Gly. ### Claim 10 (depends on 2) The method of claim 2, wherein the peptide compound is [Lip]-Glu Ala. ### Claim 11 (depends on 2) The method of claim 2, wherein the peptide compound is [Lip]-Asp Gly Asp. ### Claim 12 (depends on 2) The method of claim 2, wherein the peptide compound is [Lip]-Thr Val Ser. ### Claim 13 A method for reducing an elevated level of reactive oxygen species (ROS) and/or free radicals in a subject, the method comprising administering to the subject a peptide compound, wherein the amino acid sequence of the peptide compound is Asp Gly Asp, Asp Gly, Thr Val Ser, or Glu Ala, wherein the peptide compound is administered in an amount effective to reduce the elevated level of ROS and/or free radicals in the subject, wherein the peptide compound comprises an amino terminal capping group and/or a carboxy terminal capping group. ### Claim 14 (depends on 13) The method of claim 13, wherein the elevated level of ROS and/or free radicals is the result of an ischemic injury in the subject. ### Claim 15 A method for treating an ischemic injury in a subject, the method comprising administering to the subject a peptide compound, wherein the amino acid sequence of the peptide compound is Glu Gly, Asp Gly Asp Gly Asp, Asp Ala (SEQ ID NO:4), or Asp Gly Asp Gly Asp Phe Ala (SEQ ID NO:6), wherein the peptide compound is administered in an amount effective to treat the ischemic injury in the subject, wherein the peptide compound comprises an amino terminal capping group and/or a carboxy terminal capping group. ### Claim 16 A method for reducing an elevated level of reactive oxygen species (ROS) and/or free radicals in a subject, the method comprising administering to the subject a peptide compound, wherein the amino acid sequence of the peptide compound is Glu Gly, Asp Gly Asp Gly Asp (SEQ ID NO:4), Asp Ala, or Asp Gly Asp Gly Asp Phe Ala (SEQ ID NO:6), wherein the peptide compound is administered in an amount effective to reduce the elevated level of ROS and/or free radical in the subject, wherein the peptide compound comprises an amino terminal capping group and/or a carboxy terminal capping group. ### Claim 17 A method for treating an ischemic injury in a subject, the method comprising administering to the subject a peptide compound that has the formula: R1 Xaa1 Xaa2 Xaa3 R2, wherein Xaa1 is Asp, Asn, Glu, Gln, Thr, or Tyr; Xaa2 is absent or any amino acid; Xaa3 is Asp, Asn, Glu, Thr, Ser, Gly, or Leu; R1 is absent or is an amino terminal capping group; R2 is absent or is a carboxy terminal capping group, and wherein the peptide compound comprises an amino terminal capping group and/or a carboxy terminal capping group. ### Claim 18 A method for reducing an elevated level of reactive oxygen species (ROS) and/or free radicals in a subject, the method comprising administering to the subject a peptide compound that has the formula: R1 Xaa1 Xaa2 Xaa3 R2, wherein Xaa1 is Asp, Asn, Glu, Gln, Thr, or Tyr; Xaa2 is absent or any amino acid; Xaa3 is Asp, Asn, Glu, Thr, Ser, Gly, or Leu; R1 is absent or is an amino terminal capping group; R2 is absent or is a carboxy terminal capping group, and wherein the peptide compound comprises an amino terminal capping group and/or a carboxy terminal capping group.