Claims for Patent: 8,895,502

Summary for Patent: 8,895,502

Title:	.beta.2-glycoprotein I peptide inhibitors
Abstract:	Therapeutic peptides (and peptoids) for preventing or inhibiting tissue damage associated with ischemia and/or reperfusion are provided, along with peptides (and peptoids) for preventing or inhibiting cancerous tissue growth. The peptides are derived from .beta.2-glycoprotein I. Pharmaceutical and veterinary compositions comprising the peptides are also provided. Methods of using the peptides to prevent or inhibit tissue damage associated with ischemia and/or reperfusion and/or to prevent or inhibit tissue damage or the growth of cancerous tissue are also provided.
Inventor(s):	Fleming; Sherry (Manhattan, KS), Tomich; John M. (Manhattan, KS)
Assignee:	Kansas State University Research Foundation (Manhattan, KS)
Application Number:	13/782,881
Patent Claims:	1. A .beta.2-glycoprotein I-derived peptide, said peptide being selected from the group consisting of IHFYX.sup.1KNKEKKX.sup.1SYTVEDAQX.sup.1RDGTI, where each X.sup.1 is S (SEQ ID NO. 1); KKX.sup.1SYTVEDAQX.sup.1RDGTIEX.sup.2X.sup.3X.sup.4X.sup.1FKEHS, where each X.sup.1 is S, X.sup.2 is I or V, X.sup.3 is P or G, and X.sup.4 is R or K (SEQ ID NO. 2); KKSSYTVEDAQS (SEQ ID NO. 3); residues 3-12 of SEQ ID NO. 3; residues 3-12 of SEQ ID NO. 3 with D-amino acids; SQADEVTYSS with D-amino acids (SEQ ID NO. 4); TEDAQX.sup.1IDGTIEV, where each X.sup.1 is S (SEQ ID NO. 5); KKX.sup.1SYTEDAQX.sup.1IDGTIEVPKX.sup.1FKEHS, where each X.sup.1 is S (SEQ ID NO. 7); VSFFX.sup.1KNKEKKX.sup.1SYTEDAQX.sup.1IDGTI, where each X.sup.1 is S (SEQ ID NO. 8); IHFYX.sup.1KNKEKKX.sup.1SYTVEAHX.sup.1RDGTI, where each X.sup.1 is S (SEQ ID NO. 9); KKSSYTVEAHS (SEQ ID NO. 12); residues 3-11 of SEQ ID NO. 12; residues 3-11 of SEQ ID NO. 12 with D-amino acids; SHAEVTYSS (SEQ ID NO. 13), KKSSYTVEAHSRDGTI (SEQ ID NO. 19), and conservatively modified sequence variants thereof which retain the function of said peptide. 2. A pharmaceutical or veterinary composition comprising a .beta.2-glycoprotein I-derived peptide, said peptide being dissolved or dispersed in a pharmaceutically-acceptable carrier, wherein said peptide is selected from the group consisting of IHFYX.sup.1KNKEKKX.sup.1SYTVEDAQX.sup.1RDGTI, where each X.sup.1 is S (SEQ ID NO. 1); KKX.sup.1SYTVEDAQX.sup.1RDGTIEX.sup.2X.sup.3X.sup.4X.sup.1FKEHS, where each X.sup.1 is S, X.sup.2 is I or V, X.sup.3 is P or G, and X.sup.4 is R or K (SEQ ID NO. 2); KKSSYTVEDAQS (SEQ ID NO. 3); residues 3-12 of SEQ ID NO. 3; residues 3-12 of SEQ ID NO. 3 with D-amino acids; SQADEVTYSS with D-amino acids (SEQ ID NO. 4); TEDAQX.sup.1IDGTIEV, where each X.sup.1 is S (SEQ ID NO. 5); KKX.sup.1SYTEDAQX.sup.1IDGTIEVPKX.sup.1FKEHS, where each X.sup.1 is S (SEQ ID NO. 7); VSFFX.sup.1KNKEKKX.sup.1SYTEDAQX.sup.1IDGTI, where each X.sup.1 is S (SEQ ID NO. 8); IHFYX.sup.1KNKEKKX.sup.1SYTVEAHX.sup.1RDGTI, where each X.sup.1 is S (SEQ ID NO. 9); KKSSYTVEAHS (SEQ ID NO. 12); residues 3-11 of SEQ ID NO. 12; residues 3-11 of SEQ ID NO. 12 with D-amino acids; SHAEVTYSS (SEQ ID NO. 13), KKSSYTVEAHSRDGTI (SEQ ID NO. 19), and conservatively modified sequence variants thereof which retain the function of said peptide. 3. The composition of claim 2, said carrier being selected from the group consisting of normal saline, sterile water, phosphate buffered saline, ringers lactate and/or dextrose, dimethyl sulfoxide, ethanol, sugars, milk proteins, gelatin, animal oils, vegetable oils, glycerol, and combinations thereof. 4. The composition of claim 2, wherein said peptide is present in said composition at a concentration of from about 4 .mu.M to about 80 .mu.M. 5. The composition of claim 2, further comprising an additional prophylactic or therapeutic agent dissolved or dispersed in said carrier along with said peptide, wherein said agent is selected from the group consisting of medicines, small molecule drugs, biologics, monoclonal antibodies, vitamins, minerals, and combinations thereof. 6. The composition of claim 2, comprising a combination of two or more different .beta.2-glycoprotein I-derived peptides dissolved or dispersed in said pharmaceutically-acceptable carrier. 7. A .beta.2-glycoprotein I-derived peptide and a label, tag, or targeting moiety attached to the C- or N-terminus of said peptide, said peptide being selected from the group consisting of IHFYX.sup.1KNKEKKX.sup.1SYTVEDAQX.sup.1RDGTI, where each X.sup.1 is S (SEQ ID NO. 1); KKX.sup.1SYTVEDAQX.sup.1RDGTIEX.sup.2X.sup.3X.sup.4X.sup.1FKEHS, where each X.sup.1 is S, X.sup.2 is I or V, X.sup.3 is P or G, and X.sup.4 is R or K (SEQ ID NO. 2); KKSSYTVEDAQS (SEQ ID NO. 3); residues 3-12 of SEQ ID NO. 3; residues 3-12 of SEQ ID NO. 3 with D-amino acids; SQADEVTYSS with D-amino acids (SEQ ID NO. 4); TEDAQX.sup.1IDGTIEV, where each X.sup.1 is S (SEQ ID NO. 5); KKX.sup.1SYTEDAQX.sup.1IDGTIEVPKX.sup.1FKEHS, where each X.sup.1 is S (SEQ ID NO. 7); VSFFX.sup.1KNKEKKX.sup.1SYTEDAQX.sup.1IDGTI, where each X.sup.1 is S (SEQ ID NO. 8); IHFYX.sup.1KNKEKKX.sup.1SYTVEAHX.sup.1RDGTI, where each X.sup.1 is S (SEQ ID NO. 9); KKSSYTVEAHS (SEQ ID NO. 12); residues 3-11 of SEQ ID NO. 12; residues 3-11 of SEQ ID NO. 12 with D-amino acids; SHAEVTYSS (SEQ ID NO. 13), KKSSYTVEAHSRDGTI (SEQ ID NO. 19), and conservatively modified sequence variants thereof which retain the function of said peptide. 8. The peptide and attached label, tag, or targeting moiety of claim 7, wherein said moiety is selected from the group consisting of FLAG, polyhistidine, biotin, fluorescent markers, stable isotopes, radioactive isotopes, isotope-labeled amino acids, sugars, polyethylene glycol, covalent crosslinking moieties, toxins, lipids, sterols, and combinations thereof. 9. A pharmaceutical or veterinary composition comprising the B2-glycoprotein I-derived peptide and label, tag, or targeting moiety of claim 7, and a pharmaceutically-acceptable carrier. 10. The composition of claim 9, wherein said moiety is selected from the group consisting of FLAG, polyhistidine, biotin, fluorescent markers, stable isotopes, radioactive isotopes, isotope-labeled amino acids, sugars, polyethylene glycol, covalent crosslinking moieties, toxins, lipids, sterols, and combinations thereof.

Details for Patent 8,895,502

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		2030-09-01