Peptide for inhibition of binding between angiopoietin-2 and integrin and use thereof

Abstract

Angiopoietin-2 (Ang2) derived peptides, polypeptides, and peptide complexes, and a method for inhibition of binding between Ang2 and integrin and prevention and/or treatment of a disease caused by the activation of Ang2 or the binding between Ang2 and integrin using the peptide, polypeptides, and peptide complexes.

What is claimed is: 
     
         1 . A method of inhibition of binding between angiopoietin-2 (Ang2) and integrin in a patient, the method comprising administering at least one peptide selected from the group consisting of:
 a peptide comprising 5 to 25 consecutive amino acids of SEQ ID NO: 43 including the amino acids from the 11 th  to 15 th  positions of SEQ ID NO: 43,   a peptide comprising 11 to 20 consecutive amino acids of SEQ ID NO: 44 including amino acids from the 6 th  to 15 th  positions of SEQ ID NO: 44,   a peptide comprising the amino acid sequence of SEQ ID NO: 24, and   a peptide comprising the amino acid sequence of SEQ ID NO: 40.   
     
     
         2 . The method of  claim 1 , wherein the peptide is at least one selected from the group consisting of:
 a peptide comprising the amino acid sequence of SEQ ID NO: 15,   a peptide comprising the amino acid sequence of SEQ ID NO: 3,   a peptide comprising the amino acid sequence of SEQ ID NO: 24,   a peptide comprising the amino acid sequence of SEQ ID NO: 4,   a peptide comprising the amino acid sequence of SEQ ID NO: 40,   a peptide comprising the amino acid sequence of SEQ ID NO: 16, and   a peptide comprising the amino acid sequence of SEQ ID NO: 17.   
     
     
         3 . A method of treating a disease in a patient caused by the activation of Ang2 or binding between Ang2 and integrin selected from the group consisting of cancer, cancer metastasis, eye disease, and inflammatory disease, the method comprising administering to the patient a therapeutically effective amount of at least one peptide selected from the group consisting of:
 a peptide comprising 5 to 25 consecutive amino acids of SEQ ID NO: 43 including the amino acids from the 11 th  to 15 th  positions of SEQ ID NO: 43,   a peptide comprising 11 to 20 consecutive amino acids of SEQ ID NO: 44 including the amino acids from the 6 th  to 15 th  positions of SEQ ID NO: 44,   a peptide comprising the amino acid sequence of SEQ ID NO: 24, and   a peptide comprising the amino acid sequence of SEQ ID NO: 40.   
     
     
         4 . The method of  claim 3 , wherein the peptide is at least one selected from the group consisting of:
 a peptide comprising the amino acid sequence of SEQ ID NO: 15,   a peptide comprising the amino acid sequence of SEQ ID NO: 3,   a peptide comprising the amino acid sequence of SEQ ID NO: 24,   a peptide comprising the amino acid sequence of SEQ ID NO: 4,   a peptide comprising the amino acid sequence of SEQ ID NO: 40,   a peptide comprising the amino acid sequence of SEQ ID NO: 16, and   a peptide comprising the amino acid sequence of SEQ ID NO: 17.   
     
     
         5 . The method of  claim 3 , wherein the disease is squamous cell carcinoma, small-cell lung cancer, non-small-cell lung cancer, adenocarcinoma of the lung, squamous cell carcinoma of the lung, peritoneal carcinoma, skin cancer, melanoma in the skin or eyeball, rectal cancer, cancer near the anus, esophagus cancer, small intestinal tumor, endocrine gland cancer, parathyroid cancer, adrenal cancer, soft-tissue sarcoma, urethral cancer, chronic or acute leukemia, lymphocytic lymphoma, hepatoma, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, breast cancer, colon cancer, large intestine cancer, endometrial carcinoma or uterine carcinoma, salivary gland tumor, kidney cancer, prostate cancer, vulvar cancer, thyroid cancer, head and neck cancers, brain cancer, or osteosarcoma. 
     
     
         6 . A method of inhibition of binding between Ang2 and integrin in a patient, the method comprising administering to a patient
 (1) a polypeptide molecule comprising a first peptide and a second peptide, wherein   (a) the first peptide inhibits the binding of Ang2 and integrin and comprises:   (i) at least one peptide selected from the group consisting of a peptide comprising 5 to 25 consecutive amino acids of SEQ ID NO: 43 including the amino acids from the 11 th  to 15 th  positions of SEQ ID NO: 43, a peptide comprising 11 to 20 consecutive amino acids of SEQ ID NO: 44 including the amino acids from the 6 th  to 15 th  positions of SEQ ID NO: 44, a peptide comprising the amino acid sequence of SEQ ID NO: 24, and a peptide the amino acid sequence of SEQ ID NO: 40; or   (ii) a peptide repeat comprising the peptide (i) repeated 2 to 20 times; and   (b) the second peptide is a heavy chain or light chain of an antibody, a constant region of a heavy chain or light chain of an antibody, or an Fc fragment of an antibody;   or   (2) a polypeptide complex comprising 2 to 4 polypeptide molecules of (1).   
     
     
         7 . The method of  claim 6 , wherein the first peptide comprises at least one selected from the group consisting of:
 a peptide comprising the amino acid sequence of SEQ ID NO: 15,   a peptide comprising the amino acid sequence of SEQ ID NO: 3,   a peptide comprising the amino acid sequence of SEQ ID NO: 24,   a peptide comprising the amino acid sequence of SEQ ID NO: 4,   a peptide comprising the amino acid sequence of SEQ ID NO: 40,   a peptide comprising the amino acid sequence of SEQ ID NO: 16, and   a peptide comprising the amino acid sequence of SEQ ID NO: 17.   
     
     
         8 . The method of  claim 6 , wherein the polypeptide molecule further comprises a linker between the first peptide and the second peptide or between repeating first peptides. 
     
     
         9 . A method of treatment of a disease in a patient caused by the activation of Ang2 or binding between Ang2 and integrin selected from the group consisting of cancer, cancer metastasis, eye disease, and inflammatory disease, the method comprising administering to the patient a therapeutically effective amount of:
 (1) a polypeptide molecule comprising a first peptide and a second peptide, wherein   (a) the first peptide inhibits the binding of Ang2 and integrin and comprises:   (i) at least one peptide selected from the group consisting of a peptide comprising 5 to 25 consecutive amino acids of SEQ ID NO: 43 including the amino acids from the 11 th  to 15 th  positions of SEQ ID NO: 43, a peptide comprising 11 to 20 consecutive amino acids of SEQ ID NO: 44 including the amino acids from the 6 th  to 15 th  positions of SEQ ID NO: 44, a peptide comprising the amino acid sequence of SEQ ID NO: 24, and a peptide the amino acid sequence of SEQ ID NO: 40; or   (ii) a peptide repeat comprising the peptide (i) repeated 2 to 20 times; and   (b) the second peptide is a heavy chain or light chain of an antibody, a constant region of a heavy chain or light chain of an antibody, or an Fc fragment of an antibody;   or   (2) a polypeptide complex comprising 2 to 4 polypeptide molecules of (1).   
     
     
         10 . The method of  claim 9 , wherein the first peptide comprises at least one selected from the group consisting of:
 a peptide comprising the amino acid sequence of SEQ ID NO: 15,   a peptide comprising the amino acid sequence of SEQ ID NO: 3,   a peptide comprising the amino acid sequence of SEQ ID NO: 24,   a peptide comprising the amino acid sequence of SEQ ID NO: 4,   a peptide comprising the amino acid sequence of SEQ ID NO: 40,   a peptide comprising the amino acid sequence of SEQ ID NO: 16, and   a peptide comprising the amino acid sequence of SEQ ID NO: 17.   
     
     
         11 . The method of  claim 9 , wherein the polypeptide molecule further comprises a linker between the first peptide and the second peptide or between repeating first peptides. 
     
     
         12 . The method of  claim 9 , wherein the disease is cancer, and the cancer is squamous cell carcinoma, small-cell lung cancer, non-small-cell lung cancer, adenocarcinoma of the lung, squamous cell carcinoma of the lung, peritoneal carcinoma, skin cancer, melanoma in the skin or eyeball, rectal cancer, cancer near the anus, esophagus cancer, small intestinal tumor, endocrine gland cancer, parathyroid cancer, adrenal cancer, soft-tissue sarcoma, urethral cancer, chronic or acute leukemia, lymphocytic lymphoma, hepatoma, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, breast cancer, colon cancer, large intestine cancer, endometrial carcinoma or uterine carcinoma, salivary gland tumor, kidney cancer, prostate cancer, vulvar cancer, thyroid cancer, head and neck cancers, brain cancer, or osteosarcoma.