Cyclic peptide conjugates and methods of use
The present invention concerns cyclic compounds, compositions comprising the cyclic compounds, linkers, a method of preparing a carrying agent:cyclic compound adduct, a method for treating disorders such as proliferation disorders (e.g., malignancies), bone deficiency diseases, and autoimmune diseases, and a method for suppressing the growth of, or inducing apoptosis in, cells (e.g., malignant cells).
1. A carrying agent:cyclic compound adduct having the structure:
wherein X comprises a carrying agent.
2. The carrying agent:cyclic compound adduct of claim 1 , wherein said carrying agent comprises an amino acid, oligo(amino acid), poly(amino acid) or protein.
3. The carrying agent:cyclic compound adduct of claim 1 , wherein said carrying agent comprises an antibody, or an Fc portion of an antibody, or an antigen-binding fragment of an antibody.
4. The carrying agent:cyclic compound adduct of claim 1 , wherein said carrying agent is a monoclonal antibody (mAb), or an Fc portion of a mAb, or an antigen binding fragment of a mAb, comprising a selenocysteine residue.
5. The carrying agent:cyclic compound adduct of claim 1 , wherein said carrying agent is a monoclonal antibody (mAb), or an Fc portion of a mAb, or antigen binding fragment of a mAb, comprising a C-terminal selenocysteine residue.
6. The carrying agent:cyclic compound adduct of claim 1 , wherein said carrying agent specifically binds to a cell surface antigen.
7. The carrying agent:cyclic compound adduct of claim 1 , wherein said carrying agent specifically binds to a tumor associated antigen.
8. The carrying agent:cyclic compound adduct of claim 1 , wherein said carrying agent specifically binds to one or more antigens selected from among CD138, CD44, alpha4 integrin, alpha3 integrin, alpha6 integrin, EGFR, tumor suppressor cell antigen, cytotoxic T cell antigen, 17-1A, 707-AP, AFP, Annexin II, ART-4, BAGE, BAGE-1, β-catenin, BCG, bcr/abl, Bcr/abl e14a2 fusion junction, bcr-abl (b3a2), bcr-abl (b3a2), bcr-abl p190 (e1a2), bcr-abl p210 (b2a2), bcr-abl p210 (b3a2), bcr-abl p210 (b3a2), bullous pemphigoid antigen-1, CA19-9, CA125, CA215, CAG-3, CAMEL, Cancer-testis antigen, Caspase-8, CCL3, CCL4, CD16, CD20, CD3, CD30, CD55, CD63, CDC27, CDK-4, CDR3, CEA, cluster 5, cluster-5A, cyclin-dependent kinase-4, Cyp-B, DAM-10, DAM-6, Dek-cain, E7, EGFRvIII, EGP40, ELF2 M, EpCAM, FucGM1, G250, GA733, GAGE, GAGE-1-8, gastrin cancer associated antigen, GD2, GD3, globoH, glycophorin, GM1, GM2, GM3, GnTV, Gn-T-V, gp100, Her-2/neu, HERV-K-ME, high molecular weight-associated antigen, high molecular weight proteo-glycan (HMPG), HPV-16 E6, HPV-16 E7, HPVE6, HSP70-2M, HST-2, hTERT, human chorionic gonadotropin (HCG), Human milk fat globule (HMFG), iCE, KIAA0205, KK-LC-1, KM-HN-1, L6, LAGE-1, Lcose4Cer, LDLR/FUT, Lewis A, Lewis v/b, M protein, MAGE-1, MVC, MAGE-A1-12, MAGE-C2, MAHGE-3, MART-1/Melan-A, MC1R, ME491, MUC1, MUC2, mucin, MUM-1, MUM-2, MUM-3, mutated p53, Myosin, MZ2-E, N9 neuraminidase, NA88, NA88-A, nasopharyngeal carcinoma antigen, NGA, NK1/c-3, Novel bcr/ablk fusion BCR exons 1, 13, 14 with ABL exons 4, NY-ESO-1/LAGE-2, NY-ESO-1b, OC125, osteosarcoma associated antigen-1, P15, p190 mimor bcr-abl (e1a2), p53, Pml/RARα, Polysialic acid, PRAME, PSA, PSM, RU1, RU2, SAGE, SART-1, SART-2, SART-3, Sialyl LeA, Sp17, SSX-2, SSX-4, surface immunoglobulin, TAG-1, TAG-2, TEL/AML1, TPI, TRAG-3, TRP-1(gp75), TRP-2, TRP2-INT2, hTRT, tumor associated glycoprotein-72 (TAG-72), tyrosinase, u-PA, WT1, and XAGE-1b, or an immunogenic fragment of any of the foregoing antigens.
9. A composition comprising the carrying agent:cyclic compound adduct of claim 1 ; and a pharmaceutically acceptable carrier.