Molecules with antigen binding and polyvalent fc gamma receptor binding activity

Abstract

The current invention involves biologically active proteins termed stradobodies. The stradobodies have two or more domains that create stradobody multimers. The stradobodies have both antigen-binding capacity and the ability to bind Fc receptors (FcR), and are useful in the treatment and prevention of disease.

1 .- 128 . (canceled) 
     
     
         129 . A method of modulating an immune response in a subject comprising administering to the subject an effective amount of a stradobody comprising an Fab domain; one or more Fc domains; and one or more multimerization domains, wherein the one or more multimerization domains separates two Fc domains or is located at the carboxy terminus of the one or more Fc domains, and wherein the one or more multimerization domains is capable of multimerizing said stradobody. 
     
     
         130 . The method of  claim 129 , wherein the one or more multimerization domains are independently selected from the group consisting of an isoleucine zipper, an IgG2 hinge, and a GPP repeat. 
     
     
         131 . The method of  claim 129 , wherein the stradobody comprises at least one IgG2 hinge domain, wherein the amino acid sequence of the IgG2 hinge domain is at least 80% homologous to SEQ ID NO: 3, and wherein the IgG2 hinge is capable of multimerizing the stradobody. 
     
     
         132 . The method of  claim 129 , wherein the stradobody comprises at least one isoleucine zipper, wherein the amino acid sequence of the at least one isoleucine zipper is at least 80% homologous to SEQ ID NO: 32, and wherein the isoleucine zipper is capable of multimerizing the stradobody. 
     
     
         133 . The method of  claim 129 , wherein the stradobody comprises two multimerization domains. 
     
     
         134 . The method of  claim 133 , wherein the two multimerization domains are an isoleucine zipper and an IgG2 hinge. 
     
     
         135 . The method of  claim 134 , wherein the two multimerization domains separate two Fc domains. 
     
     
         136 . The method of  claim 134 , wherein the two multimerization domains are located at the carboxy end of the Fc region. 
     
     
         137 . The method of  claim 129 , wherein the at least one Fc domain is an IgG1 Fc domain, and wherein the IgG1 Fc domain comprises an IgG1 CH2 and IgG1 CH3. 
     
     
         138 . The method of  claim 137 , wherein the IgG1 Fc domain further comprises an IgG1 hinge. 
     
     
         139 . The method of  claim 137 , wherein the amino acid sequence of at least one IgG1 Fc domain is at least 80% homologous to SEQ ID NO: 2. 
     
     
         140 . The method of  claim 129 , wherein the Fab domain is specific for EGFR, Her2/neu, or CD20. 
     
     
         141 . The method of  claim 129 , wherein the subject is a human. 
     
     
         142 . The method of  claim 129 , wherein the stradobody is administered to the subject intravenously, subcutaneously, orally, nasally, intraperitoneally, sublingually, bucally, transdermally, by subcutaneous or subdermal implantation, or intramuscularly. 
     
     
         143 . A method of treating an inflammatory disease, autoimmune disease, infectious disease, or cancer in a subject in need thereof, comprising administering to the subject an effective amount of a stradobody comprising an Fab domain; one or more Fc domains; and one or more multimerization domains, wherein the one or more multimerization domains separates two Fc domains or is located at the carboxy terminus of the one or more Fc domains, and wherein the one or more multimerization domains is capable of multimerizing said stradobody. 
     
     
         144 . The method of  claim 143 , wherein the subject is a human. 
     
     
         145 . The method of  claim 143 , wherein the stradobody is administered to the subject intravenously, subcutaneously, orally, nasally, intraperitoneally, sublingually, bucally, transdermally, by subcutaneous or subdermal implantation, or intramuscularly. 
     
     
         146 . The method of  claim 143 , wherein the subject has cancer and the cancer is selected from the group consisting of colorectal cancer, head and neck cancer, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms' tumor, cervical cancer, testicular tumor, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, meningioma, melanoma, neuroblastoma, retinoblastoma, leukemia, lymphoma, multiple myeloma, Waldenstrom's macroglobulinemia, myelodysplastic disease, heavy chain disease, neuroendocrine tumors, and Schwanoma. 
     
     
         147 . The method of  claim 143 , wherein the subject has an autoimmune or inflammatory disease, and wherein the autoimmune or inflammatory disease is selected from the group consisting of idiopathic thrombocytopenic purpura, Guillain-Barre syndrome, myasthenia gravis, multiple sclerosis, optic neuritis, Kawasaki's disease, rheumatoid arthritis, systemic lupus erythematosus, atopic dermatitis, atherosclerosis, coronary artery disease, cardiomyopathy, reactive arthritis, Crohn's disease, ulcerative colitis, graft versus host disease, and type 1 diabetes mellitus. 
     
     
         148 . The method of  claim 143 , wherein the subject has an infectious disease, and wherein the infectious disease is selected from the group consisting of candidiasis, candidemia, aspergillosis, streptococcal pneumonia, streptococcal skin and oropharyngeal conditions, gram negative sepsis, tuberculosis, mononucleosis, influenza, respiratory illness caused by respiratory syncytial virus, human immunodeficiency virus, Hepatitis B, Hepatitis C, malaria, schistosomiasis, methicillin-resistant Staph aureus, vancomycin-resistant Enterococcus, carbapenem-resistant and carbapenemase-producing Enterobacteriaceae, mycobacterial disease, and trypanosomiasis.