Agents for Treatment of Claudin Expressing Cancer Diseases

Abstract

The present invention provides binding agents that contain a binding domain that is specific for CD3 allowing binding to T cells and a binding domain that is specific for a tumor-associated claudin molecule and methods of using these binding agents or nucleic acids encoding therefor for treating cancer.

1 .- 38 . (canceled) 
     
     
         39 . A bispecific antibody comprising a first binding domain and a second binding domain, wherein the first binding domain binds to claudin 6 (CLDN6) and the second binding domain binds to CD3, wherein
 (a) the first binding domain comprises a variable domain of a heavy chain of an immunoglobulin (VH) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 20, 22, 24, and 26 and a variable domain of a light chain of an immunoglobulin (VL) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 21, 23, 25, and 27 to 29; and   (b) the second binding domain of said bispecific antibody comprises a VH comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 30, 32, 34, and 36 and a VL comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 31, 33, 35, and 37.   
     
     
         40 . The bispecific antibody of  claim 39 , further comprising an N-terminal secretion signal. 
     
     
         41 . The bispecific antibody of  claim 39 , further comprising a C-terminal His tag or a C-terminal IgG constant region. 
     
     
         42 . The bispecific antibody of  claim 39 , wherein the first binding domain comprises a VH comprising an amino acid sequence according to SEQ ID NO: 22 and a VL comprising an amino acid sequence according to SEQ ID NO: 21. 
     
     
         43 . The bispecific antibody of  claim 39 , wherein the VH of the first binding domain is covalently linked to the VL of the first binding domain. 
     
     
         44 . The bispecific antibody of  claim 39 , wherein the bispecific antibody is conjugated to a therapeutic moiety. 
     
     
         45 . The bispecific antibody of  claim 44 , wherein the therapeutic moiety is a cytotoxin, a drug or a radioisotope. 
     
     
         46 . A recombinant nucleic acid comprising a nucleic acid sequence encoding the bispecific antibody of  claim 39 . 
     
     
         47 . A cell comprising one or more nucleic acid sequences encoding the bispecific antibody of  claim 39 . 
     
     
         48 . A composition comprising the bispecific antibody of  claim 39  or one or more nucleic acid sequences encoding the bispecific antibody of  claim 39 . 
     
     
         49 . The composition of  claim 48  further comprising pharmaceutically acceptable salts, buffer substances, preservatives, carriers, diluents and/or excipients. 
     
     
         50 . A method of treating a patient affected from a cancer characterized by cancer cells expressing claudin 6 (CLDN6), the method comprising administering to the patient a composition of  claim 49 , wherein the composition is delivered by parenteral administration. 
     
     
         51 . The method of  claim 50 , wherein the cancer is selected from the group consisting of urinary bladder cancer, ovarian cancer, in particular ovarian adenocarcinoma and ovarian teratocarcinoma, lung cancer, including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), in particular squamous cell, lung carcinoma and adenocarcinoma, gastric cancer, breast cancer, hepatic cancer, pancreatic cancer, skin cancer, in particular basal cell carcinoma and squamous cell carcinoma, malignant melanoma, head and neck cancer, in particular malignant pleomorphic adenoma, sarcoma, in particular synovial sarcoma and carcinosarcoma, bile duct cancer, cancer of the urinary bladder, in particular transitional cell carcinoma, and papillary carcinoma, kidney cancer, in particular renal cell carcinoma including clear cell renal cell carcinoma and papillary renal cell carcinoma, colon cancer, small bowel cancer, including cancer of the ileum, in particular small bowel adenocarcinoma and adenocarcinoma of the ileum, testicular embryonal carcinoma, placental choriocarcinoma, cervical cancer, testicular cancer, in particular testicular seminoma, testicular teratoma and embryonic testicular cancer, uterine cancer, germ cell tumors such as a teratocarcinoma or an embryonal carcinoma, in particular germ cell tumors of the testis, and the metastatic forms thereof. 
     
     
         52 . The method of  claim 50 , wherein the composition comprises the bispecific antibody in Ringer's lactate. 
     
     
         53 . The method of  claim 51 , wherein the composition comprises the bispecific antibody in Ringer's lactate. 
     
     
         54 . The method of  claim 50 , wherein the composition comprises the one or more nucleic acid sequences encoding the bispecific antibody of claim  1  in sterile water, Ringer's solution, Ringer's lactate solution, sterile sodium chloride solution, polyalkylene glycols, hydrogenated naphthalenes and, in particular, biocompatible lactide polymers, lactide/glycolide copolymers or polyoxyethylene/polyoxy-propylene copolymers, and wherein the recombinant nucleic acid is RNA. 
     
     
         55 . The method of  claim 51 , wherein the composition comprises the one or more nucleic acid sequences encoding the bispecific antibody of claim  1  in sterile water, Ringer's solution, Ringer's lactate solution, sterile sodium chloride solution, polyalkylene glycols, hydrogenated naphthalenes and, in particular, biocompatible lactide polymers, lactide/glycolide copolymers or polyoxyethylene/polyoxy-propylene copolymers, and wherein the recombinant nucleic acid is RNA. 
     
     
         56 . The method of  claim 54 , wherein the RNA is delivered as a liposome or viral particle. 
     
     
         57 . The method of  claim 55 , wherein the RNA is delivered as a liposome or viral particle.