Autophilic antibodies and method of making the same

Abstract

Antibodies having noncovalent, autophilic properties are disclosed. The autophilic antibodies are derived from antibodies conjugated with an autophilic peptide. Such autophilic antibodies can promote apoptosis of target cells and enhance therapeutic efficacies in the treatment of patients with diseases or disorders responsive to antibody therapy. Compositions containing the antibodies, and methods of making and using the antibodies are also disclosed.

1 . An autophilic antibody comprising an autophilic peptide conjugated to an immunoglobulin component of a non-autophilic antibody. 
     
     
         2 . An autophilic antibody according to  claim 1 , wherein the autophilic peptide comprises a conserved self-binding sequence. 
     
     
         3 . An autophilic antibody according to  claim 1 , wherein the autophilic peptide is a humanized peptide. 
     
     
         4 . An autophilic antibody according to  claim 1 , wherein the autophilic peptide is selected from the group consisting of T15 peptide, T15-scr2 peptide, R24 peptide, and R24-Charged peptide. 
     
     
         5 . An autophilic antibody according to  claim 1 , wherein the autophilic peptide comprises a peptide selected from the group consisting of: SEQ ID NO.1; SEQ ID NO.4; SEQ ID NO.5; and SEQ ID NO.6. 
     
     
         6 . An autophilic antibody according to  claim 1  comprising one or more functional peptides conjugated to the non-autophilic antibody. 
     
     
         7 . An autophilic antibody according to  claim 6 , wherein the one or more functional peptides are conjugated to the non-autophilic antibody at a site that is different from a site that the autophilic peptide is conjugated to the non-autophilic antibody. 
     
     
         8 . An autophilic antibody according to  claim 6 , wherein the one or more functional peptides comprises an MTS peptide. 
     
     
         9 . An autophilic antibody according to  claim 6 , wherein the one or more functional peptides comprises a peptide selected from the group consisting of: SEQ ID NO.2; and SEQ ID NO: 7. 
     
     
         10 . An autophilic antibody according to  claim 1 , wherein the non-autophilic antibody is selected from the group consisting of 5D10, S1C5, rituximab, anti-GM2, trastuzumab, anti-caspase antibodies, humanized TEPC-15, humanized R24, and humanized S107 or wherein the autophilic antibody is selected from the group consisting of: S1C5 antibody conjugated with T15 peptide; 5D10 antibody conjugated with T15 peptide; anti-caspase 3 antibody conjugated with MTS peptide; anti-CD20 antibody conjugated with T15 peptide; rituximab conjugated with T15 peptide; IF5 conjugated with T15 peptide; tositumomab conjugated with T15 peptide; anti-GM2 conjugated with T15 peptide; a non-human antibody to GM2 glycolipid conjugated with an autophilic peptide; and Herceptin conjugated with an autophilic peptide. 
     
     
         11 . A method of producing an autophilic antibody according to  claim 6  comprising expressing the autophilic antibody as a fusion protein containing the autophilic peptide sequence, the one or more functional peptides, and the non-autophilic antibody. 
     
     
         12 . A composition comprising one or more autophilic antibodies according to  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         13 . A composition comprising one or more autophilic antibodies according to  claim 6  and a pharmaceutically acceptable carrier. 
     
     
         14 . A method of treating a patient suffering from a disease or disorder responsive to antibody therapy comprising administering to the patient one or more autophilic antibodies according to  claim 1 , or a composition comprising one or more autophilic antibodies according to  claim 1  and a pharmaceutically acceptable carrier, in a therapeutically effective amount to alleviate symptoms of the disease or disorder. 
     
     
         15 . The method of  claim 14 , wherein the disease or disorder is a malignancy, an auto-immune disorder, transplantation rejection, Alzheimer's disease, a neuro-degenerative condition, atheroschlerosis, or any other condition responsive to antibody therapy. 
     
     
         16 . The method of  claim 14 , wherein the autophilic antibody is administered in one or more dose amounts substantially identical to amounts used to administer non-autophilic antibodies. 
     
     
         17 . The method of  claim 14 , wherein an initial dose is about 250 mg per day and a later dose is about 100 mg per week. 
     
     
         18 . The method of  claim 14 , wherein a maintenance dose is about 50 mg per week. 
     
     
         19 . A method of  claim 14 , wherein the treating comprises potentiating apoptosis, complement fixation, or cell-mediated killing of selected cells in the patient. 
     
     
         20 . A method according to  claim 19 , further comprising administering to the patient a second antibody directed to the autophilic peptide of the autophilic antibody.