Albumin-pd-1 paclitaxel nanoparticle complex compositions and methods of making and using the same

Abstract

Described herein are compositions of antibodies and carrier proteins and methods of making and using the same, in particular, as a cancer therapeutic. Also described are lyophilized compositions of antibodies and carrier proteins and methods of making and using the same, in particular, as a cancer therapeutic.

What is claimed is: 
     
         1 . A method for treating cancer in a subject in need thereof, the method comprising reconstituting a lyophilized nanoparticle composition in a pharmaceutically acceptable excipient to form a reconstituted nanoparticle composition and administering a therapeutically effective amount of the reconstituted nanoparticle composition to the subject, wherein the lyophilized composition comprises lyophilized nanoparticle complexes comprising albumin, antibodies having a PD-1-binding portion, and paclitaxel, wherein the cancer expresses PD-1 and upon reconstitution with the pharmaceutically acceptable excipient the nanoparticle complexes have binding specificity for PD-1 expressed by the cancer. 
     
     
         2 . The method of  claim 1 , wherein the nanoparticle composition is administered intravenously. 
     
     
         3 . The method of  claim 1 , further comprising
 a. administering the nanoparticle composition once a week for three weeks;   b. ceasing administration of the nanoparticle composition for one week; and   c. repeating steps a) and b) as necessary to treat the cancer.   
     
     
         4 . The method of  claim 1 , wherein the therapeutically effective amount comprises about 50 mg/m 2  to about 200 mg/m 2  of albumin. 
     
     
         5 . The method of  claim 1 , wherein the therapeutically effective amount comprises about 75 mg/m 2  to about 175 mg/m 2  of albumin. 
     
     
         6 . The method of  claim 1 , wherein the therapeutically effective amount comprises about 20 mg/m 2  to about 90 mg/m 2  of the antibodies. 
     
     
         7 . The method of  claim 1 , wherein the therapeutically effective amount comprises about 30 mg/m 2  to about 70 mg/m 2  of the antibodies. 
     
     
         8 . The method of  claim 1 , further comprising administering free antibody to the patient 12-48 hours prior to administration of the nanoparticle composition wherein the free antibody binds to the same target as the antibodies in the lyophilized nanoparticle complexes. 
     
     
         9 . The method of  claim 8 , wherein the free antibody is administered at a dose that is less than half the therapeutic dose. 
     
     
         10 . The method of  claim 8 , wherein the free antibody is pembrolizumab, and the pembrolizumab is administered at 1 mg/kg, 24 hours prior to administration of the nanoparticle composition. 
     
     
         11 . The method of  claim 8 , wherein the free antibody is nivolumab, and the nivolumab is administered at 1 mg/kg, 24 hours prior to administration of the nanoparticle composition. 
     
     
         12 . A method of making a lyophilized nanoparticle composition comprising nanoparticle complexes comprising albumin, antibodies having a PD-1-binding portion, and paclitaxel, the method comprising mixing aqueous albumin-paclitaxel nanoparticles with the antibodies in vitro under conditions to form the nanoparticle complexes, and lyophilizing the nanoparticle complexes to form the lyophilized nanoparticle composition, such that when reconstituted with an aqueous solution the nanoparticle complexes have binding specificity for PD-1. 
     
     
         13 . The method of  claim 12 , wherein said nanoparticle complexes have an average size of less than 1 μm, 
     
     
         14 . The method of  claim 12 , wherein the antibodies are associated with the albumin through non-covalent bonds. 
     
     
         15 . The method of  claim 12 , wherein said nanoparticle complexes have an average size between about 130 nm and about 800 nm. 
     
     
         16 . The method of  claim 12 , wherein the ratio of albumin-paclitaxel nanoparticle to antibodies is between 10:1 and 10:30. 
     
     
         17 . The method of  claim 12 , wherein the ratio of albumin-paclitaxel nanoparticle to antibodies is between 10:2 and 10:6. 
     
     
         18 . The method of  claim 12 , wherein the antibodies are pembrolizumab or nivolumab antibodies. 
     
     
         19 . The method of  claim 12 , wherein the paclitaxel is associated with the albumin through non-covalent bonds. 
     
     
         20 . The method of  claim 12 , wherein the nanoparticle complexes retain their, size distribution upon lyophilization.