Paclitaxel-albumin-binding agent compositions and methods for using and making the same

Abstract

Described herein are nanoparticle compositions comprising binding agents, carrier proteins and an, amount of paclitaxel derivative, and optionally a therapeutic agent. Also described herein are nanoparticle compositions comprising carrier proteins and an amount of paclitaxel, and optionally binding agents and/or a therapeutic agent, wherein the paclitaxel is present in an amount that is less than an amount that provides a therapeutic effect. Also disclosed herein are nanoparticles which contain (a) carrier protein, (b) a paclitaxel derivative, the paclitaxel derivative haying reduced toxicity compared to paclitaxel, and optionally (c) a binding agent and/or (d) a therapeutic agent. Also described are methods of making and using the same, in particular, as a cancer therapeutic.

1 - 90 . (canceled) 
     
     
         91 . A nanoparticle complex comprising albumin and paclitaxel, wherein the paclitaxel is present in an amount that is less than an amount that provides a therapeutic effect. 
     
     
         92 . The nanoparticle complex of  claim 91 , wherein the albumin and the paclitaxel have a relative weight ratio of greater than about 10:1, or about 11:1, or about 12:1, or about 13:1, or about 14:1, or about 15:1, or about 16:1, or about 17:1, or about 18:1, or about 19:1, or about 20:1, or about 21:1, or about 22:1, or about 23:1, or about 24:1, or about 25:1, or about 26:1, or about 27:1, or about 28:1, or about 29:1, about 30:1, about 31:1, about 32:1, about 33:1, about 34:1, about 35:1 or about 40:1 in the nanoparticle complex. 
     
     
         93 . The nanoparticle complex of  claim 91 , wherein the amount of paclitaxel present in the nanoparticle composition is less than about 4.54 mg/mL, or about 4.16 mg/mL, or about 3.57 mg/mL, or about 3.33 mg/mL, or about 3.12 mg/mL, or about 2.94 mg/mL, or about 2.78 mg/mL, or about 2.63 mg/mL, or about 2.5 mg/mL, or about 2.38 mg/mL, or about 2.27 mg/mL, or about 2.17 mg/mL, or about 2.08 mg/mL, or about 2 mg/mL, or about 1.92 mg/mL, or about 1.85 mg/mL, or about 1.78 mg/mL, or about 1.72 mg/mL, or about 1.67 mg/mL. 
     
     
         94 . The nanoparticle complex of  claim 91 , further comprising antibodies associated with the nanoparticle complex. 
     
     
         95 . The nanoparticle complex of  claim 94 , wherein the antibodies are selected from ado-trastuzumab emtansine, alemtuzumab, atezolizumab, bevacizumab, cetuximab, denosumab, dinutuximab, ipilimumab, nivolumab, obinutuzumab, ofatumumab, panitumumab, pembrolizumab, pertuzumab, rituximab, avelumab, durvalumab, pidilizumab, BMS 936559, OKT3, and trastuzumab. 
     
     
         96 . The nanoparticle complex of  claim 91 , wherein the albumin is human serum albumin. 
     
     
         97 . The nanoparticle complex of  claim 96 , wherein the human serum albumin is recombinant human serum albumin. 
     
     
         98 . The nanoparticle complex of  claim 91 , wherein the paclitaxel is present in an amount effective for providing stability to the nanoparticles. 
     
     
         99 . The nanoparticle complex of  claim 91 , wherein the nanoparticle complex is held together by non-covalent bonds between the albumin and the paclitaxel. 
     
     
         100 . The nanoparticle complex of  claim 91 , further comprising a therapeutic agent. 
     
     
         101 . The nanoparticle complex of  claim 100 , wherein the therapeutic agent is selected from abiraterone, bendamustine, bortezomib, carboplatin, cabazitaxel, cisplatin, chlorambucil, dasatinib, docetaxel, doxorubicin, epirubicin, erlotinib, etoposide, everolimus, gefitinib, idarubicin, imatinib, hydroxyurea, imatinib, lapatinib, leuprorelin, melphalan, methotrexate, mitoxantrone, nedaplatin, nilotinib, oxaliplatin, paclitaxel, pazopanib, pemetrexed, picoplatin, romidepsin, satraplatin, sorafenib, vemurafenib, sunitinib, teniposide, triplatin, vinblastine, vinorelbine, vincristine, or cyclophosphamide. 
     
     
         102 . The nanoparticle complex of  claim 100 , wherein the paclitaxel is present in an amount effective for providing affinity of the at least one therapeutic agent to the albumin. 
     
     
         103 . The nanoparticle complex of  claim 100 , wherein the paclitaxel is present in an amount effective for facilitating complex formation of the at least one therapeutic agent and the albumin. 
     
     
         104 . A nanoparticle composition comprising the nanoparticle complex of  claim 91 . 
     
     
         105 . The nanoparticle composition of  claim 104  that is lyophilized. 
     
     
         106 . A method for treating cancer in a patient in need thereof, the method comprising administering a nanoparticle complex of  claim 91  or a nanoparticle composition of  claim 104  to a patient having cancer. 
     
     
         107 . A method for forming an albumin-paclitaxel nanoparticle, wherein the method comprises: homogenizing the albumin with paclitaxel in a solution under high pressure, to generate the albumin-paclitaxel nanoparticle, wherein the ratio of albumin to paclitaxel is greater than 10:1. 
     
     
         108 . The method of  claim 107 , further comprising contacting the albumin-paclitaxel nanoparticle with an antibody.