Carrier-binding agent compositions and methods of making and using the same
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.
1. A lyophilized nanoparticle composition comprising nanoparticles having an outer surface, wherein each of the nanoparticles comprises:
a) albumin;
b) antibodies having an antigen-binding portion, wherein the antibodies are bound to the albumin via non-covalent hydrophobic bonds; and
c) paclitaxel;
said nanoparticles being lyophilized without the use of cryoprotectants, and wherein upon reconstitution with an aqueous solution, at least some of the antigen-binding portions of said antibodies are arranged on the outside surface of the nanoparticles and are capable of binding to a target in vivo, wherein the average diameter of said nanoparticles is less than 1 micron, and wherein the antibody is not bevacizumab, rituximab or trastuzumab.
2. The lyophilized nanoparticle composition of claim 1 , wherein the antigen-binding portion binds to CD38, CD52, PD-L1, Ly6E, HER3/EGFR, DAF, ERBB-3 receptor, CSF-1R, STEAP1, CD3, CEA, CD40, OX40, Ang2-VEGF, or VEGF.
3. The lyophilized nanoparticle composition of claim 1 wherein the antibody is obinutuzumab.
4. The lyophilized nanoparticle composition of claim 1 that is stable at about 20° C. to about 25° C. for at least 3 months.
5. The lyophilized nanoparticle composition of claim 1 , wherein each of the nanoparticles comprises between about 400 and about 800 antibodies.
6. The lyophilized nanoparticle composition of claim 3 , wherein the average size of the nanoparticles is between 130 nm and 800 nm, and further wherein less than 0.01% of nanoparticles in the composition have a size greater than 800 nm.
7. The lyophilized nanoparticle composition of claim 1 , said nanoparticles having an average size of approximately 160 nm.
8. The lyophilized nanoparticle composition of claim 1 , further comprising at least one therapeutic agent located inside the nanoparticle, arranged on the outside surface of the nanoparticle, or both.
9. The lyophilized nanoparticle composition of claim 8 , wherein the at least one 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, pazopanib, pemetrexed, picoplatin, romidepsin, satraplatin, sorafenib, vemurafenib, sunitinib, teniposide, triplatin, vinblastine, vinorelbine, vincristine, and cyclophosphamide.
10. The nanoparticle composition of claim 1 , wherein the antibodies arrange into a substantially single layer of antibodies on all or part of the surface of the nanoparticle.
11. The nanoparticle composition of claim 1 , wherein the nanoparticles have a dissociation constant between about 1×10 −11 M and about 1×10 −9 M.
12. A lyophilized nanoparticle composition comprising nanoparticles having an outer surface, wherein each of the nanoparticles comprises:
a) albumin;
b) antibodies having an antigen-binding portion, wherein the antibodies are bound to the albumin via non-covalent hydrophobic bonds; and
c) paclitaxel;
said nanoparticles being lyophilized without the use of cryoprotectants, and wherein upon reconstitution with an aqueous solution the antigen-binding portion of said antibodies are arranged on the outside surface of the nanoparticles and are capable of binding to CD20 in vivo, wherein the average diameter of said complexes is less than 1 micron, and wherein the antibody is not rituximab.
13. The lyophilized nanoparticle composition of claim 12 that is stable at about 20° C. to about 25° C. for at least 3 months.
14. The lyophilized nanoparticle composition of claim 12 , wherein each of the nanoparticles comprises between about 400 and about 800 antibodies.
15. The lyophilized nanoparticle composition of claim 12 , wherein the average size of the nanoparticles is between 130 nm and 800 nm, and further wherein less than 0.01% of nanoparticles in the composition have a size greater than 800 nm.
16. The lyophilized nanoparticle composition of claim 12 , further comprising at least one therapeutic agent located inside the nanoparticle, arranged on the outside surface of the nanoparticle, or both.
17. The lyophilized nanoparticle composition of claim 16 , wherein the at least one therapeutic agent is selected from the group consisting of 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, pazopanib, pemetrexed, picoplatin, romidepsin, satraplatin, sorafenib, vemurafenib, sunitinib, teniposide, triplatin, vinblastine, vinorelbine, vincristine, and cyclophosphamide.
18. The nanoparticle composition of claim 12 , wherein the antibodies arrange into a substantially single layer of antibodies on all or part of the surface of the nanoparticle.
19. The nanoparticle composition of claim 12 , wherein the nanoparticles have a dissociation constant between about 1×10 −11 M and about 1×10 −9 M.
20. A lyophilized nanoparticle composition comprising nanoparticles having an outer surface, wherein each of the nanoparticles comprises:
a) albumin;
b) antibodies having an antigen-binding portion, wherein the antibodies are bound to the albumin via non-covalent hydrophobic bonds; and
c) paclitaxel;
said nanoparticles being lyophilized without the use of cryoprotectants, and wherein upon reconstitution with an aqueous solution the antigen-binding portion of said antibodies are arranged on the outside surface of the nanoparticles and are capable of binding to HER2 in vivo, wherein the average diameter of said complexes is less than 1 micron, and wherein the antibody is not trastuzumab.
21. The lyophilized nanoparticle composition of claim 20 that is stable at about 20° C. to about 25° C. for at least 3 months.
22. The lyophilized nanoparticle composition of claim 20 , wherein each of the nanoparticles comprises between about 400 and about 800 antibodies and the antibodies arrange into a substantially single layer of antibodies on all or part of the surface of the nanoparticle.
23. The lyophilized nanoparticle composition of claim 20 , wherein the average size of the nanoparticles is between 130 nm and 800 nm, and further wherein less than 0.01% of nanoparticles in the composition have a size greater than 800 nm.
24. The lyophilized nanoparticle composition of claim 20 , further comprising at least one therapeutic agent located inside the nanoparticle, arranged on the outside surface of the nanoparticle, or both.
25. The lyophilized nanoparticle composition of claim 24 , wherein the at least one therapeutic agent is selected from the group consisting of 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, pazopanib, pemetrexed, picoplatin, romidepsin, satraplatin, sorafenib, vemurafenib, sunitinib, teniposide, triplatin, vinblastine, vinorelbine, vincristine, and cyclophosphamide.
26. The nanoparticle composition of claim 20 , wherein the nanoparticles have a dissociation constant between about 1×10 −11 M and about 1×10 −9 M.