Carrier-antibody 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 composition comprising nanoparticle complexes, wherein the nanoparticle complexes have an outside surface and comprise:
albumin;
paclitaxel; and
anti-CD20 antibodies, each having a CD20-binding portion and each non-covalently bound to the albumin and paclitaxel;
said nanoparticle complexes being lyophilized, and wherein upon reconstitution with an aqueous solution an amount of the antibodies are arranged on the outside surface of the nanoparticle complexes and non-covalently bound to the albumin and paclitaxel and the nanoparticle complexes are capable of binding to CD20 in vivo.
2. The lyophilized composition of claim 1 that is stable at about 20° C. to about 25° C. for at least 3 months.
3. The lyophilized composition of claim 1 , wherein each of the nanoparticle complexes comprises between about 400 and about 800 antibodies.
4. The lyophilized composition of claim 3 , wherein less than 0.01% of nanoparticle complexes have a size greater than 800 nm.
5. The lyophilized composition of claim 1 wherein said nanoparticle complexes have an average size of about 160 nm.
6. The lyophilized composition of claim 1 , wherein the albumin is human serum albumin.
7. The lyophilized composition of claim 1 , wherein the nanoparticle complexes have a dissociation constant between about 1 × 10 -11 M and about 1 × 10 -9 M.
8. A lyophilized composition comprising nanoparticle complexes, wherein the nanoparticle complexes have an outside surface and comprise:
albumin;
paclitaxel; and
anti-CD20 antibodies, each having a CD20-binding portion and each non-covalently bound to the albumin and paclitaxel;
said nanoparticle complexes being lyophilized, and wherein upon reconstitution with an aqueous solution an amount of the antibodies are arranged on the outside surface of the nanoparticle complexes and non-covalently bound to the albumin and paclitaxel and the nanoparticle complexes are capable of binding to CD20 in vivo; wherein the lyophilized composition does not contain a bulking agent.
9. The lyophilized composition of claim 8 that is stable at about 20° C. to about 25° C. for at least 3 months.
10. The lyophilized composition of claim 8 , wherein each of the nanoparticle complexes comprises between about 100 and about 1000 antibodies.
11. The lyophilized composition of claim 10 , wherein less than 0.01% of nanoparticle complexes have a size greater than 800 nm.
12. The lyophilized composition of claim 8 , wherein said nanoparticle complexes have an average size of about 160 nm.
13. The lyophilized composition of claim 8 , wherein the albumin is human serum albumin.
14. The lyophilized composition of claim 8 , wherein the nanoparticle complexes have a dissociation constant between about 1 × 10 -11 M and about 1 × 10 -9 M.
15. The lyophilized composition of claim 1 , wherein said complexes have an average size of less than 1 μm.
16. The lyophilized composition of claim 1 , wherein said nanoparticle complexes have an average size between about 130 nm and about 800 nm.
17. The lyophilized composition of claim 1 , wherein the ratio of albumin-paclitaxel nanoparticle to antibody is between 10:1 and 10:30.
18. The lyophilized composition of claim 1 , wherein the ratio of albumin-paclitaxel nanoparticle to antibody is between 10:2 and 10:6.
19. The lyophilized composition of claim 1 , wherein the antibodies are rituximab or ofatumumab.
20. The lyophilized composition of claim 19 , wherein less than 0.01% of nanoparticle complexes have a size greater than 800 nm.
21. The lyophilized composition of claim 19 , wherein said complexes have an average size of less than 1 μm.
22. The lyophilized composition of claim 19 , wherein said nanoparticle complexes have an average size between about 130 nm and about 800 nm.
23. The lyophilized composition of claim 19 , wherein the ratio of albumin-paclitaxel nanoparticle to antibody is between 10:1 and 10:30.
24. The lyophilized composition of claim 19 , wherein the ratio of albumin-paclitaxel nanoparticle to antibody is between 10:2 and 10:6.
25. The lyophilized composition of claim 1 , wherein each of the nanoparticle complexes comprises between about 100 and about 1000 antibodies.
26. The lyophilized composition of claim 1 , further comprising at least one additional cancer therapeutic agent.