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 nanoparticle composition comprising nanoparticles having an outside surface, wherein each of the nanoparticles comprises:
a) albumin;
b) between about 100 to about 1000 antibodies having an Fc portion and an antigen-binding portion; and
c) paclitaxel;
said nanoparticles being lyophilized, and wherein upon reconstitution with an aqueous solution antigen-binding portions of said antibodies are arranged on the outside surface of the nanoparticles and are capable of binding to VEGF in vivo wherein said antibody is a humanized antibody, a chimeric antibody, a non-human antibody, a monoclonal antibody, a CDR-grafted antibody, a multispecific antibody, a dual specific antibody, an anti-idiotypic antibody, a bispecific antibody, a functionally active epitope-binding fragment thereof, or a bifunctional hybrid antibody, and wherein the average size of the nanoparticles is between 130 nm and 800 nm.
2. The lyophilized nanoparticle composition of claim 1 that is stable at about 20° C. to about 25° C. for at least 3 months.
3. The lyophilized nanoparticle composition of claim 1 , wherein each of the nanoparticles comprises between about 400 and about 800 antibodies.
4. The lyophilized nanoparticle composition of claim 1 , wherein less than 0.01% of nanoparticles in the composition have a size greater than 800 nm.
5. The lyophilized nanoparticle composition of claim 1 , said nanoparticles having an average size of about 160 nm.
6. The lyophilized nanoparticle composition of claim 1 , wherein the paclitaxel is located inside the nanoparticle, arranged on the outside surface of the nanoparticle, or both.
7. The lyophilized nanoparticle composition of claim 1 wherein the antibodies arrange into a substantially single layer of antibodies on all or part of the outside surface of the nanoparticle.
8. The lyophilized nanoparticle composition of claim 1 , wherein the nanoparticles have an average size of approximately 160 nm and a dissociation constant between about 1×10 −11 M and about 1×10 −9 M.
9. The lyophilized nanoparticle composition of claim 1 , wherein the albumin is human serum albumin.
10. A lyophilized composition comprising nanoparticle complexes having an outside surface, wherein each of the nanoparticle complexes comprises:
a) albumin;
b) between about 100 to about 1000 antibodies, each having a Fc portion and an antigen-binding portion, wherein antigen-binding portions of the antibodies are arranged on the outside surface of the complex;
and
c) paclitaxel;
said nanoparticle complexes being lyophilized, and wherein upon reconstitution with an aqueous solution the nanoparticle complexes remain capable of binding to VEGF in vivo, wherein said antibody is a humanized antibody, a chimeric antibody, a non-human antibody, a monoclonal antibody, a CDR-grafted antibody, a multispecific antibody, a dual specific antibody, an anti-idiotypic antibody, a bispecific antibody, a functionally active epitope-binding fragment thereof, or a bifunctional hybrid antibody, and further wherein said complexes have an average size of from about 130 nm to about 800 nm; wherein the lyophilized composition does not contain a bulking agent.