Claims for Patent: 12,061,183

Summary for Patent: 12,061,183

Title:	Methods of assessing suitability of use of pharmaceutical compositions of albumin and poorly water soluble drug
Abstract:	The present invention provides methods of assessing suitability of a pharmaceutical composition for medical use. The pharmaceutical composition comprises nanoparticles comprising rapamycin coated with albumin and a non-nanoparticle portion comprising albumin and rapamycin.
Inventor(s):	Viktor Peykov, Willard Foss, Daniel W. Pierce, Neil P. Desai
Assignee:	Abraxis Bioscience LLC
Application Number:	US17/954,217
Patent Claims:	1. A method of assessing suitability of a pharmaceutical composition for medical use in a human individual, wherein the pharmaceutical composition comprises nanoparticles comprising rapamycin coated with albumin and a non-nanoparticle portion comprising albumin and rapamycin, the method comprising: determining a weight percentage of albumin polymers among the albumin on the nanoparticles, wherein the weight percentage of albumin polymer among the albumin on the nanoparticles being from about 15% to about 40% is indicative of suitability of the pharmaceutical composition for medical use. 2. A method of assessing suitability of a pharmaceutical composition for medical use in a human individual, wherein the pharmaceutical composition comprises nanoparticles comprising rapamycin coated with albumin and a non-nanoparticle portion comprising albumin and rapamycin, the method comprising: determining a weight percentage of albumin monomers among the albumin on the nanoparticles, wherein the weight percentage of albumin monomers among the albumin on the nanoparticles being from about 40% to about 60% is indicative of suitability of the pharmaceutical composition for medical use. 3. The method of claim 1, wherein the method further comprises determining a weight percentage of albumin monomers among the albumin on the nanoparticles, wherein the weight percentage of albumin monomers among the albumin on the nanoparticles being from about 40% to about 60% is indicative of suitability of the pharmaceutical composition for medical use. 4. The method of claim 2, wherein the method further comprises determining a weight percentage of the albumin in the nanoparticles, wherein the weight percentage of the albumin in the nanoparticles being from about 15% to about 30% is indicative of suitability of the pharmaceutical composition for medical use. 5. The method of claim 2, further comprising determining a weight ratio of albumin to rapamycin in the nanoparticles, wherein the weight ratio being from about 1:2 to about 1:6 in the nanoparticles is indicative of suitability of the pharmaceutical composition for medical use. 6. The method of claim 2, further comprising determining a thickness of the albumin coating of the nanoparticles under cryogenic transmission electron microscopy (cryo-TEM), wherein the thickness being from about 5 nm to about 7 nm is indicative of suitability of the pharmaceutical composition for medical use. 7. The method of claim 2, further comprising determining a solubility of the pharmaceutical composition, wherein the solubility being from about 50 μg/ml to about 100 μg/ml in a 5% human albumin solution is indicative of suitability of the pharmaceutical composition for medical use. 8. The method of claim 2, further comprising determining a rapamycin crystallinity of the pharmaceutical composition, wherein a non-crystalline state of the rapamycin is indicative of suitability of the pharmaceutical composition for medical use. 9. The method of claim 2, further comprising determining a rapamycin recovery following a 0.2 micron filtration of the pharmaceutical composition, wherein the rapamycin recovery being at least about 80% is indicative of suitability of the pharmaceutical composition for medical use. 10. The method of claim 2, wherein a determination of solubility, rapamycin crystalline state, or rapamycin recovery is carried out after storage. 11. The method of claim 8, wherein the rapamycin crystallinity is determined by X-ray diffraction, polarized light microscopy, or both. 12. The method of claim 2, further comprising determining a binding affinity of albumin to rapamycin in the pharmaceutical composition. 13. The method of claim 12, wherein the binding affinity is determined by equilibrium dialysis, Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), or a combination thereof. 14. The method of claim 2, further comprising determining a weight percentage of albumin dimers among the albumin on the nanoparticles, wherein the weight percentage being from about 15% to about 30% of albumin dimers among the albumin on the nanoparticles is indicative of the pharmaceutical composition for medical use. 15. The method of claim 2, further comprising determining a weight percentage of albumin oligomers among the albumin on the nanoparticles, wherein the weight percentage being from about 7% to about 15% of albumin oligomers among the albumin on the nanoparticles is indicative of the pharmaceutical composition for medical use. 16. The method of claim 2, wherein the weight percentage of albumin monomers among the albumin on the nanoparticles is determined by size-exclusion chromatography. 17. A commercial batch of a pharmaceutical composition for medical use in a human individual, wherein the pharmaceutical composition comprises (a) nanoparticles comprising rapamycin coated with a coating comprising albumin and (b) a non-nanoparticle portion comprising albumin and rapamycin, and wherein the commercial batch is validated by assessing the suitability for medical use according to claim 1. 18. A commercial batch of a pharmaceutical composition for medical use in a human individual, wherein the pharmaceutical composition comprises (a) nanoparticles comprising rapamycin coated with a coating comprising albumin and (b) a non-nanoparticle portion comprising albumin and rapamycin, and wherein the commercial batch is validated by assessing the suitability for medical use according to claim 2.