Claims
- 1. A lipid construct comprising a linking carrier, a targeting entity, and optionally a therapeutic entity.
- 2. The lipid construct of claim 1 wherein the linking carrier is selected from the group consisting of a polymerized liposome, liposome, polymer-coated liposome, and a micelle.
- 3. The lipid construct of claim 1, wherein the polymerizable lipid is 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine.
- 4. The lipid construct of claim 1, wherein the polymerizable lipid is [PDA-PEG3]2-DTTA (compound 1, FIG. 3)
- 5. The lipid construct of claim 4, wherein said lipid chelator is 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamidotriamine tetraacetic acid.
- 6. The lipid construct of claim 4, wherein the therapeutic entity is a metal ion.
- 7. The lipid construct of claim 4, wherein the metal ion is a radioactive metal ion.
- 8. The lipid construct of claim 4, wherein the metal ion is selected from the group consisting of Y-90, Bi-213, At-211, Cu-67, Sc-47, Ga-67, Rh-105, Pr-142, Nd-147, Pm-151, Sm-153, Ho-166, Gd-159, Tb-161, Eu-152, Er-171, Re-186, and Re-188.
- 9. The lipid construct of claim 4, wherein said therapeutic entity is 90Y.
- 10. The lipid construct of claim 4, wherein said lipid chelator is N,N-bis[[[[(13′,15′-pentacosadiynamido-3,6-doxaoctyl)carbamoyl]methyl](carboxymethyl)amino]ethyl]glycine ([PDA-PEG3]2-DTTA3).
- 11. The lipid construct of claim 4, wherein said lipid chelator contains a diacetylene lipid.
- 12. The lipid construct of claim 4, wherein said lipid chelator is selected from the group consisting of a derivative of diethylenetriaminepentaacetic acid, a derivative of ethylaminediaminetetracetic acid, and a derivative of 1,4,7,10-tetraazacyclododecane-N,N′,N″,N′″-tetraacetic acid (DOTA).
- 13. The lipid construct of claim 4, wherein said lipid chelator comprises an ionizable group selected from the group consisting of carboxyl, phosphate, phosphonate, sulfate, sulfonate, and sulfinate.
- 14. The lipid construct of claim 4, wherein said lipid chelator comprises a single ionizable group, said single ionizable group generating a surface capable of binding an isotope or metal with a valency of +2 or greater.
- 15. The lipid construct of claim 4, wherein said lipid chelator comprises a single ionizable group, said single ionizable group generating a surface capable of binding an isotope or metal with a valency of +3 or greater.
- 16. The lipid construct of claim 1, wherein said targeting entity is selected from the group consisting of a small molecule ligand and a protein.
- 17. The lipid construct of claim 1, wherein said targeting entity targets the lipid construct to a cell surface.
- 18. The lipid construct of claim 1, wherein the targeting entity is attached to the lipid construct through a group selected from the group consisting of amine, cyano, carboxylic acid, isothiocyanate, thiol, disulfide, α-halocarbonyl, α,β-unsaturated carbonyl and alkyl hydrazine.
- 19. The lipid construct of claim 1, wherein the targeting entity is attached to the lipid construct by non-covalent means.
- 20. The lipid construct of claim 19, wherein said non-covalent means is a biotin-avidin biotinylated antibody sandwich.
- 21. The lipid construct of claim 1, wherein said targeting entity is an antibody, protein, ligand, peptide, or nucleic acid.
- 22. The lipid construct of claim 1 wherein said targeting entity is VEGF or a derivative or portion thereof.
- 23. The lipid construct of claim 1, wherein said targeting entity is FGF or a derivative or portion thereof.
- 24. The lipid construct of claim 1, wherein said targeting entity is the peptide contains the sequence ATWLPPR, a derivative or homologue of ATWLPPR, or a peptidomimetic of a portion of this sequence.
- 25. The lipid construct of claim 1, wherein said targeting entity is an antibody against one or more of the VEGF receptors.
- 26. The lipid construct of claim 21, wherein said antibody is an anti-VEGFR-2 antibody or an anti-integrin alpha v subunit antibody.
- 27. The lipid construct of claim 26, wherein the therapeutic agent is selected from the group consisting of a radioisotope, prodrug, chemotherapeutic agent, toxin and a gene encoding a protein that exhibits cell toxicity.
- 28. The lipid construct of claim 21, wherein said antibody has a target selected from the group consisting of P-selectin, E-selectin, pleiotropin, chemokine and cytokine receptors, G-protein coupled receptors, endosialin, endoglin, VEGF receptor, PDGF receptor, FGF or EGF receptor, the matrix metalloproteases, and prostate specific membrane antigen (PSMA).
- 29. The lipid construct of claim 1, further comprising a stabilizing agent.
- 30. The lipid construct of claim 29, wherein the stabilizing agent is selected from the group consisting of dextran or aminodextran.
- 31. The lipid construct of claim 1, wherein the linking carrier is a polymerized liposome, the targeting entity is an anti-VEGFR-2 antibody or an anti-alpha v integrin subunit antibody, and the therapeutic entity is yttrium-90.
- 32. The lipid construct of claim 29, wherein the linking carrier is a polymerized liposome, the targeting entity is an anti-VEGFR-2 antibody or an anti-alpha v integrin subunit antibody, the therapeutic entity is 90Y, and the stabilizing entity is aminodextran.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. patent application Ser. No. 09/976,254 entitled “Targeted Therapeutic Agents,” filed Oct. 11, 2001, which claims the benefit of U.S. Provisional Patent Application No. 60/239,684 entitled “Vascular-Targeted Therapeutic Agents” filed Oct. 11, 2000. This application also claims the benefit of U.S. Provisional Patent Application No. 60/326,310 entitled “Targeted Therapeutic Lipid Constructs Having Cell Surface Targets” filed Oct. 1, 2001.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60239684 |
Oct 2000 |
US |
|
60326310 |
Oct 2001 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
09976254 |
Oct 2001 |
US |
Child |
10262576 |
Oct 2002 |
US |