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Last Updated: March 28, 2024

Claims for Patent: 10,335,420


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Summary for Patent: 10,335,420
Title:Nanoparticle-based tumor-targeted drug delivery
Abstract: An aqueous tumor-targeting liposome nanoparticle composition comprises an aqueous dispersion of liposome nanoparticles. The nanoparticles preferably encapsulate an anti-cancer chemotherapeutic agent, which can be added to a pre-formed liposome composition or can be incorporated in the liposomes during the formation of the liposomes. The liposome nanoparticles comprise a legumain-targeting lipid admixed with one or more other micelle or vesicle-forming lipid materials in the form of nanoparticulate liposomes dispersed in an aqueous carrier. A preferred tumor-targeting liposome nanoparticle composition comprises a legumain-targeting lipid component and polyethylene glycol-conjugated lipid component. The legumain-targeting lipid component comprising a hydrophobic lipid portion covalently attached to a legumain-binding moiety.
Inventor(s): Reisfeld; Ralph A. (La Jolla, CA), Xiang; Rong (San Diego, CA), Luo; Yunping (San Diego, CA), Liao; Debbie (San Diego, CA), Liu; Ze (Beijing, CN), Chen; Tingmei (Chongqing, CN), Chen; Si (Little Rock, AR), Lu; Dan (San Diego, CA)
Assignee: The Scripps Research Institute (La Jolla, CA)
Application Number:15/495,474
Patent Claims:1. An aqueous tumor-targeting liposome nanoparticle composition comprising an aqueous dispersion of liposome nanoparticles; the liposome nanoparticles comprising a legumain-targeting lipid component and a polyethylene glycol-conjugated lipid component; the legumain-targeting lipid component comprising a hydrophobic lipid portion covalently attached to a legumain-binding moiety, wherein the legumain-targeting lipid component comprises a compound of the Formula: ##STR00012##

2. The composition of claim 1, wherein the hydrophobic lipid portion of the legumain-targeting lipid component comprises a 1,2-diacylglycero-phosphoalkanolamine group.

3. The composition of claim 2, wherein the 1,2-diacylglycero-phosphoalkanolamine is 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine (DOPE).

4. The composition of claim 1, wherein the polyethylene glycol-conjugated lipid component comprises a polyethylene glycol-conjugated 1,2-diacylglycero-phosphoalkanolamine compound.

5. The composition of claim 4, wherein the polyethylene glycol-conjugated 1,2-diacylglycero-phosphoalkanolamine compound comprises 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine-N-[methoxy(polyethylene glycol] wherein the polyethylene glycol portion of the compound has an average molecular weight of about 2000 atomic mass units (amu).

6. The composition of claim 1, further comprising one or more of a zwitterionic lipid component; an amino-substituted lipid component; and a neutral lipid component.

7. The composition of claim 6, wherein the zwitterionic lipid component comprises a 1,2-diacylglycero-phosphocholine compound.

8. The composition of claim 7, wherein the 1,2-diacylglycero-phosphocholine compound comprises 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine (DOPC).

9. The composition of claim 6, wherein the amino-substituted lipid component comprises a 1,2-diacylglycero-phosphoalkanolamine compound.

10. The composition of claim 9, wherein the 1,2-diacylglycero-phosphoalkanolamine compound comprises DOPE.

11. The composition of claim 6, wherein the neutral lipid component comprises cholesterol.

12. The composition of claim 6, wherein the liposome nanoparticles encapsulate an anti-cancer chemotherapeutic agent.

13. The composition of claim 12, wherein the anti-cancer chemotherapeutic agent comprises doxorubicin or 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im).

14. The composition of claim 13 wherein the anti-cancer chemotherapeutic agent is doxorubicin.

15. The composition of claim 12, wherein the anti-cancer chemotherapeutic agent comprises at least one compound selected from the group consisting of cisplatin; carboplatin; oxaliplatin; mechlorethamine; cyclophosphamide; chlorambucil; ifosfamide; 5-fluorouricil; floxuridine; cytosine arabinoside; mercaptopurine; thioguanine; azathioprine; fludarabine; pentostatin; cladribine; etoposide; etoposide phosphate; teniposide; amsacrine; paclitaxel; methotrexate; trimethoprim; pyrimethamine; pemetrexed; vitaxin; anecorvate; angiostatin; endostatin; squalamine; an antiangiogenic tryptophanyl-t-RNA sythetase peptide fragment; bevacizumab; tivozanib; vandetanib; vatalanib; alemtuzumab; cetuximab; gemtuzumab; ibritumomab; pantitumumab; rituximab; tositumomab; trastuzumab; actinomycin; bleomycin; plicamycin; mitomycin; doxorubicin; epirubicin; daunorubicin; valrubicin; idarubicin; ursolic acid; a 2-cyano-3,12-dioxooleana-1,9-dien-28-oic ester, a 2-cyano-3,12-dioxooleana-1,9-dien-28-oic amide; 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (also known as CDDO-Im); as well as physiologically acceptable salts and prodrugs thereof.

16. The composition of claim 1, wherein the liposome nanoparticles encapsulate an anti-tumor agent.

17. The composition of claim 16, wherein the anti-tumor agent is an agonist or antagonist of a receptor or a receptor ligand involved in tumor growth.

Details for Patent 10,335,420

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Genentech, Inc. RITUXAN rituximab Injection 103705 11/26/1997 ⤷  Try a Trial 2030-09-02
Genentech, Inc. HERCEPTIN trastuzumab For Injection 103792 09/25/1998 ⤷  Try a Trial 2030-09-02
Genentech, Inc. HERCEPTIN trastuzumab For Injection 103792 02/10/2017 ⤷  Try a Trial 2030-09-02
Genzyme Corporation CAMPATH alemtuzumab Injection 103948 05/07/2001 ⤷  Try a Trial 2030-09-02
Genzyme Corporation LEMTRADA alemtuzumab Injection 103948 11/14/2014 ⤷  Try a Trial 2030-09-02
Genzyme Corporation CAMPATH alemtuzumab Injection 103948 10/12/2004 ⤷  Try a Trial 2030-09-02
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

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