US 12,350,337 B2
Polymeric drug delivery conjugates and methods of making and using thereof
Jiyuan Yang, Salt Lake City, UT (US); Lian Li, Salt Lake City, UT (US); C. Matthew Peterson, Bountiful, UT (US); and Jindrich Kopecek, Salt Lake City, UT (US)
Assigned to UNIVERSITY OF UTAH RESEARCH FOUNDATION, Salt Lake City, UT (US)
Appl. No. 17/754,915
Filed by UNIVERSITY OF UTAH RESEARCH FOUNDATION, Salt Lake City, UT (US)
PCT Filed Oct. 16, 2020, PCT No. PCT/US2020/055940
§ 371(c)(1), (2) Date Apr. 15, 2022,
PCT Pub. No. WO2021/076865, PCT Pub. Date Apr. 22, 2021.
Claims priority of provisional application 62/916,821, filed on Oct. 18, 2019.
Prior Publication US 2022/0249682 A1, Aug. 11, 2022
Int. Cl. A61K 45/06 (2006.01); A61K 47/68 (2017.01); A61P 35/00 (2006.01)
CPC A61K 45/06 (2013.01) [A61K 47/6811 (2017.08); A61K 47/6849 (2017.08); A61K 47/6889 (2017.08); A61P 35/00 (2018.01)] 31 Claims
 
1. A method for treating cancer in a subject, the method comprising administering to the subject:
a drug delivery conjugate or ester thereof comprising two polymeric segments P1 and P2 covalently connected to one another by a single first cleavable peptide linker, wherein at least one drug is covalently bonded to each polymeric segment of the drug delivery conjugate, and wherein the at least one drug is a PD-L1 inhibitor comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, and a combination thereof, and
an anti-cancer conjugate or ester thereof comprising:
two polymeric segments P1 and P2 covalently connected to one another by a single first cleavable peptide linker having, an amino acid sequence of SEQ ID NO: 24; and
an anti-cancer agent covalently bonded to each polymeric segment of the anti-cancer conjugate via a second cleavable peptide linker,
wherein each polymeric segment of the anti-cancer conjugate comprises the polymerization product of N-(2-hydroxypropyl) methacrylamide (HPMA) and a monomer of formula VI:

OG Complex Work Unit Chemistry
wherein Z is the anti-cancer agent comprising epirubicin, paclitaxel, doxorubicin, gemcitabine, cisplatin, methotrexate, 5-fluorouracil, betulinic acid, amphotericin B, diazepam, nystatin, propofol, testosterone, estrogen, prednisolone, prednisone, 2,3-mercaptopropanol, progesterone, docetaxel, a maytansinoid, a PD-1 inhibitor, a protein kinase inhibitor, a P-glycoprotein inhibitor, an autophagy inhibitor, a PARP inhibitor, an aromatase inhibitor, a photosensitizer, a radiosensitizer, an interleukin, an antiandrogen, a platinate, geldanamycin, 9-aminocamptothecin, or any combination thereof.