US 12,427,199 B2
Self-assembled diblock copolymers composed of pegmema and drug bearing polymeric segments
Rana Sanyal, Istanbul (TR); Amitav Sanyal, Istanbul (TR); and Sadik Kaga, Istanbul (TR)
Assigned to RS ARASTIRMA EGITIM DANISMANLIK ILAC SANAYI TICARET ANONIM SIRKETI, Istanbul (TR)
Appl. No. 16/349,419
Filed by RS ARASTIRMA EGITIM DANISMANLIK ILAC SANAYI TICARET ANONIM SIRKETI, Istanbul (TR)
PCT Filed Nov. 16, 2017, PCT No. PCT/IB2017/057155
§ 371(c)(1), (2) Date May 13, 2019,
PCT Pub. No. WO2018/092048, PCT Pub. Date May 24, 2018.
Claims priority of application No. 1619372 (GB), filed on Nov. 16, 2016.
Prior Publication US 2024/0108736 A1, Apr. 4, 2024
Int. Cl. A61K 47/58 (2017.01); A61K 47/60 (2017.01); A61K 47/65 (2017.01); C08F 220/28 (2006.01)
CPC A61K 47/58 (2017.08) [A61K 47/60 (2017.08); A61K 47/65 (2017.08); C08F 220/286 (2020.02)] 14 Claims
 
1. A polymer-drug conjugate of formula I in the form of a block co-polymer for delivery of therapeutic agents

OG Complex Work Unit Chemistry
wherein:
R1, R2 and R3 are independently selected from H or −CH3;
x is a natural number between 1-100;
y is a natural number between 1-100;
n is a natural number between 1-50;
L is a cleavable linker;
D is a therapeutic agent that is combretastatin or 5-Fluorouracil (5-FU) or gemcitabine or chloroquine or doxorubicine;
A is an end group or A may be null; and
B is an end group or B may be null,
wherein: (a) A is (i) an end group that is a fragment of a chain transfer agent (CTA), an initiator or a fragment of a CTA, or (ii) an initiator conjugated with a targeting moiety selected from the group consisting of antibodies, antibody fragments, and peptides, a fragment of a CTA or initiator having a reactive functional group selected from the group consisting of: acetal, hemiacetal, carboxylic acid, alcohol, amide, imide, anhydride, aryl halide, azo compound, diazo compound, hydrazine, azide, carbonate, chlorosilane, cyanide, ester, sulfate ester, phosphate ester, thiophosphate ester, isocyanate, isothiocyanate, thiocarbamate ester, and dithiocarbamate ester; (b) B is an end group that is a fragment of a chain transfer agent or initiator; and (c) the polymer-drug conjugate is made by a method comprising:
polymerizing PEG (meth)acrylate monomer (formula II)

OG Complex Work Unit Chemistry
to provide a polymer of formula IIa:

OG Complex Work Unit Chemistry
(ii) reacting formula IIa with a (meth)acrylate-L-D monomer (formula IIIa)

OG Complex Work Unit Chemistry
to give polymer-drug conjugate of formula I.