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US 11,529,422 B2Granted
Polymer linkers and their uses
AssigneeNovacyte Therapeutics Company., Ltd
InventorBinyuan Sun
Life of this patent
Estimating the term…
Abstract
Provided herein are poly-1-hydroxymethylethylene hydroxymethyl formal (PHF)-based drug delivery systems. Also disclosed are methods of making antibody-drug conjugates and methods of treatment using these conjugates.
Claims20
A compound of Formula (I) comprising block repeat block monomer (b):
- wherein
- L1 is a linking group selected from alkylene, heteroalkylene, cycloalkylene, heterocyclylene, arylene, heteroarylene, amidoalkylene, amidoheteroalkylene, and any combination thereof;
- L2 is absent, or can be of the formula:
- L2A is a linking group selected from alkylene, heteroalkylene, cycloalkylene, heterocyclylene, arylene, heteroarylene, —C(O)—, —NRc—, and any combination thereof;
- L2B and Lac are independently absent or a linker group selected from alkylene, heteroalkylene, cycloalkylene, heterocyclylene, arylene, heteroarylene, amidoalkylene, amidoheteroalkylene, —C(O)—, —NRc—, and any combination thereof;
- B2A and B2B are independently absent or a cleavable linker;
- T is a therapeutic agent selected from the group consisting of chemotherapeutic agents, microtubule inhibitors, DNA-damaging agents and RNA transcription inhibitors.
4 more elements
A compound comprising block repeat block monomer (d):
- wherein
- L3 is a linker group selected from alkylene, heteroalkylene, cycloalkylene, heterocyclylene, arylene, heteroarylene, amidoalkylene, amidoheteroalkylene, and any combination thereof;
- Re is a substituent selected from hydrogen, alkyl and heteroalkyl;
- L4 is a group of the formula:
- L4A is a linker group selected from alkylene, heteroalkylene, cycloalkylene, heterocyclylene, arylene, heteroarylene, —C(O)—, —NRc—, and any combination thereof;
- L4B and L4C are independently absent or a linker group selected from alkylene, heteroalkylene, cycloalkylene, heterocyclylene, arylene, heteroarylene, amidoalkylene, amidoheteroalkylene, —C(O)—, —NRc—, and any combination thereof;
- B4A and B4B are independently absent or a cleavable linker;
- C4A is a group selected from
- where
- A is —H or a targeting moiety selected from the group consisting of an antibody, a synthetically functionalized antibody, a peptide and a targeting ligand;
- “n” is independently at each occurrence an integer ranging from 0-5;
- each cleavable linker B2A, B2B, B4A and B4B, if present, is independently selected from —S—S—, —C(═O)O—, —OC(═O)—, —C(═O)NRc—, —N(Rc)C(═O)—, —OC(═O)O—, —NRcC(═O)O—, —OC(═O)N(Rc)— or —N(Rc)C(═O)N(Rd)—, —C(═O)N(Rc)C(═O)—, —C(═O)S—, —SC(═O)—, —SC(═O)S—, —OC(═O)S—, —SC(═O)O—, —OC(═S)O—, —SC(═S)S—, —N(Rc)SO2—, —SO2N(Rc)—, —N(Rc)SO2N(Rd)—, —C(═O)N(Rc)N(Rd)—, —N(Rc)N(Rd)C(═O)—, —N(Rc)N(Rd)C(═O)O—, —OC(═O)N(Rc)N(Rd)—, —C(Rc)═N—NH—C(═O)—, —C(═O)NH—N═C(Rc)—, —C(Rc)═N—O—, —O—
- Rc and Rd are independently selected at each occurrence from hydrogen, alkyl, heteroalkyl, cycloalkyl, and heterocyclyl.
10 more elements
The compound of 9, wherein the compound comprises one or more targeting moieties A and A, is an antibody or a synthetically functionalized antibody specific for an antigen over expressed in cancer cells.
A compound comprising block repeat monomer unit (e):
- wherein
- L3 is a linker group selected from alkylene, heteroalkylene, cycloalkylene, heterocyclylene, arylene, heteroarylene, amidoalkylene, amidoheteroalkylene, and any combination thereof;
- L4 is a group of the formula:
- L4A is a linker group selected from alkylene, heteroalkylene, cycloalkylene, heterocyclylene, arylene, heteroarylene, and any combination thereof;
- L4B and L4C are independently absent or a linker group selected from selected from alkylene, heteroalkylene, cycloalkylene, heterocyclylene, arylene, heteroarylene, amidoalkylene, amidoheteroalkylene, —C(O)—, —N(Rc)—, and any combination thereof;
- B4A and B4B are independently absent or a cleavable linker
- C4A is a group selected from
- A is —H or a targeting moiety selected from the group consisting of an antibody, a synthetically functionalized antibody, a peptide and a targeting ligand;
- “n” is independently at each occurrence an integer ranging from 0-5;
- Rc and Rd are independently selected at each occurrence from hydrogen, alkyl, heteroalkyl, cycloalkyl, and heterocyclyl;
- each cleavable linker B2A, B2B, B4A and B4B, if present, is independently selected from —S—S—, —C(═O)O—, —OC(═O)—, —C(═O)NRc—, —N(Rc)C(═O)—, —OC(═O)O—, —NRcC(═O)O—, —OC(═O)N(Rc)— or —N(Rc)C(═O)N(Rd)—, —C(═O)N(Rc)C(═O)—, —C(═O)S—, —SC(═O)—, —SC(═O)S—, —OC(═O)S—, —SC(═O)O—, —OC(═S)O—, —SC(═S)S—, —N(Rc)SO2—, —SO2N(Rc)—, —N(Rc)SO2N(Rd)—, —C(═O)N(Rc)N(Rd)—, —N(Rc)N(Rd)C(═O)—, —N(Rc)N(Rd)C(═O)O—, —OC(═O)N(Rc)N(Rd)—, —C(Rc)═N—NH—C(═O)—, —C(═O)NH—N═C(Rc)—, —C(Rc)═N—O—, —O—
8 more elements
Dependencies are inferred from the claim text.