Therapeutic nanoparticles having EGFR ligands and methods of making and using same

Patent metadata

Field	Value
Publication number	US-10137088-B2
Application number	US-201615241977-A
Country	US
Kind code	B2
Filing date	Aug 19, 2016
Priority date	Feb 10, 2016
Publication date	Nov 27, 2018
Grant date	Nov 27, 2018

Abstract

Provided herein in part is a therapeutic nanoparticle that includes a biocompatible polymer; a polymer—EGFR ligand conjugate, wherein the EGFR ligand is covalently bound directly or through a chemical linker to the polymer, and a therapeutic agent.

First claim

What is claimed is:

1. A therapeutic nanoparticle, comprising:
about 0.2 to about 35 weight percent of a therapeutic agent; and
about 50 to about 98 weight percent of a diblock poly(lactic)acid-poly(ethylene)glycol copolymer or a diblock poly(lactic)-co-poly(glycolic)acid-poly(ethylene)glycol copolymer; and
about 2% to about 12% PLA-PEG-EGFR ligand density, wherein the EGFR ligand is bound or associated to an azide functionalized PEG-PLA, wherein PLA is poly(lactic)acid and PEG is poly(ethylene)glycol; and wherein the EGFR ligand is a peptidyl ligand comprising a sequence selected from the group consisting of: Ac-DPCTWEVWGRECLQGGK(PEG4-DBCO)-CONH2 (SEQ ID NO: 185), Ac-DACTWEVWGRECLQGGK(PEG4-DBCO)-CONH2 (SEQ ID NO: 186), Ac-DPCT(2Ind)GEV(5MeO)WGRECLQGGK(PEG4-DBCO)-CONH2(SEQ ID NO: 187), Ac-DPPenTWEVWGREPenLQGGK(PEG4-DBCO)-CONH2 (SEQ ID NO: 188), AcDAPenTWEVWGREPenLQGGK(DBCO)-CONH2 (SEQ ID NO: 189), Ac-DACT(2Ind)GEV(5MeO)WGRECLQGGK(DBCO)-CONH2 (SEQ ID NO: 190), Ac-DPPenT(2Ind)GEV(5MeO)WGREPenLQGGK(DBCO)-CONH2 (SEQ ID NO: 191), Ac-DAPenT(2Ind)GEV(5MeO)WGREPenLQGGK(DBCO)-CONH2 (SEQ ID NO: 192), Ac-DAPenTWEVWGREPenLQGGK(DBCO)-CONH2 (SEQ ID NO: 193), Ac-DPCTWEVWGRECLQGGK(PEGS-DBCO)-CONH2 (SEQ ID NO: 194), Ac-DACT (2Ind)GEV(5MeO)WGRECLQGGK(DBCO)-CONH2 (SEQ ID NO: 195), AcDPPenT(2Ind)GEV(5MeO)WGREPenLQGGK(DBCO)-CONH2 (SEQ ID NO: 196), and AcDAPenT(2Ind)GEV(5MeO)WGREPenLQGGK(DBCO)-CONH2 (SEQ ID NO: 197), Ac-DPCTWEVWGRECLQGGK(PEG5-DBCO)-CONH 2 (SEQ ID NO: 198), or modifications thereof.

2. The therapeutic nanoparticle of claim 1 , wherein the therapeutic nanoparticle has a hydrodynamic diameter of about 60 to about 150 nm.

3. The therapeutic nanoparticle of claim 2 , wherein the hydrodynamic diameter is about 90 to about 140 nm.

4. The therapeutic nanoparticle of claim 1 , comprising about 1 to about 10 weight percent of the therapeutic agent.

5. The nanoparticle of claim 1 , comprising about 200 to about 500 of the PLA-PEG conjugated to the peptidyl ligand molecules.

6. The nanoparticle of claim 1 , wherein the PLA-PEG conjugated to the peptidyl ligand molecules by reacting azide functionalized PLA-PEG and using a strain-promoted alkyne-azide cycloadditions.

7. The nanoparticle of claim 1 , wherein the PLA of PLA-PEG has a number average molecular weight of about 15 to about 17 kDa.

8. The nanoparticle of claim 1 , wherein the PEG of the PLA-PEG has a number of about 4 to about 6kDa.

9. A pharmaceutically acceptable composition comprising a plurality of therapeutic nanoparticles of claim 1 and a pharmaceutically acceptable excipient.

Assignees

• Pfizer

Inventors

• Zale Stephen E
• Mcdonnell Kevin Andrew
• Horhota Allen Thomas

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61K47/34

  Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) · CPC title

• A61K47/62

  the modifying agent being a protein, peptide or polyamino acid · CPC title

• A61K47/6937

  the polymer being PLGA, PLA or polyglycolic acid · CPC title