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US 11,957,760 B2Granted
Folate receptor targeted nanoparticle drug conjugates and uses thereof
AssigneeElucida Oncology, Inc.
InventorsKai Ma, Aranapakam M. Venkatesan, Feng Chen, Fei Wu, Melik Ziya Türker, Thomas Courtney Gardinier, II, Geno J. Germano, Jr., Gregory Paul Adams, Francis Y. F. Lee
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Abstract
The disclosure relates to nanoparticle drug conjugates (NDC) that comprise ultrasmall nanoparticles, folate receptor (FR) targeting ligands, and linker-drug conjugates, and methods of making and using them to treat cancer.
Claims30
A nanoparticle-drug conjugate (NDC) comprising:
- (a) a silica nanoparticle;
- (b) polyethylene glycol (PEG) that is covalently bonded to the surface of the silica nanoparticle;
- (c) a targeting ligand comprising folic acid, wherein the targeting ligand is attached to the silica nanoparticle through a first spacer group;
- and
- (d) a linker-payload conjugate, wherein:
- (i) the payload is exatecan;
- (ii) the linker-payload conjugate is attached to the silica nanoparticle through a second spacer group;
- (iii) the linker is a protease-cleavable linker;
- and
- (iv) the exatecan is released upon cleavage of the linker,
- wherein the first spacer group and the second spacer group each comprise a structure of Formula (NP):
- wherein
- x is an integer of 0 to 20;
- the silicon atom (Si) is a part of the silica nanoparticle;
- and
- the adjacent to the triazole moiety denotes a point of attachment to the targeting ligand or the linker-payload conjugate, either directly or indirectly.
13 more elements
A nanoparticle-drug conjugate (NDC) comprising:
- (a) a silica nanoparticle;
- (b) polyethylene glycol (PEG) that is covalently bonded to the surface of the silica nanoparticle;
- (c) a targeting ligand comprising folic acid, wherein the targeting ligand is attached to the silica nanoparticle through a spacer group;
- and
- (d) a structure of Formula (S-1):
- wherein
- Payload comprises exatecan;
- Linker comprises a protease-cleavable linker, wherein the exatecan is released upon cleavage of the linker;
- and
- the silicon atom (Si) is a part of the silica nanoparticle.
7 more elements
A nanoparticle-drug conjugate (NDC) comprising:
- (a) a silica nanoparticle;
- (b) polyethylene glycol (PEG) that is covalently bonded to the surface of the silica nanoparticle;
- (c) a structure of Formula (S-2):
- wherein
- Targeting Ligand comprises folic acid;
- and
- the silicon atom (Si) is a part of the silica nanoparticle;
- and
- (d) a linker-payload conjugate, wherein:
- (i) the payload is exatecan;
- (ii) the linker-payload conjugate is attached to the silica nanoparticle through a spacer group;
- (iii) the linker is a protease-cleavable linker;
- and
- (iv) the exatecan is released upon cleavage of the linker.
11 more elements
A nanoparticle-drug conjugate (NDC) comprising:
- (a) a silica nanoparticle;
- (b) polyethylene glycol (PEG) that is covalently bonded to the surface of the silica nanoparticle;
- (c) a targeting ligand comprising folic acid, wherein the targeting ligand is attached to the silica nanoparticle through a first spacer group;
- and
- (d) a linker-payload conjugate that is attached to the silica nanoparticle through a second spacer group, wherein the payload is exatecan, the linker is a protease-cleavable linker, the exatecan is released upon cleavage of the linker, and wherein the linker-payload conjugate comprises a structure of Formula (I):
- or a salt thereof,
- wherein,
- denotes a point of attachment to the second spacer group;
- A is Val-Lys;
- Payload comprises a residue of the exatecan;
- Z is an —NH— group of the exatecan;
- R1, R2, R3, R4, and R5 in each occurrence is independently hydrogen;
- X is absent;
- Y is
- wherein the carbonyl in
- is bonded to Z;
- X1, X2, X3, and X4 are each independently —CH—;
- and
- n is 1.
16 more elements
Dependencies are inferred from the claim text.