Nanoparticle immunoconjugates

Patent metadata

Field	Value
Publication number	US-2020353096-A1
Application number	US-201916720176-A
Country	US
Kind code	A1
Filing date	Dec 19, 2019
Priority date	Apr 7, 2015
Publication date	Nov 12, 2020
Grant date	—

Abstract

Disclosed herein are nanoparticle immunoconjugates useful for therapeutics and/or diagnostics. The immunoconjugates have diameter (e.g., average diameter) no greater than 20 nanometers (e.g., as measured by dynamic light scattering (DLS) in aqueous solution, e.g., saline solution). In certain embodiments, the conjugates are silica-based nanoparticles with single chain antibody fragments attached thereto.

First claim

1 - 44 . (canceled)

45 . An immunoconjugate comprising:
a nanoparticle coated with an organic polymer; an antibody fragment conjugated to the organic polymer-coated nanoparticle, a therapeutic agent conjugated to the organic polymer-coated nanoparticle through a linker, wherein the nanoparticle has a diameter no greater than 20 nanometers, wherein the nanoparticle comprises a silica-based core and a silica shell surrounding at least a portion of the core, wherein the antibody fragment is a single chain variable fragment (scFv).

46 . The immunoconjugate of claim 45 , wherein the linker is a cleavable linker.

47 . The immunoconjugate of claim 46 , wherein the cleavable linker is selected from a group consisting of peptide, hydrazine and disulfide linkers.

48 . The immunoconjugate of claim 45 , wherein the linker is a peptide linker.

49 . The immunoconjugate of claim 45 , wherein the linker is a peptide linker that is cleaved by lysosomal proteases.

50 . The immunoconjugate of claim 49 , wherein the lysosomal protease is cathepsin-B.

51 . The immunoconjugate of claim 45 , wherein the linker is a dipeptide linker.

52 . The immunoconjugate of claim 51 , wherein the dipeptide linker is a valine-citrulline linker.

53 . The immunoconjugate of claim 45 , wherein the antibody fragment is from about 25 kDa to about 30 kDa.

54 . The immunoconjugate of claim 45 , wherein the nanoparticle comprises a fluorescent compound within the core.

55 . The immunoconjugate of claim 45 , wherein the nanoparticle has from one to ten antibody fragments attached thereto.

56 . The immunoconjugate of claim 45 , wherein the nanoparticle has a diameter no greater than 15 nanometers.

57 . The immunoconjugate of claim 45 , wherein the nanoparticle has a diameter in a range from 1 nm to 20 nm.

58 . The immunoconjugate of claim 45 , wherein the antibody fragment comprises anti-VEGF-A.

59 . The immunoconjugate of claim 45 , wherein the immunoconjugate comprises one or more imaging agents.

60 . The immunoconjugate of claim 59 , wherein the one or more imaging agents comprise a PET tracer.

61 . The immunoconjugate of claim 59 , wherein the one or more imaging agents comprise a fluorophore.

62 . The immunoconjugate of claim 4 , wherein the therapeutic agent comprises a chemotherapy drug.

63 . The immunoconjugate of claim 45 , wherein the therapeutic agent comprises a radioisotope.

64 . The immunoconjugate of claim 63 , wherein the radioisotope is a member selected from the group consisting of 99m Tc, 111 In, 64 Cu, 67 Ga, 186 Re, 188 Re, 153 Sm, 177 Lu, 67 Cu, 123 I, 124 I, 125 I, 11 C, 1 3N, 15 O, 18 F, 186 Re, 188 Re, 153 Sm, 166 Ho, 177 Lu, 149 Pm, 90 Y, 213 Bi, 103 Pd, 109 Pd, 159 Gd, 140 La, 198 Au, 199 Au, 169 Yb, 175 Yb, 165 Dy, 166 Dy, 67 Cu, 105 Rh, 111 Ag, 89 Zr, 225 Ac, and 192 Ir.

Assignees

• Memorial Sloan Kettering Cancer Center
• Univ Cornell
• Univ Missouri

Inventors

• Bradbury Michelle S
• Quinn Thomas P
• Chen Feng
• Yoo Barney
• Lewis Jason
• Wiesner Ulrich
• Ma Kai

Classifications

• C07K2317/55

  Fab or Fab' · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title

• A61K47/6923 Primary

  the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/52 Primary

  the modifying agent being an inorganic compound, e.g. an inorganic ion that is complexed with the active ingredient · CPC title