Botulinum neurotoxin-specific capture agents, compositions, and methods of using and making

Patent metadata

Field	Value
Publication number	US-9913875-B2
Application number	US-201615072039-A
Country	US
Kind code	B2
Filing date	Mar 16, 2016
Priority date	Mar 16, 2015
Publication date	Mar 13, 2018
Grant date	Mar 13, 2018

Abstract

The present application provides stable peptide-based Botulinum neurotoxin (BoNT) serotype A capture agents and methods of use as detection and diagnosis agents and in the treatment of diseases and disorders. The application further provides methods of manufacturing BoNT serotype A capture agents using iterative on-bead in situ click chemistry.

First claim

What is claimed is:

1. A capture agent comprising an anchor ligand that comprises a cyclic peptide comprising the formula of Dab(DNP)-R-Lys(N3)-T-Dab-Pra-L-SEQ ID NO:3).

2. The capture agent of claim 1 , wherein the anchor ligand comprises a molecule of formula Inh-1

wherein R 1 is absent or is a linker to the secondary ligand.

3. The capture agent of claim 1 , further comprising a secondary ligand comprises a cyclic peptide comprising the formula of -Pra-NYRWL-Lys(N3) (SEQ ID NO:7).

4. The capture agent of claim 1 , further comprising a secondary ligand comprises a molecule of formula L2

wherein R 2 is absent or is a linker to the anchor ligand.

5. The capture agent of claim 1 further comprising a linker.

6. The capture agent of claim 5 , wherein the linker is a tripeptide.

7. The capture agent of claim 6 , wherein the linker comprises the amino acid sequence of Gly-Aib-Leu or Leu-Aib-Gly.

8. The capture agent of claim 7 , wherein the linker comprises the amino acid sequence of Gly-Aib-Leu.

9. The capture agent of claim 7 , wherein the linker comprises the amino acid sequence of Leu-Aib-Gly.

10. The capture agent of claim 5 , wherein the linker comprises PEG 4 .

11. The capture agent of claim 5 , wherein the anchor ligand and/or the secondary ligand are linked to the linker via a 1,4-substituted-1,2,3-triazole residue (Tz4) or via a 1,5-substituted-1,2,3-triazole residue (Tz5).

12. The capture agent of claim 11 , wherein the anchor ligand is linked to the linker via a Tz4.

13. The capture agent of claim 1 , wherein the capture agent comprises a molecule of formula Inh-2

wherein R 3 is hydrogen, a capping group, or comprises a label or a spontaneously translocating peptide.

14. The capture agent of claim 13 , wherein the label is selected from the group consisting of biotin, copper-DOTA, biotin-PEG3, aminooxyacetate, 19 FB, 18 FB, 5-carboxyfluorescein, and FITC-PEG3.

15. The capture agent of claim 13 , wherein the label is a detectable moiety selected from the group consisting of 64 Cu DOTA, 68 Ga DOTA, 68 Ga NOTA, 18 F, Al 18 F NOTA, 64 Cu, 68 Ga 89 Zr, 124 I, 86 Y, 94m Tc, 110m In, 11 C and 76 Br.

16. The capture agent of claim 13 , wherein the spontaneously translocating peptide comprises the amino acid sequence of pliylrllrGqf (SEQ ID NO:24).

Assignees

• California Inst Of Techn
• Indi Molecular Inc

Inventors

• Farrow Blake
• Heath James R
• Agnew Heather Dawn

Classifications

• A61K47/64

  Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65) · CPC title

• A61K47/48215

  Human Necessities · mapped topic

• G01N33/531

  Production of immunochemical test materials · CPC title

• C07B59/008

  Peptides; Proteins · CPC title

• C07K2319/01

  containing a localisation/targetting motif · CPC title