Opioid Receptor Binding Agents and Uses Thereof

Patent metadata

Field	Value
Publication number	US-2019338024-A1
Application number	US-201916355442-A
Country	US
Kind code	A1
Filing date	Mar 15, 2019
Priority date	Jan 30, 2014
Publication date	Nov 7, 2019
Grant date	—

Abstract

Agents that specifically bind to an opioid receptor in a conformationally specific way can be used to induce a conformational change in the receptor. Such agents have therapeutic applications and can be used in X-ray crystallography studies of the receptor. Such agents can also be used to improve drug discovery via compound screening and/or structure-based drug design.

First claim

1 .- 30 . (canceled)

31 . A complex comprising:
an opioid receptor; and a binding agent specifically binding to the receptor; wherein the opioid receptor is a synthetic analog of a naturally occurring opioid receptor; wherein the binding agent is a VHH antibody that is directed to an intracellular conformational epitope on an opioid receptor; and wherein the opioid receptor comprises an epitope that is essentially the same as the intracellular conformational epitope to which the VHH antibody binds.

32 . The complex of claim 31 , wherein the intracellular conformational epitope forms a portion of a binding site for a downstream signaling protein.

33 . The complex of claim 31 , wherein the VHH antibody is directed to a G protein binding site or a β-arrestin binding site.

34 . The complex of claim 31 , wherein the VHH antibody is a G protein mimetic.

35 . The complex of claim 31 , wherein the VHH antibody is a Gi protein mimetic.

36 . The complex of claim 31 , wherein the synthetic analog of a naturally occurring opioid receptor comprises a substitution, an insertion, addition, or any combination thereof, in relation to the amino acid sequence of the naturally occurring opioid receptor.

37 . The complex of claim 31 , wherein the opioid receptor comprises a chimeric or hybrid structure.

38 . The complex of claim 31 , wherein opioid receptor is a chimeric opioid receptor comprising an N- and/or C-terminus of a first opioid receptor and loops of a second opioid receptor.

39 . A cellular composition comprising the complex of claim 31 .

40 . The cellular composition of claim 39 , wherein the cellular composition is an organism, a tissue, a cell, a cell line, or in a membrane composition or liposomal composition derived from the organism, tissue, cell or cell line.

Assignees

• Vib Vzw
• Univ Brussel Vrije
• Univ Leland Stanford Junior

Inventors

• Steyaert Jan
• Laeremans Toon
• Pardon Els
• Kobilka Brian
• Manglik Aashish

Classifications

• A61P43/00

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

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• C07K2317/567

  Framework region [FR] · CPC title

• C07K16/28 Primary

  against receptors, cell surface antigens or cell surface determinants · CPC title

• C07K2317/22

  from camelids, e.g. camel, llama or dromedary · CPC title