WO 2012/049636 A1 - Eif6 Phosphorylation Antagonists For Use In Medicine - The Lens

Eif6 Phosphorylation Antagonists For Use In Medicine

Published: Apr 19, 2012
Earliest Priority: Oct 12 2010
Family: 1
Cited Works: 74
Cited by: 1
Cites: 2
Additional Info: Cited Works Full text Published

Abstract

An antagonist of phosphorylation of Eukaryotic Initiation Factor 6 (eIF6) polypeptide for use in medicine, wherein the antagonist antagonises phosphorylation of an amino acid serine at the position corresponding to position 235, 230 and/or 243 in the polypeptide shown in Figure 5.

Claims

An antagonist of phosphorylation of Eukaryotic Initiation Factor 6 (eIF6) polypeptide for use in medicine, wherein the antagonist antagonises phosphorylation of an amino acid serine at the position corresponding to position 235, 230 and/or 243 in the polypeptide shown in Figure 5.
An isolated Eukaryotic Initiation Factor 6 (eIF6) polypeptide for use in medicine, wherein the amino acid serine at the position corresponding to position 235, 230 and/or 243 of the sequence shown in Figure 5 is replaced with another amino acid.
An isolated Eukaryotic Initiation Factor 6 (eIF6) fragment for use in medicine, wherein the fragment is a fragment of the polypeptide defined in claim 2 and wherein the fragment comprises the amino acid of the polypeptide which is replaced with another amino acid.
An antagonist as defined in claim 1, an isolated polypeptide as defined in claim 2 or an isolated Eukaryotic Initiation Factor 6 (eIF6) fragment as defined in claim 3, wherein the antagonist, polypeptide or fragment is for use in modulating cellular translation in a subject or for use in modulating the immune system or for use in the treatment of proliferative disorders.
An antagonist as defined in claim 1, an isolated polypeptide as defined in claim 2 or an isolated Eukaryotic Initiation Factor 6 (eIF6) fragment as defined in claim 3, wherein the antagonist, polypeptide or fragment is for use in the treatment of neoplastic disease, adipogenesis disorders or liver disorders.
An antagonist as defined in claim 1, an isolated polypeptide as defined in claim 2 or an isolated Eukaryotic Initiation Factor 6 (eIF6) fragment as defined in claim 3, wherein the antagonist, polypeptide or fragment is for use in modulating an immune response to an allergen or transplant, or for use in treatment of autoimmune disease or inflammation. An antagonist as defined in claim 1, an isolated polypeptide as defined in claim 2 or an isolated Eukaryotic Initiation Factor 6 (eIF6) fragment as defined in claim 3, wherein the antagonist, polypeptide or fragment is for use in treating cancer, type II diabetes, liver failure, obesity or Shwachman- Diamond syndrome.
An isolated polynucleotide for use in medicine, wherein the polynucleotide comprises a nucleotide sequence encoding the polypeptide defined in claim 2.
An isolated polynucleotide for use in medicine, wherein the polynucleotide comprises a nucleotide sequence encoding the Eukaryotic Initiation Factor 6 (eIF6) fragment defined in claim 3.
An isolated polynucleotide as defined in claim 8 or 9, wherein the polynucleotide is for use in modulating cellular translation in a subject or for modulating the immune system or for use in the treatment of proliferative disorders.
An isolated polynucleotide as defined in claim 8 or 9, wherein the polynucleotide is for use in the treatment of neoplastic disease, adipogenesis disorders or liver disorders.
An isolated polynucleotide as defined in claim 8 or 9, wherein the polynucleotide is for use in modulating an immune response to an allergen or transplant, or for use in treatment of autoimmune disease or inflammation.
An isolated polynucleotide as defined in claim 8 or 9, wherein the polynucleotide is for use in treating cancer, type II diabetes, liver failure, obesity or Shwachman-Diamond syndrome.
An isolated polynucleotide for use according to any one of claims 8-13, wherein the polynucleotide is contained in a gene transfer vector.
An isolated polynucleotide for use according to claim 14, wherein the polynucleotide is contained in a viral vector. An isolated polynucleotide for use according to claim 15, wherein the polynucleotide is contained in a lentiviral vector.
An isolated polynucleotide for use according to claim 15 or 16, wherein the vector is in the form of an integrated provirus.
A pharmaceutical composition comprising:
(i) an antagonist as defined in claim 1, an isolated polypeptide as defined in claim 2 or an isolated Eukaryotic Initiation Factor 6 (eIF6) fragment as defined in claim 3,
(ii) a liposome comprising an antagonist as defined in claim 1 , an isolated polypeptide as defined in claim 2 or an isolated Eukaryotic Initiation Factor 6 (eIF6) fragment as defined in claim 3, or
(iii) a cell comprising an antagonist as defined in claim 1, an isolated polypeptide as defined in claim 2 or an isolated Eukaryotic Initiation Factor 6 (eIF6) fragment as defined in claim 3,
and a pharmaceutically acceptable carrier, diluent or excipient.
A pharmaceutical composition comprising:
(i) an isolated polynucleotide as defined in claim 8 or 9,
(ii) a liposome comprising an isolated polynucleotide as defined in claim 8 or 9,
(iii) a vector as defined in any of any of claims 14 to 16,
(iv) a viral particle obtainable from the vector of any of claims 15 to 17, or
(v) a cell comprising an isolated polynucleotide as defined in claim 8 or 9, and a pharmaceutically acceptable carrier, diluent or excipient.
A method of diagnosing cancer, said method comprising detecting the level of Eukaryotic Initiation Factor 6 (eIF6) polypeptide expression in a sample from subject, the method further comprising detecting the occurrence of phosphorylation of an amino acid in said polypeptide in the sample, wherein the phosphorylation detected is that of the amino acid serine at the position corresponding to position 235, 230 and/or 243 in the polypeptide shown in Figure 5. 21. A method of detecting remission of a tumour after therapy, said method comprising detecting the level of Eukaryotic Initiation Factor 6 (eIF6) polypeptide expression in a sample from subject, the method further comprising detecting the occurrence of phosphorylation of an amino acid in said polypeptide in the sample, wherein the phosphorylation detected is that of the amino acid serine at the position corresponding to position 235, 230 and/or
243 in the polypeptide shown in Figure 5.
A prognostic method for determining whether a subject will be susceptible to treatment with an antagonist, polypeptide, fragment or polynucleotide for use according to any one of claims 1-17 or a pharmaceutical composition according to claim 18 or 19, said method comprising detecting the occurrence of phosphorylation of an amino acid in Eukaryotic Initiation Factor 6 (eIF6) in a sample from said subject, wherein the phosphorylation detected is that of the amino acid serine at the position corresponding to position 235, 230 and/or 243 in the polypeptide shown in Figure 5.
An ex vivo method of antagonising phosphorylation of Eukaryotic Initiation Factor 6 (eIF6), comprising contacting a cell or part of an organism with an antagonist as defined in claim 1 , an isolated polypeptide as defined in claim 2 or an isolated Eukaryotic Initiation Factor 6 (eIF6) fragment as defined in claim 3.
An ex vivo method of antagonising phosphorylation of Eukaryotic Initiation Factor 6 (eIF6), comprising contacting a cell or part of an organism with an isolated polynucleotide as defined in any one of claims 8 to 17. A method of identifying an agent that prevents phosphorylation of Eukaryotic Initiation Factor 6 (eIF6) polypeptide, wherein the phosphorylation is of an amino acid serine at the position corresponding to position 235, 230 and/or 243 in the polypeptide shown in Figure 5, the method comprising contacting Eukaryotic Initiation Factor 6 (eIF6) with said agent and detecting the occurrence of phosphorylation of Eukaryotic Initiation Factor 6 (eIF6), wherein the phosphorylation is of the amino acid serine at the position corresponding to position 235, 230 and/or 243 in the polypeptide shown in Figure 5.
An antibody capable of recognizing a phosphorylated eIF6.
A method of identifying an agent that promotes de-phosphorylation of Eukaryotic Initiation Factor 6 (eIF6) polypeptide, wherein the de- phosphorylation is of an amino acid serine at the position corresponding to position 235, 230 and/or 243 in the polypeptide shown in Figure 5, the method comprising contacting phosphorylated Eukaryotic Initiation Factor 6 (eIF6) with said agent and detecting the occurrence of de-phosphorylation of Eukaryotic Initiation Factor 6 (eIF6), wherein the de-phosphorylation is of the amino acid serine at the position corresponding to position 235, 230 and/or 243 in the polypeptide shown in Figure 5.