Polypeptides and uses thereof for reducing CD95-mediated cell motility

Patent metadata

Field	Value
Publication number	US-10556941-B2
Application number	US-201816156521-A
Country	US
Kind code	B2
Filing date	Oct 10, 2018
Priority date	Apr 17, 2014
Publication date	Feb 11, 2020
Grant date	Feb 11, 2020

Abstract

The present invention relates to polypeptides and uses thereof for reducing CD95-meditated cell motility. In particular, the present invention relates to a polypeptide having an amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the amino-acid residue at position 175 to the amino-acid residue at position 191 in SEQ ID NO:1.

First claim

The invention claimed is:

1. A nucleic acid sequence encoding for a fusion protein comprising a polypeptide having an amino acid sequence having at least 96, 97, 98, 99, or 100% identity with an amino acid sequence ranging from an amino acid residue at position 175 to an amino acid residue at position 209 or 210 as set forth in SEQ ID NO: 1, wherein said polypeptide is fused to a heterologous cell-penetrating polypeptide.

2. A vector and an expression cassette in which the nucleic acid sequence of claim 1 is associated with suitable elements for controlling transcription and, optionally translation.

3. A host cell comprising the vector of claim 2 .

4. The host cell of claim 3 which is a prokaryotic or eukaryotic host cell genetically transformed with the vector.

5. A host cell comprising the nucleic acid sequence of claim 1 .

6. The host cell of claim 5 which is a prokaryotic or eukaryotic host cell genetically transformed with the nucleic acid sequence.

7. A method of treating cancer in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a fusion protein comprising a polypeptide having an amino acid sequence having at least 96, 97, 98, 99, or 100% identity with an amino acid sequence ranging from an amino acid residue at position 175 to an amino acid residue at position 209 or 210 as set forth in SEQ ID NO: 1, wherein said polypeptide is fused to a heterologous cell-penetrating polypeptide.

8. The method of claim 7 wherein the subject suffers from a triple negative breast cancer.

9. A method of treating an auto-immune disease or an inflammatory condition in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a fusion protein comprising a polypeptide having an amino acid sequence having at least 96, 97, 98, 99, or 100% identity with an amino acid sequence ranging from an amino acid residue at position 175 to an amino acid residue at position 209 or 210 as set forth in SEQ ID NO: 1, wherein said polypeptide is fused to a heterologous cell-penetrating polypeptide.

10. The method of claim 9 wherein the subject suffers from systemic lupus erythematosus.

11. A method of treating a Th17 mediated disease condition in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a fusion protein comprising a polypeptide having an amino acid sequence having at least 96, 97, 98, 99, or 100% identity with an amino acid sequence ranging from an amino acid residue at position 175 to an amino acid residue at position 209 or 210 as set forth in SEQ ID NO: 1, wherein said polypeptide is fused to a heterologous cell-penetrating polypeptide.

12. A pharmaceutical composition comprising a fusion protein comprising a polypeptide having an amino acid sequence having at least 96, 97, 98, 99, or 100% identity with an amino acid sequence ranging from an amino acid residue at position 175 to an amino acid residue at position 209 or 210 as set forth in SEQ ID NO: 1, wherein said polypeptide is fused to a heterologous cell-penetrating polypeptide.

13. A method for screening a drug for reducing CD95-mediated cell motility comprising the steps consisting of a) determining the ability of a candidate compound to inhibit the interaction between CD95 and a fusion protein comprising a polypeptide having an amino acid sequence having at least 96, 97, 98, 99, or 100% identity with an amino acid sequence ranging from an amino acid residue at position 175 to an amino acid residue at position 209 or 210 as set forth in SEQ ID NO: 1, wherein said polypeptide is fused to a heterologous cell-penetrating polypeptide and b) positively selecting the candidate compound that inhibits said interaction.

Assignees

• Inst Nat Sante Rech Med
• Univ Bordeaux
• Univ Rennes
• Ecole Des Hautes Etudes En Sante Publique Ehesp
• Univ Des Antilles Et De La Guyane
• Inst Bergonie
• Univ Nottingham

Inventors

• Legembre Patrick
• Vacher Pierre
• Sanseau Doriane
• Penna Aubin
• Flynn Robin

Classifications

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• G01N2500/02

  Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor) · CPC title

• G01N2333/70578

  NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30 CD40 or CD95 · CPC title

• C07K16/00

  Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies · CPC title

• G01N2333/70575

  NGF/TNF-superfamily, e.g. CD70, CD95L, CD153 or CD154 · CPC title