Antibodies Directed Against ICOS and Uses Thereof

Patent metadata

Field	Value
Publication number	US-2016264666-A1
Application number	US-201615165152-A
Country	US
Kind code	A1
Filing date	May 26, 2016
Priority date	Mar 31, 2011
Publication date	Sep 15, 2016
Grant date	—

Abstract

The present invention provides antibodies directed against ICOS or a derivative thereof which neutralize ICOS engagement on Treg by inhibiting the fixation between ICOS and ICOS-L and abrogate proliferation of Treg induced by plasmacytoid dendritic cells. The present invention further provides antibodies directed against ICOS or a derivative thereof which induce IL-10 and IFNγ production, induce CD4+ T cells proliferation, reduce Tconv proliferation, and increase the immunosuppressive function of Treg.

First claim

1 - 22 . (canceled)

23 . An antibody directed against ICOS, wherein said antibody has the following 6 CDRs:

Amino acid sequence

H-CDR1
GYSFTSYWIN (SEQ ID NO: 23)

H-CDR2
NIYPSDSYTNYNQMFKD (SEQ ID NO: 24)

H-CDR3
WNLSYYFDNNYYLDY (SEQ ID NO: 25)

L-CDR1
RSSKSLLHSNGNTYLY (SEQ ID NO: 26)

L-CDR2
RMSNLAS (SEQ ID NO: 27)

L-CDR3
MQHLEYPWT (SEQ ID NO: 28)

24 . An antibody according to claim 23 , wherein the nucleotidic sequences encoding the 6 CDRs are the following:

DNA sequence

H-CDR1
GGCTACAGTTTCACCAGCTACTGGATAAAC

(SEQ ID NO: 17)

H-CDR2
AATATTTATCCTTCTGATAGTTATACTAAC

TACAATCAAATGTTCAAGGAC

(SEQ ID NO: 18)

H-CDR3
TGGAATCTTTCTTATTACTTCGATAATAAC

TACTACTTGGACTAC

(SEQ ID NO: 19)

L-CDR1
AGGTCTAGTAAGAGTCTCCTGCATAGTAAT

GGCAACACTTACTTGTAT

(SEQ ID NO: 20)

L-CDR2
CGGATGTCCAACCTTGCCTCA

(SEQ ID NO: 21)

L-CDR3
ATGCAACATCTAGAATATCCGTGGACG

(SEQ ID NO: 22)

25 . An antibody according to claim 23 or a derivative thereof which:
induces IL-10 and IFNγ production;
induces CD4+ T cells proliferation;
reduces Tconv proliferation, and
increases the immunosuppressive function of Treg.

26 . A method of treatment of a patient in need thereof comprising the step of administering to said patient the antibody according to claim 23 .

27 . The method of treatment according to claim 26 , wherein said patient suffers from a disease or a condition associated with or caused by an excessive immune response.

28 . The method of treatment according to claim 27 , wherein said disease is selected from the group consisting of autoimmune diseases, transplantation rejection or a graft versus host disease.

29 . The method of treatment according to claim 28 , wherein said disease is an inflammatory disorder.

30 . The method of treatment according to claim 29 , wherein said inflammatory disorder is selected in the group consisting of inflammatory disorder of the nervous system, mucosal inflammatory disease, inflammatory skin disease and autoimmune arthritis.

31 . The method of treatment according to claim 29 , wherein said inflammatory disorder is selected from multiple sclerosis, inflammatory bowel disease, asthma or tonsillitis, dermatitis, psoriasis, contact hypersensitivity and rheumatoid arthritis.

32 . A method for selecting patients susceptible of being treated by anti-ICOS immunotherapy, comprising the step of quantifying ICOS positive Treg cells in a sample of said patient.

33 . An antibody directed against ICOS, wherein said antibody is selected from the group consisting of Icos 53-3, Icos 88-2 and Icos 92-17, respectively obtainable from the hybridoma deposited at the CNCM on Jul. 2, 2009 under the accession numbers CNCM I-4176, CNCM I-4177, CNCM I 4178 and derivatives thereof.

Assignees

• Inserm (Institut Nat De La Sante Et De La Rech Medicale)
• Inst Jean Paoli & Irene Calmettes
• Univ Aix Marseille
• Univ Claude Bernard - Lyon 1
• Centre Leon Berard

Inventors

• Faget Julien
• Caux Christophe
• Menetrier-Caux Christine
• Nunes Jacques
• Olive Daniel

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P31/12

  Antivirals · CPC title

• A61P31/04

  Antibacterial agents · CPC title