US 12,411,143 B2
CD146 and uses thereof as a biomarker and as a therapeutic target in the diagnosis and treatment of fibrosis
Aurélie Leroyer, Marseilles (FR); Marcel Blot-Chabaud, Fuveau (FR); Christos Chadjichristos, Villers Sous Saint Leu (FR); Nathalie Bardin, Marseilles (FR); Françoise Dignat-George, Marseilles (FR); Alexandrine Bertaud, Marseilles (FR); Benjamin Guillet, Aix En Provence (FR); Christoph Thiemermann, Woodford Green (GB); and Guillaume Hache, Marseilles (FR)
Assigned to UNIVERSITE D'AIX-MARSEILLE, Marseilles (FR); ASSISTANCE PUBLIQUE HÔPITAUX DE MARSEILLE, Marseilles (FR); INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE), Paris (FR); and QUEEN MARY UNIVERSITY OF LONDON, London (GB)
Appl. No. 17/280,202
Filed by ASSISTANCE PUBLIQUE HÔPITAUX DE MARSEILLE, Marseilles (FR); INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE), Paris (FR); UNIVERSITE D'AIX-MARSEILLE, Marseilles (FR); QUEEN MARY UNIVERSITY OF LONDON, London (GB); and SORBONNE UNIVERSITÉ, Paris (FR)
PCT Filed Sep. 26, 2019, PCT No. PCT/EP2019/075966
§ 371(c)(1), (2) Date Mar. 26, 2021,
PCT Pub. No. WO2020/064897, PCT Pub. Date Apr. 2, 2020.
Claims priority of application No. 18306253 (EP), filed on Sep. 26, 2018.
Prior Publication US 2022/0003784 A1, Jan. 6, 2022
Int. Cl. G01N 33/68 (2006.01); A61K 38/17 (2006.01); A61K 39/00 (2006.01); A61P 19/04 (2006.01); C07K 16/30 (2006.01)
CPC G01N 33/6893 (2013.01) [A61K 38/1774 (2013.01); A61P 19/04 (2018.01); C07K 16/3092 (2013.01); A61K 2039/505 (2013.01); C07K 2317/56 (2013.01); C07K 2317/565 (2013.01); G01N 2333/70596 (2013.01); G01N 2800/32 (2013.01); G01N 2800/347 (2013.01); G01N 2800/50 (2013.01); G01N 2800/7052 (2013.01)] 6 Claims
 
1. An in vitro or ex vivo method of detecting predisposition to or of diagnosing and/or prognosing cardiac or renal fibrosis in a subject, the method comprises the steps of i) determining the soluble CD146 protein expression level in a biological sample of the subject, said soluble CD146 protein being selected from SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6 and SEQ ID NO:7, ii) comparing the expression level determined at step i) with a reference value and iii) concluding that the subject has predisposition to cardiac or renal fibrosis, is affected by cardiac or renal fibrosis or has a poor prognosis of cardiac or renal fibrosis, when the level determined at step i) is higher than the reference value or concluding that the patient has no predisposition to cardiac or renal fibrosis, is not affected by cardiac or renal fibrosis or has a good prognosis of cardiac or renal fibrosis when the level determined at step i) is lower than the reference value,
said method further comprising the administration of an inhibitor of a soluble CD146 protein selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 and SEQ ID NO: 7 to a subject identified in step iii) as having predisposition to cardiac or renal fibrosis, as being affected by cardiac or renal fibrosis or as having a poor prognosis of cardiac or renal fibrosis,
wherein the inhibitor is an antibody comprising:
a) heavy chain variable region (VH) CDR polypeptide sequences of SEQ ID NO: 87, SEQ ID NO: 88, and SEQ ID NO: 89, and the light chain variable region (VL) CDR polypeptide sequences of SEQ ID NO: 90, sequence QVS and SEQ ID NO: 91;
b) a light chain variable region (VL) comprising SEQ ID NO: 93 and a heavy chain variable region (VH) comprising SEQ ID NO: 92;
c) heavy chain variable region (VH) CDR polypeptide sequences of SEQ ID NO: 94, SEQ ID NO: 95, and SEQ ID NO: 96, and the light chain variable region (VL) CDR polypeptide sequence of SEQ ID NO: 97, sequence FAS and SEQ ID NO: 98; or
d) a light chain variable region (VL) comprising SEQ ID NO: 100 and a heavy chain variable region (VH) comprising SEQ ID NO: 99.