Anti CXCR4 antibodies and their use for the treatment of cancer
AssigneePierre Fabre Medicament
InventorsChristine Klinguer-Hamour, Alexandra Jouhanneaud, Véronique Grenier-Caussanel
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Abstract
The present invention relates to a novel isolated antibody, or the derived compounds or functional fragments of same, capable of binding to CXCR4 but also of inducing conformational changed of the CXCR4 homodimers and/or heterodimers. More particularly, the present invention relates to the 414H5 and 515H7 antibodies, specific to the CXCR4 protein, as well as their use for the treatment of cancer. Pharmaceutical compositions composed of such antibodies and a process for the selection of such antibodies are also covered.
Claims43
An isolated anti-CXCR4 antibody capable of inhibiting activation of CXCR4, wherein the antibody comprises:
- a light chain comprising the CDR-L1 of the sequence SEQ ID No. 40, the CDR-L2 of the sequence SEQ ID No. 2, and the CDR-L3 of the sequence SEQ ID No. 41;
- and
- a heavy chain comprising the CDR-H1 of the sequence SEQ ID No. 44, the CDR-H2 of the sequence SEQ ID No. 5, and the CDR-H3 of the sequence SEQ ID No. 45.
A murine hybridoma deposited at the Collection Nationale de Cultures de Microorganismes (CNCM), 28 rue du Docteur Roux, 75724 Paris Cedex 15 (France), on Jun. 25, 2008, under number I-4019.
An isolated anti-CXCR4 antibody wherein the isolated antibody:
- (a) binds to a CXCR4/CXCR2 heterodimer comprising:
- (1) a human CXCR4 whose amino acid sequence is that of SEQ ID No. 29 and a human CXCR2 whose amino acid sequence is that of SEQ ID No. 31;
- or
- (2) a human CXCR4 whose amino acid sequence is that of SEQ ID No. 30 and a human CXCR2 whose amino acid sequence is that of SEQ ID No. 31;
- (b) inhibits activation of CXCR4;
- and
- (c) induces a conformational change in the heterodimer;
- and wherein the antibody comprises:
- a light chain comprising the CDR-L1 of the sequence SEQ ID No. 40, the CDR-L2 of the sequence SEQ ID No. 2, and the CDR-L3 of the sequence SEQ ID No. 41;
- and
- a heavy chain comprising the CDR-H1 of the sequence SEQ ID No. 44, the CDR-H2 of the sequence SEQ ID No. 5, and the CDR-H3 of the sequence SEQ ID No. 45.
A kit for diagnosis or prognosis of a CXCR4 expressing tumor, the kit comprising at least one anti-CXCR4 antibody, wherein the anti-CXCR4 antibody comprises, according to IMGT, i) a light chain comprising CDR regions CDR-L1, CDR-L2, and CDR-L3 comprising sequences SEQ ID Nos. 40, 2, and 41, respectively and ii) a heavy chain comprising CDR regions CDR-H1, CDR-H2, and CDR-H3 comprising sequences SEQ ID Nos. 44, 5, and 45, respectively.
A recombinant anti-CXCR4 antibody capable of inhibiting activation of CXCR4, wherein the antibody comprises:
- a light chain comprising the CDR-L1 of the sequence SEQ ID No. 40, the CDR-L2 of the sequence SEQ ID No. 2, and the CDR-L3 of the sequence SEQ ID No. 41;
- and
- a heavy chain comprising the CDR-H1 of the sequence SEQ ID No. 44, the CDR-H2 of the sequence SEQ ID No. 5, and the CDR-H3 of the sequence SEQ ID No. 45.
A recombinant anti-CXCR4 antibody wherein the recombinant antibody:
- (d) binds to a CXCR4/CXCR2 heterodimer comprising:
- (3) a human CXCR4 whose amino acid sequence is that of SEQ ID No. 29 and a human CXCR2 whose amino acid sequence is that of SEQ ID No. 31;
- or
- (4) a human CXCR4 whose amino acid sequence is that of SEQ ID No. 30 and a human CXCR2 whose amino acid sequence is that of SEQ ID No. 31;
- (e) inhibits activation of CXCR4;
- and
- (f) induces a conformational change in the heterodimer;
- and wherein the recombinant antibody comprises:
- a light chain comprising the CDR-L1 of the sequence SEQ ID No. 40, the CDR-L2 of the sequence SEQ ID No. 2, and the CDR-L3 of the sequence SEQ ID No. 41;
- and
- a heavy chain comprising the CDR-H1 of the sequence SEQ ID No. 44, the CDR-H2 of the sequence SEQ ID No. 5, and the CDR-H3 of the sequence SEQ ID No. 45.
Dependencies are inferred from the claim text.