Abstract: The present invention relates to antibodies having specificity to HER4 and uses thereof, which are able to induce biased 4ICD routing/signaling. The inventors have isolated by antibody phage display three fully human anti-HER4 single-chain variable antibody fragment (scFv), selected on human HER4 extracellular domain, referred as C6 mAb, D5 mAb and F4 mAb and one fully human anti-HER4 scFv named H2 mAb, selected on NRG 1?1-stimulated EGFR/HER4 JMaCYT1-transfected NIH3T3 cells. In particular, the present invention relates to an isolated anti-HER4 antibody, wherein said antibody binds to an epitope of the HER4 protein.

Abstract: In ovarian carcinoma, Müllerian Inhibiting Substance (MIS) type II receptor (MISRII) and the MIS/MISRII signaling pathway are potential therapeutic targets. Conversely, the role of the three MIS type I receptors (MISRI; ALK2, ALK3 and ALK6) in this cancer needs to be clarified. Using four ovarian cancer cell lines and ovarian cancer cells isolated from patients' tumor ascites, the inventors found that ALK2 and ALK3 are the two main MISRIs involved in MIS signaling at low and high MIS concentrations, respectively. Moreover, high MIS concentrations were associated with apoptosis and decreased clonogenic survival, whereas low MIS concentrations improved cancer cell viability. Finally, the inventors showed that anti-MIS antibody B10 inhibited MIS pro-survival effect. These last results open the way to an innovative therapeutic approach to suppress MIS proliferative effect, instead of administering high doses of MIS to induce cancer cell apoptosis.

Abstract: In ovarian carcinoma, Müllerian Inhibiting Substance (MIS) type II receptor (MISRII) and the MIS/MISRII signaling pathway are potential therapeutic targets. Conversely, the role of the three MIS type I receptors (MISRI; ALK2, ALK3 and ALK6) in this cancer needs to be clarified. Using four ovarian cancer cell lines and ovarian cancer cells isolated from patients' tumor ascites, the inventors found that ALK2 and ALK3 are the two main MISRIs involved in MIS signaling at low and high MIS concentrations, respectively. Moreover, high MIS concentrations were associated with apoptosis and decreased clonogenic survival, whereas low MIS concentrations improved cancer cell viability. Finally, the inventors showed that MIS siRNA inhibited MIS pro-survival effect. These last results open the way to an innovative therapeutic approach to suppress MIS proliferative effect, instead of administering high doses of MIS to induce cancer cell apoptosis.

Abstract: The present disclosure relates to a neuregulin non competitive allosteric anti-human-HER3 antibody having a human constant region; and less than 65% of the glycan structures carried by the glycosylation site of the antibody comprises a fucose molecule. The antibody is characterized by its variable sequences.

Abstract: The invention concerns antibody formats comprising VH sequence of Camelidae, such as llamas; antibodies of various formats have anti-CEA or anti-CD16 VH sequences thereof; vectors expressing the antibody formats, and methods for producing the same.

Abstract: The present disclosure relates to bispecific antibodies targeting EGFR and HER2, and methods for the production of these antibodies. The bispecific antibodies consist of one complete antibody on which two VH-VL chains are attached via a linker to each NH terminal region of both VH chains of the antibody. The bispecific antibodies constructed use the amino acid sequences of the heavy chain (VH) and the light chain (VL) variable regions of two monoclonal antibodies targeting EGFR and HER2, namely cetuximab and trastuzumab, respectively.

Abstract: The present disclosure relates to neuregulin (NRG)-non competitive allosteric anti-human-HER3 antibodies and uses thereof in diagnostic and therapeutic methods.

Abstract: The disclosure relates to human anti-NRG1 neutralizing monoclonal antibodies that do not interfere with the NRG1 binding to the HER3 receptor and uses thereof. More particularly, an isolated human monoclonal antibody comprising a heavy and light chain variable regions with specific CDRs defined by their sequences is disclosed.

Abstract: The present disclosure relates to a neuregulin non competitive allosteric anti-human-HER3 antibody having a human constant region; and less than 65% of the glycan structures carried by the glycosylation site of the antibody comprises a fucose molecule. The antibody is characterized by its variable sequences.

Abstract: The invention relates to the combined use of anti-EGFR antibodies and anti-Her2 antibodies for the treatment of cancer, especially suitable for cancer expressing high levels of the EGFR type and low levels of HER2. The invention refers in particular monoclonal antibody “trastuzumab” (HERCEPTIN®) directed against the HER2 receptors the efficacy of which can be significantly increased in vivo when combined with monoclonal antibody “matuzumab” (hmAB 425, EMD 72000) directed against EGF receptors. The combination treatment is suitable for patients suffering from cancer having said receptor profile, preferably pancreatic cancer.

Abstract: The present disclosure relates to neuregulin (NRG)-non competitive allosteric anti-human-HER3 antibodies and uses thereof in diagnostic and therapeutic methods.

Abstract: The present invention relates to monoclonal antibodies and fragment thereof directed against the human Anti-Müllerian Hormone type II receptor (AMHR-II) and their use for treating and diagnosing cancer diseases, such as ovarian cancers.

Abstract: The present invention relates to anti-Axl antibodies and uses thereof in diagnostic and therapeutic methods. More particularly, the present invention relates to a monoclonal antibody having specificity for Axl comprising an heavy chain variable region comprising SEQ ID NO:2 in the H-CDR1 region, SEQ ID NO:3 in the H-CDR2 region and SEQ ID NO:4 in the H-CDR3 region; and a light chain variable region comprising SEQ ID NO: 6 in the L-CDR1 region, SEQ ID NO:7 in the L-CDR2 region and SEQ ID NO:8 in the L-CDR3 region. Said monoclonal antibody binds to the extracellular domain of Axl via, SEQ ID NO:9 and SEQ ID NO: 10.

Abstract: The invention relates to antibodies against HER3 and their use in the treatment of cancer.

Abstract: The invention concerns antibody formats comprising VHsequence of Camelidae, such as llamas; antibodies of various formats have anti-CEA or anti-CD16 VH sequences thereof; vectors expressing the antibody formats, and methods for producing the same.

Abstract: The present invention relates to anti-Axl antibodies and uses thereof in diagnostic and therapeutic methods. More particularly, the present invention relates to a monoclonal antibody having specificity for Axl comprising an heavy chain variable region comprising SEQ ID NO:2 in the H-CDR1 region, SEQ ID NO:3 in the H-CDR2 region and SEQ ID NO:4 in the H-CDR3 region; and a light chain variable region comprising SEQ ID NO: 6 in the L-CDR1 region, SEQ ID NO:7 in the L-CDR2 region and SEQ ID NO:8 in the L-CDR3 region. Said monoclonal antibody binds to the extracellular domain of Axl via, SEQ ID NO:9, SEQ ID NO: 10 and SEQ ID NO: 11.

Abstract: The invention concerns an in-vitro method for introducing a targeted genome modification into an oocyte or an egg and a method for performing a random insertion in the genome of a host cell.

Abstract: The present invention provides for isolated anti-human-HER3 antibodies or fragments thereof. More particularly the present invention provides an isolated monoclonal antibody that specifically binds to the extracellular domain of HER-3 and competes for binding to the extracellular domain of human HER-3 with the antibody produced obtainable from hybridoma deposited as CNCM-I-4486. The antibodies described in the present invention are useful for the treatment of cancer.

Abstract: The invention relates to the combined use of anti-EGFR antibodies and anti-Her2 antibodies for the treatment of cancer, especially suitable for cancer expressing high levels of the EGFR type and low levels of HER2. The invention refers in particular monoclonal antibody “trastuzumab” (HERCEPTIN®) directed against the HER2 receptors the efficacy of which can be significantly increased in vivo when combined with monoclonal antibody “matuzumab” (hmAB 425, EMD 72000) directed against EGF receptors. The combination treatment is suitable for patients suffering from cancer having said receptor profile, preferably pancreatic cancer.

Abstract: The present invention relates to anti-Axl antibodies and uses thereof in diagnostic and therapeutic methods. More particularly, the present invention relates to a monoclonal antibody having specificity for Axl comprising an heavy chain variable region comprising SEQ ID NO:2 in the H-CDR1 region, SEQ ID NO:3 in the H-CDR2 region and SEQ ID NO:4 in the H-CDR3 region; and a light chain variable region comprising SEQ ID NO: 6 in the L-CDR1 region, SEQ ID NO:7 in the L-CDR2 region and SEQ ID NO:8 in the L-CDR3 region. Said monoclonal antibody binds to the extracellular domain of Axl via, SEQ ID NO:9, SEQ ID NO: 10 and SEQ ID NO: 11.