Ose Immunotherapeutics

National Institute of Health and Medical Research

Effimune

The University of Nantes

Université D'angers

Caroline Mary

Nicolas Poirier

Bernard Vanhove

Virginie Thepenier

Sabrina Pengam

Vanessa Gauttier

Aurore Morello

Flora Coulon

Sophie Brouard

Jean-Paul Soulillou

Elise Chiffoleau

Le Hoa Mai

Marion Drouin

The invention pertains to the field of immunotherapy. The present invention provides specific humanized anti-CLEC-1A antibodies, antigen-binding fragments thereof and mimetics thereof, in particular antibodies. The compounds of the invention are able to specifically binds to CLEC-1A receptor and antagonize the binding of CLEC-1A to its endogenous ligand(s). The compounds of the invention can be used to treat deleterious conditions.

Humanized anti-CLEC-1A antibodies and antigen-binding fragments thereof

The invention relates to antibodies directed against CD127, the alpha chain of the interleukin 7 (IL-7) receptor IL-7R), and which have antagonist properties for IL-7-IL-7R interaction, may present cytotoxic activity against CD127 positive cells but do not increase the maturation of dendritic cells (DCs) induced by TSLP, a cytokine also using CD127 as part of its receptor. Alternatively, or in addition, these antibodies do not induce the internalization of CD127 and/or inhibit the IL7-induced internalization of CD127. According to another aspect of the invention antibodies are provided which recognize a human CD127 epitope comprising sequences from the 2b site of CD127, in particular the epitope comprising comprises the human CD127 sequences of domain D1 and of the 2b site of CD127, in particular the epitope comprises at least one sequence from D1 comprising SEQ ID No: 115 (in particular comprising SEQ ID No: 110) and/or SEQ ID No: 111 and/or a sequence from the 2b site comprising the sequence of SEQ ID No: 116 and optionally also comprises SEQ ID No: 117 (in particular comprises SEQ ID No: 111). The antibodies of the invention are suitable for use in order to remedy to a condition diagnosed in a human patient which results from pathogenesis related to lymphopoiesis, when IL-7 signalling pathways provide contribution to said pathogenesis, especially when an increase in the maturation, more precisely the upregulation of costimulatory molecules, of dendritic cells is undesirable.

Antibodies directed against CD127

Described herein are humanized anti-PD-1 antibodies, nucleic acids encoding such, and uses thereof in enhancing immune responses by activating T cells and treating diseases such as cancer and an infectious disease.

Humanized anti-human-PD-1 antibody and methods of using them for cancer treatment

The invention pertains to the field of immunotherapy. The present invention provides new uses of anti-SIRPg antibodies for the treatment and/or the prevention of autoimmune disorders or diseases.

Uses of anti-SIRPg antibodies

The present invention provides new anti-SIRPa antibodies able to specifically antagonize the interaction between SIRPa and CD47, without affecting the interaction between SIRPg and CD47, and their uses.

Anti-SIRPa antibodies and their therapeutic applications

The invention is in the field of antibodies useful in therapeutic and diagnostics applications targeting CD127, the alpha chain of the IL7 receptor, and provides in particular humanized monoclonal antibodies against CD127, particularly human CD127, therapeutic uses thereof, and diagnostics applications.

Antibodies and polypeptides directed against CD127

The invention is in the field of immunotherapy. The present invention provides antibodies useful in therapeutic and diagnostic applications targeting human SIRPa, said antibodies enhancing the cross-presentation of antigens to T cells. The invention also provides antibodies against specific isoforms of SIRP a and able to disrupt the interaction between those isoforms of SIRP a and human CD47 for use in treating or preventing a disease, or diagnostic applications, and methods for producing and/or selecting anti-human SIRPa antibodies that bind with different affinities to various isoforms of human SIRP members.

Use of anti-human SIRPa v1 antibodies and method for producing anti-SIRPa v1 antibodies

The present invention provides new modified anti-SIRPa antibodies linked to an immunotherapeutic agent which are bifunctional and able to specifically enhance the immune response and uses thereof.

Modified bifunctional anti-human signal regulatory protein alpha (SIRPa) antibody and method of use thereof for treating cancer

Method for treating a pathological condition involving the activation or proliferation of CD127 positive cells with an anti-CD127 antibody

Humanized anti-human-PD-1 antibody and its use in cancer treatment

The description concerns humanized antibodies directed against the extracellular domain of the alpha chain of the receptor for interleukin-7 (IL-7), especially against the receptor for human IL-7 expressed on human cells (also designated human IL-7Ralpha or IL-7Ra or CD127) and which do not interfere with the IL-7 or TSLP signaling pathways. The antibodies described do not have an antagonistic effect on the IL-7 receptor, but may still present cytotoxic activity against CD127 positive cells. In a particular embodiment, the antibody does not have an agonist effect on the IL-7 receptor.

Non-antagonistic antibodies directed against the alpha chain of the IL7 receptor extracellular domain and use thereof in cancer treatment

The invention relates to recombinant monovalent antibodies which are heterodimers of a first protein chain comprising the variable domain of the heavy chain of an antibody of interest and the CH2 and CH3 domains of an IgG immunoglobulin and a second protein chain comprising the variable domain of the light chain of said immunoglobulin of interest and the CH2 and CH3 domains of said IgG immunoglobulin. These antibodies can be used in particular as therapeutic agents in all cases where monovalent binding to a ligand such a cellular receptor is required.

Recombinant monovalent antibodies

The invention relates to antibodies directed against CD127, the alpha chain of the interleukin 7 (IL-7) receptor IL-7R), and which have antagonist properties for IL-7-IL-7R interaction, may present cytotoxic activity against CD127 positive cells but do not increase the maturation of dendritic cells (DCs) induced by TSLP, a cytokine also using CD127 as part of its receptor. Alternatively, or in addition, these antibodies do not induce the internalization of CD127 and/or inhibit the IL7-induced internalization of CD127. According to another aspect of the invention antibodies are provided which recognize a human CD127 epitope comprising sequences from the 2b site of CD127, in particular the epitope comprising comprises the human CD127 sequences of domain D1 and of the 2b site of CD127, in particular the epitope comprises at least one sequence from D1 comprising SEQ ID No: 115 (in particular comprising SEQ ID No: 10) and/or SEQ ID No: 111 and/or a sequence from the 2b site comprising the sequence of SEQ ID No: 116 and optionally also comprises SEQ ID No: 117 (in particular comprises SEQ ID No: 111). The antibodies of the invention are suitable for use in order to remedy to a condition diagnosed in a human patient which results from pathogenesis related to lymphopoiesis, when IL-7 signalling pathways provide contribution to said pathogenesis, especially when an increase in the maturation, more precisely the upregulation of costimulatory molecules, of dendritic cells is undesirable.

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Sainte Pazanne, France

Caroline Mary