Ose Immunotherapeutics

Institut National De La Sante Et De La Recherche Medicale

Université De Nantes

Assistance Publique-Hopitaux De Paris

Inserm (Institut National De La Sante Et De La Recherche Medicale)

Etablissement Francais Du Sang

Centre Hospitalier Universitaire De Nantes

Effimune

Université D'angers

Nantes Université

Inserm

Nicolas Poirier

Bernard Vanhove

Caroline Mary

Vanessa Gauttier

Virginie Thepenier

Sabrina Pengam

Elise Chiffoleau

Géraldine Teppaz

Aurore Morello

Sophie Brouard

Jean-Paul Soulillou

Richard Danger

Sebastien Maury

Geraldine Teppaz

Sylvie Chevalier

Hugues Gascan

José Cohen

Caroline Pilon

Brigitte Birebent

Marion Drouin

Le Hoa Mai

Isabelle Girault

Josy-Anne Froger

Yannick Danger

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 invention relates to methods and preparations for sorting out T effector cells from human leukocytes using anti-CD127 antibodies. Accordingly the invention relates to the use of anti-CD127 antibodies enabling discriminative depletion of subpopulations of Tregulatory cells expressing CD127+ at low levels in a population of human T lymphocytes in order to enable the use of the recovered selected cell preparations comprising essentially Teffector cells as lymphocytes and preferably devoid of Tregulatory cells, for improved efficacy in particular when administered to a patient for therapy.

Method effector cells using anti-CD127 antibodies for applications in cell therapy

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 present invention relates to methods for promoting T cells response. The inventors examined the expression and function of CLEC-1 in human DCs and demonstrated for the first time a cell-surface expression. They investigated its functional role following triggering on orchestration of T-cell responses. The inventors showed in vitro and in vivo with CLEC-1 deficient rats and rat CLEC-1 Fc fusion protein that disruption of CLEC-1 signalling enhances in vitro Th17 activation and in vivo enhances T cell priming and Th17 and Th1 activation. In particular, the present invention relates to CLEC-1 antagonists for promoting T cells response in a subject in need thereof.

Method of promoting a t-cell response or treating cancer by administering an antagonist to human c-type lectin-like receptor-1 (CLEC-1)

The invention relates to the identification of biomarkers of the response status of a patient for a treatment with anti-TN-Falpha agents, for treatment with anti-α4β7 agents or with both anti-TNFalpha agent and anti-α4β7 agents and to their use in assessing such status, in particular for assessing nonresponsive status for a treatment with anti-TNFalpha agents or respectively with anti-α4β7 agent in human patients suffering from inflammatory condition or disease, in particular Inflammatory Bowel Disease (IBD), in particular Ulcerative Colitis or Crohn's disease. The invention describes a method of in vitro assessing whether a treatment with anti-TNFalpha agent or with anti-α4β7 agent may be useful in a human patient suffering from inflammatory condition or disease, in particular when said condition or disease is a chronic and/or relapsing one, particularly a gastrointestinal, more particularly intestinal, inflammatory condition or disease which is eligible for treatment with anti-TNFalpha agent or respectively with anti-α4β7 agent. In a specific embodiment the method is suitable to assess whether such patient would be non-responsive to treatment with such anti-TNFalpha agent or respectively with anti-α4β7 agent and comprising determining a molecular signature in a biological sample previously obtained from said human patient.

Biomarkers for assessing the response status for treatment of Inflammatory condition or disease affecting the digestive tract such as inflammatory bowel disease in human patients

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

Methods for promoting t cells response by administering an antagonist of human c-type lectin-like receptor 1 (CLEC-1)

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

Growing community of inventors

Treillieres, France

Nicolas Poirier