Novimmune Sa

Giovanni Magistrelli

Nicolas Fischer

Krzysztof Masternak

Greg Elson

Ulla Ravn

Franck Gueneau

Pauline Malinge

Francois Rousseau

Limin Shang

Nicolas Fouque

Yves Poitevin

Jean-Francois Depoisier

Xavier Chauchet

François Rousseau

This disclosure provides novel bispecific antibodies that specifically bind to CD47 and Programmed Death-Ligand 1 (PD-L1). The disclosure further relates to methods of making the bispecific antibodies and nucleic acids encoding the antibodies. The disclosure further relates to therapeutic methods for use of the bispecific antibodies in the treatment of a condition associated with malignant cells expressing CD47 and/or PD-L1.

Bispecific antibodies targeting CD47 and PD-L1 and methods of use thereof

The invention relates to the generation of multispecific antibody mixtures include a subset of antibodies isolated from a mixture of two or more monospecific antibodies and one or more bispecific antibodies, wherein all antibodies in the subset have the same common heavy chain. The invention also relates to methods of isolating, purifying, or otherwise producing such a subset of antibodies by using at least one affinity chromatography step. The invention also relates to methods of using such a subset of antibodies in a variety of therapeutic indications.

Generating multispecific antibody mixtures and methods of uses thereof

The invention provides heterodimer bispecific antigen-binding molecules that include a first polypeptide that does not include an IgG CH1 domain and a second polypeptide where there is at least one mutation in the IgG CH3 domain that abolishes the ability of the second polypeptide to bind CH3-specific affinity media such that the first and second polypeptides have different affinities with respect to CH1 and CH3 specific affinity reagents that allows rapid isolation by differential binding. The invention also provides bispecific antibodies that have CH1 and CH3 regions with different affinities with respect to affinity reagents that allows rapid isolation by differential binding. The invention also concerns bispecific antibodies which are heterodimers of two IgG heavy chains that differ by at least two amino acids that allow for rapid isolation based on a differential affinity of one mutated heavy chain and a second mutated heavy chain toward two different affinity reagents.

Readily isolated bispecific binding molecules with native format having mutated constant regions

The disclosure relates to monoclonal antibodies and antigen binding fragments, variants, multimeric versions, or bispecifics thereof that specifically bind CD3 epsilon (CD3&#x3b5;), as well as methods of making and using these anti-CD3&#x3b5; antibodies and antigen binding fragments thereof in a variety of therapeutic, diagnostic and prophylactic indications.

Anti-CD3 epsilon antibodies and methods of use thereof

The invention provides novel bispecific monoclonal antibodies carrying a different specificity for each binding site of the immunoglobulin molecule and methods for producing novel bispecific monoclonal antibodies carrying a different specificity for each binding site of the immunoglobulin molecule. The antibodies are composed of a single heavy chain and two different light chains, one containing a Kappa constant domain and the other of a Lambda constant domain. The invention provides methods for the isolation of antibodies of different specificities but sharing a common heavy chain. The invention also provides methods for the controlled co-expression of two light chains and a single heavy chain leading to the assembly of monospecific and bispecific antibodies. The invention provides a mean of producing a fully human bispecific and bivalent antibody that is unaltered in sequence and does not involve the use of linkers or other non-human sequences, as well as antibody mixtures of two monospecific antibodies and one bispecific antibody. The invention also provides the means of efficiently purifying the bispecific antibody.

Methods for the generation of multispecific and multivalent antibodies

The invention relates to antigen-binding proteins or antibodies having heterodimers of heavy chains, i.e., two immunoglobulin heavy chains that differ by at least one or two amino acid(s) that allows for isolation of the antigen-binding protein based on a differential affinity of an immunoglobulin heavy chain and a modified/mutated immunoglobulin heavy chain toward an affinity reagent. The invention also relates antigen-binding proteins, including bispecific antibodies, having IgG CH1 regions with different affinities with respect to affinity reagent(s) that allows rapid isolation by differential binding of the IgG regions to the affinity reagent(s).

Readily isolated bispecific antibodies with native immunoglobulin format

Methods are provided to improve the expression of protein complexes by tuning the expression levels of each component required for the assembly of the complex. These methods are effective in limiting the expression of the dominant chain and, thus, equilibrating their relative abundance. The methods provided herein lead to a significant increase in productivity and final bispecific yields both in transient expression systems as well as in stably transfected mammalian cells.

Method for optimizing the assembly and production of hetero-multimeric protein complexes

The invention provides methods of purifying antibodies using various antibody-specific purification media to rapidly and efficiently separate mixtures of antibodies, antibody fragments and/or antibody components to isolate a desired antibody product from the mixture. The invention relates to the purification of bispecific monoclonal antibodies carrying a different specificity for each binding site of the immunoglobulin molecule, e.g., antibodies composed of a single heavy chain and two different light chains, one containing a Kappa constant domain and the other a Lambda constant domain, including antibodies of different specificities that share a common heavy chain. The invention also provides the methods of efficiently purifying intact antibodies by separating the intact antibody from non-intact antibodies including free light chains.

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Cessy, France

Giovanni Magistrelli