Monoclonal antibodies directed against programmed death-1 protein and their use in medicine

Inventors

Sahin, Ugur • FELLERMEIER-KOPF, SINA • Gieseke, Friederike • Beckmann, Karsten • Paulmann, Claudia • Muik, Alexander • KUZMANOV, Ivan • Breij, Esther Cornelia Wilhelmina • GARRIDO CASTRO, Patricia • BLUM, Jordan • Guelen, Lars • Neijssen, Joost • DE KREUK, Bart-Jan • HIBBERT, Richard • Schuurman, Janine • Labrijn, Aran Frank

Assignees

Biontech SE • Genmab AS

Abstract

The present disclosure relates to antibodies having the ability to bind to the immune checkpoint protein programmed death-1 (PD-1), such as human PD-1, or nucleic acids encoding such antibodies, wherein the antibodies comprise modifications in the Fc region eliminating or reducing a Fc-mediated effector function of the antibodies. The present disclosure also relates to compositions or kits comprising said antibodies or nucleic acids, as well as to the use of these antibodies or nucleic acids or compositions in the field of medicine, preferably in the field of immunotherapy, e.g., for the treatment of cancers. The present invention further relates to methods for inducing an immune response in a subject comprising providing to the subject an antibody of the present disclosure or one or more nucleic acids encoding such an antibody, or a composition comprising said antibody or nucleic acids.

Core Innovation

The invention relates to a PD-1-binding antibody or antigen-binding fragment thereof comprising a heavy chain with a human IgG1 heavy chain constant region and a light chain with a light chain constant region. The human IgG1 heavy chain constant region comprises phenylalanine, glutamate, and arginine at positions corresponding to EU numbering positions 234, 235, and 236, respectively, and the antibody comprises specified heavy chain variable region and light chain variable region sequences.

The invention further defines VH HCDR1, HCDR2, and HCDR3 and VL LCDR1, LCDR2, and LCDR3 by Kabat numbering or IMGT numbering, with the sequences set forth in listed SEQ ID NO values. In one alternative, the IMGT-numbered LCDR2 comprises QAS. These sequence definitions constrain the PD-1-binding antibody architecture.

The invention also encompasses nucleic acids encoding the PD-1-binding antibody or antigen-binding fragment, and pharmaceutical compositions comprising an active agent that is either the antibody or a nucleic acid encoding the antibody together with a pharmaceutically acceptable carrier. The claimed use includes treating cancer in a subject by administering the pharmaceutical composition.

Claims Coverage

The independent claims cover four core categories: an antibody or antigen-binding fragment binding PD-1, a nucleic acid encoding the defined PD-1-binding antibody, a pharmaceutical composition comprising the antibody, and a pharmaceutical composition comprising the nucleic acid. Across these claims, the coverage is organized around a human IgG1 constant region with EU 234–236 substitutions and variable regions defined by Kabat- or IMGT-numbered HCDR/LCDR sequences using specific SEQ ID NO values.

Across the independent claims, the inventive scope centers on a PD-1-binding antibody or fragment defined by human IgG1 CH substitutions at EU numbering positions 234–236 and by VH/VL regions constrained to specified HCDR/LCDR sequences using SEQ ID NOs under either Kabat or IMGT numbering. The independent claims further extend this same antibody definition to nucleic acids encoding the antibody and to pharmaceutical compositions containing either the antibody or the encoding nucleic acid.

Stated Advantages

Documented Applications