argenx BV

Methods for preparing engineered antibodies exhibiting improved pH-dependent antigen binding are disclosed. The methods are based on introduction of histidine residues at a subset of defined amino acid positions within the antibody CDRs. The set of amino acid positions selected for histidine substitution is derived from a heat-map of histidine occurrence within the CDRs of functional antibodies from a natural antibody repertoire. The methods provide a simpler and less time-consuming approach to the identification of pH-dependent antibody variants.

The present invention relates to combination therapies and to their use in the treatment of chronic airway disease, particularly use in the treatment of asthma. The combination therapies comprise (i) an antagonist of IL-5:IL-5R and (ii) an antagonist of IL-4:IL-4R and/or an antagonist of IL-13:IL-13R. The present invention also provides bispecific antibodies comprising an antigen binding domain that binds to IL-4Rα and an antigen binding domain that binds to IL-5. The bispecific antibodies may be used for the treatment of chronic airway disease, particularly asthma.

Provided are an antibody or antigen binding fragment thereof that binds to CD70 for use in treating a myeloid malignancy in a human subject, who is resistant to BCL-2 inhibitor treatment and methods of treating a myeloid malignancy in a subject, said method comprising (a) selecting a human subject having a myeloid malignancy that has a reduced sensitivity or is refractory to a BCL-2 inhibitor; and (b) administering to the subject an antibody or antigen binding fragment thereof that binds to CD70. In certain embodiments, the myeloid malignancy is acute myeloid leukemia (AML). In certain embodiments, the antibody that binds to CD70 is cusatuzumab. In certain embodiments, a BCL-2 inhibitor is co-administered with the antibody or antigen binding fragment thereof that binds to CD70. In certain embodiments, the BCL-2 inhibitor is venetoclax.

The present invention provides binding molecules (e.g., antibodies or antigen binding fragments thereof) that specifically bind to and inhibit the biological activity of IL-6 (e.g., human, mouse and non-human primate IL-6). In a preferred embodiment, the antibodies or antigen binding fragments of the invention bind to IL-6 and inhibit its binding to an IL-6 receptor. Such antibodies or antigen binding fragments are particularly useful for treating IL-6-associated diseases or disorders (e.g., inflammatory disease and cancer).

The instant disclosure provides isolated antibodies that specifically bind to IL-9 (e.g., human IL-9 or mouse IL-9). Also provided are pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies.

The present invention provides combinations and methods using same for the treatment of malignancy, particularly a myeloid malignancy such as acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), chronic myeloid leukemia (CML), and chronic myelomonocytic leukemia (CMML). The combination may comprise an antibody or antigen-binding fragment thereof that binds to CD70, and an inhibitor of BCL-2. In certain embodiments, the antibody is ARGX-110 (cusatuzumab). In certain embodiments, the BCL-2 inhibitor is venetoclax. In certain embodiments, the combination provides synergistic treatment of AML. The combination may additionally comprise at least one additional anti-cancer agent.

The present invention relates to antagonists, particularly antibodies and antigen binding fragments thereof, that bind to the protein galectin-10, particularly human galectin-10. The galectin-10 antagonists disrupt the crystallization of galectin-10 and are therefore useful in methods of preventing and treating diseases and conditions wherein the pathology is linked to the formation/presence of Charcot-Leyden crystals (CLCs).

The present invention relates to combination therapies for the treatment of malignancy, particularly myeloid malignancy such as acute myeloid leukemia (AML). The combination therapies may include an antibody molecule that binds to CD70 and at least one antibody molecule that binds to a leukemic stem cell target. Preferred leukemic stem cell targets are TIM-3, IL1R3/1L1RAP and CD47.

Provided are antibodies and antigen-binding fragments thereof that bind specifically to human complement factor C2 and are capable of inhibiting activation of the classical and lectin pathways of the complement system. The antibodies and antigen-binding fragment exhibit improved manufacturability, pharmacokinetics, and antigen sweeping. Also provided are pharmaceutical compositions comprising the antibodies and antigen-binding fragments, nucleic acids and vectors encoding the antibodies and antigen-binding fragments, host cells comprising the nucleic acids or vectors, and methods of making and using the antibodies and antigen-binding fragments. The antibodies and antigen-binding fragments can be used to inhibit the classical pathway of complement activation in a subject, e.g., a human. The antibodies and antigen-binding fragments can also be used to inhibit the lectin pathway of complement activation in a subject, e.g., a human.

The present invention provides binding molecules (e.g., antibodies or antigen binding fragments thereof) that specifically bind to and inhibit the biological activity of IL-6 (e.g., human, mouse and non-human primate IL-6). In a preferred embodiment, the antibodies or antigen binding fragments of the invention bind to IL-6 and inhibit its binding to an IL-6 receptor. Such antibodies or antigen binding fragments are particularly useful for treating IL-6-associated diseases or disorders (e.g., inflammatory disease and cancer).