The invention relates to bivalent bispecific monoclonal antibodies (bbmAb) or variants thereof for use in the treatment or for use in alleviating the symptoms of an NLRC4 inflammasomopathy, such as an NLRC4-GOF inflammasomopathy in a subject in need thereof. This invention also relates to bivalent bispecific monoclonal antibodies (bbmAb) or variants thereof for use in the treatment or for use in alleviating the symptoms of AIFEC in a subject in need thereof.

Monoclonal antibody that specifically binds IL-1RAcP, or an antigen binding fragment thereof, comprising: a) a heavy chain variable region (VH) comprising CDR1H, CDR2H and/or CDR3H, wherein the CDR1H region comprises an amino acid sequence selected from the group of SEQ ID NO: 155-231, wherein the CDR2H region comprises an amino acid sequence selected from the group of SEQ ID NO: 232-308, and wherein the CDR3H region comprises an amino acid sequence selected from the group of SEQ ID NO: 309-385; and b) a light chain variable region (VL) comprising CDR1L, CDR2L and/or CDR3L, wherein the CDR1L region comprises an amino acid sequence selected from the group of SEQ ID NO: 386-462, wherein the CDRL2 region comprises an amino acid sequence selected from the group of SEQ ID NO: 463-539, and wherein the CDR3L region comprises an amino acid sequence selected from the group of SEQ ID NO: 540-616

The monoclonal antibody is characterized in that it inhibits IL-1RAcP induced NFkB activity, useful in treatment of IL-1RAcP related diseases.

Herein is reported a method for producing an antibody-multimer-fusion polypeptide comprising (a) an antibody heavy chain and an antibody light chain, and (b) a first fusion polypeptide comprising in N- to C-terminal direction a first part of a non-antibody multimeric polypeptide, an antibody heavy chain CH1 domain or an antibody light chain constant domain, an antibody hinge region, an antibody heavy chain CH2 domain and an antibody heavy chain CH3 domain, and a second fusion polypeptide comprising in N- to C-terminal direction the second part of the non-antibody multimeric polypeptide and an antibody light chain constant domain if the first polypeptide comprises an antibody heavy chain CH1 domain or an antibody heavy chain CH1 domain if the first polypeptide comprises an antibody light chain constant domain, wherein (i) the antibody heavy chain of (a) and the first fusion polypeptide of (b), (ii) the antibody heavy chain of (a) and the antibody light chain of (a), and (iii) the first fusion polypeptide of (b) and the second fusion polypeptide of (b) are each independently of each other covalently linked to each other by at least one disulfide bond, characterized in that the antibody-multimer-fusion is expressed by a recombinant mammalian cell obtained by transfecting a mammalian cell with the expression cassettes for the antibody heavy chain, the antibody light chain, the first fusion polypeptide and the second fusion polypeptide at a stoichiometric ratio of 1:1:2:1.

The present invention relates to a method for treating or alleviating the symptoms of peripheral arterial disease (PAD) in a subject, comprising administering about 25 mg to about 300 mg of an IL-1β binding antibody or functional fragment thereof.

The present disclosure relates to inhalable dry powder formulations comprising one or more antibodies or one or more angiogenesis inhibiting active pharmaceutical ingredients, methods of manufacture of such compositions, e.g., via spray drying, as well as their local administration to the lung for use in the treatment, prevention and/or delay of progression of asthma, COPD, lung infections, cystic fibrosis, or lung cancer.

It has been discovered that lung tumor growth is associated with a dysregulation of the local microbiota, including an increased total bacterial load and reduced bacterial diversity in the airway. In the lungs, commensal bacteria, which are otherwise non-pathogenic and colonize pulmonary tissue at a much lower density in healthy individuals, provoke chronic inflammation and exacerbation of lung cancer through tumor-infiltrating immune cells. Thus, targeting the lung microbiota and its responding immune pathways is useful in treating lung cancer. Disclosed are compositions and methods targeting the lung microbiota and its responding immune pathways in a subject by specific targeting of commensal bacteria in the subject. Typically, the methods involve administering an effective amount of one or more therapeutics such as an antibiotic that reduces the local bacterial load, blocks or depletes tumor-infiltrating immune cells, and/or locally inhibits one or more cytokines or chemokines.

Hidradenitis suppurativa can be treated by administering a pharmaceutical composition that includes a pharmaceutically acceptable carrier and a therapeutically effective amount of an agent that selectively binds IL-1α.

Bispecific binding proteins that bind IL-1β or IL-1R and a checkpoint protein are provided, together with methods of making the proteins. The checkpoint protein may be PD-1 or PD-L1. The binding proteins may have immunoglobulin-like structures that contain human Fab or scFv domains. A novel bispecific antibody format is provided. Methods of making the binding proteins are provided, together with pharmaceutical compositions containing the proteins. The binding proteins and pharmaceutical compositions may be used for treating or preventing diseases such as cancer.

Use of an IL-Iβ binding antibody or a functional fragment thereof, especially canakinumab or a functional fragment thereof, or gevokizumab or a functional fragment thereof, and biomarkers for the treatment of cancer with at least partial inflammatory basis, e.g., CML.

Hidradenitis suppurativa can be treated by administering a pharmaceutical composition that includes a pharmaceutically acceptable carrier and a therapeutically effective amount of an agent that selectively binds IL-1α.