US 2018/0022811 A1 · Chemokine receptor binding polypeptides

Chemokine receptor binding polypeptides

AssigneeNovartis AG

InventorsZarin Brown, Michelle Bradley, Steven John Charlton, Gino Anselmus Van Heeke, Karen Cromie, Bruno Dombrecht, Soren Steffensen, Judith Baumeister, Marie-Paule Bouche, Carlo Boutton, Marie-Ange Buyse, Veerle Snoeck, Stephanie Staelens

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Abstract

The present invention relates to polypeptides directed against or specifically binding to chemokine receptor CXCR2 and in particular to polypeptides capable of modulating signal transduction from CXCR2. The invention also relates to nucleic acids, vectors and host cells capable of expressing the polypeptides of the invention, pharmaceutical compositions comprising the polypeptides and uses of said polypeptides and compositions for treatment of diseases involving aberrant functioning of CXCR2.

Claims4

Dependent claims

1-51. (canceled)

A method of treating chronic obstructive pulmonary disease (COPD) or exacerbations of (COPD) comprising administering to a subject a therapeutically effective amount of a polypeptide selected from:

a) a polypeptide comprising the amino acid sequence of SEQ ID NO:221 and a C-terminal extension consisting of two alanine residues;
b) a polypeptide comprising the amino acid sequence of SEQ ID NO:222 and a C-terminal extension consisting of two alanine residues;
c) a polypeptide comprising the amino acid sequence of SEQ ID NO:223 and a C-terminal extension consisting of two alanine residues;
d) a polypeptide comprising the amino acid sequence of SEQ ID NO:224 and a C-terminal extension consisting of two alanine residues;
e) a polypeptide comprising a first antigen binding domain comprising the amino acid sequence of SEQ ID NO:219, and a second antigen binding domain comprising the amino acid sequence of SEQ ID NO:215, wherein the first antigen binding domain and second antigen binding domain are separated by a linker comprising the amino acid sequence of SEQ ID NO:220, and a C-terminal extension consisting of two alanine residues;
f) a polypeptide comprising the amino acid sequence of SEQ ID NO:225 and a C-terminal extension consisting of two alanine residues;
g) a polypeptide comprising a first antigen binding domain comprising the amino acid sequence of SEQ ID NO:216, and a second antigen binding domain comprising the amino acid sequence of SEQ ID NO:217, wherein the first antigen binding domain and second antigen binding domain are separated by a linker comprising the amino acid sequence of SEQ ID NO:220, and a C-terminal extension consisting of two alanine residues;
or
h) a polypeptide comprising a first antigen binding domain, wherein the first antigen binding domain comprises three CDRS comprising the amino acid sequences of SEQ ID NOs:141, 236, and 181, a second antigen binding domain, wherein the second antigen binding domain comprises three CDRS comprising the amino acid sequences of SEQ ID NOs:
146, 237, and 186, wherein the first antibody binding domain and second antigen binding domain are separated by a linker comprising the amino acid sequence of SEQ ID NO:220, and a C-terminal extension consisting of two alanine residues;
or a pharmaceutical composition comprising one or more of the polypeptides of a)-h) and a pharmaceutically acceptable carrier or diluent.

8 more elements

A method of treating a condition selected from the group consisting of Cystic Fibrosis, Asthma, in particular severe Asthma and exacerbations of Asthma, Acute lung injury, Acute respiratory distress syndrome, Idiopathic pulmonary fibrosis, Airway remodeling, Bronchiolitis obliterans syndrome or Bronchopulmonary dysplasis comprising administering to a subject a therapeutically effective amount of a polypeptide selected from:

a) a polypeptide comprising the amino acid sequence of SEQ ID NO:221 and a C-terminal extension consisting of two alanine residues;
b) a polypeptide comprising the amino acid sequence of SEQ ID NO:222 and a C-terminal extension consisting of two alanine residues;
c) a polypeptide comprising the amino acid sequence of SEQ ID NO:223 and a C-terminal extension consisting of two alanine residues;
d) a polypeptide comprising the amino acid sequence of SEQ ID NO:224 and a C-terminal extension consisting of two alanine residues;
e) a polypeptide comprising a first antigen binding domain comprising the amino acid sequence of SEQ ID NO:219, and a second antigen binding domain comprising the amino acid sequence of SEQ ID NO:215, wherein the first antigen binding domain and second antigen binding domain are separated by a linker comprising the amino acid sequence of SEQ ID NO:220, and a C-terminal extension consisting of two alanine residues;
f) a polypeptide comprising the amino acid sequence of SEQ ID NO:225 and a C-terminal extension consisting of two alanine residues;
g) a polypeptide comprising a first antigen binding domain comprising the amino acid sequence of SEQ ID NO:216, and a second antigen binding domain comprising the amino acid sequence of SEQ ID NO:217, wherein the first antigen binding domain and second antigen binding domain are separated by a linker comprising the amino acid sequence of SEQ ID NO:220, and a C-terminal extension consisting of two alanine residues;
or
h) a polypeptide comprising a first antigen binding domain, wherein the first antigen binding domain comprises three CDRS comprising the amino acid sequences of SEQ ID NOs:141, 236, and 181, a second antigen binding domain, wherein the second antigen binding domain comprises three CDRS comprising the amino acid sequences of SEQ ID NOs:
146, 237, and 186, wherein the first antibody binding domain and second antigen binding domain are separated by a linker comprising the amino acid sequence of SEQ ID NO:220, and a C-terminal extension consisting of two alanine residues;
or a pharmaceutical composition comprising one or more of the polypeptides of a)-h) and a pharmaceutically acceptable carrier or diluent.

8 more elements

A method of treating a condition selected from the group consisting of Atherosclerosis, Glomerulonephritis, Inflammatory Bowl Disease (Crohn's), Angiogenesis and diseases characterised by new blood vessel development including Macular degeneration, Diabetic retinopathy and Diabetic neuropathy, Multiple sclerosis, Psoriasis, Pyoderma Gangrenosum, Age-related Macula degenerative disease, Ocular Behcet Disease, Uveitis, Pulmonary Arterial Hypertension (PAH) including idiopathic PAH, familial PAH and associated PAH, Chronic inflammatory diseases, Rhenumatoid arthritis, Osteoarthritis, non-small cell carcinoma, Colon cancer, Pancreatic cancer, Esophageal cancer, Ovarian cancer, Breast cancer, Solid tumors and Metasases, Melanoma, Hepatocellular carcinoma, Ischaemia perfusion injury Hemolytic transfusion induced-vaso-occlusion crisis in Sickle cell disease, Ischemia/reperfusion injury, Acute stroke/myocardial infarct, Closed head injury, Posttraumatic inflammation and Insulin resistant diabetes comprising administering to a subject an effective amount of a polypeptide selected from:

a) a polypeptide comprising the amino acid sequence of SEQ ID NO:221 and a C-terminal extension consisting of two alanine residues;
b) a polypeptide comprising the amino acid sequence of SEQ ID NO:222 and a C-terminal extension consisting of two alanine residues;
c) a polypeptide comprising the amino acid sequence of SEQ ID NO:223 and a C-terminal extension consisting of two alanine residues;
d) a polypeptide comprising the amino acid sequence of SEQ ID NO:224 and a C-terminal extension consisting of two alanine residues;
e) a polypeptide comprising a first antigen binding domain comprising the amino acid sequence of SEQ ID NO:219, and a second antigen binding domain comprising the amino acid sequence of SEQ ID NO:215, wherein the first antigen binding domain and second antigen binding domain are separated by a linker comprising the amino acid sequence of SEQ ID NO:220, and a C-terminal extension consisting of two alanine residues;
f) a polypeptide comprising the amino acid sequence of SEQ ID NO:225 and a C-terminal extension consisting of two alanine residues;
g) a polypeptide comprising a first antigen binding domain comprising the amino acid sequence of SEQ ID NO:216, and a second antigen binding domain comprising the amino acid sequence of SEQ ID NO:217, wherein the first antigen binding domain and second antigen binding domain are separated by a linker comprising the amino acid sequence of SEQ ID NO:220, and a C-terminal extension consisting of two alanine residues;
or
h) a polypeptide comprising a first antigen binding domain, wherein the first antigen binding domain comprises three CDRS comprising the amino acid sequences of SEQ ID NOs:141, 236, and 181, a second antigen binding domain, wherein the second antigen binding domain comprises three CDRS comprising the amino acid sequences of SEQ ID NOs:
146, 237, and 186, wherein the first antibody binding domain and second antigen binding domain are separated by a linker comprising the amino acid sequence of SEQ ID NO:220, and a C-terminal extension consisting of two alanine residues;
or a pharmaceutical composition comprising one or more of the polypeptides of a)-h) and a pharmaceutically acceptable carrier or diluent.

8 more elements

Dependencies are inferred from the claim text.