Multivalent peptide conjugates for sustained intra-articular treatment of joint inflammation

A method of treating a disease or disorder in an articular joint, the method comprising injecting into the articular joint an effective amount of a conjugate comprising:

• a biocompatible polymer having a molecular weight of from about 0.8 MDa to about 3 MDa;
• and a plurality of peptides, wherein the peptide has a molecular weight of from about 5 kDa to about 150 kDa;
• wherein
• the biocompatible polymer is hyaluronic acid,
• each peptide is covalently linked to the polymer,
• the peptide is covalently linked to the polymer via a sulfide bond and a linker having a molecular weight of from about 100 Da to about 500 Da,
• the peptide is a monoclonal IgG antibody, an IgG antibody fragment, a single-chain variable region antibody, a single-domain heavy chain antibody, an adnectin, an affibody, an anticalin, a DARPin, a Kunitz-type inhibitor, or a receptor decoy,
• the peptide has an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10 and SEQ ID NO:11,
• the molar ratio of the peptide to the polymer in the conjugate is at least about 5:1, and
• the disease or disorder is rheumatoid arthritis, wear-related osteoarthritis, age-related osteoarthritis, post-traumatic osteoarthritis, psoriatic arthritis, aseptic implant loosening, joint effusion, ankylosing spondylitis, bursitis, gout, reactive arthritis, synovitis, or avascular necrosis.