Methods for treatment of rheumatoid arthritis and accelerated atherosclerosis with an anti-Apo B100 antibody

Inventors

Liang, Bertrand C. • Ruiz, Stacey • Farina, Christopher John

Assignees

Abcentra LLC

Abstract

Compositions and methods for treating rheumatoid arthritis and/or accelerated atherosclerosis are provided, including an inhibitor of oxidized or malondialdehyde-modified low density lipoprotein (LDL) for administration to a subject. Exemplary inhibitors of oxidized LDL include an anti-oxidized LDL antibody, which results in a reduction in the secretion of pro-inflammatory cytokine from primary monocyte in vitro and the plasma cytokine level of inflammatory cytokine in vivo.

Core Innovation

The invention relates to anti-ApoB100 antibody therapy for treating rheumatoid arthritis and/or accelerated atherosclerosis and for reducing the likelihood of developing inflammation. The antibody targets an ApoB100 fragment defined as native, oxidized, and/or malondialdehyde (MDA)-modified epitopes, including an epitope P45 of ApoB100 (SEQ ID No.:1).

The antibody is defined by specified complementarity determining region sequences, including HCDR1, HCDR2, HCDR3 and LCDR1, LCDR2, LCDR3, with the HCDR1 sequence of SEQ ID No.:2, HCDR2 of SEQ ID No.:3, HCDR3 of SEQ ID No.:4, LCDR1 of SEQ ID No.:5, LCDR2 of SEQ ID No.:6, and LCDR3 of SEQ ID No.:7. The document also identifies orticumab (BI-204; MLDL 1278A; RG 7418) as a particular antibody defined by these sequences.

The described therapy is associated with inhibiting oxLDL-driven pro-inflammatory cytokine secretion, including MCP-1, and reducing inflammatory cytokines TNFα and IL-1β in rhesus macaques following a high-fat, high-fructose diet. The approach includes subject selection based on inflammation markers and rheumatoid arthritis clinical features, and includes the potential for combination therapy with DMARDs and anti-TNF agents.

The document further describes dosing concepts informed by pharmacokinetics, including plasma concentration thresholds (C≥4 and C≥12 μg/mL) and initial and subsequent dosing regimens. Route options are described as subcutaneous (SC) and intravenous (IV), with expanded dosing ranges and additional subsequent-dose patterns.

Claims Coverage

The provided excerpt identifies two independent claims, covering (i) treatment of rheumatoid arthritis via administration of an antibody or antibody fragment defined by specific HCDR/LCDR sequence identifiers, and (ii) reducing severity of or likelihood of developing inflammation in a subject by administering the same antibody-defined structure to a subject showing rheumatoid arthritis symptoms or diagnosed with rheumatoid arthritis.

Both independent claims center on administering an effective amount of an antibody (or antibody fragment) defined by specific HCDR1–HCDR3 and LCDR1–LCDR3 sequences (SEQ ID NOs: 2–7) to subjects with rheumatoid arthritis needs or rheumatoid arthritis symptoms/diagnosis, with one claim directed to rheumatoid arthritis management and the other directed to reducing severity of or likelihood of developing inflammation.

Stated Advantages

Documented Applications