Methods for treating systemic lupus erythematosus with an anti-apolipoprotein B antibody
Inventors
Nilsson, Jan • Abbott, Ryan Benjamin
Assignees
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Publication Number
US-10434141-B2
Publication Date
2019-10-08
Expiration Date
Abstract
Described herein are peptides and antibodies for prevention and/or therapeutic treatment of mammals, including humans, against systemic lupus erythematosus, as well as diagnosing the presence or absence of antibodies related to increased or decreased risk of developing SLE and/or to disease grading, staging, and/or prognosis.
Core Innovation
The invention relates to treating systemic lupus erythematosus (SLE) by passive immunization. A subject in need thereof is administered a therapeutically or prophylactically effective amount of an antibody that binds at least one oxidized fragment of apolipoprotein B100 (ApoB-100). The disclosed antibody comprises a heavy chain encoded by the polynucleotide set forth in SEQ ID NO: 303 and a light chain encoded by the polynucleotide set forth in SEQ ID NO: 304.
The invention further relates to treating, inhibiting, reducing the severity of, and/or promoting prophylaxis of cardiovascular disease in a subject with SLE. The cardiovascular disease includes lupus-associated cardiovascular disease, including (accelerated) atherosclerosis, using the same passive immunization approach with an antibody that binds oxidized ApoB-100 fragments. The antibody characteristics include the heavy chain and light chain encoded by SEQ ID NO: 303 and SEQ ID NO: 304, respectively.
The disclosure includes diagnostic/prognostic assays based on measuring ApoB-100 autoantibodies, with levels relative to a reference value. The assays optionally include measurement of soluble apoptosis-signaling receptors, including Fas, TNF-R1, and TRAIL-R2. Documented studies are described that associate these measurements with cardiovascular disease in SLE patients using proximity extension assay and related immunoassays, and that show treatment-associated effects in mouse lupus models with accelerated atherosclerosis.
Claims Coverage
The partial content provides two independent claims. Across these independent claims, the core inventive concept is passive immunization of a subject with an antibody that binds oxidized fragments of ApoB-100, with antibody heavy and light chains encoded by specific polynucleotides (SEQ ID NO: 303 and SEQ ID NO: 304).
Passive immunization with oxidized ApoB-100 fragment binding antibody for SLE
A method for treating SLE in a subject in need thereof by passive immunization, comprising administering a therapeutically or prophylactically effective amount of an antibody that binds at least one oxidized fragment of apolipoprotein B100 (ApoB-100) to the subject.
Antibody heavy and light chains encoded by SEQ ID NO: 303 and SEQ ID NO: 304
The antibody comprises a heavy chain encoded by the polynucleotide set forth in SEQ ID NO: 303 and comprises a light chain encoded by the polynucleotide set forth in SEQ ID NO: 304.
Cardiovascular disease modulation in SLE via oxidized ApoB-100 fragment binding antibody
A method of treating, inhibiting, reducing the severity of and/or promoting prophylaxis of cardiovascular disease in a subject with SLE by administering a therapeutically or prophylactically effective amount of an antibody that binds at least one oxidized fragment of apolipoprotein B100 (ApoB-100) to the subject.
Both independent claims cover passive immunization in SLE using an antibody that binds oxidized ApoB-100 fragments, with the antibody specified by heavy and light chain polynucleotides (SEQ ID NO: 303 and SEQ ID NO: 304). The second independent claim extends the approach to cardiovascular disease in subjects with SLE, including (accelerated) atherosclerosis as refined in dependent claims.
Stated Advantages
Treating systemic lupus erythematosus (SLE) in a subject via passive immunization.
Providing prophylaxis for SLE via passive immunization.
Treating, inhibiting, and/or reducing the severity of cardiovascular disease in a subject with SLE.
Promoting prophylaxis of cardiovascular disease in a subject with SLE.
Documented Applications
Diagnostic assays using soluble apoptosis-signaling receptors and/or autoantibodies against oxidized ApoB-100 to estimate likelihood of SLE and cardiovascular disease.
Passive immunization treatment of SLE in a subject in need thereof using an antibody binding at least one oxidized ApoB-100 fragment.
Passive immunization to treat, inhibit, reduce severity of, and/or promote prophylaxis of cardiovascular disease in a subject with SLE, including atherosclerosis and accelerated atherosclerosis.
Reducing anti-nuclear antibody titers and showing effects on plaque depth in mouse lupus models with accelerated atherosclerosis using CVX-210-B (CVX-12; p210 conjugated/formulated with alum).
Associating soluble death receptors with cardiovascular disease in SLE patients using proximity extension assays and related immunoassays.
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