Methods for treatment of psoriasis with an anti-Apo B100 antibody
Inventors
Liang, Bertrand C. • Ruiz, Stacey • Farina, Christopher John
Assignees
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Publication Number
US-12016921-B2
Publication Date
2024-06-25
Expiration Date
Abstract
Compositions and methods for treating a subject with psoriasis are provided, including an inhibitor of oxidized low density lipoprotein (LDL), malondialdehyde-modified epitope in LDL or native LDL for administration. Exemplary inhibitors of oxidized or malondialdehyde-modified LDL include orticumab, a variant antibody or peptides capable of binding oxidized or malondialdehyde-modified LDL, which results in improvement in conditions of psoriasis even in patients that are refractory to ultraviolet A/B therapy and topical steroids.
Core Innovation
The invention relates to treating, reducing the severity of, slowing progression of, or inhibiting psoriasis or psoriatic arthritis in a subject in need thereof. The approach administers an effective amount of an antibody or antibody fragment capable of binding to a fragment of apolipoprotein B100 (ApoB100), wherein the ApoB100 fragment comprises an amino acid sequence of SEQ ID NO: 1. The antibody includes specified complementarity-determining regions, with HCDR1, HCDR2, HCDR3, and LCDR1, LCDR2, LCDR3 corresponding to SEQ ID NOs: 2-7.
The antibody binding features are defined such that HCDR1 comprises SEQ ID NO: 2, HCDR2 comprises SEQ ID NO: 3, and HCDR3 comprises SEQ ID NO: 4, while LCDR1 comprises SEQ ID NO: 5, LCDR2 comprises SEQ ID NO: 6, and LCDR3 comprises SEQ ID NO: 7. In the described embodiments, the invention also includes antibodies having a variable heavy region and/or variable light region corresponding to SEQ ID NOs: 8-9, and/or having a heavy chain and/or light chain corresponding to SEQ ID NOs: 10-11.
The disclosed examples and study description support use in plaque psoriasis and in subjects refractory to UVA/UVB and topical steroids. A Phase 2 randomized double-blind placebo-controlled trial is described with monthly subcutaneous dosing and evaluation using Investigator Global Assessment (IGA) and Psoriasis Area and Severity Index (PASI) measures, with coronary inflammation imaging described for coronary artery disease.
Claims Coverage
The document includes two independent claims directed to passive administration of a specified anti-ApoB100 antibody for psoriasis or psoriatic arthritis. Across these claims, the key inventive content is the use of an antibody or antibody fragment that binds an ApoB100 fragment comprising SEQ ID NO: 1, with antibodies defined by CDR sequences SEQ ID NOs: 2-7.
Anti-ApoB100 antibody defined by ApoB100 fragment SEQ ID NO: 1 and CDR SEQ ID NOs: 2-7
Administering to the subject an effective amount of an antibody or antibody fragment capable of binding to a fragment of apolipoprotein B100 (ApoB100), wherein the fragment of ApoB100 comprises an amino acid sequence of SEQ ID NO: 1, and wherein the antibody comprises HCDR1 with SEQ ID NO: 2, HCDR2 with SEQ ID NO: 3, HCDR3 with SEQ ID NO: 4, LCDR1 with SEQ ID NO: 5, LCDR2 with SEQ ID NO: 6, and LCDR3 with SEQ ID NO: 7, for treating, reducing the severity of, slowing progression of, or inhibiting psoriasis or psoriatic arthritis.
Passive immunization using SEQ ID NO: 1 ApoB100 fragment binding antibody with CDR SEQ ID NOs: 2-7
Administering for treatment of psoriasis or psoriatic arthritis a therapeutically effective amount of an antibody or antibody fragment capable of binding to a fragment of ApoB100, wherein the fragment of ApoB100 is SEQ ID NO: 1 and wherein the antibody comprises HCDR1 with SEQ ID NO: 2, HCDR2 with SEQ ID NO: 3, HCDR3 with SEQ ID NO: 4, LCDR1 with SEQ ID NO: 5, LCDR2 with SEQ ID NO: 6, and LCDR3 with SEQ ID NO: 7.
The independent claims are centered on passive administration of a defined antibody or antibody fragment that binds an ApoB100 fragment comprising SEQ ID NO: 1, where the antibody is defined by specific HCDR and LCDR sequences (SEQ ID NOs: 2-7). One claim frames this as a general therapeutic method for psoriasis or psoriatic arthritis, while the other frames the same antibody use as passive immunization.
Stated Advantages
Treating, reducing the severity of, slowing progression of, or inhibiting psoriasis or psoriatic arthritis.
Documented Applications
A Phase 2a study reporting psoriasis improvement in a small cohort receiving orticumab.
A Phase 2 randomized double-blind placebo-controlled trial in moderate chronic plaque psoriasis with coronary artery disease, using monthly subcutaneous orticumab and assessing IGA and PASI measures, and coronary inflammation imaging including CCTA/perivascular fat attenuation.
Use in subjects refractory to UVA therapy, UVB therapy, and/or a topical steroid.
Use in subjects characterized by higher levels of TNFα, IL-6, and/or CRP compared to subjects without psoriasis or psoriatic arthritis.
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