| 主权项 |
1. A method of treating or preventing a disease or disorder associated with aberrant levels of lysophosphatidic acid (LPA), comprising administering to a subject in need of such treatment an antibody or fragment thereof that binds LPA under physiological conditions in an amount effective to reduce in vivo the effective concentration of LPA, thereby effecting treatment or prevention of the disease or disorder,
(A) wherein the disease or disorder is selected from the group consisting of a hyperproliferative disease, including cancer; an immune-related disease, including an autoimmune disease, allograft rejection and graft-vs-host disease; obesity; type 2 diabetes; an ocular disease, including macular degeneration; pain; a disease associated with aberrant angiogenesis or neovascularization; apoptosis; fibrogenesis or fibrosis, including scleroderma, pulmonary fibrosis, renal fibrosis, skin fibrosis, cardiac fibrosis, and hepatic fibrosis; wound repair and healing; and spider bite, and (B) wherein the antibody or fragment thereof that binds lysophosphatidic acid (LPA) under physiological conditions comprises at least one heavy chain variable domain and at least one light chain variable domain, wherein (i) each heavy chain variable domain comprises first, second, and third heavy chain complementarity determining regions (CDRs), wherein the first heavy chain CDR comprises an amino acid sequence having at least about 65% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NO: 56, 62, 68, 89 and 95, the second heavy chain CDR comprises an amino acid sequence having at least about 65% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NO: 57, 69, 78 and 90, and the third heavy chain CDR comprises an amino acid sequence having at least about 65% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NO: 58, 70, 79, 82 and 91; and (ii) each light chain variable domain comprises first, second, and third light chain CDRs, wherein the first light chain CDR comprises an amino acid sequence having at least about 65% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NO: 59, 71, 80, and 92, the second light chain CDR comprises an amino acid sequence having at least about 65% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NO; 60, 72 and 93, and the third light chain CDR comprises an amino acid sequence having at least about 65% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NO: 61 and 94. |
