A Phase 1a, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Lpathomab Administered Intravenously to Healthy Volunteers

The primary purpose of this study is to evaluate the safety and tolerability of Lpathomab in healthy volunteers. Additional endpoints include characterization of the pharmacokinetic (PK), pharmacodynamic (PD), and immunogenicity profiles of a single IV dose of Lpathomab in healthy volunteers.

开始日期2015-09-01

申办/合作机构

Lpath, Inc.

100 项与 Lpathomab 相关的临床结果

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100 项与 Lpathomab 相关的转化医学

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100 项与 Lpathomab 相关的专利（医药）

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110

项与 Lpathomab 相关的文献（医药）

2024-10-01·Rheumatology and Therapy

Treatment with Targeted Therapy in Patients with Psoriatic Arthritis and Inadequate Response to Methotrexate: Proposal for a Rational Strategy

Article

作者: Carvajal Alegria, Guillermo ; Wendling, Daniel ; Verhoeven, Frank ; Goupille, Philippe

INTRODUCTIONThe therapeutic arsenal for psoriatic arthritis (PsA) is gradually being expanded, but the use of these targeted treatments must be optimal. Our objective was to guide the choice of targeted therapy to use as first-line treatment in a patient with PsA in whom methotrexate (MTX) has failed.METHODSWe searched for literature data in PubMed with the appropriate keywords for the six points of our argument: (1) the tolerance of MTX; (2) the efficacy of targeted therapies combined with MTX vs monotherapy; (3) immunogenicity of anti-tumor necrosis alpha (TNFα) monoclonal antibodies (mAbs); (4) immunogenicity of anti-interleukin (IL)-17, anti-IL-12/23, and anti-IL-23 mAbs; (5) the therapeutic maintenance of anti-TNFα mAbs when combined or not with MTX; (6) the therapeutic maintenance of anti-IL-17 vs anti-TNFα mAbs as first-line targeted therapy.RESULTSThe proposed rational strategy is as follows: in case of initiation of an anti-TNFα agent, maintaining treatment with MTX seems preferable, even in the absence of evidence of the superior efficacy of the combination, to avoid immunization and reduced therapeutic maintenance; in case of initiation of anti-IL-17, anti-IL-12/23, anti-IL-23 agents, or Janus kinase (JAK) inhibitors, again in the absence of evidence of the superior efficacy of the combination, discontinuing MTX therapy may be possible, at least in two steps, after verifying the efficacy of the targeted therapy initiated on the joints and skin.CONCLUSIONWe have data from the literature to guide the choice of targeted therapy to use as first-line treatment in a patient with PsA in whom MTX has failed.

2023-12-12·Proceedings of the National Academy of Sciences1区 · 综合性期刊

Human anti-C1q autoantibodies bind specifically to solid-phase C1q and enhance phagocytosis but not complement activation

1区 · 综合性期刊

Article

作者: van de Bovenkamp, Fleur S ; Kramer, Cynthia S M ; de Vor, Lisanne ; Trouw, Leendert A ; Sharp, Thomas H ; Drijfhout, Jan W ; Slot, Linda M ; Vidarsson, Gestur ; Dijkstra, Douwe J ; Rooijakkers, Suzan H M ; Zaldumbide, Arnaud ; Zuijderduijn, Rob ; Abendstein, Leoni ; Parren, Paul W H I ; Pool, Jos ; Gelderman, Kyra A

Autoantibodies directed against complement component C1q are commonly associated with autoimmune diseases, especially systemic lupus erythematosus. Importantly, these anti-C1q autoantibodies are specific for ligand-bound, solid-phase C1q and do not bind to fluid-phase C1q. In patients with anti-C1q, C1q levels are in the normal range, and the autoantibodies are thus not depleting. To study these human anti-C1q autoantibodies at the molecular level, we isolated C1q-reactive B cells and recombinantly produced nine monoclonal antibodies (mAbs) from four different healthy individuals. The isolated mAbs were of the IgG isotype, contained extensively mutated variable domains, and showed high affinity to the collagen-like region of C1q. The anti-C1q mAbs exclusively bound solid-phase C1q in complex with its natural ligands, including immobilized or antigen-bound IgG, IgM or CRP, and necrotic cells. Competition experiments reveal that at least 2 epitopes, also targeted by anti-C1q antibodies in sera from SLE patients, are recognized. Electron microscopy with hexameric IgG-C1q immune complexes demonstrated that multiple mAbs can interact with a single C1q molecule and identified the region of C1q targeted by these mAbs. The opsonization of immune complexes with anti-C1q greatly enhanced Fc-receptor-mediated phagocytosis but did not increase complement activation. We conclude that human anti-C1q autoantibodies specifically bind neo-epitopes on solid-phase C1q, which results in an increase in Fc-receptor-mediated effector functions that may potentially contribute to autoimmune disease immunopathology.

2023-06-30·Vaccines

A Monoclonal Antibody Produced in Glycoengineered Plants Potently Neutralizes Monkeypox Virus.

Article

作者: Bonner, James ; Jugler, Collin ; Steinkellner, Herta ; Sun, Haiyan ; Esqueda, Adrian ; Chen, Qiang ; Lai, Huafang ; Kibler, Karen V

The 2022 global outbreaks of monkeypox virus (MPXV) and increased human-to-human transmission calls for the urgent development of countermeasures to protect people who cannot benefit from vaccination. Here, we describe the development of glycovariants of 7D11, a neutralizing monoclonal IgG antibody (mAb) directed against the L1 transmembrane protein of the related vaccinia virus, in a plant-based system as a potential therapeutic against the current MPVX outbreak. Our results indicated that 7D11 mAb quickly accumulates to high levels within a week after gene introduction to plants. Plant-produced 7D11 mAb assembled correctly into the tetrameric IgG structure and can be easily purified to homogeneity. 7D11 mAb exhibited a largely homogeneous N-glycosylation profile, with or without plant-specific xylose and fucose residues, depending on the expression host, namely wild-type or glycoengineered plants. Plant-made 7D11 retained specific binding to its antigen and displayed a strong neutralization activity against MPXV, as least as potent as the reported activity against vaccinia virus. Our study highlights the utility of anti-L1 mAbs as MPXV therapeutics, and the use of glycoengineered plants to develop mAb glycovariants for potentially enhancing the efficacy of mAbs to combat ever-emerging/re-emerging viral diseases.

100 项与 Lpathomab 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
脑损伤	临床1期	澳大利亚	-	-
脑损伤	临床1期	美国	-	-
糖尿病性神经病变	临床1期	美国	Lpath, Inc.	-
纤维化	临床1期	美国	Lpath, Inc.	-
肿瘤	临床1期	美国	Lpath, Inc.	-
神经痛	临床1期	-	University of California	-
神经痛	临床1期	美国	Lpath, Inc.	-
脊髓损伤	临床1期	澳大利亚	-	-
神经痛	临床前	-	University of Melbourne	-