Development of a qualified pharmacokinetic bioassay to support preclinical and clinical studies of MM-008, a non-hormonal contraceptive antibody

开发合格的药代动力学生物测定法以支持非激素避孕抗体 MM-008 的临床前和临床研究

基本信息

  • 批准号:
    10459074
  • 负责人:
  • 金额:
    $ 27.77万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-07-01 至 2024-06-30
  • 项目状态:
    已结题

项目摘要

Project Summary: Nearly half of all pregnancies in the U.S. are unintended, and most occur in women who are not using contraceptives. There are diverse reasons for not using contraceptives; one common reason is that many women have a strong aversion to using exogenous hormones due to real or perceived side effects as well as medical contraindications. It is likely that contraceptive use and satisfaction would substantially increase if there were a non-hormonal, user-controlled contraceptive method that did not require use immediately prior to intercourse, nor daily dosing. We believe we can create such a non-hormonal contraceptive based on vaginal delivery of an anti-sperm monoclonal antibody (mAb) that agglutinates and traps sperm in mucus, thereby preventing sperm from reaching the egg. This strategy, based on vaginal delivery of anti-sperm Ab, was validated in animal models in the 1980’s-90’s, and, unlike contraceptive vaccines, enables consistently reliable contraception and rapid reversibility. However, this strategy was not practical until recently due to the high costs of mAb production, and modest agglutination potencies of prior anti-sperm IgGs. We have developed a highly multivalent IgG, MM008, that targets a well-characterized and validated contraceptive antigen universally present on all human sperm. MM008 is highly homogeneous and stable, and can be produced at very high yields using conventional biomanufacturing processes. More importantly, MM008 is exceptionally potent, possesing >16-fold greater sperm-agglutinaton potency than the best anti-sperm IgG known in the literature. MM008 aggulutinates sperm even down to <100 ng/mL, and can reduce progressively motile sperm by 99.9% in the sheep vagina within 2 mins, at a dose of just 33 ug per sheep. Furthermore, we have shown that we can steadily release MM008 from a proprietary capsule-IVR system that sustains highly effective concentrations of MM008 in the sheep vagina for over 20 days (more than adequate to cover the fertility window in most women). We have also created vaginal film formulations of highly multivalent IgG mAbs that achieved complete agglutination of all sperm within 2 mins in sheep. These highly promising results motivated us to actively advance MM008 into the clinic. In this proposal, we seek to respond to the RFA HD- 22-018, and develop a highly sensitive and quantitative detection assay for measuring MM008 concentrations in a variety of biological matrices relevant for IND-enabling and clinical studies. In Specific Aim 1, we will establish a sandwich ELISA assay using a panel of anti-idiotype (anti-ID) Fabs against MM008. In Specific Aim 2, we will further optimize and qualify the assays to quantify MM008 in matrices including human serum, human cervicovaginal mucus, human mid-cycle endocervical mucus, and rat serum. These assays are part of the critical path for advancing MM008 through IND-enabling GLP studies and early clinical studies. Successful completion of the proposed work will accelerate our efforts to advance MM008 into the clinic.
项目总结:

项目成果

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会议论文数量(0)
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Keiichiro Kushiro其他文献

Keiichiro Kushiro的其他文献

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{{ truncateString('Keiichiro Kushiro', 18)}}的其他基金

Highly Acidifying Intravaginal Rings with Lactobacillus Probiotics to Treat Bacterial Vaginosis
含乳酸菌益生菌的高度酸化阴道环可治疗细菌性阴道病
  • 批准号:
    10699458
  • 财政年份:
    2023
  • 资助金额:
    $ 27.77万
  • 项目类别:
Fast dissolving antibody tablets for preventing vaginal HSV transmission
用于预防 HSV 阴道传播的快速溶解抗体片
  • 批准号:
    10547476
  • 财政年份:
    2022
  • 资助金额:
    $ 27.77万
  • 项目类别:
User-based identification of preferred design features for MM008, a non-hormonal contraceptive vaginal ring
基于用户的非激素避孕阴道环 MM008 的首选设计特征识别
  • 批准号:
    10459077
  • 财政年份:
    2022
  • 资助金额:
    $ 27.77万
  • 项目类别:
Capsule-intravaginal ring for sustained release of antibodies for non-hormonal contraception and vaginal protection against HIV
胶囊阴道环,用于持续释放抗体,用于非激素避孕和阴道艾滋病毒保护
  • 批准号:
    9799170
  • 财政年份:
    2021
  • 资助金额:
    $ 27.77万
  • 项目类别:
Capsule-intravaginal ring for sustained release of antibodies for non-hormonal contraception and vaginal protection against HIV
胶囊阴道环,用于持续释放抗体,用于非激素避孕和阴道艾滋病毒保护
  • 批准号:
    10381449
  • 财政年份:
    2021
  • 资助金额:
    $ 27.77万
  • 项目类别:

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