# Engineering Decavalent, Sperm‐Binding Laminin‐IgG Hybrid Antibodies for Potent Non‐Hormonal Contraception

## TL;DR

Scientists created a powerful non-hormonal contraceptive using a new antibody design that rapidly stops sperm movement in sheep.

## Contribution

A novel multivalent antibody platform combining laminin and IgG domains for potent, stable non-hormonal contraception.

## Key findings

- LamH10, a decavalent antibody, reduced motile sperm by >99% in sheep at low doses.
- LamH10 retains stability in acidic environments and works rapidly after vaginal dosing.
- The platform uses conventional bioprocessing and can be formulated into dissolving tablets.

## Abstract

Nearly half of pregnancies globally are unintended, reflecting the current unmet need in safe, effective non‐hormonal contraception. While anti‐sperm IgM is responsible for infertility in many women, stability and bioprocessing challenges with IgM make them ill‐suited for non‐hormonal contraception. Similarly, IgG lacks sufficient sperm agglutination potencies. To overcome these shortcomings, a novel, multivalent mAb platform is developed, based on fusing the Laminin 511 heterotrimerization domains to Fabs and IgG1‐Fc, allowing for tuning of Fab valency (from 2–12) with molecular specificity. ‘LamH10’, the most potent mAb among the panel of polyvalent antibodies against CD52g on human sperm, comprises 10 Fabs per molecule, and achieves nanomolar potencies at physiological temperatures and retains stability in the acidic environment of human cervicovaginal mucus. In sheep, LamH10 reduced progressively motile sperm in the vagina by >99% within 2 min at just 33 µg per sheep. LamH10 utilizes the same conventional bioprocessing as IgGs, and can be formulated into rapidly dissolving tablets for on‐demand contraception, achieving 100% sperm agglutination within minutes of vaginal dosing. The laminin‐IgG hybrid platform not only forms the basis of the most potent biologic for nonhormonal contraception to date, but also represents a promising platform for multivalent mAbs for other applications.

This study investigates a highly multivalent mAb platform fusing Laminin‐511 heterotrimerization domains with Fabs and IgG1‐Fc as a non‐hormonal contraceptive. The most potent molecule ‘LamH10’, possessing 10 Fabs, rapidly achieved >99% reduction in progressively motile sperm at just 33µg per dose in sheep, making the laminin‐IgG hybrid platform the basis of the most potent biologic for nonhormonal contraception to date.