Compositions and methods for in utero delivery
Inventors
Saltzman, W. Mark • Stitelman, David H. • Farrelly, James Stephen • Bianchi, Anthony
Assignees
Publication Number
US-12268774-B2
Publication Date
2025-04-08
Expiration Date
2038-04-04
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Abstract
Compositions and methods for fetal or in utero delivery of active agents are provided. The compositions are most typically administered intravenously via the vitelline vein, umbilical vein, or directly into the amniotic cavity of a pregnant mother. Fibroblast growth factor is to correct structural defects of neural tissue.
Core Innovation
The invention provides compositions and methods for the in utero delivery of active agents, particularly for fetal or embryonic subjects in need of such treatment. The compositions are designed for injection or infusion into the amniotic cavity or specific fetal blood vessels such as the vitelline or umbilical veins. A primary feature of the invention is the encapsulation, entrapment, or dispersion of therapeutic or diagnostic agents—including gene editing compositions and growth factors such as fibroblast growth factor (FGF)—in biocompatible, preferably biodegradable, microparticles or nanoparticles.
These particles are formulated to preferentially bind to exposed fetal defects, such as those present in myelomeningocele (MMC), and then release their active agents either intracellularly or extracellularly in a controlled manner. The patent particularly addresses the use of fibroblast growth factor encapsulated in negatively charged polymeric microparticles (e.g., alginate or PLGA), which are injected into the amniotic cavity to induce epithelial or skin growth over exposed spinal cord or brain tissue. This approach is demonstrated to encourage tissue coverage over significant structural birth defects in utero, thereby correcting or minimizing damage prior to birth.
The problem being solved is the lack of effective, minimally invasive interventions for serious structural birth defects such as open spina bifida (MMC), which currently result in significant morbidity, limited postnatal repair options, and substantial health and societal costs. Existing interventions like open fetal surgery are costly, invasive, and often performed late, limiting their utility. This invention provides an improved, targeted, and less invasive in utero therapeutic delivery strategy, enabling earlier intervention before irreversible fetal tissue damage occurs.
Claims Coverage
The patent contains two independent claims covering a method and a kit, each with distinctive inventive features specifically focusing on in utero delivery of fibroblast growth factor using defined polymeric microparticles.
In utero method for epithelial tissue formation using FGF-loaded microparticles
A method comprising administration by injection into the amniotic fluid of a 15 to 20 week human embryo or fetus having exposed spinal cord or brain tissue, an effective amount of a composition comprising fibroblast growth factor that is encapsulated, entrapped, complexed to, or dispersed in polymeric microparticles. - The microparticles have a diameter from about 5 to about 10 microns. - The microparticles have a zeta potential between −32.8 and −47 mV. - The microparticles are formed of alginate, poly(lactic acid)(PLA), poly(glycolic acid)(PGA), poly(lactide-co-glycolide)(PLGA), polyanhydrides, poly(ortho) esters, poly(caprolactone), poly(hydroxyalkanoates), poly(lactide-co-caprolactone), poly(beta-amino) esters (PBAEs), or poly(amine-co-ester) polymers (PACE). - The administration causes epithelial tissue to form over the exposed spinal cord or brain tissue in the embryo or fetus.
Kit for in utero injection of FGF-loaded microparticles with defined characteristics
A kit comprising: - A composition with polymeric microparticles having a diameter between 5 and 10 microns and a zeta potential between −32.8 and −47 mV. - The microparticles contain as the sole active agent fibroblast growth factor that is encapsulated, entrapped, complexed to, or dispersed in the microparticles. - The microparticles are formed of alginate, poly(lactic acid)(PLA), poly(glycolic acid)(PGA), poly(lactide-co-glycolide)(PLGA), polyanhydrides, poly(ortho) esters, poly(caprolactone), poly(hydroxyalkanoates), poly(lactide-co-caprolactone), poly(beta-amino) esters (PBAEs), or poly(amine-co-ester) polymers (PACE). - The composition is formulated for infusion or injection into the amniotic sac. - The kit includes a needle for delivery of the microparticle formulation into the amniotic sac.
The claims focus on compositions and kits using fibroblast growth factor-loaded polymeric microparticles with specified size and charge, administered in utero for the formation of epithelial tissue over fetal neural defects, with precise coverage on particle characteristics and administration methods.
Stated Advantages
The invention enables minimally invasive in utero delivery of therapeutic agents, allowing for early intervention before irreversible tissue damage occurs.
The use of biodegradable, biocompatible microparticles allows for targeted and controlled release of active agents directly at the fetal defect site.
The compositions preferentially bind to defects such as myelomeningocele, reducing exposure of sensitive tissues and promoting their protection and healing.
The method provides a lower risk and less resource-intensive alternative compared to open fetal surgery for neural tube defects.
Documented Applications
In utero treatment of myelomeningocele (open spina bifida) by promoting skin or epithelial covering of exposed fetal spinal cord or brain tissue.
Minimally invasive correction of structural birth defects in embryos or fetuses through intra-amniotic injection of growth factor-loaded microparticles.
Provision of a kit for clinical administration of fibroblast growth factor-loaded microparticles for injection into the amniotic sac during prenatal care.
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