Synthetic membrane-receiver complexes
AssigneeRubius Therapeutics, Inc.
InventorsAvak Kahvejian, Jordi Mata-Fink, John Round, David Arthur Berry, Noubar B. Afeyan
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Abstract
Compositions comprising synthetic membrane-receiver complexes, methods of generating synthetic membrane-receiver complexes, and methods of treating or preventing diseases, disorders or conditions therewith.
Claims21
1-20. (canceled)
A pharmaceutical composition formulated as a liquid suspension for intravenous administration to the circulatory system of a human subject, comprising a population of synthetic membrane-receiver polypeptide complexes which comprise:
- a receiver polypeptide that i) is encoded by an exogenous nucleic acid that is not retained by the synthetic membrane-receiver polypeptide complex, ii) is present at at least 10,000 copies, and iii) when administered is capable of binding to a self-antibody present in the circulatory system of the mammalian subject, and
- a membrane,
- wherein the synthetic membrane-receiver polypeptide complex has catalytic activity independent of the receiver polypeptide, and wherein binding to the receiver polypeptide is capable of reducing the circulatory concentration of the self-antibody.
A method of reducing the circulatory concentration of a self-antibody, the method comprising:
- administering to a human subject suffering from or at risk of developing a self-antibody-mediated disease, disorder or condition, a pharmaceutical composition comprising a synthetic membrane-receiver polypeptide complex that comprises a) a receiver polypeptide that i) is encoded by an exogenous nucleic acid that is not retained by the synthetic membrane-receiver polypeptide complex, and ii) when administered is capable of binding to the self-antibody present in the circulatory system of the human subject, and b) a membrane, wherein binding to the receiver polypeptide reduces the circulatory concentration of the self-antibody, and wherein the pharmaceutical composition is administered in an amount effective to substantially reduce the circulatory concentration of the self-antibody.
A method of generating an isolated population of functional erythroid cells comprising a receiver polypeptide, the method comprising:
- a) introducing into an isolated erythroid cell precursor an exogenous nucleic acid encoding a receiver polypeptide having affinity to a human self-antibody, and
- b) expanding the erythroid cells comprising the receiver polypeptide by at least 20,000-fold in culture, wherein the resulting population comprises at least 20% of enucleated erythroid cells comprising the receiver polypeptide in the absence of:
- i) an enrichment step and ii) co-culturing with an adherent stromal cell layer,
- wherein during enucleation the receiver polypeptide is retained by the erythroid cell whereas the exogenous nucleic acid is not retained by the erythroid cell, wherein the erythoid cell comprises at least 1,000 copies, 10,000 copies, 25,000 copies, 50,000 copies, or at least 100,000 copies of the receiver polypeptide, and wherein the culture comprises one or more culturing factors selected from the group consisting of stem cell factor, IL-3, IL-6, insulin, transferrin, erythropoietin, hydrocortisone, and estrogen.
Dependencies are inferred from the claim text.