Induction of osteogenesis by delivering BMP encoding RNA
Inventors
BALMAYOR, Elizabeth • Rudolph, Carsten • Plank, Christian
Assignees
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Publication Number
US-12263229-B2
Publication Date
2025-04-01
Expiration Date
Abstract
The present invention relates to a pharmaceutical composition comprising a polyribonucleotide (RNA) with a sequence which encodes a bone morphogenetic protein (BMP) for use in (i) treating or preventing a bone disease, bone disorder or bone injury; and/or (ii) inducing or enhancing osteogenic differentiation, osteogenesis, ossification, bone regeneration and/or bone morphogenesis in a patient. The present invention also relates to the respective BMP encoding RNAs (BMP RNAs), in particular in its chemically modified form. The present invention also relates to complexes which comprise or are complexed with the BMP RNA, in particular to the respective transfection complexes like lipofection, magnetofection and magnetolipofection complexes. The present invention further relates to a carrier and carrier body to which the RNA or complex has been loaded and to a pharmaceutical composition comprising said carrier or carrier body. The present invention further relates to a matrix or scaffold for sustained mRNA delivery and its application in bone regeneration in vivo, ex vivo and in vitro.
Core Innovation
The invention relates to treating or preventing a bone disease, bone disorder or bone injury by administering a pharmaceutical composition comprising a polyribonucleotide RNA encoding a bone morphogenetic protein (BMP). The pharmaceutical composition further includes a component comprising an oligo(alkylene amine) cationic lipidoid having the structure of formula (IV), with defined variables and one or more indicated nitrogen atoms that may be protonated.
The BMP can be specified as BMP-2 or BMP-7, and the RNA can be single-stranded RNA or chemically modified RNA with cytidine and uridine substitutions such as m5C and s2U. The composition may include additional lipid excipient sets, including combinations of DOPE, cholesterol, DMPE-PEG (2k), or DPPC, cholesterol, DMG-PEG (2k).
The cationic lipidoid can also be tied to a preparation-defined precursor mixing step involving N,N′-Bis(2-aminoethyl)-1,3-propanediamine and 1,2-Epoxydodecane, yielding the cationic lipidoid of formula (IV). The disclosed embodiments also describe matrix- or scaffold-associated depot-style delivery and reintroduction of transfected patient-derived cells for ex vivo approaches.
Claims Coverage
The provided content includes three independent claims. Each claim defines a method of treating or preventing a bone disease, bone disorder or bone injury by administering a pharmaceutical composition including a BMP-encoding polyribonucleotide RNA and a structurally defined cationic lipidoid component, with claim-to-claim differences in additional lipid components and lipidoid definition details.
Bmp-encoding RNA plus defined cationic lipidoid formula (IV)
A method of treating or preventing a bone disease, bone disorder or bone injury by administering a pharmaceutical composition comprising an RNA polyribonucleotide with a sequence encoding a BMP and a component comprising an oligo(alkylene amine) being a cationic lipidoid having the structure of formula (IV), with defined variables and optional protonation of indicated nitrogen atoms.
Bmp-encoding RNA with DPPC and cationic lipidoid formula (IV)
A method of treating or preventing a bone disease, bone disorder or bone injury by administering a pharmaceutical composition comprising an RNA polyribonucleotide with a sequence encoding a BMP, DPPC, and a component comprising an oligo(alkylene amine) being a cationic lipidoid having the structure of formula (IV), including that one or more indicated nitrogen atoms may be protonated.
Prepared cationic lipidoid from bis(2-aminoethyl)propanediamine and epoxydodecane plus BMP-encoding RNA
A method of treating or preventing a bone disease, bone disorder or bone injury by administering a pharmaceutical composition comprising an RNA polyribonucleotide with a sequence encoding a BMP and a component comprising an oligo(alkylene amine) prepared by mixing N,N′-Bis(2-aminoethyl)-1,3-propanediamine with 1,2-Epoxydodecane, wherein the resulting cationic lipidoid has the structure of formula (IV).
Across the independent claims, the core inventive concept is the administration of a pharmaceutical composition containing a polyribonucleotide RNA sequence encoding a BMP together with a specifically defined cationic lipidoid (formula (IV)). Claim variations further specify additional lipid components such as DPPC or specify that the cationic lipidoid is obtained from defined precursor mixing, while maintaining the structural constraints of formula (IV) and the optional protonation of indicated nitrogen atoms.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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