Abstract

The invention relates to improvements in drug delivery and to the use of compounds comprising cell penetrating peptides (CPPs) stabilized by: i) stapling two amino acids to form Stapled CPPs (StaPs) or ii) stitching three or more amino acids to form stitched CPPs (StiPs), and a drug or Biologically Active Compound (BAC) directly bonded to or connected to the CPP via bi-functional linker. This enables the BAC to be carried though a cell membrane by the CPP. The invention also relates to a method of synthesizing and further functionalizing the compound utilizing solid phase peptide synthesis techniques. Also provided is a method of treating a subject comprising administering a pharmaceutical composition comprising the compound and one or more pharmaceutically acceptable excipients.

IPC Classes  ?

• A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent

Abstract

The invention relates to improvements in drug delivery and to the use of compounds comprising cell penetrating peptides (CPPs) stabilized by: i) stapling two amino acids to form Stapled CPPs (StaPs) or ii) stitching three or more amino acids to form stitched CPPs (StiPs), and a drug or Biologically Active Compound (BAC) directly bonded to or connected to the CPP via bifunctional linker. This enables the BAC to be carried though a cell membrane by the CPP. The preferred BAC is an electrically low charge carrying oligonucleotide such as a phosphorodiamidate morpholino oligonucleotide (PMO). The invention also relates to a method of synthesizing and further functionalizing the compound utilizing solid phase peptide synthesis techniques. Also provided is a method of treating a subject comprising administering a pharmaceutical composition comprising the compound and one or more pharmaceutically acceptable excipients.

IPC Classes  ?

• A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
• C07K 1/107 - General processes for the preparation of peptides by chemical modification of precursor peptides

Abstract

The invention relates to improvements in drug delivery and more particularly to the use of Cell Penetrating Agents (CPA's) or Cell Penetrating Peptides (CPP's) which have been stabilized by, for example: i) stapling two amino acids to form Stapled CPP's (StaP's) or ii) stitching three or more amino acids to form stitched CPP's (StiP's). These stabilized CPP's are conjugated to a drug or Biologically Active Compound (BAC) directly or via a Bi-Functional Linker (BFL) so that the BAC can be carried though a cell membrane by the CPP. The resulting molecules are referred to as Drug Carrying Cell Penetrating Molecules (DCCPM's). The preferred BAC is an electrically low charge carrying oligonucleotide such as a phosphorodiamidate morpholino oligonucleotide (PMO). The invention also relates to a method of facilitating the uptake of a BAC into a cell, the use of a DCCPM in the treatment of a disease requiring alteration of an endogenous or exogenous gene, a method of improving the bioavailability of a drug or BAC, a method of introducing a drug or BAC to a site which is refractory to the drug or BAC in its native state, a method of treating a subject comprising administering the DCCPM's of the invention and to a pharmaceutical composition comprising the DCCPM and one or more pharmaceutically acceptable excipients.

IPC Classes  ?

• A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
• A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
• C07C 13/00 - Cyclic hydrocarbons containing rings other than, or in addition to, six-membered aromatic rings
• C07K 1/107 - General processes for the preparation of peptides by chemical modification of precursor peptides
• C07K 7/02 - Linear peptides containing at least one abnormal peptide link
• C07K 19/00 - Hybrid peptides

Abstract

The invention relates to improvements in drug delivery and more particularly to the use of Cell Penetrating Agents (CPA's) or Cell Penetrating Peptides (CPP's) which have been stabilized by, for example: i) stapling two amino acids to form Stapled CPP's (StaP's) or ii) stitching three or more amino acids to form stitched CPP's (StiP's). These stabilized CPP's are conjugated to a drug or Biologically Active Compound (BAC) directly or via a Bi-Functional Linker (BFL) so that the BAC can be carried through a cell membrane by the CPP. The resulting molecules are referred to as Drug Carrying Cell Penetrating Molecules (DCCPM's). The preferred BAC is an electrically low charge carrying oligonucleotide such as a phosphorodiamidate morpholino oligonucleotide (PMO). The invention also relates to a method of facilitating the uptake of a BAC into a cell, the use of a DCCPM in the treatment of a disease requiring alteration of an endogenous or exogenous gene, a method of improving the bioavailability of a drug or BAC, a method of introducing a drug or BAC to a site which is refractory to the drug or BAC in its native state, a method of treating a subject comprising administering the DCCPM's of the invention and to a pharmaceutical composition comprising the DCCPM and one or more pharmaceutically acceptable excipients.

IPC Classes  ?

• A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
• C07K 1/107 - General processes for the preparation of peptides by chemical modification of precursor peptides
• A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
• C07K 7/02 - Linear peptides containing at least one abnormal peptide link
• C07K 19/00 - Hybrid peptides
• C07C 13/00 - Cyclic hydrocarbons containing rings other than, or in addition to, six-membered aromatic rings