WO2008089491A2 - Modifications of peptide compositions to increase stability and delivery efficiency - Google Patents
Modifications of peptide compositions to increase stability and delivery efficiency Download PDFInfo
- Publication number
- WO2008089491A2 WO2008089491A2 PCT/US2008/051706 US2008051706W WO2008089491A2 WO 2008089491 A2 WO2008089491 A2 WO 2008089491A2 US 2008051706 W US2008051706 W US 2008051706W WO 2008089491 A2 WO2008089491 A2 WO 2008089491A2
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- WO
- WIPO (PCT)
- Prior art keywords
- peptide
- composition
- carrier
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- therapeutic
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Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C—CHEMISTRY; METALLURGY
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—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
- A61K47/645—Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/31—Fusion polypeptide fusions, other than Fc, for prolonged plasma life, e.g. albumin
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y207/00—Transferases transferring phosphorus-containing groups (2.7)
- C12Y207/11—Protein-serine/threonine kinases (2.7.11)
- C12Y207/11013—Protein kinase C (2.7.11.13)
Definitions
- Figure 4 shows illustrate the conversion of a therapeutic peptide comprising a carrier peptide and a cargo peptide linked via a disulfide bond to a therapeutic peptide in linear form.
- This linear peptide (KP-01547) has been capped at its amino and carboxy termini and contains a short amino acid sequence linker.
- an aliphatic residue is placed at the penultimate carboxy terminal position of the peptide to reduce the rate of disulfide bond exchange.
- the aliphatic residue can be place at either the amino terminal or carboxy terminal side of the residue, or at both sides.
- Disulfide bond exchange can be eliminated completely by linking the carrier and cargo peptides to form a single, linear peptide. This method is discussed below.
- Residues in the recognition sequence can be moved or removed to destroy the recognition site.
- a conservative substitution is made with one or more of the amino acids which comprise an identified protease recognition site.
- the side chains of these amino acids possess a variety of chemical properties.
- the most common amino acids are categorized into 9 groups, listed below. Substitution within these groups is considered to be a conservative substitution.
- carrier and cargo peptides are linked by a peptide bond to form a linear peptide.
- Stability and potency of the therapeutic peptides can also be increased through the construction of peptide multimers, wherein a plurality of cargo peptides is linked to one or more carrier peptides.
- An additional embodiment of the invention involving a cleavable linker sequence is also discussed.
- carries include octa-Arg, octa-D-Arg, and Antennapedia derived peptides, which are known in the art.
- Modification of the carrier showed the great propensity in improving the half life of the composition while modification of the cargo showed little effect.
- CELGSLQAEDD linked to a TAT peptide with a N-Term Cys, which is capped at both ends and disulfide conjugated to the cargo.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Claims
Priority Applications (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2008206077A AU2008206077A1 (en) | 2007-01-19 | 2008-01-22 | Modifications of peptide compositions to increase stability and delivery efficiency |
CN2008800085591A CN101675067B (en) | 2007-01-19 | 2008-01-22 | Modifications of peptide compositions to increase stability and delivery efficiency |
KR1020177024556A KR20170104634A (en) | 2007-01-19 | 2008-01-22 | Modifications of peptide compositions to increase stability and delivery efficiency |
EP17161141.1A EP3248985B1 (en) | 2007-01-19 | 2008-01-22 | Modifications of peptide compositions to increase stability and delivery efficiency |
KR1020197036654A KR102274003B1 (en) | 2007-01-19 | 2008-01-22 | Modifications of peptide compositions to increase stability and delivery efficiency |
KR1020157036605A KR101775929B1 (en) | 2007-01-19 | 2008-01-22 | Modifications of peptide compositions to increase stability and delivery efficiency |
CA2675665A CA2675665C (en) | 2007-01-19 | 2008-01-22 | Modifications of peptide compositions to increase stability and delivery efficiency |
JP2009546577A JP2010516707A (en) | 2007-01-19 | 2008-01-22 | Modification methods for increasing the stability and delivery efficiency of peptide compositions |
EP08728081.4A EP2109619B1 (en) | 2007-01-19 | 2008-01-22 | Modifications of peptide compositions to increase stability and delivery efficiency |
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US88141907P | 2007-01-19 | 2007-01-19 | |
US60/881,419 | 2007-01-19 | ||
US94528507P | 2007-06-20 | 2007-06-20 | |
US60/945,285 | 2007-06-20 |
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WO2008089491A2 true WO2008089491A2 (en) | 2008-07-24 |
WO2008089491A3 WO2008089491A3 (en) | 2008-11-27 |
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Application Number | Title | Priority Date | Filing Date |
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PCT/US2008/051706 WO2008089491A2 (en) | 2007-01-19 | 2008-01-22 | Modifications of peptide compositions to increase stability and delivery efficiency |
Country Status (8)
Country | Link |
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US (6) | US8067532B2 (en) |
EP (2) | EP3248985B1 (en) |
JP (6) | JP2010516707A (en) |
KR (4) | KR20170104634A (en) |
CN (3) | CN101675067B (en) |
AU (1) | AU2008206077A1 (en) |
CA (2) | CA2989778C (en) |
WO (1) | WO2008089491A2 (en) |
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2008
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