CA2434831A1 - Polypeptide drug substances - Google Patents
Polypeptide drug substances Download PDFInfo
- Publication number
- CA2434831A1 CA2434831A1 CA002434831A CA2434831A CA2434831A1 CA 2434831 A1 CA2434831 A1 CA 2434831A1 CA 002434831 A CA002434831 A CA 002434831A CA 2434831 A CA2434831 A CA 2434831A CA 2434831 A1 CA2434831 A1 CA 2434831A1
- Authority
- CA
- Canada
- Prior art keywords
- pharmaceutical agent
- peptide
- species
- composition
- moiety
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract 21
- 229920001184 polypeptide Polymers 0.000 title claims abstract 11
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract 11
- 229940088679 drug related substance Drugs 0.000 title claims abstract 5
- 239000008177 pharmaceutical agent Substances 0.000 claims abstract 18
- 238000000034 method Methods 0.000 claims abstract 9
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 8
- 239000000203 mixture Substances 0.000 claims abstract 6
- -1 cinnamoyl Chemical group 0.000 claims 10
- 229940002612 prodrug Drugs 0.000 claims 3
- 239000000651 prodrug Substances 0.000 claims 3
- 230000001225 therapeutic effect Effects 0.000 claims 3
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 claims 2
- 239000008186 active pharmaceutical agent Substances 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 2
- 125000003118 aryl group Chemical group 0.000 claims 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims 2
- 125000004031 fumaroyl group Chemical group C(\C=C\C(=O)*)(=O)* 0.000 claims 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims 2
- 230000004962 physiological condition Effects 0.000 claims 2
- YFGBQHOOROIVKG-FKBYEOEOSA-N Met-enkephalin Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 YFGBQHOOROIVKG-FKBYEOEOSA-N 0.000 claims 1
- 108010042237 Methionine Enkephalin Proteins 0.000 claims 1
- 230000002378 acidificating effect Effects 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 125000000539 amino acid group Chemical group 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 230000007515 enzymatic degradation Effects 0.000 claims 1
- 230000001747 exhibiting effect Effects 0.000 claims 1
- 238000001727 in vivo Methods 0.000 claims 1
- 208000015181 infectious disease Diseases 0.000 claims 1
- 230000002458 infectious effect Effects 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
- 230000003278 mimic effect Effects 0.000 claims 1
- 238000007911 parenteral administration Methods 0.000 claims 1
- 230000003612 virological effect Effects 0.000 claims 1
- 238000010521 absorption reaction Methods 0.000 abstract 1
- 230000000144 pharmacologic effect Effects 0.000 abstract 1
Classifications
-
- 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
- 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
- A61K47/54—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 an organic compound
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
Abstract
Disclosed herein are novel pharmaceutical agents and compositions, as well as novel methods, to enhance the absorption of polypeptide drug substances that normally display little if any absorbability if administered orally. Also disclosed are novel compositions and methods to significantly enhance the bioavailability and pharmacological efficacy of polypeptide drug substances whether administered orally or parenterally.
Claims (27)
1. A pharmaceutical agent comprising a carrier moiety and a therapeutically active peptide species, wherein the peptide is in the form aa n, where n is the number of amino acid residues in the peptide.
2. The pharmaceutical agent of claim 1, wherein the carrier moiety comprises an aryl or alkyl group of sufficient length or steric bulk to protect the active peptide species from enzymatic degradation in vivo.
3. The pharmaceutical agent of claim 2, wherein the carrier is selected from a group comprising cinnamoyl, benzoyl, phenylacetyl, 3,4-methylenedioxycinnamoyl, 3,4,5-trimethoxycinnamoyl, t-butoxycarbonyl, benzyloxycarbonyl, pivaloyl, N-9-fluorenylmethoxycarbonyl, and fumaroyl.
4. The pharmaceutical agent of claim 1, wherein The carrier moiety is chemically linked to a therapeutically active peptide species of the general formula aa n, where n is an integer from 2 to 40.
5. The pharmaceutical agent of claim 4, wherein the polypeptide is poorly absorbed orally.
6. The pharmaceutical agent of claim 4, wherein n is an integer from 3 to 6.
7. The pharmaceutical agent of claim 6, wherein n is 5.
8. The pharmaceutical agent of claim 4, wherein the therapeutically active peptide species comprises Tyr-Gly-Gly-Phe-Met.
9. The pharmaceutical agent of claim 1, wherein the agent further comprises a linker species linking the peptide to the carrier moiety.
10. The method of claim 1, wherein the method comprises the steps of adding a polypeptide moiety X n, where n = 1 - 3, at one end of the polypeptide drug substance, and where a terminal amino acid of the polypeptide moiety is selected from the group consisting of Pro, Met and Arg, and adding a protecting moiety to the opposite end of the polypeptide drug substance.
11. The pharmaceutical agent of claim 9, wherein the linker species is selected from the group consisting of a natural peptide, a pseudo-peptide, and a peptide mimic, each member of the group comprising 4 or fewer residues.
12. The pharmaceutical agent of claim 11, wherein the linker species is directly bound to the carrier.
13. The pharmaceutical agent of claim 11, wherein the linker species is bound to the carrier through a -C6 or -C8 acidic moiety.
14. The pharmaceutical agent of claim 9, wherein the linker species is Gly-carba-Gly, a pseudo-peptide.
15. The pharmaceutical agent of claim 14, wherein the linker species is associated with a -C n chain, where n is an integer from 6 to 8.
16. A pharmaceutical composition for administration to a patient in need thereof comprising the pharmaceutical agent of claim 1, and one or more pharmaceutically acceptable adjuvants.
17. The pharmaceutical composition of claim 16, wherein the composition is formulated for oral administration.
18. The pharmaceutical composition of claim 16, wherein the composition is formulated for parenteral administration.
19. The pharmaceutical composition of claim 18, wherein the composition is formulated for intravenous administration.
20. The pharmaceutical composition of claim 16, wherein the composition releases a biologically active form of the pharmaceutical agent into the patient's system at physiologically effective levels over a period of time of up to twelve hours.
21. The pharmaceutical composition of claim 16, wherein the composition releases a biologically active form of the pharmaceutical agent into the patient's system at physiologically effective levels over a period of time of up to twenty-four hours.
22. The pharmaceutical composition of claim 18, wherein the peptide species is an epitope or an immune sequence characteristic of an infectious, viral or cancerous disease.
23. A method for the treatment of a physiological condition through administration of a therapeutically effective species comprising the steps of chemically linking a therapeutic polypeptide of the general formula aa n, where as is an amino acid, and where n is an integer from 2 to 40, to an alkyl or aryl carrier moiety to form a pro-drug, and administering the pro-drug to a patient exhibiting the physiological condition.
24. The method of claim 23, wherein the therapeutic polypeptide is poorly absorbed orally.
25. The method of claim 23, wherein the carrier moiety is selected from the group comprising cinnamoyl, benzoyl, phenylacetyl, 3,4-methylenedioxycinnamoyl, 3,4,5-trimethoxycinnamoyl, t-butoxycarbonyl, benzyloxycarbonyl, pivaloyl, N-9-fluorenylmethoxycarbonyl, and fumaroyl
26. The method of claim 23, wherein the pro-drug is administered orally or parenterally.
27. The method of claim 23, wherein the therapeutic polypeptide is chemically linked to the carrier moiety through a linker species.
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US26233701P | 2001-01-17 | 2001-01-17 | |
| US60/262,337 | 2001-01-17 | ||
| US28788601P | 2001-05-01 | 2001-05-01 | |
| US25787201P | 2001-05-01 | 2001-05-01 | |
| US60/257,872 | 2001-05-01 | ||
| US60/287,886 | 2001-05-01 | ||
| US33263601P | 2001-11-06 | 2001-11-06 | |
| US60/332,636 | 2001-11-06 | ||
| PCT/IB2002/000133 WO2002056916A2 (en) | 2001-01-17 | 2002-01-17 | Compositions and methods for enhanced pharmacological activity through oral and parenteral administration of compositions comprising polypeptide drug substances and other poorly absorbed active ingredients |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2434831A1 true CA2434831A1 (en) | 2002-07-25 |
| CA2434831C CA2434831C (en) | 2012-03-06 |
Family
ID=27500604
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2434831A Expired - Lifetime CA2434831C (en) | 2001-01-17 | 2002-01-17 | Polypeptide drug substances |
Country Status (4)
| Country | Link |
|---|---|
| JP (2) | JP5057628B2 (en) |
| CN (2) | CN1545422B (en) |
| AU (1) | AU2002228260B2 (en) |
| CA (1) | CA2434831C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20180110187A (en) * | 2009-05-08 | 2018-10-08 | 테크필즈 바이오켐 코., 엘티디. | High penetration prodrug compositions of peptides and peptide-related compounds |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4396606A (en) * | 1979-11-05 | 1983-08-02 | Addiction Research Foundation | Novel polypeptide analgesics |
| CA1340588C (en) * | 1988-06-13 | 1999-06-08 | Balraj Krishan Handa | Amino acid derivatives |
| ES2245003T3 (en) * | 1996-08-27 | 2005-12-16 | Praecis Pharmaceuticals Incorporated | MODULATORS OF THE AGGREGATION OF BETA-AMYLOOID PEPTIDES THAT INCLUDE D-AMINO ACIDS. |
| US6174993B1 (en) * | 1997-05-21 | 2001-01-16 | The Children's Medical Center Corp. | Short peptides which selectively modulate the activity of serine/threonine kinases |
-
2002
- 2002-01-17 CA CA2434831A patent/CA2434831C/en not_active Expired - Lifetime
- 2002-01-17 CN CN028038320A patent/CN1545422B/en not_active Expired - Fee Related
- 2002-01-17 JP JP2002557423A patent/JP5057628B2/en not_active Expired - Fee Related
- 2002-01-17 AU AU2002228260A patent/AU2002228260B2/en not_active Ceased
- 2002-01-17 CN CN2010102537253A patent/CN101979093B/en not_active Expired - Fee Related
-
2009
- 2009-06-08 JP JP2009137059A patent/JP2009235082A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN1545422A (en) | 2004-11-10 |
| CN101979093A (en) | 2011-02-23 |
| CA2434831C (en) | 2012-03-06 |
| CN101979093B (en) | 2013-04-24 |
| CN1545422B (en) | 2010-09-22 |
| JP2009235082A (en) | 2009-10-15 |
| JP5057628B2 (en) | 2012-10-24 |
| JP2005505492A (en) | 2005-02-24 |
| AU2002228260B2 (en) | 2007-02-08 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |