IL155656A - Long-acting interferon and interleukin derivatives and pharmaceutical compositions comprising them - Google Patents
Long-acting interferon and interleukin derivatives and pharmaceutical compositions comprising themInfo
- Publication number
- IL155656A IL155656A IL155656A IL15565603A IL155656A IL 155656 A IL155656 A IL 155656A IL 155656 A IL155656 A IL 155656A IL 15565603 A IL15565603 A IL 15565603A IL 155656 A IL155656 A IL 155656A
- Authority
- IL
- Israel
- Prior art keywords
- ifn
- substituted
- interleukin
- cytokine
- derivatives
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract 3
- 102000014150 Interferons Human genes 0.000 title claims 9
- 108010050904 Interferons Proteins 0.000 title claims 9
- 229940079322 interferon Drugs 0.000 title claims 9
- 229940121364 interleukin derivative Drugs 0.000 title 1
- -1 2-sulfo-9-fluorenylmethoxycarbonyl Chemical group 0.000 claims abstract 5
- 125000003277 amino group Chemical group 0.000 claims abstract 5
- 108010063738 Interleukins Proteins 0.000 claims 7
- 102000015696 Interleukins Human genes 0.000 claims 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 5
- 229910006069 SO3H Inorganic materials 0.000 claims 5
- 229910052739 hydrogen Inorganic materials 0.000 claims 5
- 239000001257 hydrogen Substances 0.000 claims 5
- 108010002350 Interleukin-2 Proteins 0.000 claims 3
- 150000003839 salts Chemical class 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 102000004127 Cytokines Human genes 0.000 abstract 4
- 108090000695 Cytokines Proteins 0.000 abstract 4
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 abstract 2
- 229940002612 prodrug Drugs 0.000 abstract 2
- 239000000651 prodrug Substances 0.000 abstract 2
- 230000003190 augmentative effect Effects 0.000 abstract 1
- 230000000975 bioactive effect Effects 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 125000000524 functional group Chemical group 0.000 abstract 1
- 238000001727 in vivo Methods 0.000 abstract 1
- 230000002503 metabolic effect Effects 0.000 abstract 1
- 230000004962 physiological condition Effects 0.000 abstract 1
- 230000008929 regeneration Effects 0.000 abstract 1
- 238000011069 regeneration method Methods 0.000 abstract 1
- 230000002269 spontaneous 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
- A61K47/642—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 the peptide or protein in the drug conjugate being a cytokine, e.g. IL2, chemokine, growth factors or interferons being the inactive part of the conjugate
-
- 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
- A61K47/54—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
- A61K47/555—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 pre-targeting systems involving an organic compound, other than a peptide, protein or antibody, for targeting specific cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Peptides Or Proteins (AREA)
Abstract
Cytokine derivatives are provided bearing functional groups sensitive to mild basic conditions such as fluorenylmethoxycarbonyl (Fmoc) and 2-sulfo-9-fluorenylmethoxycarbonyl (FMS) and pharmaceutical compositions comprising them. Preferred derivates are those in which amino groups of the cytokine are substituted with FMS, for example FMS7-IFN- alpha 2 and FMS3-IL-2. These cytokine derivatives can be administered as inactive or slightly active prodrugs and are capable of undergoing spontaneous regeneration into the parent bioactive drugs under <i>in vivo physiological conditions and in a hom egenous fashion. The cytokine prodrugs present higher metabolic stability and augmented bioavailability.
Description
155656/3
Claims (9)
1. An interferon (IFN)-oc, β or γ, or interleukin (IL) in which at least one free amino or hydroxy group is substituted by a radical of the general formula (i): wherein Ri at position 2 is -SO3H; R2, 3 and R4 are hydrogen; and A is OCO- (herein FMS-IFN or IL), and pharmaceutically acceptable salts thereof.
2. The IFN of claim 1 , wherein said IFN is an IFN-a.
3. The IFN of claim 2, wherein said IFN-a is an IFN-a2.
4. The IFN-a2 of claim 3, in which up to 9 amino groups are substituted with the (2-sulfo)-9-fluorenylmethoxycarbonyl radical (i) wherein Ri at position 2 is -SO3H, R2 to R4 are hydrogen and A is OCO-.
5. The IFN-a2 of claim 4, in which 7 amino groups are substituted with 1/ the (2-sulfo)-9-fluorenylmethoxycarbonyl radical (i) wherein Ri at position 2 is -SO3H, R2 to R.J are hydrogen and A is OCO- (herein designated FMS7- IFN
6. The IL of claim 1 , wherein said interleukin is IL-2 V
7. The IL-2 of claim 6, in which up to 10 amino groups are substituted with the (2-sulfo)-9-fluorenylmethoxycarbonyl radical (i) wherein Rj at position 2 is -SO3H, R2 to R4 are hydrogen and A is OCO-. 155656/3
8. The IL-2 of claim 7, in which 3 amino groups are substituted with the (2-sulfo)-9-fluorenylmethoxycarbonyl radical (i) wherein R| at position 2 is — SO3H, R2 to R4 are hydrogen and A is OCO- (herein designated FMS3-IL-2).
9. A pharmaceutical composition comprising an interferon (IFN) or interleukin (IL) according to any one of claims 1 to 8 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. For the Applicant, Paulk fBen-Ami Ben-Ami & Associates Patent Attorneys
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL155656A IL155656A (en) | 2000-11-01 | 2003-04-29 | Long-acting interferon and interleukin derivatives and pharmaceutical compositions comprising them |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL13940000A IL139400A0 (en) | 2000-11-01 | 2000-11-01 | Long-acting cytokine derivatives and pharmaceutical compositions comprising them |
| PCT/IL2001/001005 WO2002036067A2 (en) | 2000-11-01 | 2001-10-30 | Long-acting cytokine derivatives and pharmaceutical compositions comprising them |
| IL155656A IL155656A (en) | 2000-11-01 | 2003-04-29 | Long-acting interferon and interleukin derivatives and pharmaceutical compositions comprising them |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IL155656A true IL155656A (en) | 2010-02-17 |
Family
ID=11074784
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL13940000A IL139400A0 (en) | 2000-11-01 | 2000-11-01 | Long-acting cytokine derivatives and pharmaceutical compositions comprising them |
| IL155656A IL155656A (en) | 2000-11-01 | 2003-04-29 | Long-acting interferon and interleukin derivatives and pharmaceutical compositions comprising them |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL13940000A IL139400A0 (en) | 2000-11-01 | 2000-11-01 | Long-acting cytokine derivatives and pharmaceutical compositions comprising them |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20040131586A1 (en) |
| EP (1) | EP1337270B1 (en) |
| AT (1) | ATE401098T1 (en) |
| AU (1) | AU2002214223A1 (en) |
| DE (1) | DE60134883D1 (en) |
| IL (2) | IL139400A0 (en) |
| WO (1) | WO2002036067A2 (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL1620118T3 (en) * | 2003-04-08 | 2014-11-28 | Yeda Res & Dev | Reversible pegylated drugs |
| HUE025208T2 (en) * | 2005-06-16 | 2016-03-29 | Nektar Therapeutics | Conjugates having a degradable linkage and polymeric reagents useful in preparing such conjugates |
| WO2011013128A2 (en) | 2009-07-31 | 2011-02-03 | Yeda Research And Development Co. Ltd. | Vectors for delivery of neurotherapeutics to the central nervous system |
| US10166295B2 (en) | 2011-06-02 | 2019-01-01 | Opko Biologics Ltd. | Pegylated OXM variants |
| EA201492269A1 (en) | 2012-06-04 | 2016-02-29 | Опко Байолоджикс Лтд. | PEDIED OXM OPTIONS |
| CN106554296A (en) * | 2015-09-30 | 2017-04-05 | 深圳翰宇药业股份有限公司 | A kind of Fmoc(SO with excellent hydrophilic3H) amino acid of protection and preparation method thereof |
| US12441776B2 (en) | 2018-11-30 | 2025-10-14 | Eirgen Pharma Ltd. | Oxyntomodulin peptide analog formulations |
| CN117551008B (en) * | 2023-11-10 | 2025-10-17 | 沈阳药科大学 | Deferoxamine conjugate and preparation method and application thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL119029A0 (en) * | 1996-08-07 | 1996-11-14 | Yeda Res & Dev | Long-acting drugs and pharamaceutical compositions comprising them |
-
2000
- 2000-11-01 IL IL13940000A patent/IL139400A0/en unknown
-
2001
- 2001-10-30 DE DE60134883T patent/DE60134883D1/en not_active Expired - Lifetime
- 2001-10-30 AU AU2002214223A patent/AU2002214223A1/en not_active Abandoned
- 2001-10-30 AT AT01982682T patent/ATE401098T1/en not_active IP Right Cessation
- 2001-10-30 EP EP01982682A patent/EP1337270B1/en not_active Expired - Lifetime
- 2001-10-30 WO PCT/IL2001/001005 patent/WO2002036067A2/en not_active Ceased
-
2003
- 2003-04-29 IL IL155656A patent/IL155656A/en active IP Right Grant
- 2003-09-02 US US10/415,668 patent/US20040131586A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1337270A2 (en) | 2003-08-27 |
| WO2002036067A2 (en) | 2002-05-10 |
| EP1337270B1 (en) | 2008-07-16 |
| US20040131586A1 (en) | 2004-07-08 |
| IL139400A0 (en) | 2001-11-25 |
| WO2002036067A3 (en) | 2003-01-09 |
| AU2002214223A1 (en) | 2002-05-15 |
| DE60134883D1 (en) | 2008-08-28 |
| EP1337270A4 (en) | 2005-09-14 |
| ATE401098T1 (en) | 2008-08-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| KB | Patent renewed |