AR131133A1 - PEGYLATED BOVINE INTERFERON AND METHODS OF USE THEREOF - Google Patents
PEGYLATED BOVINE INTERFERON AND METHODS OF USE THEREOFInfo
- Publication number
- AR131133A1 AR131133A1 ARP230103138A ARP230103138A AR131133A1 AR 131133 A1 AR131133 A1 AR 131133A1 AR P230103138 A ARP230103138 A AR P230103138A AR P230103138 A ARP230103138 A AR P230103138A AR 131133 A1 AR131133 A1 AR 131133A1
- Authority
- AR
- Argentina
- Prior art keywords
- protein
- amino acid
- boifnl3
- seq
- conjugated
- Prior art date
Links
- 241000283690 Bos taurus Species 0.000 title abstract 8
- 102000014150 Interferons Human genes 0.000 title abstract 7
- 108010050904 Interferons Proteins 0.000 title abstract 7
- 229940079322 interferon Drugs 0.000 title abstract 7
- 238000000034 method Methods 0.000 title abstract 2
- 102000004169 proteins and genes Human genes 0.000 abstract 17
- 108090000623 proteins and genes Proteins 0.000 abstract 17
- 125000003275 alpha amino acid group Chemical group 0.000 abstract 6
- 150000001413 amino acids Chemical class 0.000 abstract 6
- 102000039446 nucleic acids Human genes 0.000 abstract 5
- 108020004707 nucleic acids Proteins 0.000 abstract 5
- 150000007523 nucleic acids Chemical class 0.000 abstract 5
- 229920003169 water-soluble polymer Polymers 0.000 abstract 4
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 abstract 2
- 229930182817 methionine Natural products 0.000 abstract 2
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 abstract 2
- 208000007212 Foot-and-Mouth Disease Diseases 0.000 abstract 1
- 241000710198 Foot-and-mouth disease virus Species 0.000 abstract 1
- 241000282849 Ruminantia Species 0.000 abstract 1
- 230000021615 conjugation Effects 0.000 abstract 1
- 239000003937 drug carrier Substances 0.000 abstract 1
- 230000008030 elimination Effects 0.000 abstract 1
- 238000003379 elimination reaction Methods 0.000 abstract 1
- 239000002773 nucleotide Substances 0.000 abstract 1
- 125000003729 nucleotide group Chemical group 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 239000000546 pharmaceutical excipient Substances 0.000 abstract 1
- 208000023504 respiratory system disease Diseases 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/555—Interferons [IFN]
-
- 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
- A61K47/56—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Biochemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Se describe una proteína conjugada de acción prolongada que comprende una proteína l-3 de interferón bovino conjugada con una fracción de polímero soluble en agua a través de un aminoácido no codificado naturalmente en la proteína. También se describen métodos de protección de mamíferos rumiantes contra la fiebre aftosa o la enfermedad respiratoria bovina mediante la administración de la proteína conjugada de acción prolongada. También se describen variantes de la proteína interferón l-3 bovina y variantes que contienen aminoácidos codificados de forma no natural adecuados para la conjugación con sustancias capaces de prolongar la vida media de eliminación de la proteína interferón l-3 bovina, como polímeros solubles en agua. Reivindicación 1: Una proteína conjugada que comprende: una proteína manipulada de interferón l3 bovino (boIFNl3) que tiene una secuencia de aminoácidos que comprende un aminoácido no natural; y un polímero soluble en agua; en donde el polímero soluble en agua se conjuga con la proteína boIFNl3 de ingeniería. Reivindicación 50: Una composición farmacéutica que comprende una proteína conjugada de acuerdo con cualquiera de las reivindicaciones 1 a 49 y un excipiente o vehículo farmacéuticamente aceptable. Reivindicación 51: Una proteína de interferón l3 bovino modificado (boIFNl3) que tiene una secuencia de aminoácidos que comparte al menos un 90% de identidad con SEQ ID Nº 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 o 13, y que comparte menos del 100% de identidad con SEQ ID Nº 1, y opcionalmente en donde la proteína boIFNl3 comprende además una metionina N-terminal; y donde: la secuencia de aminoácidos de la proteína boIFNl3 comprende un aminoácido no natural; o la secuencia de aminoácidos de la proteína boIFNl3 no comprende un aminoácido no natural. Reivindicación 66: Un ácido nucleico que tiene la secuencia de nucleótidos de SEQ ID Nº 27. Reivindicación 67: Un vector que comprende un ácido nucleico que codifica una cualquiera de las SEQ ID Nº 2 a 24. Reivindicación 68: Un vector que comprende un ácido nucleico que codifica SEQ ID Nº 5. Reivindicación 69: Un vector que comprende un ácido nucleico que codifica SEQ ID Nº 18. Reivindicación 70: Un vector que comprende un ácido nucleico que codifica SEQ ID Nº 19. Reivindicación 71: Una proteína de interferón l3 bovino (boIFNl3) modificada que tiene una secuencia de aminoácidos que comprende un aminoácido no natural; en donde la secuencia de aminoácidos de la proteína boIFNl3 diseñada: a) comparte al menos el 90% de identidad con SEQ ID Nº 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 o 24, o b) comparte al menos un 90% de identidad con SEQ ID Nº 14, 15, 16, 17, 18, 20, 21, 22, 23 o 24, y en donde la proteína boIFNl3 comprende además una metionina N-terminal.A long-acting conjugated protein is described comprising a bovine interferon l-3 protein conjugated to a water-soluble polymer moiety via an amino acid not naturally encoded in the protein. Also described are methods of protecting ruminant mammals against foot-and-mouth disease or bovine respiratory disease by administration of the long-acting conjugated protein. Also described are variants of the bovine interferon l-3 protein and variants containing non-naturally encoded amino acids suitable for conjugation to substances capable of prolonging the elimination half-life of the bovine interferon l-3 protein, such as water-soluble polymers. Claim 1: A conjugated protein comprising: an engineered bovine interferon l3 (boIFNl3) protein having an amino acid sequence comprising a non-naturally encoded amino acid; and a water-soluble polymer; wherein the water-soluble polymer is conjugated to the engineered boIFNl3 protein. Claim 50: A pharmaceutical composition comprising a conjugated protein according to any one of claims 1 to 49 and a pharmaceutically acceptable excipient or carrier. Claim 51: A modified bovine interferon l3 (boIFNl3) protein having an amino acid sequence that shares at least 90% identity with SEQ ID NO: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13, and that shares less than 100% identity with SEQ ID NO: 1, and optionally wherein the boIFNl3 protein further comprises an N-terminal methionine; and wherein: the amino acid sequence of the boIFNl3 protein comprises a non-naturally occurring amino acid; or the amino acid sequence of the boIFNl3 protein does not comprise a non-naturally occurring amino acid. Claim 66: A nucleic acid having the nucleotide sequence of SEQ ID NO: 27. Claim 67: A vector comprising a nucleic acid encoding any one of SEQ ID NO: 2 to 24. Claim 68: A vector comprising a nucleic acid encoding SEQ ID NO: 5. Claim 69: A vector comprising a nucleic acid encoding SEQ ID NO: 18. Claim 70: A vector comprising a nucleic acid encoding SEQ ID NO: 19. Claim 71: A modified bovine interferon l3 (boIFNl3) protein having an amino acid sequence comprising a non-naturally occurring amino acid; wherein the amino acid sequence of the designed boIFNl3 protein: a) shares at least 90% identity with SEQ ID No. 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24, or b) shares at least 90% identity with SEQ ID No. 14, 15, 16, 17, 18, 20, 21, 22, 23 or 24, and wherein the boIFNl3 protein further comprises an N-terminal methionine.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202363504133P | 2023-05-24 | 2023-05-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR131133A1 true AR131133A1 (en) | 2025-02-19 |
Family
ID=88975494
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP230103138A AR131133A1 (en) | 2023-05-24 | 2023-11-22 | PEGYLATED BOVINE INTERFERON AND METHODS OF USE THEREOF |
Country Status (2)
| Country | Link |
|---|---|
| AR (1) | AR131133A1 (en) |
| WO (1) | WO2024241086A1 (en) |
Family Cites Families (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4820352A (en) | 1983-01-10 | 1989-04-11 | Bausch & Lomb Incorporated | Cleaning and conditioning solutions for contact lenses and methods of use |
| US5252714A (en) | 1990-11-28 | 1993-10-12 | The University Of Alabama In Huntsville | Preparation and use of polyethylene glycol propionaldehyde |
| US5446090A (en) | 1993-11-12 | 1995-08-29 | Shearwater Polymers, Inc. | Isolatable, water soluble, and hydrolytically stable active sulfones of poly(ethylene glycol) and related polymers for modification of surfaces and molecules |
| US7144574B2 (en) | 1999-08-27 | 2006-12-05 | Maxygen Aps | Interferon β variants and conjugates |
| WO2001062827A2 (en) | 2000-02-22 | 2001-08-30 | Shearwater Corporation | N-maleimidyl polymer derivatives |
| DE10112825A1 (en) | 2001-03-16 | 2002-10-02 | Fresenius Kabi De Gmbh | HESylation of active ingredients in aqueous solution |
| MXPA03009566A (en) | 2001-04-19 | 2004-12-06 | Scripps Research Inst | Methods and composition for the production of orthoganal trna-aminoacyltrna synthetase pairs. |
| DE10207072A1 (en) | 2002-02-20 | 2003-08-28 | Supramol Parenteral Colloids | New N-(haloacetylaminoalkyl) amides of starch carboxylic acids, useful as modifying agents for drugs containing thiol groups, e.g. to increase solubility or plasma half-life or reduce antigenicity |
| BR0314107A (en) | 2002-09-11 | 2005-07-19 | Fresenius Kabi De Gmbh | Production method of hydroxyalkyl starch derivatives |
| DE60327369D1 (en) | 2002-10-16 | 2009-06-04 | Scripps Research Inst | LOCATION-SPECIFIC INSTALLATION OF KETOAMINO ACIDS IN PROTEINS |
| US20060160175A1 (en) | 2003-07-07 | 2006-07-20 | The Scripps Research Institute | Compositions of orthogonal leucyl-trna and aminoacyl-trna synthetase pairs and uses thereof |
| US7527943B2 (en) | 2003-07-07 | 2009-05-05 | The Scripps Research Institute | Compositions of orthogonal glutamyl-tRNA and aminoacyl-tRNA synthetase pairs and uses thereof |
| SI1666604T1 (en) | 2003-07-07 | 2008-08-31 | Scripps Research Inst | Compositions of orthogonal lysyl-tRNA and aminoacyl-tRNA synthetase pairs and uses thereof |
| SG135176A1 (en) | 2004-02-02 | 2007-09-28 | Ambrx Inc | Modified human four helical bundle polypeptides and their uses |
| WO2005092369A2 (en) | 2004-03-11 | 2005-10-06 | Fresenius Kabi Deutschland Gmbh | Conjugates of hydroxyethyl starch and erythropoietin |
| EA010501B1 (en) | 2004-03-11 | 2008-10-30 | Фрезениус Каби Дойчланд Гмбх | Conjugates of hydroxyalkyl starch and a protein, prepared by reductive amination |
| WO2006017232A1 (en) | 2004-07-12 | 2006-02-16 | Taro Pharmaceuticals Industries Ltd. | Topical gel formulation comprising insecticide and its preparation thereof |
| EP1812031B1 (en) | 2004-11-01 | 2015-06-24 | The Regents of the University of California | Compositions and methods for modification of biomolecules |
| US7638491B2 (en) | 2004-12-22 | 2009-12-29 | Ambrx, Inc. | Therapies using non-natural amino acids and polypeptides |
| MX2007007581A (en) | 2004-12-22 | 2007-07-24 | Ambrx Inc | Compositions of aminoacyl-trna synthetase and uses thereof. |
| EP1912668A2 (en) * | 2005-07-20 | 2008-04-23 | ZymoGenetics, Inc. | Il28 and il29 truncated cysteine mutants and antiviral methods of using same |
| JP4829969B2 (en) | 2005-08-18 | 2011-12-07 | アンブルックス，インコーポレイテッド | tRNA compositions and uses thereof |
| KR20080079643A (en) | 2005-11-16 | 2008-09-01 | 암브룩스, 인코포레이티드 | Methods and Compositions Including Non-Natural Amino Acids |
| AU2006326404B2 (en) | 2005-12-14 | 2011-11-03 | Ambrx, Inc. | Compositions containing, methods involving, and uses of non-natural amino acids and polypeptides |
| EP1978989A4 (en) | 2005-12-30 | 2009-03-18 | Ambrx Inc | Compositions containing, methods involving, and uses of non-natural amino acids and polypeptides |
| EP1974025A4 (en) | 2006-01-19 | 2009-03-11 | Ambrx Inc | Non-natural amino acid polypeptides having modulated immunogenicity |
| KR20090100407A (en) | 2006-12-18 | 2009-09-23 | 암브룩스, 인코포레이티드 | Compositions containing non-natural amino acids and polypeptides, methods comprising non-natural amino acids and polypeptides, and uses of non-natural amino acids and polypeptides |
| JP2010514808A (en) | 2006-12-28 | 2010-05-06 | アンブルックス，インコーポレイテッド | Amino acids and polypeptides substituted with phenazine or quinoxaline |
| PE20110426A1 (en) | 2008-07-23 | 2011-07-01 | Ambrx Inc | MODIFIED BOVINE G-CSF POLYPEPTIDES |
| PT2337846T (en) | 2008-09-26 | 2018-04-05 | Ambrx Inc | Non-natural amino acid replication-dependent microorganisms and vaccines |
| US8906384B2 (en) | 2010-12-22 | 2014-12-09 | The United States Of America As Represented By The Secretary Of Agriculture | Antiviral activity of bovine type III interferon against foot-and-mouth disease virus |
| JP5773382B2 (en) | 2010-12-29 | 2015-09-02 | 株式会社Sumco | Silica glass crucible and method for producing the same |
| BR112013030362B1 (en) | 2011-05-27 | 2022-08-30 | Ambrx, Inc | COMPOUND DERIVED FROM DOLASTATIN, METHOD TO DERIVATIZE IT AND PHARMACEUTICAL COMPOSITION COMPRISING SUCH COMPOUND |
| EP2714684B1 (en) | 2011-05-27 | 2018-09-05 | Ambrx, Inc. | Compositions containing, methods involving, and uses of non-natural amino acid linked dolastatin derivatives |
| CN104619349B (en) | 2012-06-07 | 2018-07-10 | Ambrx公司 | Prostate Specific Membrane Antigen Antibody Drug Conjugate |
| US10294273B2 (en) | 2014-04-02 | 2019-05-21 | University Of Rochester | Macrocyclic peptidomimetics for alpha-helix mimicry |
| KR102409470B1 (en) | 2016-06-20 | 2022-06-16 | 엘랑코 유에스 인코포레이티드 | PEGylated porcine interferon and methods of use thereof |
| CN109982714A (en) * | 2016-09-30 | 2019-07-05 | 小利兰·斯坦福大学托管委员会 | Variant type iii interferon and composition-factor |
| PT3630977T (en) | 2017-06-02 | 2024-04-24 | Ambrx Inc | Methods and compositions for promoting non-natural amino acid-containing protein production |
| CN110272479B (en) * | 2018-03-14 | 2023-02-28 | 江苏科技大学 | Bovine lambda 3 interferon mutant and its preparation method and application |
| US20220275041A1 (en) * | 2018-08-23 | 2022-09-01 | Exalt Therapeutics, Llc | Modified ifnl3 polypeptides comprising a pharmacokinetic enhancing moiety and their uses |
-
2023
- 2023-11-22 WO PCT/IB2023/061789 patent/WO2024241086A1/en active Pending
- 2023-11-22 AR ARP230103138A patent/AR131133A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2024241086A1 (en) | 2024-11-28 |
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