ES2550040T3 - Péptidos de unión al receptor del factor 1 de crecimiento similar a la insulina - Google Patents
Péptidos de unión al receptor del factor 1 de crecimiento similar a la insulina Download PDFInfo
- Publication number
- ES2550040T3 ES2550040T3 ES11787324.0T ES11787324T ES2550040T3 ES 2550040 T3 ES2550040 T3 ES 2550040T3 ES 11787324 T ES11787324 T ES 11787324T ES 2550040 T3 ES2550040 T3 ES 2550040T3
- Authority
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- Prior art keywords
- insulin
- growth factor
- binding peptides
- receptor binding
- binding
- Prior art date
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- 108090000765 processed proteins & peptides Proteins 0.000 title abstract description 12
- 102000004196 processed proteins & peptides Human genes 0.000 title abstract description 9
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 title abstract description 6
- 230000027455 binding Effects 0.000 title description 14
- 101710184277 Insulin-like growth factor 1 receptor Proteins 0.000 title 1
- 101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 abstract description 5
- 229920001184 polypeptide Polymers 0.000 abstract 3
- 210000002889 endothelial cell Anatomy 0.000 abstract 1
- 230000004927 fusion Effects 0.000 description 8
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 4
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 2
- 108091006027 G proteins Proteins 0.000 description 2
- 102000030782 GTP binding Human genes 0.000 description 2
- 108091000058 GTP-Binding Proteins 0.000 description 2
- 239000006180 TBST buffer Substances 0.000 description 2
- 101710120037 Toxin CcdB Proteins 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 1
- FBKFDSUZBVDZIX-FFGDOFBPSA-N (4s)-4-[[(2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-acetamido-3-phenylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-2-methylpropanoyl]amino]-3-[4-(phosphonomethyl)phenyl]propanoyl]amino]-3-(6-chloro-1h-indol-3-yl)propanoyl]amino]-5-[[1-[[(2s)-1-amino-4-meth Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NC(C)(C)C(=O)N[C@@H](CC=1C=CC(CP(O)(O)=O)=CC=1)C(=O)N[C@@H](CC=1C2=CC=C(Cl)C=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)NC1(CC1)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(C)=O)C1=CC=CC=C1 FBKFDSUZBVDZIX-FFGDOFBPSA-N 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000003746 Insulin Receptor Human genes 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- BTKMJKKKZATLBU-UHFFFAOYSA-N [2-(1,3-benzothiazol-2-yl)-1,3-benzothiazol-6-yl] dihydrogen phosphate Chemical compound C1=CC=C2SC(C3=NC4=CC=C(C=C4S3)OP(O)(=O)O)=NC2=C1 BTKMJKKKZATLBU-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
Classifications
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- 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
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/715—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
- C07K14/7155—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons for interleukins [IL]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
- C07K2319/21—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/61—Fusion polypeptide containing an enzyme fusion for detection (lacZ, luciferase)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Cell Biology (AREA)
- Veterinary Medicine (AREA)
- Wood Science & Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Abstract
Un polipéptido aislado que comprende un polipéptido que tiene la secuencia mostrada en SEC ID Nº: 1-13, en el que dicho polipéptido puede: (a) unirse a IGF1R; y (b) transcitosarse a través de células endoteliales.
Description
E11787324
13-10-2015
Tabla 1a. Secuencias de polipéptidos de péptidos de unión a IGF1R identificados
La unión de proteínas de fusión de péptido-AP purificadas a sIGF1R se evaluó usando ELISA contra sIGF1R inmovilizado. Brevemente, las bacterias transformadas con cada vector de expresión de fusión de péptido-AP se cultivaron durante la noche y al día siguiente los cultivos se clarificaron por centrifugación a 4.500 rpm, 4 ºC. Los
35 sobrenadantes se recogieron y se ensayaron 75 µl de cada sobrenadante para unirse a 2 µg/ml de sIGF1R inmovilizado sobre placas de ELISA. Los péptidos unidos se detectaron usando el sustrato Attophos (Roche, Indianápolis, IN) siguiendo la recomendación del fabricante y se leyeron usando un lector de placas M5 de Molecular Devices. Las fusiones con los clones de péptido 7 y 10 no se expresaron bien. Todas las otras fusiones de péptido-AP mostraron actividad de unión a sIGF1R (Figura 2).
40 Tabla 1b. Secuencias de polinucleótidos de los péptidos de unión a IGF1R
8 E11787324
13-10-2015
25
Se clonaron los péptidos de unión a IGF1R identificados en marco en el extremo C del dominio IgG de la proteína G (PG) en un vector pET17b modificado (EMD Chemicals, Gibbstown, NJ) que tenía un sitio de clonación 30 independiente de la ligación (LIC) para generar fusiones de PG-péptido. El dominio de unión de IgG de la proteína G es estable y así permitió la fácil purificación de la proteína de fusión de lisados bacterianos. La secuencia de aminoácidos del dominio IgG de la proteína G usada se muestra en SEC ID Nº: 31. Las fusiones de PG-péptido se expresaron en bacterias tras la inducción con IPTG 1 mM y se purificaron usando perlas de IgG-Sepharose (GE Healthcare Life Sciences, Piscataway, NJ) a partir de los lisados bacterianos aclarados por centrifugación a 16.000
35 g, 4 ºC durante 20 min.
Se midieron afinidades de unión relativas de las fusiones de PG-péptido para sIGF1R usando ELISA. Las Kd se determinaron usando el software GraphPad Prism 4 con una ecuación de unión a un sitio. Se recubrieron 100 µl de 2 µg/ml de sIGF1R (R&D Systems, Mineápolis, MN) en solución salina tamponada con fosfato de Dulbecco (DPBS (-/40 )) sobre placas Black Maxisorp de 96 pocillos (Nunc, Rochester, NY) durante la noche a 4 ºC. Las placas se lavaron con TBST y los pocillos se bloquearon con 200 µl/pocillo de Starting Block T20 (TBS) (Pierce, Rockford, IL) durante 1 h, temperatura ambiente, con 300 rpm de agitación. Se añadieron 75 µl/pocillo de fusiones de PG-péptido purificadas, diluidas sucesivamente, a partir de la concentración 40 µM, a los pocillos y se incubaron durante 1 h, temperatura ambiente con 300 rpm de mezcla; el volumen se llevó hasta 100 µl con Starting Block T20. Las placas 45 se lavaron 3X con TBST y a continuación se sondaron con 100 µl/pocillo de anticuerpo de conejo marcado con peroxidasa (1:5000) (Rockland, Gilbertsville, PA), se lavaron y la señal se detectó usando 100 µl/pocillo de sustrato POD (Roche, Indianápolis, IN). Se detectó quimioluminiscencia usando un lector de placas M5 de Molecular Devices. Para los ensayos de competición, se añadió factor de crecimiento similar a la insulina 1 (IGF-1) (R&D Systems, Mineápolis, MN) a Starting Block T20 usado para llevar el volumen hasta 100 µl a una concentración de
50 400 nM final.
La caracterización de las fusiones de PG-péptido se resume en la Tabla 2. La mayoría de los péptidos se unieron con afinidades relativas en el intervalo de µM bajo (0,75-8 µM). La proteína de fusión con el clon de péptido 17 fue única en su perfil de unión en el que la curva de unión tuvo forma de campana. Esto es similar a la unión de insulina
55 al receptor de insulina e IGF-1 al IFG1R, induciendo los ligandos desplazamientos conformacionales en los receptores tras la unión y teniendo perfiles de cooperatividad negativos a mayores concentraciones de los ligandos. Los resultados de los estudios de competición con IGF-1 se muestran en la Tabla 2.
60
65
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Claims (1)
-
imagen1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US34893710P | 2010-05-27 | 2010-05-27 | |
| US348937P | 2010-05-27 | ||
| PCT/US2011/037904 WO2011150061A1 (en) | 2010-05-27 | 2011-05-25 | Insulin-like growth factor 1 receptor binding peptides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2550040T3 true ES2550040T3 (es) | 2015-11-04 |
Family
ID=45004356
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES11787324.0T Active ES2550040T3 (es) | 2010-05-27 | 2011-05-25 | Péptidos de unión al receptor del factor 1 de crecimiento similar a la insulina |
Country Status (28)
| Country | Link |
|---|---|
| US (1) | US8415306B2 (es) |
| EP (1) | EP2575846B1 (es) |
| JP (1) | JP5864556B2 (es) |
| KR (1) | KR101898502B1 (es) |
| CN (1) | CN103025341B (es) |
| AU (1) | AU2011258301B2 (es) |
| BR (1) | BR112012030084B1 (es) |
| CA (1) | CA2800744C (es) |
| CY (1) | CY1116757T1 (es) |
| DK (1) | DK2575846T3 (es) |
| EA (1) | EA023541B1 (es) |
| ES (1) | ES2550040T3 (es) |
| HK (1) | HK1183234A1 (es) |
| HR (1) | HRP20151084T1 (es) |
| HU (1) | HUE026269T2 (es) |
| IL (1) | IL223030A (es) |
| ME (1) | ME02206B (es) |
| MX (1) | MX337134B (es) |
| NZ (1) | NZ603611A (es) |
| PL (1) | PL2575846T3 (es) |
| PT (1) | PT2575846E (es) |
| RS (1) | RS54278B1 (es) |
| SG (1) | SG186068A1 (es) |
| SI (1) | SI2575846T1 (es) |
| SM (1) | SMT201500222B (es) |
| UA (1) | UA107596C2 (es) |
| WO (1) | WO2011150061A1 (es) |
| ZA (1) | ZA201209689B (es) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015131256A1 (en) * | 2014-03-06 | 2015-09-11 | National Research Council Of Canada | Insulin-like growth factor 1 receptor -specific antibodies and uses thereof |
| CA2942154C (en) * | 2014-03-06 | 2023-06-27 | National Research Council Of Canada | Insulin-like growth factor 1 receptor -specific antibodies and uses thereof |
| BR112016020643B1 (pt) * | 2014-03-06 | 2023-05-02 | National Research Council Of Canada | Anticorpos específicos para receptor de fator de crescimento semelhante à insulina tipo 1 e uso dos mesmos |
| KR101706296B1 (ko) | 2015-12-21 | 2017-02-13 | 주식회사 브레인온 | 기억력, 학습력, 인지력 향상용 조성물 |
| JP6463499B2 (ja) | 2015-12-21 | 2019-02-06 | ブラインオン， インク | 記憶力、学習力、認知力向上用組成物 |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US6329508B1 (en) | 1989-09-07 | 2001-12-11 | Alkermes, Inc. | Transferrin receptor reactive chimeric antibodies |
| JPH06228199A (ja) * | 1992-11-27 | 1994-08-16 | Takeda Chem Ind Ltd | 血液脳関門通過可能なペプチド結合体 |
| EP1006184A1 (en) * | 1998-12-03 | 2000-06-07 | F. Hoffmann-La Roche Ag | IGF-1 receptor interacting proteins (IIPs) genes coding therefor and uses thereof |
| US20100293669A2 (en) * | 1999-05-06 | 2010-11-18 | Jingdong Liu | Nucleic Acid Molecules and Other Molecules Associated with Plants and Uses Thereof for Plant Improvement |
| US20090087878A9 (en) | 1999-05-06 | 2009-04-02 | La Rosa Thomas J | Nucleic acid molecules associated with plants |
| WO2001007084A1 (en) * | 1999-07-23 | 2001-02-01 | Regents Of The University Of California | Anti-growth factor receptor avidin fusion proteins as universal vectors for drug delivery |
| MXPA02003176A (es) | 1999-10-04 | 2002-09-30 | Shearwater Corp | Neuropeptidos estabilizados por polimero. |
| US20020009491A1 (en) | 2000-02-14 | 2002-01-24 | Rothbard Jonathan B. | Compositions and methods for enhancing drug delivery across biological membranes and tissues |
| ATE402958T1 (de) * | 2000-09-26 | 2008-08-15 | Genentech Inc | Antagonisten des ige-rezeptors |
| US20040142325A1 (en) | 2001-09-14 | 2004-07-22 | Liat Mintz | Methods and systems for annotating biomolecular sequences |
| WO2003082206A2 (en) * | 2002-03-26 | 2003-10-09 | Centocor, Inc. | Multiple sclerosis-related immunoglobulin derived proteins, compositions, methods and uses |
| US7388079B2 (en) * | 2002-11-27 | 2008-06-17 | The Regents Of The University Of California | Delivery of pharmaceutical agents via the human insulin receptor |
| US20050026823A1 (en) | 2003-06-20 | 2005-02-03 | Biomarin Pharmaceutical Inc. | Use of the chaperone receptor-associated protein (RAP) for the delivery of therapeutic compounds to the brain and other tissues |
| US8017151B2 (en) | 2004-09-07 | 2011-09-13 | Board Of Regents Of The University Of Nebraska By And Behalf Of The University Of Nebraska Medical Center | Amphiphilic polymer-protein conjugates and methods of use thereof |
| US20060286103A1 (en) * | 2005-06-15 | 2006-12-21 | Parag Kolhe | Stable antibody formulation |
| US8142781B2 (en) * | 2005-10-07 | 2012-03-27 | Armagen Technologies, Inc. | Fusion proteins for blood-brain barrier delivery |
| WO2008143679A2 (en) * | 2006-06-01 | 2008-11-27 | Verenium Corporation | Nucleic acids and proteins and methods for making and using them |
| EP2197490A2 (en) * | 2007-08-28 | 2010-06-23 | Biogen Idec MA, Inc. | Compositions that bind multiple epitopes of igf-1r |
| ES2564523T3 (es) | 2007-12-19 | 2016-03-23 | Janssen Biotech, Inc. | Diseño y generación de bibliotecas de presentación en fago por pIX de novo humanas mediante fusión con pIX o pVII, vectores, anticuerpos y métodos |
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2011
- 2011-05-25 MX MX2012013710A patent/MX337134B/es active IP Right Grant
- 2011-05-25 HU HUE11787324A patent/HUE026269T2/en unknown
- 2011-05-25 CA CA2800744A patent/CA2800744C/en active Active
- 2011-05-25 US US13/115,523 patent/US8415306B2/en active Active
- 2011-05-25 PL PL11787324T patent/PL2575846T3/pl unknown
- 2011-05-25 DK DK11787324.0T patent/DK2575846T3/en active
- 2011-05-25 SI SI201130557T patent/SI2575846T1/sl unknown
- 2011-05-25 EP EP11787324.0A patent/EP2575846B1/en active Active
- 2011-05-25 CN CN201180025866.2A patent/CN103025341B/zh active Active
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