WO2007130302A2 - Rage fusion proteins, formulations, and methods of use thereof - Google Patents

Rage fusion proteins, formulations, and methods of use thereof Download PDF

Info

Publication number
WO2007130302A2
WO2007130302A2 PCT/US2007/010125 US2007010125W WO2007130302A2 WO 2007130302 A2 WO2007130302 A2 WO 2007130302A2 US 2007010125 W US2007010125 W US 2007010125W WO 2007130302 A2 WO2007130302 A2 WO 2007130302A2
Authority
WO
WIPO (PCT)
Prior art keywords
rage
seq
fusion protein
amino acid
sequence
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.)
Ceased
Application number
PCT/US2007/010125
Other languages
English (en)
French (fr)
Other versions
WO2007130302A3 (en
Inventor
Adnan M.M. Mjalli
Robert Rothlein
Ye Edward Tian
Jeffrey C. Webster
Eric J. Benjamin
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
vTv Therapeutics LLC
Original Assignee
Trans Tech Pharma Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority to BRPI0711193-2A priority Critical patent/BRPI0711193A2/pt
Application filed by Trans Tech Pharma Inc filed Critical Trans Tech Pharma Inc
Priority to AU2007248784A priority patent/AU2007248784B2/en
Priority to EA200870502A priority patent/EA017291B1/ru
Priority to NZ571692A priority patent/NZ571692A/en
Priority to JP2009509615A priority patent/JP5558810B2/ja
Priority to MX2008013863A priority patent/MX2008013863A/es
Priority to CA002651348A priority patent/CA2651348A1/en
Priority to EP07794379A priority patent/EP2021474A2/en
Publication of WO2007130302A2 publication Critical patent/WO2007130302A2/en
Publication of WO2007130302A3 publication Critical patent/WO2007130302A3/en
Priority to IL194482A priority patent/IL194482A0/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

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
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • 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
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • 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
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • 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
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
    • 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
    • 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
    • C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Definitions

  • AGEs display specific and saturable binding to cell surface receptors on monocytes, macrophages, endothelial cells of the micro vasculature, smooth muscle cells, mesengial cells, and neurons.
  • the Receptor for Advanced Glycated Endproducts is a member of the immunoglobulin supergene family of molecules.
  • the extracellular (N-terminal) domain of RAGE includes three immunoglobulin-type regions: one V (variable) type domain followed by two C-type (constant) domains (Neeper et al, J. Biol. Chem., 267:14998-15004 (1992); Schmidt et al, Circ. (Supply 96# 194 (1997)).
  • a modulator compound may increase or decrease activity, or change the characteristics, or functional or immunological properties of the RAGE, or a portion threof
  • a modulator compound may include natural and/or chemically synthesized or artificial peptides, modified peptides (e.g., phosphopeptides), antibodies, carbohydrates, monosaccharides, oligosaccharides, polysaccharides, glycolipids, heterocyclic compounds, nucleosides or nucleotides or parts thereof, and small organic or inorganic molecules.
  • a modulator compound may be an endogenous physiological compound or it may be a natural or synthetic compound. Or, the modulator compound may be a small organic molecule.
  • modulator compound also includes a chemically modified ligand or compound, and includes isomers and racemic forms.
  • an "antagonist” comprises a compound that binds to an agonist or to a receptor to form a complex that does not give rise to a substantial pharmacological response and can inhibit the biological response induced by an agonist.
  • composition is used herein to denote a composition that may be administered to a mammalian host, e.g., orally, parenterally, topically, by inhalation spray, intranasally, or rectally, in unit dosage formulations containing conventional non- toxic carriers, diluents, adjuvants, vehicles and the like.
  • parenteral as used herein, includes subcutaneous injections, intravenous, intramuscular, intracisternal injection, or infusion techniques.
  • the lyoprotectant may be added to the pre-lyophilized formulation in a "lyoprotecting amount" which means that, following lyophilization of the protein in the presence of the lyoprotecting amount of the lyoprotectant, the RAGE fusion protein essentially retains its physical and chemical stability and biological activity upon lyophilization and storage.
  • the "diluent" for a lyophilized formulation herein is one which is pharmaceutically acceptable (safe and non-toxic for administration to a human) and is useful for the preparation of a reconstituted formulation.
  • Exemplary diluents include sterile water, bacteriostatic water for injection (BWFI), a pH buffered solution (e.g.
  • the ligand binding site may comprise, a RAGE V domain or a portion thereof such as the RAGE ligand binding domain (e.g., amino acids 1-118, 23-118, 24-118, 31-118, 1-116, 23-116, 24-116, 31-116, 1-54, 23-54, 24- 54, 31-54, 1-53, 23-53, 24-53, or 31-53 of SEQ ID NO: 1, or fragments thereof).
  • RAGE V domain e.g., amino acids 1-118, 23-118, 24-118, 31-118, 1-116, 23-116, 24-116, 31-116, 1-54, 23-54, 24- 54, 31-54, 1-53, 23-53, 24-53, or 31-53 of SEQ ID NO: 1, or fragments thereof.
  • fragments of the polypeptides that functionally bind a RAGE ligand may be used.
  • the RAGE polypeptide may comprise amino acids 227-317 of human RAGE (SEQ ID NO: 12) or a sequence at least 90% identical thereto, corresponding to the C2 domain of RAGE.
  • the RAGE polypeptide may comprise amino acids 23-123 of human RAGE (SEQ ID NO: 13) or a sequence at least 90% identical thereto, or amino acids 24-123 of human RAGE (SEQ ID NO: 14) or a sequence at least 90% identical thereto, corresponding to the V domain of RAGE and a downstream interdomain linker.
  • the RAGE polypeptide may comprise amino acids 24-123 of human RAGE where Q24 cyclizes to form pE (SEQ ID NO: 48) or a sequence at least 90% identical thereto.
  • the RAGE fusion protein of the present invention may comprise a single or multiple domains from RAGE.
  • the RAGE polypeptide comprising an interdomain linker linked to a RAGE polypeptide domain may comprise a fragment of full-length RAGE protein.
  • the RAGE polypeptide may comprise amino acids 23-136 of human RAGE (SEQ ID NO: 15) or a sequence at least 90% identical thereto or amino acids 24-136 of human RAGE (SEQ ID NO: 16) or a sequence at least 90% identical thereto, or amino acids 24-136 of human RAGE where Q24 cyclizes to form pE (SEQ ID NO: 49), or a sequence at least 90% identical thereto, corresponding to the V domain of RAGE and a downstream interdomain linker.
  • the RAGE fusion protein may comprise a first RAGE immunoglobulin domain and a first RAGE interdomain linker linked to a second RAGE immunoglobulin domain and a second RAGE interdomain linker, such that the N-terminal amino acid of the first interdomain linker is linked to the C-terminal amino acid of the first RAGE immunoglobulin domain, the N-terminal amino acid of the second RAGE immunoglobulin domain is linked to C-terminal amino acid of the first interdomain linker, the N-terminal amino acid of the second interdomain linker is linked to C-terminal amino acid of the second RAGE immunoglobulin domain, and the C-terminal amino acid of the RAGE second interdomain linker is directly linked to the N-terminal amino acid of the C H 2 immunoglobulin domain.
  • sRAGE can have a therapeutic benefit in the modulation of RAGE- mediated diseases
  • human sRAGE may have limitations as a stand-alone therapeutic based on the relatively short half-life of sRAGE in plasma. For example, whereas rodent sRAGE has a half-life in normal and diabetic rats of approximately 20 hours, human sRAGE has a half-life of less than 2 hours when assessed by retention of imrnunoreactivity sRAGE (Renard et al., J. Pharmacol. Exp. liter., 290:1458-1466 (1999)).
  • the present invention may also comprise methods for the treatment of RAGE- mediated disorder in a human subject.
  • the method may comprise administering to a subject a RAGE fusion protein comprising a RAGE polypeptide comprising a RAGE ligand binding site linked to a second, non-RAGE polypeptide.
  • the RAGE formulation comprises a lyophilized
  • the reconstituted RAGE fusion protein formulation may be suitable for administration by various routes and as is required for treatment of the RAGE- mediated disorder of interest.
  • the reconstituted RAGE fusion protein formulation is suitable for at least one of intravenous, intraperitoneal, or subcutaneous administration of the formulation to a subject.
  • the RAGE fusion proteins TTP-4000 (TT4) and TTP- 3000 (TT3) specifically interact with known RAGE ligands amyloid-beta (Abeta), SlOOb (S 100), and amphoterin (Ampho).
  • amyloid-beta amyloid-beta
  • SlOOb S 100
  • Ampho amphoterin
  • BSA coating alone BSA or BSA + wash
  • amyloid beta is used as the labeled ligand it may be necessary to preincubate the amyloid beta before the assay. Preincubation may allow the amyloid beta to self-aggregate into pleated sheet form, as amyloid beta may preferentially bind to RAGE in the form of a pleated sheet.
  • TTP-4000 was also compared to sRAGE in a disease relevant animal model of stroke.
  • the middle carotid artery of a mouse was ligated for 1 hour followed by 23 hours of reperfusion at which point the mice were sacrificed and the area of the infarct in the brain was assessed.
  • Mice were treated with sRAGE or TTP- 4000 or control immunoglobulin just prior to reperfusion.
  • male C57BL/6 were injected with vehicle at 250 ⁇ l/mouse or TTP test articles (TTP-3000, TTP-4000 at 250 ⁇ l ⁇ nouse). Mice were injected intraperitoneally, 1 hour after the initiation of ischemia.
  • RAGE blockade may be expected to block allogeneic transplant rejection.
  • mice were made diabetic by a single intravenous injection of streptozotocin (STZ) (Sigma Chemical Co., St. Louis, MO) at 200 mg/kg.
  • STZ streptozotocin
  • BALB BALB mice served as donors for islet transplantation, thus providing ah allo-mismatch for islet transplants.
  • lyoprotectants and buffers were initially screened by measuring the stability of the protein after lyophilization and reconstitution.
  • the lyophilized protein in each formulation was also subjected to accelerated stability studies to determine the potential stability of the protein over its shelf-life.
  • the pre-lyophilized formulation (16.67 mL) was added to each 50 mL vial.
  • the samples were exposed to a freeze-drying cycle where the samples cooled at a shelf temperature of between 5 0 C and -5 0 C for 30 min, followed by cooling at a shelf temperature of -50 0 C for approximately 3 hours.
  • the samples were dried at a reduced pressure of 100 mTorr and a shelf temperature of between -20 0 C and -10 0 C for approximately 34 hours, followed by a shelf temperature of between 5 0 C and 20 0 C for approximately 11 hours.
  • the vials were stoppered, and the tops were crimped.
  • a pharmaceutically elegant, white cake was produced. The cake appeared rugged and did not lose its structure during handling and storage.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Zoology (AREA)
  • Molecular Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Rheumatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Diabetes (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Neurosurgery (AREA)
  • Cardiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Toxicology (AREA)
  • Cell Biology (AREA)
  • Urology & Nephrology (AREA)
  • Heart & Thoracic Surgery (AREA)
PCT/US2007/010125 2006-05-05 2007-04-25 Rage fusion proteins, formulations, and methods of use thereof Ceased WO2007130302A2 (en)

Priority Applications (9)

Application Number Priority Date Filing Date Title
EP07794379A EP2021474A2 (en) 2006-05-05 2007-04-25 Rage fusion proteins, formulations, and methods of use thereof
AU2007248784A AU2007248784B2 (en) 2006-05-05 2007-04-25 RAGE fusion proteins, formulations, and methods of use thereof
EA200870502A EA017291B1 (ru) 2006-05-05 2007-04-25 Белки слияния на основе rage, их композиции и способы их применения
NZ571692A NZ571692A (en) 2006-05-05 2007-04-25 Rage fusion proteins, formulations, and methods of use thereof
JP2009509615A JP5558810B2 (ja) 2006-05-05 2007-04-25 Ｒａｇｅ融合タンパク質、製剤及びその使用方法
BRPI0711193-2A BRPI0711193A2 (pt) 2006-05-05 2007-04-25 proteÍnas de fusço rage, formulaÇÕes e mÉtodos de uso dos mesmos
CA002651348A CA2651348A1 (en) 2006-05-05 2007-04-25 Rage fusion proteins, formulations, and methods of use thereof
MX2008013863A MX2008013863A (es) 2006-05-05 2007-04-25 Proteinas de fusion de rage y sus metodos de uso.
IL194482A IL194482A0 (en) 2006-05-05 2008-10-02 Rage fusion proteins, formulations, and methods of use thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US79845506P 2006-05-05 2006-05-05
US60/798,455 2006-05-05

Publications (2)

Publication Number Publication Date
WO2007130302A2 true WO2007130302A2 (en) 2007-11-15
WO2007130302A3 WO2007130302A3 (en) 2008-04-03

Family

ID=38521887

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2007/010125 Ceased WO2007130302A2 (en) 2006-05-05 2007-04-25 Rage fusion proteins, formulations, and methods of use thereof

Country Status (21)

Country Link
US (2) US7981424B2 (OSRAM)
EP (2) EP2380983A3 (OSRAM)
JP (1) JP5558810B2 (OSRAM)
KR (1) KR20090008459A (OSRAM)
CN (1) CN101548012A (OSRAM)
AR (1) AR060862A1 (OSRAM)
AU (1) AU2007248784B2 (OSRAM)
BR (1) BRPI0711193A2 (OSRAM)
CA (1) CA2651348A1 (OSRAM)
DO (1) DOP2007000089A (OSRAM)
EA (1) EA017291B1 (OSRAM)
IL (1) IL194482A0 (OSRAM)
MX (1) MX2008013863A (OSRAM)
NL (1) NL2000626A1 (OSRAM)
NZ (1) NZ571692A (OSRAM)
PE (1) PE20080397A1 (OSRAM)
SG (1) SG171670A1 (OSRAM)
TW (1) TW200801036A (OSRAM)
UY (1) UY30324A1 (OSRAM)
WO (1) WO2007130302A2 (OSRAM)
ZA (1) ZA200809394B (OSRAM)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008100470A3 (en) * 2007-02-15 2008-12-24 Transtech Pharma Inc Rage - immunoglobulin fusion proteins
US20100173277A1 (en) * 2007-02-15 2010-07-08 Fukuoka University Agent for Suppressing Rejection in Organ Transplantation Comprising Anti-HMGB-1 Antibody
WO2011102860A1 (en) * 2010-02-18 2011-08-25 Transtech Pharma, Inc. Rage fusion protein compositions and methods of use
US20120039908A1 (en) * 2009-04-20 2012-02-16 Pfizer Inc Control of Protein Glycosylation and Compositions and Methods Relating Thereto
US8398977B2 (en) 2007-06-14 2013-03-19 Galactica Pharmaceuticals, Inc. Rage fusion proteins
US8470325B2 (en) 2007-02-15 2013-06-25 Kagoshima University Method of treating amykloidosis comprising administering an anti-HMGB-1 antibody
US8877192B2 (en) 2004-08-03 2014-11-04 Transtech Pharma, Llc Rage fusion proteins and methods of use
US11311002B2 (en) 2014-10-01 2022-04-26 National Agriculture And Food Research Organization Biotinylated and oxidized LDL receptor and advanced glycation end product receptor produced using genetically engineered silkworm

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101010430A (zh) * 2004-08-03 2007-08-01 转化技术制药公司 Rage融合蛋白及使用方法
WO2007073272A1 (en) * 2005-12-23 2007-06-28 Gcoder Systems Ab Positioning pattern
US20090004190A1 (en) * 2006-02-09 2009-01-01 Mjalli Adnan M M Rage Fusion Proteins And Methods Of Use
EP2380983A3 (en) 2006-05-05 2012-12-05 TransTech Pharma Inc. RAGE fusion proteins, formulations, and methods of use thereof
WO2008099920A1 (ja) * 2007-02-15 2008-08-21 Kyushu University, National University Corporation 抗hmgb-1抗体を含む間質性肺疾患治療剤
WO2013074820A1 (en) 2011-11-16 2013-05-23 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Immunogenic tumor associated stromal cell antigen peptides and methods of their use
US10251935B2 (en) 2012-11-28 2019-04-09 Nono Inc. Lyophilized formulation comprising tat-NR2B9C, histidine and trehalose
PT2925338T (pt) * 2012-11-28 2019-05-31 Nono Inc Formulação liofilizada de tat-nr2b9c
EP3633381A3 (en) 2013-12-05 2020-07-29 The Broad Institute, Inc. Compositions and methods for identifying and treating cachexia or pre-cachexia
WO2016201368A1 (en) 2015-06-10 2016-12-15 The Broad Institute Inc. Antibodies, compounds and screens for identifying and treating cachexia or pre-cachexia
WO2017106196A1 (en) 2015-12-14 2017-06-22 The Broad Institute, Inc. Compositions and methods for treating cardiac dysfunction
CN112699601B (zh) * 2020-12-28 2022-05-31 电子科技大学 一种传感器网络数据的空时重构方法
US20230246158A1 (en) * 2022-02-02 2023-08-03 Enevate Corporation Cycle life in si/li batteries using high temperature deep discharge cycling

Family Cites Families (69)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4867973A (en) 1984-08-31 1989-09-19 Cytogen Corporation Antibody-therapeutic agent conjugates
US6018026A (en) 1988-01-22 2000-01-25 Zymogenetics, Inc. Biologically active dimerized and multimerized polypeptide fusions
US5567584A (en) 1988-01-22 1996-10-22 Zymogenetics, Inc. Methods of using biologically active dimerized polypeptide fusions to detect PDGF
NZ235148A (en) 1989-09-05 1991-12-23 Immunex Corp Tumour necrosis factor receptor protein and dna sequences
MX9204374A (es) 1991-07-25 1993-03-01 Idec Pharma Corp Anticuerpo recombinante y metodo para su produccion.
SE9201073D0 (sv) 1992-04-03 1992-04-03 Kabi Pharmacia Ab Protein formulation
JP3589665B2 (ja) 1992-10-23 2004-11-17 イミュネックス・コーポレーション 可溶性オリゴマー蛋白質の調製法
US5656261A (en) 1995-01-18 1997-08-12 The Picower Institute For Medical Research Preventing and reversing advanced glycosylation endproducts
CN1142778C (zh) 1995-01-18 2004-03-24 奥尔顿有限公司 噻唑鎓化合物用于预防和逆转高级糖基化终产物形成的用途
NO315930B1 (no) 1995-01-18 2003-11-17 Picower Inst For Medical Res T Anvendelse av tiazoliumforbindelser ved fremstilling av farmasöytiske preparater, preparater som inneholder forbindelsene, samt nyetiazoliumforbindelser
EP0827511A1 (en) 1995-04-05 1998-03-11 The Picower Institute For Medical Research Agents for binding to advanced glycosylation endproducts, and methods of their use
US5747035A (en) 1995-04-14 1998-05-05 Genentech, Inc. Polypeptides with increased half-life for use in treating disorders involving the LFA-1 receptor
US6267958B1 (en) * 1995-07-27 2001-07-31 Genentech, Inc. Protein formulation
AU1832797A (en) 1996-01-26 1997-08-20 Trustees Of Columbia University In The City Of New York, The A polypeptide from lung extract which binds amyloid-beta peptide
WO1997039121A1 (en) 1996-04-16 1997-10-23 Schering Aktiengesellschaft Advanced glycosylation end-product receptor peptides and uses therefor
US5864018A (en) 1996-04-16 1999-01-26 Schering Aktiengesellschaft Antibodies to advanced glycosylation end-product receptor polypeptides and uses therefor
US7081241B1 (en) 1998-10-06 2006-07-25 The Trustees Of Columbia University In The City Of New York Extracellular rage binding protein (EN-RAGE) and uses thereof
US6555651B2 (en) 1997-10-09 2003-04-29 The Trustees Of Columbia University In The City Of New York Ligand binding site of rage and uses thereof
US6790443B2 (en) 1996-11-22 2004-09-14 The Trustees Of Columbia University In The City Of New York Method for treating symptoms of diabetes
US7258857B2 (en) 1996-11-22 2007-08-21 The Trustees Of Columbia University In The City Of New York Rage-related methods for treating inflammation
WO2000020621A1 (en) 1998-10-06 2000-04-13 The Trustees Of Columbia University In The City Of New York Extracellular novel rage binding protein (en-rage) and uses thereof
AU748768B2 (en) 1997-03-11 2002-06-13 General Hospital Corporation, The Identification of agents for use in the treatment of Alzheimer's disease
US7101838B2 (en) 1997-08-05 2006-09-05 The Trustees Of Columbia University In The City Of New York Method to prevent accelerated atherosclerosis using (sRAGE) soluble receptor for advanced glycation endproducts
ZA988461B (en) 1997-09-18 1999-03-30 Idec Pharma Corp Synergistic composition and methods for treating neoplastic or cancerous growths and for restoring or boosting hematopoiesis
US6380165B1 (en) 1997-09-19 2002-04-30 The Picower Institute For Medical Research Immunological advanced glycation endproduct crosslink
US6761888B1 (en) 2000-05-26 2004-07-13 Neuralab Limited Passive immunization treatment of Alzheimer's disease
US6323218B1 (en) 1998-03-11 2001-11-27 The General Hospital Corporation Agents for use in the treatment of Alzheimer's disease
US20020102604A1 (en) 1999-12-08 2002-08-01 Milne Edwards Jean-Baptiste Dumas Full-length human cDNAs encoding potentially secreted proteins
US6465422B1 (en) 1998-04-17 2002-10-15 The Trustees Of Columbia University In The City Of New York Method for inhibiting tumor invasion or spreading in a subject
EP1118681A1 (en) 1998-09-29 2001-07-25 Asahi Kasei Kabushiki Kaisha Method for controlling the release of granules
DE69918146T2 (de) * 1998-10-05 2005-07-07 Pharmexa A/S Verfahren zur therapeutischen impfung
US6753150B2 (en) 1998-10-05 2004-06-22 The Trustees Of Columbia University In The City Of New York Method for determining whether a compound is capable of inhibiting the interaction of a peptide with rage
US6197294B1 (en) 1998-10-26 2001-03-06 Neurotech S.A. Cell surface molecule-induced macrophage activation
US6605642B2 (en) 1999-04-05 2003-08-12 City Of Hope Inhibitors of formation of advanced glycation endproducts (AGES)
US6589944B1 (en) 1999-04-05 2003-07-08 City Of Hope Breakers of advanced glycation endproducts
US6787566B2 (en) 1999-04-05 2004-09-07 City Of Hope Breakers of advanced glycation endproducts
US6939545B2 (en) 1999-04-28 2005-09-06 Genetics Institute, Llc Composition and method for treating inflammatory disorders
US6835200B2 (en) 1999-06-22 2004-12-28 Ndo Surgical. Inc. Method and devices for tissue reconfiguration
FR2797402B1 (fr) 1999-07-15 2004-03-12 Biomerieux Stelhys Utilisation d'un polypeptide pour detecter, prevenir ou traiter un etat pathologique associe a une maladie degenerative, neurologique ou autoimmune
CA2382095A1 (en) 1999-08-13 2001-02-22 The Trustees Of Columbia University In The City Of New York Methods of inhibiting binding of .beta.-sheet fibril to rage and consequences thereof
WO2001018060A1 (fr) 1999-09-08 2001-03-15 Toray Industries, Inc. Materiaux de circulation extracorporelle, adsorbants de facteurs de complication diabetique, reservoirs servant a eliminer des facteurs de complication diabetique et procede d'elimination de facteurs de complication diabetique
US20050170382A1 (en) 1999-10-06 2005-08-04 The Trustees Of Columbia University In The City Of New York. RAGE-related compositions
WO2001029269A2 (en) 1999-10-21 2001-04-26 Case Western Reserve University Gene expression profiling of inflammatory bowel disease
US6716635B2 (en) 2000-04-14 2004-04-06 University Of Kentucky Research Foundation Method for identifying regulators of protein-advanced glycation end product (protein-AGE) formation
US20010041349A1 (en) 2000-04-17 2001-11-15 Andrew Patron Protein expression system arrays and use in biological screening
US6563015B1 (en) 2000-08-14 2003-05-13 The Trustees Of Columbia University In The City Of New York Transgenic mice over-expressing receptor for advanced glycation endproduct (RAGE) and mutant APP in brain and uses thereof
US6825164B1 (en) 2000-08-14 2004-11-30 The Trustees Of Columbia University In The City Of New York Method to increase cerebral blood flow in amyloid angiopathy
EP1334207A2 (en) 2000-10-02 2003-08-13 Reddy US Therapeutics, Inc. Methods and compositions for the treatment of inflammatory diseases
WO2002030889A2 (en) 2000-10-13 2002-04-18 The Trustees Of Columbia University In The City Of New York A method for inhibiting new tissue growth in blood vessels in a patient subjected to blood vessel injury
US20050244849A1 (en) 2000-12-15 2005-11-03 Genetics Institute, Llc Screening assays for rheumatoid arthritis
WO2002066978A2 (en) 2000-12-29 2002-08-29 Reddy Us Therapeutics, Inc. Detection of compounds that modulate inflammatory responses
BR0207267A (pt) 2001-02-19 2004-02-10 Merck Patent Gmbh Proteìnas artificiais com imunogenicidade reduzida
JP3837494B2 (ja) 2001-03-19 2006-10-25 国立大学法人金沢大学 可溶型ｒａｇｅタンパク質
US7304034B2 (en) 2001-05-15 2007-12-04 The Feinstein Institute For Medical Research Use of HMGB fragments as anti-inflammatory agents
BR0313491A (pt) * 2002-08-16 2007-08-14 Wyeth Corp composições e métodos para tratar distúrbios associados ao rage
US8067371B2 (en) 2003-05-09 2011-11-29 The Trustees Of Columbia University In The City Of New York RAGE G82S-related methods and compositions for treating inflammatory disorders
US20050008649A1 (en) 2003-06-02 2005-01-13 University Of Miami Chimeric molecules and methods of use
ZA200601810B (en) 2003-09-05 2008-05-28 Univ Columbia Rage-related methods and compositions for treating glomerular injury
WO2005042032A1 (en) 2003-10-31 2005-05-12 The Trustees Of Columbia University In The City Of New York Methods for treating multiple sclerosis
US20060012414A1 (en) * 2004-07-15 2006-01-19 Texas Instruments Incorporated Circuit and method for generating a polyphase clock signal and system incorporating the same
WO2006012414A2 (en) 2004-07-20 2006-02-02 Critical Therapeutics, Inc. Novel polyadenylation signal for use in expression vectors
US7470521B2 (en) 2004-07-20 2008-12-30 Critical Therapeutics, Inc. RAGE protein derivatives
NZ552128A (en) 2004-08-03 2009-09-25 Transtech Pharma Inc Rage fusion proteins without Fc hinge region and methods of use
CN101010430A (zh) 2004-08-03 2007-08-01 转化技术制药公司 Rage融合蛋白及使用方法
JP2008537874A (ja) 2004-09-27 2008-10-02 セントカー・インコーポレーテツド ｓＲＡＧＥミメティボディ、組成物、方法および使用
US20080207499A1 (en) 2005-06-29 2008-08-28 Gaetano Barile Rage-related methods for treating and preventing diabetic retinopathy
US20090004190A1 (en) 2006-02-09 2009-01-01 Mjalli Adnan M M Rage Fusion Proteins And Methods Of Use
EP2380983A3 (en) 2006-05-05 2012-12-05 TransTech Pharma Inc. RAGE fusion proteins, formulations, and methods of use thereof
WO2008100470A2 (en) 2007-02-15 2008-08-21 Transtech Pharma, Inc. Rage - immunoglobulin fusion proteins

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8877192B2 (en) 2004-08-03 2014-11-04 Transtech Pharma, Llc Rage fusion proteins and methods of use
WO2008100470A3 (en) * 2007-02-15 2008-12-24 Transtech Pharma Inc Rage - immunoglobulin fusion proteins
US20100173277A1 (en) * 2007-02-15 2010-07-08 Fukuoka University Agent for Suppressing Rejection in Organ Transplantation Comprising Anti-HMGB-1 Antibody
US8470325B2 (en) 2007-02-15 2013-06-25 Kagoshima University Method of treating amykloidosis comprising administering an anti-HMGB-1 antibody
US8398977B2 (en) 2007-06-14 2013-03-19 Galactica Pharmaceuticals, Inc. Rage fusion proteins
US9066927B2 (en) 2007-06-14 2015-06-30 Galactica Pharmaceuticals, Inc. Methods of treatment using rage fusion proteins
US9399668B2 (en) 2007-06-14 2016-07-26 Galactica Pharmaceuticals, Inc. Nucleic acids encoding rage fusion proteins
US20120039908A1 (en) * 2009-04-20 2012-02-16 Pfizer Inc Control of Protein Glycosylation and Compositions and Methods Relating Thereto
US9034341B2 (en) * 2009-04-20 2015-05-19 Transtech Pharma, Llc Control of RAGE fusion protein glycosylation and RAGE fusion protein compositions
WO2011102860A1 (en) * 2010-02-18 2011-08-25 Transtech Pharma, Inc. Rage fusion protein compositions and methods of use
US11311002B2 (en) 2014-10-01 2022-04-26 National Agriculture And Food Research Organization Biotinylated and oxidized LDL receptor and advanced glycation end product receptor produced using genetically engineered silkworm

Also Published As

Publication number Publication date
US8344120B2 (en) 2013-01-01
US20110282035A1 (en) 2011-11-17
EP2380983A3 (en) 2012-12-05
CN101548012A (zh) 2009-09-30
EA200870502A1 (ru) 2009-06-30
PE20080397A1 (es) 2008-04-28
EA017291B1 (ru) 2012-11-30
IL194482A0 (en) 2011-08-01
EP2380983A2 (en) 2011-10-26
US7981424B2 (en) 2011-07-19
SG171670A1 (en) 2011-06-29
US20080045455A1 (en) 2008-02-21
JP5558810B2 (ja) 2014-07-23
AU2007248784A1 (en) 2007-11-15
NZ571692A (en) 2012-01-12
WO2007130302A3 (en) 2008-04-03
KR20090008459A (ko) 2009-01-21
UY30324A1 (es) 2008-01-02
NL2000626A1 (nl) 2007-11-06
JP2009536201A (ja) 2009-10-08
CA2651348A1 (en) 2007-11-15
EP2021474A2 (en) 2009-02-11
ZA200809394B (en) 2009-07-29
AR060862A1 (es) 2008-07-16
MX2008013863A (es) 2008-11-14
DOP2007000089A (es) 2007-11-15
BRPI0711193A2 (pt) 2013-06-18
AU2007248784B2 (en) 2013-11-21
TW200801036A (en) 2008-01-01

Similar Documents

Publication Publication Date Title
AU2007248784B2 (en) RAGE fusion proteins, formulations, and methods of use thereof
EP1781700B1 (en) Rage fusion proteins and methods of use
US20090004190A1 (en) Rage Fusion Proteins And Methods Of Use
US20090060925A1 (en) Rage Fusion Proteins and Methods of Use
US20110110945A1 (en) Immunoglobulin Fusion Proteins and Methods of Making
US20130142792A1 (en) RAGE Fusion Protein Compositions And Methods Of Use
NL2001555C2 (nl) Rage-fusie-eiwitten, preparaten en werkwijzen voor het gebruik ervan.
NL2001554C2 (nl) Rage-fusie-eiwitten, preparaten en werkwijzen voor het gebruik ervan.
NL2001553C2 (nl) Rage-fusie-eiwitten, preparaten en werkwijzen voor het gebruik ervan.
NL2001556C2 (nl) Rage-fusie-eiwitten, preparaten en werkwijzen voor het gebruik ervan.
NL2001551C2 (nl) Rage-fusie-eiwitten, preparaten en werkwijzen voor het gebruik ervan.
NL2001557C2 (nl) Rage-fusie-eiwitten, preparaten en werkwijzen voor het gebruik ervan.
NL2001552C2 (nl) Rage-fusie-eiwitten, preparaten en werkwijzen voor het gebruik ervan.
NL2001558C2 (nl) Rage-fusie-eiwitten, preparaten en werkwijzen voor het gebruik ervan.
HK1133042A (en) Rage fusion proteins, formulations, and methods of use thereof

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 200780018207.X

Country of ref document: CN

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 07794379

Country of ref document: EP

Kind code of ref document: A2

WWE Wipo information: entry into national phase

Ref document number: 571692

Country of ref document: NZ

WWE Wipo information: entry into national phase

Ref document number: 194482

Country of ref document: IL

WWE Wipo information: entry into national phase

Ref document number: 2007248784

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: MX/a/2008/013863

Country of ref document: MX

WWE Wipo information: entry into national phase

Ref document number: 2651348

Country of ref document: CA

Ref document number: 2009509615

Country of ref document: JP

WWE Wipo information: entry into national phase

Ref document number: 9250/DELNP/2008

Country of ref document: IN

ENP Entry into the national phase

Ref document number: 2007248784

Country of ref document: AU

Date of ref document: 20070425

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 2007794379

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 1020087029731

Country of ref document: KR

Ref document number: 200870502

Country of ref document: EA

ENP Entry into the national phase

Ref document number: PI0711193

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20081104