WO2004072100A2 - Nell peptide expression systems and bone formation activity of nell peptide - Google Patents

Nell peptide expression systems and bone formation activity of nell peptide Download PDF

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Publication number
WO2004072100A2
WO2004072100A2 PCT/US2004/003808 US2004003808W WO2004072100A2 WO 2004072100 A2 WO2004072100 A2 WO 2004072100A2 US 2004003808 W US2004003808 W US 2004003808W WO 2004072100 A2 WO2004072100 A2 WO 2004072100A2
Authority
WO
WIPO (PCT)
Prior art keywords
seq
peptide
nell1
cell
nucleic acid
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/US2004/003808
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English (en)
French (fr)
Other versions
WO2004072100A3 (en
Inventor
Kang Ting
Shunichi Kuroda
Ben Wu
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.)
University of California Berkeley
University of California San Diego UCSD
Original Assignee
University of California Berkeley
University of California San Diego UCSD
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 claimed from PCT/US2003/028281 external-priority patent/WO2004025936A1/en
Priority to US10/544,553 priority Critical patent/US7544486B2/en
Priority to JP2006503442A priority patent/JP2007524360A/ja
Priority to EP04709500A priority patent/EP1594889B1/en
Priority to CA002515208A priority patent/CA2515208A1/en
Priority to DE602004032107T priority patent/DE602004032107D1/de
Application filed by University of California Berkeley, University of California San Diego UCSD filed Critical University of California Berkeley
Priority to AT04709500T priority patent/ATE504649T1/de
Publication of WO2004072100A2 publication Critical patent/WO2004072100A2/en
Anticipated expiration legal-status Critical
Priority to US11/594,510 priority patent/US7687462B2/en
Priority to US11/601,529 priority patent/US7691607B2/en
Priority to US11/713,366 priority patent/US7884066B2/en
Publication of WO2004072100A3 publication Critical patent/WO2004072100A3/en
Priority to US12/400,714 priority patent/US7807787B2/en
Priority to US12/400,715 priority patent/US8048646B2/en
Priority to US12/700,630 priority patent/US8053412B2/en
Priority to US12/700,644 priority patent/US8044026B2/en
Priority to US13/011,736 priority patent/US8207120B2/en
Priority to US13/253,859 priority patent/US20120077742A1/en
Priority to US13/769,222 priority patent/US9598480B2/en
Ceased legal-status Critical Current

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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
    • C07K14/475—Growth factors; Growth regulators
    • C07K14/51—Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
    • 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
    • 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
    • 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

Definitions

  • the substrate may include a carrier that is in the form of a flowable gel.
  • the gel may be selected so as to be injectable, such as via a syringe at the site where bone formation is desired.
  • the gel may be a chemical gel which may be a chemical gel formed by primary bonds, and controlled by pH, ionic groups, and/or solvent concentration.
  • the gel may also be a physical gel which may be formed by secondary bonds and controlled by temperature and viscosity.
  • the carrier may have a surface that is decorated and/or immobilized with cell adhesion molecules, adhesion peptides, and adhesion peptide analogs which may promote cell-matrix attachment via receptor mediated mechanisms, and/or molecular moieties which may promote adhesion via non-receptor mediated mechanisms binding such as, but not limited to polycationic polyamino-acid-peptides (e.g. poly-lysine), polyanionic polyamino-acid-peptides, Mefp-class adhesive molecules and other DOPA-rich peptides (e.g. poly-lysine- DOPA), polysaccharides, and proteoglycans. See for example, PCT Int. Appl. WO/2004005421; WO/2003008376; WO/9734016, herein incorporated by reference.
  • polycationic polyamino-acid-peptides e.g. poly-lysine
  • the dosage regimen will be determined by the clinical indication being addressed, as well as by various patient variables (e.g. weight, age, sex) and clinical presentation (e.g. extent of injury, site of injury, etc.).
  • patient variables e.g. weight, age, sex
  • clinical presentation e.g. extent of injury, site of injury, etc.
  • a plZT- NELL1-FLC plasmid was constructed by inserting the rat NELL1 cDNA fused to a FLAG epitope sequence derived from the pTB701-NELL1-FLC plasmid (Kuroda, BBRC) into insect expression vector plZT/V5-His (Invitrogen). Furthermore, NELL1 original secretory signal sequence was replaced to honeybee mellitin signal sequence using PCR methods. High Five cells were purchased from Invitrogen, and were cultured in High Five Serum-Free Medium (Invitrogen).
  • a plZT- NELL1-FLC plasmid was constructed by inserting the rat NELL2 cDNA fused to a FLAG epitope sequence derived from the pTB701-NELL2-FLC plasmid into insect expression vector plZT/V5-His (Invitrogen). High Five cells were purchased from Invitrogen, and were cultured in High Five Serum-Free Medium (Invitrogen). High Five cells were transfected with the plZT-NELL1-FLC plasmid using FuGene ⁇ (Roche).
  • Fig. 19 is a blot illustrating the expression of NELL1 and NELL2 from Five SFM.
  • ESF921 refers to a commercial name of a serum-free medium;
  • Five SFM refers to a commercial name of a medium.
  • the constructs for the expression of both NELL proteins are similar to those described above.
  • Example 3 Increases in alkaline phosphatase activity is an early cellular marker of osteoblastic differentiation.
  • fetal rat calvarial cells were grown in the presence of: NELL1 (1 ng/ml, 10ng/ml, 100ng/ml) produced using the methods described herein, or BMP4 (100ng/ml) for duration of time.
  • Alkaline phosphatase was assayed in each sample by conventional methods.
  • Fig. DC depicts skeletal defects of a Cbfal +/" + NELL1 overexp animal demonstrating significantly increased calvarial bone formation relative to the Cbfal +/" haploid deficient animal on skeletal staining and micro-CT. Also, a significantly lesser degree of clavicle hypoplasia relative to the Cbfal +/" haploid deficient animal (middle).

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Toxicology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biophysics (AREA)
  • Peptides Or Proteins (AREA)
  • Rheumatology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicinal Preparation (AREA)
  • Materials For Medical Uses (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
PCT/US2004/003808 1999-10-05 2004-02-09 Nell peptide expression systems and bone formation activity of nell peptide Ceased WO2004072100A2 (en)

Priority Applications (16)

Application Number Priority Date Filing Date Title
AT04709500T ATE504649T1 (de) 2003-02-07 2004-02-09 Nell-peptidexpressionssysteme und knochenbildende aktivität des nell-peptids
JP2006503442A JP2007524360A (ja) 2003-02-07 2004-02-09 Ｎｅｌｌペプチドの発現系及びｎｅｌｌペプチドの骨形成活性
EP04709500A EP1594889B1 (en) 2003-02-07 2004-02-09 Nell peptide expression systems and bone formation activity of nell peptide
CA002515208A CA2515208A1 (en) 2003-02-07 2004-02-09 Nell peptide expression systems and bone formation activity of nell peptide
DE602004032107T DE602004032107D1 (de) 2003-02-07 2004-02-09 Nell-peptidexpressionssysteme und knochenbildende aktivität des nell-peptids
US10/544,553 US7544486B2 (en) 2003-02-07 2004-02-09 Nell peptide expression systems and bone formation activity of nell peptide
US11/594,510 US7687462B2 (en) 1999-10-05 2006-11-07 Composition for promoting cartilage formation or repair comprising a nell gene product and method of treating cartilage-related conditions using such composition
US11/601,529 US7691607B2 (en) 2004-02-09 2006-11-17 Expression system of NELL peptide
US11/713,366 US7884066B2 (en) 1999-10-05 2007-03-01 NELL-1 enhanced bone mineralization
US12/400,714 US7807787B2 (en) 2003-02-07 2009-03-09 NELL-1 peptide
US12/400,715 US8048646B2 (en) 2003-02-07 2009-03-09 NELL peptide expression systems and bone formation activity of NELL peptide
US12/700,644 US8044026B2 (en) 1999-10-05 2010-02-04 Composition for promoting cartilage formation or repair comprising a NELL gene product and method of treating cartilage-related conditions using such composition
US12/700,630 US8053412B2 (en) 2004-02-09 2010-02-04 NELL-1 peptides
US13/011,736 US8207120B2 (en) 1999-10-05 2011-01-21 NELL-1 enhanced bone mineralization
US13/253,859 US20120077742A1 (en) 2004-02-09 2011-10-05 Expression System Of NELL Peptide
US13/769,222 US9598480B2 (en) 2004-02-09 2013-02-15 Recombinant NEL-like (NELL) protein production

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US44567203P 2003-02-07 2003-02-07
US60/445,672 2003-02-07
PCT/US2003/028281 WO2004025936A1 (en) 2002-09-13 2003-09-09 Method of searching-by-number and device including a search-by-number feature
USPCT/US03/28281 2003-09-15

Related Parent Applications (2)

Application Number Title Priority Date Filing Date
PCT/US2006/005473 Continuation-In-Part WO2006089023A2 (en) 1999-10-05 2006-02-16 Pharmaceutical compositions for treating or preventing bone conditions
US11/392,294 Continuation-In-Part US7776361B2 (en) 1999-10-05 2006-03-28 NELL-1 enhanced bone mineralization

Related Child Applications (11)

Application Number Title Priority Date Filing Date
US10/544,553 A-371-Of-International US7544486B2 (en) 1999-10-05 2004-02-09 Nell peptide expression systems and bone formation activity of nell peptide
PCT/US2006/005476 A-371-Of-International WO2006089024A1 (en) 2005-02-17 2006-02-16 Improved process for preparing (disubstitutedpropenyl) phenylalkyl substituted dihydrobenzofurans
PCT/US2006/005473 A-371-Of-International WO2006089023A2 (en) 1999-10-05 2006-02-16 Pharmaceutical compositions for treating or preventing bone conditions
US11/544,553 Continuation US7515863B2 (en) 2005-10-21 2006-10-10 Cleaning unit and image forming apparatus using the same
US11/544,553 Continuation-In-Part US7515863B2 (en) 2005-10-21 2006-10-10 Cleaning unit and image forming apparatus using the same
US11/594,510 Continuation-In-Part US7687462B2 (en) 1999-10-05 2006-11-07 Composition for promoting cartilage formation or repair comprising a nell gene product and method of treating cartilage-related conditions using such composition
US11/601,529 Continuation-In-Part US7691607B2 (en) 2004-02-09 2006-11-17 Expression system of NELL peptide
US11/713,366 Continuation-In-Part US7884066B2 (en) 1999-10-05 2007-03-01 NELL-1 enhanced bone mineralization
US12/400,714 Continuation US7807787B2 (en) 2003-02-07 2009-03-09 NELL-1 peptide
US12/400,715 Division US8048646B2 (en) 2003-02-07 2009-03-09 NELL peptide expression systems and bone formation activity of NELL peptide
US13/011,736 Continuation-In-Part US8207120B2 (en) 1999-10-05 2011-01-21 NELL-1 enhanced bone mineralization

Publications (2)

Publication Number Publication Date
WO2004072100A2 true WO2004072100A2 (en) 2004-08-26
WO2004072100A3 WO2004072100A3 (en) 2007-03-15

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2004/003808 Ceased WO2004072100A2 (en) 1999-10-05 2004-02-09 Nell peptide expression systems and bone formation activity of nell peptide

Country Status (9)

Country Link
US (3) US7544486B2 (https=)
EP (1) EP1594889B1 (https=)
JP (1) JP2007524360A (https=)
CN (1) CN101018562A (https=)
AT (1) ATE504649T1 (https=)
CA (1) CA2515208A1 (https=)
DE (1) DE602004032107D1 (https=)
ES (1) ES2366950T3 (https=)
WO (1) WO2004072100A2 (https=)

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WO2010042654A2 (en) 2008-10-07 2010-04-15 The Regents Of The University Of California Recombinant nell protein production
EP2089048A4 (en) * 2006-11-07 2011-02-23 Univ California COMPOSITION FOR CARTLE
WO2010111421A3 (en) * 2009-03-25 2011-03-03 The Regents Of The University Of California Isoform nell-1 peptide
US7910542B2 (en) 2007-09-28 2011-03-22 Ut-Battelle, Llc Methods for promoting wound healing and muscle regeneration with the cell signaling protein Nell1
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US20120237476A1 (en) * 2006-07-11 2012-09-20 Foressee Pharmaceuticals, LLC Pharmaceutical Compositions for Sustained Release Delivery of Peptides
US8722625B2 (en) 2007-09-28 2014-05-13 Ut-Battelle, Llc Treatment of cardiovascular disorders using the cell differentiation signaling protein Nell1
CN110420350A (zh) * 2019-08-28 2019-11-08 深圳先进技术研究院 复合生物玻璃的粘附温敏水凝胶及其制备方法和应用
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DE602004032107D1 (de) * 2003-02-07 2011-05-19 Univ California Nell-peptidexpressionssysteme und knochenbildende aktivität des nell-peptids
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US20110002893A1 (en) * 2008-11-03 2011-01-06 Ut-Battelle, Llc Diagnosis and treatment of congenital heart defects using nell1
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Cited By (51)

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EP1860189A1 (en) * 1996-03-19 2007-11-28 Otsuka Pharmaceutical Co., Ltd. Human gene
EP2272960A1 (en) * 1996-03-19 2011-01-12 Otsuka Pharmaceutical Co., Ltd. Human protein NELL2 gene
US7674889B2 (en) 1996-03-19 2010-03-09 Otsuka Pharmaceutical Co., Ltd. Human skeletal muscle-specific ubiquitin-conjugating enzyme
US7420048B2 (en) 1996-03-19 2008-09-02 Otsuka Pharmaceutical Co., Ltd. Human skeletal muscle-specific ubiquitin-conjugating enzyme
US8106171B2 (en) 1996-03-19 2012-01-31 Otsuka Pharmaceutical Co., Ltd Nel-related type 1 polypeptide
US7858754B2 (en) 1996-03-19 2010-12-28 Otsuka Pharmaceutical Co., Ltd. Nel-related protein type 1 antibody
US8048995B2 (en) 1996-03-19 2011-11-01 Otsuka Pharmaceutical Co., Ltd. Human skeletal muscle-specific ubiquitin-conjugating enzyme
US7592438B2 (en) 1996-03-19 2009-09-22 Otsuka Pharmaceutical Co., Ltd. Human gene
EP2135618A3 (en) * 2003-11-19 2010-01-20 DeveloGen Aktiengesellschaft Use of secreted protein products for preventing and treating pancreatic diseases and/or obesity and/or metabolic syndrome
US8053412B2 (en) 2004-02-09 2011-11-08 The Regents Of The University Of California NELL-1 peptides
US9598480B2 (en) 2004-02-09 2017-03-21 The Regents Of The University Of California Recombinant NEL-like (NELL) protein production
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US20100249376A1 (en) 2010-09-30
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