[특허]Vascular endothelial growth factor variants

[미국특허] Vascular endothelial growth factor variants 원문보기

IPC분류정보
국가/구분	United States(US) Patent 등록
국제특허분류(IPC7판)	A61K-038/00 C07K-014/00 C12N-015/63
출원번호	US-0268447 (2002-10-10)
발명자 / 주소	Pollitt, N. Stephen Abraham, Judith A.
출원인 / 주소	Scios, Inc.
대리인 / 주소	Morrison &
인용정보	피인용 횟수 : 2 인용 특허 : 29

초록 ▼

The invention is directed to a method of enhancing the biological activity of vascular endothelial growth factors (VEGF). The invention further concerns certain VEGF variants having enhanced biological activity, methods and means for preparing these variants, and pharmaceutical compositions comprising them. In a further aspect, the invention concerns methods of treatment using, and articles of manufacture containing such VEGF variants.

대표청구항 ▼

1. A method of inducing angiogenesis comprising:administering an effective amount of a vascular endothelial growth factor VEGF (hVEGF121) variant to a patient in need thereof, wherein the VEGF variant comprises amino acids 27-147 of SEQ ID NO:2, and wherein SEQ ID NO:2 has been altered by an amino acid substitution or deletion at (position 142 of SEQ ID NO:2); and wherein SEQ ID NO:2 has been altered by an amino acid substitution or deletion at position 101, 102, or 103, such that the variant is not glycosylated, said variant having at least 85% sequence identity with hVEGF121 polypeptide (amino acids 27-147 of SEQ ID NO:2), whereby angiogenesis is induced by the VEGF variant administered. 2. The method of claim 1, wherein angiogenesis is induced to prevent or repair injury to blood vessels.3. The method of claim 2, wherein said injury is associated with microvascular angiopathy.4. The method of claim 3, wherein said microvascular angiopathy is thrombotic microangiopathy (TMA).5. The method of claim 2, wherein said injury is associated with hemolytic-uremic syndrome (HUS).6. The method of claim 1, wherein the cysteine (C) residue is substituted by a different amino acid residue.7. The method of claim 6, wherein the different amino acid residue is a serine (S) residue.8. The method of claim 6, wherein, apart from the substitution at position 142 and the removal of the glycosylation site at position 101-103, the VEGF variant retains the amino acid sequence of hVEGF121 (amino acids 27-147 of SEQ ID NO:2).9. The method of claim 1, wherein removing the N-linked glycosylation site from the encoding nucleic acid sequence to produce a VEGF variant comprises removing the N-linked glycosylation site using site-directed mutagenesis.10. The method of claim 9, wherein removing the N-linked glycosylation site from the encoding nucleic acid sequence to produce a VEGF variant comprises substituting at least one residue in the asparagine-isoleucine-threonine (N-I-T) glycosylation site at position 101-103 of hVEGF121.11. The method of claim 10, wherein asparagine (N) at position 101 is substituted by another amino acid.12. The method of claim 11, wherein the another amino acid is glutamine (Q).13. The method of claim 1, wherein the VEGF variant is C142S of SEQ ID NO: 2 hVEGF121.14. The method of claim 1, wherein the VEGF variant additionally comprises an N-terminal substitution of SEQ ID NO: 2.15. The method of claim 14, wherein said substitution is within the first 10 amino acids of hVEGF121.16. The method of claim 15, wherein said substitution is at amino acid position 5 of hVEGF121.17. The method of claim 16, wherein said substitution is X5D, wherein X is an amino acid at position 5 of hVEGF121.

이 특허에 인용된 특허 (29) 인용/피인용 타임라인 분석

Hagenson Mary Jane (Bartlesville OK) Barr Kathryn A. (Bartlesville OK) Stroman David W. (Richardson TX) Gaertner Frank H. (San Diego CA) Harpold Michael M. (San Diego CA) Klein Ronald D. (Schoolcraft, Pichia pastoris linear plasmids and DNA fragments thereof.
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Cregg James M. (San Diego CA) Sperl George T. (Gurnee IL), Pichia pastoris argininosuccinate lyase gene and uses thereof.
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Waters ; IV William C. (1255 Kingsley Cir. Atlanta GA 30324) Wilmer Charles I. (922 Dean Dr. Atlanta GA 30328), Aerosol inhaler.
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Johnson ; IV John J. (80 Calle San Blas Albuquerque NM 87109) Johnson ; Jr. John J. (720 University Ave. Las Vegas NM 87701), Apparatus for actuating an inhaler.
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Stogner Clarence H. (Cincinnati OH) Koerner David J. (Cincinnati OH), Apparatus for moving a controlled member to a predetermined position.
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Landis Robert (New York NY) Kassay Joseph E. (Laurence Harbor NJ), Breath activated medication spray.
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Studier F. William (Stony Brook NY) Davanloo Parichehre (Basel CHX) Rosenberg Alan H. (Setauket NY) Moffatt Barbara A. (Waterloo CAX) Dunn John J. (Bellport NY), Cloning and expression of the gene for bacteriophage T7 RNA polymerase.
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Studier F. William (Stony Brook NY) Davanloo Parichehre (Basel NY CHX) Rosenberg Alan H. (Setauket NY) Moffatt Barbara A. (East Lansing MI) Dunn John J. (Bellport NY), Cloning and expression of the gene for bacteriophage T7 RNA polymerase.
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Tischer Edmund G. (Palo Alto CA) Abraham Judith A. (Sunnyvale CA) Fiddes John C. (Palo Alto CA) Mitchell Richard L. (Sunnyvale CA), DNA sequences encoding bVEGF120 and hVEGF121 and methods for the production of bovine and human vascular endothelial cel.
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Keck Pamela J. (St. Louis MO) Connolly Daniel T. (Manchester MO) Feder Joseph (University City MO), DNA sequences encoding human vascular permeability factor having 189 amino acids.
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Howlett David J. (Grimston GBX), Dispensing apparatus for metered quantities of pressurised fluid.
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Lair Stephen V. (La Jolla CA) Digan Mary E. (San Diego CA), Double auxotrophic mutants of Pichia pastoris and methods for preparation.
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Thim Lars,DKX ; Norris Kjeld,DKX ; Norris Fanny,DKX ; Bj.o slashed.rn S.o slashed.ren Erik,DKX ; Christensen Mogens,DKX ; Nielsen Per Franklin,DKX, Human spasmolytic polypeptide in glycosylated form.
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Van den Berg Johan A. (Ad Reeuwijk NLX) Van Ooyen Albert J. J. (AR Voorburg NLX) Rietveld Krijn (TL Vlaardingen NLX), Kluyveromyces as a host strain.
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Zoltan Bart J. (Old Tappan NJ) Laube Beth L. (Baltimore MD) Adams ; III George K. (Baltimore MD), Medication delivery system.
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Zoltan Bart J. (Old Tappan NJ) Laube Beth L. (Baltimore MD) Adams ; III George K. (Baltimore MD), Medication delivery system phase one.
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Belagaje Rama M. (Indianapolis IN), Method for increased expression of low molecular weight recombinant polypeptides.
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Edgar Brian W. (Auckland NZX) Elliott Robert B. (Auckland NZX 4), Method of dispensing and/or a dispenser.
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Unger Ellis F. (Silver Spring MD) Epstein Stephen E. (Rockville MD), Method to foster myocardial blood vessel growth and improve blood flow to the heart.
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Bonekamp AlfonsusJohannes,NLX ; Van Tilborg Marcellis Wilhelmus Elisabeth Maria,NLX, Modified signal sequences.
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Yamaguchi Kyoji (Oomiya JPX) Shima Nobuyuki (Oyama JPX) Murakami Akihiko (Tochigi JPX) Goto Masaaki (Tochigi JPX) Tsuda Eisuke (Tochigi JPX) Masunaga Hiroaki (Tochigi JPX) Takahira Reiko (Tochigi JPX, Modified tumor cytotoxic factor (TCF) and DNA encoding such.
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Hu Jing-Shan ; Rosen Craig A. ; Cao Liang,HKX, Polynucleotides encoding vascular endothelial growth factor 2.
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Tischer Edmund G. (Palo Alto) Abraham Judith A. (Sunnyvale) Fiddes John C. (Palo Alto) Mitchell Richard L. (Sunnyvale CA), Production of vascular endothelial cell growth factor.
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Ferrara Napoleone (Belvedere CA) Leung David W.-H. (Foster City CA), Production of vascular endothelial cell growth factor and DNA encoding same.
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Gray Patrick W. (San Francisco CA) Rinderknecht Ernst H. (San Carlos CA), Recombinant methods of making gamma interferon compositions.
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Keel Beat (Prior Lake MN) Calderon Arthur (Minnetonka MN) Liao Simon (Santa Barbara CA), Self aligned magnetic poles using sacrificial mask.
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Pratt Richard E. ; Dzau Victor J., VEGF gene transfer into endothelial cells for vascular prosthesis.
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Neufeld Gera,ILX ; Keshet Eli,ILX ; Vlodavsky Israel,ILX ; Poltorak Zoya,ILX, VEGF.sub.145 expression vectors.
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N. Stephen Pollitt ; Judith A. Abraham, Vascular endothelial growth factor variants.
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이 특허를 인용한 특허 (2) 인용/피인용 타임라인 분석

Liu, Yijia; Lu, Patrick Y.; Woodle, Martin C.; Xie, Frank Y., Composition and methods of RNAi therapeutics for treatment of cancer and other neovascularization diseases.
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Liu, Yijia; Lu, Patrick Y.; Woodle, Martin C.; Xie, Frank Y., Composition and methods of RNAi therapeutics for treatment of cancer and other neovascularization diseases.
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[미국특허] Vascular endothelial growth factor variants 원문보기