WO1998014591A1 - Nouveaux vecteurs d'expression destines a la production de proteines exogenes sous formes solubles - Google Patents

Nouveaux vecteurs d'expression destines a la production de proteines exogenes sous formes solubles Download PDF

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Publication number
WO1998014591A1
WO1998014591A1 PCT/KR1997/000186 KR9700186W WO9814591A1 WO 1998014591 A1 WO1998014591 A1 WO 1998014591A1 KR 9700186 W KR9700186 W KR 9700186W WO 9814591 A1 WO9814591 A1 WO 9814591A1
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WIPO (PCT)
Prior art keywords
expression vector
protein
gene
lys
coli
Prior art date
Application number
PCT/KR1997/000186
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English (en)
Inventor
Seong Il Choi
Baik Lin Seong
Original Assignee
Hanil Synthetic Fiber Co., Ltd.
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
Application filed by Hanil Synthetic Fiber Co., Ltd. filed Critical Hanil Synthetic Fiber Co., Ltd.
Priority to AU44735/97A priority Critical patent/AU725755B2/en
Priority to EP97943210A priority patent/EP0871741A1/fr
Publication of WO1998014591A1 publication Critical patent/WO1998014591A1/fr

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    • 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
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/93—Ligases (6)
    • 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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/70—Vectors or expression systems specially adapted for E. coli
    • 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
    • C07K14/53—Colony-stimulating factor [CSF]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/81—Protease inhibitors
    • C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
    • C07K14/8146—Metalloprotease (E.C. 3.4.24) inhibitors, e.g. tissue inhibitor of metallo proteinase, TIMP
    • 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
    • C12N15/625—DNA sequences coding for fusion proteins containing a sequence coding for a signal sequence
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • 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
    • C07K2319/35—Fusion polypeptide containing a fusion for enhanced stability/folding during expression, e.g. fusions with chaperones or thioredoxin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/50—Fusion polypeptide containing protease site
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
    • C07K2319/75—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor containing a fusion for activation of a cell surface receptor, e.g. thrombopoeitin, NPY and other peptide hormones

Definitions

  • the present invention relates to novel expression vectors which can
  • the present invention relates to the expression
  • E. coli has been exploited as a popular host cell to produce foreign proteins
  • the refolding process for preparing a active protein can be any suitable refolding process.
  • proteins having high molecular weight such as
  • chaperone genes such as groES, groEL, dnaK and the like to obtain
  • translation initiation signal of the fusion partner protein can be
  • Lac Z or Trp E protein have been utilized as a fusion partner
  • transformant should be cultured at low temperature such as 15°C in order to produce
  • Lysyl-tRNA synthetase (hereinafter it refers to "Lys RS") and its gene have been investigated as described below, which is preferable for the
  • lys S gene is expressed constitutively in normal condition
  • Lys U protein is
  • NMR nuclear magnetic resonance
  • Lys S lys S gene
  • Lys U protein and Lys S protein share a high degree of identity in the amino acid sequences, the N-terminal structures of the two
  • N-terminal domain of lysyl-tRNA synthetase has
  • H4 ⁇ -helix
  • Lys S protein has
  • Lys S protein is
  • Lys S protein as a fusion partner makes heterodimer with Lys S protein of E. coli.
  • Lys S protein is not appropriate as a fusion partner protein
  • Lys RS protein has a secondary structure which facilitates protein folding
  • lysyl-tRNA synthetase can be utilized as a fusion partner protein to
  • the object of the present invention is to provide expression vectors
  • aminoacyl-tRNA synthetase gene can be obtained from all kinds of cells.
  • the expression vectors of the present invention are composed of
  • linker peptide sequence linker peptide sequence, tag sequence, protease recognition site, restriction
  • the object of the present invention is to provide the E.
  • the lysyl-tRNA synthetase gene can be selected among lys S gene
  • the present invention provides the expression vector
  • the object of the present invention is to provide the
  • the present invention provides the expression vectors containing
  • the present invention provides the expression vector
  • the expression vectors contain the N-terminal domain gene of lysyl-tRNA
  • the present invention provides the E. coli expression
  • the object of the present invention is to provide a process for
  • the present invention provides the expression vector
  • GMcsf human granulocyte and macrophage
  • colony stimulating factor gene into the expression vector pGE-lysN.
  • GMcsf protein as a fusion protein.
  • E. coli preferably, E. coli
  • HMS 174 strain can be used as a host cell.
  • the present invention provides the expression vector plysN-Gcsf by inserting Gcsf (human granulocyte colony stimulating
  • the present invention provides the expression vector
  • TIMP2 human tissue inhibitor of TIMP2
  • metalloprotease 2 gene into the expression vector.
  • TIMP2 protein is prepared.
  • Fig. 1 depicts the secondary structure of lysyl-tRNA synthetase
  • Stick is helix structure and arrow is ⁇ -sheet structure.
  • Fig. 2 depicts a strategy for constructing the expression vector
  • Fig. 3 depicts the expression of Lys S protein by performing SDS-
  • lane 1 standard protein marker
  • lane 2 total proteins of E. coli induced for the protein expression ;
  • Fig. 4 depicts a strategy for constructing the expression vector
  • Fig. 5 depicts a strategy for constructing the E. coli expression
  • vector pLysN-GMcsf which expresses GMcsf protein by using the
  • Fig. 6 depicts the expression of GMcsf protein by performing
  • Fig. 7 depicts the expression of GMcsf protein for comparison by
  • Fig. 8 depicts a strategy for constructing the E. coli expression
  • vector pLysN-Gcsf which expresses Gcsf protein by using the expression
  • Fig. 9 depicts the expression of Gcsf protein by performing SDS-
  • Fig. 11 depicts the expression of TIMP2 protein by performing SDS-
  • lane 3 total proteins of is. co///pGE-lysN transformant induced for
  • the present invention provides expression vectors which produce
  • aminoacyl-tRNA synthetase characteristics of aminoacyl-tRNA synthetase. All kinds of aminoacyl-tRNA synthetase.
  • tRNA synthetase genes can be used to prepare expression vectors of the
  • the present invention provides expression vectors which use lysyl-
  • Lys RS protein gene can be selected among lys S gene and lys
  • Lys RS protein gene can be obtained by performing polymerase
  • PCR chain reaction
  • plasmid vector such as pGEMEX M -l (Promega) so as to
  • E. coli strains proper for the expression have been transformed with
  • Lys RS protein was expressed well, to 80% of total soluble proteins of the host cell.
  • E. coli transformants are cultured at
  • the present invention provides expression vectors which uses the
  • N- terminal domain of Lys RS protein as a fusion partner protein N- terminal domain of Lys RS protein as a fusion partner protein.
  • expression vector of the present invention contains linker peptide sequence
  • vectors can be produced as forms of soluble proteins in the host cells and
  • N-terminal domain gene of Lys RS protein can be
  • the E. coli HMS 174 strain was transformed by the expresseion
  • the expression vector constructed by the above process has the
  • T7 promoter which regulates transcription of the fusion protein.
  • coli strans such as tac promoter, ⁇ pL promoter and the like, is available for
  • Lys RS protein constructed in order to exploit the N-terminal domain of Lys RS protein as a
  • enteropeptidase from digesting fusion protein and affect protein folding.
  • helix 1 structure can be removed from the expression
  • the present invention provides the expression vector removed at the
  • the expression vector of the present invention contains
  • the expression vector also contains the N-
  • invention contains OB fold gene which is involved in folding process of Lys
  • the expression vector contains the N-terminal
  • Lys RS protein which is deleted at the amino acid residues 1 to
  • the expression vector of the present invention can also contain OB
  • Staphylococcal nuclease can be utilized for the construction of the
  • the expression vector of the present invention contains linker
  • This linker peptide is very useful since it is protruded on the
  • the expression vector can also contain
  • the expression vector of the present invention also contains
  • histidine tag of 6 histidine residues after the above linker peptide This
  • histidine tag enables the fusion proteins expressed with the expression
  • histidine tagged fusion protein can be purified easily. Practically, histidine tagged fusion protein can be purified easily. Practically, histidine tagged fusion protein can be purified easily. Practically, histidine tagged fusion protein can be used.
  • Fusion proteins can be inserted into the expression vector. Fusion proteins
  • the expression vector of the present invention contains protease recognition site in order to separate only foreign protein from fusion protein
  • invention contains enteropeptidase recognition site (DDDDK sequence)
  • enteropeptidase digests the C-terminus of the above enteropeptidase
  • thrombin recognition site LVPRGS sequence
  • Xa factor thrombin recognition site
  • the expression vector of the present invention contains restriction
  • lysN of the present invention contains restriction enzyme recognition sites
  • the present invention provides the expression vectors
  • GMcsf human granulocyte colony stimulating factor
  • Gcsf human granulocyte colony stimulating factor
  • TMP 2 human tissue inhibitor of metalloprotease
  • the present invention constructs the expression vector which
  • GMcsf gene was obtained by performing polymerase chain reaction
  • GMcsf protein fused with thioredoxin according to their expression.
  • the present invention constructs the expression vector which produces Gcsf protein as a soluble form.
  • Gcsf gene was
  • the present invention constructs the expression vector
  • TIMP 2 protein as a soluble protein.
  • TIMP 2 TIMP 2
  • the E. coli strains proper for the expression have been transformed
  • Lys N protien namely, Lys
  • fusion protein was expressed as an inclusion
  • Lys N protein of the present invention is
  • PCR polymerase chain reaction
  • PBS phosphate buffered saline
  • each sample was mixed with 7 ⁇ l of 5 X SDS loading buffer, and boiled for
  • the present invention expresses Lys S protein highly at the ratio of 80% of
  • Example 1 as a template (see Sequence Listing).
  • the expression vector containing the N-terminal domain gene of Lys S protein was constructed and named as the expression vector
  • PCR was performed by utilizing
  • primer 4 of SEQ ID. NO: 4 primer 5 of SEQ ID. NO: 5 and the expression
  • present invention was also digested with Kpnl and Hindlll. And the above
  • E. coli was transformed with the expression vector
  • fusion protein was constructed by subcloning GMcsf gene into Kpnl and
  • present invention was cultured at 37°C, fusion proteins were expressed as
  • thioredoxin was less effective than Lys N protein as a
  • LysN-Gcsf fusion protein In order to express human Gcsf (granulocyte colony stimulating
  • Example 1 were ligated after elution by performing the same method of Example 1.
  • fusion protein was expressed by fransfoiming E. coli
  • Lys-Gcsf fusion protein was expressed as a
  • metalloprotease 2 as a soluble protein, which has been expressed as an
  • TIMP2 gene was inserted into the expression
  • vector pGE-lysN of the present invention vector pGE-lysN of the present invention.
  • fusion protein was expressed by transforming E. coli
  • Lys N-TIMP2 fusion protein was expressed as a
  • the expression vectors of the present invention expresses lysyl-
  • the expression vector of the present invention expresses
  • Lys RS protein highly at the ratio of 80% of total soluble proteins
  • Lys N protein is more effective than thioredoxin
  • the expression vectors of the present invention can be any expression vectors of the present invention.
  • the expression vectors of the present invention can be any expression vectors of the present invention.
  • present invention is useful to produce foreign proteins which are difficult or
  • the expression vector of the present invention is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoe

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  • Genetics & Genomics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Biophysics (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

Cette invention concerne de nouveaux vecteurs d'expression qui permettent de produire des protéines exogènes sous des formes solubles en utilisant une synthétase lysyl-ARNt. Cette invention concerne également un procédé de préparation de protéines exogènes faisant appel à ces vecteurs d'expression. Cette invention concerne plus particulièrement des vecteurs d'expression qui permettent d'obtenir des protéines exogènes sous des formes fusionnées et solubles, lequel procédé consiste à utiliser la structure et le diagramme d'expression de synthétase lysyl-ARNt. Cette invention concerne enfin des procédés qui permettent de préparer efficacement des protéines exogènes dans des E. coli, et qui peuvent être utilisés dans l'industrie afin de produire de grandes quantités de protéines actives.
PCT/KR1997/000186 1996-10-04 1997-10-04 Nouveaux vecteurs d'expression destines a la production de proteines exogenes sous formes solubles WO1998014591A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU44735/97A AU725755B2 (en) 1996-10-04 1997-10-04 Novel expression vectors for production of foreign proteins as soluble forms
EP97943210A EP0871741A1 (fr) 1996-10-04 1997-10-04 Nouveaux vecteurs d'expression destines a la production de proteines exogenes sous formes solubles

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1996/44010 1996-10-04
KR1019960044010A KR100203919B1 (ko) 1996-10-04 1996-10-04 수용성 단백질을 생산하는 새로운 발현 플라스미드

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US09077868 A-371-Of-International 1998-06-04
US09/974,248 Division US6852512B2 (en) 1996-10-04 2001-10-09 Expression vectors for production of foreign proteins as soluble forms

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WO1998014591A1 true WO1998014591A1 (fr) 1998-04-09

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EP (1) EP0871741A1 (fr)
KR (1) KR100203919B1 (fr)
AU (1) AU725755B2 (fr)
WO (1) WO1998014591A1 (fr)

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WO2001040487A1 (fr) * 1999-11-30 2001-06-07 Bioroad Gene Development Ltd. Shanghai NOUVEAU POLYPEPTIDE, SYNTHASE HUMAINE 9 DE TYPE II A BASE AMINEE D'ARNt, ET POLYNUCLEOTIDE CODANT POUR CE POLYPEPTIDE
WO2001055415A1 (fr) * 2000-01-26 2001-08-02 Biodoor Gene Technology Ltd. Shanghai Nouveau polypeptide, aminoacyl-arnt synthetase humaine de type ii 75, et polynucleotide codant pour ce polypeptide
KR20020010241A (ko) * 2000-07-28 2002-02-04 허영섭 Ｃ형 간염 바이러스 ｒｎａ-의존성 ｒｎａ 중합효소의대량 발현 기구 및 이로부터 발현된 융합단백질을 이용한효소활성 분석방법
WO2002010396A1 (fr) * 2000-07-28 2002-02-07 Mogam Biotechnology Research Institute Systeme d'expression genetique pour production en masse d'arn polymerase dependante de l'arn du virus de l'hepatite c, et dosage enzymatique utilisant la proteine de fusion exprimee a partir de ce systeme
US7811786B1 (en) 2004-05-06 2010-10-12 Daewoong Co., Ltd. Preparation method for the production of active and soluble proteins in prokaryotes and polycistronic vectors therefor
WO2011153277A3 (fr) * 2010-06-01 2012-05-24 Atyr Pharma, Inc. Découverte innovante de compositions thérapeutiques, diagnostiques, et d'anticorps associés à des fragments de protéine de lysyl-tarn synthétases
US8945541B2 (en) 2010-05-14 2015-02-03 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of phenylalanyl-beta-tRNA synthetases
US8946157B2 (en) 2010-05-03 2015-02-03 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of seryl-tRNA synthetases
US8961961B2 (en) 2010-05-03 2015-02-24 a Tyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related protein fragments of arginyl-tRNA synthetases
US8961960B2 (en) 2010-04-27 2015-02-24 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of isoleucyl tRNA synthetases
US8969301B2 (en) 2010-07-12 2015-03-03 Atyr Pharma Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of aspartyl-tRNA synthetases
US8980253B2 (en) 2010-04-26 2015-03-17 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of cysteinyl-tRNA synthetase
US8981045B2 (en) 2010-05-03 2015-03-17 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of methionyl-tRNA synthetases
US8986680B2 (en) 2010-04-29 2015-03-24 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of Asparaginyl tRNA synthetases
US8986681B2 (en) 2010-04-27 2015-03-24 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of threonyl-tRNA synthetases
US8993723B2 (en) 2010-04-28 2015-03-31 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of alanyl-tRNA synthetases
US8999321B2 (en) 2010-07-12 2015-04-07 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of glycyl-tRNA synthetases
US9029506B2 (en) 2010-08-25 2015-05-12 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of tyrosyl-tRNA synthetases
US9034320B2 (en) 2010-04-29 2015-05-19 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of Valyl-tRNA synthetases
US9034598B2 (en) 2010-05-17 2015-05-19 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of leucyl-tRNA synthetases
US9034321B2 (en) 2010-05-03 2015-05-19 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of phenylalanyl-alpha-tRNA synthetases
US9062301B2 (en) 2010-05-04 2015-06-23 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of glutamyl-prolyl-tRNA synthetases
US9062302B2 (en) 2010-05-04 2015-06-23 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of p38 multi-tRNA synthetase complex
US9068177B2 (en) 2010-04-29 2015-06-30 Atyr Pharma, Inc Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of glutaminyl-tRNA synthetases
US9399770B2 (en) 2010-10-06 2016-07-26 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of tryptophanyl-tRNA synthetases
US9422539B2 (en) 2010-07-12 2016-08-23 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of histidyl-tRNA synthetases
US9587235B2 (en) 2013-03-15 2017-03-07 Atyr Pharma, Inc. Histidyl-tRNA synthetase-Fc conjugates
US9688978B2 (en) 2011-12-29 2017-06-27 Atyr Pharma, Inc. Aspartyl-tRNA synthetase-Fc conjugates
US9714419B2 (en) 2011-08-09 2017-07-25 Atyr Pharma, Inc. PEGylated tyrosyl-tRNA synthetase polypeptides
US9796972B2 (en) 2010-07-12 2017-10-24 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of glycyl-tRNA synthetases
US9816084B2 (en) 2011-12-06 2017-11-14 Atyr Pharma, Inc. Aspartyl-tRNA synthetases
US9822353B2 (en) 2011-12-06 2017-11-21 Atyr Pharma, Inc. PEGylated aspartyl-tRNA synthetase polypeptides
US11767520B2 (en) 2017-04-20 2023-09-26 Atyr Pharma, Inc. Compositions and methods for treating lung inflammation

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KR101360375B1 (ko) * 2011-08-19 2014-02-10 연세대학교 산학협력단 수용성 ｂｍｐ-2를 생산하는 재조합 대장균 및 이를 이용한 수용성 ｂｍｐ-2의 제조방법
KR101908438B1 (ko) * 2016-02-05 2018-10-16 (주)피앤피바이오팜 Arsntd를 융합파트너로 이용한 수용성 및 활성형 재조합단백질의 생산방법 및 그 생산물
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AU4473597A (en) 1998-04-24

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