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1. 发明申请

WO2006113957A3 PRODUCTION OF RECOMBINANT PROTEINS BY AUTOPROTEOLYTIC CLEAVAGE OF A FUSION PROTEIN 审中-公开
标题翻译：通过融合蛋白自动清除生产重组蛋白
公开(公告)号：WO2006113957A3
公开(公告)日：2007-06-07
申请号：PCT/AT2006000165
申请日：2006-04-25
申请人： SANDOZ AG , BOEHRINGER INGELHEIM AUSTRIA , WERTHER FLORIAN , ACHMUELLER CLEMENS , WECHNER PHILIPP , AUER BERNHARD , PODMIRSEG SILVIO
发明人： WERTHER FLORIAN , ACHMUELLER CLEMENS , WECHNER PHILIPP , AUER BERNHARD , PODMIRSEG SILVIO
IPC分类号： C12N15/62 , C12N9/50 , C12P21/06
CPC分类号： C12P21/02 , C07K1/22 , C07K17/06 , C12N9/506 , C12N15/62
摘要： The invention relates to a process for the recombinant production of a heterologous polypeptide of interest, comprising, (i) cultivation of a bacterial host cell which is transformed with an expression vector which comprises a nucleic acid molecule which codes for a fusion polypeptide, the fusion polypeptide comprising a derivative of an autoprotease N pro of Pestivirus, wherein at least one cysteine residue of the naturally occuring autoprotease N pro of Pestivirus is replaced by another amino acid residue, and a second polypeptide which is connected to the first polypeptide at the C-terminus of the first polypeptide in a manner such, that the second polypeptide is capable of being cleaved from the fusion polypeptide by the autoproteolytic activity of the first polypeptide, said second polypeptide being a heterologous polypeptide, wherein cultivation occurs under conditions which cause expression of the fusion polypeptide and formation of corresponding cytoplasmic inclusion bodies, (ii) isolation of the inclusion bodies from the host cell, (iii) solubilization of the isolated inclusion bodies, (iv) induction of autoproteolytic cleavage of the heterologous polypeptide of interest from the fusion polypeptide, and (v) isolation of the cleaved heterologous polypeptide of interest.
摘要翻译：本发明涉及重组产生感兴趣的异源多肽的方法，其包括（i）培养用表达载体转化的细菌宿主细胞，所述表达载体包含编码融合多肽的核酸分子，所述融合其包含蚜虫病毒的自身蛋白酶N N a a a a a a a a，，，，，，，，，，，and and and and and and and and and and and and and and and and and and and and and and and and and and and and and and and and 第二多肽以第一多肽的C末端连接到第一多肽的方式，使得第二多肽能够通过第一多肽的自身蛋白水解活性从融合多肽切割，所述第二多肽是异源多肽，其中培养在引起融合多肽表达和形成相应细胞质的条件下发生包涵体，（ii）从宿主细胞中分离包涵体，（iii）分离的包涵体的溶解，（iv）从融合多肽诱导感兴趣的异源多肽的自体蛋白水解切割，和（v）分离切断的感兴趣的异源多肽。

2. 发明申请

WO2006113958A3 AFFINITY LIGANDS 审中-公开
公开(公告)号：WO2006113958A3
公开(公告)日：2006-11-02
申请号：PCT/AT2006/000167
申请日：2006-04-25
申请人： SANDOZ AG , BOEHRINGER INGELHEIM AUSTRIA GMBH , JUNGBAUER, Alois , HAHN, Rainer , KAAR, Waltraud , SEIFERT, Michael , AUER, Bernhard , ACHMÜLLER, Clemens , WECHNER, Philipp
发明人： JUNGBAUER, Alois , HAHN, Rainer , KAAR, Waltraud , SEIFERT, Michael , AUER, Bernhard , ACHMÜLLER, Clemens , WECHNER, Philipp
IPC分类号： C07K17/06 , C07K1/22
摘要： Disclosed is an affinity matrix comprising a solid phase and an affinity ligand comprising peptide bonds coupled to this solid phase, wherein the affinity ligand comprising peptide bond is selected from the following group of ligands: a) peptides comprising the formula X 1 X 2 X 3 X 4 , wherein X 1 to X 4 are amino acid residues and at least two of X 1 to X 4 is W, Y or F; b) peptides comprising the formula X 5 X 6 X 7 X 8 , wherein X 5 to X 8 are amino acid residues, at least one of X 5 to X 8 is W, and at least one of X 5 to X 8 is E or D; and c) poly-amino acids consisting of an amino acid monomer of the group consisting of R, K, E and D and an amino acid monomer of the group consisting of Y, F and W, preferably poly-KY, poly-KF, poly-KW, poly-RY, poly-RF, poly-RW, poly-EY, poly-DY, poly-EF, poly-EW, poly-DF and poly-DW, with the proviso that the peptides according to a) and b) have a maximum length of 35 amino acid residues and that the poly-amino acids according to c) have a minimum length of 20 amino acid residues.

3. 发明申请

WO2008132134A1 NOVEL ANTIBODY MOLECULES AND NUCLEIC ACIDS BINDING TO FUNGAL STRESS PROTEIN HSP90 审中-公开
标题翻译：新型抗体分子和核酸结合真菌应激蛋白HSP90
公开(公告)号：WO2008132134A1
公开(公告)日：2008-11-06
申请号：PCT/EP2008055006
申请日：2008-04-24
申请人： NOVARTIS AG , BURNIE JAMES , WECHNER PHILIPP
发明人： BURNIE JAMES , WECHNER PHILIPP
IPC分类号： C07K16/14 , A61K35/00 , A61K39/395 , A61P31/00 , A61P37/06 , C07K16/18 , C12N15/10
CPC分类号： C07K16/14 , A61K2039/505 , C07K16/18 , C07K2317/622 , C07K2319/21
摘要： An scFv peptide comprising a V H domain and a V L domain linked by an amino acid spacer is disclosed. The V H domain comprises a sequence with at least 80% sequence identity to the sequence of SEQ ID NO. 64. The V L domain comprises a sequence with at least 80% sequence identity to the sequence of SEQ ID NO. 66. The scFv peptide also comprises the substitution or deletion of an amino acid in the V H domain at the position corresponding to C 28 .
摘要翻译：公开了包含由氨基酸间隔物连接的V H H结构域和V L L结构域的scFv肽。 V H结构域包含与SEQ ID NO：1的序列具有至少80％的序列同一性的序列。 V L区包含与SEQ ID NO：1的序列具有至少80％的序列同一性的序列。 scFv肽还包括在对应于C 28 C的位置上的V H H区域中的氨基酸的取代或缺失。

4. 发明申请

WO2006113957A8 ORGANIC COMPOUNDS 审中-公开
标题翻译：有机化合物
公开(公告)号：WO2006113957A8
公开(公告)日：2007-04-26
申请号：PCT/AT2006000165
申请日：2006-04-25
申请人： SANDOZ AG , BOEHRINGER INGELHEIM AUSTRIA , WERTHER FLORIAN , ACHMUELLER CLEMENS , WECHNER PHILIPP , AUER BERNHARD , PODMIRSEG SILVIO
发明人： WERTHER FLORIAN , ACHMUELLER CLEMENS , WECHNER PHILIPP , AUER BERNHARD , PODMIRSEG SILVIO
IPC分类号： C12N15/62 , C12N9/50 , C12P21/06
CPC分类号： C12P21/02 , C07K1/22 , C07K17/06 , C12N9/506 , C12N15/62
摘要： The invention relates to a process for the recombinant production of a heterologous polypeptide of interest, comprising, (i) cultivation of a bacterial host cell which is transformed with an expression vector which comprises a nucleic acid molecule which codes for a fusion polypeptide, the fusion polypeptide comprising a derivative of an autoprotease N pro of Pestivirus, wherein at least one cysteine residue of the naturally occuring autoprotease N pro of Pestivirus is replaced by another amino acid residue, and a second polypeptide which is connected to the first polypeptide at the C-terminus of the first polypeptide in a manner such, that the second polypeptide is capable of being cleaved from the fusion polypeptide by the autoproteolytic activity of the first polypeptide, said second polypeptide being a heterologous polypeptide, wherein cultivation occurs under conditions which cause expression of the fusion polypeptide and formation of corresponding cytoplasmic inclusion bodies, (ii) isolation of the inclusion bodies from the host cell, (iii) solubilization of the isolated inclusion bodies, (iv) induction of autoproteolytic cleavage of the heterologous polypeptide of interest from the fusion polypeptide, and (v) isolation of the cleaved heterologous polypeptide of interest.
摘要翻译：本发明涉及重组产生感兴趣的异源多肽的方法，其包括（i）培养用表达载体转化的细菌宿主细胞，所述表达载体包含编码融合多肽的核酸分子，所述融合多肽，其包含蚜虫病毒的自身蛋白酶N N a a a a a a a，，，，，，，，，，，and and and and and and and and and and and and and and and and and and and and and and and and and and and and and and 第二多肽以第一多肽的C-末端连接到第一多肽的方式，使得第二多肽能够通过第一多肽的自身蛋白水解活性从融合多肽切割，所述第二多肽是异源多肽，其中培养在引起融合多肽表达和形成相应细胞质的条件下进行包含体，（ii）从宿主细胞中分离包涵体，（iii）分离的包涵体的溶解，（iv）从融合多肽诱导感兴趣的异源多肽的自体蛋白水解切割，和（v）分离切断的异源多肽。

5. 发明申请

WO2006113957A2 ORGANIC COMPOUNDS 审中-公开
标题翻译：有机化合物
公开(公告)号：WO2006113957A2
公开(公告)日：2006-11-02
申请号：PCT/AT2006/000165
申请日：2006-04-25
申请人： SANDOZ AG , BOEHRINGER INGELHEIM AUSTRIA GMBH , WERTHER, Florian , ACHMÜLLER, Clemens , WECHNER, Philipp , AUER, Bernhard , PODMIRSEG, Silvio
发明人： WERTHER, Florian , ACHMÜLLER, Clemens , WECHNER, Philipp , AUER, Bernhard , PODMIRSEG, Silvio
IPC分类号： C12N15/62 , C12N9/50 , C12P21/06
CPC分类号： C12P21/02 , C07K1/22 , C07K17/06 , C12N9/506 , C12N15/62
摘要： The invention relates to a process for the recombinant production of a heterologous polypeptide of interest, comprising, (i) cultivation of a bacterial host cell which is transformed with an expression vector which comprises a nucleic acid molecule which codes for a fusion polypeptide, the fusion polypeptide comprising a derivative of an autoprotease N pro of Pestivirus, wherein at least one cysteine residue of the naturally occuring autoprotease N pro of Pestivirus is replaced by another amino acid residue, and a second polypeptide which is connected to the first polypeptide at the C-terminus of the first polypeptide in a manner such, that the second polypeptide is capable of being cleaved from the fusion polypeptide by the autoproteolytic activity of the first polypeptide, said second polypeptide being a heterologous polypeptide, wherein cultivation occurs under conditions which cause expression of the fusion polypeptide and formation of corresponding cytoplasmic inclusion bodies, (ii) isolation of the inclusion bodies from the host cell, (iii) solubilization of the isolated inclusion bodies, (iv) induction of autoproteolytic cleavage of the heterologous polypeptide of interest from the fusion polypeptide, and (v) isolation of the cleaved heterologous polypeptide of interest.
摘要翻译：本发明涉及重组产生感兴趣的异源多肽的方法，其包括（i）培养用表达载体转化的细菌宿主细胞，所述表达载体包含编码融合多肽的核酸分子，所述融合其包含蚜虫病毒的自身蛋白酶N N a a a a a a a a，，，，，，，，，，，and and and and and and and and and and and and and and and and and and and and and and and and and and and and and 第二多肽以第一多肽的C末端连接到第一多肽的方式，使得第二多肽能够通过第一多肽的自身蛋白水解活性从融合多肽切割，所述第二多肽是异源多肽，其中培养在引起融合多肽表达和形成相应细胞质的条件下发生包含体，（ii）从宿主细胞分离包涵体，（iii）分离的包涵体的溶解，（iv）从融合多肽诱导感兴趣的异源多肽的自体蛋白水解切割，和（v）分离切断的感兴趣的异源多肽。

6. 发明申请

WO2008132152A1 NOVEL ANTIBODY MOLECULES AND NUCLEIC ACIDS BINDING TO FUNGAL STRESS PROTEIN HSP90 审中-公开
标题翻译：新型抗体分子和核酸结合真菌应激蛋白HSP90
公开(公告)号：WO2008132152A1
公开(公告)日：2008-11-06
申请号：PCT/EP2008/055037
申请日：2008-04-24
申请人： NOVARTIS AG , MASSACHUSETTS INSTITUTE OF TECHNOLOGY , CHENNAMSETTY, Naresh , EWERT, Stefan , HELK, Bernhard , TROUT, Bernhardt , WECHNER, Philipp
发明人： CHENNAMSETTY, Naresh , EWERT, Stefan , HELK, Bernhard , TROUT, Bernhardt , WECHNER, Philipp
IPC分类号： C07K16/14 , C07K16/18 , A61K39/395 , A61P31/00 , A61K35/00 , C12N15/10 , A61P37/06
CPC分类号： C07K16/14 , A61K2039/505 , C07K16/18 , C07K2317/622 , C07K2319/21
摘要： An scFv peptide comprising a V H domain and a V L domain linked by an amino acid spacer is disclosed. The V H domain comprises a sequence with at least 80% sequence identity to the sequence of SEQ ID NO. 64. The V L domain comprises a sequence with at least 80% sequence identity to the sequence of SEQ ID NO. 66. The scFv peptide comprises an additional feature selected from (a) to (e) and combinations thereof. (a) A substitution or deletion of an amino acid in the V H domain at a position corresponding to that selected from the group consisting of : I 29 , H 68 , N 85 , C 97 and combinations thereof. (b) A substitution or deletion of an amino acid in the V L domain at a position corresponding to that selected from the group consisting of : V 2 , V 3 , F 10 , F 14 , A 39 , N 76 and combinations thereof. (c) The amino acid spacer comprises the sequence (GGGGS) n wherein n is between 4 and 6. (d) The V H domain further comprises an N-terminal pelB signal sequence comprising the sequence of SEQ ID NO. 68 or a sequence having at least 80% sequence identity thereto. (e) The V L domain is located at the N-terminal end of the V H domain. (f) The substitution of the cysteine residue in the V H domain corresponding to position 28 with a serine residue.
摘要翻译：公开了包含由氨基酸间隔物连接的V H H结构域和V L L结构域的scFv肽。 V H结构域包含与SEQ ID NO：1的序列具有至少80％的序列同一性的序列。 V L区包含与SEQ ID NO：1的序列具有至少80％的序列同一性的序列。 scFv肽包含选自（a）至（e）的附加特征及其组合。（a）在对应于选自以下的位置的位置上的V H H区域中的氨基酸的取代或缺失：I 68 N，N 85，C 97，及其组合。（b）在对应于选自以下的位置的位置上的V L区域中的氨基酸的取代或缺失：V 2， 3，F 10，F 14，A 39，N 76和它们的组合。（c）氨基酸间隔物包含序列（GGGGS）N，其中n在4和6之间。（d）V H区还包含N末端pelB 信号序列，其包含SEQ ID NO： 68或与其具有至少80％序列同一性的序列。（e）V L领域位于V H领域的N末端。（f）用丝氨酸残基取代对应于位置28的V H H区中的半胱氨酸残基。

7. 发明申请

WO2006113958A2 AFFINITY LIGANDS 审中-公开
标题翻译：亲属关系
公开(公告)号：WO2006113958A2
公开(公告)日：2006-11-02
申请号：PCT/AT2006000167
申请日：2006-04-25
申请人： SANDOZ AG , BOEHRINGER INGELHEIM AUSTRIA , JUNGBAUER ALOIS , HAHN RAINER , KAAR WALTRAUD , SEIFERT MICHAEL , AUER BERNHARD , ACHMUELLER CLEMENS , WECHNER PHILIPP
发明人： JUNGBAUER ALOIS , HAHN RAINER , KAAR WALTRAUD , SEIFERT MICHAEL , AUER BERNHARD , ACHMUELLER CLEMENS , WECHNER PHILIPP
IPC分类号： C07K17/06 , C07K1/22
CPC分类号： C12P21/02 , C07K1/22 , C07K17/06 , C12N9/506 , C12N15/62
摘要： Disclosed is an affinity matrix comprising a solid phase and an affinity ligand comprising peptide bonds coupled to this solid phase, wherein the affinity ligand comprising peptide bond is selected from the following group of ligands: a) peptides comprising the formula X 1 X 2 X 3 X 4 , wherein X 1 to X 4 are amino acid residues and at least two of X 1 to X 4 is W, Y or F; b) peptides comprising the formula X 5 X 6 X 7 X 8 , wherein X 5 to X 8 are amino acid residues, at least one of X 5 to X 8 is W, and at least one of X 5 to X 8 is E or D; and c) poly-amino acids consisting of an amino acid monomer of the group consisting of R, K, E and D and an amino acid monomer of the group consisting of Y, F and W, preferably poly-KY, poly-KF, poly-KW, poly-RY, poly-RF, poly-RW, poly-EY, poly-DY, poly-EF, poly-EW, poly-DF and poly-DW, with the proviso that the peptides according to a) and b) have a maximum length of 35 amino acid residues and that the poly-amino acids according to c) have a minimum length of 20 amino acid residues.
摘要翻译：公开了包含固相和包含与该固相偶联的肽键的亲和配体的亲和基质，其中包含肽键的亲和配体选自下列配体组：a）包含式X 1的肽， X 2 X 3 X 4其中X 1至X 4 是氨基酸残基，X 1至X 4中的至少两个是W，Y或F; b）包含式X 5 X 6 X 7 X 8的肽，其中X 5， / SUB> X 8是氨基酸残基，X 5至X 8中的至少一个是W，并且X X 8是E或D; 和c）由R，K，E和D组成的组的氨基酸单体和由Y，F和W组成的组的氨基酸单体组成的聚氨基酸，优选聚KY，聚-KF， poly-KW，poly-RY，poly-RF，poly-RW，poly-EY，poly-DY，poly-EF，poly-EW，poly-DF和poly-DW，条件是根据a）和b）具有35个氨基酸残基的最大长度，并且根据c）的多氨基酸具有20个氨基酸残基的最小长度。

8. 发明申请

WO2008132134A9 NOVEL ANTIBODY MOLECULES AND NUCLEIC ACIDS BINDING TO FUNGAL STRESS PROTEIN HSP90 审中-公开
公开(公告)号：WO2008132134A9
公开(公告)日：2008-11-06
申请号：PCT/EP2008/055006
申请日：2008-04-24
申请人： NOVARTIS AG , BURNIE, James , WECHNER, Philipp
发明人： BURNIE, James , WECHNER, Philipp
IPC分类号： C07K16/14 , A61K39/395 , A61P31/00 , A61K35/00 , C12N15/10 , C07K16/18 , A61P37/06
摘要： An scFv peptide comprising a V H domain and a V L domain linked by an amino acid spacer is disclosed. The V H domain comprises a sequence with at least 80% sequence identity to the sequence of SEQ ID NO. 64. The V L domain comprises a sequence with at least 80% sequence identity to the sequence of SEQ ID NO. 66. The scFv peptide also comprises the substitution or deletion of an amino acid in the V H domain at the position corresponding to C 28 .

9. 发明申请

WO2006113958A8 AFFINITY LIGANDS 审中-公开
标题翻译：亲和力配体
公开(公告)号：WO2006113958A8
公开(公告)日：2007-01-18
申请号：PCT/AT2006000167
申请日：2006-04-25
申请人： SANDOZ AG , BOEHRINGER INGELHEIM AUSTRIA , JUNGBAUER ALOIS , HAHN RAINER , KAAR WALTRAUD , SEIFERT MICHAEL , AUER BERNHARD , ACHMUELLER CLEMENS , WECHNER PHILIPP
发明人： JUNGBAUER ALOIS , HAHN RAINER , KAAR WALTRAUD , SEIFERT MICHAEL , AUER BERNHARD , ACHMUELLER CLEMENS , WECHNER PHILIPP
IPC分类号： C07K17/06 , C07K1/22
CPC分类号： C12P21/02 , C07K1/22 , C07K17/06 , C12N9/506 , C12N15/62
摘要： Disclosed is an affinity matrix comprising a solid phase and an affinity ligand comprising peptide bonds coupled to this solid phase, wherein the affinity ligand comprising peptide bond is selected from the following group of ligands: a) peptides comprising the formula X 1 X 2 X 3 X 4 , wherein X 1 to X 4 are amino acid residues and at least two of X 1 to X 4 is W, Y or F; b) peptides comprising the formula X 5 X 6 X 7 X 8 , wherein X 5 to X 8 are amino acid residues, at least one of X 5 to X 8 is W, and at least one of X 5 to X 8 is E or D; and c) poly-amino acids consisting of an amino acid monomer of the group consisting of R, K, E and D and an amino acid monomer of the group consisting of Y, F and W, preferably poly-KY, poly-KF, poly-KW, poly-RY, poly-RF, poly-RW, poly-EY, poly-DY, poly-EF, poly-EW, poly-DF and poly-DW, with the proviso that the peptides according to a) and b) have a maximum length of 35 amino acid residues and that the poly-amino acids according to c) have a minimum length of 20 amino acid residues.
摘要翻译：公开了包含固相和亲和配体的亲和基质，所述亲和配体包含与该固相偶联的肽键，其中所述包含肽键的亲和配体选自以下配体组：a）包含式X 1，其中X _{1 至X _{4 ，其中X _{2 3 >是氨基酸残基并且X 1至X 4中的至少两个是W，Y或F; b）包含下式的肽：其中X 5，X 5，X 5，X 5，X 5，其中X至X 8至少是氨基酸残基，X 5至X 8中至少一个是W，并且X _{5 至X _{8 是E或D; 和c）由选自R，K，E和D的氨基酸单体和选自Y，F和W的氨基酸单体组成的聚氨基酸，优选聚-KY，聚-KF， poly-KW，poly-RY，poly-RF，poly-RW，poly-EY，poly-DY，poly-EF，poly-EW，poly-DF和poly-DW，条件是a）和b）具有35个氨基酸残基的最大长度，并且根据c）的聚氨基酸具有20个氨基酸残基的最小长度。}}}}}

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