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1. 发明授权

US07750136B2 Modified bouganin proteins, cytotoxins and methods and uses thereof 有权
标题翻译：改良的bouganin蛋白，细胞毒素及其方法和用途
公开(公告)号：US07750136B2
公开(公告)日：2010-07-06
申请号：US11971660
申请日：2008-01-09
申请人： Matthew Baker , Francis J. Carr , Koen Hellendoorn , Jeannick Cizeau , Glen Christopher MacDonald , Joycelyn Entwistle , Denis Georges Bosc , Nicholas Ronald Glover
发明人： Matthew Baker , Francis J. Carr , Koen Hellendoorn , Jeannick Cizeau , Glen Christopher MacDonald , Joycelyn Entwistle , Denis Georges Bosc , Nicholas Ronald Glover
IPC分类号： C07H21/04
CPC分类号： C07K16/30 , A61K38/00 , A61K47/6825 , A61K2039/505 , C07K14/415 , C07K2317/34 , C07K2317/55 , C07K2317/622 , C07K2319/00 , C07K2319/30 , C07K2319/33 , C07K2319/55
摘要： The invention provides modified forms of bouganin protein having biological activity and a reduced propensity to activate human T cells as compared to the non-modified bouganin protein. The invention also provides T-cell epitope peptides of bouganin, and modified T-cell epitope peptides of bouganin which have a reduced propensity to activate human T cells as compared to the non-modified T-cell epitope peptide. The invention also provides cytotoxins having the having a ligand that binds to a cancer cells attached to the modified bouganin proteins. Also provided are methods of inhibiting or destroying mammalian cancer cells using the cytotoxins of the invention and pharmaceutical compositions for treating human cancer.
摘要翻译：本发明提供具有生物活性的bouganin蛋白质的修饰形式，与非修饰的bouganin蛋白质相比，活化人类T细胞的倾向降低。本发明还提供了与非修饰的T细胞表位肽相比，bouganin的T细胞表位肽和bouganin的修饰的T细胞表位肽，其具有降低的活化人T细胞的倾向。本发明还提供了具有与附着于改良的bouganin蛋白的癌细胞结合的配体的细胞毒素。还提供了使用本发明的细胞毒素和用于治疗人类癌症的药物组合物来抑制或破坏哺乳动物癌细胞的方法。

2. 发明申请

US20080219994A1 MODIFIED BOUGANIN PROTEINS, CYTOTOXINS AND METHODS AND USES THEREOF 有权
标题翻译：改良的布基甘宁蛋白，细胞因子及其方法及其用途
公开(公告)号：US20080219994A1
公开(公告)日：2008-09-11
申请号：US11971660
申请日：2008-01-09
申请人： Matthew Baker , Francis J. Carr , Koen Hellendoorn , Jeannick Cizeau , Glen Christopher MacDonald , Joycelyn Entwistle , Denis Georges Bosc , Nicholas Ronald Glover
发明人： Matthew Baker , Francis J. Carr , Koen Hellendoorn , Jeannick Cizeau , Glen Christopher MacDonald , Joycelyn Entwistle , Denis Georges Bosc , Nicholas Ronald Glover
IPC分类号： A61K39/395 , A61P35/00
CPC分类号： C07K16/30 , A61K38/00 , A61K47/6825 , A61K2039/505 , C07K14/415 , C07K2317/34 , C07K2317/55 , C07K2317/622 , C07K2319/00 , C07K2319/30 , C07K2319/33 , C07K2319/55
摘要： The invention provides modified forms of bouganin protein having biological activity and a reduced propensity to activate human T cells as compared to the non-modified bouganin protein. The invention also provides T-cell epitope peptides of bouganin, and modified T-cell epitope peptides of bouganin which have a reduced propensity to activate human T cells as compared to the non-modified T-cell epitope peptide. The invention also provides cytotoxins having the having a ligand that binds to a cancer cells attached to the modified bouganin proteins. Also provided are methods of inhibiting or destroying mammalian cancer cells using the cytotoxins of the invention and pharmaceutical compositions for treating human cancer.
摘要翻译：本发明提供具有生物活性的bouganin蛋白质的修饰形式，与非修饰的bouganin蛋白质相比，活化人类T细胞的倾向降低。本发明还提供了与非修饰的T细胞表位肽相比，bouganin的T细胞表位肽和bouganin的修饰的T细胞表位肽，其具有降低的活化人T细胞的倾向。本发明还提供了具有与附着于改良的bouganin蛋白的癌细胞结合的配体的细胞毒素。还提供了使用本发明的细胞毒素和用于治疗人类癌症的药物组合物来抑制或破坏哺乳动物癌细胞的方法。

3. 发明授权

US08716234B2 Cytotoxins comprising modified bouganin toxin for the treatment of cancer 有权
标题翻译：细胞毒素包含改良的bouganin毒素用于治疗癌症
公开(公告)号：US08716234B2
公开(公告)日：2014-05-06
申请号：US12784820
申请日：2010-05-21
申请人： Matthew Baker , Francis J. Carr , Koen Hellendoorn , Jeannick Cizeau , Glen Christopher MacDonald , Joycelyn Entwistle , Denis Georges Bosc , Nicholas Ronald Glover
发明人： Matthew Baker , Francis J. Carr , Koen Hellendoorn , Jeannick Cizeau , Glen Christopher MacDonald , Joycelyn Entwistle , Denis Georges Bosc , Nicholas Ronald Glover
IPC分类号： A61P35/00
CPC分类号： C07K16/30 , A61K38/00 , A61K47/6825 , A61K2039/505 , C07K14/415 , C07K2317/34 , C07K2317/55 , C07K2317/622 , C07K2319/00 , C07K2319/30 , C07K2319/33 , C07K2319/55
摘要： The invention provides modified forms of bouganin protein having biological activity and a reduced propensity to activate human T cells as compared to the non-modified bouganin protein. The invention also provides T-cell epitope peptides of bouganin, and modified T-cell epitope peptides of bouganin which have a reduced propensity to activate human T cells as compared to the non-modified T-cell epitope peptide. The invention also provides cytotoxins having the having a ligand that binds to a cancer cells attached to the modified bouganin proteins. Also provided are methods of inhibiting or destroying mammalian cancer cells using the cytotoxins of the invention and pharmaceutical compositions for treating human cancer.
摘要翻译：本发明提供具有生物活性的bouganin蛋白质的修饰形式，与非修饰的bouganin蛋白质相比，活化人类T细胞的倾向降低。本发明还提供了与非修饰的T细胞表位肽相比，bouganin的T细胞表位肽和bouganin的修饰的T细胞表位肽，其具有降低的活化人T细胞的倾向。本发明还提供了具有与附着于改良的bouganin蛋白的癌细胞结合的配体的细胞毒素。还提供了使用本发明的细胞毒素和用于治疗人类癌症的药物组合物来抑制或破坏哺乳动物癌细胞的方法。

4. 发明申请

US20100254964A1 Modified Bouganin Proteins, Cytotoxins and Methods and Uses Thereof 有权
标题翻译：改良的Bouganin蛋白，细胞毒素及其用途
公开(公告)号：US20100254964A1
公开(公告)日：2010-10-07
申请号：US12784820
申请日：2010-05-21
申请人： Matthew Baker , Francis J. Carr , Koen Hellendoorn , Jeannick Cizeau , Glen Christopher MacDonald , Joycelyn Entwistle , Denis Georges Bosc , Nicholas Ronald Glover
发明人： Matthew Baker , Francis J. Carr , Koen Hellendoorn , Jeannick Cizeau , Glen Christopher MacDonald , Joycelyn Entwistle , Denis Georges Bosc , Nicholas Ronald Glover
IPC分类号： A61K38/47 , A61P35/00
CPC分类号： C07K16/30 , A61K38/00 , A61K47/6825 , A61K2039/505 , C07K14/415 , C07K2317/34 , C07K2317/55 , C07K2317/622 , C07K2319/00 , C07K2319/30 , C07K2319/33 , C07K2319/55
摘要： The invention provides modified forms of bouganin protein having biological activity and a reduced propensity to activate human T cells as compared to the non-modified bouganin protein. The invention also provides T-cell epitope peptides of bouganin, and modified T-cell epitope peptides of bouganin which have a reduced propensity to activate human T cells as compared to the non-modified T-cell epitope peptide. The invention also provides cytotoxins having the having a ligand that binds to a cancer cells attached to the modified bouganin proteins. Also provided are methods of inhibiting or destroying mammalian cancer cells using the cytotoxins of the invention and pharmaceutical compositions for treating human cancer.
摘要翻译：本发明提供具有生物活性的bouganin蛋白质的修饰形式，与非修饰的bouganin蛋白质相比，活化人类T细胞的倾向降低。本发明还提供了与非修饰的T细胞表位肽相比，bouganin的T细胞表位肽和bouganin的修饰的T细胞表位肽，其具有降低的活化人T细胞的倾向。本发明还提供了具有与附着于改良的bouganin蛋白的癌细胞结合的配体的细胞毒素。还提供了使用本发明的细胞毒素和用于治疗人类癌症的药物组合物来抑制或破坏哺乳动物癌细胞的方法。

5. 发明授权

US07339031B2 Modified bouganin proteins, cytotoxins and methods and uses thereof 有权
标题翻译：改良的bouganin蛋白，细胞毒素及其方法和用途
公开(公告)号：US07339031B2
公开(公告)日：2008-03-04
申请号：US11084080
申请日：2005-03-18
申请人： Matthew Baker , Francis J. Carr , Koen Hellendoorn , Jeannick Cizeau , Glen Christopher MacDonald , Joycelyn Entwistle , Denis Georges Bosc , Nicholas Ronald Glover
发明人： Matthew Baker , Francis J. Carr , Koen Hellendoorn , Jeannick Cizeau , Glen Christopher MacDonald , Joycelyn Entwistle , Denis Georges Bosc , Nicholas Ronald Glover
IPC分类号： C07K14/00 , C07K16/40 , C12P21/04
CPC分类号： C07K16/30 , A61K38/00 , A61K47/6825 , A61K2039/505 , C07K14/415 , C07K2317/34 , C07K2317/55 , C07K2317/622 , C07K2319/00 , C07K2319/30 , C07K2319/33 , C07K2319/55
摘要： The invention provides modified forms of bouganin protein having biological activity and a reduced propensity to activate human T cells as compared to the non-modified bouganin protein. The invention also provides T-cell epitope peptides of bouganin, and modified T-cell epitope peptides of bouganin which have a reduced propensity to activate human T cells as compared to the non-modified T-cell epitope peptide. The invention also provides cytotoxins having the having a ligand that binds to a cancer cells attached to the modified bouganin proteins. Also provided are methods of inhibiting or destroying mammalian cancer cells using the cytotoxins of the invention and pharmaceutical compositions for treating human cancer.
摘要翻译：本发明提供具有生物活性的bouganin蛋白质的修饰形式，与非修饰的bouganin蛋白质相比，活化人类T细胞的倾向降低。本发明还提供了与非修饰的T细胞表位肽相比，bouganin的T细胞表位肽和bouganin的修饰的T细胞表位肽，其具有降低的活化人T细胞的倾向。本发明还提供了具有与附着于改良的bouganin蛋白的癌细胞结合的配体的细胞毒素。还提供了使用本发明的细胞毒素和用于治疗人类癌症的药物组合物来抑制或破坏哺乳动物癌细胞的方法。

6. 发明授权

US07524502B2 Modified anti-TNF alpha antibody 失效
标题翻译：修饰的抗TNFα抗体
公开(公告)号：US07524502B2
公开(公告)日：2009-04-28
申请号：US10495146
申请日：2002-11-11
申请人： Koen Hellendoorn , Matthew Baker , Francis J. Carr
发明人： Koen Hellendoorn , Matthew Baker , Francis J. Carr
IPC分类号： A61K39/395
CPC分类号： C07K7/08 , C07K16/241 , C07K2317/24 , C07K2317/56
摘要： The invention relates to the modification of antibodies reactive to human tumor necrosis factor alpha (TNF alpha) to result in anti-TNF alpha antibodies that are substantially non-immunogenic or less immunogenic than any non-modified parental antibody when used in vivo. The invention relates also to peptide molecules comprising T-cell epitopes of the V-regions of the parental antibody which are modified by amino acid alteration in order to reduce or eliminate said T-cell epitopes.
摘要翻译：本发明涉及对人肿瘤坏死因子α（TNFα）具有反应性的抗体的修饰，以产生当在体内使用时与任何未修饰的亲本抗体基本上不具有免疫原性或较低免疫原性的抗TNFα抗体。本发明还涉及包含通过氨基酸改变修饰的亲本抗体的V区的T细胞表位的肽分子，以便减少或消除所述T细胞表位。

7. 发明授权

US07754853B2 TNF alpha-binding polypeptide compositions and methods 失效
标题翻译： TNFα结合多肽组合物和方法
公开(公告)号：US07754853B2
公开(公告)日：2010-07-13
申请号：US11005726
申请日：2004-12-07
申请人： Koen Hellendoorn , Matthew Baker , Francis J. Carr
发明人： Koen Hellendoorn , Matthew Baker , Francis J. Carr
IPC分类号： A61K38/00
CPC分类号： C07K7/08 , C07K16/241 , C07K2317/24 , C07K2317/56
摘要： This invention pertains to a TNF alpha-binding polypeptide composition comprising at least one of a modified heavy chain variable region polypeptide or a modified light chain variable region polypeptide that is capable of specifically binding to human TNF alpha. The modified heavy and light chain variable region polypeptides of the TNF alpha binding polypeptide are modified by at least one amino acid residue substitution, deletion or addition and are homologous to the heavy and light chain variable regions, respectively, of a non-human monoclonal antibody that specifically binds human TNF alpha. The polypeptide compositions of the invention comprising modified heavy and light chain variable region polypeptides are less immunogenic in a human than are the homologous heavy and light chain variable region polypeptides from a non-human animal.
摘要翻译：本发明涉及包含能够特异性结合人TNFα的修饰的重链可变区多肽或修饰的轻链可变区多肽中的至少一种的TNFα结合多肽组合物。通过至少一个氨基酸残基取代，缺失或添加修饰TNFα结合多肽的修饰的重链和轻链可变区多肽，并分别与非人单克隆抗体的重链和轻链可变区同源其特异性结合人TNFα。包含修饰的重链和轻链可变区多肽的本发明的多肽组合物在人类中比来自非人动物的同源重链和轻链可变区多肽的免疫原性较低。

8. 发明授权

US07939295B2 Methods for reducing immunogenicity of polypeptides 失效
标题翻译：降低多肽免疫原性的方法
公开(公告)号：US07939295B2
公开(公告)日：2011-05-10
申请号：US10483153
申请日：2002-07-12
申请人： Francis J. Carr , Graham Carter , Koen Hellendoorn
发明人： Francis J. Carr , Graham Carter , Koen Hellendoorn
IPC分类号： C12N15/09
CPC分类号： C12N9/6472 , C07K14/47
摘要： This invention relates to the fields of immunology and protein therapeutics. The therapeutic proteins are polypeptides to be administered especially to humans. The polypeptides are modified whereby the modification results in a reduced propensity for the polypeptide to elicit an immune response upon administration to the human subject. The invention therefor provides methods for the development of therapeutic polypeptides that are less immunogenic than any non-modified counterpart when used in vivo. The modifications used according to this invention relate, for example, to the introduction of protease cleavage sites, attachment of different molecules or insertion of non-natural amino acids.
摘要翻译：本发明涉及免疫学和蛋白质治疗领域。治疗性蛋白质是特别施用于人的多肽。修饰多肽，由此修饰导致多肽在施用于人受试者时引起免疫应答的倾向降低。本发明提供了用于开发当在体内使用时比任何未修饰的对应物具有较少免疫原性的治疗性多肽的方法。根据本发明使用的修饰涉及例如引入蛋白酶切割位点，附着不同分子或插入非天然氨基酸。

9. 发明授权

US07615615B2 Modified interferon beta with reduced immunogenicity 失效
标题翻译：修饰的干扰素β具有降低的免疫原性
公开(公告)号：US07615615B2
公开(公告)日：2009-11-10
申请号：US12077120
申请日：2008-03-17
申请人： Francis J. Carr , Graham Carter , Tim Jones , John Watkins , Matthew Baker
发明人： Francis J. Carr , Graham Carter , Tim Jones , John Watkins , Matthew Baker
IPC分类号： C07K14/00 , A61K38/19 , C12N15/24
CPC分类号： C07K14/565
摘要： The present invention relates a modified human interferon beta (INFβ) which is less immunogenic than human INFβ (SEQ ID NO: 1) when administered in vivo to a human. The modified human INFβ comprises an amino acid residue sequence that differs from SEQ ID NO: 1 by an amino acid residue substitution selected from the group consisting of L57A, L57C, L57D L57E, L57G, L57H, L57K, L57N, L57P, L57Q, L57R, L57S, and L57T and an additional substitution selected from the group consisting of the H140A, H140C, H140G, and H140P.
摘要翻译：本发明涉及当在体内施用于人时，比人INFbeta（SEQ ID NO：1）具有较少的免疫原性的修饰的人干扰素β（INFbeta）。修饰的人INFbeta包含与SEQ ID NO：1不同的氨基酸残基，其选自L57A，L57C，L57D，L57E，L57G，L57H，L57K，L57N，L57P，L57Q，L57R ，L57S和L57T以及选自H140A，H140C，H140G和H140P的另外的取代基。

10. 发明申请

US20090043076A1 Modified interferon beta with reduced immunogenicity 失效
公开(公告)号：US20090043076A1
公开(公告)日：2009-02-12
申请号：US12077120
申请日：2008-03-17
申请人： Francis J. Carr , Graham Carter , Tim Jones , John Watkins , Matthew Baker
发明人： Francis J. Carr , Graham Carter , Tim Jones , John Watkins , Matthew Baker
IPC分类号： C07K14/565
CPC分类号： C07K14/565
摘要： The present invention relates a modified human interferon beta (INFβ) which is less immunogenic than human INFβ (SEQ ID NO: 1) when administered in vivo to a human. The modified human INFβ comprises an amino acid residue sequence that differs from SEQ ID NO: 1 by an amino acid residue substitution selected from the group consisting of L57A, L57C, L57D L57E, L57G, L57H, L57K, L57N, L57P, L57Q, L57R, L57S, and L57T and an additional substitution selected from the group consisting of the H140A, H140C, H140G, and H140P.

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