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1. 发明专利

JP2009055902A IMPROVED ANTI-IgE ANTIBODY AND METHOD OF IMPROVING POLYPEPTIDE 有权
标题翻译：改进的抗IgE抗体和改善多肽的方法
公开(公告)号：JP2009055902A
公开(公告)日：2009-03-19
申请号：JP2008151343
申请日：2008-06-10
申请人： Genentech Inc , ジェネンテック・インコーポレーテッドGenentech,Inc.
发明人： LOWMAN HENRY B , PRESTA LEONARD G , JARDIEU PAULA M , LOWE JOHN
IPC分类号： C12N15/02 , C12P21/08 , A61K38/00 , A61K39/395 , A61P37/00 , A61P37/06 , A61P37/08 , A61P43/00 , C07K16/00 , C07K16/42 , C12N15/09 , C12N15/13
CPC分类号： C07K16/00 , A61K38/00 , C07K16/4291 , C07K2317/24 , Y10S424/81 , Y10S530/868
摘要： PROBLEM TO BE SOLVED: To provide a method for adjusting the affinity of a polypeptide to a target molecule. SOLUTION: The method includes (1) the identification of aspartyl residues which are prone to isomerization; and (2) the substitution of alternative residues and the screening of the resulting mutants for affinity against the target molecule. In a preferred embodiment, the method of substituting residues is affinity maturation with phage display (AMPD). In a further preferred embodiment, the polypeptide is an antibody and the target molecule is an antigen. In a further preferred embodiment, the antibody is anti-IgE and the target molecule is IgE. In another embodiment, the invention relates to an anti-IgE antibody having improved affinity to IgE. COPYRIGHT: (C)2009,JPO&INPIT
摘要翻译：待解决的问题：提供一种调节多肽与靶分子的亲和力的方法。解决方案：该方法包括（1）易于异构化的天冬氨酰残基的鉴定; 和（2）替代残基并筛选得到的突变体对靶分子的亲合力。在优选的实施方案中，取代残基的方法是用噬菌体展示（AMPD）进行亲和力成熟。在另一个优选的实施方案中，多肽是抗体，靶分子是抗原。在另一个优选的实施方案中，抗体是抗IgE，靶分子是IgE。在另一个实施方案中，本发明涉及对IgE具有改善的亲和力的抗IgE抗体。版权所有（C）2009，JPO＆INPIT

2. 发明专利

JP2007289200A Method and composition for prolonging elimination half-time of bioactive compound 有权
标题翻译：用于促进生物活性化合物消除半衰期的方法和组合物
公开(公告)号：JP2007289200A
公开(公告)日：2007-11-08
申请号：JP2007154102
申请日：2007-06-11
申请人： Genentech Inc , ジェネンテック・インコーポレーテッドGenentech,Inc.
发明人： DELANO WARREN L , DENNIS MARK S , LOWMAN HENRY B
IPC分类号： C12N15/09 , A61K38/00 , A61K39/395 , A61K47/48 , A61P43/00 , C07K1/04 , C07K7/08 , C07K9/00 , C07K14/00 , C07K14/005 , C07K16/00 , C07K16/22 , C07K16/24 , C07K16/46 , C07K19/00
CPC分类号： C07K1/047 , A61K38/00 , A61K47/62 , A61K47/643 , A61K47/65 , A61K47/68 , A61K2039/505 , C07K7/08 , C07K14/001 , C07K16/22 , C07K16/24 , C07K16/461 , C07K2317/55
摘要： PROBLEM TO BE SOLVED: To provide a method and a composition for prolonging the elimination half-time of a bioactive compound administered into a living body for the purpose of therapy or diagnosis. SOLUTION: A peptide ligand having an affinity for IgG or serum albumin or a conjugate (hybrid molecule) comprising a peptide ligand domain and an active domain and a polynucleotide encoding the conjugate are provided. The elimination half-time is improved by forming the hybrid molecule in which the peptide ligand has a binding affinity for a plasma protein. In a preferred embodiment, a bioactive molecule having a short elimination half-time is incorporated as the active domain of the hybrid molecule. COPYRIGHT: (C)2008,JPO&INPIT
摘要翻译：待解决的问题：为了提供用于治疗或诊断目的的延长施用于生物体的生物活性化合物的消除半衰期的方法和组合物。提供了对IgG或血清白蛋白具有亲和力的肽配体或包含肽配体结构域和活性结构域的缀合物（杂合分子）和编码该缀合物的多核苷酸。通过形成其中肽配体对血浆蛋白具有结合亲和力的杂交分子来改善消除半衰期。在优选的实施方案中，引入具有短消除半衰期的生物活性分子作为杂合分子的活性结构域。版权所有（C）2008，JPO＆INPIT

3. 发明专利

JP2009159950A Immunoglobulin variant, method for using the same, and use thereof 审中-公开
标题翻译：免疫球蛋白变体，使用它们的方法及其用途
公开(公告)号：JP2009159950A
公开(公告)日：2009-07-23
申请号：JP2008297806
申请日：2008-11-21
申请人： Genentech Inc , ジェネンテック・インコーポレーテッドGenentech,Inc.
发明人： ADAMS CAMELLIA W , CHAN ANDREW C , CROWLEY CRAIG W , LOWMAN HENRY B , NAKAMURA GERALD R , PRESTA LEONARD G
IPC分类号： C12N15/09 , A61K20060101 , A61K9/08 , A61K31/475 , A61K31/519 , A61K31/573 , A61K31/675 , A61K31/704 , A61K39/395 , A61K45/00 , A61K47/22 , A61K47/26 , A61K47/34 , A61K51/00 , A61P1/04 , A61P1/12 , A61P1/16 , A61P3/10 , A61P5/00 , A61P5/14 , A61P5/40 , A61P7/04 , A61P7/06 , A61P9/00 , A61P9/10 , A61P9/14 , A61P11/00 , A61P11/02 , A61P11/06 , A61P13/12 , A61P15/08 , A61P17/00 , A61P17/02 , A61P17/06 , A61P17/14 , A61P19/02 , A61P21/04 , A61P25/00 , A61P27/02 , A61P29/00 , A61P31/06 , A61P35/00 , A61P35/02 , A61P37/02 , A61P37/06 , A61P37/08 , A61P43/00 , C07H21/04 , C07K14/705 , C07K16/00 , C07K16/28 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/63 , C12P21/08
CPC分类号： C07K16/2887 , A61K2039/505 , C07K2317/24 , C07K2317/41 , C07K2317/52 , C07K2317/522 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/72 , C07K2317/73 , C07K2317/732 , C07K2317/734 , C07K2317/92
摘要： PROBLEM TO BE SOLVED: To provide an anti-CD20 antibody, and to provide a method for treating B-cell-associated diseases. SOLUTION: The anti-CD20 antibody is a monoclonal antibody and the antibody binding to the CD20 is humanized or chimeric. Humanized 2H7 variants include those that have amino acid substituents in FR and maturation variants having changes in grafted CDRs. The anti-CD20 antibody is effective in depleting B cells of primates in vivo and treatment of CD20 positive malignancies and autoimmune diseases can be carried out. COPYRIGHT: (C)2009,JPO&INPIT
摘要翻译：待解决的问题：提供抗CD20抗体，并提供治疗B细胞相关疾病的方法。解决方案：抗CD20抗体是单克隆抗体，与CD20结合的抗体是人源化或嵌合的。人源化2H7变体包括在FR中具有氨基酸取代基的那些变体和具有接枝CDR变化的成熟变体。抗CD20抗体在体内消耗灵长类动物的B细胞是有效的，可以进行CD20阳性恶性肿瘤和自身免疫性疾病的治疗。版权所有（C）2009，JPO＆INPIT

4. 发明专利

JP2009149661A Anti-her2 antibody variants 审中-公开
标题翻译：抗HER2抗体变异体
公开(公告)号：JP2009149661A
公开(公告)日：2009-07-09
申请号：JP2009023157
申请日：2009-02-03
申请人： Genentech Inc , ジェネンテック・インコーポレーテッドGenentech,Inc.
发明人： LOWMAN HENRY B , GERSTNER RESI B , CARTER PAUL J
IPC分类号： A61K39/395 , C07K16/46 , A61K38/16 , A61P35/00 , A61P35/02 , C07K16/18 , C07K16/28 , C07K16/32 , C12N15/09 , G01N33/53
CPC分类号： C07K16/32 , A61J1/00 , A61J1/18 , A61J2205/30 , C07K16/3015 , C07K2317/21 , C07K2317/24 , C07K2317/54 , C07K2317/55 , C07K2317/56 , C07K2317/92
摘要： PROBLEM TO BE SOLVED: To provide novel antibody variants, particularly anti-HER2 antibody variants having substitutions at positions within the variable domains of the heavy and light chains. SOLUTION: The present invention is based on the finding that particular amino acids of the humanized anti-HER2 antibody hu4D5-8, determined by alanine scanning to be necessary for antigen binding, and other amino acids found by alanine scanning to be relatively unimportant for antigen binding, may be substituted to produce variants having high affinity for HER2. COPYRIGHT: (C)2009,JPO&INPIT
摘要翻译：要解决的问题：提供新的抗体变体，特别是在重链和轻链的可变结构域内具有取代的抗HER2抗体变体。解决方案：本发明是基于以下发现：通过丙氨酸扫描测定的抗原结合所必需的人源化抗HER2抗体hu4D5-8的特定氨基酸和通过丙氨酸扫描发现的其它氨基酸相对于不重要的抗原结合，可以被取代以产生对HER2具有高亲和力的变体。版权所有（C）2009，JPO＆INPIT

5. 发明专利

JP2007291120A Igf antagonist peptide 有权
标题翻译： IGF拮抗肽
公开(公告)号：JP2007291120A
公开(公告)日：2007-11-08
申请号：JP2007155555
申请日：2007-06-12
申请人： Genentech Inc , ジェネンテック・インコーポレーテッドGenentech,Inc.
发明人： DESHAYES KURT , LOWMAN HENRY B , SCHAFFER MICHELLE L , SIDHU SACHDEV S
IPC分类号： C07K7/08 , G01N33/53 , A61K38/00 , A61K38/04 , A61K39/395 , A61K45/00 , A61P3/10 , A61P5/24 , A61P9/10 , A61P13/12 , A61P17/00 , A61P17/02 , A61P27/02 , A61P35/00 , A61P43/00 , C07K7/06 , C07K14/47 , G01N33/574
CPC分类号： C07K14/4743 , A61K38/00 , C07K2299/00
摘要： PROBLEM TO BE SOLVED: To provide a peptide antagonizing the interaction of IGF-1 (insulin-like growth factor-1) with a binding protein thereof, an insulin receptor and an IGF receptor. SOLUTION: The peptide has a specific amino acid sequence. The peptide is conjugated to a cytotoxic agent or polyethylene glycol. A pharmaceutical composition comprises the peptide in a carrier. The IGF antagonist peptide is useful for treating disorders involving the IGF-1 as a causative substance such as, for example various cancers. COPYRIGHT: (C)2008,JPO&INPIT
摘要翻译：待解决的问题：提供拮抗IGF-1（胰岛素样生长因子-1）与其结合蛋白，胰岛素受体和IGF受体的相互作用的肽。肽解决方案：肽具有特定的氨基酸序列。该肽与细胞毒性剂或聚乙二醇缀合。药物组合物包含载体中的肽。 IGF拮抗剂肽可用于治疗涉及IGF-1作为致病物质的疾病，例如各种癌症。版权所有（C）2008，JPO＆INPIT

6. 发明专利

JP2007289187A Method and composition for prolonging elimination half-time of bioactive compound 有权
标题翻译：用于促进生物活性化合物消除半衰期的方法和组合物
公开(公告)号：JP2007289187A
公开(公告)日：2007-11-08
申请号：JP2007107978
申请日：2007-04-17
申请人： Genentech Inc , ジェネンテック・インコーポレーテッドGenentech,Inc.
发明人： DELANO WARREN L , DENNIS MARK S , LOWMAN HENRY B
IPC分类号： C12N15/09 , A61K38/00 , A61K39/395 , A61K47/48 , A61P43/00 , C07K1/04 , C07K7/00 , C07K7/08 , C07K9/00 , C07K14/00 , C07K16/22 , C07K16/24 , C07K16/46 , C07K19/00
CPC分类号： C07K1/047 , A61K38/00 , A61K47/62 , A61K47/643 , A61K47/65 , A61K47/68 , A61K2039/505 , C07K7/08 , C07K14/001 , C07K16/22 , C07K16/24 , C07K16/461 , C07K2317/55
摘要： PROBLEM TO BE SOLVED: To provide a composition and a method for prolonging the elimination half-time of a therapeutic or a diagnostic substance. SOLUTION: A conjugate comprises a peptide having a specific amino acid sequence designed so as to have an ability to bind to a plasma protein (immunoglobulin) in which the peptide is conjugated to the therapeutic or diagnostic substance. The elimination half-time of the conjugate exceeds that of an unconjugated therapeutic or diagnostic substance. The method for prolonging the elimination half-time of the therapeutic or diagnostic substance comprises utilizing the conjugate. COPYRIGHT: (C)2008,JPO&INPIT
摘要翻译：待解决的问题：提供用于延长治疗剂或诊断物质的消除半衰期的组合物和方法。解决方案：缀合物包含具有特定氨基酸序列的肽，其设计为具有与肽结合至治疗或诊断物质的血浆蛋白（免疫球蛋白）结合的能力。共轭物的消除半衰期超过非共轭治疗或诊断物质的半衰期。用于延长治疗或诊断物质的消除半衰期的方法包括利用缀合物。版权所有（C）2008，JPO＆INPIT

7. 发明专利

JP2006104205A Human growth hormone variant 审中-公开
标题翻译：人类生长激素变异
公开(公告)号：JP2006104205A
公开(公告)日：2006-04-20
申请号：JP2005304574
申请日：2005-10-19
申请人： Genentech Inc , ジェネンテック・インコーポレーテッドGenentech,Inc.
发明人： GARRARD LISA J , HENNER DENNIS J , BASS STEVEN , GREENE RONALD , LOWMAN HENRY B , WELLS JAMES A , MATTHEWS DAVID J
IPC分类号： C07K14/61 , C12N15/09 , A61K38/27 , A61P5/06 , A61P5/10 , C07K14/01 , C07K14/47 , C07K14/475 , C07K14/52 , C07K14/575 , C07K19/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N7/00 , C12N7/02 , C12P21/02 , C12Q1/02 , C12R1/19 , G01N33/53
摘要： PROBLEM TO BE SOLVED: To provide human growth hormone variants in the production of a therapeutic or diagnostic compound which imitates a protein or non-peptidyl molecule such as a hormone, a drug, and other small molecules (particularly a biologically active molecule such as a growth hormone). SOLUTION: The human growth hormone variants have (a) the amino acids of hGH at positions 172 and the like which are replaced with (1) other amino acids selected from the group consisting of R, S, F, R and the like, (b) the amino acids at positions 10 and the like which are replaced with (1) other amino acids selected from the group consisting of H, G, N, N and the like, (c) the amino acid at position 174 being serine and the amino acid at position 176 being tyrosine, and the amino acids at positions 167 and the like which are replaced with (1) other amino acids selected from the group consisting of N, S, T, T and the like, (d) glutamate 174 being replaced with tyrosine 174 , phenylalanine 176 being replaced with tyrosine 176 , and 8 amino acids which are replaced with other amino acids, (e) in the hGH variant (d), 8 of amino acid F10 and the like which are replaced with (1) other amino acids selected from the group (1) consisting of H, G, N, N, N, S, T, T and the like in the order named, (f) in the (e), leucine 15 being replaced with arginine 15 and the amino acid at position 168 being replaced with arginine 168 , and (g) the (e) further containing phenylalanine 176 . COPYRIGHT: (C)2006,JPO&NCIPI
摘要翻译：待解决的问题：提供人生长激素变体在制备模拟蛋白质或非肽基分子如激素，药物和其他小分子（特别是生物活性分子）的治疗或诊断化合物如生长激素）。解决方案：人生长激素变体具有（a）位置172等处的hGH的氨基酸，其被替换为（1）选自R，S，F，R的其它氨基酸，和如（1）选自H，G，N，N等的其它氨基酸，（c）位置10上的氨基酸等位置上的氨基酸，是丝氨酸，第176位的氨基酸是酪氨酸，167位的氨基酸被替换为（1）选自N，S，T，T等的其它氨基酸（ d）用酪氨酸 174 替代谷氨酸酯 174 ，用酪氨酸 176 替代苯丙氨酸 176 和8个氨基酸其被替换为其他氨基酸，（e）在hGH变体（d）中，氨基酸F10等的8等被（1）选自由H，G， N，N，N，S，T，T （f）在（e）中，亮氨酸 15 被精氨酸 15 替代，位置168处的氨基酸被精氨酸 SB> 168 ，和（g）（e）还含有苯丙氨酸 176 。版权所有（C）2006，JPO＆NCIPI

8. 发明专利

JP2006328074A Insulin-like growth factor (igf) i mutant 审中-公开
标题翻译：胰岛素样生长因子（IGF）I MUTANT
公开(公告)号：JP2006328074A
公开(公告)日：2006-12-07
申请号：JP2006171517
申请日：2006-06-21
申请人： Genentech Inc , ジェネンテック・インコーポレーテッドGenentech,Inc.
发明人： DUBAQUIE YVES , FIELDER PAUL J , LOWMAN HENRY B , MORTENSEN DEBORAH L
IPC分类号： C07K14/65 , C12N15/09 , A61K38/00 , A61K38/27 , A61K38/30 , A61K45/00 , A61P1/16 , A61P3/02 , A61P3/10 , A61P5/02 , A61P5/10 , A61P9/04 , A61P13/12 , A61P43/00
CPC分类号： C07K14/65 , A61K38/00
摘要： PROBLEM TO BE SOLVED: To provide an agonist having insulin-like growth factor (IGFs) useful for the treatment of diseases characterized by dysregulation of GH/IGF axis such as renal disorder. SOLUTION: The invention provides a mutant of insulin-like growth factor I having alanine, glycine or serine residue substituting the amino acid residue at position 16, 25 or 49, or at positions 3 and 49 of native-sequence human IGF-I. COPYRIGHT: (C)2007,JPO&INPIT
摘要翻译：待解决的问题：提供一种具有胰岛素样生长因子（IGF）的激动剂，其可用于治疗特征为GH / IGF轴异常的疾病如肾病。解决方案：本发明提供了具有丙氨酸，甘氨酸或丝氨酸残基的胰岛素样生长因子I的突变体，其代替天然序列人IGF-I的第16,25或49位或第3和49位的氨基酸残基，一世。版权所有（C）2007，JPO＆INPIT

9. 发明专利

JP2005065705A Method for enriching mutant protein having modified bonding property 审中-公开
标题翻译：用于增强具有改性结合性质的突变蛋白的方法
公开(公告)号：JP2005065705A
公开(公告)日：2005-03-17
申请号：JP2004327565
申请日：2004-11-11
申请人： Genentech Inc , ジェネンテック・インコーポレーテッドGenentech,Inc.
发明人： GARRARD LISA J , HENNER DENNIS J , BASS STEVEN , GREENE RONALD , LOWMAN HENRY B , WELLS JAMES A , MATTHEWS DAVID J
IPC分类号： C12N15/09 , A61K38/27 , A61P5/06 , C07K14/01 , C07K14/47 , C07K14/475 , C07K14/52 , C07K14/575 , C07K14/61 , C07K19/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N7/00 , C12N7/02 , C12P21/02 , C12Q1/02 , C12R1/19
摘要： PROBLEM TO BE SOLVED: To provide a phagemid expression vector containing a transcription control element functionally bonded to a gene fusion encoding a fusion protein. SOLUTION: Disclosed is a phagemid expression vector, wherein the gene fusion comprises a first gene encoding a polypeptide and a second gene encoding at least one part of a phage coat protein and wherein (a) the vector contains no gene encoding a mature coat protein and (b) no perfect phage genome, (c) host cell transformation caused by the vector produces no phage particle in the absence of a helper phage, or (d) a DNA triplet codon encoding a termination codon capable of controlling mRNA is inserted between the fusion terminals of the first and the second genes or substituted instead of an amino acid-encoded triplet codon adjacent to the gene fusion connecting point. COPYRIGHT: (C)2005,JPO&NCIPI
摘要翻译：待解决的问题：提供含有与编码融合蛋白的基因融合物功能结合的转录调控元件的噬菌粒表达载体。解决方案：公开了一种噬菌粒表达载体，其中所述基因融合物包含编码多肽的第一基因和编码噬菌体外壳蛋白的至少一部分的第二基因，其中（a）载体不含编码成熟的基因外壳蛋白和（b）没有完美的噬菌体基因组，（c）由载体引起的宿主细胞转化在不存在辅助噬菌体的情况下不产生噬菌体颗粒，或（d）编码能够控制mRNA的终止密码子的DNA三联密码子是插入在第一和第二基因的融合末端之间，或代替与基因融合连接点相邻的氨基酸编码的三联密码子。版权所有（C）2005，JPO＆NCIPI

10. 发明专利

JP2005021157A Human growth hormone variants 有权
标题翻译：人类生长激素变异
公开(公告)号：JP2005021157A
公开(公告)日：2005-01-27
申请号：JP2004126082
申请日：2004-04-21
申请人： Genentech Inc , ジェネンテック・インコーポレーテッドGenentech,Inc.
发明人： CUNNINGHAM BRIAN C , LOWMAN HENRY B , WELLS JAMES A , CLARK ROSS G , OLSON KENNETH , FUH GERMAINE G
IPC分类号： C12N15/09 , A61K31/00 , A61K38/00 , A61K38/27 , A61K47/48 , A61P3/00 , A61P3/10 , A61P5/00 , A61P5/08 , A61P5/12 , A61P13/12 , A61P35/00 , A61P37/00 , A61P43/00 , C07K1/107 , C07K14/61 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/18 , C12N15/63 , C12P21/02 , C12R1/19
CPC分类号： C07K14/61 , A61K38/00 , A61K47/60 , C07K2319/00 , Y10S514/866 , Y10S930/12
摘要： PROBLEM TO BE SOLVED: To provide a human growth hormone variant having an enhanced affinity for a growth hormone receptor and also a human growth hormone variant conjugated to one or more chemical groups, such as poly(ethylene glycol), which is believed to prolong the in vivo half-life of the variant. SOLUTION: The human growth hormone variants comprise a plurality of specific amino acid substitutions. The human growth hormone variants are used as agonists or antagonists of human growth hormone. COPYRIGHT: (C)2005,JPO&NCIPI

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