CN1154736C - 分泌异源多肽的方法和组合物 - Google Patents
分泌异源多肽的方法和组合物 Download PDFInfo
- Publication number
- CN1154736C CN1154736C CNB961930578A CN96193057A CN1154736C CN 1154736 C CN1154736 C CN 1154736C CN B961930578 A CNB961930578 A CN B961930578A CN 96193057 A CN96193057 A CN 96193057A CN 1154736 C CN1154736 C CN 1154736C
- Authority
- CN
- China
- Prior art keywords
- seq
- nucleic acid
- sequence
- varient
- atg
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Lifetime
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/24—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
- C07K14/245—Escherichia (G)
-
- 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
- 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
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/61—Fusion polypeptide containing an enzyme fusion for detection (lacZ, luciferase)
Landscapes
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Electrotherapy Devices (AREA)
- External Artificial Organs (AREA)
Abstract
本发明公开了一种出乎意料的结果,即与野生型信号序列相比,翻译强度下降的突变型信号序列可提供基本上完整的加工并高水平地表达感兴趣的多肽。而且许多哺乳动物多肽需要窄范围的翻译水平才能实现最大的分泌。一套信号序列载体提供了用于优化感兴趣多肽表达的一定范围内的翻译强度。
Description
发明领域
本发明涉及从细菌中分泌异源多肽的信号序列。
背景及相关技术的描述
将异源多肽分泌人大肠杆菌和其他原核生物的周质间隙中或培养基中,受各种不同因素的影响。一般,用于分泌感兴趣多肽的载体被加以改造,以便将编码分泌信号序列的DNA置于编码感兴趣多肽的DNA的5′端。有2个反复出现的问题困扰着多肽的分泌。首先,信号序列常常被不完全地加工或去除。其次,分泌的多肽数量常常低或不可检测。克服这些问题的努力分成3个主要方面:尝试若干种不同的信号序列,使信号序列的氨基酸序列突变,以及改变宿主细菌中的分泌途径。
已有许多信号序列可用于第一种克服分泌问题的方法。Watson(Nucleic AcidsResearch 12:5145-5164(1984))公开了一组信号序列。美国专利4,963,495公开了,用原核分泌信号序列DNA,在宿主生物体的周质间隙中表达和分泌成熟的真核蛋白质,该信号序列的3′端连于编码成熟蛋白质的DNA的5′端。特别是,优选编码大肠杆菌肠毒素信号的DNA,尤其是STII。Chang等人(
基因,55:189-196(1987))公开了,使用STII信号序列在大肠杆菌中分泌hGH。Gray等人(
基因,39:247-245(1985))公开了,使用人生长激素的天然信号序列以及使用大肠杆菌碱性磷酸酶的启动子和信号序列,在大肠杆菌中分泌人生长激素。Wong等人(
基 因,68:193-203(1988))公开了,在大肠杆菌中分泌融合于LamB和OmpF分泌前导序列的胰岛素样生长因子1(IGF-1),并且在存在prlA4突变的情况下可提高这些信号序列的加工效率。Fujimoto等人(
J.Biotech.8:77-86(1988))公开了,使用4种不同的大肠杆菌肠毒素信号序列STI、STII、LT-A和LT-B在大肠杆菌中分泌人表皮生长因子(hEGF)。Denefle等人(
基因,85:499-510(1989))公开了,使用OmpA和phoA信号肽来分泌成熟的人白细胞介素1β。
一般,诱变信号序列对于克服分泌问题并不特别有效。例如,Morioka-Fujimoto等人(
生物化学杂志266:1728-1732(1991))公开了,在LTA信号序列中的氨基酸改变会增加人表皮生长因子在大肠杆菌中分泌的数量。Goldstein等人(
J.Bact.172:1225-1231(1990))公开了,在OmpA的疏水区域的氨基酸置换可实现核酸酶A的分泌,但是不能实现TEM β-内酰胺酶的分泌。Matteucci等人(
Biotech.4:51-55(1986))公开了,在人生长激素的信号序列中的突变可增加hGH的分泌。Lehnhardt等人(
生物化学杂志262:1716-1719(1987))公开了,OmpA信号肽的缺失突变对核酸酶A和TEM β-内酰胺酶分泌的影响。
最后,通过调整宿主的机制而改善大肠杆菌中异源分泌的努力,目前为止在克服分泌问题方面仅显示出有限的改善。例如,van Dijl等人(
Mol.Gen.Genet.227:40-48(1991))公开了,大肠杆菌信号肽酶I(Spase I)的过量产生对前体加工的影响。Klein等人(
Protein Engineering 5:511-517(1992))公开了,LamB信号序列的诱变对牛促生长素的分泌有少量影响,而且牛促生长素的分泌似乎由成熟蛋白质所决定,而不是由信号序列的改变所决定。Perez-Perez等人(
Bio/Technology 12:179-1 80(1994))公开了,使大肠杆菌宿主有额外拷贝的prLA4(secY等位基因)和secE基因(它们编码“转运蛋白”(即将运输蛋白质机械地通过膜的分子装置)的主要成分),可以将成熟hIL-6对hIL-6前体的比例从1.2增加至10.8。美国专利5,232,840公开了新的核糖体结合位点,它们可用于通过更强的和/或更有效的翻译而增加细菌中蛋白质的产生。美国专利5,082,783公开了,通过使用与异源DNA分泌信号序列具有最中间强度的启动子,可以增加宿主如酵母分泌异源蛋白。1984年12月19日申请的欧洲专利申请No.84308928.5公开了可通用于高水平表达异源基因的启动子-核糖体结合位点表达元件。
本发明公开了一种出乎意料的结果,即与野生型信号序列相比,改变的、翻译强度降低的翻译起始区域可提供感兴趣多肽基本上完整的加工和高水平的表达,而且许多哺乳动物多肽需要窄范围的翻译水平来实现最大的分泌。一套具有变异翻译起始区域的载体可提供一定范围的翻译强度,以优化感兴趣多肽的分泌。
发明概述
本发明的一个方面是优化感兴趣的异源多肽在细胞中分泌的方法,它包括:比较在一套翻译起始区域的核酸变异体的控制下多肽的表达水平,其中该套变异体代表了一定范围内的翻译强度,然后确定用于产生成熟多肽的最佳翻译强度,其中最佳翻译强度小于野生型翻译起始区域的翻译强度。
在本发明的另一方面,该变异体是信号序列变异体,尤其是STII信号序列的变异体。
附图简述
图1显示了phoA启动子、trp和STII Shine-Dalgarno区域和STII信号序列。
图2是质粒pLS33有关特征的示意图。
图3是构建文库pSTIIBK的示意图。
图4是IFG-1表达水平的比较图,其中用pLS33、pSTIIBK#131和pSTIIC培养基上清液中测得的IGF-1数量加以确定。实验1-8代表在8个不同日期获得的测量值。
图5是构建质粒pSTIIC的示意图。
图6是构建质粒pSTIILys的示意图。
图7是构建质粒ppho21的示意图。
图8是构建质粒ppho31的示意图。
图9是构建质粒ppho41的示意图。
图10是构建质粒pphp51的示意图。
图11是文库pSTIICBK有关特征的示意图。
图12是构建文库pSTBKphoA的示意图。
图13显示了在pSTBKphoA文库的分离物中的phoA活性。
图14显示了所列出的STII信号序列变异体的核苷酸序列。
图15是构建质粒pNT3PST116的示意图。
图16是构建质粒pST116pho的示意图。
图17显示了实施例中所用的“A类”质粒的有关特征。
图18显示了实施例中所用的“B类”质粒的有关特征。
图19是考马斯蓝染色的多肽凝胶照片,它显示在变异STII信号序列的控制下,在大肠杆菌中分泌成熟的ICAM-1胞外结构域1和2。相对强度9的TIR由ppho31 STII变异体所提供;相对强度3的TIR由ppho41 STII变异体所提供。多肽的前体和成熟形式示于图中。
图20是考马斯蓝染色的多肽凝胶照片,它显示在变异STII信号序列的控制下,在大肠杆菌中分泌成熟的NT3.相对强度9的TIR由ppho31 STII变异体所提供;相对强度7的TIR由ppho21 STII变异体所提供;相对强度3的TIR由ppho41STII变异体所提供;相对强度1的TIR由ppho51 STII变异体所提供。多肽的前体和成熟形式示于图中。
图21是考马斯蓝染色的多肽凝胶照片,它显示在变异STII信号序列的控制下,在大肠杆菌中分泌成熟的RANTES。在图中从左至右,相对强度9的TIR由ppho31和pSTBKphoA#116 STII变异体所提供;相对强度7的TIR由ppho21STII变异体所提供;相对强度4的TIR由pSTBKphoA#81 STII变异体所提供;相对强度3的TIR由ppho41 STII变异体所提供;相对强度2的TIR由pSTBKphoA#107 STII变异体所提供;相对强度1的TIR由pSTBKphoA#86和ppho51 STII变异体所提供。多肽的前体和成熟形式示于图中。
优选实施例的详细描述
A.定义
如本文所用,“翻译起始区域”或TIR指确定感兴趣基因翻译起始的位置和效率的RNA(或其编码DNA)区域。(参见,例如McCarthy等人,
Trends in Genetics6:78-85(1990))。一个特定基因的TIR可以从核糖体结合位点(rbs)延伸出去以包括位于rbs 5′和3′端的序列。rbs被定义为最小地包括Shine-Dalgarno区域和起始密码子,再加上两者之间的碱基,但是可以包括由结合的核糖体保护不被核糖核酸酶消化的mRNA扩展部分。因此,TIR可包括不翻译的前导序列或上游顺反子的末端,即翻译终止密码子。
如本文所用,“分泌信号序列”或“信号序列”指位于多肽的氨基端的、指导多肽通过膜而转运的序列。一般,前体多肽通过切除信号序列而被加工后,产生成熟的多肽。
如本文所用,术语“翻译强度”指在对照体系中分泌多肽的测量值,其中用一个或多个TIR变异体来指导报道基因所编码多肽的分泌,并将数据与野生型TIR或者在相同培养和分析条件下的一些其他对照相比较。例如,在这些试验中,将碱性磷酸酶作为在phoA启动子的基础水平控制下表达的报道基因而测定翻译强度,其中phoA多肽的分泌由STII信号序列的变异体所指导。存在于宿主中的成熟碱性磷酸酶的数量是分泌多肽的测量值,它可相对阴性对照而定量分析。不受任何一种理论的束缚,因此如本文所用,“翻译强度”可包括例如:mRNA稳定性的测定、核糖体结合于核糖体结合位点的效率、转运通过膜的方式。
如本文所用,“多肽”通指具有至少2个氨基酸的肽和多肽。
B.通用方法
本发明表明,翻译强度是确定许多异源多肽是否能大量分泌的关键因素。因此,对于给定的TIR,可以产生一系列的、具有一定范围翻译强度的氨基酸或核酸序列变异体,从而提供一种方便的、调节该因素以使许多不同多肽的分泌最佳化的手段。使用在这些变异体如phoA控制之下的报道基因,可以提供一种定量不同翻译起始区域相对翻译强度的方法。突变的或变异的TIR可提供质粒载体的基础,从而提供一套质粒,在该套质粒中可插入感兴趣的基因并测量其表达,以便建立成熟多肽的最大化表达所需的最佳翻译强度范围。
因此,可以使用例如来自任何原核或真核生物的信号序列。较佳地,信号序列是STII、OmpA、phoE、LamB、MBP、或phoA。
TIR的诱变是通过常规技术完成的,它导致密码子的改变。这种改变可以改变氨基酸序列,尽管核苷酸序列中的沉默改变是优选的。TIR的改变可以包括例如:Shine-Dalgarno序列的数目或间距的改变,以及信号序列的改变。一种优选的产生突变信号序列的方法是,产生位于编码序列开始处的“密码子库”,而不改变信号序列的氨基酸序列(即,改变是沉默的)。这可以通过改变每个密码子的第3位上的核苷酸而做到;此外,某些氨基酸,如亮氨酸、丝氨酸和精氨酸,它们由多种可能的第一位和第二位,这增加了构建库的复杂性。这种诱变方法在Yansura等人(
Methods:A Companion to Methods in Enzymol.4:151-158(1992))中有详细描述。基本上而言,就是合成编码信号序列的DNA片段和成熟多肽的开始部分,使前6-12个密码子中每个密码子的第三位(如上所述,还可能是第一位或第二位)被改变。在这些密码子下游的额外核苷酸提供结合用于产生底链(bottomstrand)的互补引物的位置。用DNA聚合酶I(Klenow)处理顶编码链(top codingstrand)和底链引物,可以产生一组含有随机化密码子的双链DNA片段。这些引物被设计成含有有用的克隆位点,这些位点随后可用于将DNA片段插入合适的载体,从而可以扩增密码子文库。其他方法包括,例如,用随机核苷酸替换整个rbs(Wilson等人,
BioTechniques 17:944-952(1994)),以及使用噬菌体展示文库(参见,例如Barbas等人,
美国科学院院报89:4457-4461(1992); Garrard等人,
基 因128:103-109(1993))。
一般,TIR变异体可装在质粒载体中,该载体带有表达感兴趣基因所需的合适元件。例如,典型的构建物含有:位于信号序列5′端的启动子、位于信号序列3′端的限制性酶识别位点(用于插入感兴趣的基因或报道基因)、以及用于选择和/或维持形成的质粒所转化的细菌的选择基因,如抗药性标记。
适用于原核宿主的启动子包括β-内酰胺酶和乳糖启动子系统(Chang等人,
自 然275:617-624(1978);和Goeddel等人,
自然281:544-548(1979))、碱性磷酸酶、色氨酸(trp)启动子系统(Goeddel.
核酸研究8(18):4057-4074(1980)和EP36,776)以及杂合启动子如tac启动子(deBoer等人,
美国科学院院报80:21-25(1983))。
合适的用于酵母宿主的启动序列包括:3-磷酸甘油酸激酶的启动子(Hitzeman等人,
J.Biol.Chem.255(24):12073-80(1980))或其他糖酵解酶的启动子(Hess等人,
J. Adv.Enzyme Reg.7:149:67(1968);和Holland.
Biochemistry 17:4900-4907(1978))如烯醇化酶、甘油醛-3-磷酸脱氢酶、己糖激酶、丙酮酸脱羧酶、磷酸果糖激酶、葡萄糖-6-磷酸异构酶、磷酸甘油酸变位酶、丙酮酸激酶、丙糖磷酸异构酶、磷酸葡萄糖异构酶和葡萄糖激酶。
其他的酵母启动子,即那些具有可用生长条件加以控制的优势的诱导型启动子,是下列酶的启动子区域:醇脱氢酶2、异细胞色素C(isocytochrome C)、酸性磷酸酶、与氮代谢有关的降解酶、金属硫蛋白、甘油醛-3-磷酸脱氢酶、以及负责麦芽糖和半乳糖利用的酶。用于在酵母中表达的合适载体和启动子还描述于Hitzeman等人,EP 73,657A中。酵母增强子也可有利地与酵母启动子一起使用。
任何报道基因都可以使用,并以某种方式被定量。因此,例如碱性磷酸酶的产生可用phoA基因产物分泌量的测量值来定量。其他例子包括例如β-内酰胺酶基因。
较佳地,产生一套具有一定范围内翻译强度的载体,可在这些载体中插入编码感兴趣多肽的DNA。这套有限的载体提供了多肽分泌水平的比较工具。多肽的分泌水平可通过下列方法确定:如通过感兴趣多肽(如果存在)的功能分析、放射免疫测定(RIA)、酶联免疫测定(ELISA)、或PAGE以及观察感兴趣多肽的正确分子量。这样构建的载体可用于转化合适的宿主。较佳地,宿主是原核宿主。更佳地,宿主是大肠杆菌。
本发明的进一步的细节可见下列实施例,它们进一步限定了发明范围。本文中所提及的所有文献都完整地引用作为参考。
实施例
1.质粒构建物
A.基础质粒的构建
所有在本专利申请中描述的质粒都是从基础的pBR322(Sutcliffe,
Cold Spring Harb Symp Quant Biol.43:77-90(1978))骨架构建而得。尽管在每个例子中所表达的有关基因不同,但是表达每个基因所需的转录和翻译序列是由phoA启动子和trp Shine-Dalgarno序列(Chang等人,
基因,55:189-196(1987))所提供。此外,在一个指明的例子中,还存在第二个Shine-Dalgarno序列,即STII的Shine-Dalgarno序列(Picken等人,
Infect.Immun 42(1):269-275(1983))。通过STII信号序列或其变异体而指导多肽的分泌(Picken等人,
Infect.Immun 42(1):269-275(1983))。phoA启动子、trp和STII Shine-Dalgarno序列、以及野生型STII信号序列的序列在图1中给出。
B.pLS33的构建
质粒pLS33来自phGH1(Chang等人,基因,55:189-196(1987)),它被构建用于表达脱(1,3)-IGF-。在质粒pLS33中,编码这种形式的胰岛素样生长因子I的基因(通过去除N端的前3个氨基酸而与原始序列(Elmblad等人,
Third European Congress on biotechnology III.Weinheim:Verlag Chemie.pp.287-292(1984))有所不同)替换了编码人生长激素的基因。pLS33维持了phGH1中所描述的phoA启动子、trp和STII Shine-dalgarno区域和野生型STII信号序列的序列。然而,在脱(1,3)-IGF-I的终止密码子之后的3′端与phGH1中所描述的不同。在pLS33情况下,紧接在终止密码子下游,构建了一个Hind III限制性位点,随后是pBR322(Sutcliffe,
Cold Spring Harb Symp Quant Biol.43:77-90(1978))的四环素抗性基因的甲硫氨酸起始密码子。质粒pLS33的结构图示于图2。
C.构建pSTIIBK
构建含有STII信号序列可变密码子库的质粒文库(pSTIIBK),以筛选该信号的更好的核苷酸序列。用XbaI和BstEII消化pLS33,然后分离最长的片段,从而产生用于构建pSTIIBK的载体片段。该载体片段含有编码phoA启动子、trpShine-Dalgarno序列和脱(1,3)-IGF-I的氨基酸16-67的序列。脱(1,3)-IGF-I氨基酸3-15的编码区域,通过从另一IGF-I表达质粒pLS33LamB中分离出DraIII-BstEII片段(约45bp)而提供。STII信号的核苷酸序列的变化衍生自下列所示的双链合成DNA:5′-GCATGTCTAGAATT ATG
AAR
AAR
AAY
ATH
GCN
TTY
CTN
CTN
GCN
TCN ATG
TTY GTN
TTY
TCN
ATH GCT ACA AAC GCG TAT GCC ACTCT-3′(SEQ ID NO:1)
3′-CGA TGT TTG CGC ATA CGG TGAGACACGCCACGACTT-5′(S EQ IDNO:2)R:A,GY:T,CH:A,T,CN:G,A,T,C
将这两条合成DNA进行退火,用DNA聚合酶I(Klenow片段)处理,形成约101bp的双链DNA。再用XbaI和DraIII消化该双链DNA,产生约82bp的、编码具有可变密码子的STII信号序列和脱(1,3)-IGF-I前2个氨基酸的片段。再如图3将这些片段连接起来,构建成文库pSTIIBK。
D.选择pSTIIBK#131
针对转化子的生长是否更好以及IGF-I的分泌是否增加,来筛选含有STII信号序列可变密码子库的质粒文库(pSTIIBK)。一般,将质粒转入宿主菌株27C7(见下文),然后基于OD600下细胞密度测量值,根据能在添加羧苄青霉素(50μg/ml)的低磷酸盐培养基(见Chang等人,同上)中更好地生长而加以筛选。如下测试候选菌落是否IGF-1分泌水平上升。将菌落接种在3-5毫升添加羧苄青霉素(50μg/ml)LB,在37℃振荡生长约5-15小时。培养物按1∶100稀释在1-3毫升添加羧苄青霉素(50μg/ml)的低磷酸盐培养基,然后在37℃振荡诱导24小时。诱导后的培养物在微离心管中离心5分钟。上清液被稀释成IGF RIA稀释液,并储存在-20℃以供分析。分泌人培养基的IGF-1数量用放射免疫测定进行测定。
用在培养上清液中检测到的IGF-1数量所测得的IGF-1表达水平,在图4中针对pLS33、pSTIIBK#131和pSTIIC进行比较。变异体#131的IGF-1表达持续地高于“原始的”或野生型STII信号序列。pSTIIC的表达稍高于野生型序列。pSTIIBK#121与野生型STII在12个密码子上有差异,并缺失一个Shine-Dalgarno序列。如下构建pSTIIC作为对照质粒,它只有一个Shine-Dalgarno序列并且在非常靠近信号肽的3′端处有3个氨基酸变化。
E.构建pSTIIC
在pSTIIC中,从质粒pLS33中去除STII Shine-Dalgarno序列。此外,通过在靠近STII信号3′端处引入沉默突变,将一个MluI位点引人pSTIIC中。将构建pSTIIBK中所述的相同片段(来自pLS33的载体和来自pLS33LamB的约45bpDraIII-BstEII片段)用于构建该质粒。然而,合成的DNA不同于上述的用于构建pSTIIBK的合成DNA。对于构建pSTIIC,编码STII信号序列和脱(1,3)-IG3F-1前2个氨基酸的合成DNA如下:5′-CTAGAATT ATG AAA AAG AAT ATC GCA TTT CTT CTT GCA TCT ATG TTC GTT
3′-TTAA TAC TTT TTC TTA TAG CGT AAA GAA GAA CGT AGA TAC AAG CAA
_MluI_TTT TCT ATT GCT ACA AAC GCG TAT GCC ACTCT-3′(SEQ ID NO:3)AAA AGA TAA CGA TGT TTG CGC ATA CGG TG-5′(SEQ ID NO:4)
如图5所示,将这些片段连接在一起,构建成质粒pSTIIC。
F.构建pSTIILys
质粒pSTIILys所含有的STII信号序列与pSTIIC的信号序列的差别,仅在于第2位密码子处的一个核苷酸变化。该信号序列是用合成DNA构建的,并被置于表达多肽RANTES的pBR322衍生质粒(Schall等人,
免疫学杂志141(3):1018-1025(1988))。用于该构建的XbaI-MluI载体片段是从质粒pBK131Ran(质粒pSTIIBK#131的衍生质粒,其中用编码RANTES的基因替换编码脱(1,3)-IGF-1的基因)中分离出的。该质粒含有phoA启动子、trp Shine-Dalgarno序列、STIIC信号序列的最后3个氨基酸以及编码多肽RANTES的基因。如图6所示,再将该片段与下列的合成的DNA链连接,以构建质粒pSTIILys(SEQ ID NO:3):5′-CTAGAATT ATG AAG AAG AAT ATC GCA TTT CTT CTT GCA TCT ATG TTC GTT
3′-TTAA TAC TTC TTC TTA TAG CGT AAA GAA GAA CGT AGA TAC AAG CAATTT TCT ATT GCT ACA AA-3′(SEQ ID NO:5)AAA AGA TAA CGA TGT TTG CGC-5′(SEQ ID NO:6)
G.构建碱性磷酸酶质粒
为了确定每种所述STII信号序列的定量TIR值,将大肠杆菌的碱性磷酸酶基因用作报道基因。在每种构建物中,将phoA基因置于phoA启动子、trp Shine-Dalgarno下列和一种类型的STII信号序列的下游。质粒ppho21、ppho31、ppho41和ppho51分别含有来自pSTIC、pLS33、pSTIIBK#131和pSTIILys的信号序列。在ppho31中,构建物还含有STII Shine-Dalgarno区域。
H.构建ppho21
通过用EcoRI和BamHI消化pBR322,并分离最大的片段而得到用于构建ppho21的载体片段。phoA启动子、trp Shine-Dalgarno序列和STII信号序列(氨基酸1-20),是通过用EcoRI和MluI消化后分离出pCN131Tsc的约484bp片段而提供的。相同的约484bp片段还可用pSTIIC产生,pSTIIC质粒在前面已有描述。通过用Bsp1286和BamHI消化质粒pb0525(Inouye等人,
细菌学杂志146(2):668-675(1981))而产生编码碱性磷酸酶氨基酸24-450的phoA基因片段(约1430bp)。在碱性磷酸酶的终止密码子之后,该Bsp1286-BamHI片段还含有约142bp的SV40DNA(Fiers等人,
自然273:113-120(1978))。使用合成DNA将STII信号序列与phoA基因相连。这个编码STII信号序列最后3个氨基酸以及碱性磷酸酶氨基酸1-23的DNA序列如下:5′-CGCGTATGCCCGGACACCAGAAATGCCTGTTCTGGAAAACCGGGCTGCTCAGGGCGATATTACTG
3′-ATACGGGCCTGTGGTCTTTACGGACAAGACCTTTTGGCCCGACGAGTCCCGCTATAATGACCACCCGGCGGTGCT-3′(SEQ ID NO:7)GTGGGCCGCC-5′(SEQ ID NO:8)
为了便于构建该质粒,将合成DNA预先连于pCN131Tsc的EcoRI-MluI片段。该预先连接产生一个约575bp的片段。如图7所示,将预先连接所产生的片段与其他所述的片段连接在一起,构建ppho21。
I.构建ppho31
用于构建该质粒的载体片段是与所述的用于ppho21的相同载体。phoA启动子、trp Shine-Dalgarno序列、STII Shine-Dalgarno序列和STII信号序列(氨基酸1-20)是从pJAL55中产生的。来自pJAL55的必要片段(约496bp)是用EcoRI和MluI消化后分离出的。该EcoRI-MluI片段与pLS33的相同区域的差别仅在于,引入一个从STII信号序列氨基酸20处开始的MluI位点(如pSTIIC中所述)。通过用MluI和BamHI消化质粒ppho21,然后分离约1505bp片段而提供STII信号序列的后3个氨基酸以及编码phoA基因的序列。如图8所示,将这些片段连接在一起,构建ppho31。
J.构建ppho41
用于构建该质粒的载体片段是与所述的用于ppho21的相同载体。phoA启动子、trp Shine-Dalgarno序列和具有pSTIIBK#13 1密码子的STII信号序列(氨基酸1-20),是通过分离pNGF131的484bp EcoRI-MluI片段而提供的。相同的片段还可从pSTIIBK#131中产生。通过用MluI和BamHI消化质粒ppho21,然后分离约1505bp片段而提供STII信号序列的后3个氨基酸以及编码phoA基因的序列。如图9所示,将这些片段连接在一起,构建ppho41。
K.构建ppho51
用XbaI-BamHI消化质粒pLS18,然后分离最大的片段,从而产生用于构建ppho51的载体片段。质粒pLS18是phGH1(Chang等人,
基因55:189-196(1987))的衍生质粒,而且如果使用phGH1来替换pLS18,会产生相同的载体。XbaI-BamHI片段含有phoA启动子和trp Shine-Dalgarno序列。用XbaI和MluI消化pSTIILys,然后分离所产生的约67bp的片段,而提供具有pSTIILys密码子的STII信号序列(氨基酸1-20)。通过用MluI和BamHI消化质粒ppho21,然后分离约1505bp片段而提供STII信号序列的后3个氨基酸以及编码phoA的基因。图10中给出了构建ppho51的示意图。
L.构建pSTIICBK
构建第二个STII信号序列的可变密码子文库pSTIICBK。这第二个密码子文库被设计成仅针对最靠近STII信号序列甲硫氨酸起始密码子处的密码子。如图11所示,pSTIICBK是一种pBR322衍生质粒,它含有处于phoA启动子和trpShine-Dalgarno序列控制之下的、编码RANTES多肽的基因(Schall等人,
免疫学 杂志141(3):1018-1025(1980))。在该质粒中,RANTES的分泌由STII信号序列密码子文库所指导,该密码子文库来自下列的两条合成的DNA链:5′-GCATGTCTAGAATT ATG
AAR
AAR
AAY
ATH
GCN TTT CTT CTT GCA TCT ATG TTCGTT TTT TCT ATT GCT ACA AAC GCG TAT GCC-3′(SEQ ID NO:9)
3′-AGA TAA CGA TGT TTG CGC ATA CGG TGA-5′(SEQ ID NO:10)R:A.GY:T.CH:A.T.CN:G.A.T.C
将这两条合成DNA链进行退火,用DNA聚合酶I(Klenow片段)处理,形成约86bp的双链DNA。再用XbaI和MluI消化该双链DNA,产生编码STII信号序列前20个氨基酸并且在2-6位上具有可变密码子的约67bp片段。
M.构建pSTBKphoA
为了增加可利用的、具有不同的相对TIR强度的STII信号序列数目,需要一种筛选pSTIICBK密码子文库的方便方法。构建了质粒pSTBKphoA作为这一问题的解决方法。在质粒pSTBKphoA中,pSTIICBK的STII密码子文库被插入在phoA基因的上游和phoA启动子和trp Shine-Dalgarno下列的下游。这样phoA活性便提供了一种区分不同类型STII信号序列的手段。
通过用XbaI和BamHI消化p131TGF,然后分离最大的片段而产生用于该构建物的载体片段。相同的载体还可从phGH1(Chang等人,
基因55:189-196(1987))产生。该载体含有phoA启动子和trp Shine-Dalgarno序列。用XbaI和MluI消化后,分离从pSTIICBK产生的约67bp片段,从而提供STII信号序列的密码子库。通过用MluI和BamHI消化质粒ppho21,然后分离约1505bp片段而提供STII信号序列的后3个氨基酸以及编码phoA基因的序列。如图12所示,将这些片段连接在一起,构建pSTBKphoA。
N.选择pSTBKphoA#81、86、107、116
根据基础phoA活性水平(图13),从pSTBKphoA密码子文库中选择出pSTBKphoA#81、86、107、116。如图14所示,每种都具有不同的编码STII信号序列的核苷酸序列。
O.构建pST116pho
这种类型的STII信号序列,即ST116,将Chang等人(
基因55:189-196(1987))所述的双Shine-Dalgarno序列和选定的STII序列pSTBKphoA#116的密码子合并在一起。该信号序列先被构建在设计用于分泌NT3的pro区域的质粒(pNT3PST116)中,然后转入含有phoA基因的质粒中,以获得相对的TIR测量工具(pST116pho)。
P.构建pNT3PST116
用XbaI和BamHI消化质粒pLS18,然后分离最大的片段,从而产生用于该构建的载体。质粒pLS18是phGH1(Chang等人,
基因55:189-196(1987))的衍生质粒,而且可以用phGH1来产生相同的载体。该XbaI-BamHI片段含有phoA启动子和trp Shine-Dalgarno序列。用MluI和BamHI消化pNT3P,从中产生约682bp的片段,该片段含有STII信号序列的后3个氨基酸以及proNT3氨基酸19-138的编码区域(Jones等人,
美国科学院院报 87:8060-8064(1990))。质粒pNT3是pBR322衍生质粒,它含有phoA启动子、STIIBK#131型STII信号序列和proNT3氨基酸19-138的编码区域。列于下面的合成DNA链,给出了STII Shine-Dalgarno序列和STII信号序列前20个氨基酸的序列:5′-CTAGAGGTTGAGGTGATTTT ATG AAA AAA AAC ATC GCA TTT CTT CTT GCA TCT
3′-TCCAACTCCACTAAAA TAC TTT TTT TTG TAG CGT AAA GAA GAA CGT AGAATG TTC GTT TTT TCT ATT GCT ACA AA-3′(SEQ ID NO:11)TAC AAG CAA AAA AGA TAA CGA TGT TTG CGC-5′(SEQ ID NO:12)
如图15所示,将这些片段连接在一起,构建pNT3PST116。
Q.构建pST116pho
用于构建该质粒的载体片段是与所述的用于pNT3PST116的相同载体。用XbaI和MluI消化pNT3PST116之后,分离出月79bp的片段,从而产生STII Shine-Dalgarno序列和STII信号序列的前20个氨基酸(pSTBKphoA#116密码子)。通过用MluI和BamHI消化,从pSTBKphoA#116中分离STII信号序列的后3个氨基酸以及编码phoA基因的序列(约1505bp的片段)。如图16所示,将这些片段连接在一起,导致构建出pST116pho。
I1.碱性磷酸酶测试
在这些试验中,通过改动过的Amemuura等人(
细菌学杂志152:692-701,1982)的方法,分析采用phoA报道基因的各种TIR构建物的相对翻译强度。一般而言,使用方法如下。用携带不同序列的质粒转化大肠杆菌株27C7(ATCC 55,244),然而任何phoA-的大肠杆菌菌株都可使用,其中不同序列的不同之处可以是TIR、Shine-Dalgarno区域、Shine-Dalgarno区域和信号序列起始密码子之间的核苷酸序列、或信号序列本身,也可以是氨基酸序列的变异体或核苷酸序列的变异体。将转化子菌落接种在添加添加羧苄青霉素(50μg/ml,Sigma,Inc.)的LB培养基(Luria-Bertani培养基)上。培养物在37℃振荡生长4-8小时。将相当于1OD600的各种培养物进行离心,然后再悬浮于1毫升添加有羧苄青霉素(50μg/ml)的严格AP培养基(0.4%葡萄糖、20mM氯化铵、1.6mM硫酸镁、50mM氯化钾、20mM氯化钠、120mM三乙醇胺,pH7.4)中。混合物立刻被置于-20℃过夜。在融化之后,将1滴甲苯加至1微升融化的培养物中。在涡旋振荡之后,将混合物转移至16×125mm测试管中,并在轮(wheel)上于37℃通气1小时。然后,将40微升每种用甲苯处理过的培养物加至1毫升添加有1mM PNPP(4-硝基苯基磷酸二钠六水合物)的1M Tris-HCl,pH 8中,然后在室温下放置1小时。反应通过添加100毫升1M磷酸钠(pH 6.5)而终止。在30分钟内测量OD410。计算酶活性,单位为:所释放的对硝基苯酚微摩尔数每分钟每1OD600当量细胞。结果总结于表1。
表1.TIR相对强度的确定:将phoA用作报道基因
TIR | phoA活性1 | 标准差 | 相对强度 |
pBR322 | 0.0279 | 0.0069 | --- |
ppho512 | 0.0858 | 0.0165 | 1 |
pSTBKphoA#86 | 0.1125 | 0.0246 | 1 |
pSTBKphoA#107 | 0.1510 | 0.0267 | 2 |
ppho413 | 0.1986 | 0.0556 | 3 |
pSTBKphoA#81 | 0.2796 | 0.0813 | 4 |
ppho214 | 0.4174 | 0.1145 | 7 |
pSTBKphoA#116 | 0.5314 | 0.1478 | 9 |
ppho315 | 0.5396 | 0.0869 | 9 |
pST116pho | 0.7760 | 0.1272 | 13 |
1对硝基苯酚微摩尔数/分钟/OD600细胞
2与pSTIILys相同的STII变异体
3与pSTIIBK#131相同的STII变异体
4与STIIC相同的STII变异体
5野生型STII+MluI位点,最后密码子GCC
III.分泌异源多肽的实施例
用于这些实施例中的质粒都与上述设计中的质粒非常相似。这些表达质粒在此概括性地描述,而不对每个构建物都详细地描述。尽管在每个实施例中表达不同的感兴趣的多肽,但是在这些构建物之间唯一的不同之处是在每个编码区域3′端之后的核苷酸序列。因此,出于描述的目的,根据其3′序列,将这些质粒粗略地分成下列2类。
A类:在每个感兴趣基因终止密码子3′约25bp内,便开始了编码Scholtissek和Groos所述的转录终止子(
核酸研究15(7):3185(1987))的序列,随后是pBR322的四环素抗性基因(Sutcliffe,
Cold Spring Harb Symp Quant Biol 43:77-90(1978)).在该类别中的例子包括:设计用于分泌成熟NGF(Ullrich等人,
自然303:821-825(1983))、成熟的TGF-β1(Derynck等人,
自然316:701-705(1985))、和ICAM-1的结构域1和2(staunton等人,
细胞52:925-933(1988))的质粒。这些质粒的示意图示于图17。
B类:该类别中的例子包括:设计用于分泌成熟的VEGF(Leung等人,
科学246:1306-1309(1989))、成熟的NT3(Jones等人,
美国科学院院报87:8060-8064(1990))、RANTES(Schall等人,
免疫学杂志141(3):1018-1025(1980))和phoA的质粒。在每种这些质粒的终止密码子的3′方向后面为不翻译的DNA片段(VEGF:约43bp;成熟的NT3:约134bp;RANTES:约7bp;phoA:约142bp).在这个3′不翻译区域之后,又是pBR322的序列,其中或者从HindIII位点(如在分泌成熟NT3的质粒中)或BamHI位点(分泌phoA、VEGF、RANTES的质粒)开始。该类别中所包括的这些例子的示意图示于图18。
用这些质粒转化宿主大肠杆菌株27C7。将转化子菌落接种于添加有羧苄青霉素(50微克/毫升)的3-5毫升LB中。培养物在37℃振荡培养3-8小时。培养物按1:100稀释在1-3毫升低磷酸盐培养基(Chang等人,同上),然后在37℃振荡诱导约20小时。对于每种生长后的培养物,将每份0.5 OD600样品在微离心管中离心。
然后,每份0.5OD600沉淀物被制备用于下面的凝胶分析。将每种沉淀物再悬浮于50微升TE(10mM Tris pH 7.6,1mM EDTA)中。在添加10微升10%SDS、5微升还原剂(1M二硫苏糖醇或1M β-巯基乙醇),样品在约90℃加热2分钟,然后涡旋振荡。让样品冷却至室温,随后加人500微升丙酮。涡旋振荡样品,然后在室温下放置约15放置。离心样品5分钟。弃去上清液,将沉淀物再悬浮于20微升水、5微升还原剂、25微升NOVEX2×样品缓冲液中。样品在约90℃加热3-5分钟,然后涡旋振荡。在离心样品5分钟之后,将上清液转至干净的管中,同时弃去沉淀物。将5-10微升的各种样品上样于10孔的1.0mm NOVES制造的凝胶(San Diego,CA.),在120伏特下电泳1.5-2小时。用考马斯蓝染色使多肽可以被看见(图19-21)。
为了提供数据的定量分析,用光密度法分析部分凝胶。这些数据列于下表2中。多肽凝胶和光密度数据都表明,当翻译强度降低的STII变异体被用于指导多肽的分泌时,被测试的异源多肽都更有效地持续分泌。
表2.通过TIR修饰来改善多肽分泌的例子:
对多肽凝胶用光密度计进行扫描
多肽 | TIR(相对强度) | 分泌数量(占宿主总多肽的百分比) |
VEGF | 9 | 0.6 |
3 | 5.9 | |
NGF | 9 | 1.6 |
7 | 1.8 | |
4 | 5.7 | |
1 | 5.5 | |
RANTES | 9 | 0.3 |
9 | 0.2 | |
7 | 0.4 | |
4 | 3.9 | |
3 | 3.6 | |
2 | 3.5 | |
1* | 1.6 | |
1 | 1.7 | |
TGF-β1 | 7 | 1.7 |
3 | 9.2 |
*pSTBKphoA#86信号序列
(1)一般信息:
(i)申请人:Genentech,Inc.
(ii)发明名称:分泌异源多肽的方法和组合物
(iii)序列数目:23
(iv)通信地址:
(A)收信人:Genentech,Inc.
(B)街道:1 DNA Way
(C)城市:South San Francisco
(D)州:California
(E)国家:USA
(F)邮编:94080
(v)计算机可读形式:
(A)记录介质类型:3.5inch,1.44Mb软盘
(B)计算机:IBM PC兼容型
(C)操作系统:PC-DOS/MS-DOS
(D)软件:WinPatin(Genentech)
(vi)本申请资料:
(A)申请号:
(B)申请日:
(C)分类:
(vii)在先申请资料:
(A)申请号:08/398615
(B)申请日:01-3月-1995
(viii)律师/代理人信息:
(A)姓名:Lee,Wendy M.
(B)登记号:40.378
(C)参考/案卷号:P0889PCT
(ix)通讯信息:
(A)电话:650/225-1994
(B)传真:650/952-9881
(2)SEQ ID NO:1的信息:
(i)序列特征:
(A)长度:88碱基对
(B)类型:核酸
(C)股性:单链
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:1:
GCATGTCTAG AATTATGAAR AARAAYATHG CNTTYCTNCT NGCNTCNATG 50
TTYGTNTTYT CNATHGCTAC AAACGCGTAT GCCACTCT 88
(2)SEQ ID NO:2的信息:
(i)序列特征:
(A)长度:36碱基对
(B)类型:核酸
(C)股性:单链
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:2:
TTCAGCACCG CACAGAGTGG CATACGCGTT TGTAGC 36
(2)SEQ ID NO:3的信息:
(i)序列特征:
(A)长度:82碱基对
(B)类型:核酸
(C)股性:单链
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:3:
CTAGAATTAT GAAAAAGAAT ATCGCATTTC TTCTTGCATC TATGTTCGTT 50
TTTTCTATTG CTACAAACGC GTATGCCACT CT 82
(2)SEQ ID NO:4的信息:
(i)序列特征:
(A)长度:75碱基对
(B)类型:核酸
(C)股性:单链
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:4:
GTGGCATACG CGTTTGTAGC AATAGAAAAA ACGAACATAG ATGCAAGAAG 50
AAATGCGATA TTCTTTTTCA TAATT 75
(2)SEQ ID NO:5的信息:
(i)序列特征:
(A)长度:67碱基对
(B)类型:核酸
(C)股性:单链
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:5:
CTAGAATTAT GAAGAAGAAT ATCGCATTTC TTCTTGCATC TATGTTCGTT 50
TTTTCTATTG CTACAAA 67
(2)SEQ ID NO:6的信息:
(i)序列特征:
(A)长度:67碱基对
(B)类型:核酸
(C)股性:单链
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:6:
CGCGTTTGTA GCAATAGAAA AAACGAACAT AGATGCAAGA AGAAATGCGA 50
TATTCTTCTT CATAATT 67
(2)SEQ ID NO:7的信息:
(i)序列特征:
(A)长度:79碱基对
(B)类型:核酸
(C)股性:单链
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:7:
CGCGTATGCC CGGACACCAG AAATGCCTGT TCTGGAAAAC CGGGCTGCTC 50
AGGGCGATAT TACTGCACCC GGCGGTGCT 79
(2)SEQ ID NO:8的信息:
(i)序列特征:
(A)长度:71碱基对
(B)类型:核酸
(C)股性:单链
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:8:
CCGCCGGGTG CAGTAATATC GCCCTGAGCA GCCCGGTTTT CCAGAACAGG 50
CATTTCTGGT GTCCGGGCAT A 71
(2)SEQ ID NO:9的信息:
(i)序列特征:
(A)长度:83碱基对
(B)类型:核酸
(C)股性:单链
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:9:
GCATGTCTAG AATTATGAAR AARAAYATHG CNTTTCTTCT TGCATCTATG 50
TTCGTTTTTT CTATTGCTAC AAACGCGTAT GCC 83
(2)SEQ ID NO:10的信息:
(i)序列特征:
(A)长度:27碱基对
(B)类型:核酸
(C)股性:单链
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:1O:
AGTGGCATAC GCGTTTGTAG CAATAGA 27
(2)SEQ ID NO:11的信息:
(i)序列特征:
(A)长度:79碱基对
(B)类型:核酸
(C)股性:单链
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:11:
CTAGAGGTTG AGGTGATTTT ATGAAAAAAA ACATCGCATT TCTTCTTGCA 50
TCTATGTTCG TTTTTTCTAT TGCTACAAA 79
(2)SEQ ID NO:12的信息:
(i)序列特征:
(A)长度:79碱基对
(B)类型:核酸
(C)股性:单链
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:12:
CGCGTTTGTA GCAATAGAAA AAACGAACAT AGATGCAAGA AGAAATGCGA 50
TGTTTTTTTT CATAAAATCA CCTCAACCT 79
(2)SEQ ID NO:13的信息:
(i)序列特征:
(A)长度:506碱基对
(B)类型:核酸
(C)股性:双链
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:13:
GAATTCAACT TCTCCATACT TTGGATAAGG AAATACAGAC ATGAAAAATC 50
TCATTGCTGA GTTGTTATTT AAGCTTGCCC AAAAAGAAGA AGAGTCGAAT 100
GAACTGTGTG CGCAGGTAGA AGCTTTGGAG ATTATCGTCA CTGCAATGCT 150
TCGCAATATG GCGCAAAATG ACCAACAGCG GTTGATTGAT CAGGTAGAGG 200
GGGCGCTGTA CGAGGTAAAG CCCGATGCCA GCATTCCTGA CGACGATACG 250
GAGCTGCTGC GCGATTACGT AAAGAAGTTA TTGAAGCATC CTCGTCAGTA 300
AAAAGTTAAT CTTTTCAACA GCTGTCATAA AGTTGTCACG GCCGAGACTT 350
ATAGTCGCTT TGTTTTTATT TTTTAATGTA TTTGTAACTA GTACGCAAGT 400
TCACGTAAAA AGGGTATCTA GAGGTTGAGG TGATTTTATG AAAAAGAATA 450
TCGCATTTCT TCTTGCATCT ATGTTCGTTT TTTCTATTGC TACAAATGCC 500
TATGCA 506
(2)SEQ ID NO:14的信息:
(i)序列特征:
(A)长度:23氨基酸
(B)类型:氨基酸
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:14:
Met Lys Lys Asn Ile Ala Phe Leu Leu Ala Ser Met Phe Val Phe
1 5 10 15
Ser Ile Ala Thr Asn Ala Tyr Ala
20 23
(2)SEQ ID NO:15的信息:
(i)序列特征:
(A)长度:90碱基对
(B)类型:核酸
(C)股性:双链
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:15:
TCTAGAGGTT GAGGTGATTT TATGAAAAAG AATATCGCAT TTCTTCTTGC 50
ATCTATGTTC GTTTTTTCTA TTGCTACAAA YGCSTATGCM 90
(2)SEQ ID NO:16的信息:
(i)序列特征:
(A)长度:78碱基对
(B)类型:核酸
(C)股性:双链
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:16:
TCTAGAATTA TGAAAAAGAA TATCGCATTT CTTCTTGCAT CTATGTTCGT 50
TTTTTCTATT GCTACAAACG CGTATGCM 78
(2)SEQ ID NO:17的信息:
(i)序列特征:
(A)长度:78碱基对
(B)类型:核酸
(C)股性:双链
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:17:
TCTAGAATTA TGAAGAAGAA TATTGCGTTC CTACTTGCCT CTATGTTTGT 50
CTTTTCTATA GCTACAAACG CGTATGCM 78
(2)SEQ ID NO:18的信息:
(i)序列特征:
(A)长度:78碱基对
(B)类型:核酸
(C)股性:双链
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:18:
TCTAGAATTA TGAAGAAGAA TATCGCATTT CTTCTTGCAT CTATGTTCGT 50
TTTTTCTATT GCTACAAACG CGTATGCM 78
(2)SEQ ID NO:19的信息:
(i)序列特征:
(A)长度:78碱基对
(B)类型:核酸
(C)股性:双链
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:19:
TCTAGAATTA TGAAAAAAAA CATCGCATTT CTTCTTGCAT CTATGTTCGT 50
TTTTTCTATT GCTACAAACG CGTATGCM 78
(2)SEQ ID NO:20的信息:
(i)序列特征:
(A)长度:78碱基对
(B)类型:核酸
(C)股性:双链
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:20:
TCTAGAATTA TGAAAAAAAA CATTGCCTTT CTTCTTGCAT CTATGTTCGT 50
TTTTTCTATT GCTACAAACG CGTATGCM 78
(2)SEQ ID NO:21的信息:
(i)序列特征:
(A)长度:78碱基对
(B)类型:核酸
(C)股性:双链
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:21:
TCTAGAATTA TGAAGAAAAA CATCGCTTTT CTTCTTGCAT CTATGTTCGT 50
TTTTTCTATT GCTACAAACG CGTATGCM 78
(2)SEQ ID NO:22的信息:
(i)序列特征:
(A)长度:78碱基对
(B)类型:核酸
(C)股性:双链
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:22:
TCTAGAATTA TGAAAAAGAA CATAGCGTTT CTTCTTGCAT CTATGTTCGT 50
TTTTTCTATT GCTACAAACG CGTATGCM 78
(2)SEQ ID NO:23的信息:
(i)序列特征:
(A)长度:90碱基对
(B)类型:核酸
(C)股性:双链
(D)拓扑结构:线性
(xi)序列描述:SEQ ID NO:23:
TCTAGAGGTT GAGGTGATTT TATGAAAAAA AACATCGCAT TTCTTCTTGC 50
ATCTATGTTC GTTTTTTCTA TTGCTACAAA CGCGTATGCM 90
Claims (34)
1.一种核酸,它是编码STII分泌信号序列的核酸的变异体,其特征在于,它具有选自以下SEQ ID NO:15-SEQ ID NO:23的核苷酸序列:
5’TCTAGAGGTTGAGGTGATTTT ATG AAA AAG AAT ATC GCA TTT CTT CTT
GCA TCT ATG TTC GTT TTT TCT ATT GCT ACA AAY GCS TAT GCM 3’
SEQ ID NO:15;
5’TCTAGAATT ATG AAA AAG AAT ATC GCA TTT CTT CTT GCA TCT ATG TTC
GTT TTT TCT ATT GCT ACA AAC GCG TAT GCM 3’SEQ ID NO:16;
5’TCTAGAATT ATG AAG AAG AAT ATT GCG TTC CTA CTT GCC TCT ATG TTT
GTC TTT TCT ATA GCT ACA AAC GCG TAT GCM 3’SEQ ID NO:17;
5’TCTAGAATT ATG AAG AAG AAT ATC GCA TTT CTT CTT GCA TCT ATG TTC
GTT TTT TCT ATT GCT ACA AAC GCG TAT GCM 3’SEQ ID NO:18;
5’TCTAGAATT ATG AAA AAA AAC ATC GCA TTT CTT CTT GCA TCT ATG TTC
GTT TTT TCT ATT GCT ACA AAC GCG TAT GCM 3’SEQ ID NO:19;
5’TCTAGAATT ATG AAA AAA AAC ATT GCC TTT CTT CTT GCA TCT ATG TTC
GTT TTT TCT ATT GCT ACA AAC GCG TAT GCM 3’SEQ ID NO:20;
5’TCTAGAATT ATG AAG AAA AAC ATC GCT TTT CTT CTT GCA TCT ATG TTC
GTT TTT TCT ATT GCT ACA AAC GCG TAT GCM 3’SEQ ID NO:21;
5’TCTAGAATT ATG AAA AAG AAC ATA GCG TTT CTT CTT GCA TCT ATG TTC
GTT TTT TCT ATT GCT ACA AAC GCG TAT GCM 3’SEQ ID NO:22;和
5’TCTAGAGGTTGAGGTGATTTT ATG AAA AAA AAC ATC GCA TTT CTT CTT
GCA TCT ATG TTC GTT TTT TCT ATT GCT ACA AAC GCG TAT GCM 3’
SEQ ID NO:23。
2.如权利要求1所述的核酸,其特征在于,所述变异体不改变所述STII分泌信号的氨基酸序列。
3.如权利要求1所述的核酸,其特征在于,当编码异源多肽的核酸操作性连接于所述变异体并在宿主细胞中表达时,分泌的所述异源多肽的量大于该核酸操作性连接于编码所述STII分泌信号序列的野生型核酸时所分泌的量。
4.如权利要求1所述的核酸,其特征在于,所述核酸序列为SEQ ID NO:15。
5.如权利要求1所述的核酸,其特征在于,所述核酸序列为SEQ ID NO:16。
6.如权利要求1所述的核酸,其特征在于,所述核酸序列为SEQ ID NO:17。
7.如权利要求1所述的核酸,其特征在于,所述核酸序列为SEQ ID NO:18。
8.如权利要求1所述的核酸,其特征在于,所述核酸序列为SEQ ID NO:19。
9.如权利要求1所述的核酸,其特征在于,所述核酸序列为SEQ ID NO:20。
10.如权利要求1所述的核酸,其特征在于,所述核酸序列为SEQ ID NO:21。
11.如权利要求1所述的核酸,其特征在于,所述核酸序列为SEQ ID NO:22。
12.如权利要求1所述的核酸,其特征在于,所述核酸序列为SEQ ID NO:23。
13.一种优化异源多肽在宿主细胞中分泌的方法,其特征在于,它包括:比较在一套权利要求1所述的核酸变异体的控制下多肽的表达水平,鉴别一种或多种变异体,该变异体具有提供成熟多肽的优化分泌的翻译强度。
14.如权利要求13所述的方法,其特征在于,所述鉴别的变异体不改变所述STII分泌信号的氨基酸序列。
15.如权利要求13所述的方法,其特征在于,所述宿主细胞是原核生物细胞。
16.如权利要求13所述的方法,其特征在于,当编码所述多肽的核酸操作性连接于至少一种所述鉴别的变异体时,分泌的多肽的量大于该核酸操作性连接于编码所述STII分泌信号序列的野生型核酸时所分泌的量。
17.一种在宿主细胞中分泌异源多肽的方法,其特征在于,所述方法包括:用含有权利要求1所述的核酸的载体转化细胞,其中,该核酸操作性连接于编码所述异源多肽的核酸以使该异源多肽分泌,所述异源多肽被分泌。
18.如权利要求17所述的方法,其特征在于,所述变异体不改变所述STII分泌信号的氨基酸序列。
19.如权利要求17所述的方法,其特征在于,当编码所述异源多肽的所述核酸操作性连接于编码变异体STII分泌信号序列的所述核酸时,分泌的多肽的量大于编码所述异源多肽的该核酸操作性连接于编码所述STII分泌信号序列的野生型核酸时所分泌的量。
20.如权利要求19所述的方法,其特征在于,所述宿主细胞是原核生物细胞。
21.一种表达载体,其特征在于,它含有权利要求1所述的核酸,该核酸操作性连接于用于表达基因的额外元件。
22.一种宿主细胞,其特征在于,它含有权利要求21所述的表达载体。
23.如权利要求22所述的宿主细胞,其特征在于,所述宿主细胞是原核生物细胞。
24.如权利要求23所述的宿主细胞,其特征在于,所述宿主细胞是大肠杆菌。
25.STII分泌信号序列的变异体,其特征在于,它由选自下述SEQ IDNO:15-SEQ ID NO:23的核酸序列编码:
5’TCTAGAGGTTGAGGTGATTTT ATG AAA AAG AAT ATC GCA TTT CTT CTT
GCA TCT ATG TTC GTT TTT TCT ATT GCT ACA AAY GCS TAT GCM 3’
SEQ ID NO:15;
5’TCTAGAATT ATG AAA AAG AAT ATC GCA TTT CTT CTT GCA TCT ATG TTC
GTT TTT TCT ATT GCT ACA AAC GCG TAT GCM 3’SEQ ID NO:16;
5’TCTAGAATT ATG AAG AAG AAT ATT GCG TTC CTA CTT GCC TCT ATG TTT
GTC TTT TCT ATA GCT ACA AAC GCG TAT GCM 3’SEQ ID NO:17;
5’TCTAGAATT ATG AAG AAG AAT ATC GCA TTT CTT CTT GCA TCT ATG TTC
GTT TTT TCT ATT GCT ACA AAC GCG TAT GCM 3’SEQ ID NO:18;
5’TCTAGAATT ATG AAA AAA AAC ATC GCA TTT CTT CTT GCA TCT ATG TTC
GTT TTT TCT ATT GCT ACA AAC GCG TAT GCM 3’SEQ ID NO:19;
5’TCTAGAATT ATG AAA AAA AAC ATT GCC TTT CTT CTT GCA TCT ATG TTC
GTT TTT TCT ATT GCT ACA AAC GCG TAT GCM 3’SEQ ID NO:20;
5’TCTAGAATT ATG AAG AAA AAC ATC GCT TTT CTT CTT GCA TCT ATG TTC
GTT TTT TCT ATT GCT ACA AAC GCG TAT GCM 3’SEQ ID NO:21;
5’TCTAGAATT ATG AAA AAG AAC ATA GCG TTT CTT CTT GCA TCT ATG TTC
GTT TTT TCT ATT GCT ACA AAC GCG TAT GCM 3’SEQ ID NO:22;和
5’TCTAGAGGTTGAGGTGATTTT ATG AAA AAA AAC ATC GCA TTT CTT CTT
GCA TCT ATG TTC GTT TTT TCT ATT GCT ACA AAC GCG TAT GCM 3’
SEQ ID NO:23。
26.如权利要求25所述的变异体,其特征在于,所述序列是SEQ ID NO:15。
27.如权利要求25所述的变异体,其特征在于,所述序列是SEQ ID NO:16。
28.如权利要求25所述的变异体,其特征在于,所述序列是SEQ ID NO:17。
29.如权利要求25所述的变异体,其特征在于,所述序列是SEQ ID NO:18。
30.如权利要求25所述的变异体,其特征在于,所述序列是SEQ ID NO:19。
31.如权利要求25所述的变异体,其特征在于,所述序列是SEQ ID NO:20。
32.如权利要求25所述的变异体,其特征在于,所述序列是SEQ ID NO:21。
33.如权利要求25所述的变异体,其特征在于,所述序列是SEQ ID NO:22。
34.如权利要求25所述的变异体,其特征在于,所述序列是SEQ ID NO:23。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/398,615 US5840523A (en) | 1995-03-01 | 1995-03-01 | Methods and compositions for secretion of heterologous polypeptides |
US08/398,615 | 1995-03-01 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1180379A CN1180379A (zh) | 1998-04-29 |
CN1154736C true CN1154736C (zh) | 2004-06-23 |
Family
ID=23576066
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB961930578A Expired - Lifetime CN1154736C (zh) | 1995-03-01 | 1996-02-27 | 分泌异源多肽的方法和组合物 |
Country Status (18)
Country | Link |
---|---|
US (1) | US5840523A (zh) |
EP (1) | EP0815246B1 (zh) |
JP (1) | JP3375970B2 (zh) |
CN (1) | CN1154736C (zh) |
AT (1) | ATE358181T1 (zh) |
AU (1) | AU701476B2 (zh) |
BR (1) | BR9607464B1 (zh) |
CA (1) | CA2213813C (zh) |
DE (1) | DE69636996T2 (zh) |
DK (1) | DK0815246T3 (zh) |
ES (1) | ES2285711T3 (zh) |
FI (1) | FI120357B (zh) |
IL (1) | IL117314A0 (zh) |
NO (1) | NO324920B1 (zh) |
NZ (1) | NZ303619A (zh) |
RU (1) | RU2208639C2 (zh) |
WO (1) | WO1996027016A1 (zh) |
ZA (1) | ZA961688B (zh) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102933600A (zh) * | 2009-11-05 | 2013-02-13 | 弗·哈夫曼-拉罗切有限公司 | 分泌异源多肽的方法和组合物 |
US10240207B2 (en) | 2014-03-24 | 2019-03-26 | Genentech, Inc. | Cancer treatment with c-met antagonists and correlation of the latter with HGF expression |
US10435694B2 (en) | 2014-03-14 | 2019-10-08 | Genentech, Inc. | Methods and compositions for secretion of heterologous polypeptides |
Families Citing this family (747)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6242177B1 (en) * | 1995-03-01 | 2001-06-05 | Genentech, Inc. | Methods and compositions for secretion of heterologous polypeptides |
US6824780B1 (en) | 1999-10-29 | 2004-11-30 | Genentech, Inc. | Anti-tumor antibody compositions and methods of use |
WO2001094418A2 (en) | 2000-06-05 | 2001-12-13 | Corixa Corporation | Leader peptides for enhancing secretion of recombinant protein from a host cell |
DK1356052T3 (da) * | 2000-12-14 | 2008-12-08 | Genentech Inc | Produktion af hele antistoffer i prokaryotiske celler |
US6979556B2 (en) * | 2000-12-14 | 2005-12-27 | Genentech, Inc. | Separate-cistron contructs for secretion of aglycosylated antibodies from prokaryotes |
MXPA03011985A (es) | 2001-06-20 | 2004-03-26 | Genentech Inc | Composiciones y metodos para el diagnostico y tratamiento de tumores. |
US20030077739A1 (en) * | 2001-08-27 | 2003-04-24 | Genentech, Inc. | System for antibody expression and assembly |
KR101008758B1 (ko) | 2001-09-18 | 2011-01-14 | 제넨테크, 인크. | 종양의 진단 및 치료를 위한 방법 및 이를 위한 조성물 |
EP2067472A1 (en) | 2002-01-02 | 2009-06-10 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of tumor |
NZ535925A (en) | 2002-04-16 | 2008-06-30 | Genentech Inc | An isolated antibody that binds to a particular polypeptide |
US7705195B2 (en) * | 2002-06-07 | 2010-04-27 | Genentech, Inc. | Screening method |
MXPA05004677A (es) | 2002-10-31 | 2005-11-17 | Genentech Inc | Metodos y composiciones para aumentar la produccion de anticuerpos. |
CN103833854B (zh) | 2002-12-16 | 2017-12-12 | 健泰科生物技术公司 | 免疫球蛋白变体及其用途 |
AU2004205684A1 (en) * | 2003-01-23 | 2004-08-05 | Genentech, Inc. | Methods for producing humanized antibodies and improving yield of antibodies or antigen binding fragments in cell culture |
US7619068B2 (en) | 2003-05-09 | 2009-11-17 | Diadexus, Inc. | Ovr110 antibody compositions and methods of use |
WO2005012531A2 (en) * | 2003-08-01 | 2005-02-10 | Genentech, Inc. | Antibody cdr polypeptide sequences with restricted diversity |
AU2004273791A1 (en) * | 2003-09-05 | 2005-03-31 | Genentech, Inc. | Antibodies with altered effector functions |
EP2161283B1 (en) | 2003-11-17 | 2014-06-04 | Genentech, Inc. | Compositions comprising antibodies against CD79b conjugated to a growth inhibitory agent or cytotoxic agent and methods for the treatment of tumor of hematopoietic origin |
KR100956913B1 (ko) | 2003-12-19 | 2010-05-11 | 제넨테크, 인크. | 치료제로서 유용한 일가 항체 단편 |
AU2005244751A1 (en) * | 2004-04-16 | 2005-12-01 | Genentech, Inc. | Method for augmenting B cell depletion |
US20150017671A1 (en) | 2004-04-16 | 2015-01-15 | Yaping Shou | Methods for detecting lp-pla2 activity and inhibition of lp-pla2 activity |
RU2398777C2 (ru) * | 2004-08-05 | 2010-09-10 | Дженентек, Инк. | ГУМАНИЗИРОВАННЫЕ АНТАГОНИСТЫ, НАПРАВЛЕННЫЕ ПРОТИВ c-met |
WO2006028936A2 (en) * | 2004-09-02 | 2006-03-16 | Genentech, Inc. | Heteromultimeric molecules |
WO2006028956A2 (en) * | 2004-09-02 | 2006-03-16 | Genentech, Inc. | Anti-fc-gamma riib receptor antibody and uses therefor |
US7662926B2 (en) * | 2004-09-02 | 2010-02-16 | Genentech, Inc. | Anti-Fc-gamma receptor antibodies, bispecific variants and uses therefor |
US7655229B2 (en) * | 2004-09-02 | 2010-02-02 | Chan Andrew C | Anti-FC-gamma RIIB receptor antibody and uses therefor |
HUE058817T2 (hu) | 2004-09-03 | 2022-09-28 | Genentech Inc | Humanizált anti-béta7 antagonisták és alkalmazásaik |
WO2006069403A2 (en) | 2004-12-22 | 2006-06-29 | Genentech, Inc. | Methods for producing soluble multi-membrane-spanning proteins |
ES2343746T3 (es) | 2005-01-07 | 2010-08-09 | Diadexus, Inc. | Composiciones de anticuerpo ovr110 y metodos de uso. |
WO2007094842A2 (en) * | 2005-12-02 | 2007-08-23 | Genentech, Inc. | Binding polypeptides and uses thereof |
US7422899B2 (en) * | 2005-10-05 | 2008-09-09 | Biogen Idec Ma Inc. | Antibodies to the human prolactin receptor |
EP1957531B1 (en) | 2005-11-07 | 2016-04-13 | Genentech, Inc. | Binding polypeptides with diversified and consensus vh/vl hypervariable sequences |
WO2007056411A2 (en) * | 2005-11-08 | 2007-05-18 | Genentech, Inc. | Method of producing pan-specific antibodies |
AU2006342792A1 (en) | 2005-12-02 | 2007-11-08 | Genentech, Inc. | Compositions and methods for the treatment of diseases and disorders associated with cytokine signaling involving antibodies that bind to IL-22 and IL-22R |
CN103396485B (zh) | 2005-12-15 | 2016-08-10 | 健泰科生物技术公司 | 靶向多聚泛蛋白的方法和组合物 |
EP2330202A3 (en) | 2006-01-06 | 2011-09-14 | University Of Georgia Research Foundation, Inc. | Cyst nematode resistant transgenic plants |
CA2647277A1 (en) | 2006-04-05 | 2007-11-08 | Genentech, Inc. | Method for using boc/cdo to modulate hedgehog signaling |
PL2446904T3 (pl) | 2006-05-30 | 2015-10-30 | Genentech Inc | Przeciwciała anty-CD22, ich immunokoniugaty oraz ich zastosowania |
KR20090078349A (ko) | 2006-10-12 | 2009-07-17 | 제넨테크, 인크. | 림포톡신-알파에 대한 항체 |
EP2502938B1 (en) | 2006-10-27 | 2015-02-18 | Genentech, Inc. | Antibodies and immunoconjugates and uses therefor |
AU2007325283B2 (en) | 2006-11-27 | 2012-08-30 | Diadexus, Inc. | Ovr110 antibody compositions and methods of use |
JP2010518115A (ja) | 2007-02-09 | 2010-05-27 | ジェネンテック, インコーポレイテッド | 抗Robo4抗体およびそれらのための使用 |
ES2379413T3 (es) | 2007-02-22 | 2012-04-25 | Genentech, Inc. | Procedimientos para detectar la enfermedad inflamatoria del intestino |
US7960139B2 (en) | 2007-03-23 | 2011-06-14 | Academia Sinica | Alkynyl sugar analogs for the labeling and visualization of glycoconjugates in cells |
CN101802012B (zh) | 2007-07-16 | 2014-08-06 | 健泰科生物技术公司 | 抗cd79b抗体和免疫偶联物及使用方法 |
US9845355B2 (en) | 2007-07-16 | 2017-12-19 | Genentech, Inc. | Humanized anti-CD79b antibodies and immunoconjugates and methods of use |
SG193868A1 (en) | 2007-09-26 | 2013-10-30 | Chugai Pharmaceutical Co Ltd | Modified antibody constant region |
CA2705007A1 (en) | 2007-11-07 | 2009-05-14 | Genentech, Inc. | Compositions and methods for treatment of microbial disorders |
WO2010135521A2 (en) | 2009-05-20 | 2010-11-25 | Theraclone Sciences, Inc. | Compositions and methods for the therapy and diagnosis of influenza |
ES2395784T3 (es) | 2007-11-12 | 2013-02-15 | Theraclone Sciences, Inc. | Composiciones y métodos para la terapia y diagnosis de la influenza |
US20110033476A1 (en) * | 2007-11-12 | 2011-02-10 | Theraclone Sciences Inc. | Compositions and methods for the therapy and diagnosis of influenza |
TWI580694B (zh) | 2007-11-30 | 2017-05-01 | 建南德克公司 | 抗-vegf抗體 |
EP2235063B1 (en) | 2007-12-28 | 2015-09-02 | Genentech, Inc. | Anti-hedgehog antibodies |
KR100958095B1 (ko) * | 2007-12-31 | 2010-05-14 | 한국과학기술원 | 번역 동반 시스템을 이용한 항균 펩타이드의 대량 발현방법 |
IL287292B (en) | 2008-01-31 | 2022-09-01 | Genentech Inc | and fusion antibody-drug-cd79b engineered antibodies cysteine- |
US20090226455A1 (en) * | 2008-03-06 | 2009-09-10 | Genentech, Inc. | Combination therapy with c-met and her antagonists |
MX2010009885A (es) * | 2008-03-10 | 2010-11-30 | Theraclone Sciences Inc | Composiciones y métodos para la terapia y diagnóstico de citomegalovirus. |
CR20170001A (es) | 2008-04-28 | 2017-08-10 | Genentech Inc | Anticuerpos anti factor d humanizados |
US8680020B2 (en) | 2008-07-15 | 2014-03-25 | Academia Sinica | Glycan arrays on PTFE-like aluminum coated glass slides and related methods |
KR20220047668A (ko) | 2008-12-09 | 2022-04-18 | 제넨테크, 인크. | 항-pd-l1 항체 및 t 세포 기능을 향상시키기 위한 그의 용도 |
BRPI0923034A2 (pt) | 2008-12-17 | 2015-12-15 | Genentech Inc | terapia de combinação para virus da hepatite c |
WO2010078376A2 (en) | 2008-12-30 | 2010-07-08 | Ventana Medical Systems, Inc. | Fc-specific polymer-conjugated antibodies and their diagnostic use |
SI3260136T1 (sl) | 2009-03-17 | 2021-05-31 | Theraclone Sciences, Inc. | Humani imunodeficientni virus (HIV)-nevtralizirajoča protitelesa |
ES2572728T3 (es) | 2009-03-20 | 2016-06-02 | F. Hoffmann-La Roche Ag | Anticuerpos anti-HER biespecíficos |
SG174992A1 (en) | 2009-04-01 | 2011-11-28 | Genentech Inc | Anti-fcrh5 antibodies and immunoconjugates and methods of use |
US20100256340A1 (en) | 2009-04-07 | 2010-10-07 | Ulrich Brinkmann | Trivalent, bispecific antibodies |
US20100297127A1 (en) | 2009-04-08 | 2010-11-25 | Ghilardi Nico P | Use of il-27 antagonists to treat lupus |
CN102459340A (zh) * | 2009-04-23 | 2012-05-16 | 特罗科隆科学有限公司 | 粒性白血细胞-巨噬细胞菌落-刺激因子(gm-csf)中和抗体 |
US9676845B2 (en) | 2009-06-16 | 2017-06-13 | Hoffmann-La Roche, Inc. | Bispecific antigen binding proteins |
SG178210A1 (en) | 2009-08-04 | 2012-03-29 | Hoffmann La Roche | Beta cell marker antibody |
DK2473522T3 (en) | 2009-09-02 | 2016-11-28 | Genentech Inc | Smoothened MUTANT AND METHODS OF USING THE SAME |
US20120302737A1 (en) | 2009-09-16 | 2012-11-29 | Genentech, Inc. | Coiled coil and/or tether containing protein complexes and uses thereof |
US20110206704A1 (en) * | 2009-10-19 | 2011-08-25 | Genentech, Inc. | Methods and compositions for modulating hepatocyte growth factor activator |
MX2012002013A (es) | 2009-10-19 | 2012-03-16 | Genentech Inc | Moduladores de activador del factor de crecimiento de hepatocitos. |
WO2011050194A1 (en) | 2009-10-22 | 2011-04-28 | Genentech, Inc. | Methods and compositions for modulating hepsin activation of macrophage-stimulating protein |
BR112012012213A2 (pt) | 2009-11-26 | 2017-01-10 | Hoffmann La Roche | proteína marcada para diabetes do tipo 2 |
CA2781887C (en) | 2009-11-30 | 2018-03-27 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of tumor |
US11377485B2 (en) | 2009-12-02 | 2022-07-05 | Academia Sinica | Methods for modifying human antibodies by glycan engineering |
US10087236B2 (en) | 2009-12-02 | 2018-10-02 | Academia Sinica | Methods for modifying human antibodies by glycan engineering |
ES2565208T3 (es) | 2009-12-11 | 2016-04-01 | F. Hoffmann-La Roche Ag | Anticuerpos anti-VEGF-C y métodos de uso de los mismos |
CN107095846A (zh) | 2009-12-21 | 2017-08-29 | 霍夫曼-拉罗奇有限公司 | 抗体配制剂 |
PL2536748T3 (pl) | 2010-02-18 | 2015-01-30 | Genentech Inc | Antagoniści neureguliny i ich zastosowanie w leczeniu nowotworu |
CA2787657A1 (en) | 2010-02-23 | 2011-09-01 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of tumor |
SG184033A1 (en) | 2010-03-24 | 2012-10-30 | Genentech Inc | Anti-lrp6 antibodies |
TW201138821A (en) | 2010-03-26 | 2011-11-16 | Roche Glycart Ag | Bispecific antibodies |
WO2011130332A1 (en) | 2010-04-12 | 2011-10-20 | Academia Sinica | Glycan arrays for high throughput screening of viruses |
WO2011133931A1 (en) | 2010-04-22 | 2011-10-27 | Genentech, Inc. | Use of il-27 antagonists for treating inflammatory bowel disease |
BR112012028010A2 (pt) | 2010-05-03 | 2017-09-26 | Genentech Inc | anticorpo isolado, célula, ácido nucleíco isolado, método de identificação de um primeiro anticorpo que se liga a um epítopo antigênico tat425 ligado or um anticorpo, métodos de inibir o crescimento de uma célula, de tratamento terapêutico de determinação da presença de uma proteína de tat425 e de diagnóstico da presença de um tumor em um mamífero |
DK2975409T3 (en) | 2010-05-10 | 2018-12-17 | Academia Sinica | Zanamivir phosphonate congeners with anti-influenza activity and determination of oseltamivir sensitivity in influenza viruses |
MX370828B (es) | 2010-05-25 | 2020-01-08 | Genentech Inc | Métodos de purificación de polipéptidos. |
WO2011147834A1 (en) | 2010-05-26 | 2011-12-01 | Roche Glycart Ag | Antibodies against cd19 and uses thereof |
CN103119442A (zh) | 2010-06-03 | 2013-05-22 | 霍夫曼-拉罗奇有限公司 | 抗体和免疫偶联物的免疫peg成像及其用途 |
WO2011159980A1 (en) | 2010-06-18 | 2011-12-22 | Genentech, Inc. | Anti-axl antibodies and methods of use |
WO2011161119A1 (en) | 2010-06-22 | 2011-12-29 | F. Hoffmann-La Roche Ag | Antibodies against insulin-like growth factor i receptor and uses thereof |
WO2011161189A1 (en) | 2010-06-24 | 2011-12-29 | F. Hoffmann-La Roche Ag | Anti-hepsin antibodies and methods of use |
NZ605449A (en) | 2010-07-09 | 2015-03-27 | Genentech Inc | Anti-neuropilin antibodies and methods of use |
WO2012007495A1 (en) | 2010-07-15 | 2012-01-19 | F. Hoffmann-La Roche Ag | Antibodies specifically binding to human tslpr and methods of use |
WO2012010582A1 (en) | 2010-07-21 | 2012-01-26 | Roche Glycart Ag | Anti-cxcr5 antibodies and methods of use |
WO2012017003A1 (en) | 2010-08-05 | 2012-02-09 | F. Hoffmann-La Roche Ag | Anti-mhc antibody anti-viral cytokine fusion protein |
WO2012021786A2 (en) | 2010-08-12 | 2012-02-16 | Theraclone Sciences, Inc. | Anti-hemagglutinin antibody compositions and methods of use thereof |
EA034742B1 (ru) | 2010-08-13 | 2020-03-16 | Роше Гликарт Аг | Антитела к fap, полинуклеотид, вектор и клетка для их получения и их применения |
EP2603525A1 (en) | 2010-08-13 | 2013-06-19 | F.Hoffmann-La Roche Ag | Antibodies to il-1beta and il-18, for treatment of disease |
KR101653030B1 (ko) | 2010-08-13 | 2016-08-31 | 로슈 글리카트 아게 | 항-테나신-c a2 항체 및 이의 사용 방법 |
KR101586128B1 (ko) | 2010-08-24 | 2016-01-15 | 에프. 호프만-라 로슈 아게 | 디술피드 안정화 ― Fv 단편을 포함하는 이중특이적 항체 |
WO2012025536A1 (en) | 2010-08-25 | 2012-03-01 | F. Hoffmann-La Roche Ag | Antibodies against il-18r1 and uses thereof |
CA3201524A1 (en) | 2010-08-31 | 2012-03-08 | Theraclone Sciences, Inc. | Human immunodeficiency virus (hiv)-neutralizing antibodies |
EP2625197B1 (en) | 2010-10-05 | 2016-06-29 | Genentech, Inc. | Mutant smoothened and methods of using the same |
AU2011326564A1 (en) | 2010-11-10 | 2013-05-09 | Genentech, Inc. | Methods and compositions for neural disease immunotherapy |
WO2012083132A2 (en) | 2010-12-16 | 2012-06-21 | Genentech, Inc. | Diagnosis and treatments relating to th2 inhibition |
TWI589589B (zh) | 2010-12-20 | 2017-07-01 | 建南德克公司 | 抗間皮素(mesothelin)抗體及免疫接合物 |
TW201307391A (zh) | 2010-12-22 | 2013-02-16 | Genentech Inc | 抗-pcsk9抗體及其使用方法 |
JP5766296B2 (ja) | 2010-12-23 | 2015-08-19 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | ポリペプチド−ポリヌクレオチド複合体、およびエフェクター成分の標的化された送達におけるその使用 |
KR20130113493A (ko) | 2011-01-03 | 2013-10-15 | 에프. 호프만-라 로슈 아게 | 항―dig 항체 및 펩티드에 접합되어 있는 디그옥시게닌의 복합체의 약학적 조성물 |
SG192727A1 (en) | 2011-02-14 | 2013-09-30 | Theraclone Sciences Inc | Compositions and methods for the therapy and diagnosis of influenza |
EP2681240B1 (en) | 2011-02-28 | 2017-08-16 | F. Hoffmann-La Roche AG | Monovalent antigen binding proteins |
RU2607038C2 (ru) | 2011-02-28 | 2017-01-10 | Ф. Хоффманн-Ля Рош Аг | Антигенсвязывающие белки |
KR20140012131A (ko) | 2011-03-15 | 2014-01-29 | 테라클론 사이언시스, 아이엔씨. | 인플루엔자의 치료 및 진단을 위한 조성물 및 방법 |
CN103476795B (zh) | 2011-03-29 | 2016-07-06 | 罗切格利卡特公司 | 抗体Fc变体 |
WO2012138975A1 (en) | 2011-04-07 | 2012-10-11 | Genentech, Inc. | Anti-fgfr4 antibodies and methods of use |
CA2828662A1 (en) | 2011-04-20 | 2012-10-26 | Roche Glycart Ag | Method and constructs for the ph dependent passage of the blood-brain-barrier |
WO2012146630A1 (en) | 2011-04-29 | 2012-11-01 | F. Hoffmann-La Roche Ag | N-terminal acylated polypeptides, methods for their production and uses thereof |
CA2833212C (en) | 2011-05-12 | 2020-06-09 | Genentech, Inc. | Multiple reaction monitoring lc-ms/ms method to detect therapeutic antibodies in animal samples using framework signature peptides |
PT2710035T (pt) | 2011-05-16 | 2017-06-05 | Hoffmann La Roche | Agonistas do fgfr1 e métodos de utilização |
WO2012171896A1 (en) | 2011-06-15 | 2012-12-20 | F. Hoffmann-La Roche Ag | Antibody binding to abca1 polypeptide |
EP2721067B1 (en) | 2011-06-15 | 2019-07-31 | F.Hoffmann-La Roche Ag | Anti-human epo receptor antibodies and methods of use |
CA2835772C (en) | 2011-06-22 | 2020-12-01 | F. Hoffmann-La Roche Ag | Removal of target cells by circulating virus-specific cytotoxic t-cells using mhc class i comprising complexes |
WO2013003680A1 (en) | 2011-06-30 | 2013-01-03 | Genentech, Inc. | Anti-c-met antibody formulations |
JP2013040160A (ja) | 2011-07-01 | 2013-02-28 | Genentech Inc | 自己免疫疾患を治療するための抗cd83アゴニスト抗体の使用 |
WO2013025853A1 (en) | 2011-08-17 | 2013-02-21 | Genentech, Inc. | Neuregulin antibodies and uses thereof |
KR20140048292A (ko) | 2011-08-23 | 2014-04-23 | 로슈 글리카트 아게 | 항-mcsp 항체 |
US8822651B2 (en) | 2011-08-30 | 2014-09-02 | Theraclone Sciences, Inc. | Human rhinovirus (HRV) antibodies |
CA2846083A1 (en) | 2011-09-15 | 2013-03-21 | Genentech, Inc. | Methods of promoting differentiation |
BR112014006537A2 (pt) | 2011-09-23 | 2017-11-28 | Roche Glycart Ag | anticorpos biespecíficos, formulação farmacêutica, usos de um anticorpo biespecífico, método de tratamento, ácido nucleico, vetores de expressão, célula hospedeira e método para a produção de um anticorpo biespecífico |
MX2014004074A (es) | 2011-10-05 | 2014-06-05 | Genentech Inc | Metodo de tratamiento de condiciones del higado utilizando antagonistas de notch2. |
LT2766393T (lt) | 2011-10-14 | 2018-10-10 | F. Hoffmann-La Roche Ag | Antikūnai prieš htra1 ir jų naudojimo būdai |
JP6254087B2 (ja) | 2011-10-15 | 2017-12-27 | ジェネンテック, インコーポレイテッド | 癌を治療するためのscd1アンタゴニスト |
WO2013059531A1 (en) | 2011-10-20 | 2013-04-25 | Genentech, Inc. | Anti-gcgr antibodies and uses thereof |
AU2012328512A1 (en) | 2011-10-26 | 2014-05-08 | The Regents Of The University Of California | CD44 monoclonal antibody for the treatment of B-cell chronic lymphocytic leukemia and other hematological malignancies |
MX2014004991A (es) | 2011-10-28 | 2014-05-22 | Genentech Inc | Combinaciones terapeuticas y metodos para tratar el melanoma. |
WO2013066866A1 (en) | 2011-10-31 | 2013-05-10 | Genentech, Inc. | Antibody formulations |
KR20140095096A (ko) | 2011-11-21 | 2014-07-31 | 제넨테크, 인크. | 항-c-met 항체의 정제 |
RU2641968C2 (ru) | 2011-11-29 | 2018-01-23 | Дженентек, Инк. | Композиции и способы анализа рака предстательной железы |
US9988611B2 (en) | 2011-12-01 | 2018-06-05 | Ap Biosciences, Inc. | Protein inhibitors to complement and VEGF pathways and methods of use thereof |
EP2788024A1 (en) | 2011-12-06 | 2014-10-15 | F.Hoffmann-La Roche Ag | Antibody formulation |
WO2013091903A1 (en) | 2011-12-22 | 2013-06-27 | Novo Nordisk A/S | Anti-crac channel antibodies |
KR102280111B1 (ko) | 2011-12-22 | 2021-07-21 | 에프. 호프만-라 로슈 아게 | 발현 벡터 구성, 신규한 생산 세포 생성 방법 및 폴리펩티드의 재조합 생산을 위한 그의 용도 |
SG11201403445YA (en) | 2011-12-22 | 2014-07-30 | Hoffmann La Roche | Full length antibody display system for eukaryotic cells and its use |
JP6096802B2 (ja) | 2011-12-22 | 2017-03-15 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 発現ベクター要素の組み合わせ、新規の産生細胞生成法、およびポリペプチドの組換え産生のためのそれらの使用 |
AR089434A1 (es) | 2011-12-23 | 2014-08-20 | Genentech Inc | Procedimiento para preparar formulaciones con alta concentracion de proteinas |
CN104411717A (zh) | 2012-01-09 | 2015-03-11 | 斯克利普斯研究所 | 具有超长cdr3s的人源化抗体 |
CA2863224A1 (en) | 2012-01-09 | 2013-07-18 | The Scripps Research Institute | Ultralong complementarity determining regions and uses thereof |
IN2014DN05885A (zh) | 2012-01-18 | 2015-06-05 | Hoffmann La Roche | |
WO2013109856A2 (en) | 2012-01-18 | 2013-07-25 | Genentech, Inc. | Methods of using fgf19 modulators |
JP2015506950A (ja) | 2012-01-31 | 2015-03-05 | ジェネンテック, インコーポレイテッド | 抗ig−em1’抗体およびそれを用いる方法 |
CN104105711B (zh) | 2012-02-10 | 2018-11-30 | 弗·哈夫曼-拉罗切有限公司 | 单链抗体及其他异多聚体 |
RU2014133069A (ru) | 2012-02-11 | 2016-04-10 | Дженентек, Инк. | Транслокации r-спондина и способы с их использованием |
EP2814587B1 (en) | 2012-02-15 | 2018-05-02 | F.Hoffmann-La Roche Ag | Fc-receptor based affinity chromatography |
CN104159613B (zh) | 2012-03-08 | 2016-11-23 | 霍夫曼-拉罗奇有限公司 | Abeta抗体制剂 |
JP2015514710A (ja) | 2012-03-27 | 2015-05-21 | ジェネンテック, インコーポレイテッド | Her3阻害剤に関する診断及び治療 |
WO2013148373A1 (en) | 2012-03-28 | 2013-10-03 | Genentech, Inc. | Anti-hcmv idiotypic antibodies and uses thereof |
AR090549A1 (es) | 2012-03-30 | 2014-11-19 | Genentech Inc | Anticuerpos anti-lgr5 e inmunoconjugados |
US10130714B2 (en) | 2012-04-14 | 2018-11-20 | Academia Sinica | Enhanced anti-influenza agents conjugated with anti-inflammatory activity |
EP2839011B1 (en) | 2012-04-17 | 2016-09-14 | F. Hoffmann-La Roche AG | Method for the expression of polypeptides using modified nucleic acids |
KR20150006000A (ko) | 2012-05-01 | 2015-01-15 | 제넨테크, 인크. | 항-pmel17 항체 및 면역접합체 |
WO2013170191A1 (en) | 2012-05-11 | 2013-11-14 | Genentech, Inc. | Methods of using antagonists of nad biosynthesis from nicotinamide |
CN104335047B (zh) | 2012-05-23 | 2017-08-15 | 弗·哈夫曼-拉罗切有限公司 | 治疗剂的选择方法 |
CA2875096A1 (en) | 2012-06-15 | 2013-12-19 | Genentech, Inc. | Anti-pcsk9 antibodies, formulations, dosing, and methods of use |
AR091476A1 (es) | 2012-06-21 | 2015-02-04 | Univ Indiana Res & Tech Corp | POLIPEPTIDOS DE FUSION DE REGION Fc DE POLIPEPTIDO DE LIGANDO RECEPTOR DE INCRETINA Y CONJUGADOS CON FUNCION EFECTORA Fc ALTERADA |
BR112014029888A2 (pt) | 2012-06-27 | 2020-05-12 | Hoffmann La Roche | Métodos de produção de um anticorpo, de determinação de uma combinação de sítios de ligação e de tratamento de um indivíduo com câncer, formulação farmacêutica, anticorpo e uso de um anticorpo |
CN104411718B (zh) | 2012-06-27 | 2018-04-24 | 弗·哈夫曼-拉罗切有限公司 | 用于制备包含特异性结合靶的至少一种结合实体的抗体Fc区缀合物的方法及其用途 |
CN104395339A (zh) | 2012-06-27 | 2015-03-04 | 弗·哈夫曼-拉罗切有限公司 | 用于选择并产生含有至少两种不同结合实体的定制高度选择性和多特异性靶向实体的方法及其用途 |
EP3138580B1 (en) | 2012-07-04 | 2021-03-03 | F. Hoffmann-La Roche AG | Covalently linked antigen-antibody conjugates |
HUE029435T2 (en) | 2012-07-04 | 2017-02-28 | Hoffmann La Roche | Anti-theophylline antibodies and methods of their application |
EP3339328A1 (en) | 2012-07-04 | 2018-06-27 | F. Hoffmann-La Roche AG | Anti-biotin antibodies and methods of use |
EP2870247B1 (en) | 2012-07-05 | 2019-06-26 | F.Hoffmann-La Roche Ag | Expression and secretion system |
AR091702A1 (es) | 2012-07-09 | 2015-02-25 | Genentech Inc | Anticuerpos anti-cd79b e inmunoconjugados |
SG11201500093TA (en) | 2012-07-09 | 2015-02-27 | Genentech Inc | Immunoconjugates comprising anti-cd79b antibodies |
PE20150615A1 (es) | 2012-07-09 | 2015-05-28 | Genentech Inc | Inmunoconjugados que comprenden un anticuerpo anti-cd22 ligado a una pirrolobenzodiazepina |
US20140030281A1 (en) | 2012-07-09 | 2014-01-30 | Genentech, Inc. | Anti-cd22 antibodies and immunoconjugates |
ES2690312T3 (es) | 2012-07-13 | 2018-11-20 | Roche Glycart Ag | Anticuerpos biespecíficos anti-VEGF/anti-ANG-2 y su uso en el tratamiento de enfermedades vasculares oculares |
ES2602030T3 (es) | 2012-08-02 | 2017-02-17 | F. Hoffmann-La Roche Ag | Método para producir RFc solubles como fusión de Fc con la región Fc de inmunoglobulina inerte y usos de los mismos |
CA2880701A1 (en) | 2012-08-18 | 2014-02-27 | Academia Sinica | Cell-permeable probes for identification and imaging of sialidases |
WO2014031762A1 (en) | 2012-08-21 | 2014-02-27 | Academia Sinica | Benzocyclooctyne compounds and uses thereof |
CA2879499A1 (en) | 2012-09-14 | 2014-03-20 | F. Hoffmann-La Roche Ag | Method for the production and selection of molecules comprising at least two different entities and uses thereof |
JP6479661B2 (ja) | 2012-09-19 | 2019-03-06 | ジェネンテック, インコーポレイテッド | タンパク質へのノルロイシン誤取り込みを防ぐための方法及び組成物 |
CA2884431A1 (en) | 2012-11-08 | 2014-05-15 | F. Hoffmann-La Roche Ag | Her3 antigen binding proteins binding to the beta-hairpin of her3 |
BR112015010817A8 (pt) | 2012-11-13 | 2018-01-23 | Genentech Inc | anticorpos anti-hemaglutinina isolado, método de tratamento, inibição ou prevenção de infecções, composição, composição farmacêutica, ácido nucleico isolado, célula hospedeira, método de produção de anticorpos e uso do anticorpo anti-hemaglutinina |
ES2700984T3 (es) | 2012-12-21 | 2019-02-20 | Hoffmann La Roche | Proteínas multifuncionales que comprenden MHC de clase I multivalente unida por disulfuro |
WO2014107739A1 (en) | 2013-01-07 | 2014-07-10 | Eleven Biotherapeutics, Inc. | Antibodies against pcsk9 |
WO2014116749A1 (en) | 2013-01-23 | 2014-07-31 | Genentech, Inc. | Anti-hcv antibodies and methods of using thereof |
RU2015140921A (ru) | 2013-02-26 | 2017-04-03 | Роше Гликарт Аг | Антитела к mcsp |
IL269947B (en) | 2013-03-13 | 2022-08-01 | Genentech Inc | The compounds with reduced oxidation |
CN110538322A (zh) | 2013-03-13 | 2019-12-06 | 豪夫迈·罗氏有限公司 | 抗体配制剂 |
US10653779B2 (en) | 2013-03-13 | 2020-05-19 | Genentech, Inc. | Formulations with reduced oxidation |
HUE049707T2 (hu) | 2013-03-13 | 2020-11-30 | Hoffmann La Roche | Csökkent oxidációjú kiszerelések |
US20140314778A1 (en) | 2013-03-13 | 2014-10-23 | Genentech, Inc. | Formulations with reduced oxidation |
JP6436965B2 (ja) | 2013-03-14 | 2018-12-12 | ジェネンテック, インコーポレイテッド | 抗b7−h4抗体及びイムノコンジュゲート |
US20140271634A1 (en) | 2013-03-14 | 2014-09-18 | The Regents Of The University Of California | Combinations of a mek inhibitor compound with an her3/egfr inhibitor compound and methods of use |
US9562099B2 (en) | 2013-03-14 | 2017-02-07 | Genentech, Inc. | Anti-B7-H4 antibodies and immunoconjugates |
WO2014144865A2 (en) | 2013-03-15 | 2014-09-18 | Genentech, Inc. | Anti-crth2 antibodies and methods of use |
JP6527132B2 (ja) | 2013-03-15 | 2019-06-05 | ジェネンテック, インコーポレイテッド | 肝臓がんの診断及び治療のための組成物及び方法 |
SG11201507429TA (en) | 2013-03-15 | 2015-10-29 | Genentech Inc | Il-22 polypeptides and il-22 fc fusion proteins and methods of use |
MX2015012872A (es) | 2013-03-15 | 2016-02-03 | Ac Immune Sa | Anticuerpos anti-tau y metodos de uso. |
CN105121628B (zh) | 2013-03-15 | 2020-03-24 | 豪夫迈·罗氏有限公司 | 具有抗氧化剂的细胞培养组合物和多肽生产方法 |
US20140283157A1 (en) | 2013-03-15 | 2014-09-18 | Diadexus, Inc. | Lipoprotein-associated phospholipase a2 antibody compositions and methods of use |
AR095348A1 (es) | 2013-03-15 | 2015-10-07 | Genentech Inc | Medios de cultivo celular y métodos de producción de anticuerpos |
WO2014169076A1 (en) | 2013-04-09 | 2014-10-16 | Annexon,,Inc. | Methods of treatment for neuromyelitis optica |
SG11201508910WA (en) | 2013-04-29 | 2015-11-27 | Hoffmann La Roche | Fcrn-binding abolished anti-igf-1r antibodies and their use in the treatment of vascular eye diseases |
ES2746136T3 (es) | 2013-04-29 | 2020-03-04 | Hoffmann La Roche | Anticuerpos modificados de unión a FcRn humano y procedimientos de uso |
ES2871383T3 (es) | 2013-04-29 | 2021-10-28 | Hoffmann La Roche | Anticuerpos asimétricos modificados que se unen al receptor de Fc y procedimientos de uso |
EP4324480A3 (en) | 2013-05-20 | 2024-05-08 | F. Hoffmann-La Roche AG | Anti-transferrin receptor antibodies and methods of use |
EP3013365B1 (en) | 2013-06-26 | 2019-06-05 | Academia Sinica | Rm2 antigens and use thereof |
US9981030B2 (en) | 2013-06-27 | 2018-05-29 | Academia Sinica | Glycan conjugates and use thereof |
SG11201510316UA (en) | 2013-07-09 | 2016-01-28 | Annexon Inc | Anti-complement factor c1q antibodies and uses thereof |
ES2705700T3 (es) | 2013-07-12 | 2019-03-26 | Hoffmann La Roche | Elucidación de la optimización de entrada en cromatografía de intercambio iónico |
CN111518199A (zh) | 2013-07-18 | 2020-08-11 | 图鲁斯生物科学有限责任公司 | 具有超长互补决定区的人源化抗体 |
EP3022224A2 (en) | 2013-07-18 | 2016-05-25 | Fabrus, Inc. | Antibodies with ultralong complementarity determining regions |
EP2832854A1 (en) | 2013-08-02 | 2015-02-04 | F. Hoffmann-La Roche AG | Method for improving the recombinant expression of a polypeptide by C-terminal fusion to human neprilysin |
WO2015023355A1 (en) | 2013-08-12 | 2015-02-19 | Genentech, Inc. | 1-(chloromethyl)-2,3-dihydro-1h-benzo[e]indole dimer antibody-drug conjugate compounds, and methods of use and treatment |
AU2014317889B2 (en) | 2013-09-06 | 2020-03-05 | Academia Sinica | Human iNKT cell activation using glycolipids with altered glycosyl groups |
CN105518027A (zh) | 2013-09-17 | 2016-04-20 | 豪夫迈·罗氏有限公司 | 使用抗lgr5抗体的方法 |
ES2914176T3 (es) | 2013-09-17 | 2022-06-07 | Obi Pharma Inc | Composiciones de una vacuna glucídica para inducir respuestas inmunitarias y usos de las mismas en el tratamiento de cáncer |
EP3049441B1 (en) | 2013-09-27 | 2019-11-27 | F. Hoffmann-La Roche AG | Anti-pdl1 antibody formulations |
WO2015044083A1 (en) | 2013-09-27 | 2015-04-02 | F. Hoffmann-La Roche Ag | Thermus thermophilus slyd fkbp domain specific antibodies |
RU2016117978A (ru) | 2013-10-11 | 2017-11-17 | Дженентек, Инк. | Ингибиторы nsp4 и способы их применения |
CN105612182B (zh) | 2013-10-11 | 2019-12-10 | 豪夫迈·罗氏有限公司 | 多特异性结构域交换共有可变轻链抗体 |
TWI658052B (zh) | 2013-10-18 | 2019-05-01 | 美商建南德克公司 | 抗-rspo抗體及使用方法 |
WO2015061441A1 (en) | 2013-10-23 | 2015-04-30 | Genentech, Inc. | Methods of diagnosing and treating eosinophilic disorders |
MX2016006301A (es) | 2013-11-13 | 2016-12-16 | Zymeworks Inc | Construcciones de unión a antígeno monovalente que se dirigen a egfr y/o her2, y sus usos. |
RU2697098C1 (ru) | 2013-11-21 | 2019-08-12 | Ф.Хоффманн-Ля Рош Аг | Антитела к альфа-синуклеину и способы применения |
JP6817064B2 (ja) | 2013-11-27 | 2021-01-20 | ザイムワークス,インコーポレイテッド | Her2を標的とする二重特異性抗原結合性コンストラクト |
SG10201808835QA (en) | 2013-12-09 | 2018-11-29 | Allakos Inc | Anti-siglec-8 antibodies and methods of use thereof |
TW201533060A (zh) | 2013-12-13 | 2015-09-01 | Genentech Inc | 抗cd33抗體及免疫結合物 |
KR20160092024A (ko) | 2013-12-16 | 2016-08-03 | 제넨테크, 인크. | 1-(클로로메틸)-2,3-디히드로-1H-벤조[e]인돌 이량체 항체-약물 접합체 화합물, 및 사용 및 치료 방법 |
NZ720515A (en) | 2013-12-17 | 2022-12-23 | Genentech Inc | Methods of treating cancers using pd-1 axis binding antagonists and taxanes |
MX2016007965A (es) | 2013-12-17 | 2016-10-28 | Genentech Inc | Terapia de combinacion que comprende agonistas de union a ox40 y antagonistas de union al eje pd-1. |
CN105899535A (zh) | 2013-12-17 | 2016-08-24 | 豪夫迈·罗氏有限公司 | 用pd-1轴结合拮抗剂和抗cd20抗体治疗癌症的方法 |
CA2932958A1 (en) | 2013-12-20 | 2015-06-25 | F. Hoffmann-La Roche Ag | Humanized anti-tau(ps422) antibodies and methods of use |
US10137170B2 (en) | 2013-12-20 | 2018-11-27 | Indiana University Research And Technology Corporation | Lipidated incretin receptor ligand human immunoglobulin Fc-region fusion polypeptides |
TWI728373B (zh) | 2013-12-23 | 2021-05-21 | 美商建南德克公司 | 抗體及使用方法 |
JP6602304B2 (ja) | 2014-01-03 | 2019-11-06 | エフ.ホフマン−ラ ロシュ アーゲー | 共有結合で連結されたヘリカー−抗ヘリカー抗体コンジュゲートおよびその用途 |
CA2930046A1 (en) | 2014-01-03 | 2015-07-09 | F. Hoffmann-La Roche Ag | Covalently linked polypeptide toxin-antibody conjugates |
EP3089996B1 (en) | 2014-01-03 | 2021-07-28 | F. Hoffmann-La Roche AG | Bispecific anti-hapten/anti-blood brain barrier receptor antibodies, complexes thereof and their use as blood brain barrier shuttles |
BR112016015589A2 (pt) | 2014-01-06 | 2017-10-31 | Hoffmann La Roche | módulos de trânsito monovalentes para a barreira hematoencefálica |
EP3835318A1 (en) | 2014-01-15 | 2021-06-16 | F. Hoffmann-La Roche AG | Fc-region variants with modified fcrn- and maintained protein a-binding properties |
WO2016114819A1 (en) | 2015-01-16 | 2016-07-21 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
EP3094352B1 (en) | 2014-01-16 | 2020-09-23 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
US10150818B2 (en) | 2014-01-16 | 2018-12-11 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
KR20160111469A (ko) | 2014-01-24 | 2016-09-26 | 제넨테크, 인크. | 항-steap1 항체 및 면역접합체를 사용하는 방법 |
WO2015116902A1 (en) | 2014-01-31 | 2015-08-06 | Genentech, Inc. | G-protein coupled receptors in hedgehog signaling |
US20170044232A1 (en) | 2014-02-04 | 2017-02-16 | Genentech, Inc. | Mutant smoothened and methods of using the same |
TWI785472B (zh) | 2014-02-08 | 2022-12-01 | 美商建南德克公司 | 治療阿茲海默症之方法 |
CA2938466C (en) | 2014-02-08 | 2021-11-02 | Genentech, Inc. | Methods of treating alzheimer's disease |
WO2015123325A1 (en) | 2014-02-12 | 2015-08-20 | Genentech, Inc. | Anti-jagged1 antibodies and methods of use |
BR112016018980A2 (pt) | 2014-02-21 | 2017-10-10 | Genentech Inc | método de tratamento de um distúrbio, anticorpo multiespecífico, ácido nucleico isolado, célula hospedeira, métodos de produzir um anticorpo, de produção de uma metade de anticorpo ou de um anticorpo multiespecífico e de produção de um anticorpo multiespecífico, imunoconjugado e formulação farmacêutica |
EP3110446B1 (en) | 2014-02-28 | 2021-12-01 | Allakos Inc. | Methods and compositions for treating siglec-8 associated diseases |
WO2015140591A1 (en) | 2014-03-21 | 2015-09-24 | Nordlandssykehuset Hf | Anti-cd14 antibodies and uses thereof |
WO2015148915A1 (en) | 2014-03-27 | 2015-10-01 | Academia Sinica | Reactive labelling compounds and uses thereof |
JP6588461B2 (ja) | 2014-03-31 | 2019-10-09 | ジェネンテック, インコーポレイテッド | 抗血管新生剤及びox40結合アゴニストを含む併用療法 |
CR20160500A (es) | 2014-03-31 | 2016-12-14 | Genentech Inc | Anticuerpos anti-ox40 y métodos de uso |
WO2015150446A1 (en) | 2014-04-02 | 2015-10-08 | F. Hoffmann-La Roche Ag | Method for detecting multispecific antibody light chain mispairing |
WO2015164615A1 (en) | 2014-04-24 | 2015-10-29 | University Of Oslo | Anti-gluten antibodies and uses thereof |
RU2016150370A (ru) | 2014-05-22 | 2018-06-26 | Дженентек, Инк. | Антитела и иммуноконъюгаты против GPC3 |
CA2944717A1 (en) | 2014-05-23 | 2015-11-26 | Genentech, Inc. | Mit biomarkers and methods using the same |
US10118969B2 (en) | 2014-05-27 | 2018-11-06 | Academia Sinica | Compositions and methods relating to universal glycoforms for enhanced antibody efficacy |
US20150344585A1 (en) | 2014-05-27 | 2015-12-03 | Academia Sinica | Anti-cd20 glycoantibodies and uses thereof |
EP3149037A4 (en) | 2014-05-27 | 2018-01-10 | Academia Sinica | Anti-her2 glycoantibodies and uses thereof |
EP3904388A1 (en) | 2014-05-27 | 2021-11-03 | Academia Sinica | Fucosidase from bacteroides and methods using the same |
KR102494193B1 (ko) | 2014-05-28 | 2023-01-31 | 아카데미아 시니카 | 항-tnf-알파 글리코항체 및 이의 용도 |
EP3155015A1 (en) | 2014-06-11 | 2017-04-19 | F. Hoffmann-La Roche AG | Anti-lgr5 antibodies and uses thereof |
AR100978A1 (es) | 2014-06-26 | 2016-11-16 | Hoffmann La Roche | LANZADERAS CEREBRALES DE ANTICUERPO HUMANIZADO ANTI-Tau(pS422) Y USOS DE LAS MISMAS |
JP6654581B2 (ja) | 2014-06-26 | 2020-02-26 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 抗brdu抗体および使用方法 |
DK3309174T3 (da) | 2014-07-11 | 2022-06-07 | Ventana Med Syst Inc | ANTI-PD-L1-antistoffer og diagnostiske anvendelser deraf |
KR20170029490A (ko) | 2014-07-11 | 2017-03-15 | 제넨테크, 인크. | 노치 경로 억제 |
AU2015300787A1 (en) | 2014-08-08 | 2017-02-02 | Alector Llc | Anti-TREM2 antibodies and methods of use thereof |
KR102422375B1 (ko) | 2014-09-08 | 2022-07-18 | 아카데미아 시니카 | 당지질을 사용한 인간 iNKT 세포 활성화 |
SI3191135T1 (sl) | 2014-09-12 | 2021-01-29 | Genentech, Inc. | Anti-HER2 protitelesa in imunokonjugati |
AR101846A1 (es) | 2014-09-12 | 2017-01-18 | Genentech Inc | Anticuerpos anti-cll-1 e inmunoconjugados |
US10149913B2 (en) | 2014-09-12 | 2018-12-11 | Genentech, Inc. | Anthracycline disulfide intermediates, antibody-drug conjugates and methods |
TW201625689A (zh) | 2014-09-12 | 2016-07-16 | 建南德克公司 | 抗-b7-h4抗體及免疫結合物 |
AU2015318001B2 (en) | 2014-09-15 | 2021-03-25 | Genentech, Inc. | Antibody formulations |
MX2017003472A (es) | 2014-09-17 | 2017-10-31 | Genentech Inc | Inmunoconjugados que comprenden anticuerpos anti-her2. |
US20160082120A1 (en) | 2014-09-23 | 2016-03-24 | Genentech, Inc. | METHODS OF USING ANTI-CD79b IMMUNOCONJUGATES |
JP2017536102A (ja) | 2014-10-16 | 2017-12-07 | ジェネンテック, インコーポレイテッド | 抗アルファ−シヌクレイン抗体及び使用方法 |
US20160161485A1 (en) | 2014-11-03 | 2016-06-09 | Genentech, Inc. | Assays for detecting t cell immune subsets and methods of use thereof |
JP2017536842A (ja) | 2014-11-03 | 2017-12-14 | ジェネンテック, インコーポレイテッド | Ox40アゴニスト治療薬の有効性及び評価を予測するための方法及びバイオマーカー |
CN108064308B (zh) | 2014-11-05 | 2023-06-09 | 豪夫迈·罗氏有限公司 | 细菌中产生双链蛋白的方法 |
WO2016073685A1 (en) | 2014-11-05 | 2016-05-12 | Annexon, Inc. | Humanized anti-complement factor c1q antibodies and uses thereof |
MX2017005925A (es) | 2014-11-05 | 2017-11-08 | Genentech Inc | Metodos de producción de proteínas de cadena doble en bacterias. |
WO2016073157A1 (en) | 2014-11-06 | 2016-05-12 | Genentech, Inc. | Anti-ang2 antibodies and methods of use thereof |
HUE045466T2 (hu) | 2014-11-06 | 2019-12-30 | Hoffmann La Roche | Fc-régió-variánsok módosított FcRn-kötéssel és alkalmazási eljárások |
CA2960569A1 (en) | 2014-11-06 | 2016-05-12 | F. Hoffmann-Laroche Ag | Fc-region variants with modified fcrn- and protein a-binding properties |
EP3217787B1 (en) | 2014-11-10 | 2019-04-17 | F.Hoffmann-La Roche Ag | Animal model for nephropathy and agents for treating the same |
CR20170240A (es) | 2014-11-10 | 2018-04-03 | Genentech Inc | Anticuerpos anti-interleucina-33 y sus usos |
BR112017010198A2 (pt) | 2014-11-17 | 2017-12-26 | Genentech Inc | terapia de combinação compreendendo agonistas de ligação a ox40 e antagonistas de ligação ao eixo de pd-1 |
JP6859259B2 (ja) | 2014-11-19 | 2021-04-14 | ジェネンテック, インコーポレイテッド | BACElに対する抗体及び神経疾患免疫療法のためのその使用 |
EP3221362B1 (en) | 2014-11-19 | 2019-07-24 | F.Hoffmann-La Roche Ag | Anti-transferrin receptor antibodies and methods of use |
US11008403B2 (en) | 2014-11-19 | 2021-05-18 | Genentech, Inc. | Anti-transferrin receptor / anti-BACE1 multispecific antibodies and methods of use |
EP3223848A4 (en) | 2014-11-27 | 2018-07-18 | Zymeworks Inc. | Methods of using bispecific antigen-binding constructs targeting her2 |
EP3227332B1 (en) | 2014-12-03 | 2019-11-06 | F.Hoffmann-La Roche Ag | Multispecific antibodies |
EA201790984A1 (ru) | 2014-12-05 | 2018-05-31 | Дженентек, Инк. | Анти-cd79b антитела и способы их применения |
JP2018502840A (ja) | 2014-12-10 | 2018-02-01 | ジェネンテック, インコーポレイテッド | 血液脳関門受容体抗体及び使用方法 |
RU2714963C2 (ru) | 2014-12-17 | 2020-02-21 | Ф. Хоффманн-Ля Рош Аг | Новые способы опосредованного ферментами конъюгирования полипептидов с использованием сортазы |
KR20170094787A (ko) | 2014-12-18 | 2017-08-21 | 에프. 호프만-라 로슈 아게 | Cdc 유발 항체를 측정하기 위한 검정 및 방법 |
SG11201700841QA (en) | 2014-12-19 | 2017-03-30 | Chugai Pharmaceutical Co Ltd | Anti-myostatin antibodies, polypeptides containing variant fc regions, and methods of use |
LT3233921T (lt) | 2014-12-19 | 2021-12-10 | Chugai Seiyaku Kabushiki Kaisha | Anti-c5 antikūnai ir panaudojimo būdai |
US9975965B2 (en) | 2015-01-16 | 2018-05-22 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
US10495645B2 (en) | 2015-01-16 | 2019-12-03 | Academia Sinica | Cancer markers and methods of use thereof |
WO2016117346A1 (en) | 2015-01-22 | 2016-07-28 | Chugai Seiyaku Kabushiki Kaisha | A combination of two or more anti-c5 antibodies and methods of use |
JP6779887B2 (ja) | 2015-01-24 | 2020-11-04 | アカデミア シニカAcademia Sinica | 新規なグリカンコンジュゲートおよびその使用方法 |
CA2972731A1 (en) | 2015-01-24 | 2016-07-28 | Chi-Huey Wong | Cancer markers and methods of use thereof |
CN114702581A (zh) | 2015-01-30 | 2022-07-05 | 台湾地区“中央研究院” | 增进抗体功效的通用糖型组合物及方法 |
CN107636170A (zh) | 2015-02-04 | 2018-01-26 | 健泰科生物技术公司 | 突变型Smoothened及其使用方法 |
WO2016125495A1 (en) | 2015-02-05 | 2016-08-11 | Chugai Seiyaku Kabushiki Kaisha | Antibodies comprising an ion concentration dependent antigen-binding domain, fc region variants, il-8-binding antibodies, and uses therof |
MX2017011486A (es) | 2015-03-16 | 2018-06-15 | Genentech Inc | Métodos de detección y cuantificación de il-13 y sus usos en el diagnóstico y tratamiento de enfermedades asociadas a th2. |
AU2016245807B2 (en) | 2015-04-07 | 2022-05-19 | Alector Llc | Anti-sortilin antibodies and methods of use thereof |
CN108064245A (zh) | 2015-04-17 | 2018-05-22 | 埃尔萨里斯生物技术公司 | 抗Tyro3抗体及其用途 |
WO2016172160A1 (en) | 2015-04-21 | 2016-10-27 | Genentech, Inc. | Compositions and methods for prostate cancer analysis |
EP3913052A1 (en) | 2015-04-24 | 2021-11-24 | F. Hoffmann-La Roche AG | Methods of identifying bacteria comprising binding polypeptides |
EP3778640A1 (en) | 2015-05-01 | 2021-02-17 | Genentech, Inc. | Masked anti-cd3 antibodies and methods of use |
CN116196414A (zh) | 2015-05-11 | 2023-06-02 | 豪夫迈·罗氏有限公司 | 治疗狼疮性肾炎的组合物和方法 |
MX2017015011A (es) | 2015-05-28 | 2018-03-23 | Genentech Inc | Ensayo a base de celulas para detectar homodimeros anti-cd3. |
JP6884111B2 (ja) | 2015-05-29 | 2021-06-09 | ジェネンテック, インコーポレイテッド | 癌におけるpd−l1プロモーターのメチル化 |
EP3302563A1 (en) | 2015-05-29 | 2018-04-11 | H. Hoffnabb-La Roche Ag | Humanized anti-ebola virus glycoprotein antibodies and methods of use |
CN107810012A (zh) | 2015-06-02 | 2018-03-16 | 豪夫迈·罗氏有限公司 | 使用抗il‑34抗体治疗神经疾病的组合物和方法 |
AU2016270858B2 (en) | 2015-06-05 | 2022-04-28 | Ac Immune Sa | Anti-Tau antibodies and methods of use |
JP2018521019A (ja) | 2015-06-08 | 2018-08-02 | ジェネンテック, インコーポレイテッド | 抗ox40抗体を使用して癌を治療する方法 |
CA2988420A1 (en) | 2015-06-08 | 2016-12-15 | Genentech, Inc. | Methods of treating cancer using anti-ox40 antibodies and pd-1 axis binding antagonists |
JP7497953B2 (ja) | 2015-06-12 | 2024-06-11 | アレクトル エルエルシー | 抗cd33抗体及びその使用方法 |
CA2988982A1 (en) | 2015-06-12 | 2016-12-15 | Alector Llc | Anti-cd33 antibodies and methods of use thereof |
US10017577B2 (en) | 2015-06-15 | 2018-07-10 | Genentech, Inc. | Antibodies and immunoconjugates |
EP3310811B1 (en) | 2015-06-16 | 2021-06-16 | Genentech, Inc. | Anti-cd3 antibodies and methods of use |
US10501545B2 (en) | 2015-06-16 | 2019-12-10 | Genentech, Inc. | Anti-CLL-1 antibodies and methods of use |
AR105026A1 (es) | 2015-06-16 | 2017-08-30 | Genentech Inc | ANTICUERPOS MADURADOS POR AFINIDAD Y HUMANIZADOS PARA FcRH5 Y MÉTODOS PARA SU USO |
CA2986592A1 (en) | 2015-06-17 | 2016-12-22 | Genentech, Inc. | Anti-her2 antibodies and methods of use |
AU2016280070B2 (en) | 2015-06-17 | 2022-09-15 | Genentech, Inc. | Methods of treating locally advanced or metastatic breast cancers using PD-1 axis binding antagonists and taxanes |
US10774145B2 (en) | 2015-06-17 | 2020-09-15 | Allakos Inc. | Methods and compositions for treating fibrotic diseases |
WO2016207240A1 (en) | 2015-06-24 | 2016-12-29 | F. Hoffmann-La Roche Ag | Anti-transferrin receptor antibodies with tailored affinity |
CN107810196B (zh) | 2015-06-24 | 2021-11-05 | 豪夫迈·罗氏有限公司 | 人源化的抗-Tau(pS422)抗体和使用方法 |
KR20180021864A (ko) | 2015-06-29 | 2018-03-05 | 제넨테크, 인크. | 장기 이식에서 사용하기 위한 유형 ii 항-cd20 항체 |
CA2990214A1 (en) | 2015-06-29 | 2017-01-05 | Spring Bioscience Corporation | Materials and methods for performing histochemical assays for human pro-epiregulin and amphiregulin |
EP3124976B1 (en) | 2015-07-28 | 2018-09-12 | F. Hoffmann-La Roche AG | Improved bacterial endotoxin test for the determination of endotoxins |
TW202340452A (zh) | 2015-08-04 | 2023-10-16 | 美商再生元醫藥公司 | 補充牛磺酸之細胞培養基及用法 |
CN105384825B (zh) | 2015-08-11 | 2018-06-01 | 南京传奇生物科技有限公司 | 一种基于单域抗体的双特异性嵌合抗原受体及其应用 |
EP3341411A1 (en) | 2015-08-28 | 2018-07-04 | Alector LLC | Anti-siglec-7 antibodies and methods of use thereof |
WO2017040342A1 (en) | 2015-08-28 | 2017-03-09 | Genentech, Inc. | Anti-hypusine antibodies and uses thereof |
US10935544B2 (en) | 2015-09-04 | 2021-03-02 | Obi Pharma, Inc. | Glycan arrays and method of use |
IL258088B2 (en) | 2015-09-18 | 2024-02-01 | Chugai Pharmaceutical Co Ltd | Antibodies that bind to IL-8 and their uses |
JP6904947B2 (ja) | 2015-09-22 | 2021-07-21 | スプリング バイオサイエンス コーポレーション | 抗ox40抗体及びその診断用途 |
EP3353203A2 (en) | 2015-09-23 | 2018-08-01 | H. Hoffnabb-La Roche Ag | Optimized variants of anti-vegf antibodies |
EP3662930A1 (en) | 2015-09-24 | 2020-06-10 | AbVitro LLC | Hiv antibody compositions and methods of use |
EP3353310B1 (en) | 2015-09-25 | 2020-04-29 | H. Hoffnabb-La Roche Ag | Process for producing thioesters employing a sortase a |
BR112018003594A2 (pt) | 2015-09-25 | 2018-09-25 | Hoffmann La Roche | cadeia pesada de imunoglobulina recombinante, anticorpos, método de produção de conjugado e conjugados |
EP3353314A1 (en) | 2015-09-25 | 2018-08-01 | H. Hoffnabb-La Roche Ag | Transamidation employing sortase a in deep eutectic solvents |
CN108138158B (zh) | 2015-09-25 | 2021-11-09 | 豪夫迈·罗氏有限公司 | 可溶性分选酶a |
WO2017053748A2 (en) | 2015-09-25 | 2017-03-30 | Genentech, Inc. | Anti-tigit antibodies and methods of use |
AR106189A1 (es) | 2015-10-02 | 2017-12-20 | Hoffmann La Roche | ANTICUERPOS BIESPECÍFICOS CONTRA EL A-b HUMANO Y EL RECEPTOR DE TRANSFERRINA HUMANO Y MÉTODOS DE USO |
RU2746409C1 (ru) | 2015-10-02 | 2021-04-13 | Ф. Хоффманн-Ля Рош Аг | Антитела к pd1 и способы их применения |
US10287352B2 (en) | 2015-10-02 | 2019-05-14 | Hoffman-La Roche Inc. | Bispecific antibodies specific for PD1 and TIM3 |
EP3150636A1 (en) | 2015-10-02 | 2017-04-05 | F. Hoffmann-La Roche AG | Tetravalent multispecific antibodies |
MA43345A (fr) | 2015-10-02 | 2018-08-08 | Hoffmann La Roche | Conjugués anticorps-médicaments de pyrrolobenzodiazépine et méthodes d'utilisation |
JP6657392B2 (ja) | 2015-10-02 | 2020-03-04 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | 二重特異性抗ヒトcd20/ヒトトランスフェリン受容体抗体及び使用方法 |
CN117069841A (zh) | 2015-10-06 | 2023-11-17 | 艾利妥 | 抗trem2抗体及其使用方法 |
MA45326A (fr) | 2015-10-20 | 2018-08-29 | Genentech Inc | Conjugués calichéamicine-anticorps-médicament et procédés d'utilisation |
US10604577B2 (en) | 2015-10-22 | 2020-03-31 | Allakos Inc. | Methods and compositions for treating systemic mastocytosis |
CN116003596A (zh) | 2015-10-29 | 2023-04-25 | 艾利妥 | 抗siglec-9抗体及其使用方法 |
BR112018006562A2 (pt) | 2015-10-29 | 2018-12-11 | Hoffmann La Roche | anticorpos, ácido nucleico, célula hospedeira, método para produzir um anticorpo, conjugado e uso de um anticorpo |
EP3184547A1 (en) | 2015-10-29 | 2017-06-28 | F. Hoffmann-La Roche AG | Anti-tpbg antibodies and methods of use |
JP2018534930A (ja) | 2015-10-30 | 2018-11-29 | ジェネンテック, インコーポレイテッド | 抗d因子抗体及びコンジュゲート |
CN109071674B (zh) | 2015-10-30 | 2022-08-05 | 豪夫迈·罗氏有限公司 | 铰链修饰的抗体片段和其制备方法 |
CA3088612C (en) | 2015-10-30 | 2022-04-12 | Genentech, Inc. | Anti-htra1 antibodies and methods of use thereof |
CN108602884B (zh) | 2015-11-08 | 2024-06-25 | 豪夫迈·罗氏有限公司 | 筛选多特异性抗体的方法 |
EA036756B1 (ru) | 2015-12-18 | 2020-12-16 | Чугаи Сейяку Кабусики Кайся | Антитела к с5 и способы их применения |
JP7008023B2 (ja) | 2015-12-30 | 2022-01-25 | ジェネンテック, インコーポレイテッド | 低減されたポリソルベート分解を有する製剤 |
AU2016381694A1 (en) | 2015-12-30 | 2018-07-05 | Genentech, Inc. | Use of tryptophan derivatives for protein formulations |
AU2017205089B2 (en) | 2016-01-08 | 2023-10-05 | F. Hoffmann-La Roche Ag | Methods of treating CEA-positive cancers using PD-1 axis binding antagonists and anti-CEA/anti-CD3 bispecific antibodies |
WO2017127764A1 (en) | 2016-01-20 | 2017-07-27 | Genentech, Inc. | High dose treatments for alzheimer's disease |
JP7438662B2 (ja) | 2016-01-25 | 2024-02-27 | ジェネンテック, インコーポレイテッド | T細胞依存性二重特異的抗体をアッセイするための方法 |
EA037855B1 (ru) | 2016-01-29 | 2021-05-27 | Сорренто Терапьютикс, Инк. | Полностью человеческое антитело класса igg, связывающееся с эпитопом pd-l1 |
AU2017213826A1 (en) | 2016-02-04 | 2018-08-23 | Curis, Inc. | Mutant smoothened and methods of using the same |
JP7023853B2 (ja) | 2016-03-04 | 2022-02-22 | アレクトル エルエルシー | 抗trem1抗体及びその使用方法 |
WO2017156032A1 (en) | 2016-03-07 | 2017-09-14 | Charlestonpharma, Llc | Anti-nucleolin antibodies |
CN109195996A (zh) | 2016-03-08 | 2019-01-11 | 中央研究院 | N-聚醣及其阵列的模组化合成方法 |
US11767362B1 (en) | 2016-03-15 | 2023-09-26 | Chugai Seiyaku Kabushiki Kaisha | Methods of treating cancers using PD-1 axis binding antagonists and anti-GPC3 antibodies |
EP4273551A3 (en) | 2016-03-25 | 2024-01-17 | F. Hoffmann-La Roche AG | Multiplexed total antibody and antibody-conjugated drug quantification assay |
US10980894B2 (en) | 2016-03-29 | 2021-04-20 | Obi Pharma, Inc. | Antibodies, pharmaceutical compositions and methods |
EP3436482A4 (en) | 2016-03-29 | 2020-03-11 | OBI Pharma, Inc. | ANTIBODIES, PHARMACEUTICAL COMPOSITIONS AND METHODS |
CN109072212B (zh) | 2016-03-30 | 2022-10-04 | 豪夫迈·罗氏有限公司 | 改善的分选酶 |
EP3443004A1 (en) | 2016-04-14 | 2019-02-20 | H. Hoffnabb-La Roche Ag | Anti-rspo3 antibodies and methods of use |
BR112018071683A2 (pt) | 2016-04-22 | 2019-02-19 | Obi Pharma, Inc. | método para tratar um câncer de mama, método para tratamento de um tumor em um paciente, método para tratar um indivíduo sofrendo com câncer por imunoterapia, método para induzir/melhorar uma resposta imune em um indivíduo, método para melhorar a vacina obi-822 induzida pela resposta imune em um indivíduo necessitando da mesma, método para identificar um paciente adequado para terapia do câncer e método para determinar o prognóstico do tratamento do câncer ou resposta do fármaco de um paciente |
CR20180509A (es) | 2016-05-02 | 2019-02-15 | Hoffmann La Roche | Contorsbody - un ligante de diana monocatenario |
EP3455252B1 (en) | 2016-05-11 | 2022-02-23 | F. Hoffmann-La Roche AG | Modified anti-tenascin antibodies and methods of use |
EP3458101B1 (en) | 2016-05-20 | 2020-12-30 | H. Hoffnabb-La Roche Ag | Protac antibody conjugates and methods of use |
WO2017205741A1 (en) | 2016-05-27 | 2017-11-30 | Genentech, Inc. | Bioanalytical method for the characterization of site-specific antibody-drug conjugates |
CN109476648B (zh) | 2016-06-06 | 2022-09-13 | 豪夫迈·罗氏有限公司 | 司维司群抗体-药物缀合物和使用方法 |
JP6921943B2 (ja) | 2016-06-06 | 2021-08-18 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 増加した眼球保持を伴う眼科用融合タンパク質 |
EP3475298A1 (en) | 2016-06-24 | 2019-05-01 | H. Hoffnabb-La Roche Ag | Anti-polyubiquitin multispecific antibodies |
JP6983824B2 (ja) | 2016-07-04 | 2021-12-17 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 新規抗体フォーマット |
WO2018014260A1 (en) | 2016-07-20 | 2018-01-25 | Nanjing Legend Biotech Co., Ltd. | Multispecific antigen binding proteins and methods of use thereof |
KR20230117482A (ko) | 2016-07-27 | 2023-08-08 | 오비아이 파머 인코퍼레이티드 | 면역원성/치료 글리칸 조성물 및 그의 용도 |
CN117986372A (zh) | 2016-07-29 | 2024-05-07 | 中外制药株式会社 | 显示增加的备选fviii辅因子功能活性的双特异性抗体 |
US11643456B2 (en) | 2016-07-29 | 2023-05-09 | Obi Pharma, Inc. | Human antibodies, pharmaceutical compositions and methods |
TWI693940B (zh) | 2016-08-05 | 2020-05-21 | 日商中外製藥股份有限公司 | Il-8相關疾病之治療用或預防用組成物 |
CN109476748B (zh) | 2016-08-08 | 2023-05-23 | 豪夫迈·罗氏有限公司 | 用于癌症的治疗和诊断方法 |
CN115598231A (zh) | 2016-08-15 | 2023-01-13 | 豪夫迈·罗氏有限公司(Ch) | 定量包含非离子表面活性剂和多肽的组合物中非离子表面活性剂的层析方法 |
EP3500594A4 (en) | 2016-08-22 | 2020-03-11 | Cho Pharma Inc. | ANTIBODIES, BINDING FRAGMENTS AND METHOD FOR USE |
SG10201607778XA (en) | 2016-09-16 | 2018-04-27 | Chugai Pharmaceutical Co Ltd | Anti-Dengue Virus Antibodies, Polypeptides Containing Variant Fc Regions, And Methods Of Use |
CN109689682B (zh) | 2016-09-19 | 2022-11-29 | 豪夫迈·罗氏有限公司 | 基于补体因子的亲和层析 |
CA3031589A1 (en) | 2016-09-23 | 2018-03-29 | Genentech, Inc. | Uses of il-13 antagonists for treating atopic dermatitis |
EP3522933B1 (en) | 2016-10-05 | 2021-12-15 | F. Hoffmann-La Roche AG | Methods for preparing antibody drug conjugates |
WO2018068201A1 (en) | 2016-10-11 | 2018-04-19 | Nanjing Legend Biotech Co., Ltd. | Single-domain antibodies and variants thereof against ctla-4 |
CN110366558A (zh) | 2016-10-28 | 2019-10-22 | 班扬生物标记公司 | 针对泛素c末端水解酶l1(uch-l1)和胶质纤维酸性蛋白(gfap)的抗体及相关方法 |
CN110267678A (zh) | 2016-10-29 | 2019-09-20 | 霍夫曼-拉罗奇有限公司 | 抗mic抗体和使用方法 |
TW201829463A (zh) | 2016-11-18 | 2018-08-16 | 瑞士商赫孚孟拉羅股份公司 | 抗hla-g抗體及其用途 |
US11697680B2 (en) | 2016-11-21 | 2023-07-11 | Cureab Gmbh | Anti-GP73 antibodies and immunoconjugates |
CN110290800A (zh) | 2016-11-21 | 2019-09-27 | 台湾浩鼎生技股份有限公司 | 缀合生物分子、医药组合物及方法 |
UA128383C2 (uk) | 2016-12-07 | 2024-07-03 | Дженентек, Інк. | Антитіло до тау-білка та спосіб його застосування |
JP2020511937A (ja) | 2016-12-07 | 2020-04-23 | ジェネンテック, インコーポレイテッド | 抗tau抗体及び使用方法 |
CA3044920C (en) | 2016-12-21 | 2022-06-28 | Roberto Falkenstein | In vitro glycoengineering of antibodies |
EP3559249A1 (en) | 2016-12-21 | 2019-10-30 | H. Hoffnabb-La Roche Ag | Method for in vitro glycoengineering of antibodies |
EP3559250A1 (en) | 2016-12-21 | 2019-10-30 | H. Hoffnabb-La Roche Ag | Re-use of enzymes in in vitro glycoengineering of antibodies |
CN108239150A (zh) | 2016-12-24 | 2018-07-03 | 信达生物制药(苏州)有限公司 | 抗pcsk9抗体及其用途 |
KR20190104411A (ko) | 2017-01-18 | 2019-09-09 | 제넨테크, 인크. | 항-pd-l1 항체에 대한 이디오타입 항체 및 이의 용도 |
TWI778018B (zh) | 2017-02-10 | 2022-09-21 | 美商建南德克公司 | 抗類胰蛋白酶抗體、其組合物及其用途 |
WO2018152496A1 (en) | 2017-02-17 | 2018-08-23 | The Usa, As Represented By The Secretary, Dept. Of Health And Human Services | Compositions and methods for the diagnosis and treatment of zika virus infection |
NZ756132A (en) | 2017-03-10 | 2022-02-25 | Hoffmann La Roche | Method for producing multispecific antibodies |
JP7216006B2 (ja) | 2017-03-22 | 2023-01-31 | ジェネンテック, インコーポレイテッド | ヒドロゲル架橋ヒアルロン酸プロドラッグ組成物及び方法 |
BR112019019706A2 (pt) | 2017-03-22 | 2020-04-28 | Genentech Inc | conjugado de anticorpo, anticorpo, composição farmacêutica, métodos para reduzir ou inibir angiogênese e para tratar um distúrbio ocular |
CN108623686A (zh) | 2017-03-25 | 2018-10-09 | 信达生物制药(苏州)有限公司 | 抗ox40抗体及其用途 |
MA48996A (fr) | 2017-03-28 | 2020-02-05 | Genentech Inc | Méthodes de traitement de maladies neurodégénératives |
TWI707871B (zh) | 2017-04-05 | 2020-10-21 | 瑞士商赫孚孟拉羅股份公司 | 抗lag3抗體 |
UA128451C2 (uk) | 2017-04-05 | 2024-07-17 | Ф. Хоффманн-Ля Рош Аг | Біспецифічне антитіло, яке специфічно зв'язується з pd1 і lag3 |
US11236151B2 (en) | 2017-04-25 | 2022-02-01 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Antibodies and methods for the diagnosis and treatment of Epstein Barr virus infection |
CA3059468A1 (en) | 2017-04-27 | 2018-11-01 | Tesaro, Inc. | Antibody agents directed against lymphocyte activation gene-3 (lag-3) and uses thereof |
EA201992626A1 (ru) | 2017-05-05 | 2020-04-24 | Аллакос Инк. | Способы и композиции для лечения аллергических заболеваний глаз |
EP3625251A1 (en) | 2017-05-15 | 2020-03-25 | University Of Rochester | Broadly neutralizing anti-influenza monoclonal antibody and uses thereof |
US11359014B2 (en) | 2017-05-16 | 2022-06-14 | Alector Llc | Anti-siglec-5 antibodies and methods of use thereof |
US11827669B2 (en) | 2017-07-19 | 2023-11-28 | The Usa, As Represented By The Secretary, Dept. Of Health And Human Services | Antibodies and methods for the diagnosis and treatment of hepatitis b virus infection |
CR20190486A (es) | 2017-08-03 | 2020-02-10 | Alector Llc | Anti-cd33 antibodies and methods of use thereof |
MX2019012868A (es) | 2017-08-03 | 2019-11-28 | Alector Llc | Anticuerpos anti-trem2 y metodos para utilizarlos. |
AU2018316343A1 (en) | 2017-08-11 | 2020-02-13 | Genentech, Inc. | Anti-CD8 antibodies and uses thereof |
WO2019036855A1 (en) | 2017-08-21 | 2019-02-28 | Adagene Inc. | ANTI-CD137 MOLECULES AND THEIR USE |
US11578426B2 (en) | 2017-08-21 | 2023-02-14 | Adagene Inc. | Dynamic human heavy chain antibody libraries |
KR20200054209A (ko) | 2017-08-21 | 2020-05-19 | 아다진 인크. | 동적 인간 항체 경쇄 라이브러리 |
CN109422811A (zh) | 2017-08-29 | 2019-03-05 | 信达生物制药(苏州)有限公司 | 抗cd47抗体及其用途 |
WO2019051102A2 (en) | 2017-09-08 | 2019-03-14 | Maverick Therapeutics, Inc. | BOND PROTEINS WITH RESTRICTED CONDITIONAL ACTIVATION |
CN111315773A (zh) | 2017-09-08 | 2020-06-19 | 马弗里克治疗公司 | 含有Fc区的条件性活化的结合部分 |
AU2018338859A1 (en) | 2017-09-29 | 2020-02-06 | Chugai Seiyaku Kabushiki Kaisha | Multispecific antigen-binding molecule having blood coagulation factor VIII (FVIII) cofactor function-substituting activity, and pharmaceutical formulation containing said molecule as active ingredient |
CA3185107A1 (en) | 2017-10-12 | 2019-04-18 | Immunowake Inc. | Vegfr-antibody light chain fusion protein |
US10882915B2 (en) | 2017-10-24 | 2021-01-05 | Magenta Therapeutics, Inc. | Compositions and methods for the depletion of CD117+ cells |
CA3078676A1 (en) | 2017-10-30 | 2019-05-09 | F. Hoffmann-La Roche Ag | Method for in vivo generation of multispecific antibodies from monospecific antibodies |
WO2019086394A1 (en) | 2017-11-01 | 2019-05-09 | F. Hoffmann-La Roche Ag | The compbody - a multivalent target binder |
WO2019086395A1 (en) | 2017-11-01 | 2019-05-09 | F. Hoffmann-La Roche Ag | Trifab-contorsbody |
CN111918876B (zh) | 2017-11-30 | 2024-02-02 | 豪夫迈·罗氏有限公司 | 抗pd-l1抗体及使用其检测pd-l1的方法 |
WO2019129136A1 (zh) | 2017-12-27 | 2019-07-04 | 信达生物制药(苏州)有限公司 | 抗pd-l1抗体及其用途 |
CN115925943A (zh) | 2017-12-27 | 2023-04-07 | 信达生物制药(苏州)有限公司 | 抗pd-l1抗体及其用途 |
WO2019129137A1 (zh) | 2017-12-27 | 2019-07-04 | 信达生物制药(苏州)有限公司 | 抗lag-3抗体及其用途 |
WO2019129221A1 (en) | 2017-12-28 | 2019-07-04 | Nanjing Legend Biotech Co., Ltd. | Single-domain antibodies and variants thereof against tigit |
EP3732193A1 (en) | 2017-12-29 | 2020-11-04 | Alector LLC | Anti-tmem106b antibodies and methods of use thereof |
EP3731865A1 (en) | 2017-12-29 | 2020-11-04 | F. Hoffmann-La Roche AG | Method for improving vegf-receptor blocking selectivity of an anti-vegf antibody |
WO2019134981A1 (en) | 2018-01-05 | 2019-07-11 | Ac Immune Sa | Misfolded tdp-43 binding molecules |
SG11202004233UA (en) | 2018-01-15 | 2020-06-29 | Nanjing Legend Biotech Co Ltd | Single-domain antibodies and variants thereof against pd-1 |
CA3088649A1 (en) | 2018-01-16 | 2019-07-25 | Lakepharma, Inc. | Bispecific antibody that binds cd3 and another target |
AR114565A1 (es) | 2018-01-26 | 2020-09-23 | Genentech Inc | Proteínas de fusión fc il-22 y métodos de uso |
AU2019212703A1 (en) | 2018-01-26 | 2020-08-13 | Genentech, Inc. | Compositions and methods of use |
JP7268038B2 (ja) | 2018-01-31 | 2023-05-02 | アレクトル エルエルシー | 抗ms4a4a抗体及びその使用方法 |
TWI732176B (zh) | 2018-02-01 | 2021-07-01 | 大陸商信達生物製藥(蘇州)有限公司 | 全人源的抗b細胞成熟抗原(bcma)單鏈抗體及其應用 |
WO2019148444A1 (en) | 2018-02-02 | 2019-08-08 | Adagene Inc. | Anti-ctla4 antibodies and methods of making and using the same |
WO2019148445A1 (en) | 2018-02-02 | 2019-08-08 | Adagene Inc. | Precision/context-dependent activatable antibodies, and methods of making and using the same |
CR20200391A (es) | 2018-02-08 | 2020-10-19 | Genentech Inc | Moléculas biespecíficas de unión al antígeno y métodos de uso |
WO2019158645A1 (en) | 2018-02-14 | 2019-08-22 | Abba Therapeutics Ag | Anti-human pd-l2 antibodies |
EP3755364A1 (en) | 2018-02-21 | 2020-12-30 | F. Hoffmann-La Roche AG | Dosing for treatment with il-22 fc fusion proteins |
MX2020008882A (es) | 2018-02-26 | 2021-01-08 | Genentech Inc | Dosificación para tratamiento con anticuerpos antagonistas anti-tigit y anti-pd-l1. |
EP3533459A1 (en) | 2018-03-02 | 2019-09-04 | Diaccurate | Anti-pla2-gib antibodies and the uses thereof |
EP3533460A1 (en) | 2018-03-02 | 2019-09-04 | Diaccurate | Therapeutic anti-spla2-gib antibodies and the uses thereof |
AU2019232523A1 (en) | 2018-03-05 | 2020-09-03 | Etablissement Francais Du Sang | Recombinant single chain immunoglobulins |
US20200040103A1 (en) | 2018-03-14 | 2020-02-06 | Genentech, Inc. | Anti-klk5 antibodies and methods of use |
TWI827585B (zh) | 2018-03-15 | 2024-01-01 | 日商中外製藥股份有限公司 | 對茲卡病毒具有交叉反應性的抗登革病毒抗體及其使用方法 |
AU2019241350A1 (en) | 2018-03-30 | 2020-07-30 | Nanjing Legend Biotech Co., Ltd. | Single-domain antibodies against LAG-3 and uses thereof |
EP3778639A4 (en) | 2018-04-02 | 2021-06-09 | Mab-Venture Biopharm Co., Ltd. | ANTIBODIES BINDING TO LYMPHOCYTAIR ACTIVATION GENE 3 (LAG-3) AND ITS USE |
TW202011029A (zh) | 2018-04-04 | 2020-03-16 | 美商建南德克公司 | 偵測及定量fgf21之方法 |
AR114789A1 (es) | 2018-04-18 | 2020-10-14 | Hoffmann La Roche | Anticuerpos anti-hla-g y uso de los mismos |
AR115052A1 (es) | 2018-04-18 | 2020-11-25 | Hoffmann La Roche | Anticuerpos multiespecíficos y utilización de los mismos |
FR3080621B1 (fr) | 2018-04-26 | 2022-12-09 | Univ Limoges | Nouvelle classe d'immunoglobuline recombinante de type g : igg5, codee par le pseudo-gene gamma humain de chaine lourde |
EP3788071A1 (en) | 2018-05-02 | 2021-03-10 | The United States Of America, As Represented By The Secretary, Department of Health and Human Services | Antibodies and methods for the diagnosis, prevention, and treatment of epstein barr virus infection |
CA3096703A1 (en) | 2018-05-03 | 2019-11-07 | University Of Rochester | Anti-influenza neuraminidase monoclonal antibodies and uses thereof |
TWI840364B (zh) | 2018-05-25 | 2024-05-01 | 美商阿列克特有限責任公司 | 抗-sirpa抗體及其使用方法 |
US20210238308A1 (en) | 2018-06-04 | 2021-08-05 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule showing changed half-life in cytoplasm |
EP3804759A4 (en) | 2018-06-06 | 2022-07-20 | Osaka University | METHODS OF TREATMENT OF DANDRUFF OR PREVENTION OF GNASE 1 SECONDARY DISEASES |
CA3100626A1 (en) | 2018-06-08 | 2019-12-12 | Alector Llc | Anti-siglec-7 antibodies and methods of use thereof |
CA3103017A1 (en) | 2018-06-23 | 2019-12-26 | Genentech, Inc. | Methods of treating lung cancer with a pd-1 axis binding antagonist, a platinum agent, and a topoisomerase ii inhibitor |
TW202035444A (zh) | 2018-06-27 | 2020-10-01 | 台灣浩鼎生技股份有限公司 | 用於糖蛋白工程的糖苷合成酶變體及其使用方法 |
EA202190138A1 (ru) | 2018-06-29 | 2021-05-27 | ЭЛЕКТОР ЭлЭлСи | Анти-sirp-бета1 антитела и способы их использования |
EP4212210A1 (en) | 2018-07-13 | 2023-07-19 | Alector LLC | Anti-sortilin antibodies and methods of use thereof |
US20210284718A1 (en) | 2018-07-17 | 2021-09-16 | Humabs Biomed Sa | Antibodies against campylobacter species |
AU2019306628A1 (en) | 2018-07-20 | 2021-02-11 | Surface Oncology, LLC | Anti-CD112R compositions and methods |
CA3107383A1 (en) | 2018-07-23 | 2020-01-30 | Magenta Therapeutics, Inc. | Use of anti-cd5 antibody drug conjugate (adc) in allogeneic cell therapy |
BR112021001201A2 (pt) | 2018-07-25 | 2021-04-27 | Innovent Biologics (Suzhou) Co., Ltd. | anticorpo anti-tigit e uso do mesmo |
AU2019310597A1 (en) | 2018-07-27 | 2021-03-11 | Alector Llc | Anti-siglec-5 antibodies and methods of use thereof |
BR112021001693A2 (pt) | 2018-08-03 | 2021-05-04 | Chugai Seiyaku Kabushiki Kaisha | molécula de ligação ao antígeno contendo dois domínios de ligação ao antígeno q ligados entre si |
CA3106537A1 (en) | 2018-08-08 | 2020-02-13 | Genentech, Inc. | Use of tryptophan derivatives and l-methionine for protein formulation |
CA3108369A1 (en) | 2018-08-10 | 2020-02-13 | Tomoyuki Igawa | Anti-cd137 antigen-binding molecule and utilization thereof |
EA202190235A1 (ru) | 2018-08-31 | 2021-07-02 | Алектор Ллс | Антитела к cd33 и способы их применения |
GB201814281D0 (en) | 2018-09-03 | 2018-10-17 | Femtogenix Ltd | Cytotoxic agents |
EP3857230B1 (en) | 2018-09-21 | 2023-06-07 | F. Hoffmann-La Roche AG | Diagnostic methods for triple-negative breast cancer |
WO2020081493A1 (en) | 2018-10-16 | 2020-04-23 | Molecular Templates, Inc. | Pd-l1 binding proteins |
JP2022506108A (ja) | 2018-10-23 | 2022-01-17 | グリカルディアル ダイアグノスティクス エセ. エレ. | グリコシル化ApoJに特異的な抗体およびその使用 |
JP2022505450A (ja) | 2018-10-24 | 2022-01-14 | エフ・ホフマン-ラ・ロシュ・アクチェンゲゼルシャフト | コンジュゲート化された化学的分解誘導物質および使用方法 |
US20200140533A1 (en) | 2018-11-02 | 2020-05-07 | Annexon, Inc. | Compositions and methods for treating brain injury |
JP2022506156A (ja) | 2018-11-05 | 2022-01-17 | ジェネンテック, インコーポレイテッド | 原核宿主細胞における2鎖タンパク質の産生方法 |
CA3101670C (en) | 2018-11-27 | 2024-02-06 | Innovent Biologics (Suzhou) Co., Ltd. | Anti-il-23p19 antibody and use thereof |
BR112021010908A2 (pt) | 2018-12-06 | 2021-08-31 | Genentech, Inc. | Método para tratamento de linfoma difuso de grandes células b, kit e imunoconjugado |
WO2020123275A1 (en) | 2018-12-10 | 2020-06-18 | Genentech, Inc. | Photocrosslinking peptides for site specific conjugation to fc-containing proteins |
JP7498714B2 (ja) | 2018-12-19 | 2024-06-12 | ヒューマブス・バイオメッド・ソシエテ・アノニム | B型肝炎ウイルスを中和する抗体およびその使用 |
CN113227131A (zh) | 2018-12-20 | 2021-08-06 | 豪夫迈·罗氏有限公司 | 经修饰的抗体Fc及其使用方法 |
AR117468A1 (es) | 2018-12-21 | 2021-08-11 | Hoffmann La Roche | ANTICUERPO QUE SE UNE A VEGF Y A IL-1b Y MÉTODOS DE UTILIZACIÓN |
WO2020141145A1 (en) | 2018-12-30 | 2020-07-09 | F. Hoffmann-La Roche Ag | Anti-rabbit cd19 antibodies and methods of use |
MX2021008621A (es) | 2019-01-22 | 2021-08-19 | Genentech Inc | Anticuerpos de inmunoglobulina a y metodos de produccion y uso. |
GB201901197D0 (en) | 2019-01-29 | 2019-03-20 | Femtogenix Ltd | G-A Crosslinking cytotoxic agents |
EP3931220A1 (en) | 2019-02-27 | 2022-01-05 | F. Hoffmann-La Roche AG | Dosing for treatment with anti-tigit and anti-cd20 or anti-cd38 antibodies |
US20220144949A1 (en) | 2019-03-05 | 2022-05-12 | Takeda Pharmaceutical Limited Company | CONDITIONALLY ACTIVATED BINDING PROTEINS CONTAINING Fc REGIONS AND MOIETIES TARGETING TUMOR ANTIGENS |
EP3934762A1 (en) | 2019-03-05 | 2022-01-12 | Takeda Pharmaceutical Company Limited | Constrained conditionally activated binding proteins |
JP7402247B2 (ja) | 2019-03-08 | 2023-12-20 | ジェネンテック, インコーポレイテッド | 細胞外小胞の膜結合タンパク質を検出及び定量化するための方法 |
US20220153875A1 (en) | 2019-03-19 | 2022-05-19 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule containing antigen-binding domain of which binding activity to antigen is changed depending on mta, and library for obtaining said antigen-binding domain |
JP2022528804A (ja) | 2019-04-18 | 2022-06-15 | ジェネンテック, インコーポレイテッド | 抗体力価試験 |
CN114364703A (zh) | 2019-04-19 | 2022-04-15 | 豪夫迈·罗氏有限公司 | 抗mertk抗体及它们的使用方法 |
KR20220003572A (ko) | 2019-04-24 | 2022-01-10 | 하이델베르크 파마 리서치 게엠베하 | 아마톡신 항체-약물 결합체 및 이의 용도 |
CN113924314A (zh) | 2019-04-25 | 2022-01-11 | 豪夫迈·罗氏有限公司 | 通过多肽链交换活化的治疗性多特异性多肽 |
AU2020261250A1 (en) | 2019-04-25 | 2021-10-14 | F. Hoffmann-La Roche Ag | Generation of antibody-derived polypeptides by polypeptide chain exchange |
AU2020263910A1 (en) | 2019-04-25 | 2021-10-21 | F. Hoffmann-La Roche Ag | Activatable therapeutic multispecific polypeptides with extended half-life |
MX2021013825A (es) | 2019-05-14 | 2022-01-18 | Genentech Inc | Procedimientos de uso de inmunoconjugados anti-cd79b para tratar el linfoma folicular. |
JP2022533432A (ja) | 2019-05-23 | 2022-07-22 | エイシー イミューン ソシエテ アノニム | 抗tdp-43結合分子およびその使用 |
TW202112817A (zh) | 2019-06-11 | 2021-04-01 | 美商阿列克特有限責任公司 | 抗揀選蛋白抗體之使用方法 |
CR20220049A (es) | 2019-07-10 | 2022-03-02 | Chugai Pharmaceutical Co Ltd | Moléculas de unión a claudina-6 y usos de las mismas |
AR119382A1 (es) | 2019-07-12 | 2021-12-15 | Hoffmann La Roche | Anticuerpos de pre-direccionamiento y métodos de uso |
JP2022542964A (ja) | 2019-07-31 | 2022-10-07 | アレクトル エルエルシー | 抗ms4a4a抗体、及びその使用方法 |
AU2020325770B2 (en) | 2019-08-06 | 2022-08-25 | Aprinoia Therapeutics Limited | Antibodies that bind to pathological tau species and uses thereof |
EP3786180A1 (en) | 2019-08-27 | 2021-03-03 | Diaccurate | Antibodies and the uses thereof |
US20220306728A1 (en) | 2019-08-29 | 2022-09-29 | Vir Biotechnology, Inc. | Compositions and methods for treatment of influenza a infection |
AU2020336980A1 (en) | 2019-08-29 | 2022-03-24 | Vir Biotechnology, Inc. | Antibody compositions and methods for treating hepatitis B virus infection |
US20230192853A1 (en) | 2019-09-04 | 2023-06-22 | Genentech, Inc. | Cd8 binding agents and uses thereof |
CA3146616A1 (en) | 2019-09-12 | 2021-03-18 | Matthew Dominic CASCINO | Compositions and methods of treating lupus nephritis |
US20210130492A1 (en) | 2019-09-18 | 2021-05-06 | Genentech, Inc. | Anti-klk7 antibodies, anti-klk5 antibodies, multispecific anti-klk5/klk7 antibodies, and methods of use |
US11918649B2 (en) | 2019-09-18 | 2024-03-05 | Molecular Templates, Inc. | PD-L1-binding molecules comprising Shiga toxin a subunit scaffolds |
WO2021055881A1 (en) | 2019-09-20 | 2021-03-25 | Denali Therapeutics Inc. | Anti-alpha-synuclein antibodies and methods of use thereof |
PE20221110A1 (es) | 2019-09-27 | 2022-07-11 | Genentech Inc | Administracion de dosis para tratamiento con anticuerpos antagonistas anti-tigit y anti-pd-l1 |
WO2021057978A1 (zh) | 2019-09-27 | 2021-04-01 | 南京金斯瑞生物科技有限公司 | 抗vhh域抗体及其用途 |
US11760801B2 (en) | 2019-09-27 | 2023-09-19 | Janssen Biotech, Inc. | Anti-CEACAM antibodies and uses thereof |
CA3153880A1 (en) | 2019-10-18 | 2020-06-09 | Juana Elva HERNANDEZ MONTALVO | Methods of using anti-cd79b immunoconjugates to treat diffuse large b-cell lymphoma |
EP4048405A2 (en) | 2019-10-24 | 2022-08-31 | Minotaur Therapeutics, Inc. | Chimeric cytokine modified antibodies and methods of use thereof |
CA3155922A1 (en) | 2019-11-06 | 2021-05-14 | Huang Huang | Diagnostic and therapeutic methods for treatment of hematologic cancers |
CN117106068B (zh) | 2019-11-11 | 2024-04-16 | 珠海泰诺麦博制药股份有限公司 | 抗水痘-带状疱疹病毒的抗体 |
IL292903A (en) | 2019-11-15 | 2022-07-01 | Univ Tennessee Res Found | Derivatives of immunoglobulins for the detection of amyloid deposits |
CN114641270A (zh) | 2019-11-15 | 2022-06-17 | 豪夫迈·罗氏有限公司 | 防止水性蛋白质溶液中可见颗粒的形成 |
IL293386A (en) | 2019-12-05 | 2022-07-01 | Alector Llc | Methods for using anti-trem2 antibodies |
CN115066437A (zh) | 2019-12-12 | 2022-09-16 | 艾利妥 | 使用抗cd33抗体的方法 |
CR20220329A (es) | 2019-12-13 | 2022-11-23 | Alector Llc | Anticuerpos anti–mertk y metodos de uso de los mismos |
IL293423A (en) | 2019-12-13 | 2022-07-01 | Genentech Inc | Anti-ly6g6d antibodies and methods of use |
BR112022012010A2 (pt) | 2019-12-18 | 2022-08-30 | Hoffmann La Roche | Anticorpos, ácido nucleico isolado, célula hospedeira, formulação farmacêutica, uso do anticorpo, método de produção de um anticorpo, método de tratamento de um indivíduo que tem câncer e método de tratamento de um indivíduo que tem uma doença inflamatória ou autoimune |
PE20221186A1 (es) | 2019-12-23 | 2022-08-05 | Genentech Inc | Anticuerpos especificos de apolipoproteina l1 y metodos de uso |
US20230058982A1 (en) | 2019-12-27 | 2023-02-23 | Chugai Seiyaku Kabushiki Kaisha | Anti-ctla-4 antibody and use thereof |
CN110818795B (zh) | 2020-01-10 | 2020-04-24 | 上海复宏汉霖生物技术股份有限公司 | 抗tigit抗体和使用方法 |
AU2021208553A1 (en) | 2020-01-15 | 2022-09-08 | Trutino Biosciences Inc. | Cytokine IL-2 prodrugs comprising a cleavable linker |
WO2022050954A1 (en) | 2020-09-04 | 2022-03-10 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
WO2021194481A1 (en) | 2020-03-24 | 2021-09-30 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
AU2021214795A1 (en) | 2020-01-31 | 2022-08-18 | The Cleveland Clinic Foundation | Anti-Müllerian Hormone Receptor 2 antibodies and methods of use |
EP4100434A1 (en) | 2020-02-03 | 2022-12-14 | VIR Biotechnology, Inc. | Antibodies against sars-cov-2 and methods of using the same |
CN115427453B (zh) | 2020-02-10 | 2024-07-12 | 上海诗健生物科技有限公司 | Cldn18.2抗体及其用途 |
CA3167349A1 (en) | 2020-02-10 | 2021-08-19 | Qing Zhou | Claudin 18.2 antibody and use thereof |
TW202144395A (zh) | 2020-02-12 | 2021-12-01 | 日商中外製藥股份有限公司 | 用於癌症之治療的抗cd137抗原結合分子 |
JP2023515478A (ja) | 2020-02-24 | 2023-04-13 | アレクトル エルエルシー | 抗trem2抗体の使用方法 |
KR20220164465A (ko) | 2020-02-26 | 2022-12-13 | 비르 바이오테크놀로지, 인코포레이티드 | Sars-cov-2에 대한 항체 및 이의 사용 방법 |
PE20230252A1 (es) | 2020-03-13 | 2023-02-07 | Genentech Inc | Anticuerpos anti-interleucina-33 y sus usos de estos |
JP2023518408A (ja) | 2020-03-19 | 2023-05-01 | ジェネンテック, インコーポレイテッド | アイソフォーム選択的抗tgf-ベータ抗体及び使用方法 |
MX2022011752A (es) | 2020-03-24 | 2022-10-18 | Genentech Inc | Agentes de fijacion a tie2 y metodos de uso. |
JP2023520414A (ja) | 2020-03-30 | 2023-05-17 | エフ. ホフマン-ラ ロシュ アーゲー | Vegf及びpdgf-bに結合する抗体及び使用方法 |
US20230121511A1 (en) | 2020-03-31 | 2023-04-20 | Chugai Seiyaku Kabushiki Kaisha | Method for producing multispecific antigen-binding molecules |
JP2023519962A (ja) | 2020-03-31 | 2023-05-15 | アレクトル エルエルシー | 抗mertk抗体及びその使用方法 |
CA3170570A1 (en) | 2020-04-01 | 2021-10-07 | James J. KOBIE | Monoclonal antibodies against the hemagglutinin (ha) and neuraminidase (na) of influenza h3n2 viruses |
CN115380210A (zh) | 2020-04-02 | 2022-11-22 | 中外制药株式会社 | 含多特异性抗原结合分子的组合物中的杂质分子的分析方法 |
AU2021247286A1 (en) | 2020-04-03 | 2022-10-20 | Alector Llc | Methods of use of anti-TREM2 antibodies |
WO2021203053A1 (en) | 2020-04-03 | 2021-10-07 | Vir Biotechnology, Inc. | Immunotherapy targeting a conserved region in sars coronaviruses |
WO2021207662A1 (en) | 2020-04-10 | 2021-10-14 | Genentech, Inc. | Use of il-22fc for the treatment or prevention of pneumonia, acute respiratory distress syndrome, or cytokine release syndrome |
BR112022020706A2 (pt) | 2020-04-14 | 2022-11-29 | Vir Biotechnology Inc | Anticorpos contra sars-cov-2 e métodos de uso dos mesmos |
CN117186219B (zh) | 2020-04-17 | 2024-07-12 | 珠海泰诺麦博制药股份有限公司 | 抗人神经生长因子的抗体 |
BR112022021441A2 (pt) | 2020-04-24 | 2022-12-13 | Genentech Inc | Métodos para tratar linfoma folicular e linfoma difuso de grandes células b e kits |
IL296664A (en) | 2020-04-24 | 2022-11-01 | Hoffmann La Roche | Enzyme and pathway modulation with sulfhydryl compounds and their derivatives |
MX2021015024A (es) | 2020-04-28 | 2022-01-18 | Univ Rockefeller | Anticuerpos anti-sars-cov-2 ampliamente neutralizantes y métodos de uso de los mismos. |
MX2022013310A (es) | 2020-04-30 | 2022-11-14 | Genentech Inc | Anticuerpos especificos para kras y sus usos. |
KR20230087414A (ko) | 2020-05-03 | 2023-06-16 | 레베나 (쑤저우) 바이오파마 컴퍼니 리미티드 | 항-Trop-2 항체를 포함하는 항체-약물 접합체 (ADCS), 상기 ADCS를 포함하는 조성물, 및 이의 제조 및 사용 방법 |
JP2023525039A (ja) | 2020-05-08 | 2023-06-14 | ヴィア・バイオテクノロジー・インコーポレイテッド | Sars-cov-2に対する抗体 |
WO2021228917A1 (en) | 2020-05-15 | 2021-11-18 | F. Hoffmann-La Roche Ag | Prevention of visible particle formation in parenteral protein solutions |
WO2021233853A1 (en) | 2020-05-19 | 2021-11-25 | F. Hoffmann-La Roche Ag | The use of chelators for the prevention of visible particle formation in parenteral protein solutions |
WO2021247925A1 (en) | 2020-06-03 | 2021-12-09 | Vir Biotechnology, Inc. | Structure-guided immunotherapy against sars-cov-2 |
BR112022024996A2 (pt) | 2020-06-08 | 2022-12-27 | Hoffmann La Roche | Anticorpos, ácido nucleico, célula hospedeira, método para produzir um anticorpo, composição farmacêutica, agente terapêutico, uso do anticorpo e método para tratar um indivíduo com hepatite b |
CA3180477A1 (en) | 2020-06-12 | 2021-12-16 | Elizabeth Alexander | Antibody therapies for sars-cov-2 infection |
AU2021293038A1 (en) | 2020-06-16 | 2023-02-02 | F. Hoffmann-La Roche Ag | Methods and compositions for treating triple-negative breast cancer |
WO2021257124A1 (en) | 2020-06-18 | 2021-12-23 | Genentech, Inc. | Treatment with anti-tigit antibodies and pd-1 axis binding antagonists |
EP4171747A1 (en) | 2020-06-24 | 2023-05-03 | VIR Biotechnology, Inc. | Engineered hepatitis b virus neutralizing antibodies and uses thereof |
JP2023532764A (ja) | 2020-07-07 | 2023-07-31 | エフ. ホフマン-ラ ロシュ アーゲー | 治療用タンパク質製剤の安定剤としての代替界面活性剤 |
CA3187277A1 (en) | 2020-07-10 | 2022-01-13 | F. Hoffmann-La Roche Ag | Antibodies which bind to cancer cells and target radionuclides to said cells |
EP4182688A1 (en) | 2020-07-14 | 2023-05-24 | F. Hoffmann-La Roche AG | Assays for fixed dose combinations |
EP3939999A1 (en) | 2020-07-14 | 2022-01-19 | Fundación del Sector Público Estatal Centro Nacional de Investigaciones Oncológicas Carlos III (F.S.P. CNIO) | Interleukin 11 receptor alpha subunit (il11ra) neutralizing antibodies and uses thereof |
AU2021308653A1 (en) | 2020-07-17 | 2023-02-16 | Genentech, Inc. | Anti-Notch2 antibodies and methods of use |
WO2022020288A1 (en) | 2020-07-21 | 2022-01-27 | Genentech, Inc. | Antibody-conjugated chemical inducers of degradation of brm and methods thereof |
GB2597532A (en) | 2020-07-28 | 2022-02-02 | Femtogenix Ltd | Cytotoxic compounds |
AU2021316017A1 (en) | 2020-07-31 | 2023-02-16 | F. Hoffmann-La Roche Ag | Anti-integrin beta7 antibody formulations and devices |
PE20230983A1 (es) | 2020-08-07 | 2023-06-21 | Genentech Inc | Proteinas de fusion del ligando para flt3 y metodos de uso |
JP2023537761A (ja) | 2020-08-14 | 2023-09-05 | エイシー イミューン ソシエテ アノニム | ヒト化抗tdp-43結合分子およびその使用 |
EP4204448A2 (en) | 2020-08-27 | 2023-07-05 | cureab GmbH | Anti-golph2 antibodies for macrophage and dendritic cell differentiation |
WO2022049165A1 (en) | 2020-09-04 | 2022-03-10 | F. Hoffmann-La Roche Ag | Antibody that binds to vegf-a and ang2 and methods of use |
WO2022066965A2 (en) | 2020-09-24 | 2022-03-31 | Fred Hutchinson Cancer Research Center | Immunotherapy targeting sox2 antigens |
WO2022066973A1 (en) | 2020-09-24 | 2022-03-31 | Fred Hutchinson Cancer Research Center | Immunotherapy targeting pbk or oip5 antigens |
JP2023545322A (ja) | 2020-09-28 | 2023-10-27 | ヴィア・バイオテクノロジー・インコーポレイテッド | Sars-cov-2に対する抗体 |
JP2023544407A (ja) | 2020-10-05 | 2023-10-23 | ジェネンテック, インコーポレイテッド | 抗FcRH5/抗CD3二重特異性抗体による処置のための投与 |
EP4229093A1 (en) | 2020-10-16 | 2023-08-23 | Genentech, Inc. | Anti-cleaved icaspase substrate antibodies and methods of use |
AU2021366287A1 (en) | 2020-10-20 | 2023-04-13 | Kantonsspital St. Gallen | Antibodies or antigen-binding fragments specifically binding to Gremlin-1 and uses thereof |
AR123855A1 (es) | 2020-10-20 | 2023-01-18 | Genentech Inc | Anticuerpos anti-mertk conjugados con peg y métodos de uso |
IL302217A (en) | 2020-11-04 | 2023-06-01 | Genentech Inc | Dosage for treatment with bispecific anti-CD20/anti-CD3 antibodies and anti-CD79B drug antibody conjugates |
US11919945B2 (en) | 2020-11-04 | 2024-03-05 | The Rockefeller University | Neutralizing anti-SARS-CoV-2 antibodies |
EP4240766A2 (en) | 2020-11-04 | 2023-09-13 | Genentech, Inc. | Subcutaneous dosing of anti-cd20/anti-cd3 bispecific antibodies |
JP7402381B2 (ja) | 2020-11-04 | 2023-12-20 | ジェネンテック, インコーポレイテッド | 抗cd20/抗cd3二重特異性抗体による処置のための投与 |
CA3199429A1 (en) | 2020-11-23 | 2022-05-27 | Davide Corti | Anti-influenza antibodies and combinations thereof |
CA3197537A1 (en) | 2020-11-23 | 2022-05-27 | Davide Corti | Antibodies against influenza a viruses |
KR20230137293A (ko) | 2020-11-23 | 2023-10-04 | 비르 바이오테크놀로지, 인코포레이티드 | 인플루엔자 뉴라미니다제에 대한 광범위 중화 항체 |
JP2023550785A (ja) | 2020-11-25 | 2023-12-05 | ヴィア・バイオテクノロジー・インコーポレイテッド | 複数のベータコロナウイルスに結合する抗体 |
WO2022120352A1 (en) | 2020-12-02 | 2022-06-09 | Alector Llc | Methods of use of anti-sortilin antibodies |
WO2022122654A1 (en) | 2020-12-07 | 2022-06-16 | UCB Biopharma SRL | Multi-specific antibodies and antibody combinations |
AR124250A1 (es) | 2020-12-07 | 2023-03-01 | UCB Biopharma SRL | Anticuerpos |
JP2023553888A (ja) | 2020-12-08 | 2023-12-26 | ヴィア・バイオテクノロジー・インコーポレイテッド | A型インフルエンザ感染の治療のための抗体及び方法 |
CR20230263A (es) | 2020-12-17 | 2023-08-21 | Hoffmann La Roche | Anticuerpos anti-hla-g y uso de estos |
CN117098548A (zh) | 2020-12-23 | 2023-11-21 | 信达生物制药(苏州)有限公司 | 抗b7-h3抗体及其用途 |
WO2022140797A1 (en) | 2020-12-23 | 2022-06-30 | Immunowake Inc. | Immunocytokines and uses thereof |
AU2022206061A1 (en) | 2021-01-06 | 2023-07-06 | F. Hoffmann-La Roche Ag | Combination therapy employing a pd1-lag3 bispecific antibody and a cd20 t cell bispecific antibody |
WO2022152656A1 (en) | 2021-01-12 | 2022-07-21 | F. Hoffmann-La Roche Ag | Split antibodies which bind to cancer cells and target radionuclides to said cells |
JP2024505636A (ja) | 2021-01-15 | 2024-02-07 | ザ ロックフェラー ユニバーシティー | 抗sars-cov-2中和抗体 |
KR20230148169A (ko) | 2021-01-22 | 2023-10-24 | 엘피스 바이오파마슈티컬즈 | 항-pd-l1 모노클로날 항체 및 인터루킨-15 (il-15), 인터루킨-15 수용체 15 알파 또는 인터루킨-2와의 융합 단백질 |
WO2022159842A1 (en) | 2021-01-25 | 2022-07-28 | Vir Biotechnology, Inc. | Antibody combination therapies for sars-cov-2 infection |
JP2024504167A (ja) | 2021-01-26 | 2024-01-30 | ヴィア・バイオテクノロジー・インコーポレイテッド | B型肝炎ウイルス感染を処置するための抗体組成物および方法 |
WO2022162587A1 (en) | 2021-01-27 | 2022-08-04 | Centre Hospitalier Universitaire Vaudois (C.H.U.V.) | Anti-sars-cov-2 antibodies and use thereof in the treatment of sars-cov-2 infection |
WO2022162203A1 (en) | 2021-01-28 | 2022-08-04 | Vaccinvent Gmbh | Method and means for modulating b-cell mediated immune responses |
KR20230147099A (ko) | 2021-01-28 | 2023-10-20 | 백신벤트 게엠베하 | B 세포 매개 면역 반응을 조절하기 위한 방법 및 수단(method and means for modulating b-cell mediated immune responses) |
CN117120084A (zh) | 2021-01-28 | 2023-11-24 | 维肯芬特有限责任公司 | 用于调节b细胞介导的免疫应答的方法和手段 |
JP2024509695A (ja) | 2021-02-03 | 2024-03-05 | ジェネンテック, インコーポレイテッド | 多重特異性結合タンパク質分解プラットフォームおよび使用方法 |
AU2022217845A1 (en) | 2021-02-04 | 2023-08-24 | Innovent Biologics (Suzhou) Co., Ltd. | Anti-tnfr2 antibody and use thereof |
EP4289866A2 (en) | 2021-02-04 | 2023-12-13 | Genuv Inc. | Anti-pd-1 antibody and use thereof |
JP2024506321A (ja) | 2021-02-09 | 2024-02-13 | ヒューマブス・バイオメッド・ソシエテ・アノニム | 呼吸器合胞体ウイルスおよび他のパラミクソウイルスに対する抗体およびその使用方法 |
JP2024509169A (ja) | 2021-03-03 | 2024-02-29 | ソレント・セラピューティクス・インコーポレイテッド | 抗bcma抗体を含む抗体-薬物コンジュゲート |
AU2022232951A1 (en) | 2021-03-10 | 2023-10-19 | Immunowake Inc. | Immunomodulatory molecules and uses thereof |
AR125074A1 (es) | 2021-03-12 | 2023-06-07 | Genentech Inc | Anticuerpos anti-klk7, anticuerpos anti-klk5, anticuerpos multiespecíficos anti-klk5 / klk7 y métodos de uso |
JP2024511970A (ja) | 2021-03-15 | 2024-03-18 | ジェネンテック, インコーポレイテッド | ループス腎炎の治療の組成物及び方法 |
CA3213295A1 (en) | 2021-03-17 | 2022-09-22 | Molecular Templates, Inc. | Pd-l1 binding proteins comprising shiga toxin a subunit scaffolds and cd8+ t cell antigens |
CN116981696A (zh) | 2021-03-18 | 2023-10-31 | 艾莱克特有限责任公司 | 抗tmem106b抗体及其使用方法 |
WO2022197877A1 (en) | 2021-03-19 | 2022-09-22 | Genentech, Inc. | Methods and compositions for time delayed bio-orthogonal release of cytotoxic agents |
WO2022204202A1 (en) | 2021-03-23 | 2022-09-29 | Vir Biotechnology, Inc. | Antibodies that bind to multiple sarbecoviruses |
WO2022204274A1 (en) | 2021-03-23 | 2022-09-29 | Alector Llc | Anti-tmem106b antibodies for treating and preventing coronavirus infections |
TW202300648A (zh) | 2021-03-25 | 2023-01-01 | 美商當康生物科技有限公司 | 抗-igfbp7構築體及其用途 |
EP4067376A1 (en) | 2021-03-30 | 2022-10-05 | Diaccurate | Anti-pla2g1b monoclonal antibodies and uses thereof |
AR125344A1 (es) | 2021-04-15 | 2023-07-05 | Chugai Pharmaceutical Co Ltd | Anticuerpo anti-c1s |
CA3217865A1 (en) | 2021-04-28 | 2022-11-03 | Minotaur Therapeutics, Inc. | Humanized chimeric bovine antibodies and methods of use |
EP4330282A1 (en) | 2021-04-30 | 2024-03-06 | F. Hoffmann-La Roche AG | Dosing for combination treatment with anti-cd20/anti-cd3 bispecific antibody and anti-cd79b antibody drug conjugate |
US20240254224A1 (en) | 2021-05-03 | 2024-08-01 | UCB Biopharma SRL | Antibodies |
US20240218057A1 (en) | 2021-05-06 | 2024-07-04 | The Rockefeller University | Neutralizing anti- sars-cov-2 antibodies and methods of use thereof |
CA3218170A1 (en) | 2021-05-12 | 2022-11-17 | Jamie Harue HIRATA | Methods of using anti-cd79b immunoconjugates to treat diffuse large b-cell lymphoma |
CN117396510A (zh) | 2021-05-14 | 2024-01-12 | 基因泰克公司 | Trem2的激动剂 |
TW202306978A (zh) | 2021-05-24 | 2023-02-16 | 美商維爾生物科技股份有限公司 | 經工程化的多肽 |
TW202307006A (zh) | 2021-06-03 | 2023-02-16 | 美商表面腫瘤學公司 | 用抗cd39抗體及派姆單抗治療癌症之方法 |
TW202306994A (zh) | 2021-06-04 | 2023-02-16 | 日商中外製藥股份有限公司 | 抗ddr2抗體及其用途 |
JP2024527262A (ja) | 2021-06-16 | 2024-07-24 | アレクトル エルエルシー | 二重特異性抗MerTK及び抗PDL1抗体ならびにその使用方法 |
US20240279358A1 (en) | 2021-06-16 | 2024-08-22 | Alector Llc | Monovalent anti-mertk antibodies and methods of use thereof |
WO2022263638A1 (en) | 2021-06-17 | 2022-12-22 | Centre Hospitalier Universitaire Vaudois (C.H.U.V.) | Anti-sars-cov-2 antibodies and use thereof in the treatment of sars-cov-2 infection |
JP2024526103A (ja) | 2021-06-17 | 2024-07-17 | ジェネンテック, インコーポレイテッド | 抗ユビキチン化抗体および使用方法 |
KR20240021859A (ko) | 2021-06-18 | 2024-02-19 | 에프. 호프만-라 로슈 아게 | 이중특이적 항-ccl2 항체 |
IL308633A (en) | 2021-06-25 | 2024-01-01 | Chugai Pharmaceutical Co Ltd | Use of anti-CTLA-4 antibodies |
TW202317627A (zh) | 2021-06-25 | 2023-05-01 | 日商中外製藥股份有限公司 | 抗ctla-4抗體 |
EP4370545A1 (en) | 2021-07-12 | 2024-05-22 | Genentech, Inc. | Structures for reducing antibody-lipase binding |
KR20240032889A (ko) | 2021-07-14 | 2024-03-12 | 제넨테크, 인크. | 항-c-c 모티프 케모카인 수용체 8(ccr8) 항체 및 사용 방법 |
IL310137A (en) | 2021-07-21 | 2024-03-01 | Trutino Biosciences Inc | Polypeptide linkages |
EP4373859A1 (en) | 2021-07-22 | 2024-05-29 | F. Hoffmann-La Roche AG | Heterodimeric fc domain antibodies |
EP4373576A1 (en) | 2021-07-22 | 2024-05-29 | Genentech, Inc. | Brain targeting compositions and methods of use thereof |
CN117794953A (zh) | 2021-08-03 | 2024-03-29 | 豪夫迈·罗氏有限公司 | 双特异性抗体及使用方法 |
EP4388015A1 (en) | 2021-08-18 | 2024-06-26 | Philip Morris Products S.A. | Antibody and antigen binding fragments thereof |
EP4388014A1 (en) | 2021-08-19 | 2024-06-26 | F. Hoffmann-La Roche AG | Multivalent anti-variant fc-region antibodies and methods of use |
GB202111905D0 (en) | 2021-08-19 | 2021-10-06 | UCB Biopharma SRL | Antibodies |
TW202315895A (zh) | 2021-08-27 | 2023-04-16 | 瑞士商休曼生物醫藥股份公司 | 經工程化的組成物 |
AU2022332303A1 (en) | 2021-08-27 | 2024-02-01 | Genentech, Inc. | Methods of treating tau pathologies |
TW202325727A (zh) | 2021-08-30 | 2023-07-01 | 美商建南德克公司 | 抗聚泛素多特異性抗體 |
WO2023034866A1 (en) | 2021-09-01 | 2023-03-09 | Vir Biotechnology, Inc. | Antibody therapies for sars-cov-2 infection in pediatric subjects |
WO2023034871A1 (en) | 2021-09-01 | 2023-03-09 | Vir Biotechnology, Inc. | High concentration antibody therapies for sars-cov-2 infection |
EP4399228A1 (en) | 2021-09-07 | 2024-07-17 | Etablissement Français du Sang | Targeted regulation of platelet and megakaryocyte activation by heteroreceptor co-clustering |
WO2023039442A1 (en) | 2021-09-08 | 2023-03-16 | Vir Biotechnology, Inc. | Broadly neutralizing antibody combination therapies for sars-cov-2 infection |
WO2023053282A1 (ja) | 2021-09-29 | 2023-04-06 | 中外製薬株式会社 | がんの治療に用いるための細胞傷害誘導治療剤 |
WO2023056403A1 (en) | 2021-09-30 | 2023-04-06 | Genentech, Inc. | Methods for treatment of hematologic cancers using anti-tigit antibodies, anti-cd38 antibodies, and pd-1 axis binding antagonists |
KR20240082388A (ko) | 2021-10-08 | 2024-06-10 | 추가이 세이야쿠 가부시키가이샤 | 프리필드 시린지 제제의 조제 방법 |
WO2023069919A1 (en) | 2021-10-19 | 2023-04-27 | Alector Llc | Anti-cd300lb antibodies and methods of use thereof |
KR20240099315A (ko) | 2021-11-05 | 2024-06-28 | 아메리칸 다이어그노스틱스 앤드 테라피, 엘엘씨 (에이디엑스알엑스) | 암배아성 항원에 대한 단클론성 항체 및 이의 용도 |
WO2023081898A1 (en) | 2021-11-08 | 2023-05-11 | Alector Llc | Soluble cd33 as a biomarker for anti-cd33 efficacy |
WO2023086807A1 (en) | 2021-11-10 | 2023-05-19 | Genentech, Inc. | Anti-interleukin-33 antibodies and uses thereof |
CA3236006A1 (en) | 2021-11-16 | 2023-05-25 | Genentech, Inc. | Methods and compositions for treating systemic lupus erythematosus (sle) with mosunetuzumab |
AR127692A1 (es) | 2021-11-16 | 2024-02-21 | Ac Immune Sa | Anticuerpos anti-asc para uso en tratamientos antiinflamatorios |
AU2022411573A1 (en) | 2021-12-17 | 2024-06-27 | Shanghai Henlius Biologics Co., Ltd. | Anti-ox40 antibodies and methods of use |
KR20240116755A (ko) | 2021-12-17 | 2024-07-30 | 상하이 헨리우스 바이오테크, 인크. | 항-ox40 항체, 다중 특이적 항체 및 이의 사용 방법 |
WO2023141445A1 (en) | 2022-01-19 | 2023-07-27 | Genentech, Inc. | Anti-notch2 antibodies and conjugates and methods of use |
WO2023147399A1 (en) | 2022-01-27 | 2023-08-03 | The Rockefeller University | Broadly neutralizing anti-sars-cov-2 antibodies targeting the n-terminal domain of the spike protein and methods of use thereof |
WO2023156549A1 (en) | 2022-02-16 | 2023-08-24 | Ac Immune Sa | Humanized anti-tdp-43 binding molecules and uses thereof |
WO2023164516A1 (en) | 2022-02-23 | 2023-08-31 | Alector Llc | Methods of use of anti-trem2 antibodies |
EP4238988A1 (en) | 2022-03-01 | 2023-09-06 | Consejo Superior De Investigaciones Científicas | Antibodies against sars-cov-2 and uses thereof |
US20230414750A1 (en) | 2022-03-23 | 2023-12-28 | Hoffmann-La Roche Inc. | Combination treatment of an anti-cd20/anti-cd3 bispecific antibody and chemotherapy |
WO2023191816A1 (en) | 2022-04-01 | 2023-10-05 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2023194565A1 (en) | 2022-04-08 | 2023-10-12 | Ac Immune Sa | Anti-tdp-43 binding molecules |
WO2023201256A1 (en) | 2022-04-12 | 2023-10-19 | Vir Biotechnology, Inc. | High dose antibody therapies for sars-cov-2 infection |
US11958906B2 (en) | 2022-04-13 | 2024-04-16 | Genentech, Inc. | Pharmaceutical compositions of mosunetuzumab and methods of use |
WO2023201299A1 (en) | 2022-04-13 | 2023-10-19 | Genentech, Inc. | Pharmaceutical compositions of therapeutic proteins and methods of use |
WO2023198727A1 (en) | 2022-04-13 | 2023-10-19 | F. Hoffmann-La Roche Ag | Pharmaceutical compositions of anti-cd20/anti-cd3 bispecific antibodies and methods of use |
WO2023203177A1 (en) | 2022-04-20 | 2023-10-26 | Kantonsspital St. Gallen | Antibodies or antigen-binding fragments pan-specifically binding to gremlin-1 and gremlin-2 and uses thereof |
WO2023215737A1 (en) | 2022-05-03 | 2023-11-09 | Genentech, Inc. | Anti-ly6e antibodies, immunoconjugates, and uses thereof |
WO2023213969A1 (en) | 2022-05-05 | 2023-11-09 | Juno Therapeutics Gmbh | Viral-binding protein and related reagents, articles, and methods of use |
TW202402810A (zh) | 2022-05-11 | 2024-01-16 | 瑞士商赫孚孟拉羅股份公司 | 與vegf—a及il6結合之抗體及其使用方法 |
WO2023219613A1 (en) | 2022-05-11 | 2023-11-16 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2023230439A1 (en) | 2022-05-23 | 2023-11-30 | Vir Biotechnology, Inc. | Fc-engineered hepatitis b virus neutralizing antibodies and uses thereof |
WO2023230448A1 (en) | 2022-05-23 | 2023-11-30 | Vir Biotechnology, Inc. | Combination immunotherapy for influenza |
WO2023230445A2 (en) | 2022-05-23 | 2023-11-30 | Humabs Biomed Sa | Broadly neutralizing antibodies against influenza neuraminidase |
WO2023240058A2 (en) | 2022-06-07 | 2023-12-14 | Genentech, Inc. | Prognostic and therapeutic methods for cancer |
WO2023237706A2 (en) | 2022-06-08 | 2023-12-14 | Institute For Research In Biomedicine (Irb) | Cross-specific antibodies, uses and methods for discovery thereof |
WO2023245078A1 (en) | 2022-06-15 | 2023-12-21 | Humabs Biomed Sa | Anti-parvovirus antibodies and uses thereof |
AU2023295035A1 (en) | 2022-06-17 | 2024-08-15 | Genentech, Inc. | Use of kosmotropes to enhance yield of an affinity chromatography purification step |
WO2024006472A1 (en) | 2022-06-30 | 2024-01-04 | Vir Biotechnology, Inc. | Antibodies that bind to multiple sarbecoviruses |
WO2024015897A1 (en) | 2022-07-13 | 2024-01-18 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2024020432A1 (en) | 2022-07-19 | 2024-01-25 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2024020564A1 (en) | 2022-07-22 | 2024-01-25 | Genentech, Inc. | Anti-steap1 antigen-binding molecules and uses thereof |
WO2024026411A1 (en) | 2022-07-27 | 2024-02-01 | Humabs Biomed Sa | Broadly neutralizing antibodies against rsv and mpv paramyxoviruses |
WO2024026447A1 (en) | 2022-07-29 | 2024-02-01 | Alector Llc | Anti-gpnmb antibodies and methods of use thereof |
WO2024052922A1 (en) | 2022-09-11 | 2024-03-14 | Yeda Research And Development Co. Ltd. | Anti-klk4 antibodies and uses thereof |
WO2024068996A1 (en) | 2022-09-30 | 2024-04-04 | Centre Hospitalier Universitaire Vaudois (C.H.U.V.) | Anti-sars-cov-2 antibodies and use thereof in the treatment of sars-cov-2 infection |
WO2024077239A1 (en) | 2022-10-07 | 2024-04-11 | Genentech, Inc. | Methods of treating cancer with anti-c-c motif chemokine receptor 8 (ccr8) antibodies |
WO2024079074A1 (en) | 2022-10-10 | 2024-04-18 | Universite D'aix Marseille | ANTI-sCD146 ANTIBODIES AND USES THEREOF |
WO2024086796A1 (en) | 2022-10-20 | 2024-04-25 | Alector Llc | Anti-ms4a4a antibodies with amyloid-beta therapies |
WO2024091991A1 (en) | 2022-10-25 | 2024-05-02 | Genentech, Inc. | Therapeutic and diagnostic methods for multiple myeloma |
WO2024102734A1 (en) | 2022-11-08 | 2024-05-16 | Genentech, Inc. | Compositions and methods of treating childhood onset idiopathic nephrotic syndrome |
WO2024100200A1 (en) | 2022-11-09 | 2024-05-16 | Cis Pharma Ag | Anti-l1-cam antibodies and their uses for diagnostic and therapeutic applications |
WO2024104988A1 (en) | 2022-11-15 | 2024-05-23 | F. Hoffmann-La Roche Ag | Recombinant binding proteins with activatable effector domain |
WO2024107749A1 (en) | 2022-11-16 | 2024-05-23 | Attralus, Inc. | Fusion proteins that bind amyloid and the transferrin receptor and uses thereof |
WO2024112818A1 (en) | 2022-11-22 | 2024-05-30 | Humabs Biomed Sa | Engineered anti-sars-cov-2 antibodies and uses thereof |
WO2024118998A2 (en) | 2022-12-01 | 2024-06-06 | Vir Biotechnology, Inc. | Engineered anti-sars-cov-2 antibodies and methods of using the same |
WO2024121632A1 (en) | 2022-12-09 | 2024-06-13 | Crispr Therapeutics Ag | Use of anti-cd117 antibody drug conjugate (adc) |
WO2024148232A2 (en) | 2023-01-06 | 2024-07-11 | Alector Llc | Anti-il18 binding protein antibodies and methods of use thereof |
WO2024155807A1 (en) | 2023-01-18 | 2024-07-25 | Genentech, Inc. | Multispecific antibodies and uses thereof |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4963495A (en) * | 1984-10-05 | 1990-10-16 | Genentech, Inc. | Secretion of heterologous proteins |
US5232840A (en) * | 1986-03-27 | 1993-08-03 | Monsanto Company | Enhanced protein production in bacteria by employing a novel ribosome binding site |
-
1995
- 1995-03-01 US US08/398,615 patent/US5840523A/en not_active Expired - Lifetime
-
1996
- 1996-02-27 ES ES96906659T patent/ES2285711T3/es not_active Expired - Lifetime
- 1996-02-27 JP JP52643696A patent/JP3375970B2/ja not_active Expired - Lifetime
- 1996-02-27 WO PCT/US1996/002858 patent/WO1996027016A1/en active IP Right Grant
- 1996-02-27 AU AU49984/96A patent/AU701476B2/en not_active Expired
- 1996-02-27 DK DK96906659T patent/DK0815246T3/da active
- 1996-02-27 AT AT96906659T patent/ATE358181T1/de active
- 1996-02-27 EP EP96906659A patent/EP0815246B1/en not_active Expired - Lifetime
- 1996-02-27 RU RU97116138/13A patent/RU2208639C2/ru active
- 1996-02-27 CN CNB961930578A patent/CN1154736C/zh not_active Expired - Lifetime
- 1996-02-27 CA CA002213813A patent/CA2213813C/en not_active Expired - Lifetime
- 1996-02-27 BR BRPI9607464-7A patent/BR9607464B1/pt not_active IP Right Cessation
- 1996-02-27 NZ NZ303619A patent/NZ303619A/en not_active IP Right Cessation
- 1996-02-27 DE DE69636996T patent/DE69636996T2/de not_active Expired - Lifetime
- 1996-02-29 IL IL11731496A patent/IL117314A0/xx not_active IP Right Cessation
- 1996-03-01 ZA ZA9601688A patent/ZA961688B/xx unknown
-
1997
- 1997-08-29 FI FI973559A patent/FI120357B/fi not_active IP Right Cessation
- 1997-08-29 NO NO19973985A patent/NO324920B1/no not_active IP Right Cessation
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102933600A (zh) * | 2009-11-05 | 2013-02-13 | 弗·哈夫曼-拉罗切有限公司 | 分泌异源多肽的方法和组合物 |
CN102933600B (zh) * | 2009-11-05 | 2015-11-25 | 弗·哈夫曼-拉罗切有限公司 | 分泌异源多肽的方法和组合物 |
US10227416B2 (en) | 2009-11-05 | 2019-03-12 | Genentech, Inc. | Methods and composition for secretion of heterologous polypeptides |
US10435694B2 (en) | 2014-03-14 | 2019-10-08 | Genentech, Inc. | Methods and compositions for secretion of heterologous polypeptides |
US11390872B2 (en) | 2014-03-14 | 2022-07-19 | Genentech, Inc. | Methods and compositions for secretion of heterologous polypeptides |
US10240207B2 (en) | 2014-03-24 | 2019-03-26 | Genentech, Inc. | Cancer treatment with c-met antagonists and correlation of the latter with HGF expression |
Also Published As
Publication number | Publication date |
---|---|
BR9607464B1 (pt) | 2009-01-13 |
NO973985D0 (no) | 1997-08-29 |
IL117314A0 (en) | 1996-06-18 |
NO324920B1 (no) | 2008-01-07 |
CA2213813A1 (en) | 1996-09-06 |
DK0815246T3 (da) | 2007-08-06 |
JPH10507368A (ja) | 1998-07-21 |
EP0815246A1 (en) | 1998-01-07 |
FI120357B (fi) | 2009-09-30 |
JP3375970B2 (ja) | 2003-02-10 |
ZA961688B (en) | 1997-09-01 |
AU4998496A (en) | 1996-09-18 |
DE69636996D1 (de) | 2007-05-10 |
FI973559A (fi) | 1997-10-29 |
BR9607464A (pt) | 1997-12-23 |
RU2208639C2 (ru) | 2003-07-20 |
WO1996027016A1 (en) | 1996-09-06 |
ATE358181T1 (de) | 2007-04-15 |
DE69636996T2 (de) | 2007-12-06 |
NO973985L (no) | 1997-10-29 |
AU701476B2 (en) | 1999-01-28 |
NZ303619A (en) | 2000-02-28 |
CN1180379A (zh) | 1998-04-29 |
ES2285711T3 (es) | 2007-11-16 |
CA2213813C (en) | 2008-05-27 |
MX9706607A (es) | 1997-11-29 |
EP0815246B1 (en) | 2007-03-28 |
FI973559A0 (fi) | 1997-08-29 |
US5840523A (en) | 1998-11-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1154736C (zh) | 分泌异源多肽的方法和组合物 | |
CN1196792C (zh) | 新型的基于营养缺陷型互补的非抗生素筛选的大肠杆菌宿主/载体系统 | |
CN1208456C (zh) | 体内重组 | |
CN1253574C (zh) | 来自米曲霉的areA基因和其中areA基因已被修饰的真菌 | |
CN1230991A (zh) | 仓鼠EF-1α转录调节DNA | |
CN1203274A (zh) | 用于发酵制备l-半胱氨酸、l-胱氨酸、n-乙酰丝氨酸或四氢噻唑衍生物的微生物和方法 | |
CN1144874C (zh) | 具酶活性的重组羧肽酶b的生产 | |
CN1513057A (zh) | 宿主微生物 | |
CN1110323A (zh) | 新多肽和编码它们的脱氧核糖核酸 | |
CN1258593C (zh) | 腐胺-n-甲基转移酶启动子 | |
CN1265143A (zh) | 通过内源基因活化制备促红细胞生成素 | |
CN1195859C (zh) | 修饰化人源粒细胞-集落刺激因子及其制备方法 | |
CN1269838C (zh) | 用于由大肠杆菌向培养基中分泌来制备Leu-水蛭素的信号序列 | |
CN1916017A (zh) | 生产疏水多肽、蛋白质或肽的方法 | |
CN1224707C (zh) | 白细胞介素-1受体拮抗剂的细胞内同种型 | |
CN1221033A (zh) | 致癌基因或病毒受控表达系统 | |
CN1133594A (zh) | 单纯性疱疹病毒-2ul26基因,衣壳蛋白,免疫测定和蛋白酶抑制剂 | |
CN1309716A (zh) | 包含具重组转录因子结合位点的嵌合启动子的表达系统 | |
CN1639320A (zh) | 冷休克诱导的异源多肽的表达和生产 | |
CN1219883C (zh) | 改造合成的苏云金芽孢杆菌杀虫晶体蛋白基因CrylC* | |
CN1726228A (zh) | 用于检测蛋白质加工的探测蛋白质 | |
CN1720329A (zh) | 来自红球菌属的新表达系统 | |
CN1763203A (zh) | 一种基因重组人巨细胞病毒融合蛋白pp150/MDBP及其制备方法与应用 | |
CN1214041C (zh) | 信号序列捕获方法 | |
CN1788092A (zh) | 构建分泌细菌重组蛋白的前导肽 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CX01 | Expiry of patent term |
Granted publication date: 20040623 |
|
EXPY | Termination of patent right or utility model |