CN1043875A - 新的白细胞介素-2受体特异性免疫球蛋白 - Google Patents

新的白细胞介素-2受体特异性免疫球蛋白 Download PDF

Info

Publication number
CN1043875A
CN1043875A CN89109618A CN89109618A CN1043875A CN 1043875 A CN1043875 A CN 1043875A CN 89109618 A CN89109618 A CN 89109618A CN 89109618 A CN89109618 A CN 89109618A CN 1043875 A CN1043875 A CN 1043875A
Authority
CN
China
Prior art keywords
immunoglobulin
antibody
aminoacid
human
chain
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.)
Granted
Application number
CN89109618A
Other languages
English (en)
Other versions
CN1057013C (zh
Inventor
卡里·L·奎因
哈罗德·E·塞里克
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
PDL Biopharma Inc
Original Assignee
Protein Design Labs Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26966505&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CN1043875(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Protein Design Labs Inc filed Critical Protein Design Labs Inc
Publication of CN1043875A publication Critical patent/CN1043875A/zh
Application granted granted Critical
Publication of CN1057013C publication Critical patent/CN1057013C/zh
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/081—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from DNA viruses
    • C07K16/085—Herpetoviridae, e.g. pseudorabies virus, Epstein-Barr virus
    • C07K16/087—Herpes simplex virus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/081—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from DNA viruses
    • C07K16/085—Herpetoviridae, e.g. pseudorabies virus, Epstein-Barr virus
    • C07K16/088—Varicella-zoster virus
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/249—Interferons
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/461—Igs containing Ig-regions, -domains or -residues form different species
    • C07K16/464—Igs containing CDR-residues from one specie grafted between FR-residues from another
    • C07K16/465—Igs containing CDR-residues from one specie grafted between FR-residues from another with additional modified FR-residues
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—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
    • C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Virology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Diabetes (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Neurology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Pain & Pain Management (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Transplantation (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

与人体IL-2受体特异性反应的类人体免疫球蛋白采用重组DNA技术制备，用于治疗T细胞介导的疾病。

Description

本发明涉及用于开发新的治疗药物的重组DNA与单克隆抗体技术的结合，更具体讲，本发明涉及对人体白细胞介素-2受体特异的非致免疫抗体的制备及其应用。
在哺乳动物中，免疫反应是由两类细胞调节的，这两类细胞可与外来物质即抗原特异地相互作用。这些细胞种类之一的B细胞是产生抗体的。第二类细胞，T-细胞，包括各种细胞亚群，这些细胞亚群在体内可控制B-细胞和各种其它造血细胞（包括T-细胞）的功能。
T-细胞产生这种控制的一种途径是通过产生称为白细胞介素-2（IL-2）的淋巴因子，原称为T-细胞生长因子。IL-2的基本功能是刺激和维持T-细胞。实际上，一些免疫学家认为IL-2可能是整个免疫反应的中心（见，Farrar，J.等，Immunol    Rev.63：129-166（1982），这里作为参考文献）。
IL-2与特异的高亲和性膜受体相互作用来发挥它的生物学作用（Greene，W.等，Progress    in    Hematology    XIV，E.Brown，Ed，Grune和Statton，纽约（1986），283页）。人体IL-2受体是一种复合的多链糖蛋白，其中一个链被称为Tac肽，大小约为55KD（见，Leonard，W.，等，J.Biol.Chem    260：1872（1985），这里作为参考文献）。编码该蛋白的基因已分离出来，并预测为-272个氨基酸的肽，它包括-21个氨基酸的单肽（见，Leonard，W.，等;Nature    311：62611984）。P55    Tac蛋白质的219氨基末端氨基酸明显包括一个细胞外区（见，Leonard，W.，等，Science，230：633-639（1985），这里用作参考文献）。
对人体IL-2受体的结构和功能的许多解释都是由于特异反应性的单克隆抗体的研究速度。具体讲，一种称为抗-Tac的小鼠单克隆抗体（Uchiyama等，J.Immunol.126：1393（1981）已表明IL-2受体可在T-细胞上检测，而且也可用单核巨噬细胞家族的细胞，肝中的星形细胞），皮肤中的郎格罕氏细胞，当然，活化的T细胞也可以。重要的是，局部余下的T细胞，B细胞或循环的巨噬细胞不显示IL-2受体（Herrmann，等，J.Exp.Med.162：1111（1985））。
抗Tac单克隆抗体也已被用来限定需与IL-2相互作用的淋巴细胞功能并已表明了它可抑制各种T细胞功能，这包括在细胞培养中胞毒和抑制基因T淋巴细胞的增殖。基于对抗-Tac和其它抗体的研究，目前的各种疾病都与T细胞对IL-2受体的不正确表达有关，尤其是成人T细胞白血病。
最近发现，IL-2受体是T细胞介异的疾病新的治疗方法的理想目标。已建议将IL-2受体特异性抗体（如抗Tac单克隆抗体）单独使用或用作免疫结合物（例如，与蓖麻子蛋白A，同位素等结合）从而有效地除去带有IL-2受体的细胞。这些试剂理论上可消除与病症有关的表达IL-2受体的白血病细胞，某些B细胞或活化的T细胞，但可保留成熟的正常T细胞和它们的前体以确保能够进行所需的正常T细胞免疫反应。通常大多数其它T细胞特异性药物可基本上杀伤所有外周T细胞，这限制了这些药物的疗效。综上所述，使用对IL-2受体特异的适宜单克隆抗体对于自身免疫疾病，器官移植和由活化T细胞引起的任何不需要的反应具有治疗作用。实际上，已开始用例如，抗-Tac抗体进行临床试验（一般见Waldman，T.，等，Cancer    Res.45：625（1985）和Waldman，T.，Science    232：727-732（1986），这里一起用作参考文献）。
但不幸的是，使用抗-Tac和其它非人体单克隆抗体出现了一些缺点，尤其是在如下面解释的重复治疗方案中。例如，当小鼠单克隆抗体用于人体时，它们不能很好地固定补体并缺乏其它重要免疫球蛋白的功能性特征。
也许更重要的是，抗Tac和其它非人体单克隆抗体含实质伸长的氨基酸序列，当该抗体注射给人类患者时，这些氨基酸序列是致免疫的。大量研究表明，外来抗体注射后，患者对抗体产生的免疫反应是十分强烈的，该免疫反应实际在最初治疗后，基本消除了抗体的治疗作用。而且，尽管可以期望生产出越来越多的治疗各种疾病的不同的小鼠或其它抗原性（对人）的单克隆抗体，但用任何不同的非人体抗体进行第一步和第二步治疗后，甚至用于无关疗法的随后治疗可能也是无效的甚至是危险的。
虽然所谓“嵌合抗体”（例如小鼠可变区与人恒定区连接）的制备已取得一些成功。但仍保留了致免疫性问题。通常采用典型的人体单克隆抗体制备技术生产可与人体IL-2受体（如许多人体抗原）反应的人体免疫球蛋白是十分困难的。类似地，采用重组DNA技术制备所谓“人体属性”的抗体（见，欧洲专利申请公开号，0239400）得到的是不确定的结果，这部分是由于不可预测的结合亲和力。
因此，需要改良形式的对人体IL-2受体特异的类人体免疫球蛋白（在体内它们基本上是非致免疫的），它们可以适用于治疗制剂和其它用途的方式简单而经济地制成。本发明满足了这些和其它需要。
本发明提供了新的用于治疗T细胞介异的人体疾病的组合物，该组合物含类人体免疫球蛋白，它们能特异地阻断人体IL-2与其受体的结合或能结合到人体IL-2受体上的P55 Tac蛋白质上。该免疫球蛋白可能有两对轻链/重链复合物，典型的是至少一对具有包括小鼠互补决定区的链，互补决定区功能性地与人体骨架区片段连接。例如，带或不带其它天然小鼠氨基酸残基的小鼠互补决定区可用来制备类人体抗体，该抗体能以比108M-1更强的亲和力与人体IL-2受体结合。
本发明的包括结合阶段及其其它衍生物的免疫球蛋白可通过各种重组DNA技术，采用转染细胞中的最终表达（优选不灭的真核细胞，如骨髓瘤或杂交瘤细胞）很容易地制备。包括编码类人体免疫球蛋白骨架区的第一序列和编码所要免疫球蛋白互补决定区的第二序列的多核苷酸可合成制备或通过将适宜的cDNA与基因组DNA片段组合来制备。
类人体免疫球蛋白可以基本上纯的形式单独使用或与胞毒剂（如放射性核素，核糖体抑制蛋白或在细胞表面有活性的胞毒剂）复合使用。所有这些化合物都可用于治疗T细胞介导的疾病。类人体免疫球蛋白或它们的复合物可制备成药用剂型，这些剂型依据服药方式而变化。
本发明还提供了研制含1或多个来自供体免疫球蛋白的互补决定区（CDR′S）和来自人体免疫球蛋白骨架区的类人体免疫球蛋白链的新方法，优选的方法包括首先将供体免疫球蛋白的骨架或可变区氨基酸序列与所收集的人体免疫球蛋白链中的相应序列比较，然后从收集物中选择较为同源的序列之一作为人体免疫球蛋白。人体免疫球蛋白或接受体免疫球蛋白序列典型地选自所收集的至少10至20个免疫球蛋白链序列，它们通常与收集的供体免疫球蛋白序列有最高的同源性。人体免疫球蛋白骨架序列典型地与供体免疫球蛋白骨架序列有约65至70%或更高的同源性。供体免疫球蛋白既可是重链也可是轻链（或二者都是），收集的人体免疫球蛋白含同样的链。人体属性的轻链和重链可用来形成完全的人体属性免疫球蛋白或抗体，它们具有两对轻/重链，可带或不带一段或整段的人体恒定区和其它蛋白质。
在本发明的另一个实施方案中，既可与上面的比较步骤相结合也可单独独立出来，在受体免疫球蛋白链中的其它氨基酸可被CDR供体免疫球蛋白链中的氨基酸取代。更具体讲，来自供体免疫球蛋白的相应氨基酸对受体免疫球蛋白的人体骨架氨基酸的进一步选择性的取代可在免疫球蛋白中定位进行：
（a）受体免疫球蛋白的人体骨架区中的氨基酸在人体免疫球蛋白序列中的该位置是少见的，而在供体免疫球蛋白中的相应氨基酸在该位置是常见的;或
（b）该氨基酸与COR之一直接相邻;或
（c）该氨基酸被预测位于三维免疫球蛋白模型中CDR的约3A°之内并能与抗原或人体属性的免疫球蛋白的CDR相互作用。
人体属性的免疫球蛋白链除包括CDR外，典型地包含至少3个来自供体免疫球蛋白的氨基酸，通常至少有一个氨基酸与供体免疫球蛋白的CDR直接相邻。重链和轻链可通过用这三个氨基酸的一或三个位置标准来确定。
当本发明的人体属性重链和轻链结合到完整的抗体中时，它们在人体中基本上是非致免疫的并基本保留了与供体免疫球蛋白一样的对抗原（如含某一抗原决定簇的蛋白质或其它化合物）的亲和力。该亲和力大约为108M-1或更高，并且可以在供体免疫球蛋白对抗原原始亲和力的大约4倍范围内变化。
图的描述
图1.比较抗-Tac重链序列（上线）和Eu重链序列（下线）。对氨基酸采用一字编码。每条线上的第一个氨基酸在左边编码两个序列中的同样氨基酸用线连接。3个CDR下面划线。其它氨基酸位置（指在人体属性的抗Tac重链中使用的抗-Tac氨基酸而不是Eu氨基酸）是由＊表示的。
图2.比较抗Tac轻链序列（上线）和Eu轻链序列（下线）对氨基酸采用单字编码。每条线上的第一个氨基酸在左边编号。在两个序列中相同的氨基酸用线连接。3个CDR下面划线。其它氨基酸位置（指人体属性的抗Tac重链中采用的抗Tac氨基酸而不是Eu氨基酸）用＊表示。
图3.用作人体属性的抗Tac重链可变区基因的基因核苷酸序列。编码蛋白质的部分基因的转译氨基酸序列位于核苷酸序列的下部。基因始端和末端的核苷酸TCTAGA为xbaⅠ位点。成熟的重链序列由氨基酸＃20Q起始。
图4.用作人体属性的抗Tac轻链可变区基因的基因核苷酸序列。编码蛋白质的部分基因的转译氨基酸序列位于核苷酸序列的下部。该基因始端和末端的核苷酸TCTAGA为xbaⅠ位点。成熟的轻链序列由氨基酸＃21D起始。
图5.A.用于合成人体属性抗Tac重链基因的四个寡核苷酸序列，标明5′至3′。
B.寡核苷酸的相关位置。箭头指向每个寡核苷酸的3′方向。
图6.（A）用于合成人体属性抗Tac轻链基因的四个寡核苷酸序列，标有5′至3′。（B）寡核苷酸的相关位置。箭头指向每个寡核苷酸的3′方向。标明Hind    Ⅲ位点在重叠的JFD2和JFD3中的位置。
图7.用于表达人体属性抗Tac重链的质粒pHUGTACl的图解。标明有关的限制位点，将重链的编码区用方框标出。免疫球蛋白（Ig）启动子的转录方向用箭头表示。EH＝重链增强子，HYg＝抗潮霉素基因。
图8.用于表达人体属性抗Tac轻链的质粒pHULTAC的图解。标明相关的限制位点，轻链的编码区用方框标出。Ig启动子的转录方向用箭头表示。
图9.将HUT102和Jurkat细胞用抗Tac抗体和人体属性抗Tac抗体染色，随后分别用带有荧光粉的山羊抗小鼠Ig抗体或山羊抗人体Ig抗体染色标记，对这些染色细胞进行荧光细胞检测。在每个方框图中，当删去第一抗体时，用虚线表示该结果，实线表示含有第一和第二（结合的）抗体时的结果。
图10.（A）HUT102细胞用所示的0-40ng抗Tac染色，随后用生物素化的抗-Tac染色。再后用与藻红蛋白结合的抗生物素蛋白染色，最后进行荧光细胞测量。
（B）HUT102细胞用所示抗体染色，然后用生物素化的抗Tac染色，再用与藻红蛋白结合的抗生物素蛋白染色，最后进行荧光细胞检测。
本发明提供一种可与人T细胞上的IL-2受体特异性反应的类似人的免疫球蛋白。这些免疫球蛋白的结合亲和力至少约为108M-1，较好的是109M-1～1016M-1或更强，它们能够阻止IL-2与人IL-2受体的结合。类似人的免疫球蛋白应具有类似人的结构并可能具有互补性决定区（CDR′S），CDR′S来自免疫球蛋白，特别是小鼠免疫球蛋白，它们可与P55 Tac蛋白质上的抗原决定簇特异性反应。可大量廉价生产本发明的免疫球蛋白，通过各种技术可用这些免疫球蛋白治疗人类患者T细胞介导的疾病。
已知基本的抗体结构单位由四聚体组成。每个四聚体由两个相同的多肽链对组成，每一对都有一条“轻”链（大约25KD）和一条“重”链（大约50-70KD）。每条链的NH2末端开始都有一个主要负责抗原识别，含大约100-110或更多的氨基酸的可变区。每条链的COOH末端都限定一个主要负责效应子功能的恒定区。
可将轻链分为卡巴链或入链。重链则可分为γ，ν，α，δ，或ε，并将抗体的同型分别定义为IgG，IgM，IgD和IgE。在轻链和重链内，可变区和恒定区是通过一个由大约12或更多个氨基酸组成的“J”区连接起来的，重链还包括一个由大约12或更多个氨基酸组成的“D”区。（见，Fundamental    Immuno-logy，Paul，W.，Ed.，第7章，131-166页，Raven    Press，N.Y.（1984），在此列为本文参考文献）。
每一重链/轻链对的可变区都形成抗体结合位点。这些链都具有相同的一般结构，即都具有由三个超可变区连接的相对保存下来的骨架区，也称为CDR′S（见：“Sequences    of    pro-teins    of    Immunological    Interest”，Kabat，E.，et    al.，U.S.Department    of    Health    and    Human    Services，（1983）;and    Chol-thia    and    Lesk，J.Mol.Biol.，196：901-917（1987），在此列为本文参考文献）。来自每对的两条链的CDR′S通过骨架区连成一线，从而结合到特定的抗原决定簇上。
本文所采用的术语“免疫球蛋白”是指一种由一种或多种实际被免疫球蛋白基因编码的多肽组成的蛋白质。被识别的免疫球蛋白基因包括K，λ，α，γ，δ，ε和ν恒定区基因，以及无数免疫球蛋白可变区基因。免疫球蛋白除了抗体以外也可以各种形式存在，例如包括Fv，Fab，和F（ab）2，以及以单链形式存在（例如，Huston，et al.，Proc.Nat.Acad.Sci.U.S.A.85：5879-5883（1988）and Bird，et    al.，Science，242：423-426（1988）在此列为本文参考文献）。（见：Hood，et    al.，“Immunology”，Benjamin，N.Y.，Znd    ed.（1984），and    Hunkapiller    and    Hood，Nature，323：15-16（1986），在此列为本文参考文献）。
嵌合抗体为已通过遗传工程从属于不同物种的免疫球蛋白基因片段构建了其轻链和重链基因的抗体。例如，来自小鼠单克隆抗体的基因的可变（v）片段可与人恒定（c）片段，如γ1和γ3连接。因此典型的治疗用嵌合抗体是一种由来自小鼠抗体的V或抗原结合区和来自人体体的C或效应子区组成的杂交蛋白（例如，A.T.C.C.储存号为CRL 9688的菌株分泌一种抗-Tac嵌合抗体），尽管也可使用其它哺乳动物种。
本文所采用的术语“骨架区”是指在单一物种的不同免疫球蛋白中相对保存下来的免疫球蛋白轻链和重链可变区部分（即不是CDR′S），其定义如所引用的Kabat等人的文章中所述。本文所采用的“类似人的骨架区”是每条现有的链中至少含有大约70或更多个氨基酸残基，特别是75-85或更多个残基，与人免疫球蛋白中的骨架区相同的骨架区。
本文所采用的术语“类似人的免疫球蛋白”是指包含类似人的骨架区且其中任何存在的恒定区是基本上与人免疫球蛋白恒定区同源（即至少大约85-90%，最好是大约95%相同）的免疫球蛋白。因而，除CDR′S可能例外，类似人的免疫球蛋白的所有部分都是基本上与一种或多种天然人免疫球蛋白序列的相应部分同源的。例如，类似人的免疫球蛋白不会包含小鼠可变区/人恒定区嵌合抗体。
本发明还包括选择在类似人的免疫球蛋白链中有限数目的氨基酸的标准，为了增强包含类似人的免疫球蛋白的抗体的亲和力，应选择与在供体而不是受体的那些位置上的氨基酸相同的氨基酸。
本发明部分地基于这样一种模式，即在以前生产类似人的抗体的方法中（例如用小鼠抗体作为CDR′S源）亲和力丧失的两个动因是：
（1）当将小鼠CDR′S与人骨架结合时，骨架中接近于CDR′S的氨基酸变为人的而不是小鼠的。在不打算与理论相结合的情况下，我们认为这些改变了的氨基酸可使CDR′S略微反常，因为它们可产生不同于供体小鼠抗体的静电或疏水力，并且反常的CDR′S不可能象在供体抗体中的CDR′S一样有效地与抗原接触;
（2）同样，在原来小鼠抗体中接近于（但非部分的）CDR′S的氨基酸（即仍为部分骨架），可与有助于亲和力的抗原接触。当将这些抗体变成类似人的抗体时，这些氨基酸丧失，因为全部骨架氨基酸都变成人的了。
为了避免这些问题，和生产对目的抗原具有很强亲和力的类似人的抗体，本发明使用下列四种标准来设计类似人的免疫球蛋白。这些标准可单个使用，必要时也可结合使用，以达到所需亲和力或其它特征。
标准Ⅰ：用来自与待变成类似人的供体免疫球蛋白异常同源的特定人免疫球蛋白的骨架，或用来自许多人抗体的同感骨架作为受体。例如，小鼠重（或轻）链可变区序列与人重（或轻）链可变区在数据库（例如，National    Biomedical    Research    Foundation    Protein    Identification    Resource中的比较表明人类不同区的同源程度变化范围很大，一般从大约40%到大约60-70%。选择与供体免疫球蛋白重（轻）链可变区最为同源的人重（轻）链可变区之一作为受体免疫球蛋白，只有少数氨基酸会随着从供体免疫球蛋白变为类似人的免疫球蛋白而改变。因此，并且仍在不打算与理论相结合的情况下，认为有一个在其构象异常的CDR′S附近改变一个氨基酸的较小的机会。而且，包含类似人的免疫球蛋白链的类似人的抗体的精确轮廓可能更接近供体抗体的形状，这也减少了使CDR′S反常的机会。
一般说来，应在至少有大约10-20条不同的人重链的代表性收集物中选择3-5个最为同源的重链可变区序列之一作为受体以提供重链骨架，轻链与之类似。最好使用1-3个最为同源的可变区之一。所选受体免疫球蛋白链最好在骨架区至少约65%与供体免疫球蛋白同源。
不管如何选择受体免疫球蛋白，都可通过在类似人的免疫球蛋白链的骨架中选择少量与在供体而不是受体的那些位置上的氨基酸相同的氨基酸而获得较高的亲和力。下列标准限定什么氨基酸可如此选择。较好的是，在符合这些标准之一的大多数或全部氨基酸位置上，实际上应选择供体氨基酸。
标准Ⅱ：如果在人受体免疫球蛋白骨架中的某一氨基酸是异常的（即，“稀有的”，如本文所用的，它表明在代表性数据库中并不大于10%的人重（轻）链V区序列的那个位置上出现的氨基酸），并且如果在那个位置上的供体氨基酸对人序列是典型的（即，“普通的”，如本文所用的，它表明在代表性数据库中至少约25%序列上出现的氨基酸），则可选择供体氨基酸而不是受体氨基酸。这个标准有助于确保人骨架中的某一典型氨基酸不破坏抗体结构。而且，通过用来自对人抗体恰好是典型的供体抗体的氨基酸取代异常氨基酸，可使类似人的抗体的免疫原性变小。
标准Ⅲ：在类似人的免疫球蛋白链中与3个CDR′S直接相邻的位置上，可选择供体氨基酸而不是受体氨基酸。这些氨基酸极有可能与CDR′S中的氨基酸相互作用，若从受体中选择，则会使供体CDR′S反常并减小亲和力。而且，相邻的氨基酸可直接与抗原相互作用（Amit    et    al.Science    233，747-753（1986），在此列为本文参考文献）并且从供体中选择这些氨基酸可利于保持所有抗原在原始抗体中提供亲和力的接触。
标准Ⅳ：一个典型的原始供体抗体的三维模型显示出某些CDR′S外的氨基酸与CDR′S接近并具有通过氢键、范德华力、疏水作用等与CDR′S中的氨基酸相互作用的良好可能性。在那些氨基酸位置上，可选择供体氨基酸而不是受体免疫球蛋白氨基酸。符合这一标准的氨基酸一般应在CDR′S中某些位点的大约3埃单位内具有一个侧链原子并且必须含有能够借助所建立的化学力（如上面所列举的）与CDR原子相互作用的原子。建立象抗体这样的蛋白质模型的计算机程序一般可以找到并为本领域技术人员熟知的（见，Loew    et    al.Int.J.Quant.Chem.，Quant.Biol.Symp.，15：55-66（1988）;Bruccoleri    et    al.，Nature，335，564-568（1988）;Chothia    et    al.，Science，233：755-758（1986），所有这些都列为本文参考文献）。这些参考文献不构成部分发明。实际上，因为所有抗体都具有相似的结构，所以必要的话可以采用已知抗体的结构，这可从Brookhaven蛋白质资料库中得到，作为其它抗体的大致模型。可以使用商业上可得到的计算机程序在计算机监示器上显示这些模型，计算原子间的距离，和估计不同氨基酸相互作用的可能性（见，Ferrin    et    al.，J.Mol.Graphics，6：13-27（1988））。
类似人的抗体一般至少具有三个优于小鼠或在某些情况下优于用于人类治疗的嵌合抗体的潜在优点：
1）因为效应子部分是人，所以它可与人免疫系统的其它部分更好地相互作用（例如，通过补体依赖性细胞毒性（CDC）或抗体依赖性细胞毒性（ADCC）更有效地破坏靶细胞）。
2）人免疫系统不应将类似人的抗体的骨架或恒定区识别为补来物，因此对这种注射用抗体的抗体反应应小于对全部外源小鼠抗体或部分外源嵌合抗体的抗体反应。
3）据报导注射用小鼠抗体在人循环中的半衰期比正常抗体的半衰期短得多（D.Shaw    et    al.，J.Immunol.，138：4534-4538（1987））。注射用类似人的抗体可能具有与天然存在的人抗体更加类似的半衰期，因而使得所给的常用剂量少而低。
一方面，本发明涉及编码重链和/或轻链CDR′S的重组DNA片段，CDR′S来自能与人IL-2受体上的所需抗原决定簇结合的免疫球蛋白，例如抗Tac单克隆抗体。编码这些区的DNA片段将与编码合适的类似人的骨架区的DNA片段连接。图1和图2分别给出了优选的DNA序列，它们在表达时编码含有抗Tac重链和轻链超可变区（具有类似人的骨架区）的多肽链。由于密码子简并性和非关键氨基酸取代，其它DNA序列可容易地取代那些序列，如下所述。
DNA片段一般还应包括一个可操作地连接到类似人的抗体编码序列上的表达控制DNA序列，包括自然联合或异源启动子区。表达控制序列最好是在载体中能够转化或转染真核宿主细胞的真核启动子系统，但也可使用原核宿主的控制序列。一旦载体已插入到合适的宿主中，就可在适合于核苷酸序列高水平表达的条件下供养宿主，根据需要，可收集并纯化轻链，重链，轻/重链二聚体或完整抗体，结合片段或其它免疫球蛋白形式。
可按照众所周知的方法从各种人细胞，但最好是不灭的B细胞中分离人恒定区DNA序列（见，Kabat    op.Cit.和Wp87/02671）。同样可从能够与人IL-2受体结合的单克隆抗体中得到产生本发明免疫球蛋白的CDR′S，该CDR′S来源于任何合适的哺乳动物（包括小鼠，大鼠，兔子）或能够通过众所周知的方法产生抗体的其它脊椎动物。DNA序列合适的来源细胞和用于免疫球蛋白表达和分泌的宿主细胞可从许多地方得到，例如美国典型培养物保藏中心（“Catalogue时Cell    Lines    and    Hybridomas，”Fifth    edition（1985）Rockville，Maryland，U.S.A.，在此列为本文参考文献）。
除了本文具体描述的类似人的免疫球蛋白以外，可利用各种本领域技术人员熟知的重组DNA技术设计并生产其它“基本同源的”改良免疫球蛋白。例如，从图3和图4的序列看，骨架区可在一级结构水平变化，如几个氨基酸被取代，末端或中间加入或删除几个氨基酸等等。而且，可单独或结合使用各种不同的人骨架区作为本发明类似人的免疫球蛋白的基础。一般说来，可以通过各种众所周知的技术，如位点针对性诱变（见，Gillman    and    Smith，Gene    8：81-97（1979）和Roberts，S.et    al.Nature    328：731-734（1987），这两篇文章均列为本文参考文献）容易地完成基因的修饰。
此外，可以生产只含一部分抗体一级结构的多肽片段，该片段具有一种或多种免疫球蛋白活性（例如，补体结合活性）。还因为象许多基因一样，免疫球蛋白相关基因含有独立的功能区，每个功能区都具有一种或多种截然不同的生物学活性，可将这些基因与来自其它基因的功能区融合（如，酶，见1987年12月15日提交的共同转让的U.S.S.N.132，387，在此列为本文参考文献）以生产具有新特性的融合蛋白（例如免疫毒素）。
能够最终表达所需类似人的抗体的本发明的核酸序列可从各种不同的多核苷酸（基因组或CDNA，RNA，合成寡核甘酸等）和成分（如V.J.D，和C区），以及通过各种不同的技术制成。连接合适的基因组序列是目前最常用的生产方法，但也可利用CDNA序列（见，欧洲专利公开0239400号和Reichmann，L.，et    al.，Nature    332：323-327（1988），这两篇文章均列为本文参考文献）。
如前所述，当DNA序列被可操作地连接到（即定位以确保起作用的）表达控制序列上以后，它将在宿主中得以表达。这些表达载体一般可作为游离基团或作为宿主染色体DNA的一个整合部分在宿主体内复制。表达载体通常含有选择标记物，例如四环素或新霉素，以便检测那些用所需DNA序列转化的细胞（见，例如美国专利4，704，362，在此列为本文参考文献）。
大肠杆菌是一种特别适用于克隆本发明的DNA序列的原核宿主。其它适用的微生物宿主包括杆菌，例如枯草杆菌，和其它肠道细菌属，例如沙门氏菌属，沙雷氏菌属，及各种假单胞菌属的菌种。在这些原核宿主中，人们也可以制造表达载体，该载体一般应含有与宿主细胞一致的表达控制序列（如复制起点）。此外，应具有一定数量的各种众所周知的启动子，例如乳糖启动子系统，色氨酸（trp）启动子系统，B-内酰胺酶启动子系统，或来自λ噬菌体的启动子系统。这些启动子将控制表达，有时也可与操纵子序列一起控制表达，并具有用于开始并完成转录和转译的核糖体结合位点序列等。
也可用其它微生物，如酵母进行表达。酵母属是理想的宿主，其具有含表达控制序列的合适载体，例如启动子，包括3-磷酸甘油酸激酶或其它糖酵解酶，和复制起点，终止序列等。
除微生物之外，也可用哺乳动物组织细胞培养物表达和生产本发明的多肽（见，Winnacker，“From    Genes    to    Clones，”VCH    Publishers，N.Y.，N.Y.（1987），在此列为本文参考文献），真核细胞是最为理想的，因为在本领域中已培育了许多能够分泌完整免疫球蛋白的合适的宿主细胞系，包括CHO细胞系，各种COS细胞系，Hela细胞，骨髓瘤细胞系等，但较好的是转化的B细胞或杂交瘤。这些细胞的表达载体可包括表达控制序列，例如复制起点，启动子，增强子（Queen，C.，et    al.，Immunol.Rev.89：49-68（1986），在此列为本文参考文献），必要的加工信息位点，例如核糖体结合位点，RNA拼接位点，多聚腺苷酸化位点，和转录终止子序列。优选的表达控制序列是得自免疫球蛋白基因，SV40，腺病毒，牛乳头状瘤病毒等的启动子。
含有感兴趣的DNA片段（如重链和轻链编码序列和表达控制序列）的载体可通过众所周知的方法被转移到宿主细胞中，所用方法依宿主细胞类型的不同而改变。例如，对原核细胞通常采用氯化钙转染而对其它细胞宿主可采用磷酸钙处理或电击。（见，Maniatis，et    al.，Mclecular    Cloning：A    Laboratory    Manual，Cold    Spring    Harbor    Press，（1982），在此列为本文参考文献。）
表达后，可按照本领域的标准方法，包括硫酸铵沉淀，亲和柱，柱层析，凝胶电泳等纯化整个抗体，其二聚体，轻链和重链，或本发明的其它免疫球蛋白形式（见，Scopes，R.，Protein    Purification，Springer-Verlag，N.Y.（1982））。为了药用，至少约90-95%同源的基本上纯的免疫球蛋白是较好的，98-99%或更多同源性最好。一旦部分纯化或按要求纯化到同源，则可在治疗上（包括体外）或在显象和演示测定方法，免疫荧光染色等方面采用这些多肽（见，Immunolo-gical    Methods，Vols，Ⅰ  and    Ⅱ，Lefkovits    and    Pernis，eds.，Academic    Press，New    York，N.Y.（1979    and    1981））。
本发明的抗体可分别用于治疗T细胞介导的病症。一般说来，在鉴别出与疾病相关的细胞带有IL-2受体时，能够阻止IL-2与人IL-2受体结合的类似人的抗体是适宜的（见，U.S.S.N.085，707，题为“Treating    Human    Malign-ancies    and    Disorders，”在此列为本文参考文献）。
例如适于治疗的典型病症包括移植病毒宿主疾病和在经历器官移植（如心，肺，肾，肝等）的患者中移植排斥。其它疾病包括自身免疫疾病，如I型糖尿病，多发性硬化，类风湿性关节炎，系统性红斑狼疮，和重症肌无力。
本发明的类似人的抗体也可与其它抗体，特别是可与在引起疾病细胞上的其它标记物反应的人单克隆抗体结合起来使用。例如，适宜的T细胞标记物可包括那些聚集到所谓“分化丛”（“Clusters    of    Differentiation”）中的标记物，“分化丛”是由First    International    Leukocyte    Different-iation    Workshop命名的（Leukocyte    Typing，Bernard，et    al.，Eds.，Springer-Verlag    N.Y.（1984），在此列本文参考文献）。
这些抗体也可用作单独给药的组合物，这些组合物与化学治疗剂或免疫抑制剂一起给药。这些药剂一般包括环孢多肽A或嘌呤类似物（如，甲氨蝶呤，6-巯基嘌呤等），但也可利用许多本领域技术人员熟知的其它药剂（如环磷酰胺，泼尼松等）。
本发明的一个较好药用组合物包括将主题抗体用于免疫毒素，免疫毒素的特征在于其两个组分，且主要用于在体外或体内杀死所选择的细胞。其成分之一为细胞毒性剂。当它被吸附或吸收时通常使细胞致死。已知为“传递载体”的第二个成分负责将毒性剂传递至特定的细胞类型，如包括癌细胞在内的细胞。这两种成分通常是按各种熟知的化学方法中的任何一种将其化学结合在一起。例如，当细胞毒性剂为一蛋白质，第二成分为一完整的免疫球蛋白时，可利用异双官能交联剂如SPDP、碳化二亚胺、戊二醛等将它们连接在一起。各种免疫毒素的生产方法是现有技术中熟知的，例如可从下处查到：“Monoclonal    Antibody-Toxin    Conjugates：Aiming    the    Magic    Bullet，”Thorpe等，Monoclonal    Antibodies    in    Clinical    Medicine，Academic    Press，168-190页（1982），该文章在此引用以作参考。
各种细胞毒性剂均适用于免疫毒素，细胞毒性剂可包括：放射性核素，如碘-131、钇-90、铼-188和铋-212;各种化学疗剂，如长春花碱酰胺、氨甲蝶呤、阿霉素和顺氯氨铂;以及细胞毒性蛋白，如商陆抗病毒蛋白、假单胞菌外毒素A、蓖麻蛋白、白喉毒素、蓖麻蛋白A链等核蛋白体抑制蛋白，或在细胞表面具有活性的试剂，如磷脂酶（如磷脂酶C）〔一般见，Commonly    assigned    U.S.S.N.07/290，968    filed    on    December    28，1988），“Chimeric    Texins”，Olsnes    and    phil，pharmac.Ther.25：355-381（1982），以及“Monoclonal    Antibodies    for    Cancer    Detection    and    Therapy，”eds，Baldwin    and    Byers，pp159-179，224-226，Academic    Press（1985），所有这些文献均在此引用以作参考〕。
免疫毒素的传递成分包括本发明的类似人体免疫球蛋白。最好使用完整的免疫球蛋白或其结合片段，如Fab，免疫毒素中的抗体一般为同型的人IgM或IgG，但根据需要也可使用其它哺乳动物的恒定区。
本发明的类似人体抗体和其药用组合物主要用于非肠道给药，即皮下肌内或静脉内给药。用于非肠道给药的组合物通常包括溶解在一种可接受载体（优选水溶性载体）内的抗体溶液或其鸡尾酒液。各种水溶性载体，如水、缓冲水、0.4%盐水、0.3%甘氨酸等，均可使用。这些溶液无菌，且一般无颗粒物。可采用常规的、熟知的灭菌技术对这些组合物进行灭菌。组合物中也可含有达到近似生理条件所需要的可作药用的辅助剂，如pH调节和缓冲剂、毒性调节剂等，例如乙酸钠、氯化钠、氯化钾、氯化钙、乳酸钠等。这些配方中抗体的浓度可广泛改变，即从小于约0.5%（重量），通常在或至少约1%，直至大于15%或20%，这主要取决于液体体积、粘度以及所选择的具体服用方式。
因此，用于肌内注射的一种典型药用组合物可含有1ml无菌的缓冲水及50mg抗体。用于静脉内输液的一种典型组合物可含有250ml无菌Ringer氏溶及150mg抗体，非肠道给药的组合物的实际制备方法是本领域熟练技术人员所知道的，或是明显的。其详细情况可见Remington′s    Pharmaceutical    Science，15th    ed.，Mack    Publishing    Company，Easton，Pennsylvania（1980），该文章在此引用以作参考。
本发明的抗体可被冷冻保藏，且在使用前在合适的载体上被重新组配。这一技术已被证明对于常规的免疫球蛋白是有效的。现有技术中已知的冷冻及重建技术均可使用。本领域技术人员知道，冷冻和重新组配可导致抗体活性的不同程度丧失（例如，使用常规的系统的免疫球蛋白，IgM抗体具有比IgG抗体更大程度的活性丧失），因此必须对用量进行调节以补偿损失。
可服用含有本发明类似人抗体或其混合物的组合物以用于预防或治疗。对于治疗用途，是给已患有疾病的病人服用足以治疗或至少部分抑制该疾病量的组合物。足以达到这一目的的量被称作“有效治疗剂量”，该用途的有效量取决于感染的程度以及患者自身免疫系统的所处的状态，但一般为每剂量约1-200mg抗体，更常用的剂量为5-25mg/患者。必须注意，本发明的物质一般可在严重的疾病状态（即危及生命或潜在的危及生命）情况下使用。在这些情况下，为了将过量物质减少至最低程度以及使“外源物质”排斥反应的可能性降低（通过本发明的类似人抗体达到），主治医师可能且感到有必要给患者服用实际过量的这些抗体。
对于预防目的，是给未处在疾病状态的患者服用含有本发明抗体或其混合物的组合物，以增强患者的抵抗力。这种用量被定义为“预防有效剂量”。对于这一用途，精确的用途同样取决于患者的健康状况及总体免疫水平，但一般为每剂量0.1-25mg，尤其是每个患者0.5-2.5mg，一个较好的预防应用就是防止肾移植排斥反应。
组合物的单个或复合服法可按主治医师所选定的剂量和方式进行。在任何情况下，药用配方应提供足以有效治疗患者的定量抗体。
本发明的类似人抗体可进一步在体外找到各种用途。例如，该抗体可用于T-细胞分型、用于分离带有特定的IL-2受体或该受体的片段的细胞，用于制备疫苗等。
用于诊断目的，该抗体可被标记或不被标记。未标记的抗体可与其它的标记抗体（第二抗体）结合使用，该抗体与类似人体抗体反应，如针对于人免疫球蛋白恒定区的特异抗体。或者，可直接标记抗体。各种标记物均可使用。如放射性核素、荧光物质、酶、酶底物、酶辅助因子、酶抑制剂、配位体（尤其是半抗原）等。各种免疫检测法均可得到。且对于本领域熟练技术人员来说均是熟知的。
药盒也可与主抗体结合使用，以保护或检测细胞活性，或检测所选择的抗原的存在。因此，一般是以单独冷冻在容器中或与特异地针对所需细胞类型的补助抗体一起冷冻在容器中的形式提供本发明的主抗体组合物。与一标记物或毒素连接的抗体或未连接的抗体包括在药盒中，药盒中还带有缓冲液，如Tris、磷酸盐、碳酸盐等，稳定剂，杀生物剂，惰性蛋白如血清白蛋白等，以及一份使用说明。这些物质的含量一般低于活性抗体重量的5%，且一般总重量至少约为抗体浓度的0.001%（wt）。该药盒中通常还需要包括一种膨胀剂或赋形剂，以稀释活性成分，其中赋形剂可以占组合物总重量的1-99%的量存在。当使用能够与嵌合抗体结合的第二抗体进行检测时，它通常被装在一个单独的瓶中。第二抗体通常与一标记物连接，且按上述抗体配方的类似方式配剂。
下面的例子是用于说明而不是进行限定。
实验
类似人轻链和重链基因的设计
利用人抗体Eu的序列（Sequences    of    Proteins    of    lmmunological    lnterest，Kabat，E.，等，U.S.Dept    of    Health    and    Human    Services    1983）为类似人抗体提供构架，因为抗-Tac重链的氨基酸序列与该抗体重链的同源性要超过National    Biomedical    Foundation    Protein    Identification    Resource中的任何其它重链序列。
为了选择类似人重链的序列，将抗-Tac重链序列（see，commonly    assigned    U.S.S.N.′s    186，862和223，037，在此引用以作参考）与Eu重链序列匹配（图1），在每一位置，选择Eu氨基酸用于类似人的序列，除非该位置落入以下类别，在此情况下选择抗-Tac氨基酸：
（1）该位置落入互补决定区（CDR），如Kabat等所述。（氨基酸31-35，50-66，99-106）;
（2）对于在该位置的人重链Eu氨基酸异常，而对于该位置的人重链抗-Tac氨基酸正常（氨基酸27，93，95，98，107-109，111）
（3）在抗-Tac重链的氨基酸序列中，该位置紧邻CDR（氨基酸30和67）;
（4）抗-Tac抗体的三维模型指出该氨基酸结构上靠近抗原结合区（氨基酸48和68）。
有些氨基酸落入一个以上的上述类型，但只在其中之一列出。
为了选择类似人轻链的序列，将抗-Tac轻链序列与Eu轻链序列匹配（图2）。在每一位置选择Eu氨基酸，除非该位置又落入类型1-4之一（在分类定义中用轻链取代重链）：
（1）CDRs（氨基酸24-34，50-56，89-97）。
（2）比Eu更典型的抗-Tac氨基酸（氨基酸48和63）
（3）邻近CDRs（无氨基酸;在所有这些位置Eu和抗-Tac已经相同）。
（4）可能三维接近结合区（氨基酸60）。
所选择的重链（图3）和轻链（图4）基因的实际核苷酸序列如下：
（1）编码如上所述的选择氨基酸序列的核苷酸序列。？
（2）这些编码序列的5′端，该核苷酸序列编码前导（信号）序列，即抗体MOPC63的轻链前导序列和抗体PCH108A的重链前导序列（Kabat等）。选择这些前导序列作为抗体的代表。
（3）3′端编码序列，该核苷酸序列为鼠轻链J5片段和鼠重链J2片段后面的序列，它们为抗-Tac序列的一部分。之所以包括这些序列是因为它们含有拼接供体信号。
（4）在该序列的每一端是-xba    Ⅰ位点，它能够在xba    Ⅰ位点切割，且将一载体克隆进xbaⅠ位点。
类似人轻链和重链基因的构建
为合成重链，利用Applied    Biosystems    380BDNA合成仪合成4个寡核苷酸HES12，HES13，HES14和HES15。其中有两种寡核苷酸为每条重链的一部分，且每种寡核苷酸与其下一个重叠约20个核苷酸，以使退火（图5B）。这些寡核苷酸一起包括了整个类似人重链（图3），另外还在每一末端带有额外核苷酸，以允许位xba    Ⅰ位点进行切割。用聚丙烯酰胺凝胶纯化这些寡核苷酸。
按标准方法（见Maniatis等的文章），利用ATP和T4多核苷酸激酶将每种寡核苷酸磷酸化。为了让磷酸化的寡核苷酸退火，将每种寡核甘酸以3.75μm的浓度与40μl    TA（33mM    Tris乙酸，pH7.9，66mM乙酸钾，10mM乙酸镁）一起悬浮，于95℃加热4分钟，然后缓慢冷却至4℃。为了通过合成寡核苷酸的反义链来从寡核苷酸合成完整基因，加进最终体积为100μl的以下成分：
10μl退火的寡核苷酸
0.16mM的每种脱氧核糖核苷酸
0.5mM    ATP
0.5mM    DTT
100μg/ml    BSA
3.5μg/ml    T4g43蛋白（DNA多聚酶）
25μg/ml    T4g44/62蛋白（多聚酶辅助蛋白）
25μg/mL    45蛋白（多聚酶辅助蛋白）
于37℃将该混合物保温30分钟。然后加入10μT4DNA连接酶，于37℃继续保温30分钟。于70℃将反应保温15分钟使多聚酶和连接酶灭活。为了用xba    Ⅰ消化基因，向反应物中加入50μl2XTA（含有200μg/ml    BSA和1mM    DTT）、43μl水及5μl的50μ    xba    Ⅰ。37℃保温3小时后进行凝胶电泳。从凝胶上纯化出431bp    xba    Ⅰ片段，利用标准方法将其克隆进质粒PUc19的xba    Ⅰ位点。纯化四个质粒分离物，利用双脱氧法测定其序列。其中之一具有正确的序列（图3）。
为了合成轻链，合成四个寡核苷酸JFD1，JFD2，JFD3和JFD4（图6A）。其中有两个寡核苷酸为每条轻链的一部分，且每个寡核苷酸与其下一个重叠约20个核苷酸，以便能够退火（图6B）。这些寡核苷酸一起包括了整个类似人的轻链（图4），并在每一末端还带有几个额外的核苷酸，以便允许在xbaⅠ位点进行切割。用聚丙烯酰胺凝胶纯化寡核苷酸。
分两部分从这些寡核苷酸合成轻链基因，将JFD1和JFD2各0.5μg结合在20μl序列酶缓冲液（40mM    Tris-HCl，pH7.5，20mM氯化镁，50mM氯化钠）中，于70℃加热3分钟，然后慢慢冷至23℃，以便让寡核苷酸退火。JFD3和JFD4按同样方式处理，向每一反应中加入10mM    DTT和0.5mM每种脱氧核糖核苷酸，及6.5μ序列酶（US    Biochemicals），至最终体积为24μl。然后于37℃保温1小时，以合成寡核苷酸的反义链。向每一反应物中加入xba    Ⅰ和Hind    Ⅲ以消化DNA（在JFD2和JFD3重叠的部分有一个Hird    Ⅲ位点，因此在每种合成的DNA中也有一个Hind    Ⅲ位点;图6B）。将反应物进行聚丙烯酰胺凝胶电泳，纯化xba    Ⅰ-Hind    Ⅲ片段，且按标准方法将其克隆至pUC18。利用双脱氧法分析每个片段的几个质粒分离物的序列，选择正确的分离物。
表达类似人轻链和重链的质粒的构建
从已插入重链xba    Ⅰ片段的pUC19质粒中分离出重链xba    Ⅰ片段，利用标准方法将其按正确方向插入载体pVν1（see，Commonly    assigned    U.S.S.N.223，037）的xba    Ⅰ位点，产生质粒pHuGTAC1（图7）。当将该质粒转染进合适的宿主细胞时它能够高水平地表达完整的重链。
从已插入轻链xba    Ⅰ-Hind    Ⅲ片段的pUC18质粒中分离出轻链xba    Ⅰ-Hind    Ⅲ片段，用xba    Ⅰ切割载体质粒pVk1（See，Commonly    assigned    U.S.S.N.223，037），去磷酸化，按标准方法与两个片段连接。所需反应产物具有环状形式：载体-xba    Ⅰ-片段1-Hind    Ⅲ-片段2-xba    Ⅰ-载体。利用限制图谱和序列来分析几个质粒分离物。选择具有以上形式的分离物。因此，该质粒pHuLTAC（图8）含有完整的类似人轻链（图4），当转染进适当的宿主细胞时，该质粒将高水平地表达轻链。
类似人抗体的合成及亲和力
将质粒pHuGTAC1和pHULTAC转染进鼠Sp2/0细胞，根据对霉酚酸和/或潮霉素的抗性按标准方法选择整合了质粒的细胞，该抗性由质粒上的gpt和hyg基因提供（图7，8），为了检验这些细胞分泌与IL-2受体结合的抗体，将细胞上清液与已知表达IL-2受体的HUT-102细胞一起保温。冲洗之后，将细胞与结合荧光素的山羊抗人抗体一起保温，冲洗，于FACSCAN细胞荧光仪上分析荧光。结果（图9A）清楚地表明，类似人抗体与这些细胞结合，不与不表达IL-2受体的Jurkat    F细胞（图9D）结合。作为对照，也使用原始鼠抗-Tac抗体给这些细胞染色（图9B，C），产生类似结果。
为了进一步实验，将产生类似人抗体的细胞注射进小鼠，收集产生的腹水，通过山羊抗人免疫球蛋白抗体亲和柱将类似人的抗体纯化至基本均质〔该亲和柱按标准方法在Affigel-10支持物（Bco-Rad Laboratories，Inc.，Richimond CA）上制备〕。为了测定类似人抗体相对于原始抗Tac抗体的亲和性，进行竞争性结合实验。将约5×105HUT-102细胞与已知量（10-40ng）的抗-Tac抗体和类似人的抗-Tac抗体一起于4℃保温10分钟。然后向细胞中加入100ng生物素化的抗-Tac，于4℃保温30分钟。该抗-Tac的量已被预先测定，它足以饱和细胞上的结合位点，但并不大量过量。然后用含有0.1%叠氮化钠的磷酸盐缓冲盐水2ml洗涤细胞两次。将细胞与250ng与藻红素连接的抗生物素蛋白一起于4℃保温30分钟，该抗生物素蛋白与已经结合于细胞上的生物素化的抗-Tac结合。如上法再次洗涤细胞，固定在含1%仲甲醛的PBS中，于FACSCAN细胞荧光仪上分析荧光。
在第一步通过增加作为竞争物的抗-Tac抗体的量（10-40ng）来减少能在第二步与细胞结合的生物素化的抗-Tac的量，从而减少了在最后一步结合的与藻红素连接的抗生物素蛋白的量，减少了荧光（图10A）。用等量（20ng）的抗-Tac和类似人抗-Tac作为竞争物使荧光减少约相同程度（图10B）。它表明这些抗体具有近似相同的亲和性。因为如果一个的亲和性更大，它将更有效地与生物素化的抗-Tac竞争，从而使荧光更加减少。
类似人的抗体的生物学性质
为了有效地用于治疗人类疾病，类似人的抗体应能够破坏体内表达IL-2受体的T-细胞，该抗体破坏靶细胞的机制之一就是抗体依赖的细胞介导的细胞毒性，简称为ADCC（Fundamental Immunology，Paul，W.，Ed.，Raven Press，New York（1984），at Pg.691），其中抗体在靶细胞与效应细胞（如巨噬细胞，它能够溶解靶细胞）之间形成一桥。为了测定类似人的抗体及原始鼠抗-Tac抗体是否能介导ADCC，利用标准方法进行铬释放检测。具体地说，就是将表达IL-2受体的人白血病HUT-102细胞与51Cr一起保温以让细胞吸收这一放射性核素。然后将HUT-102细胞与过量的抗-Tac或类似人抗-Tac抗体一起保温。再将HUT-102细胞与30∶1或100∶1的效应细胞一起保温4小时，该效应细胞为正常纯化的人外周血单核细胞，它已通过与人重组IL-2一起保温20小时而被活化。测定释放的51Cr（它表明HUT-102靶细胞溶解），且减去本底。（表1）。结果表明，在每种比率的效应细胞中，抗-Tac不溶解大量的靶细胞（低于5%），而类似人的抗体则大量溶解靶细胞（高于20%）。因此，在治疗T-细胞白血病或其它T-细胞介导的疾病方面，类似人的抗体比原始小鼠抗体更加有效。
表1
ADCC后释放的51Cr百分数
效应细胞与靶细胞比值
抗体    30∶1    100∶1
抗-Tac    4%    ＜1%
类似人的抗-Tac    24%    23%
从上述可知，本发明类似人的免疫球蛋白比其它人IL-2受体专一的抗体具有许多优点。当抗-Tac鼠单克隆抗体相比较，本发明的类似人的免疫球蛋白可更经济地生产，且实际含有较少的外源氨基酸序列。这种在注射进病人体内后减少抗原性的可能代表了明显的治疗改进。
为了便于清楚和理解，虽然通过说明和实施例对本发明进行了叙述。但很明显，某些改动和改进都在所附权利要求的保护范围之内。

Claims (21)

1、一种含基本上纯的能与P55Tac蛋白质特异性反应的类人体免疫球蛋白的组合物。
2、根据权利要求1的组合物，其中免疫球蛋白包括两对轻/重链二聚物，每条链包括可变区和恒定区。
3、一种含基本上纯的能抑制人体白细胞介素-2（IL-2）与人体IL-2受体结合的类人体免疫球蛋白的组合物。
4、根据权利要求1的组合物，其中该免疫球蛋白对人体IL-2受体显示出约108M-1或更强的结合亲和力。
5、根据权利要求1的组合物，其中该免疫球蛋白包括来自一免疫球蛋白的互补决定区和来自至少一种不同免疫球蛋白的骨架区。
6、一种重组免疫球蛋白组合物，该组合物含类人体免疫球蛋白骨架和与该骨架无天然联系的一或多个外来互补决定区，其中该免疫球蛋白能与人体白细胞介素-2受体结合。
7、根据权利要求6的组合物，其中该免疫球蛋白是同型的IgG1免疫球蛋白。
8、根据权利要求6的组合物，其中该成熟的轻和重可变区蛋白质序列基本上与图3和图4中的序列同源。
9、一种含两对轻/重链二聚物并能与人体白细胞介素-2受体上的抗原决定簇特异性反应的类人体免疫球蛋白，其亲和力至少为108M-1所说的轻和重链包括互补决定区（CDR′S）和类人体骨架区，其中CDR′S来自不同免疫球蛋白分子而不是骨架区。
10、根据权利要求9的免疫球蛋白，其能阻断白细胞介素-2（IL-2）与人体IL-2受体的结合。
11、一种能与人体白细胞介素-2受体结合的人体属性的免疫球蛋白，该免疫球蛋白包括一或多个来自类人体骨架中抗Tac抗体的互补决定区（CDR′S），其中，类人体骨架区包括至少一个选自抗Tac抗体的氨基酸。
12、根据权利要求11的人体属性免疫球蛋白，其具有图3所示的成熟重链可变序列和图4所示的成熟轻链序列。
13、根据权利要求11的人体属性免疫球蛋白，其中来自抗Tac抗体的其它氨基酸与CDR直接相邻。
14、一种治疗人类患者T细胞介导的疾病的方法，该方法包括给患者服用有效治疗剂量的权利要求1的免疫球蛋白。
15、根据权利要求1的免疫球蛋白，其可在骨髓瘤或杂交瘤细胞中产生。
16、一种多核苷酸分子，包括编码类人体免疫球蛋白骨架区的第一序列和编码1或多个小鼠免疫球蛋白互补决定区的第二序列，其中表达后，该多核苷酸编码免疫球蛋白，该免疫球蛋白与P55Tac蛋白质特异性反应并能阻断白细胞介素-2（IL-2）与人体T细胞上IL-2受体的结合。
17、一种用权利要求16的多核苷酸转染的细胞系。
18、设计一人体属性免疫球蛋白（Ig）链的方法，该链含1或多个来自供体Ig的互补决定区（CDR′S）和来自人体Ig的骨架区，所说方法包括：将供体Ig的骨架或可变区的氨基酸序列与所收集的人体Ig链中的相应序列比较;为提供人体Ig骨架，从收集的免疫球蛋白中选择大约三个最为同源的序列之一。
19、设计一人体属性的免疫球蛋白链的方法，该链含来自人体免疫球蛋白受体的骨架区和来自能与抗原结合的免疫球蛋白供体的互补决定区（CDR′S），该方法包括用来自免疫球蛋白供体的相应氨基酸于免疫球蛋白中的某一位置上取代免疫球蛋白受体的至少一人体骨架氨基酸的步骤，其中：
（a）免疫球蛋白受体的人体骨架区中氨基酸在人体免疫球蛋白序列的所述位置中是少见的，而在免疫球蛋白供体中相应的氨基酸在此位置是常见的;或
（b）该氨基酸与CDR之一直接相邻;或
（c）该氨基酸被预测在三维免疫球蛋白模型的CDR′S的约3埃范围内有一侧链原子，并且其能与抗原或人体属性免疫球蛋白的CDR′S相互作用。
20、根据权利要求19的方法，其中人体属性的免疫球蛋白链除包括CDR′S外，还包括至少三个来自免疫球蛋白供体的氨基酸，该免疫球蛋白选自标准（a）、（b）或（c）。
21、根据权利要求20的方法，其中由供体取代的至少一个氨基酸与CDR直接相邻。
CN89109618A 1988-12-28 1989-12-28 新的白细胞介素－２受体特异性免疫球蛋白 Expired - Lifetime CN1057013C (zh)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US29097588A 1988-12-28 1988-12-28
US290,975 1988-12-28
US31025289A 1989-02-13 1989-02-13
US310,252 1989-02-13

Publications (2)

Publication Number Publication Date
CN1043875A true CN1043875A (zh) 1990-07-18
CN1057013C CN1057013C (zh) 2000-10-04

Family

ID=26966505

Family Applications (1)

Application Number Title Priority Date Filing Date
CN89109618A Expired - Lifetime CN1057013C (zh) 1988-12-28 1989-12-28 新的白细胞介素－２受体特异性免疫球蛋白

Country Status (32)

Country Link
EP (6) EP0451216B9 (zh)
JP (6) JP2828340B2 (zh)
KR (1) KR0178385B1 (zh)
CN (1) CN1057013C (zh)
AT (2) ATE183753T1 (zh)
AU (1) AU647383B2 (zh)
BG (1) BG61095B2 (zh)
CA (2) CA2328851C (zh)
CZ (1) CZ418691A3 (zh)
DD (1) DD296964A5 (zh)
DE (14) DE68925536T3 (zh)
DK (2) DK119191D0 (zh)
ES (5) ES2492815T3 (zh)
FI (1) FI108797B (zh)
FR (1) FR14C0070I1 (zh)
HK (1) HK1014718A1 (zh)
HR (1) HRP920500B1 (zh)
HU (1) HU211174A9 (zh)
IE (1) IE20000331A1 (zh)
IL (2) IL162181A (zh)
LU (8) LU90411I2 (zh)
MC (1) MC2146A1 (zh)
NL (8) NL990020I2 (zh)
NO (9) NO310473B1 (zh)
NZ (2) NZ231984A (zh)
PT (1) PT92758B (zh)
RU (1) RU2126046C1 (zh)
SG (1) SG78258A1 (zh)
SI (1) SI8912489B (zh)
WO (1) WO1990007861A1 (zh)
YU (1) YU48700B (zh)
ZA (1) ZA899956B (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102775493A (zh) * 2005-06-21 2012-11-14 佐马技术有限公司 IL-1β结合抗体及其片段
CN113361141A (zh) * 2021-07-11 2021-09-07 西南石油大学 一种dna图谱算法及其改进试验算法

Families Citing this family (985)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5800815A (en) * 1903-05-05 1998-09-01 Cytel Corporation Antibodies to P-selectin and their uses
US5851526A (en) * 1985-04-19 1998-12-22 Ludwig Institute For Cancer Research Methods of treating colon cancer utilizing tumor-specific antibodies
US5449760A (en) * 1987-12-31 1995-09-12 Tanox Biosystems, Inc. Monoclonal antibodies that bind to soluble IGE but do not bind IGE on IGE expressing B lymphocytes or basophils
US5530101A (en) * 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
US7247453B1 (en) * 1988-12-30 2007-07-24 Oklahoma Medical Research Foundation Calcium binding recombinant antibody against protein C
DE3900534A1 (de) * 1989-01-10 1990-07-12 Boehringer Mannheim Gmbh Diagnostischer nachweis unter verwendung von chimaeren antikoerpern
US5859205A (en) 1989-12-21 1999-01-12 Celltech Limited Humanised antibodies
US6750325B1 (en) 1989-12-21 2004-06-15 Celltech R&D Limited CD3 specific recombinant antibody
GB8928874D0 (en) * 1989-12-21 1990-02-28 Celltech Ltd Humanised antibodies
GR1001050B (el) * 1990-01-09 1993-04-28 Protein Design Labs Inc Νεος il-2 υποδοχευς ιδιαζοντων ανθρωπινων ανοσοσφαιρινων.
HUT60768A (en) 1990-03-16 1992-10-28 Sandoz Ag Process for producing cd25 fixing molecules
GB9020282D0 (en) 1990-09-17 1990-10-31 Gorman Scott D Altered antibodies and their preparation
US5858725A (en) * 1990-10-10 1999-01-12 Glaxo Wellcome Inc. Preparation of chimaeric antibodies using the recombinant PCR strategy
US5994510A (en) * 1990-12-21 1999-11-30 Celltech Therapeutics Limited Recombinant antibodies specific for TNFα
ES2204890T3 (es) * 1991-03-06 2004-05-01 Merck Patent Gmbh Anticuerpos monoclonales humanizados.
IL101147A (en) * 1991-03-07 2004-06-20 Gen Hospital Corp Change of direction of cellular immunity by chimera receptors
ES2118820T3 (es) * 1991-04-05 1998-10-01 Univ Washington Anticuerpos monoclonales para receptores de factores de celulas pluripotentes.
DK0628639T3 (da) * 1991-04-25 2000-01-24 Chugai Pharmaceutical Co Ltd Rekonstitueret humant antistof mod human interleukin-6-receptor
DE69233482T2 (de) * 1991-05-17 2006-01-12 Merck & Co., Inc. Verfahren zur Verminderung der Immunogenität der variablen Antikörperdomänen
LU91067I2 (fr) 1991-06-14 2004-04-02 Genentech Inc Trastuzumab et ses variantes et dérivés immuno chimiques y compris les immotoxines
WO1994004679A1 (en) * 1991-06-14 1994-03-03 Genentech, Inc. Method for making humanized antibodies
US6800738B1 (en) 1991-06-14 2004-10-05 Genentech, Inc. Method for making humanized antibodies
GB9115010D0 (en) * 1991-07-11 1991-08-28 Wellcome Found Antibody
GB9115364D0 (en) 1991-07-16 1991-08-28 Wellcome Found Antibody
US5756096A (en) * 1991-07-25 1998-05-26 Idec Pharmaceuticals Corporation Recombinant antibodies for human therapy
US5709860A (en) * 1991-07-25 1998-01-20 Idec Pharmaceuticals Corporation Induction of cytotoxic T-lymphocyte responses
DE69225710T3 (de) * 1991-07-25 2004-10-14 Idec Pharmaceuticals Corp., San Diego Anregung von antworten zytotoxischer t-lymphozyten
IE922437A1 (en) * 1991-07-25 1993-01-27 Idec Pharma Corp Recombinant antibodies for human therapy
US6136310A (en) * 1991-07-25 2000-10-24 Idec Pharmaceuticals Corporation Recombinant anti-CD4 antibodies for human therapy
US6699472B2 (en) 1991-08-14 2004-03-02 Genentech, Inc. Method of treating allergic disorders
US6329509B1 (en) 1991-08-14 2001-12-11 Genentech, Inc. Anti-IgE antibodies
ES2145004T3 (es) * 1991-08-21 2000-07-01 Novartis Ag Derivados de anticuerpos.
GB9120467D0 (en) * 1991-09-26 1991-11-06 Celltech Ltd Anti-hmfg antibodies and process for their production
JP3024311B2 (ja) * 1991-10-03 2000-03-21 味の素株式会社 Ｉｌ−２受容体重鎖に結合するポリペプチド
US5474771A (en) 1991-11-15 1995-12-12 The Trustees Of Columbia University In The City Of New York Murine monoclonal antibody (5c8) recognizes a human glycoprotein on the surface of T-lymphocytes, compositions containing same
US7070777B1 (en) 1991-11-15 2006-07-04 The Trustees Of Columbia University In The City Of New York Method for inhibiting inflammation with an antibody that binds the 5C8 protein
US5817310A (en) * 1991-12-02 1998-10-06 Cor Therapeutics, Inc. Inhibitory immunoglobulin polypeptides to human PDGF beta receptor
JPH05244982A (ja) * 1991-12-06 1993-09-24 Sumitomo Chem Co Ltd 擬人化ｂ−ｂ１０
US5869619A (en) * 1991-12-13 1999-02-09 Xoma Corporation Modified antibody variable domains
ES2202310T3 (es) * 1991-12-13 2004-04-01 Xoma Corporation Metodos y materiales para la preparacion de dominios variables de anticuerpos modificados y sus usos terapeuticos.
US5777085A (en) * 1991-12-20 1998-07-07 Protein Design Labs, Inc. Humanized antibodies reactive with GPIIB/IIIA
US5824307A (en) 1991-12-23 1998-10-20 Medimmune, Inc. Human-murine chimeric antibodies against respiratory syncytial virus
CA2372813A1 (en) * 1992-02-06 1993-08-19 L.L. Houston Biosynthetic binding protein for cancer marker
GB9203459D0 (en) * 1992-02-19 1992-04-08 Scotgen Ltd Antibodies with germ-line variable regions
US5714350A (en) 1992-03-09 1998-02-03 Protein Design Labs, Inc. Increasing antibody affinity by altering glycosylation in the immunoglobulin variable region
US5387676A (en) * 1992-03-11 1995-02-07 Ciba Corning Diagnostics Corp. MN gene and protein
US6129914A (en) * 1992-03-27 2000-10-10 Protein Design Labs, Inc. Bispecific antibody effective to treat B-cell lymphoma and cell line
US7381803B1 (en) 1992-03-27 2008-06-03 Pdl Biopharma, Inc. Humanized antibodies against CD3
US6033667A (en) * 1992-05-05 2000-03-07 Cytel Corporation Method for detecting the presence of P-selectin
US5397703A (en) 1992-07-09 1995-03-14 Cetus Oncology Corporation Method for generation of antibodies to cell surface molecules
US5874082A (en) * 1992-07-09 1999-02-23 Chiron Corporation Humanized anti-CD40 monoclonal antibodies and fragments capable of blocking B cell proliferation
US5639641A (en) * 1992-09-09 1997-06-17 Immunogen Inc. Resurfacing of rodent antibodies
US5958708A (en) * 1992-09-25 1999-09-28 Novartis Corporation Reshaped monoclonal antibodies against an immunoglobulin isotype
US6066718A (en) * 1992-09-25 2000-05-23 Novartis Corporation Reshaped monoclonal antibodies against an immunoglobulin isotype
GB9223377D0 (en) * 1992-11-04 1992-12-23 Medarex Inc Humanized antibodies to fc receptors for immunoglobulin on human mononuclear phagocytes
US7744877B2 (en) 1992-11-13 2010-06-29 Biogen Idec Inc. Expression and use of anti-CD20 Antibodies
US5648267A (en) * 1992-11-13 1997-07-15 Idec Pharmaceuticals Corporation Impaired dominant selectable marker sequence and intronic insertion strategies for enhancement of expression of gene product and expression vector systems comprising same
CA2149326C (en) * 1992-11-13 2007-04-17 Mitchell E. Reff Fully impaired consensus kozak sequences for mammalian expression
ATE196606T1 (de) 1992-11-13 2000-10-15 Idec Pharma Corp Therapeutische verwendung von chimerischen und markierten antikörpern, die gegen ein differenzierung-antigen gerichtet sind, dessen expression auf menschliche b lymphozyt beschränkt ist, für die behandlung von b-zell-lymphoma
US5736137A (en) * 1992-11-13 1998-04-07 Idec Pharmaceuticals Corporation Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma
US5804187A (en) * 1992-11-16 1998-09-08 Cancer Research Fund Of Contra Costa Modified antibodies with human milk fat globule specificity
NZ261259A (en) 1993-01-12 1996-12-20 Biogen Inc Humanised recombinant anti-vla4 antibody and diagnostic compositions and medicaments
US5817311A (en) * 1993-03-05 1998-10-06 Universite Catholique De Louvain Methods of inhibiting T-cell medicated immune responses with LO-CD2a-specific antibodies
US5951983A (en) * 1993-03-05 1999-09-14 Universite Catholique De Louvain Methods of inhibiting T cell mediated immune responses with humanized LO-CD2A-specific antibodies
US5730979A (en) * 1993-03-05 1998-03-24 Universite Catholique Delouvain LO-CD2a antibody and uses thereof for inhibiting T cell activation and proliferation
EP0804235A4 (en) * 1993-05-04 2001-09-19 Aeres Biomedical Ltd ANTIBODIES AGAINST SELECTIN P AND USES THEREOF
DE69434812D1 (de) * 1993-05-28 2006-09-14 Scripps Research Inst Methoden für inhibition der cd14-abhängigen zellaktivierung
AU6808194A (en) * 1993-05-31 1994-12-20 Chugai Seiyaku Kabushiki Kaisha Reconstructed human antibody against human interleukin-6
US6180377B1 (en) * 1993-06-16 2001-01-30 Celltech Therapeutics Limited Humanized antibodies
US5914110A (en) * 1993-09-07 1999-06-22 Smithkline Beecham Corporation Recombinant IL4 antibodies useful in treatment of IL4 mediated disorders
US20020193575A1 (en) 1993-09-07 2002-12-19 Smithkline Beecham P.L.C. Recombinant IL4 antibodies useful in treatment of IL4 mediated disorders
BR9407575A (pt) * 1993-09-07 1996-07-16 Smithkline Beecham Corp Recombinaçao il4 de anticorpos uteis no tratamento de desordens do il4
US5928904A (en) * 1993-09-07 1999-07-27 Smithkline Beecham Corporation DNA encoding recombinant IL4 antibodies useful in treatment of IL4 mediated disorders
AU7949394A (en) 1993-11-19 1995-06-06 Chugai Seiyaku Kabushiki Kaisha Reconstituted human antibody against human medulloblastomatous cell
WO1995015181A1 (en) * 1993-11-30 1995-06-08 Protein Design Labs, Inc. Reperfusion therapy using antibodies to l-selectin
GB9325182D0 (en) * 1993-12-08 1994-02-09 T Cell Sciences Inc Humanized antibodies or binding proteins thereof specific for t cell subpopulations exhibiting select beta chain variable regions
US7435802B2 (en) 1994-01-25 2008-10-14 Elan Pharaceuticals, Inc. Humanized anti-VLA4 immunoglobulins
EP0804237B8 (en) * 1994-01-25 2006-11-08 Elan Pharmaceuticals, Inc. Humanized antibodies against leukocyte adhesion molecule vla-4
US5840299A (en) * 1994-01-25 1998-11-24 Athena Neurosciences, Inc. Humanized antibodies against leukocyte adhesion molecule VLA-4
JPH09512705A (ja) 1994-03-29 1997-12-22 セルテック セラピューティクス リミテッド Ｅ−セレクチンに対する抗体
US5635597A (en) * 1994-05-27 1997-06-03 Affymax Technologies, N.V. Peptides that bind IL-2 receptors
US5622701A (en) * 1994-06-14 1997-04-22 Protein Design Labs, Inc. Cross-reacting monoclonal antibodies specific for E- and P-selectin
USRE39548E1 (en) * 1994-06-17 2007-04-03 Celltech R&D Limited Interleukin-5 specific recombinant antibodies
GB9412230D0 (en) 1994-06-17 1994-08-10 Celltech Ltd Interleukin-5 specific recombiant antibodies
US6048972A (en) * 1994-07-13 2000-04-11 Chugai Pharmaceutical Co., Ltd. Recombinant materials for producing humanized anti-IL-8 antibodies
DE4425115A1 (de) * 1994-07-15 1996-01-18 Boehringer Mannheim Gmbh Verfahren zur Modifizierung der Stabilität von Antikörpern
EP0696455A1 (en) * 1994-08-11 1996-02-14 Cellena (Cell Engineering) A.G. Transferrin compositions to alleviate the side effects of cytotoxic drugs
US8771694B2 (en) * 1994-08-12 2014-07-08 Immunomedics, Inc. Immunoconjugates and humanized antibodies specific for B-cell lymphoma and leukemia cells
US5707621A (en) * 1994-08-31 1998-01-13 Chugai Pharmaceutical Co., Ltd. Supression of nephritis-induced protein excretion by anti-IL-8
US6309636B1 (en) * 1995-09-14 2001-10-30 Cancer Research Institute Of Contra Costa Recombinant peptides derived from the Mc3 anti-BA46 antibody, methods of use thereof, and methods of humanizing antibody peptides
US5693323A (en) * 1994-12-23 1997-12-02 Smithkline Beecham Corporation Recombinant IL-5 antagonists useful in treatment of IL-5 mediated disorders
US5811524A (en) * 1995-06-07 1998-09-22 Idec Pharmaceuticals Corporation Neutralizing high affinity human monoclonal antibodies specific to RSV F-protein and methods for their manufacture and therapeutic use thereof
US6113898A (en) 1995-06-07 2000-09-05 Idec Pharmaceuticals Corporation Human B7.1-specific primatized antibodies and transfectomas expressing said antibodies
US7153508B2 (en) 1995-06-07 2006-12-26 Biogen Idec Inc. Treatment of B cell lymphoma using anti-CD80 antibodies that do not inhibit the binding of CD80 to CTLA-4
US7175847B1 (en) 1995-06-07 2007-02-13 Biogen Idec Inc. Treating intestinal inflammation with anti-CD80 antibodies that do not inhibit CD80 binding to CTLA-4
WO1996040249A1 (en) * 1995-06-07 1996-12-19 Sloan-Kettering Institute For Cancer Research Therapeutic uses of ta99
US6001358A (en) * 1995-11-07 1999-12-14 Idec Pharmaceuticals Corporation Humanized antibodies to human gp39, compositions containing thereof
US6440418B1 (en) 1995-11-07 2002-08-27 Idec Pharmaceuticals Corporation Methods of treating autoimmune diseases with gp39-specific antibodies
GB9600660D0 (en) 1996-01-12 1996-03-13 Ciba Geigy Ag Protein
AU2527397A (en) * 1996-03-13 1997-10-01 Protein Design Labs, Inc. Fas ligand fusion proteins and their uses
US5882644A (en) * 1996-03-22 1999-03-16 Protein Design Labs, Inc. Monoclonal antibodies specific for the platelet derived growth factor β receptor and methods of use thereof
US6713305B1 (en) 1996-04-29 2004-03-30 Novartis Ag Metastasis-associated antigen and antibodies thereto
EP1378525A3 (en) 1996-06-07 2004-01-14 Neorx Corporation Humanized antibodies that bind to the antigen bound by antibody NR-LU-13 and their use in pretargeting methods
US6833255B1 (en) 1996-07-24 2004-12-21 Novartis, Ag Drosophila melanogaster p70 S6 kinase
US6534311B2 (en) 1996-07-24 2003-03-18 Novartis Ag Drosophila melanogaster p70S6 kinase
US7147851B1 (en) * 1996-08-15 2006-12-12 Millennium Pharmaceuticals, Inc. Humanized immunoglobulin reactive with α4β7 integrin
EP0957166A4 (en) * 1996-09-02 2004-12-15 Ko Okumura HUMANIZED IMMUNOGLOBULIN SPECIFICALLY REACTING WITH A LIGAND Fas OR ONE OF ITS ACTIVE FRAGMENTS AND REGION FOR INDUCING APOPTOSIS BORN IN A LIGAND Fas
US6013256A (en) * 1996-09-24 2000-01-11 Protein Design Labs, Inc. Method of preventing acute rejection following solid organ transplantation
HUP9904177A3 (en) 1996-09-26 2001-10-29 Chugai Pharmaceutical Co Ltd Antibody against human parathormone related peptides
UA76934C2 (en) 1996-10-04 2006-10-16 Chugai Pharmaceutical Co Ltd Reconstructed human anti-hm 1.24 antibody, coding dna, vector, host cell, method for production of reconstructed human antibody, pharmaceutical composition and drug for treating myeloma containing reconstructed human anti-hm 1.24 antibody
US7883872B2 (en) 1996-10-10 2011-02-08 Dyadic International (Usa), Inc. Construction of highly efficient cellulase compositions for enzymatic hydrolysis of cellulose
US7910096B2 (en) 1996-11-15 2011-03-22 Trustees Of Tufts College Human neutralizing antibodies against hemolytic uremic syndrome
US20020160005A1 (en) 1996-11-15 2002-10-31 Trustees Of Tufts College Human neutralizing antibodies against hemolytic urmec syndrome
JP2002509431A (ja) 1996-12-23 2002-03-26 イミュネックス・コーポレーション ＮＦ−κＢのレセプター活性化因子−レセプターはＴＮＦレセプタースーパーファミリーの一員である−
US6262238B1 (en) * 1997-01-14 2001-07-17 Roche Diagnostic, Gmbh Process for modifying the stability of antibodies
US6596850B1 (en) 1998-01-30 2003-07-22 Ixsys, Incorporated Anti-αv3β3 recombinant human antibodies, nucleic acids encoding same
US6590079B2 (en) 1997-01-30 2003-07-08 Ixsys, Incorporated Anti-αvβ3 recombinant human antibodies, nucleic acids encoding same
US7749498B2 (en) 1997-03-10 2010-07-06 Genentech, Inc. Antibodies for inhibiting blood coagulation and methods of use thereof
US5986065A (en) 1997-03-10 1999-11-16 Sunol Molecular Corporation Antibodies for inhibiting blood coagulation and methods of use thereof
US20060235209A9 (en) 1997-03-10 2006-10-19 Jin-An Jiao Use of anti-tissue factor antibodies for treating thromboses
US20030109680A1 (en) 2001-11-21 2003-06-12 Sunol Molecular Corporation Antibodies for inhibiting blood coagulation and methods of use thereof
AU736287B2 (en) * 1997-03-21 2001-07-26 Sankyo Company Limited Humanized anti-human Fas antibody
US6972323B1 (en) 1997-04-01 2005-12-06 Sankyo Company, Limited Anti-Fas antibodies
US7365166B2 (en) 1997-04-07 2008-04-29 Genentech, Inc. Anti-VEGF antibodies
US20020032315A1 (en) 1997-08-06 2002-03-14 Manuel Baca Anti-vegf antibodies
US6884879B1 (en) 1997-04-07 2005-04-26 Genentech, Inc. Anti-VEGF antibodies
NZ500078A (en) 1997-04-07 2001-10-26 Genentech Inc Humanized anti-VEGF antibodies and their use in inhibiting VEGF-induced angiogenesis in mammals
IL132896A0 (en) 1997-05-15 2001-03-19 Chugai Pharmaceutical Co Ltd Cachexia remedy
DE69833755T2 (de) 1997-05-21 2006-12-28 Biovation Ltd. Verfahren zur herstellung von nicht-immunogenen proteinen
DE69821011T3 (de) 1997-10-02 2009-01-08 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Verfahren zur Modulierung der Neovaskularisierung und/oder des Wachstums kollateraler Arterien und/oder anderer Arterien aus bestehenden arteriolären Verbindungen
ES2293691T3 (es) 1997-10-03 2008-03-16 Chugai Seiyaku Kabushiki Kaisha Anticuerpo humano natural.
TWI239847B (en) * 1997-12-02 2005-09-21 Elan Pharm Inc N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease
US7179892B2 (en) 2000-12-06 2007-02-20 Neuralab Limited Humanized antibodies that recognize beta amyloid peptide
US20080050367A1 (en) 1998-04-07 2008-02-28 Guriq Basi Humanized antibodies that recognize beta amyloid peptide
US7964192B1 (en) 1997-12-02 2011-06-21 Janssen Alzheimer Immunotherapy Prevention and treatment of amyloidgenic disease
EP1745799B1 (en) 1998-03-04 2015-09-02 The Trustees of The University of Pennsylvania Compositions and methods of treating tumors
ATE512225T1 (de) 1998-04-03 2011-06-15 Chugai Pharmaceutical Co Ltd Humanisierter antikörper gegen den menschlichen gewebefaktor (tf) und verfahren für die konstruktion eines solchen humanisierten antikörpers.
DE69939939D1 (de) 1998-08-11 2009-01-02 Idec Pharma Corp Kombinationstherapien gegen b-zell-lymphome beinhaltend die verabreichung von anti-cd20-antikörpern
JP4689781B2 (ja) * 1998-09-03 2011-05-25 独立行政法人科学技術振興機構 アミノ酸輸送蛋白及びその遺伝子
ES2319831T3 (es) 1998-09-14 2009-05-12 Board Of Regents, The University Of Texas System Metodos de tratamiento de mieloma multiple y resorcion osea inducida por mieloma usando antagonistas de la union receptor/integrina.
EP1117808B1 (en) 1998-10-06 2004-12-29 Mark Aaron Emalfarb Transformation system in the field of filamentous fungal hosts: in chrysosporium
DE69839740D1 (de) 1998-10-22 2008-08-28 Univ Montana Vakzine enthaltend Omp85 Proteine von Neisseria gonorrhoeae und Neisseria meningitidis
KR20010103655A (ko) 1998-11-09 2001-11-23 케네쓰 제이. 울코트 키메라 항-ｃｄ２０항체를 이용한 순환성 종양세포와관련된 혈액학적 악성종양의 치료법
GB9825632D0 (en) 1998-11-23 1999-01-13 Novartis Ag Organic compounds
US20030035798A1 (en) 2000-08-16 2003-02-20 Fang Fang Humanized antibodies
WO2000051628A2 (en) 1999-03-03 2000-09-08 Biogen, Inc. Methods of modulating lipid metabolism and storage
GB9906380D0 (en) * 1999-03-19 1999-05-12 Melvin William T Monoclonal antibodies specific for cypibi
CN100360183C (zh) 1999-04-22 2008-01-09 比奥根艾迪克Ma公司 整联蛋白α4亚单位的拮抗剂在制备治疗纤维变性的药物中的用途
IT1306704B1 (it) * 1999-05-26 2001-10-02 Sirs Societa Italiana Per La R Anticorpi monoclonali e suoi derivati sintetici o biotecnologici ingrado di agire come molecole antagoniste per il ngf.
NZ515686A (en) 1999-06-01 2005-01-28 Biogen Inc A blocking monoclonal antibody to integrin VLA-1 and its use for the treatment of inflammatory disorders such as arthritis
UA81216C2 (en) 1999-06-01 2007-12-25 Prevention and treatment of amyloid disease
US7144991B2 (en) 1999-06-07 2006-12-05 Aletheon Pharmaceuticals, Inc. Streptavidin expressed gene fusions and methods of use thereof
US6531580B1 (en) 1999-06-24 2003-03-11 Ixsys, Inc. Anti-αvβ3 recombinant human antibodies and nucleic acids encoding same
TWI255718B (en) 1999-07-02 2006-06-01 Chugai Pharmaceutical Co Ltd Ameliorative agent for low vasopressin concentration
US8557244B1 (en) 1999-08-11 2013-10-15 Biogen Idec Inc. Treatment of aggressive non-Hodgkins lymphoma with anti-CD20 antibody
DE60038252T2 (de) * 1999-09-30 2009-03-19 Kyowa Hakko Kogyo Co., Ltd. Menschlicher Antikörper gegen Gangliosid GD3 für die Transplantationskomplentarität bestimmende Region und Derivate des Antikörpers gegen das Gangliosid GD3
US6849425B1 (en) 1999-10-14 2005-02-01 Ixsys, Inc. Methods of optimizing antibody variable region binding affinity
AU784634B2 (en) 1999-11-30 2006-05-18 Mayo Foundation For Medical Education And Research B7-H1, a novel immunoregulatory molecule
EP1242118B1 (en) 1999-12-16 2009-11-11 Biogen Idec MA Inc. Methods of treating central nervous system ischemic or hemorrhagic injury using anti alpha4 integrin antagonists
AU2001240020B9 (en) 2000-03-01 2008-12-04 Medimmune, Llc High potency recombinant antibodies and method for producing them
ATE474854T1 (de) 2000-01-27 2010-08-15 Medimmune Llc Rsv neutralisierende antikörper mit sehr hohen affinität
MXPA02007449A (es) * 2000-02-03 2003-04-14 Millennium Pharm Inc Anticuerpos anti-ccr2 humanizados y metodos para el uso de los mismos.
AU3495301A (en) 2000-02-11 2001-08-20 Biogen Inc Heterologous polypeptide of the tnf family
WO2001062801A2 (en) 2000-02-24 2001-08-30 Washington University Humanized antibodies that sequester amyloid beta peptide
JP2003527439A (ja) 2000-03-17 2003-09-16 ミレニアム・ファーマシューティカルズ・インコーポレイテッド 抗ｃｄ１８抗体と抗ｃｃｒ２抗体の混合物を用いる狭窄および再狭窄を抑制する方法
US20010046496A1 (en) 2000-04-14 2001-11-29 Brettman Lee R. Method of administering an antibody
ATE420661T1 (de) 2000-04-28 2009-01-15 Chugai Pharmaceutical Co Ltd Zellproliferation-inhibitoren
US7030219B2 (en) 2000-04-28 2006-04-18 Johns Hopkins University B7-DC, Dendritic cell co-stimulatory molecules
DE60136272D1 (de) 2000-04-29 2008-12-04 Univ Iowa Res Found Diagnostika und therapeutika für makula degeneration erkrankungen
TWI318983B (en) * 2000-05-02 2010-01-01 Uab Research Foundation An antibody selective for a tumor necrosis factor-related apoptosis-inducing ligand receptor and uses thereof
US7476383B2 (en) 2000-05-02 2009-01-13 The Uab Research Foundation Antibody selective for DR4 and uses thereof
US7279160B2 (en) 2000-05-02 2007-10-09 The Uab Research Foundation Combinations of DR5 antibodies and other therapeutic agents
GB0013810D0 (en) 2000-06-06 2000-07-26 Celltech Chiroscience Ltd Biological products
GB0020685D0 (en) 2000-08-22 2000-10-11 Novartis Ag Organic compounds
CA2424296A1 (en) 2000-10-02 2002-04-11 Chiron Corporation Human anti-cd40 antibodies
US7459287B2 (en) 2004-01-30 2008-12-02 Dana Farber Cancer Institute, Inc. Method for determination and quantification of radiation or genotoxin exposure
US7179900B2 (en) 2000-11-28 2007-02-20 Medimmune, Inc. Methods of administering/dosing anti-RSV antibodies for prophylaxis and treatment
US6989247B2 (en) 2000-11-28 2006-01-24 Celltech R & D, Inc. Compositions and methods for diagnosing or treating psoriasis
PE20020574A1 (es) 2000-12-06 2002-07-02 Wyeth Corp Anticuerpos humanizados que reconocen el peptido amiloideo beta
KR20080110687A (ko) * 2001-04-06 2008-12-18 더 유니버시티 오브 브리스톨 스테로이드-내성 환자에서의 ｃｄ25 결합 분자의 용도
KR100927670B1 (ko) 2001-04-13 2009-11-20 바이오겐 아이덱 엠에이 인코포레이티드 Ｖｌａ-1에 대한 항체들
CA2443437A1 (en) * 2001-05-18 2002-11-28 Boehringer Ingelheim International Gmbh Antibodies specific for cd44v6
US6972324B2 (en) 2001-05-18 2005-12-06 Boehringer Ingelheim Pharmaceuticals, Inc. Antibodies specific for CD44v6
US7541443B2 (en) * 2001-06-14 2009-06-02 Tolerrx, Inc. Anti-CD4 antibodies
WO2002102972A2 (en) 2001-06-20 2002-12-27 Prochon Biotech Ltd. Antibodies that block receptor protein tyrosine kinase activation, methods of screening for and uses thereof
US20030013081A1 (en) 2001-06-26 2003-01-16 Olson William C. Uses of DC-SIGN and DC-SIGNR for inhibiting hepatitis C virus infection
JP4675512B2 (ja) * 2001-07-10 2011-04-27 三井化学株式会社 熱殺菌方法
CA2898314A1 (en) 2001-07-19 2003-07-31 Perian Therapeutics, Inc. Multimeric proteins and methods of making and using same
JP4729717B2 (ja) 2001-08-03 2011-07-20 株式会社医学生物学研究所 ＧＭ１ガングリオシド結合型アミロイドβタンパク質を認識する抗体、及び該抗体をコードするＤＮＡ
DK1944040T3 (da) 2001-08-17 2012-10-29 Univ Washington Analysefremgangsmåde for Alzheimers sygdom
US7691605B2 (en) 2001-09-20 2010-04-06 Immunex Corporation Selection of cells expressing heteromeric polypeptides
WO2003027151A1 (fr) 2001-09-25 2003-04-03 Immuno-Biological Laboratories Co., Ltd. Anticorps recombinant anti-osteopontine et son utilisation
GB0124317D0 (en) 2001-10-10 2001-11-28 Celltech R&D Ltd Biological products
US20030190705A1 (en) * 2001-10-29 2003-10-09 Sunol Molecular Corporation Method of humanizing immune system molecules
WO2003042247A2 (en) * 2001-11-12 2003-05-22 Merck Patent Gmbh Modified anti-tnf alpha antibody
EP1944043A1 (en) 2001-11-21 2008-07-16 The Trustees of the University of Pennsylvania Simian adenovirus nucleic acid and amino acid sequences, vectors containing same, and methods of use
NZ532383A (en) 2001-11-21 2007-03-30 Univ Pennsylvania Pan-7 simian adenovirus nucleic acid and amino acid sequences, vectors containing same, and methods of use
DK1461300T3 (da) 2001-11-30 2011-10-24 Biogen Idec Inc Antistoffer mod kemotaktiske monocytproteiner
US7393648B2 (en) 2001-12-03 2008-07-01 Alexion Pharmaceuticals, Inc. Hybrid antibodies
EP2298817A1 (en) 2001-12-03 2011-03-23 Alexion Pharmaceuticals, Inc. Hybrid antibodies
GB0129105D0 (en) 2001-12-05 2002-01-23 Celltech R&D Ltd Expression control using variable intergenic sequences
AU2003208415B2 (en) * 2002-02-14 2009-05-28 Immunomedics, Inc. Anti-CD20 antibodies and fusion proteins thereof and methods of use
RU2322454C2 (ru) 2002-02-22 2008-04-20 Проджиникс Фармасьютикалз, Инк. Антитело против ccr5
US20040009169A1 (en) 2002-02-25 2004-01-15 Julie Taylor Administration of agents for the treatment of inflammation
MY139983A (en) 2002-03-12 2009-11-30 Janssen Alzheimer Immunotherap Humanized antibodies that recognize beta amyloid peptide
EP2287199B1 (en) 2002-03-13 2017-08-02 Biogen MA Inc. Anti-alpha V beta 6 antibodies
DE60336214D1 (de) 2002-03-20 2011-04-14 Ucb Pharma Sa Methoden zur analyse von antikörperdisulfidisomere
JP4432031B2 (ja) 2002-03-22 2010-03-17 ズィナイス オペレーションズ ピーティーワイ．エルティーディー． インターロイキン１３受容体α１（ＩＬ−１３Ｒα１）に対するモノクローナル抗体
GB0210121D0 (en) 2002-05-02 2002-06-12 Celltech R&D Ltd Biological products
EP2243837A1 (en) 2002-05-14 2010-10-27 Martek Biosciences Corporation Carotene synthase gene and uses therefor
ATE518885T1 (de) 2002-05-28 2011-08-15 Ucb Pharma Sa Peg-positionsisomer von einem antikorper gegen tnfalpha (cdp870)
BR0311471A (pt) * 2002-05-30 2007-04-27 Macrogenics Inc anticorpo anti-cd16a, e, métodos de redução de uma resposta imune deletéria em um mamìfero e de tratamento de uma resposta imune deletéria em um mamìfero
GB0213745D0 (en) 2002-06-14 2002-07-24 Univ Edinburgh Enzyme
DE60230071D1 (de) 2002-06-14 2009-01-08 Monier Tadros Methode für die herstellung von protamin
US7132100B2 (en) 2002-06-14 2006-11-07 Medimmune, Inc. Stabilized liquid anti-RSV antibody formulations
CA2490804C (en) * 2002-06-28 2016-12-06 The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Method of treating autoimmune diseases with interferon-beta and il-2r antagonist
WO2010011999A2 (en) 2008-07-25 2010-01-28 The Regents Of The University Of California Methods and compositions for eliciting an amyloid-selective immune response
US7432351B1 (en) 2002-10-04 2008-10-07 Mayo Foundation For Medical Education And Research B7-H1 variants
GB0228832D0 (en) 2002-12-10 2003-01-15 Novartis Ag Organic compound
US8506959B2 (en) 2002-11-01 2013-08-13 Neotope Biosciences Limited Prevention and treatment of synucleinopathic and amyloidogenic disease
TW200509968A (en) 2002-11-01 2005-03-16 Elan Pharm Inc Prevention and treatment of synucleinopathic disease
EP1578397B1 (en) 2002-11-15 2012-12-26 Genmab A/S Human monoclonal antibodies against cd25
CA2537263C (en) 2002-11-27 2017-05-30 Minerva Biotechnologies Corporation Techniques and compositions for the diagnosis and treatment of cancer (muc1)
EP2301966A1 (en) 2002-12-16 2011-03-30 Genentech, Inc. Immunoglobulin variants and uses thereof
US7575893B2 (en) 2003-01-23 2009-08-18 Genentech, Inc. Methods for producing humanized antibodies and improving yield of antibodies or antigen binding fragments in cell culture
WO2004066931A2 (en) 2003-01-24 2004-08-12 Elan Pharmaceuticals Inc. Composition for and treatment of demyelinating diseases and paralysis by administration of remyelinating agents
EP1460088A1 (en) 2003-03-21 2004-09-22 Biotest AG Humanized anti-CD4 antibody with immunosuppressive properties
US7321065B2 (en) 2003-04-18 2008-01-22 The Regents Of The University Of California Thyronamine derivatives and analogs and methods of use thereof
US7619070B2 (en) 2003-04-23 2009-11-17 Medarex, Inc. Humanized antibodies to interferon alpha receptor-1 (IFNAR-1)
CA2823468A1 (en) 2003-04-23 2004-11-04 Medarex, L.L.C. Compositions and methods for the therapy of inflammatory bowel disease
US7358331B2 (en) 2003-05-19 2008-04-15 Elan Pharmaceuticals, Inc. Truncated fragments of alpha-synuclein in Lewy body disease
SI2361928T1 (sl) 2003-05-19 2017-07-31 Prothena Biosciences Limited Skrajšani fragmenti alfa-sinukleina pri bolezni Lewyjevih telesc
DE602004029252D1 (de) 2003-06-13 2010-11-04 Biogen Idec Inc Aglycosyl-anti-cd154 (cd40-ligand) antikörper und deren verwendungen
US20060162014A1 (en) 2003-07-07 2006-07-20 Jaffe Eileen K Alternate morpheeins of allosteric proteins as a target for the development of bioactive molecules
US8153410B2 (en) 2003-07-07 2012-04-10 Fox Chase Cancer Center Alternate morpheein forms of allosteric proteins as a target for the development of bioactive molecules
MX341074B (es) 2003-07-08 2016-08-05 Genentech Inc Polipeptidos heterologos il-17 a/f y usos terapeuticos de los mismos.
TWI476206B (zh) 2003-07-18 2015-03-11 Amgen Inc 對肝細胞生長因子具專一性之結合劑
US7834155B2 (en) 2003-07-21 2010-11-16 Immunogen Inc. CA6 antigen-specific cytotoxic conjugate and methods of using the same
US20060228350A1 (en) * 2003-08-18 2006-10-12 Medimmune, Inc. Framework-shuffling of antibodies
GB0321997D0 (en) 2003-09-19 2003-10-22 Novartis Ag Organic compound
EP1693385A4 (en) * 2003-11-11 2009-11-04 Chugai Pharmaceutical Co Ltd ANTI-CD47 ANTIBODIES HUMANIZED
CA2544253A1 (en) 2003-11-12 2005-05-26 Progenics Pharmaceuticals, Inc. Novel sequences encoding hepatitis c virus glycoproteins
ES2484340T3 (es) 2003-12-05 2014-08-11 Multimmune Gmbh Anticuerpos anti hsp70 terapéuticos y diagnósticos
US7332584B2 (en) 2003-12-08 2008-02-19 Morphotek, Inc. Antibodies that specifically bind PMS2
EP2241331A3 (en) 2003-12-15 2011-03-09 Alexion Pharmaceuticals, Inc. Novel anti-DC-SIGN antibodies
ITRM20030601A1 (it) * 2003-12-24 2005-06-25 Lay Line Genomics Spa Metodo per l'umanizzazione di anticorpi e anticorpi umanizzati con esso ottenuti.
ES2689328T3 (es) 2004-01-07 2018-11-13 Novartis Vaccines And Diagnostics, Inc. Anticuerpo monoclonal M-CSF-específico y usos del mismo
WO2005068504A1 (ja) 2004-01-19 2005-07-28 Medical And Biological Laboratories Co., Ltd. 炎症性サイトカイン抑制剤
CA2561531C (en) 2004-02-10 2017-05-02 The Regents Of The University Of Colorado Inhibition of factor b, the alternative complement pathway and methods related thereto
TWI359026B (en) 2004-02-12 2012-03-01 Sankyo Co Pharmaceutical composition for the osteoclast rela
EP1716179A2 (en) 2004-02-12 2006-11-02 Morphotek, Inc. Monoclonal antibodies that specifically bind to folate receptor alpha
US7807157B2 (en) 2004-02-20 2010-10-05 Intellect Neurosciences Inc. Monoclonal antibodies and use thereof
NZ549787A (en) 2004-03-12 2010-05-28 Vasgene Therapeutics Inc Antibodies binding to EphB4 for inhibiting angiogenesis and tumor growth
US20050260679A1 (en) 2004-03-19 2005-11-24 Sirid-Aimee Kellerman Reducing the risk of human anti-human antibodies through V gene manipulation
US7625549B2 (en) 2004-03-19 2009-12-01 Amgen Fremont Inc. Determining the risk of human anti-human antibodies in transgenic mice
MY162179A (en) 2004-04-01 2017-05-31 Elan Pharm Inc Steroid sparing agents and methods of using same
AU2005229015C1 (en) 2004-04-02 2013-01-17 The Regents Of The University Of California Methods and compositions for treating and preventing disease associated with alphaVbeta5 integrin
EP1761784B1 (en) 2004-05-24 2016-10-26 Universität Zu Köln Identification of ergothioneine transporter and therapeutic uses thereof
EP1602926A1 (en) 2004-06-04 2005-12-07 University of Geneva Novel means and methods for the treatment of hearing loss and phantom hearing
PL1781705T3 (pl) 2004-06-21 2015-03-31 Squibb & Sons Llc Antyciała receptora interferonów alfa I oraz ich zastosowania
GB0414054D0 (en) 2004-06-23 2004-07-28 Owen Mumford Ltd Improvements relating to automatic injection devices
GEP20105059B (en) 2004-07-26 2010-08-10 Biogen Idec Inc Anti-cd154 antibodies
GB0417487D0 (en) 2004-08-05 2004-09-08 Novartis Ag Organic compound
EA013752B1 (ru) 2004-08-09 2010-06-30 Элан Фармасьютикалз, Инк. Предупреждение и лечение синуклеинопатических и амилоидогенных заболеваний
CA2478458A1 (en) 2004-08-20 2006-02-20 Michael Panzara Treatment of pediatric multiple sclerosis
FI20041204A0 (fi) 2004-09-16 2004-09-16 Riikka Lund Menetelmät immuunivälitteisiin sairauksiin liittyvien uusien kohdegeenien hyödyntämiseksi
WO2006037604A1 (en) 2004-10-01 2006-04-13 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Novel antibodies directed to the mammalian eag1 ion channel protein
MX2007004176A (es) 2004-10-06 2007-06-15 Mayo Foundation B7-h1 y metodos de diagnosis, prognosis, y tratamiento de cancer.
KR101370253B1 (ko) 2004-10-22 2014-03-05 암젠 인크 재조합 항체의 재접힘 방법
BRPI0516962A (pt) 2004-10-25 2008-09-30 Univ Northwestern anticorpo isolado, ou fragmento do mesmo, composição farmacêutica, métodos para prevenir a ligação de ligantes difundìveis derivados de abeta a um neurÈnio, para inibir a constituição de ligantes difundìveis, para bloquear a fosforilação de proteìna, para tratar profilaticamente ou terapeuticamente uma doença, para identificar um agente terapêutico, para detectar ligantes difundìveis, e para diagnosticar uma doença, e, kit para detectar ligantes difundìveis
CN101102792A (zh) 2004-11-19 2008-01-09 比奥根艾迪克Ma公司 治疗多发性硬化
AR052051A1 (es) 2004-12-15 2007-02-28 Neuralab Ltd Anticuerpos ab humanizados usados en mejorar la cognicion
EA018897B1 (ru) 2005-01-05 2013-11-29 Ф-Стар Биотехнологише Форшунгс- Унд Энтвиклунгсгез.М.Б.Х. Молекулы иммуноглобулина, содержащие модифицированные участки структурных петель, обладающие свойством связывания, и способ их получения
AU2006208208B2 (en) 2005-01-27 2011-05-19 Children's Hospital & Research Center At Oakland GNA1870-based vesicle vaccines for broad spectrum protection against diseases caused by Neisseria meningitidis
CN103920142A (zh) 2005-02-14 2014-07-16 爱荷华大学研究基金会 治疗和诊断年龄相关性黄斑变性的方法和试剂
US20090124993A1 (en) 2005-02-17 2009-05-14 Burkly Linda C Treating neurological disorders
JP4942644B2 (ja) 2005-02-28 2012-05-30 株式会社抗体研究所 抗ＩｇＳＦ４抗体及びその利用
ATE478707T1 (de) 2005-03-02 2010-09-15 Biogen Idec Inc Kim-1-antikörper zur behandlung von th2- vermittelten erkrankungen
EP1861425B1 (en) 2005-03-10 2012-05-16 Morphotek, Inc. Anti-mesothelin antibodies
CA2601400A1 (en) 2005-03-19 2006-09-28 Medical Research Council Improvements in or relating to treatment and prevention of viral infections
WO2006105021A2 (en) 2005-03-25 2006-10-05 Tolerrx, Inc. Gitr binding molecules and uses therefor
ES2720288T3 (es) 2005-03-30 2019-07-19 Minerva Biotechnologies Corp Proliferación de células que expresan MUC1
JP2008543276A (ja) 2005-03-30 2008-12-04 ミネルバ バイオテクノロジーズ コーポレーション Ｍｕｃ１発現細胞の増殖
KR20070119710A (ko) 2005-03-31 2007-12-20 더 제너럴 하스피탈 코포레이션 Ｈｇｆ／ｈｇｆｒ 활성의 모니터링 및 조정
EP1872136B9 (en) 2005-04-04 2023-02-08 Biogen MA Inc. Methods and products for evaluating an immune response to a therapeutic protein
WO2006116451A2 (en) 2005-04-22 2006-11-02 Morphotek, Inc. Antibodies with immune effector activity and that internalize in endosialin-positive cells
EP2172487A1 (en) 2005-04-22 2010-04-07 Morphotek Inc. Antibodies with Immune Effector Activity that Internalize in Folate Receptor Alpha-Positive Cells
WO2006117910A1 (ja) 2005-04-28 2006-11-09 Mochida Pharmaceutical Co., Ltd. 抗血小板膜糖蛋白質ⅵモノクローナル抗体
EP1885396A2 (en) 2005-05-04 2008-02-13 Quark Pharmaceuticals, Inc. Recombinant antibodies against cd55 and cd59 and uses thereof
WO2006122150A1 (en) 2005-05-10 2006-11-16 Incyte Corporation Modulators of indoleamine 2,3-dioxygenase and methods of using the same
CA2609038A1 (en) 2005-05-18 2006-11-23 Trinity Biosystems, Inc. Methods and compositions for immunizing against chlamydia infection
CA2607663C (en) 2005-05-19 2014-08-12 Amgen Inc. Compositions and methods for increasing the stability of antibodies
CA2610340C (en) 2005-05-26 2016-02-16 Vernon Michael Holers Inhibition of the alternative complement pathway for treatment of traumatic brain injury, spinal cord injury and related conditions
SI2460831T1 (sl) 2005-05-27 2017-01-31 Biogen Ma Inc. Protitelesa, ki se vežejo na TWEAK
WO2006138429A2 (en) 2005-06-16 2006-12-28 The Feinstein Institute For Medical Research Antibodies against hmgb1 and fragments thereof
US8901281B2 (en) 2005-06-17 2014-12-02 Merck Sharp & Dohme Corp. ILT3 binding molecules and uses therefor
CN104072614B (zh) 2005-07-08 2017-04-26 生物基因Ma公司 抗-αvβ6 抗体及其用途
CA2616189C (en) 2005-07-22 2019-03-26 Progenics Pharmaceuticals, Inc. Methods for reducing viral load in hiv-1-infected patients
FR2888850B1 (fr) 2005-07-22 2013-01-11 Pf Medicament Nouveaux anticorps anti-igf-ir et leurs applications
EP2311876A3 (en) 2005-07-28 2011-04-27 Novartis AG M-CSF-specific monoclonal antibody and uses thereof
WO2007030560A2 (en) 2005-09-08 2007-03-15 Philadelphia Health & Education Corporation, D/B/A Drexel University College Of Medicine Identification of modulators of serine protease inhibitor kazal and their use as anti-cancer and anti-viral agents
CN101313216A (zh) 2005-09-22 2008-11-26 普洛茨股份有限公司 酵母突变体中产生的糖基化多肽及其使用方法
WO2007049770A1 (ja) 2005-10-28 2007-05-03 Meiji Seika Kaisha, Ltd. 緑膿菌の外膜タンパク質ｐａ５１５８
WO2007051077A2 (en) 2005-10-28 2007-05-03 The Regents Of The University Of California Methods and compounds for lymphoma cell detection and isolation
US7919264B2 (en) 2005-11-01 2011-04-05 Abbott Biotechnology Ltd. Methods and compositions for determining the efficacy of a treatment for ankylosing spondylitis using biomarkers
EP1957541A2 (en) 2005-11-21 2008-08-20 Laboratoires Serono SA Compositions and methods of producing hybrid antigen binding molecules and uses thereof
DK1976877T4 (en) † 2005-11-30 2017-01-16 Abbvie Inc Monoclonal antibodies to amyloid beta protein and uses thereof
DOP2006000277A (es) 2005-12-12 2007-08-31 Bayer Pharmaceuticals Corp Anticuerpos anti mn y métodos para su utilización
TWI428143B (zh) 2006-01-18 2014-03-01 Gen Hospital Corp 增加淋巴功能之方法
US20080317710A1 (en) 2006-02-22 2008-12-25 University Of Zurich Methods For Treating Autoimmune or Demyelinating Diseases
EP2377887A1 (en) 2006-03-10 2011-10-19 Zymogenetics Inc Antibodies that bind both IL-17A and IL-17F and methods of using the same
US9315578B2 (en) 2006-03-23 2016-04-19 Tohoku Univeristy High functional bispecific antibody
CN101454446A (zh) 2006-03-30 2009-06-10 明治制果株式会社 绿脓杆菌的外膜蛋白pa0427
KR20150006085A (ko) 2006-04-05 2015-01-15 애브비 바이오테크놀로지 리미티드 항체 정제
US9624295B2 (en) 2006-04-10 2017-04-18 Abbvie Biotechnology Ltd. Uses and compositions for treatment of psoriatic arthritis
EP2708242A3 (en) 2006-04-10 2014-03-26 Abbott Biotechnology Ltd Uses and compositions for treatment of ankylosing spondylitis
CA2564435A1 (en) 2006-04-10 2007-10-10 Abbott Biotechnology Ltd. Methods for monitoring and treating intestinal disorders
JP5496658B2 (ja) 2006-05-25 2014-05-21 バイオジェン・アイデック・エムエイ・インコーポレイテッド 脳卒中を処置する方法
MX2008015309A (es) 2006-05-31 2009-03-02 Astellas Pharma Inc Anticuerpo humanizado de osteopontina anti-humana.
CA2653628C (en) 2006-06-01 2015-07-14 Elan Pharmaceuticals, Inc. Neuroactive fragments of app
CA2655504A1 (en) 2006-06-15 2007-12-21 Fibron Ltd. Antibodies blocking fibroblast growth factor receptor activation and methods of use thereof
JP5597793B2 (ja) 2006-06-19 2014-10-01 メルク・シャープ・アンド・ドーム・コーポレーション Ｉｌｔ３結合分子およびその使用
CN101484199B (zh) 2006-06-30 2014-06-25 艾伯维生物技术有限公司 自动注射装置
AT503889B1 (de) 2006-07-05 2011-12-15 Star Biotechnologische Forschungs Und Entwicklungsges M B H F Multivalente immunglobuline
EP2287189A1 (en) 2006-07-07 2011-02-23 Intercell AG Small Streptococcus pyogenes antigens and their use
SG173364A1 (en) 2006-07-10 2011-08-29 Biogen Idec Inc Compositions and methods for inhibiting growth of smad4-deficient cancers
WO2008007648A1 (fr) 2006-07-10 2008-01-17 Institute For Antibodies Co., Ltd. Procédé de classification d'antigène, procédé d'identification d'antigène, procédé d'obtention d' un ensemble d'antigènes ou d'anticorps, procédés de construction d'un panel d'anticorps, anticorps et ens
US8586716B2 (en) 2006-08-04 2013-11-19 Novartis Ag EPHB3-specific antibody and uses thereof
EP2056709A4 (en) 2006-08-11 2013-05-01 Univ New Jersey Med DOUBLE-SENSITIZER WITH LUMINESCENCE COMPOUNDS, CONJUGATES AND USE
EA201201533A1 (ru) 2006-08-18 2014-11-28 Новартис Аг Prlr-специфическое антитело и его применения
SG10201510384UA (en) 2006-09-13 2016-01-28 Abbvie Inc Cell culture improvements
EP2500414A1 (en) 2006-09-13 2012-09-19 Abbott Laboratories Cell culture improvements
JPWO2008032833A1 (ja) 2006-09-14 2010-01-28 株式会社医学生物学研究所 Ａｄｃｃ活性を増強させた抗体及びその製造方法
FR2906533B1 (fr) 2006-09-28 2013-02-22 Pf Medicament Procede de generation d'anticorps actifs contre un antigene de resistance,anticorps obtenus par ledit procede et leurs utilisations
US8394927B2 (en) 2006-11-03 2013-03-12 U3 Pharma Gmbh FGFR4 antibodies
CN103073641B (zh) 2006-11-10 2015-01-21 株式会社立富泰克 在体内具有抗肿瘤活性的抗人Dlk-1抗体
KR20090078353A (ko) 2006-11-17 2009-07-17 노파르티스 아게 Ｌｉｎｇｏ 결합 분자 및 그의 제약학적 용도
EP1923069A1 (en) 2006-11-20 2008-05-21 Intercell AG Peptides protective against S. pneumoniae and compositions, methods and uses relating thereto
US8288110B2 (en) 2006-12-04 2012-10-16 Perkinelmer Health Sciences, Inc. Biomarkers for detecting cancer
EA200900767A1 (ru) 2006-12-07 2009-12-30 Новартис Аг Антагонистические антитела против ephb3
EP2505651A3 (en) 2006-12-10 2013-01-09 Dyadic International, Inc. Isolated fungus with reduced protease activity
US8440185B2 (en) 2006-12-26 2013-05-14 The Johns Hopkins University Compositions and methods for the treatment of immunologic disorders
US7989173B2 (en) 2006-12-27 2011-08-02 The Johns Hopkins University Detection and diagnosis of inflammatory disorders
CA2673659A1 (en) 2006-12-27 2008-07-10 The Johns Hopkins University Methods of detecting and diagnosing inflamatory responses and disorders by determining the level of soluble b7-h4
CN101646781B (zh) 2006-12-29 2016-06-22 科罗拉多大学董事会 自身免疫病的诊断和治疗靶标及其用途
AU2008203703C1 (en) 2007-01-05 2014-04-03 University Of Zurich Method of providing disease-specific binding molecules and targets
CA2675379A1 (en) 2007-01-12 2008-07-17 Intercell Ag Protective proteins of s. agalactiae, combinations thereof and methods of using the same
WO2008098139A2 (en) 2007-02-07 2008-08-14 The Regents Of The University Of Colorado Axl tyrosine kinase inhibitors and methods of making and using the same
AU2008219097B2 (en) 2007-02-16 2011-06-23 Genzyme Corporation Method of identifying risk for thyroid disorder
ES2546863T3 (es) 2007-02-23 2015-09-29 Prothena Biosciences Limited Prevención y tratamiento de enfermedad sinucleinopática y amiloidogénica
CA2678493A1 (en) 2007-02-23 2008-08-28 The Trustees Of Columbia University In The City Of New York Methods to activate or block the hla-e/qa-1 restricted cd8+ t cell regulatory pathway to treat immunological disease
EP2118300B1 (en) 2007-02-23 2015-05-27 Prothena Biosciences Limited Prevention and treatment of synucleinopathic and amyloidogenic disease
US8519106B2 (en) 2007-03-13 2013-08-27 University Of Zurich Monoclonal human tumor-specific antibody
JP5721951B2 (ja) 2007-03-22 2015-05-20 バイオジェン アイデック マサチューセッツ インコーポレイテッド 抗体、抗体誘導体、および抗体断片を含む、ｃｄ１５４に特異的に結合する結合タンパク質ならびにその使用
RS55447B1 (sr) 2007-04-05 2017-04-28 Morphotek Inc Metode za inhibiranje vezivanja endosijalina za ligande
ES2465223T3 (es) 2007-04-27 2014-06-05 Zymogenetics, Inc. Antagonistas de IL-17A, IL-17F e IL-23P19 y procedimientos de uso
EP2152731A2 (en) 2007-05-02 2010-02-17 Intercell AG Klebsiella antigens
US8962273B2 (en) 2007-05-11 2015-02-24 Genzyme Corporation Methods of producing a secreted protein
US7709215B2 (en) 2007-06-01 2010-05-04 Cytonics Corporation Method for diagnosing and treating acute joint injury
EP1997830A1 (en) 2007-06-01 2008-12-03 AIMM Therapeutics B.V. RSV specific binding molecules and means for producing them
WO2008154543A2 (en) 2007-06-11 2008-12-18 Abbott Biotechnology Ltd. Methods for treating juvenile idiopathic arthritis
US8048420B2 (en) 2007-06-12 2011-11-01 Ac Immune S.A. Monoclonal antibody
US8613923B2 (en) 2007-06-12 2013-12-24 Ac Immune S.A. Monoclonal antibody
CN101778640A (zh) 2007-06-14 2010-07-14 比奥根艾迪克Ma公司 抗体制剂
CN101883782A (zh) 2007-06-18 2010-11-10 英特塞尔股份公司 衣原体抗原
EP3241842B1 (en) 2007-06-26 2024-01-31 F-star Therapeutics Limited Display of binding agents
KR101560843B1 (ko) 2007-06-27 2015-10-15 고꾸리쯔 다이가꾸 호우징 오사까 다이가꾸 페리오스틴의 Ｅｘｏｎ-17 부위에 의해 코드되는 펩티드에 대한 항체를 함유하는 암 치료제
EP2014681A1 (en) 2007-07-12 2009-01-14 Pierre Fabre Medicament Novel antibodies inhibiting c-met dimerization, and uses thereof
JP5932217B2 (ja) 2007-07-12 2016-06-08 ジーアイティーアール， インコーポレイテッド Ｇｉｔｒ結合分子を使用する併用療法
JP2010533649A (ja) 2007-07-13 2010-10-28 ザ ジョンズ ホプキンス ユニバーシティー Ｂ７−ｄｃ改変体
ES2402334T3 (es) 2007-08-02 2013-04-30 Gilead Biologics, Inc Procedimientos y composiciones para el tratamiento y el diagnóstico de la fibrosis
KR101561403B1 (ko) 2007-08-30 2015-10-16 다이이찌 산쿄 가부시키가이샤 항ｅｐｈａ２ 항체
JPWO2009031230A1 (ja) * 2007-09-06 2010-12-09 国立大学法人大阪大学 抗ｃｄ２０モノクローナル抗体
WO2009033071A2 (en) 2007-09-07 2009-03-12 Dyadic International, Inc. Novel fungal enzymes
US20100239570A1 (en) 2007-09-13 2010-09-23 Roger Nitsch Moncolonal amyloid beta (abeta) - specific antibody and uses thereof
MX2010002683A (es) 2007-09-14 2010-03-26 Amgen Inc Poblaciones de anticuerpos homogeneos.
US9403902B2 (en) 2007-10-05 2016-08-02 Ac Immune S.A. Methods of treating ocular disease associated with amyloid-beta-related pathology using an anti-amyloid-beta antibody
HUE025262T2 (en) 2007-10-11 2016-02-29 Daiichi Sankyo Co Ltd Antibody targeting osteoclast-linked Siglec-15 protein
JO3076B1 (ar) 2007-10-17 2017-03-15 Janssen Alzheimer Immunotherap نظم العلاج المناعي المعتمد على حالة apoe
SG185316A1 (en) 2007-10-19 2012-11-29 Immunas Pharma Inc ANTIBODY CAPABLE OF SPECIFICALLY BINDING TO Aβ OLIGOMER, AND USE THEREOF
WO2009059317A2 (en) 2007-11-01 2009-05-07 University Of Iowa Research Foundation Predicting amd with snps within or near c2, factor b, plekha1, htra1, prelp, or loc387715
DK2207808T3 (da) 2007-11-02 2013-08-05 Novartis Ag Forbedrede Nogo-A-bindingsmolekyler samt deres farmaceutiske anvendelse
WO2010008411A1 (en) 2007-11-09 2010-01-21 The Salk Institute For Biological Studies Use of tam receptor inhibitors as immunoenhancers and tam activators as immunosuppressors
CN101939336B (zh) 2007-11-12 2014-05-14 U3制药有限公司 Axl抗体
EP2463362B1 (en) 2007-11-28 2017-11-08 The Trustees Of The University Of Pennsylvania Simian subfamily c adenovirus SAdv-31 and uses thereof
CN101883858B (zh) 2007-11-28 2015-07-22 宾夕法尼亚大学托管会 猿猴亚家族E腺病毒SAdV-39、-25.2、-26、-30、-37和-38及其应用
EP2808345A3 (en) 2007-12-05 2015-03-11 Massachusetts Institute of Technology Aglycosylated immunoglobulin mutants
WO2009078799A1 (en) 2007-12-17 2009-06-25 Marfl Ab New vaccine for the treatment of mycobacterium related disorders
CA2709500A1 (en) 2007-12-25 2009-07-02 Meiji Seika Kaisha, Ltd. Type iii secretion system component protein pa1698 of pseudomonas aeruginosa
EA036059B1 (ru) 2007-12-28 2020-09-21 Протена Байосайенсиз Лимитед Способ получения антитела или его фрагмента, которое специфически связывается с агрегированным амилоидным белком
HUE031207T2 (hu) 2008-01-11 2017-07-28 Adheron Therapeutics Inc Cadherin-11 EC1 domén elleni antitestek gyulladásos ízületi rendellenességek kezeléséhez
WO2009088105A1 (en) * 2008-01-11 2009-07-16 Gene Techno Science Co., Ltd. HUMANIZED ANTI-α9 INTEGRIN ANTIBODIES AND THE USES THEREOF
US8603476B2 (en) 2008-01-11 2013-12-10 Astellas Pharma Inc. Humanized anti-human α9-integrin antibody
CA2714413C (en) 2008-02-08 2017-01-24 Immunas Pharma, Inc. Antibody capable of binding specifically to ab-oligomer, and use thereof
EP2325298B1 (en) 2008-03-04 2016-10-05 The Trustees Of The University Of Pennsylvania SIMIAN ADENOVIRUSES SAdV-36, -42.1, -42.2, AND -44 AND USES THEREOF
AU2009235622C9 (en) 2008-03-13 2015-07-02 Biotest Ag Agent for treating disease
KR20100135257A (ko) 2008-03-13 2010-12-24 바이오테스트 아게 질병 치료제
KR20100135808A (ko) 2008-03-13 2010-12-27 바이오테스트 아게 질병 치료제
CN101977927A (zh) 2008-03-17 2011-02-16 英特塞尔股份公司 针对肺炎链球菌保护的肽以及与其有关的组合物、方法和用途
EP2664339A3 (en) 2008-03-17 2013-12-11 Universitätsklinikum Münster YopM as delivery vehicle for cargo molecules and as biological therapeutic for immunomodulation of inflammatory reactions
EP2275537B1 (en) 2008-03-17 2014-12-24 Livtech Inc. Anti-human dlk-1 antibody having anti-tumor activity in vivo
US20110028697A1 (en) 2008-03-27 2011-02-03 Takara Bio Inc. Prophylactic/therapeutic agent for infectious disease
WO2009126934A2 (en) 2008-04-11 2009-10-15 Seattle Genetics, Inc. Detection and tratment of pancreatic, ovarian and other cancers
EP2113255A1 (en) 2008-05-02 2009-11-04 f-star Biotechnologische Forschungs- und Entwicklungsges.m.b.H. Cytotoxic immunoglobulin
CA2723197C (en) 2008-05-02 2017-09-19 Seattle Genetics, Inc. Methods and compositions for making antibodies and antibody derivatives with reduced core fucosylation
JP2011523560A (ja) 2008-06-02 2011-08-18 ダナ−ファーバー キャンサー インスティテュート インク． Ｘｂｐ１ペプチド、ｃｄ１３８ペプチドおよびｃｓ１ペプチド
WO2009154025A1 (ja) 2008-06-20 2009-12-23 国立大学法人岡山大学 酸化LDL/β2GPI複合体に対する抗体及びその用途
KR102007492B1 (ko) 2008-06-25 2019-08-05 에스바테크 - 어 노바티스 컴파니 엘엘씨 보편적 항체 프레임워크를 사용한 래빗 항체의 인간화
HUE056007T2 (hu) 2008-06-25 2022-01-28 Novartis Ag Nyúl ellenanyagok humanizálása univerzális ellenanyagváz alkalmazásával
PT2307457T (pt) 2008-06-25 2018-10-16 Esbatech Alcon Biomed Res Unit Anticorpos estáveis e solúveis que inibem o tnf
LT2824100T (lt) 2008-07-08 2018-05-10 Incyte Holdings Corporation 1,2,5-oksadiazolai, kaip indolamino 2,3-dioksigenazės inhibitoriai
EP2322610B1 (en) 2008-07-16 2016-12-14 Medical and Biological Laboratories Co., Ltd. Anti-human clcp1 antibody and use thereof
CN102170905B (zh) 2008-08-01 2016-08-03 阿克西斯股份有限公司 骨关节炎治疗剂及预防剂
US8795981B2 (en) 2008-08-08 2014-08-05 Molecular Devices, Llc Cell detection
US8417011B2 (en) 2008-09-18 2013-04-09 Molecular Devices (New Milton) Ltd. Colony detection
EP2172485A1 (en) 2008-10-01 2010-04-07 Pierre Fabre Medicament Novel anti CXCR4 antibodies and their use for the treatment of cancer
EP2346525A4 (en) 2008-10-02 2012-05-09 Celtaxsys Inc METHODS OF MODULATION OF NEGATIVE CHIMOTAXIA OF IMMUNE CELLS
JP2012505636A (ja) 2008-10-09 2012-03-08 ミネルバ バイオテクノロジーズ コーポレーション 細胞において多能性を誘導する方法
DK3199553T3 (da) 2008-10-29 2019-07-22 Circular Commitment Company Fremgangsmåder og midler til diagnosticering og behandling af hepatocellulært carcinom
US9067981B1 (en) 2008-10-30 2015-06-30 Janssen Sciences Ireland Uc Hybrid amyloid-beta antibodies
DK2350269T3 (en) 2008-10-31 2015-12-07 Univ Pennsylvania ABE ADENOVIRUS WITH SADV-46 HEXONCAPSIDE PROTEINS AND APPLICATIONS THEREOF
US9469691B2 (en) 2008-12-02 2016-10-18 Pierre Fabre Medicament Anti-cMET antibody
AR074439A1 (es) 2008-12-02 2011-01-19 Pf Medicament Anticuerpo anti-cmet (receptor c-met)
US8545839B2 (en) 2008-12-02 2013-10-01 Pierre Fabre Medicament Anti-c-Met antibody
CA2746778C (en) 2008-12-19 2019-04-23 University Of Zurich Human anti-alpha-synuclein autoantibodies
US8313915B2 (en) 2009-01-21 2012-11-20 Gundersen Lutheran Medical Foundation, Inc. Early detection of canine lyme disease by specific peptides and antibodies
US20100260752A1 (en) 2009-01-23 2010-10-14 Biosynexus Incorporated Opsonic and protective antibodies specific for lipoteichoic acid of gram positive bacteria
WO2010089340A2 (en) 2009-02-05 2010-08-12 Intercell Ag Peptides protective against e. faecalis, methods and uses relating thereto
WO2010092176A2 (en) 2009-02-13 2010-08-19 Intercell Ag Nontypable haemophilus influenzae antigens
WO2010096658A1 (en) 2009-02-19 2010-08-26 The Cleveland Clinic Foundation Corin as a marker for heart failure
CN103415534A (zh) 2009-03-10 2013-11-27 贝勒研究院 靶向抗原呈递细胞的癌症疫苗
CN102770457A (zh) 2009-03-10 2012-11-07 贝勒研究院 靶向抗原呈递细胞的疫苗
BRPI1009455A2 (pt) 2009-03-10 2016-03-01 Baylor Res Inst anticorpos anti-c40 e usos dos mesmos
US9315584B2 (en) 2009-03-25 2016-04-19 Tohoku University LH-type bispecific antibody
KR101690340B1 (ko) 2009-04-09 2016-12-27 다이이찌 산쿄 가부시키가이샤 항 Ｓｉｇｌｅｃ-15 항체
DE202010018378U1 (de) 2009-04-10 2016-04-07 Tufts Medical Center, Inc. PAR-1-Aktivierung durch Metalloproteinase-1 (MMP-1)
EP2419447B1 (en) 2009-04-17 2017-08-23 Immunas Pharma, Inc. Antibodies that specifically bind to a beta oligomers and use thereof
CN102458517B (zh) 2009-04-29 2014-07-23 阿布维生物技术有限公司 自动注射装置
EP2246364A1 (en) 2009-04-29 2010-11-03 Pierre Fabre Médicament Anti CXCR4 antibodies for the treatment of HIV
EP2270053A1 (en) 2009-05-11 2011-01-05 U3 Pharma GmbH Humanized AXL antibodies
EP2435559A1 (en) 2009-05-29 2012-04-04 The Trustees Of The University Of Pennsylvania Simian adenovirus 41 and uses thereof
EP2260864A1 (en) 2009-06-10 2010-12-15 University of Melbourne Therapeutic applications
TWI513465B (zh) 2009-06-25 2015-12-21 Regeneron Pharma 以ｄｌｌ４拮抗劑與化學治療劑治療癌症之方法
AU2010275367B2 (en) 2009-07-24 2015-09-03 The Regents Of The University Of California Methods and compositions for treating and preventing disease associated with avB5 integrin
CA2768330A1 (en) 2009-07-28 2011-02-03 F. Hoffmann-La Roche Ag Non-invasive in vivo optical imaging method
EP2462451B1 (en) 2009-08-05 2016-02-17 Nexigen GmbH Human hcv-interacting proteins and methods of use
WO2011024114A1 (en) 2009-08-25 2011-03-03 Ecole Polytechnique Federale De Lausanne (Epfl) Targeting extracellular matrix molecules for the treatment of cancer
TWI412375B (zh) 2009-08-28 2013-10-21 Roche Glycart Ag 人類化抗ｃｄｃｐ１抗體
CN102666581A (zh) 2009-08-31 2012-09-12 艾普利穆恩公司 用于抑制移植物排斥的方法和组合物
EP2477647B1 (en) 2009-09-14 2016-01-13 The Regents of the University of Colorado Modulation of yeast-based immunotherapy products and responses
EP2305285A1 (en) 2009-09-29 2011-04-06 Julius-Maximilians-Universität Würzburg Means and methods for treating ischemic conditions
US8568726B2 (en) 2009-10-06 2013-10-29 Medimmune Limited RSV specific binding molecule
EP2308897A1 (en) 2009-10-09 2011-04-13 Pierre Fabre Medicament Chimeric antibodies specific for CD151 and use thereof in the treatment of cancer
CA2776756A1 (en) 2009-10-11 2011-04-14 Biogen Idec Ma Inc. Anti-vla-4 related assays
JP5818003B2 (ja) 2009-11-18 2015-11-18 国立大学法人東北大学 ヒト型化抗ｅｇｆｒ抗体可変領域の高機能性変異体
EP2332929A1 (en) 2009-11-25 2011-06-15 ArisGen SA Orthoester derivatives of crown ethers as carriers for pharmaceutical and diagnostic compositions
GB0920944D0 (en) 2009-11-30 2010-01-13 Biotest Ag Agents for treating disease
US9872905B2 (en) 2009-12-01 2018-01-23 President And Fellows Of Harvard College Modulation of NK cell antigen specific effector activity by modulation of CXCR6 (CD186)
US20110150891A1 (en) 2009-12-16 2011-06-23 Philip Bosch Methods of Treating Interstitial Cystitis
WO2011088193A2 (en) 2010-01-13 2011-07-21 University Of Medicine And Dentistry Of New Jersey Fluorophore chelated lanthanide luminiscent probes with improved quantum efficiency
EP2525813B1 (en) 2010-01-20 2017-01-04 Merck Sharp & Dohme Corp. Anti-ilt5 antibodies and ilt5-binding antibody fragments
EP2525822B1 (en) 2010-01-20 2017-05-10 Merck Sharp & Dohme Corp. Immunoregulation by anti-ilt5 antibodies and ilt5-binding antibody fragments
KR20120115383A (ko) 2010-01-29 2012-10-17 가부시키가이샤 아크시스 변형성 관절증 치료 또는 예방용 의약 조성물 및 이의 제조 방법
JP5792636B2 (ja) 2010-01-29 2015-10-14 Ａｘｉｓ株式会社 変形性関節症治療剤を含有する注射剤
JP2012246222A (ja) 2010-01-29 2012-12-13 Axis Inc 変形性関節症治療剤または予防剤を製造するための使用
CN102959088A (zh) 2010-02-02 2013-03-06 艾博特生物技术有限公司 用于预测对TNF-α抑制剂治疗的反应性的方法和组合物
MX2012008884A (es) 2010-02-08 2012-08-31 Agensys Inc Conjugados de anticuerpo y farmaco (adc) que se unen a proteinas 161p2f10b.
EP4219560A3 (en) 2010-02-18 2023-08-23 The Regents of The University of California Integrin alpha v beta 8 neutralizing antibody
WO2011109398A2 (en) 2010-03-02 2011-09-09 President And Fellows Of Harvard College Methods and compositions for treatment of angelman syndrome and autism spectrum disorders
WO2011106885A1 (en) 2010-03-03 2011-09-09 The University Of British Columbia Oligomer-specific amyloid beta epitope and antibodies
CA2794551A1 (en) 2010-03-26 2011-09-29 Westfaelische Wilhelms-Universitaet Muenster Substitute therapy for glucocorticoids
EP2371863A1 (en) 2010-03-30 2011-10-05 Pierre Fabre Médicament Humanized anti CXCR4 antibodies for the treatment of cancer
CN103154027B (zh) 2010-04-09 2016-06-29 重症监护诊断股份有限公司 可溶性人st-2抗体和分析法
PL2558499T3 (pl) 2010-04-16 2017-10-31 Biogen Ma Inc Przeciwciała anty-VLA-4
CN103118737B (zh) 2010-04-21 2015-05-20 艾伯维生物技术有限公司 用于治疗药剂的受控输送的可佩戴自动注射装置
JP6145404B2 (ja) 2010-05-07 2017-06-14 エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト エクスビボでの細胞の検出のための診断的方法
BR112012029281B1 (pt) 2010-05-17 2020-12-08 Livtech, Inc anticorpo contra trop-2 humano, anticorpo monoclonal contra trop-2 humano, fragmento de anticorpo derivado de anticorpo, hibridoma, conjugado, composição farmacêutica, uso de composição farmacêutica, método para detectar um tumor e kit para tratar, diagnosticar ou detectar um tumor
US20110287018A1 (en) 2010-05-19 2011-11-24 Philip Bosch Methods of Treating Interstitial Cystitis
WO2012005076A1 (ja) 2010-07-08 2012-01-12 本田技研工業株式会社 高周波加熱用コイル
EP2593475B1 (en) 2010-07-14 2016-03-02 Merck Sharp & Dohme Corp. Anti-addl monoclonal antibody and uses thereof
HUE038000T2 (hu) 2010-07-15 2018-09-28 Adheron Therapeutics Inc A cadherin-11 EC1 doménját célzó humanizált ellenanyagok kapcsolódó készítmények és eljárások
KR102080704B1 (ko) 2010-07-29 2020-02-24 세센 바이오, 아이엔씨. 키메라 il-1 수용체 유형 i 항진제 및 길항제들
CA2806909C (en) 2010-07-30 2019-12-17 Ac Immune S.A. Safe and functional humanized antibodies
JP2012034668A (ja) 2010-08-12 2012-02-23 Tohoku Univ ヒト型化抗ｅｇｆｒ抗体リジン置換可変領域断片及びその利用
WO2012027494A1 (en) 2010-08-24 2012-03-01 Regents Of The University Of Minnesota Bispecific targeting reagents
CA2807244A1 (en) 2010-08-27 2012-03-01 University Of Zurich A novel diagnostic and therapeutic target in inflammatory and/or cardiovascular diseases
WO2012025636A1 (en) 2010-08-27 2012-03-01 University Of Zurich Method for target and drug validation in inflammatory and/or cardiovascular diseases
WO2012028697A1 (en) 2010-09-01 2012-03-08 Eth Zürich, Institute Of Molecular Biology And Biophysics Affinity purification system based on donor strand complementation
US20120244141A1 (en) 2010-09-28 2012-09-27 Boehringer Ingelheim International Gmbh Stratification of cancer patients for susceptibility to therapy with PTK2 inhibitors
US8497138B2 (en) 2010-09-30 2013-07-30 Genetix Limited Method for cell selection
WO2012043747A1 (ja) 2010-09-30 2012-04-05 独立行政法人理化学研究所 グリオーマの治療方法、グリオーマの検査方法、所望の物質をグリオーマに送達させる方法、及びそれらの方法に用いられる薬剤
WO2012049570A1 (en) 2010-10-11 2012-04-19 Panima Pharmaceuticals Ag Human anti-tau antibodies
RU2600444C2 (ru) 2010-10-13 2016-10-20 Янссен Байотек, Инк. Человеческие антитела к онкостатину м и способы их применения
WO2012052230A1 (en) 2010-10-18 2012-04-26 Mediapharma S.R.L. Erbb3 binding antibody
AR083495A1 (es) 2010-10-22 2013-02-27 Esbatech Alcon Biomed Res Unit Anticuerpos estables y solubles
US9272052B2 (en) 2010-10-22 2016-03-01 Seattle Genetics, Inc. Synergistic effects between auristatin-based antibody drug conjugates and inhibitors of the PI3K-AKT mTOR pathway
EP3326645B1 (en) 2010-10-25 2020-03-18 Biogen MA Inc. Methods for determining differences in alpha-4 integrin activity by correlating differences in svcam and/or smadcam levels
AU2011322508A1 (en) 2010-10-27 2013-05-02 Pierre Fabre Medicament Antibodies for the treatment of HIV
NZ610153A (en) 2010-10-29 2014-07-25 Daiichi Sankyo Co Ltd Novel anti-dr5 antibody
EP2640425A2 (en) 2010-11-18 2013-09-25 Beth Israel Deaconess Medical Center, Inc. Methods of treating obesity by inhibiting nicotinamide n-methyl transferase (nnmt)
EP2640744A4 (en) 2010-11-19 2014-05-28 Eisai R&D Man Co Ltd NEUTRALIZATION OF ANTIBODIES TO CCL20
AU2011332025B2 (en) 2010-11-23 2015-06-25 The Trustees Of The University Of Pennsylvania Subfamily E simian adenoviruses A1321, A1325, A1295, A1309 and A1322 and uses thereof
EP3628689A1 (en) 2010-12-17 2020-04-01 Neurimmune Holding AG Human anti-sod1 antibodies
WO2012090939A1 (ja) 2010-12-27 2012-07-05 国立大学法人名古屋大学 受容体型チロシンキナーゼが仲介する癌細胞の生存促進性シグナルを抑制する方法
EP2663580B1 (en) 2011-01-10 2016-12-07 CT Atlantic Ltd. Combination therapy including tumor associated antigen binding antibodies
PT2663579T (pt) 2011-01-14 2017-07-28 Univ California Terapêutica de anticorpos contra a proteína r0r-1 e métodos para sua utilização
EP2749305B1 (en) 2011-01-24 2017-11-01 AbbVie Biotechnology Ltd Automatic injection devices having overmolded gripping surfaces
WO2012104824A1 (en) 2011-02-04 2012-08-09 Ecole polytechnique fédérale de Lausanne (EPFL) Therapeutic antibodies targeting app-c99
WO2012107589A1 (en) 2011-02-11 2012-08-16 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for the treatment and prevention of hcv infections
WO2012110843A1 (en) 2011-02-18 2012-08-23 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for promoting fibrinolysis and thrombolysis
WO2012113775A1 (en) 2011-02-21 2012-08-30 University Of Zurich Ankyrin g and modulators thereof for the treatment of neurodegenerative disorders
JP6385060B2 (ja) 2011-03-07 2018-09-05 エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト 治療的に活性な抗体のインビボにおける選択
EP2683290B1 (en) 2011-03-07 2018-11-07 F.Hoffmann-La Roche Ag Methods for in vivo testing of therapeutic antibodies
US10139420B2 (en) 2011-03-09 2018-11-27 ISNERM (Institut National de la Sante et de la Recherche Medicale) Methods for treating vaso-occlusive crisis using non-modified annexin V
WO2012125680A1 (en) 2011-03-16 2012-09-20 Novartis Ag Methods of treating vasculitis using an il-17 binding molecule
EP2686418A4 (en) 2011-03-17 2015-04-22 Minerva Biotechnologies Corp METHOD FOR THE PRODUCTION OF PLURIPOTENTAL STEM CELLS
KR101551555B1 (ko) 2011-03-17 2015-09-08 밀테니 비오텍 게앰베하 Tcr 알파/베타가 고갈된 세포 제제
EP2688592A4 (en) 2011-03-25 2015-07-22 Baylor Res Inst COMPOSITIONS AND METHODS FOR IMMUNIZATION AGAINST HEPATITIS C VIRUS
TW201249867A (en) 2011-04-01 2012-12-16 Astellas Pharma Inc Novel anti-human il-23 receptor antibody
CN107096098A (zh) 2011-04-21 2017-08-29 艾伯维公司 可佩戴式自动注射装置
PL2703486T3 (pl) 2011-04-25 2018-07-31 Daiichi Sankyo Company, Limited Przeciwciało anty-b7-h3
UA116189C2 (uk) 2011-05-02 2018-02-26 Мілленніум Фармасьютікалз, Інк. КОМПОЗИЦІЯ АНТИ-α4β7 АНТИТІЛА
EP2704742B1 (en) 2011-05-02 2017-07-12 Millennium Pharmaceuticals, Inc. Formulation for anti- 4 7 antibody
UA117218C2 (uk) 2011-05-05 2018-07-10 Мерк Патент Гмбх Поліпептид, спрямований проти il-17a, il-17f та/або il17-a/f
EP2707711A1 (en) 2011-05-09 2014-03-19 The Cleveland Clinic Foundation Serum s100b and uses thereof
WO2012163848A1 (en) 2011-05-27 2012-12-06 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for the treatment of crohn's disease
EP2530088A1 (en) 2011-05-30 2012-12-05 Klinikum rechts der Isar der Technischen Universität München Means and methods for diagnosing and treating multiple sclerosis
EP2714742A1 (en) 2011-06-03 2014-04-09 CT Atlantic Ltd. Magea3 binding antibodies
JP2014524891A (ja) 2011-06-03 2014-09-25 シーティー アトランティック リミテッド Ｍａｇｅａ３結合抗体
JP6305919B2 (ja) 2011-06-06 2018-04-04 プロセナ バイオサイエンシーズ リミテッド Ｍｃａｍアンタゴニスト及び治療の方法
WO2012172449A1 (en) 2011-06-13 2012-12-20 Pfizer Inc. Lactams as beta secretase inhibitors
US20140120555A1 (en) 2011-06-20 2014-05-01 Pierre Fabre Medicament Anti-cxcr4 antibody with effector functions and its use for the treatment of cancer
CA2839563C (en) 2011-06-23 2019-10-29 Biogen Idec International Neuroscience Gmbh Anti-alpha synuclein binding molecules
DE202011103324U1 (de) 2011-07-12 2012-01-02 Nekonal S.A.R.L. Therapeutische anti-TIRC7 Antikörper für die Verwendung in Immun und anderen Krankheiten
GB201112056D0 (en) 2011-07-14 2011-08-31 Univ Leuven Kath Antibodies
US20140308275A1 (en) 2011-07-27 2014-10-16 Inserm (Institut National De La Sante Et De La Recherche Medicale Methods for diagnosing and treating myhre syndrome
BR112014002576B1 (pt) 2011-08-11 2022-08-23 Astellas Pharma Inc. Fragmento fab de anticorpo anti-ngf humano, método para produzir o mesmo e vetor de expressão compreendendo um polinucleotídeo que codifica o dito fragmento fab'
WO2013024022A1 (en) 2011-08-12 2013-02-21 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for treatment of pulmonary hypertension
US20140242085A1 (en) 2011-08-12 2014-08-28 Medical & Biological Laboratories Co., Ltd. Methods and composition for testing, preventing, and treating aspergillus fumigatus infection
GB201116092D0 (en) 2011-09-16 2011-11-02 Bioceros B V Antibodies and uses thereof
DK2758433T3 (en) 2011-09-19 2018-01-15 Axon Neuroscience Se PROTEIN-BASED THERAPY AND DIAGNOSIS OF TAU-MEDIATED PATHOLOGY OF ALZHEIMER'S DISEASE
GB2495115A (en) * 2011-09-29 2013-04-03 Oxford Plastic Sys Ltd Base for supporting temporary fence panels or posts.
TW201329105A (zh) 2011-10-04 2013-07-16 Thr Trustees Of Columbia University In The City Of New York 人類ｎｏｔｃｈ１引誘物
WO2013050441A1 (en) 2011-10-05 2013-04-11 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical composition for inhibiting or preventing platelet aggregation
US20140248294A1 (en) 2011-10-05 2014-09-04 University Of Bremen Wnt4 and med12 for use in the diagnosis and treatment of tumor diseases
WO2013054320A1 (en) 2011-10-11 2013-04-18 Tel Hashomer Medical Research Infrastructure And Services Ltd. Antibodies to carcinoembryonic antigen-related cell adhesion molecule (ceacam)
US10378060B2 (en) 2011-10-14 2019-08-13 Dana-Farber Cancer Institute, Inc. ZNF365/ZFP365 biomarker predictive of anti-cancer response
AU2012326137B2 (en) 2011-10-17 2018-11-29 Minerva Biotechnologies Corporation Media for stem cell proliferation and induction
EP2768971A1 (en) 2011-10-20 2014-08-27 Institut National de la Santé et de la Recherche Médicale (INSERM) Methods for the detection and the treatment of cardiac remodeling
EP2589609A1 (en) 2011-11-03 2013-05-08 Pierre Fabre Medicament Antigen binding protein and its use as addressing product for the treatment of cancer
US9427464B2 (en) 2011-11-22 2016-08-30 Chiome Bioscience Inc. Anti-human TROP-2 antibody having an antitumor activity in vivo
JP2015506911A (ja) 2011-11-22 2015-03-05 アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル 気道過敏症を低減させるための方法および薬学的組成物
EP2785365B1 (en) 2011-11-28 2017-07-19 Institut National de la Sante et de la Recherche Medicale (INSERM) Pharmaceutical composition for use in the treatment of dysfunction associated with aging
EP2602621A1 (en) 2011-12-08 2013-06-12 Julius-Maximilians-Universität Würzburg LASP-1, a novel urinary marker for transitional cell carcinoma detection
SG11201403134PA (en) * 2011-12-13 2014-07-30 Nordic Nanovector As Chimeric therapeutic anti - cd37 antibodie hh1
WO2013093122A2 (en) 2011-12-23 2013-06-27 Phenoquest Ag Antibodies for the treatment and diagnosis of affective and anxiety disorders
FR2984750B1 (fr) 2011-12-23 2014-01-10 Lfb Biotechnologies Nouvelles compositions pharmaceutiques comprenant un anticorps liant le recepteur humain de l'hormone anti-mullerienne de type ii
PL2797951T3 (pl) 2011-12-28 2018-07-31 Immunoqure Ag Sposób izolacji ludzkich przeciwciał
CA2858336A1 (en) 2012-01-01 2013-07-04 Qbi Enterprises Ltd. Endo180-targeted particles for selective delivery of therapeutic and diagnostic agents
EP2812702B1 (en) 2012-02-10 2019-04-17 Seattle Genetics, Inc. Diagnosis and management of CD30-expressing cancers
ES2732243T3 (es) 2012-02-16 2019-11-21 Santarus Inc Composiciones farmacéuticas de anticuerpos ANTI-VLA1 (CD49A)
US10357566B2 (en) 2012-02-23 2019-07-23 Daiichi Sankyo Europe Gmbh HER3 inhibitor for modulating radiosensitivity
ES2701064T3 (es) 2012-02-28 2019-02-20 Astellas Pharma Inc Novedoso anticuerpo antirreceptor IL-23 humano
EA030828B1 (ru) 2012-03-15 2018-10-31 Янссен Байотек, Инк. Человеческие антитела к cd27, методы и применение
ES2731757T3 (es) 2012-03-20 2019-11-18 Biogen Ma Inc Anticuerpos neutralizantes de JCV
ES2660472T3 (es) 2012-03-30 2018-03-22 Daiichi Sankyo Company, Limited Anticuerpo anti-Siglec-15 modificado con CDR
CN104321430A (zh) 2012-03-30 2015-01-28 第一三共株式会社 新颖的抗-siglec-15抗体
EP2833900B1 (en) 2012-04-01 2018-09-19 Technion Research & Development Foundation Limited Extracellular matrix metalloproteinase inducer (emmprin) peptides and binding antibodies
CN103382223B (zh) 2012-04-01 2015-06-10 上海益杰生物技术有限公司 针对表皮生长因子受体隐蔽表位和t细胞抗原的多功能抗体多肽
CA2869394A1 (en) 2012-04-02 2013-10-10 Gundersen Lutheran Health System, Inc. Reagents, methods, and kits for the classification of cancer
AU2013247645B2 (en) 2012-04-09 2019-02-14 Daiichi Sankyo Company, Limited Anti-FGFR2 antibody
WO2013160879A1 (en) 2012-04-27 2013-10-31 Daiichi Sankyo Company, Limited Anti-robo4-antibody
US9062120B2 (en) 2012-05-02 2015-06-23 Janssen Biotech, Inc. Binding proteins having tethered light chains
EP2848633B1 (en) 2012-05-11 2019-02-06 Microbial Chemistry Research Foundation Anti-cxadr antibody
BR112014028306A2 (pt) 2012-05-15 2018-04-17 Morphotek, Inc. métodos para tratamento de câncer gástrico.
CN105473723A (zh) 2012-05-18 2016-04-06 宾夕法尼亚大学托管会 亚家族e猿腺病毒a1302、a1320、a1331和a1337及其用途
JP2015520373A (ja) 2012-05-22 2015-07-16 アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル 巣状分節性糸球体硬化症を診断及び処置するための方法
EP3508497A1 (en) 2012-05-24 2019-07-10 Mountgate Group Limited Compositions and methods related to prevention and treatment of rabies infection
ES2859522T3 (es) 2012-07-13 2021-10-04 Univ Pennsylvania Control de la toxicidad para la actividad antitumoral de CAR
US20150184155A1 (en) 2012-07-18 2015-07-02 Inserm (Institut National De La Sante Et De La Recherche Medicale) Methods for preventing and treating chronic kidney disease (ckd)
IN2015DN00552A (zh) 2012-07-19 2015-06-26 Redwood Bioscience Inc
EP2881467B1 (en) 2012-07-30 2018-10-31 National University Corporation Nagoya University Monoclonal antibody against human midkine
EP2888283B1 (en) 2012-08-24 2018-09-19 The Regents of The University of California Antibodies and vaccines for use in treating ror1 cancers and inhibiting metastasis
TWI660972B (zh) 2012-09-10 2019-06-01 愛爾蘭商尼歐托普生物科學公司 抗ｍｃａｍ抗體及相關使用方法
EP2896291B1 (en) 2012-09-13 2019-03-20 Chugai Seiyaku Kabushiki Kaisha Gene knock-in non-human animal
EP2711016A1 (en) 2012-09-21 2014-03-26 Covagen AG Novel IL-17A binding molecules and medical uses thereof
US9303086B2 (en) 2012-10-03 2016-04-05 Livtech, Inc. Anti-hDlk-1 antibody having an antitumor activity in vivo
ES2776029T3 (es) 2012-10-08 2020-07-28 St Jude Childrens Res Hospital Terapias basadas en el control de la estabilidad y función de las células T reguladoras por medio de un eje neuropilina-1:semaforina
NZ740948A (en) 2012-10-11 2019-11-29 Daiichi Sankyo Co Ltd Glycinamide derivatives and production methods thereof
DE102012020496A1 (de) 2012-10-18 2014-04-24 Charité - Universitätsmedizin Berlin Biomarker zur Diagnostik und Behandlung von Neurofibromatose Typ 1
ES2782248T3 (es) 2012-10-19 2020-09-11 Daiichi Sankyo Co Ltd Conjugado de anticuerpo y fármaco producido por la unión a través de un enlazador que tiene estructura hidrófila
US20150246118A1 (en) 2012-10-26 2015-09-03 INSERM (Institut National de la Santé et de la Recherche Médicale) Lyve-1 antagonists for preventing or treating a pathological condition associated with lymphangiogenesis
AU2013340799B2 (en) 2012-11-01 2018-08-09 Max-Delbruck-Centrum Fur Molekulare Medizin (Mdc) An antibody that binds CD269 (BCMA) suitable for use in the treatment of plasma cell diseases such as multiple myeloma and autoimmune diseases
CN104955842B (zh) 2012-11-05 2018-04-10 皮埃尔法布雷医药公司 抗原结合蛋白及其作为定位产品用于治疗癌症的用途
JP6445446B2 (ja) 2012-11-08 2018-12-26 アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル 骨転移の治療のための方法及び医薬組成物
AR093445A1 (es) 2012-11-14 2015-06-10 Regeneron Pharma Metodos para tratar el cancer de ovario con antagonistas de dll4
US9902775B2 (en) 2012-12-10 2018-02-27 Biogen Ma Inc. Anti-blood dendritic cell antigen 2 antibodies and uses thereof
CA2894225A1 (fr) 2012-12-17 2014-06-26 Laboratoire Francais Du Fractionnement Et Des Biotechnologies Utilisation d'anticorps monoclonaux pour le traitement de l'inflammation et d'infections bacteriennes
US10024844B2 (en) 2012-12-20 2018-07-17 Hospital For Special Surgery Identification of an inhibitor of iRhom1 or an inhibitor of iRhom2
LT2935326T (lt) 2012-12-21 2020-12-10 Biogen Ma Inc. Žmogaus antikūnai prieš tau baltymą
EP2938631B1 (en) 2012-12-31 2018-12-19 Neurimmune Holding AG Recombinant human antibodies for therapy and prevention of polyomavirus-related diseases
EP2752426A1 (en) 2013-01-03 2014-07-09 Covagen AG Human serum albumin binding compounds and fusion proteins thereof
AU2013375015A1 (en) 2013-01-28 2015-08-13 Evec Inc. Humanized anti-HMGB1 antibody or antigen-binding fragment thereof
WO2014118317A1 (en) 2013-02-01 2014-08-07 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for predicting and preventing metastasis in triple negative breast cancers
US9932396B2 (en) 2013-02-08 2018-04-03 Medical & Biological Laboratories Co., Ltd. Antibody against human NRG1 protein
AU2013378628A1 (en) 2013-02-15 2015-06-11 Esbatech - A Novartis Company Llc Acceptor framework for CDR grafting
JP2016506752A (ja) 2013-02-20 2016-03-07 エスバテック − ア ノバルティスカンパニー エルエルシー Ｃｄｒグラフトのためのアクセプターフレームワーク
FR3004184B1 (fr) 2013-02-26 2016-03-18 Agronomique Inst Nat Rech Anticorps anti-gluten desamide et utilisations.
US9429584B2 (en) 2013-02-28 2016-08-30 National Cancer Center Antibody against insoluble fibrin
ES2811060T3 (es) 2013-03-08 2021-03-10 Univ Osaka Anticuerpo contra péptido codificado por exón-21 de periostina y composición farmacéutica para prevenir o tratar enfermedades asociadas a inflamación que contienen el mismo
JP6450364B2 (ja) 2013-03-13 2019-01-09 セセン バイオ， インコーポレイテッド 眼送達のためのキメラサイトカイン製剤
US10023608B1 (en) 2013-03-13 2018-07-17 Amgen Inc. Protein purification methods to remove impurities
US9302005B2 (en) 2013-03-14 2016-04-05 Mayo Foundation For Medical Education And Research Methods and materials for treating cancer
US10081673B2 (en) 2013-03-14 2018-09-25 Ffe Therapeutics Llc Compositions and methods for treating angiogenesis-related disorders
WO2014144466A1 (en) 2013-03-15 2014-09-18 Biogen Idec Ma Inc. Anti-alpha v beta 6 antibodies and uses thereof
US10035860B2 (en) 2013-03-15 2018-07-31 Biogen Ma Inc. Anti-alpha V beta 6 antibodies and uses thereof
EA201591806A1 (ru) 2013-03-15 2016-01-29 Байоджен Ма Инк. Лечение и профилактика острой почечной недостаточности с применением анти-альфа-v-бета-5 антител
DK2976361T3 (en) 2013-03-18 2018-10-01 Biocerox Prod Bv HUMANIZED ANTI-CD134- (0X40) ANTIBODIES AND APPLICATIONS THEREOF
ES2823648T3 (es) 2013-04-01 2021-05-07 Univ California Métodos y composiciones para tratar y prevenir enfermedades asociadas con la integrina AVB8
WO2014174596A1 (ja) 2013-04-23 2014-10-30 株式会社医学生物学研究所 ヘパリン結合上皮増殖因子様増殖因子に対する機能性モノクローナル抗体
US9717648B2 (en) 2013-04-24 2017-08-01 Corning Incorporated Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients
CN104140974B (zh) 2013-05-08 2017-09-29 科济生物医药（上海）有限公司 编码gpc‑3嵌合抗原受体蛋白的核酸及表达gpc‑3嵌合抗原受体蛋白的t淋巴细胞
JP6652916B2 (ja) 2013-06-20 2020-02-26 ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア 膵臓がんを診断するための方法
US10112995B2 (en) 2013-07-03 2018-10-30 Immunoqure Ag Human anti-IFN-α antibodies
JP6450381B2 (ja) 2013-07-05 2019-01-09 ユニバーシティ オブ ワシントン スルー イッツ センター フォー コマーシャリゼーション がんを処置するための可溶性ｍｉｃ中和モノクローナル抗体
US20160176943A1 (en) 2013-07-05 2016-06-23 Inserm (Insititut National De La Sante Et De La Recherche Medicale) Novel alternative splice transcripts for mhc class i related chain alpha (mica) and uses thereof
HUE043111T2 (hu) 2013-08-09 2019-08-28 Astellas Pharma Inc Új humán TSLP receptor elleni antitest
EP3055695A1 (en) 2013-09-12 2016-08-17 Institut National de la Santé et de la Recherche Médicale Method for in vitro quantifying allo-antibodies, auto-antibodies and/or therapeutic antibodies
CA2924020A1 (en) 2013-09-20 2015-03-26 Westfaelische Wilhelms-Universitaet Muenster Cell-penetrating bacterial e3-ubiqitin-ligases for use in immunotherapy
JP6615100B2 (ja) 2013-09-24 2019-12-04 ザ ファインスタイン インスティチュート フォー メディカル リサーチ 低温誘導性ｒｎａ結合タンパク質活性を阻害するペプチド
WO2015048531A1 (en) 2013-09-26 2015-04-02 Beth Israel Deaconess Medical Center, Inc. Inhibition of sgk1 in the treatment of heart conditions
JP6494519B6 (ja) 2013-09-30 2019-07-31 第一三共株式会社 抗ｌｐｓ ｏ１１抗体
EP3052131B1 (en) 2013-10-01 2018-12-05 Mayo Foundation for Medical Education and Research Methods for treating cancer in patients with elevated levels of bim
CN105792844B (zh) 2013-10-08 2021-03-02 第一三共株式会社 抗fgfr2抗体和另一药剂的组合
WO2015069865A1 (en) 2013-11-06 2015-05-14 Janssen Biotech, Inc. Anti-ccl17 antibodies
WO2015068781A1 (ja) 2013-11-06 2015-05-14 国立大学法人大阪大学 インフルエンザウイルスａ型のグループ１に対して広域な中和活性を有する抗体
JP2016538286A (ja) 2013-11-15 2016-12-08 アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル 膵臓癌を処置するための方法及び医薬組成物
WO2015082446A1 (en) 2013-12-02 2015-06-11 F. Hoffmann-La Roche Ag Treatment of cancer using an anti-cdcp1 antibody and a taxane
EP3088519A4 (en) 2013-12-24 2017-09-13 Astellas Pharma Inc. Novel anti-human bdca-2 antibody
SG11201605215YA (en) 2013-12-25 2016-08-30 Daiichi Sankyo Co Ltd Anti-trop2 antibody-drug conjugate
JP6682438B2 (ja) 2014-01-09 2020-04-15 ハダシット メディカル リサーチ サービシーズ アンド ディベロップメント リミテッドＨａｄａｓｉｔ Ｍｅｄｉｃａｌ Ｒｅｓｅａｒｃｈ Ｓｅｒｖｉｃｅｓ ａｎｄ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｔｄ． 癌治療のための改善された細胞組成物および方法
EP3992210A1 (en) 2014-01-13 2022-05-04 Baylor Research Institute Novel vaccines against hpv and hpv-related diseases
CN104774264B (zh) 2014-01-15 2018-09-14 上海易乐生物技术有限公司 抗人proBDNF单克隆抗体及其在疼痛中的作用
KR102275925B1 (ko) 2014-01-31 2021-07-12 다이이찌 산쿄 가부시키가이샤 항-her2 항체-약물 접합체
WO2015124570A1 (en) 2014-02-18 2015-08-27 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical composition for the treatment of influenza a virus infection
EP3108255B1 (en) 2014-02-18 2020-08-12 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for the treatment of diseases mediated by the nrp-1/obr complex signaling pathway
EP3415160B1 (en) 2014-03-04 2021-08-18 Klinikum der Universität München Polypeptides derived from enterococcus and their use for vaccination and the generation of therapeutic antibodies
WO2015140351A1 (en) 2014-03-21 2015-09-24 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for enhancing myelination
WO2015145449A2 (en) 2014-03-27 2015-10-01 Yeda Research And Development Co. Ltd. T-cell receptor cdr3 peptides and antibodies
CN111228511B (zh) 2014-04-10 2024-06-18 第一三共株式会社 抗her3抗体-药物偶联物
WO2015158765A1 (en) 2014-04-15 2015-10-22 Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) Differential diagnosis of eczema and psoriasis
CA2944903A1 (en) 2014-04-24 2015-10-29 Dana-Farber Cancer Institute, Inc. Tumor suppressor and oncogene biomarkers predictive of anti-immune checkpoint inhibitor response
MA39378B2 (fr) 2014-04-25 2021-02-26 Pf Medicament Anticorps igf-1r et son utilisation comme véhicule d'adressage pour le traitement du cancer
DK3134124T3 (da) 2014-04-25 2019-05-06 Pf Medicament Igf-1r-antistof-lægemiddel-konjugat og dens anvendelse til behandling af kræft
SI3134125T1 (sl) 2014-04-25 2020-02-28 Pierre Fabre Medicament Konjugat zdravila s protitelesom in uporaba le-tega za zdravljenje raka
US11427647B2 (en) 2014-04-27 2022-08-30 Famewave Ltd. Polynucleotides encoding humanized antibodies against CEACAM1
MD20160130A2 (ro) 2014-04-27 2017-04-30 Ccam Biotherapeutics Ltd. Anticorpi umanizaţi contra CEACAM1
US10302653B2 (en) 2014-05-22 2019-05-28 Mayo Foundation For Medical Education And Research Distinguishing antagonistic and agonistic anti B7-H1 antibodies
TWI713453B (zh) 2014-06-23 2020-12-21 美商健生生物科技公司 干擾素α及ω抗體拮抗劑
AU2015279712B2 (en) 2014-06-26 2021-03-25 Yale University Compositions and methods to regulate renalase in the treatment of diseases and disorders
EP3998273A1 (en) 2014-07-17 2022-05-18 The Trustees Of The University Of Pennsylvania Methods for using exosomes to monitor transplanted organ status
CN112979828A (zh) 2014-07-17 2021-06-18 恺兴生命科技(上海)有限公司 靶向cld18a2的t淋巴细胞及其制备方法和应用
US10517875B2 (en) 2014-07-23 2019-12-31 Mayo Foundation for Medical Engineering and Research Targeting DNA-PKcs and B7-H1 to treat cancer
AU2015295441B2 (en) 2014-07-29 2020-05-14 Neurimmune Holding Ag Human-derived anti-huntingtin (HTT) antibodies and uses thereof
BR112017006598A2 (pt) 2014-09-30 2018-04-17 Neurimmune Holding Ag anticorpo de repetições antidipeptídeo derivado de ser humano (dprs)
AU2015327819B2 (en) 2014-10-03 2021-07-01 Massachusetts Institute Of Technology Antibodies that bind ebola glycoprotein and uses thereof
US20170248603A1 (en) 2014-10-06 2017-08-31 Dana-Farber Cancer Institute, Inc. Angiopoiten-2 biomarkers predictive of anti-immune checkpoint response
CA2963602A1 (en) 2014-10-09 2016-04-14 Dana-Farber Cancer Institute, Inc. Multiple-variable il-2 dose regimen for treating immune disorders
WO2016081835A2 (en) 2014-11-21 2016-05-26 University Of Maryland, Baltimore Targeted structure-specific particulate delivery systems
US20170319661A1 (en) 2014-12-03 2017-11-09 Inserm (Institut National De La Sante Et De La Recherche Medicale) Methods and Pharmaceutical Compositions Using Orexins (OXA, OXB) for the Treatment of Prostate Cancers
WO2016128523A1 (en) 2015-02-12 2016-08-18 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for predicting the responsiveness of a patient affected with malignant hematological disease to chemotherapy treatment and methods of treatment of such disease
AU2016229238B2 (en) 2015-03-06 2022-06-02 Dana-Farber Cancer Institute, Inc. PD-L2 biomarkers predictive of PD-1 pathway inhibitor responses in esophagogastric cancers
EP3067062A1 (en) 2015-03-13 2016-09-14 Ipsen Pharma S.A.S. Combination of tasquinimod or a pharmaceutically acceptable salt thereof and a pd1 and/or pdl1 inhibitor, for use as a medicament
CN108368169A (zh) 2015-03-18 2018-08-03 约翰霍普金斯大学 靶向钾通道kcnk9的新的单克隆抗体抑制剂
EP3273981B1 (en) 2015-03-24 2020-04-29 INSERM - Institut National de la Santé et de la Recherche Médicale Method and pharmaceutical composition for use in the treatment of diabetes
EP3277309A1 (en) 2015-04-03 2018-02-07 Alienor Farma Monoclonal antibody to human line-1 orf2 protein and method for early detection of transforming cells in pre-neoplastic tissues of a human subject
WO2016166110A1 (en) 2015-04-13 2016-10-20 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for treatment of haemorrhagic diseases
US20180298104A1 (en) 2015-04-22 2018-10-18 Inserm (Institut National De La Sante Et De La Recherche Medicale) Methods and pharmaceutical compositions for the treatment of th17 mediated diseases
NZ737423A (en) 2015-06-01 2019-08-30 Medigene Immunotherapies Gmbh Method for generating antibodies against t cell receptor
CN107922950B (zh) 2015-06-01 2021-12-31 基因医疗免疫疗法有限责任公司 T细胞受体文库
JP2018517712A (ja) 2015-06-01 2018-07-05 メディジーン イミュノテラピーズ ゲーエムベーハー Ｔ細胞受容体特異的抗体
WO2016205738A2 (en) 2015-06-19 2016-12-22 Cytrx Corporation Delivery systems for controlled drug release
CA2990852A1 (en) 2015-06-26 2016-12-29 Beth Israel Deaconess Medical Center, Inc. Cancer therapy targeting tetraspanin 33 (tspan33) in myeloid derived suppressor cells
CN116059395A (zh) 2015-06-29 2023-05-05 第一三共株式会社 用于选择性制造抗体-药物缀合物的方法
EP3331563B1 (en) 2015-08-05 2023-04-19 Janssen Biotech, Inc. Anti-cd154 antibodies and methods of using them
WO2017046335A1 (en) 2015-09-18 2017-03-23 INSERM (Institut National de la Santé et de la Recherche Médicale) T cell receptors (tcr) and uses thereof for the diagnosis and treatment of diabetes
WO2017050793A1 (en) 2015-09-22 2017-03-30 INSERM (Institut National de la Santé et de la Recherche Médicale) Polypeptides capable of inhibiting the binding between leptin and neuropilin-1
RU2769379C2 (ru) 2015-09-24 2022-03-30 Дайити Санкио Компани, Лимитед Антитело против garp
MA43053A (fr) 2015-09-30 2018-08-08 Janssen Biotech Inc Anticorps antagonistes se liant spécifiquement au cd40 humain et procédés d'utilisation
JP6857360B2 (ja) 2015-10-08 2021-04-14 国立大学法人東海国立大学機構 キメラ抗原受容体を発現する遺伝子改変ｔ細胞の調製方法
US11161912B2 (en) 2015-10-13 2021-11-02 Technion Research & Development Foundation Limited Heparanase-neutralizing monoclonal antibodies
WO2017064302A1 (en) 2015-10-16 2017-04-20 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for the treatment of autoimmune inflammatory diseases
JP6968790B2 (ja) 2015-10-26 2021-11-17 ピエール、ファーブル、メディカマン Ｉｇｆ−１ｒ発現癌の処置のための組成物
US10875923B2 (en) 2015-10-30 2020-12-29 Mayo Foundation For Medical Education And Research Antibodies to B7-H1
ITUB20155272A1 (it) 2015-11-02 2017-05-02 Scuola Normale Superiore Intracellular antibody
CR20180234A (es) 2015-11-03 2018-09-11 Janssen Biotech Inc Anticuerpos que se unen especificamente a pd-1 y sus usos
CN108350077A (zh) 2015-11-03 2018-07-31 糖模拟物有限公司 产生单克隆抗体、造血干细胞的方法和组合物以及利用所述抗体和造血干细胞的方法
ITUB20155097A1 (it) 2015-11-05 2017-05-05 Biouniversa Srl Anticorpi umanizzati anti-BAG3
EP3386542B1 (en) 2015-12-10 2020-11-18 Katholieke Universiteit Leuven Anti adamts13 antibodies and their use for treatment or prevention of haemorrhagic disorders due to ventricular assist device
JP2019502698A (ja) 2015-12-17 2019-01-31 ヤンセン バイオテツク，インコーポレーテツド Ｈｌａ−ｄｒに特異的に結合する抗体及びその使用
GB201522394D0 (en) 2015-12-18 2016-02-03 Ucb Biopharma Sprl Antibodies
EA201891459A1 (ru) 2015-12-23 2018-11-30 Медиджин Иммьюнотерапиз Гмбх Новое поколение антигенспецифических tcr
AU2017204682B2 (en) 2015-12-31 2021-07-29 Progastrine Et Cancers S.À R.L. Compositions and methods for detecting and treating ovarian cancer
EA037027B1 (ru) 2015-12-31 2021-01-27 Прогастрин Э Кансер С.А Р.Л. Применение и способ для профилактики или лечения рака желудка с использованием композиции, содержащей моноклональное прогастринсвязывающее антитело
CA3193481A1 (en) 2015-12-31 2017-07-06 Progastrine Et Cancers S.A R.L. Compositions and methods for detecting and treating esophageal cancer
EP3202788A1 (en) 2016-02-05 2017-08-09 MediaPharma S.r.l. Endosialin-binding antibody
WO2017140684A2 (en) 2016-02-15 2017-08-24 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for the treatment of post-operative cognitive dysfunction
EP3205663A1 (en) 2016-02-15 2017-08-16 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Means and methods for inhibiting gene expression
MX2018010445A (es) 2016-03-01 2019-10-17 Yissum Res Dev Co Of Hebrew Univ Jerusalem Ltd Anticuerpos especificos del receptor de poliovirus humano (rvp).
US11340233B2 (en) 2016-03-07 2022-05-24 Pierre Fabre Medicament Universal method to capture and analyze ADCs for characterization of drug distribution and the drug-to-antibody ratio in biological samples
WO2017156263A1 (en) 2016-03-09 2017-09-14 Memorial Sloan-Kettering Cancer Center Enigma and cdh18 as companion diagnostics for cdk4 inhibitors
EP3779447B1 (en) 2016-03-15 2023-02-08 INSERM (Institut National de la Santé et de la Recherche Médicale) Method to activate the anti-tumoral cd8+t cell response of a patient affected with a cancer
WO2017158396A1 (en) 2016-03-16 2017-09-21 INSERM (Institut National de la Santé et de la Recherche Médicale) Cytidine deaminase inhibitors for the treatment of pancreatic cancer
US20190086392A1 (en) 2016-03-21 2019-03-21 Inserm (Institut National De La Sante Et De La Recherch Medicale) Methods for diagnosis and treatment of solar lentigo
WO2017161976A1 (en) 2016-03-23 2017-09-28 Mabspace Biosciences (Suzhou) Co., Ltd Novel anti-pd-l1 antibodies
TWI753892B (zh) 2016-03-28 2022-02-01 美商英塞特公司 作為ｔａｍ抑制劑之吡咯并三嗪化合物
ITUA20162242A1 (it) 2016-04-01 2017-10-01 St Biochimico Italiano Giovanni Lorenzini Spa Un nuovo anticorpo anti-erbb2
WO2017182705A1 (en) 2016-04-18 2017-10-26 Faron Pharmaceuticals Oy Humanized anti clever-1 antibodies and their use
EP3452512B1 (en) 2016-05-03 2023-03-08 Institut National de la Santé et de la Recherche Médicale (INSERM) Methods and pharmaceutical compositions for the treatment of tissue lesions
BR112018073316A2 (pt) 2016-05-11 2019-06-04 Amgen Inc seleção direta de células que expressam altos níveis de proteínas heteroméricas usando vetores de complementação intragênica da glutamina sintetase
JP2019516799A (ja) 2016-05-20 2019-06-20 カール、クリストフＫＡＲＬ， Ｃｈｒｉｓｔｏｐｈ 骨代謝の障害および低カルシウム血症などの治療誘発性副作用の処置および／または予防に適した、抗ｒａｎｋｌ抗体、カルシウムおよびビタミンｄを含む薬学的組成物
WO2017202813A1 (en) 2016-05-24 2017-11-30 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for the treatment of pulmonary bacterial infections
WO2017202814A1 (en) 2016-05-24 2017-11-30 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for the treatment of neuropathological disorders characterized by a loss of cortical neurons
EP3463396A1 (en) 2016-06-07 2019-04-10 Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft Chimeric antigen receptor and car-t cells that bind bcma
GB201610198D0 (en) 2016-06-10 2016-07-27 Ucb Biopharma Sprl Anti-ige antibodies
HUE055402T2 (hu) 2016-07-06 2021-11-29 Prothena Biosciences Ltd Esszé összes és S129 foszforilezett alfa-szinuklein kimutatására
JP2018035137A (ja) 2016-07-13 2018-03-08 マブイミューン ダイアグノスティックス エイジーＭａｂｉｍｍｕｎｅ Ｄｉａｇｎｏｓｔｉｃｓ Ａｇ 新規な抗線維芽細胞活性化タンパク質（ｆａｐ）結合薬剤およびその使用
US20190330318A1 (en) 2016-07-25 2019-10-31 Biogen Ma Inc. Anti-hspa5 (grp78) antibodies and uses thereof
WO2018019990A1 (en) 2016-07-28 2018-02-01 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods of treatement of cancer disease by targetting tumor associated macrophage
SG11201900746RA (en) 2016-08-12 2019-02-27 Janssen Biotech Inc Engineered antibodies and other fc-domain containing molecules with enhanced agonism and effector functions
CA3033665A1 (en) 2016-08-12 2018-02-15 Janssen Biotech, Inc. Fc engineered anti-tnfr superfamily member antibodies having enhanced agonistic activity and methods of using them
AU2017332721B2 (en) 2016-09-20 2023-11-09 Sara BUHRLAGE Compositions and methods for identification, assessment, prevention, and treatment of AML using USP10 biomarkers and modulators
CA3036941C (en) 2016-10-07 2023-02-21 Daiichi Sankyo Company, Limited Therapy for drug-resistant cancer by administration of anti-her2 antibody/drug conjugate
EP3527225A4 (en) 2016-10-12 2020-06-10 Daiichi Sankyo Company, Limited COMPOSITION CONTAINING ANTI-ROBO4 ANTIBODY AND OTHER AGENT
EP3525815A2 (en) 2016-10-13 2019-08-21 Massachusetts Institute of Technology Antibodies that bind zika virus envelope protein and uses thereof
IT201600111877A1 (it) 2016-11-07 2018-05-07 Biouniversa Srl Anti-BAG3 antibodies in combination with inhibitors of immune check-point for therapeutic use
CA3043816A1 (en) 2016-11-18 2018-05-24 Astellas Pharma Inc. Novel anti-human muc1 antibody fab fragment
TW201828993A (zh) 2016-12-12 2018-08-16 日商第一三共股份有限公司 抗體－藥物結合物與免疫檢查點抑制劑之組合
US11180554B2 (en) 2016-12-13 2021-11-23 Astellas Pharma Inc. Anti-human CD73 antibody
JP2020514256A (ja) 2016-12-15 2020-05-21 ザ ナショナル インスティチュート フォー バイオテクノロジー イン ザ ネゲヴ，リミテッド 抗ｐｃｎａモノクローナル抗体及びその使用
BR112019012901A2 (pt) 2016-12-22 2020-01-07 Daiichi Sankyo Company, Limited Anticorpo ou fragmento de ligação a antígeno do anticorpo, polinucleotídeo, vetor, célula, métodos para produzir um anticorpo ou um fragmento de ligação a antígeno do anticorpo e uma molécula que se ligue ao cd3 humano e ao cd3 de macaco cinomolgo, composição farmacêutica, e, molécula
US20180179490A1 (en) 2016-12-27 2018-06-28 Miltenyi Biotec Gmbh CELL COMPOSITION DEPLETED FROM TCRab and CD45RA POSITIVE CELLS
US11773182B2 (en) 2017-01-05 2023-10-03 The Johns Hopkins University Development of new monoclonal antibodies recognizing human prostate-specific membrane antigen (PSMA)
BR112019012847A2 (pt) 2017-01-17 2019-12-10 Daiichi Sankyo Co Ltd anticorpo ou fragmento funcional do anticorpo, polinucleotídeo, vetor de expressão, células hospedeiras, método para produção de um anticorpo de interesse ou de um fragmento funcional do anticorpo e para produção de um conjugado de anticorpo-fármaco, conjugado de anticorpo-fármaco, composição farmacêutica, fármaco antitumoral, e, método de tratamento de um tumor.
WO2018140510A1 (en) 2017-01-25 2018-08-02 Biogen Ma Inc. Compositions and methods for treatment of stroke and other cns disorders
BR112019016204A2 (pt) 2017-02-07 2020-07-07 Daiichi Sankyo Company, Limited anticorpo ou fragmento de ligação a antígeno do anticorpo, polinucleotídeo, vetor, célula, imunócito artificial, métodos para produzir um anticorpo ou um fragmento de ligação a antígeno do anticorpo, para produzir uma molécula que se liga ao cd3 humano e cd3 de macaco cinomolgo e ao gprc5d humano, composição medicinal para tratamento e/ou prevenção, moléculas tendo atividade de ligação a antígeno e que se ligam ao cd3 humano e cd3 de macaco cinomolgo e ao gprc5d humano, e, usos para preparar um medicamento para tratar e/ou prevenir um câncer, para induzir citotoxicidade para as células expressando gprc5d e para redirecionamento de células t para as células expressando gprc5d
EP3363459A1 (en) 2017-02-17 2018-08-22 Alexander Klimka Polypeptide epitopes of s. aureus and respective monoclonal antibodies for the treatment of infections and immune-diagnosis
WO2018157169A1 (en) 2017-02-27 2018-08-30 Caerus Therapeutics, Inc. Antibody constructs and methods of treating cancer
CA3053749A1 (en) 2017-02-28 2018-09-07 Kinki University Method for treating egfr-tki-resistant non-small cell lung cancer by administration of anti-her3 antibody-drug conjugate
JP7216424B2 (ja) 2017-03-15 2023-02-01 チンファ ユニバーシティ 新規の抗ＴｒｋＢ抗体
JOP20180021A1 (ar) 2017-03-16 2019-01-30 Janssen Biotech Inc الأجسام المضادة لتكتلات خيوط بروتين تاو (tau) الحلزونية المزدوجة واستخداماتها
US11879014B2 (en) 2017-03-17 2024-01-23 Tusk Therapeutics Ltd. Method of treating cancer or depleting regulatory T cells in a subject by administering a human IGG1 anti-CD25 antibody
WO2018167283A1 (en) 2017-03-17 2018-09-20 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for the diagnosis and treatment of pancreatic ductal adenocarcinoma associated neural remodeling
KR102616819B1 (ko) 2017-03-30 2023-12-21 프로가스트린 에 캔서스 에스.에이 알.엘. 폐암을 치료하기 위한 조성물 및 방법
US11614448B2 (en) 2017-03-30 2023-03-28 Ecs-Progastrin Sa Compositions and methods for detecting prostate cancer
TWI782000B (zh) 2017-03-30 2022-11-01 日商第一三共股份有限公司 抗ｇｐｒ２０抗體、其製造方法及其應用
US10722589B2 (en) 2017-04-03 2020-07-28 Covagen Ag FGFR3 binding molecules
WO2018185516A1 (en) 2017-04-05 2018-10-11 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for treating cardiovascular toxicity induced by anti-cancer therapy
US20200088732A1 (en) 2017-04-13 2020-03-19 INSERM (Institut National de la Santé et de la Recherche Mèdicale) Methods for the diagnosis and treatment of pancreatic ductal adenocarcinoma
WO2018189403A1 (en) 2017-04-14 2018-10-18 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for the treatment of cancer
WO2018209301A1 (en) 2017-05-11 2018-11-15 Cytodyn Inc. Methods for treating or preventing graft-versus-host disease involving the administration of anti-ccr5 receptor agents
TWI794230B (zh) 2017-05-15 2023-03-01 日商第一三共股份有限公司 抗ｃｄｈ６抗體及抗ｃｄｈ６抗體-藥物結合物、以及其製造方法
KR102692379B1 (ko) 2017-06-05 2024-08-05 얀센 바이오테크 인코포레이티드 Pd-1과 특이적으로 결합하는 항체 및 사용 방법
EP3634496A4 (en) 2017-06-06 2021-09-08 Dana-Farber Cancer Institute, Inc. METHOD FOR RISING AWARENESS IN CANCER CELLS AGAINST T-CELL-MEDIATED KILLING BY MODULATING MOLECULAR SIGNAL PATHS
WO2019005503A1 (en) 2017-06-29 2019-01-03 Rutgers, The State University Of New Jersey COMPOSITIONS AND METHODS TARGETING G12 SIGNALING FOR BRONCHODILATORY THERAPY
CN110913905A (zh) 2017-06-30 2020-03-24 国立大学法人北海道大学 不产生生长障碍的小儿骨质疏松症治疗药
TWI795415B (zh) 2017-07-07 2023-03-11 日商安斯泰來製藥股份有限公司 新穎的抗人類ＣＥＡＣＡＭ５抗體Ｆａｂ片段
BR112020001255A2 (pt) 2017-07-21 2020-07-28 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services composições imunogênicas de neisseria meningitidis
MX2020000966A (es) 2017-07-27 2020-09-28 Daiichi Sankyo Co Ltd Anticuerpo anti-cd147.
CA3107625A1 (en) 2017-07-28 2019-01-31 Biouniversa S.R.L. Anti-bag3 antibodies as therapeutic reagent in cardiovascular diseases
CN117050176A (zh) 2017-07-31 2023-11-14 豪夫迈·罗氏有限公司 基于三维结构的人源化方法
EP3444272A1 (en) 2017-08-17 2019-02-20 International-Drug-Development-Biotech Treatment of ck8 positive cancers in relation with k-ras gene status
CN110944667B (zh) 2017-08-23 2024-08-27 第一三共株式会社 抗体-药物缀合物制剂及其冻干
CN111094349A (zh) 2017-08-23 2020-05-01 马克思-德布鲁克-分子医学中心亥姆霍兹联合会 嵌合抗原受体和结合cxcr5的car-t细胞
KR102422860B1 (ko) 2017-08-31 2022-07-19 다이이찌 산쿄 가부시키가이샤 항체-약물 콘주게이트의 신규 제조 방법
JP7366745B2 (ja) 2017-08-31 2023-10-23 第一三共株式会社 抗体－薬物コンジュゲートの改良製造方法
US10610585B2 (en) 2017-09-26 2020-04-07 Inserm (Institut National De La Sante Et De La Recherche Medicale) Methods and compositions for treating and preventing HIV
IL301637B2 (en) 2017-09-29 2024-10-01 Daiichi Sankyo Co Ltd Conjugation of an antibody with a pyrrolobenzodiazepine derivative
CN111065400A (zh) 2017-10-03 2020-04-24 公益财团法人东京都医学总合研究所 抗流感药物
US20200262917A1 (en) 2017-10-05 2020-08-20 Daiichi Sankyo Company, Limited Composition for cytotoxic t cell depletion
KR101966362B1 (ko) * 2017-10-20 2019-04-05 주식회사 녹십자 항-msln 항체 및 이를 포함하는 암 치료용 약학적 조성물
CN111587123A (zh) 2017-11-09 2020-08-25 品通治疗有限公司 用于生成和使用人源化构象特异性磷酸化的τ抗体的方法和组合物
JP7359449B2 (ja) 2017-11-30 2023-10-11 センチュリオン バイオファーマ コーポレイション オーリスタチンｅ誘導体のアルブミン結合プロドラッグ
KR20200117988A (ko) 2017-11-30 2020-10-14 센추리온 바이오파마 코포레이션 메이탄시노이드계 약물 전달 시스템
WO2019106126A1 (en) 2017-12-01 2019-06-06 INSERM (Institut National de la Santé et de la Recherche Médicale) Mdm2 modulators for the diagnosis and treatment of liposarcoma
KR102461238B1 (ko) 2017-12-05 2022-11-01 프로가스트린 에 캔서스 에스.에이 알.엘. 암을 치료하기 위한 항-프로가스트린 항체와 면역치료 사이의 병용 치료
WO2019121872A1 (en) 2017-12-20 2019-06-27 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for the diagnosis and treatment of liver cancer
US20190225689A1 (en) 2018-01-22 2019-07-25 Janssen Biotech, Inc. Methods of treating cancers with antagonistic anti-pd-1 antibodies
TW201940881A (zh) 2018-01-26 2019-10-16 瑞士商Ｅｃｓ前胃泌激素公司 在癌症診斷中結合前胃泌激素檢測與其他癌症生物標記的技術
WO2019155474A1 (en) 2018-02-12 2019-08-15 Hadasit Medical Research Services & Development Ltd. Modulation of slamf6 splice variants for cancer therapy
WO2019158512A1 (en) 2018-02-13 2019-08-22 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for the prognosis and the treatment of glioblastoma
CN112384515A (zh) 2018-02-27 2021-02-19 因赛特公司 作为a2a/a2b抑制剂的咪唑并嘧啶和三唑并嘧啶
EP3759492A1 (en) 2018-02-27 2021-01-06 ECS-Progastrin SA Progastrin as a biomarker for immunotherapy
SG11202008280TA (en) 2018-03-05 2020-09-29 Univ Saitama Medical Pharmaceutical composition for treating or preventing heterotopic ossification
US20210047696A1 (en) 2018-03-28 2021-02-18 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for treating cancer
EP3775908A1 (en) 2018-04-13 2021-02-17 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for predicting outcome and treatment of patients suffering from prostate cancer or breast cancer
EP3781590A1 (en) 2018-04-20 2021-02-24 Medizinische Hochschule Hannover Chimeric antigen receptor and car-t cells that bind a herpes virus antigen
WO2019207066A1 (en) 2018-04-26 2019-10-31 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and compositions for the treatment of sjögren's syndrome
WO2019211370A1 (en) 2018-05-03 2019-11-07 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for treating cancer
WO2019211369A1 (en) 2018-05-03 2019-11-07 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for treating cancer
KR20210009308A (ko) 2018-05-09 2021-01-26 이슘 리서치 디벨롭먼트 컴퍼니 오브 더 히브루 유니버시티 오브 예루살렘 엘티디. 인간 넥틴4에 특이적인 항체
US20210163549A1 (en) 2018-05-11 2021-06-03 Astellas Pharma Inc. Nucleic acid for treating crustacean allergy
TW202003542A (zh) 2018-05-11 2020-01-16 日商安斯泰來製藥股份有限公司 用於塵蟎過敏治療之核酸
WO2019221269A1 (ja) 2018-05-17 2019-11-21 アステラス製薬株式会社 抗ヒトＭＵＣ１抗体Ｆａｂフラグメント、ペプチドリンカー及び／又は配位子を含む複合体
JP7391046B2 (ja) 2018-05-18 2023-12-04 インサイト・コーポレイション Ａ２ａ／ａ２ｂ阻害剤としての縮合ピリミジン誘導体
AU2019274652A1 (en) 2018-05-24 2020-11-26 Janssen Biotech, Inc. Monospecific and multispecific anti-TMEFF2 antibodies and there uses
EA202092839A1 (ru) 2018-05-24 2021-02-12 Янссен Байотек, Инк. Агенты, связывающиеся с psma, и виды их применения
PE20210132A1 (es) 2018-05-24 2021-01-19 Janssen Biotech Inc Anticuerpos anti-cd3 y usos de estos
IL278988B2 (en) 2018-05-28 2024-10-01 Daiichi Sankyo Co Ltd Anti-HER2 drug and antibody conjugates for use in the treatment of cancer with a HER2 mutation
AR126019A1 (es) 2018-05-30 2023-09-06 Novartis Ag Anticuerpos frente a entpd2, terapias de combinación y métodos de uso de los anticuerpos y las terapias de combinación
EP3805389A4 (en) 2018-05-31 2022-03-23 Daiichi Sankyo Company, Limited HUMAN ANTI-TLR7 ANTIBODY
CN112384531B (zh) 2018-06-01 2024-05-14 诺华股份有限公司 针对bcma的结合分子及其用途
EP3800999A4 (en) 2018-06-04 2022-06-01 Biogen MA Inc. ANTI-VLA-4 ANTIBODIES WITH REDUCED EFFECTOR FUNCTION
WO2019234099A1 (en) 2018-06-06 2019-12-12 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for diagnosing, predicting the outcome and treating a patient suffering from heart failure with preserved ejection fraction
WO2019234221A1 (en) 2018-06-08 2019-12-12 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for stratification and treatment of a patient suffering from chronic lymphocytic leukemia
TW202423480A (zh) 2018-06-20 2024-06-16 美商英塞特公司 抗pd-1抗體及其用途
WO2019244107A1 (en) 2018-06-21 2019-12-26 Daiichi Sankyo Company, Limited Compositions including cd3 antigen binding fragments and uses thereof
TWI832871B (zh) 2018-06-29 2024-02-21 美商英塞特公司 Axl/mer 抑制劑之調配物
WO2020007898A1 (en) 2018-07-04 2020-01-09 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and compositions for treating brain injury or neurodegenerative disease
EP3818063A1 (en) 2018-07-05 2021-05-12 Incyte Corporation Fused pyrazine derivatives as a2a / a2b inhibitors
EP3828206A4 (en) 2018-07-25 2022-04-20 Daiichi Sankyo Company, Limited METHOD OF PREPARING AN ANTIBODY DRUG CONJUGATE
CN112512584A (zh) 2018-07-27 2021-03-16 国立大学法人大阪大学 用于抑制衰老、预防、改善或治疗衰老相关疾病或症状、或者延长寿命的组合物
CA3107732A1 (en) 2018-07-27 2020-01-30 Daiichi Sankyo Company, Limited Protein recognizing drug moiety of antibody-drug conjugate
BR112021001509A2 (pt) 2018-07-31 2021-04-27 Daiichi Sankyo Company, Limited agente terapêutico para um tumor de cérebro metastásico
TW202019487A (zh) 2018-08-06 2020-06-01 日商第一三共股份有限公司 抗體-藥物結合物及微管蛋白抑制劑之組合
US20220008549A1 (en) 2018-09-06 2022-01-13 Daiichi Sankyo Company, Limited Novel cyclic dinucleotide derivative and antibody-drug conjugate thereof
CN112912109A (zh) 2018-09-20 2021-06-04 第一三共株式会社 通过施用抗her3抗体-药物缀合物治疗her3-突变的癌症
WO2020059847A1 (ja) 2018-09-21 2020-03-26 国立大学法人 東京医科歯科大学 ヒトｈｍｇｂ１に特異的に結合するヒトモノクローナル抗体、及びそれを含有するアルツハイマー病を治療又は予防するための医薬組成物
MX2021003295A (es) 2018-09-27 2021-07-16 Pf Medicament Enlazadores basados en sulfomaleimida y sus correspondientes conjugados.
BR112021005665A2 (pt) 2018-09-28 2021-06-22 Pierre Fabre Medicament novas imunocitocinas para o tratamento de câncer
TWI835880B (zh) 2018-10-10 2024-03-21 日商安斯泰來製藥股份有限公司 含有標識部－抗人類抗體Ｆａｂ片段複合體之醫藥組成物
UY38407A (es) 2018-10-15 2020-05-29 Novartis Ag Anticuerpos estabilizadores de trem2
CN112955462B (zh) 2018-10-18 2024-05-07 国家医疗保健研究所 用于治疗实体瘤的βIG-H3拮抗剂和免疫检查点抑制剂的组合
AU2019369771A1 (en) 2018-10-31 2021-06-03 Astellas Pharma Inc. Anti-human Fn14 antibody
WO2020099235A1 (en) 2018-11-12 2020-05-22 Mediapharma S.R.L. Bispecific antibodies directed against human 90k and either endosialin or her3
AU2019379418A1 (en) 2018-11-14 2021-06-03 Daiichi Sankyo Company, Limited Anti-CDH6 antibody-pyrrolobenzodiazepine derivative conjugate
KR20210102341A (ko) 2018-12-11 2021-08-19 다이이찌 산쿄 가부시키가이샤 항체-약물 컨쥬게이트와 parp 저해제의 조합
BR112021012103A2 (pt) 2018-12-21 2021-09-08 Aim Immunotech Inc. Composições e métodos para terapia de câncer
WO2020130125A1 (ja) 2018-12-21 2020-06-25 第一三共株式会社 抗体－薬物コンジュゲートとキナーゼ阻害剤の組み合わせ
JPWO2020145228A1 (ja) 2019-01-07 2021-11-11 アステラス製薬株式会社 配位子及びＣＥＡＣＡＭ５抗体Ｆａｂフラグメントからなる複合体
CN113573729A (zh) 2019-01-10 2021-10-29 詹森生物科技公司 前列腺新抗原及其用途
CA3125962A1 (en) 2019-01-13 2020-07-16 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Antibodies specific to human nectin-2
TWI829857B (zh) 2019-01-29 2024-01-21 美商英塞特公司 作為a2a / a2b抑制劑之吡唑并吡啶及三唑并吡啶
EP3917515A1 (en) 2019-01-29 2021-12-08 Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) Treating the causative agent in adhesiogenesis
US11028176B2 (en) 2019-02-13 2021-06-08 The Brigham And Women's Hospital, Inc. Anti-peripheral lymph node addressin antibodies and uses thereof
WO2020178193A1 (en) 2019-03-01 2020-09-10 INSERM (Institut National de la Santé et de la Recherche Médicale) Method of treatment of sarcoidosis
WO2020185763A1 (en) 2019-03-11 2020-09-17 Memorial Sloan Kettering Cancer Center Cd22 antibodies and methods of using the same
US20220154153A1 (en) 2019-03-22 2022-05-19 Université de Paris New inhibitors of lrrk2/pp1 interaction
WO2020196474A1 (ja) 2019-03-25 2020-10-01 第一三共株式会社 抗体－ピロロベンゾジアゼピン誘導体コンジュゲート
BR112021017616A2 (pt) 2019-03-25 2021-11-09 Daiichi Sankyo Co Ltd Conjugado de derivado de anticorpo anti-her2-pirrolobenzodiazepina
JP2022526340A (ja) 2019-03-25 2022-05-24 マックス－デルブリュック－ツェントルム フューア モレキュラーレ メディツィン イン デア ヘルムホルツ－ゲマインシャフト Ｅｂａｇ９を阻害することによる細胞溶解性ｔ細胞の活性の増強
TWI841715B (zh) 2019-03-27 2024-05-11 日商第一三共股份有限公司 抗體-吡咯并苯二氮呯衍生物結合物及ｐａｒｐ抑制劑之組合及其用途
CN113660954A (zh) 2019-04-01 2021-11-16 凯奥目生物科学株式会社 癌症治疗用药物
JP2022527860A (ja) 2019-04-02 2022-06-06 ケンジョッケティ バイオテクノロジー，インク． 排出ポンプ－癌抗原マルチ特異性抗体ならびにそれに関する組成物、試薬、キットおよび方法
CN113747944A (zh) 2019-04-19 2021-12-03 詹森生物科技公司 用抗psma/cd3抗体治疗前列腺癌的方法
US20220289854A1 (en) 2019-04-30 2022-09-15 Dana-Farber Cancer Institute, Inc. Methods for treating cancer using combinations of anti-cx3cr1 and immune checkpoint blockade agents
KR20220016083A (ko) 2019-04-30 2022-02-08 센티 바이오사이언시스, 인코포레이티드 키메라 수용체 및 이의 사용 방법
JP2022533591A (ja) 2019-05-14 2022-07-25 アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル リンホトキシンアルファ遮断剤によりターゲットされた制御性ｔ細胞及びその使用
JP2022534725A (ja) 2019-05-29 2022-08-03 第一三共株式会社 抗体薬物複合体の用量
TW202115114A (zh) 2019-06-24 2021-04-16 瑞士商諾華公司 針對靶向ｂ細胞成熟抗原的多特異抗體之給藥方案及組合療法
WO2021020282A1 (ja) 2019-07-26 2021-02-04 学校法人埼玉医科大学 Ａｌｋ２／ａｃｖｒ１の細胞外領域を認識する抗体
MX2022001049A (es) 2019-07-26 2022-05-03 Janssen Biotech Inc Proteínas que comprenden dominios de unión al antígeno de la peptidasa 2 relacionada con la calicreína y sus usos.
WO2021019706A1 (ja) 2019-07-31 2021-02-04 国立大学法人信州大学 Ｃａｒ発現免疫細胞を含む細胞集団の製造方法
JP2022543062A (ja) 2019-08-01 2022-10-07 インサイト・コーポレイション Ｉｄｏ阻害剤の投与レジメン
CA3146474A1 (en) 2019-08-02 2021-02-11 Denis BURGER Methods for treating or preventing cancers involving the administration of anti-ccr5 receptor agents
JP7284256B2 (ja) 2019-08-12 2023-05-30 ビオンド バイオロジクス リミテッド Ｉｌｔ２に対する抗体およびその使用
EP3792632A1 (en) 2019-09-16 2021-03-17 Vito NV Immunotherapy markers
TW202124446A (zh) 2019-09-18 2021-07-01 瑞士商諾華公司 與ｅｎｔｐｄ２抗體之組合療法
JP2022548881A (ja) 2019-09-18 2022-11-22 ノバルティス アーゲー Ｅｎｔｐｄ２抗体、組合せ療法並びに抗体及び組合せ療法を使用する方法
US20220290151A1 (en) 2019-09-27 2022-09-15 INSERM (Institut National de la Santé et de la Recherche Médicale) Use of müllerian inhibiting substance inhibitors for treating cancer
CN114746119A (zh) 2019-09-27 2022-07-12 詹森生物科技公司 抗-ceacam抗体及其用途
EP4049675A4 (en) 2019-10-25 2023-11-22 Daiichi Sankyo Company, Limited COMBINATION OF ANTI-GARP ANTIBODY AND IMMUNOREGULATOR
EP4058481A1 (en) 2019-11-15 2022-09-21 Pliant Therapeutics, Inc. Compositions and methods for activation of integrins
IL293051A (en) 2019-11-18 2022-07-01 Janssen Biotech Inc calr and jak2 mutant-based vaccines and their uses
CA3159975A1 (en) * 2019-12-10 2021-06-17 CCOA Therapeutics Inc. Humanized anti-glycoprotein ib alpha (gpibalpha) antibodies
AU2020409124A1 (en) 2019-12-20 2022-06-30 Novarock Biotherapeutics, Ltd. Anti-interleukin-23 p19 antibodies and methods of use thereof
US20210205311A1 (en) 2020-01-03 2021-07-08 Incyte Corporation Combination Therapy Comprising A2A/A2B and PD-1/PD-L1 Inhibitors
WO2021140173A1 (en) 2020-01-10 2021-07-15 Biouniversa S.R.L. Methods and uses for treating fibrotic solid tumors with bags inhibitors
WO2021156329A1 (en) 2020-02-05 2021-08-12 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods of treatment of cancer disease by targeting an epigenetic factor
TW202140012A (zh) 2020-02-12 2021-11-01 比利時商健生藥品公司 用於治療尿路上皮癌的ｆｇｆｒ酪胺酸激酶抑制劑和抗ｐｄ１藥劑
TW202144388A (zh) 2020-02-14 2021-12-01 美商健生生物科技公司 在卵巢癌中表現之新抗原及其用途
TW202144389A (zh) 2020-02-14 2021-12-01 美商健生生物科技公司 在多發性骨髓瘤中表現之新抗原及其用途
KR20220149579A (ko) 2020-03-03 2022-11-08 액티브 바이오테크 에이비 조합 요법에 사용하기 위한 타스퀴니모드 또는 이의 약학적으로 허용가능한 염
CA3168368A1 (en) 2020-03-06 2021-09-10 Masayuki Ishizaki Antibody-drug conjugate including novel cyclic dinucleotide derivative
US20210275666A1 (en) 2020-03-06 2021-09-09 Incyte Corporation Combination therapy comprising axl/mer and pd-1/pd-l1 inhibitors
KR20220167276A (ko) 2020-03-10 2022-12-20 매사추세츠 인스티튜트 오브 테크놀로지 NPM1c-양성 암의 면역치료를 위한 조성물 및 방법
KR20220154728A (ko) 2020-03-13 2022-11-22 얀센 바이오테크 인코포레이티드 Siglec-3/cd33을 결합시키기 위한 물질 및 방법
CA3173263A1 (en) 2020-03-30 2021-10-07 Yasuhiro Matsumura Antibody drug conjugate
US11045546B1 (en) 2020-03-30 2021-06-29 Cytodyn Inc. Methods of treating coronavirus infection
EP3889183A1 (en) 2020-04-01 2021-10-06 Pierre Fabre Medicament A protein complex comprising an immunocytokine
JP2023520587A (ja) 2020-04-06 2023-05-17 イッサム リサーチ デベロップメント カンパニー オブ ザ ヘブリュー ユニバーシティー オブ エルサレム エルティーディー． 癌及び感染症の治療のためのＮＫｐ４６に対する抗体及びそのコンストラクト
WO2021228218A1 (zh) 2020-05-14 2021-11-18 江苏恒瑞医药股份有限公司 抗cd25抗体、其抗原结合片段及其医药用途
JP2023526529A (ja) 2020-05-19 2023-06-21 アンスティテュ・クリー サイトカイン放出症候群の診断及び処置の方法
TW202210510A (zh) 2020-05-27 2022-03-16 美商健生生物科技公司 包含ｃｄ３抗原結合域之蛋白質及其用途
BR112022023931A2 (pt) 2020-05-27 2023-04-11 Arialys Therapeutics Inc Derivado de anticorpo nr1 anti-humano
US20230192902A1 (en) 2020-06-04 2023-06-22 Kenjockety Biotechnology, Inc. Abcg2 efflux pump-cancer antigen multi-specific antibodies and compositions, reagents, kits and methods related thereto
WO2021260582A1 (en) 2020-06-24 2021-12-30 Astrazeneca Uk Limited Combination of antibody-drug conjugate and aurora b inhibitor
CA3183867A1 (en) 2020-06-24 2021-12-30 Jerome Thomas Mettetal Ii Combination of antibody-drug conjugate and atr inhibitor
US20230233540A1 (en) 2020-06-24 2023-07-27 Astrazeneca Uk Limited Combination of antibody-drug conjugate and cdk9 inhibitor
WO2021260583A1 (en) 2020-06-24 2021-12-30 Astrazeneca Uk Limited Combination of antibody-drug conjugate and dna-pk inhibitor
EP4171651A1 (en) 2020-06-24 2023-05-03 AstraZeneca UK Limited Combination of antibody-drug conjugate and atm inhibitor
US20230305023A1 (en) 2020-06-25 2023-09-28 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods of treatment and diagnostic of pathological conditions associated with intense stress
US20230277679A1 (en) 2020-07-17 2023-09-07 Daiichi Sankyo Company, Limited Method for producing antibody-drug conjugate
US20230293714A1 (en) 2020-07-20 2023-09-21 Daiichi Sankyo Company, Limited Combination of anti-her2 antibody-drug conjugate with her dimerization inhibitor
TW202221028A (zh) 2020-07-29 2022-06-01 美商健生生物科技公司 包括hla-g抗原結合域之蛋白及其用途
RU2764216C1 (ru) * 2020-08-10 2022-01-14 Федеральное государственное бюджетное образовательное учреждение высшего образования "Чувашский государственный университет имени И.Н. Ульянова" Способ лечения гломерулонефритов с нефротическим синдромом рецидивирующего течения
IL300588A (en) 2020-08-12 2023-04-01 Biond Biologics Ltd Antibodies against ILT-2 and their use
AU2021334950A1 (en) 2020-08-24 2023-03-02 Charité - Universitätsmedizin Berlin Chimeric antigen receptor (CAR)-expressing cells recognizing CEA
US20240009310A1 (en) 2020-08-24 2024-01-11 Charité - Universitätsmedizin Berlin A CHIMERIC ANTIGEN RECEPTOR CONSTRUCT ENCODING A CHECKPOINT INHIBITORY MOLECULE AND AN IMMUNE STIMULATORY CYTOKINE AND CAR-EXPRESSING CELLS RECOGNIZING CD44v6
JP2023540526A (ja) 2020-09-04 2023-09-25 ノヴァロック バイオセラピューティクス， リミテッド ネクチン－４抗体およびそれの使用
EP4210722A1 (en) 2020-09-07 2023-07-19 Institut National de la Santé et de la Recherche Médicale (INSERM) Methods of treatment of inflammatory bowel diseases
KR20230066094A (ko) 2020-09-12 2023-05-12 아스트라제네카 유케이 리미티드 항-her2 항체-약물 접합체 치료법을 위한 채점 방법
KR20230083296A (ko) 2020-10-05 2023-06-09 치오메 바이오사이언스 가부시키가이샤 암 치료용 의약
CA3195117A1 (en) 2020-10-09 2022-04-14 Jerome Thomas Mettetal Ii Combination of antibody-drug conjugate and parp1 selective inhibitor
CN116635052A (zh) 2020-10-13 2023-08-22 詹森生物科技公司 用于调节分化簇iv和/或viii的生物工程t细胞介导的免疫、材料和其他方法
EP4232064A1 (en) 2020-10-21 2023-08-30 Institut National de la Santé et de la Recherche Médicale (INSERM) C-terminal sparc fragments for treating cancer
WO2022084915A1 (en) 2020-10-22 2022-04-28 Janssen Biotech, Inc. Proteins comprising delta-like ligand 3 (dll3) antigen binding domains and their uses
WO2022097090A1 (en) 2020-11-05 2022-05-12 Novartis Ag Dosing regimen for combination therapies with multispecific antibodies targeting b-cell maturation antigen and gamma secretase inhibitors
CN116917502A (zh) 2020-11-06 2023-10-20 Inserm(法国国家健康医学研究院) 诊断和治疗多囊卵巢综合征（pcos）的方法
CA3198330A1 (en) 2020-11-11 2022-05-19 Mayumi SUE Combination of an antibody-drug conjugate with anti-sirp.alpha. antibody
EP4245322A1 (en) 2020-11-12 2023-09-20 Daiichi Sankyo Company, Limited Treatment for mesothelioma through administration of anti-b7-h3 antibody-drug conjugate
AU2021378575A1 (en) 2020-11-16 2023-06-22 Astellas Pharma Inc. Anti-tspan8-anti-cd3 bispecific antibody and anti-tspan8 antibody
EP4251282A1 (en) 2020-11-27 2023-10-04 Institut National de la Santé et de la Recherche Médicale (INSERM) Methods for diagnosis and monitoring of toxic epidermal necrolysis
WO2022115120A1 (en) 2020-11-30 2022-06-02 Incyte Corporation Combination therapy with an anti-cd19 antibody and parsaclisib
US20220241411A1 (en) 2020-11-30 2022-08-04 Incyte Corporation Combination therapy with an anti-cd19 antibody and parsaclisib
WO2022124247A1 (ja) 2020-12-09 2022-06-16 国立大学法人 東京医科歯科大学 前頭側頭葉変性症の予防又は治療剤
WO2022147092A1 (en) 2020-12-29 2022-07-07 Incyte Corporation Combination therapy comprising a2a/a2b inhibitors, pd-1/pd-l1 inhibitors, and anti-cd73 antibodies
US20240115721A1 (en) 2021-01-13 2024-04-11 Memorial Sloan Kettering Cancer Center Anti-dll3 antibody-drug conjugate
WO2022153212A1 (en) 2021-01-13 2022-07-21 Axon Neuroscience Se Antibodies neutralizing sars-cov-2
AU2022207708A1 (en) 2021-01-13 2023-07-27 Daiichi Sankyo Company, Limited Antibody-pyrrolobenzodiazepine derivative conjugate
PE20240761A1 (es) 2021-01-28 2024-04-17 Janssen Biotech Inc Proteinas de union a psma y usos de estas
EP4284510A1 (en) 2021-01-29 2023-12-06 Novartis AG Dosage regimes for anti-cd73 and anti-entpd2 antibodies and uses thereof
TW202241454A (zh) 2021-02-01 2022-11-01 日商第一三共股份有限公司 抗體－免疫賦活化劑共軛物之新穎製造方法
US20240270840A1 (en) 2021-02-11 2024-08-15 Nectin Therapeutics Ltd. Antibodies against cd112r and uses thereof
JP2024508736A (ja) 2021-02-12 2024-02-28 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 補体ｃ３抗原結合タンパク質
US20220378929A1 (en) 2021-02-25 2022-12-01 MediBoston Limted Anti-her2 antibody-drug conjugates and uses thereof
IL305575A (en) 2021-03-02 2023-10-01 Dana Farber Cancer Inst Inc Methods for treating red blood cell disorders
EP4305064A1 (en) 2021-03-12 2024-01-17 Fibrosys S.r.l. Monoclonal antibodies for the treatment of viral infections
WO2022191313A1 (ja) 2021-03-12 2022-09-15 第一三共株式会社 糖鎖及び糖鎖を含む医薬品の製造方法
JP2024512035A (ja) 2021-03-24 2024-03-18 ヤンセン バイオテツク，インコーポレーテツド Ｃｄ２２及びｃｄ７９ｂを標的とする抗体
WO2022201053A1 (en) 2021-03-24 2022-09-29 Janssen Biotech, Inc. Proteins comprising cd3 antigen binding domains and uses thereof
MX2023011340A (es) 2021-03-26 2023-12-14 Janssen Biotech Inc Anticuerpos humanizados contra el filamento helicoidal emparejado tau y usos de estos.
WO2022218998A1 (en) 2021-04-13 2022-10-20 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for treating hepatitis b and d virus infection
KR20230170672A (ko) 2021-04-14 2023-12-19 빌라리스 테라퓨틱스 인코포레이티드 항-cd122 항체 및 이의 용도
CA3217637A1 (en) 2021-04-22 2022-10-27 Astellas Pharma Inc. Anti-cldn4/anti-cd137 bispecific antibody
WO2022261183A2 (en) 2021-06-08 2022-12-15 Dana-Farber Cancer Institute, Inc. Compositions and methods for treating and/or identifying an agent for treating intestinal cancers
MX2024002476A (es) 2021-08-27 2024-05-20 Janssen Biotech Inc Anticuerpos anti-psma y usos de estos.
CA3231632A1 (en) 2021-09-15 2023-03-23 Daiichi Sankyo Company, Limited Antibody-drug conjugate for use in methods of treating chemotherapy-resistant cancer
WO2023041744A1 (en) 2021-09-17 2023-03-23 Institut Curie Bet inhibitors for treating pab1 deficient cancer
EP4405392A1 (en) 2021-09-24 2024-07-31 Janssen Biotech, Inc. Proteins comprising cd20 binding domains, and uses thereof
WO2023052541A1 (en) 2021-09-30 2023-04-06 Imcheck Therapeutics Combination of an anti-btn3a activating antibody and an il-2 agonist for use in therapy
EP4420683A1 (en) 2021-10-18 2024-08-28 Daiichi Sankyo Company, Limited Anti-cd37 antibody-drug conjugate
CA3234598A1 (en) 2021-10-27 2023-05-04 Daniel Olive Butyrophilin (btn) 3a activating antibodies for use in methods for treating infectious disorders
EP4177266A1 (en) 2021-11-05 2023-05-10 Katholieke Universiteit Leuven Neutralizing anti-sars-cov-2 human antibodies
CN118414173A (zh) 2021-11-18 2024-07-30 阿斯利康(英国)有限公司 抗体-药物缀合物和parp1选择性抑制剂的组合
EP4433089A1 (en) 2021-11-19 2024-09-25 Institut Curie Methods for the treatment of hrd cancer and brca-associated cancer
EP4440594A2 (en) 2021-11-29 2024-10-09 Dana-Farber Cancer Institute, Inc. Methods and compositions to modulate riok2
WO2023099763A1 (en) 2021-12-03 2023-06-08 Institut Curie Sirt6 inhibitors for use in treating resistant hrd cancer
JP7235262B1 (ja) 2021-12-07 2023-03-08 国立大学法人大阪大学 抗体又はその抗原結合性断片
WO2023105528A1 (en) 2021-12-12 2023-06-15 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Antibodies specific to ceacam1
AU2022419233A1 (en) 2021-12-22 2024-07-04 Incyte Corporation Treatment paradigm for an anti-cd19 antibody therapy
IL313929A (en) 2021-12-28 2024-08-01 Astrazeneca Uk Ltd Combining an antibody-drug conjugate and an ATR inhibitor
TW202333800A (zh) 2021-12-28 2023-09-01 英商阿斯特捷利康英國股份有限公司 抗體-藥物結合物及rasg12c抑制劑之組合
CN118591554A (zh) 2022-01-27 2024-09-03 凯奥目生物科学株式会社 抗人cxcl1抗体
WO2023152581A1 (en) 2022-02-09 2023-08-17 Janssen Biotech, Inc. Method of treating cancer with psmaxcd3 antibody
WO2023166081A1 (en) 2022-03-02 2023-09-07 Heidelberg Immunotherapeutics Gmbh Vaccine comprising an antibody or an fc-containing fusion protein comprising an fc part of an antibody
IL315341A (en) 2022-03-02 2024-10-01 Daiichi Sankyo Co Ltd A method for producing a molecule containing Fc
IL314907A (en) 2022-03-15 2024-10-01 Yeda Res & Dev Antibodies against GITR and their uses
WO2023175483A1 (en) 2022-03-16 2023-09-21 Astrazeneca Uk Limited A scoring method for an anti-trop2 antibody‑drug conjugate therapy
TW202400140A (zh) 2022-04-27 2024-01-01 日商第一三共股份有限公司 抗體-藥物結合物與ezh1及/或ezh2抑制劑之組合
TW202400650A (zh) 2022-05-11 2024-01-01 日商第一三共股份有限公司 抗體與cd47抑制劑之組合
WO2023228095A1 (en) 2022-05-24 2023-11-30 Daiichi Sankyo Company, Limited Dosage regimen of an anti-cdh6 antibody-drug conjugate
WO2024013724A1 (en) 2022-07-15 2024-01-18 Pheon Therapeutics Ltd Antibody-drug conjugates
WO2024023750A1 (en) 2022-07-28 2024-02-01 Astrazeneca Uk Limited Combination of antibody-drug conjugate and bispecific checkpoint inhibitor
TW202421193A (zh) 2022-09-28 2024-06-01 美商英塞特公司 抗ｐｄ－１／ｌａｇ－３雙特異性抗體及其用途
WO2024074498A1 (en) 2022-10-04 2024-04-11 Imcheck Therapeutics Combination of a btn3a activating antibody, a bcl2 inhibitor and hypomethylating agent for use in treating cancer
WO2024116094A1 (en) 2022-11-30 2024-06-06 Daiichi Sankyo Company, Limited Combination of antibody-drug conjugates and dnmt inhibitors
WO2024121380A1 (en) 2022-12-08 2024-06-13 Pierre Fabre Medicament Vaccinal composition and adjuvant
WO2024127366A1 (en) 2022-12-16 2024-06-20 Pheon Therapeutics Ltd Antibodies to cub domain-containing protein 1 (cdcp1) and uses thereof
WO2024170505A1 (en) 2023-02-13 2024-08-22 Institut National de la Santé et de la Recherche Médicale Methods of treatment of iron overload associated diseases
WO2024175699A1 (en) 2023-02-23 2024-08-29 Imcheck Therapeutics Combination of btn3a activating antibody and immune checkpoint inhibitors
WO2024184476A1 (en) 2023-03-07 2024-09-12 Institut Curie Ung/udg inhibition in brca-associated cancer
WO2024194402A1 (en) 2023-03-21 2024-09-26 Institut Curie Farnesyl transferase inhibitor for use in methods for the treatment of hrd cancer
WO2024194401A1 (en) 2023-03-21 2024-09-26 Institut Curie Vps4b inhibitor for use in methods for the treatment of hrd cancer
WO2024194673A1 (en) 2023-03-21 2024-09-26 Institut Curie Methods for the treatment of dedifferentiated liposarcoma

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4704362A (en) 1977-11-08 1987-11-03 Genentech, Inc. Recombinant cloning vehicle microbial polypeptide expression
JPS6033453B2 (ja) * 1978-08-17 1985-08-02 富士電機株式会社 魚切断加工自動化装置
US4816567A (en) * 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
JPS6014678A (ja) * 1983-07-04 1985-01-25 Taiheiyo Kogyo Kk 電磁弁
GB8607679D0 (en) 1986-03-27 1986-04-30 Winter G P Recombinant dna product
GB2188941B (en) * 1986-04-14 1990-06-06 Bayer Ag Monoclonal antibodies recognizing human interleukin-2-receptor
DK554986A (da) * 1986-11-19 1988-07-18 Novo Industri As Human-human hybride cellelinier samt dermed producerede monoklonale cancerantistoffer
GB8720833D0 (en) * 1987-09-04 1987-10-14 Celltech Ltd Recombinant dna product
AU618989B2 (en) * 1988-02-12 1992-01-16 British Technology Group Limited Improvements in or relating to antibodies
KR900700134A (ko) * 1988-04-15 1990-08-11 원본미기재 Il-2 수용체-특이적 키메릭 항체
JP5598363B2 (ja) 2011-02-15 2014-10-01 ソニー株式会社 記憶装置およびその動作方法

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102775493A (zh) * 2005-06-21 2012-11-14 佐马技术有限公司 IL-1β结合抗体及其片段
CN102775493B (zh) * 2005-06-21 2015-10-28 爱克索马美国有限责任公司 IL-1β结合抗体及其片段
CN113361141A (zh) * 2021-07-11 2021-09-07 西南石油大学 一种dna图谱算法及其改进试验算法

Also Published As

Publication number Publication date
DE122005000057I1 (de) 2009-04-09
DE122005000057I2 (de) 2009-07-16
NO2007006I2 (no) 2009-12-07
HRP920500B1 (en) 1999-12-31
NZ314793A (en) 1999-11-29
ES2523810T3 (es) 2015-01-12
DE122006000036I1 (de) 2007-04-19
DE04076439T1 (de) 2014-12-18
PT92758A (pt) 1990-06-29
NL990020I2 (nl) 1999-11-01
NL300239I2 (nl) 2007-03-01
SG78258A1 (en) 2001-02-20
CN1057013C (zh) 2000-10-04
NO912385L (no) 1991-06-19
NL300005I2 (nl) 2000-10-02
NO2006009I2 (no) 2009-12-07
DK199800941A (da) 1998-07-16
NO2007006I1 (no) 2007-05-07
CZ418691A3 (en) 1993-10-13
NL300023I1 (nl) 2001-01-02
DE122009000071I1 (de) 2010-03-25
EP1491556A1 (en) 2004-12-29
DE68925536T4 (de) 1996-09-19
NO2009026I1 (no) 2009-11-30
FR14C0070I1 (fr) 2014-10-24
HU211174A9 (en) 1995-11-28
LU91208I2 (fr) 2006-02-28
NL300213I1 (nl) 2006-02-01
DE98204240T1 (de) 2014-08-21
NO2006009I1 (no) 2006-08-07
NO2001025I2 (no) 2005-03-21
EP0939127A3 (en) 2004-07-21
ES2492815T1 (es) 2014-09-10
HK1014718A1 (en) 1999-09-30
IL92904A0 (en) 1990-09-17
DE10075038I2 (de) 2004-08-12
DE04076438T1 (de) 2014-02-27
DK174317B1 (da) 2002-12-02
JP2828340B2 (ja) 1998-11-25
JPH114694A (ja) 1999-01-12
NL300279I2 (nl) 2007-10-01
EP0939127B1 (en) 2014-09-17
AU5153290A (en) 1990-08-13
LU91139I2 (fr) 2005-04-04
ES2136760T3 (es) 1999-12-01
RU2126046C1 (ru) 1999-02-10
NO2001024I1 (no) 2002-01-21
NL300239I1 (nl) 2006-10-02
DD296964A5 (de) 1991-12-19
DE122005000007I1 (de) 2005-06-30
NL300005I1 (nl) 2000-04-03
JP3604058B2 (ja) 2004-12-22
DE68925536T2 (de) 1996-06-20
EP0451216B2 (en) 2012-06-13
ES2492815T3 (es) 2014-10-08
LU90411I2 (fr) 1999-09-02
EP1477497B1 (en) 2014-11-26
YU248989A (en) 1991-10-31
DE68925536D1 (de) 1996-03-07
DE19975047I2 (de) 2008-07-03
EP0451216B9 (en) 2012-09-26
KR0178385B1 (ko) 1999-04-01
LU90676I2 (fr) 2001-02-05
LU91627I2 (fr) 2010-02-09
KR910700350A (ko) 1991-03-14
NL300279I1 (nl) 2007-07-02
SI8912489A (sl) 1999-02-28
EP0451216B1 (en) 1996-01-24
NL300173I1 (nl) 2005-04-01
NL990020I1 (nl) 1999-09-01
WO1990007861A1 (en) 1990-07-26
EP0451216A1 (en) 1991-10-16
DE68929061D1 (de) 1999-09-30
HRP920500A2 (en) 1996-04-30
ES2523810T1 (es) 2014-12-01
LU91333I2 (fr) 2007-06-11
ES2081974T3 (es) 1996-03-16
EP1477497A1 (en) 2004-11-17
SI8912489B (sl) 2000-04-30
YU48700B (sh) 1999-07-28
CA2006865C (en) 2002-08-20
CA2328851C (en) 2002-08-13
DE122007000037I1 (de) 2007-08-02
NL300426I1 (nl) 2010-02-01
IE20000331A1 (en) 2001-02-21
NO912385D0 (no) 1991-06-19
EP0939127A2 (en) 1999-09-01
FI912436A0 (fi) 1991-05-20
NO2005026I2 (no) 2009-01-19
CA2006865A1 (en) 1990-06-28
NL300173I2 (nl) 2006-05-01
FI108797B (fi) 2002-03-28
ES2081974T5 (es) 2012-10-29
EP2341080A1 (en) 2011-07-06
LU91272I2 (fr) 2006-10-09
NZ231984A (en) 1997-06-24
DE10075005I1 (de) 2000-11-23
NO310473B1 (no) 2001-07-09
IL162181A0 (en) 2005-11-20
JP2007145863A (ja) 2007-06-14
NL300023I2 (nl) 2001-09-03
EP1491556B1 (en) 2014-04-30
ES2440825T1 (es) 2014-01-30
DE68929061T2 (de) 2000-04-27
ZA899956B (en) 1990-10-31
LU90528I2 (fr) 2000-04-11
MC2146A1 (fr) 1992-02-18
DK119191A (da) 1991-06-19
ATE183753T1 (de) 1999-09-15
DE68925536T3 (de) 2012-11-22
BG61095B2 (en) 1996-10-31
AU647383B2 (en) 1994-03-24
JP2009165488A (ja) 2009-07-30
NO2005026I1 (no) 2005-12-27
ES2440825T3 (es) 2014-05-19
NO2001026I2 (no) 2006-11-20
NO2005005I2 (no) 2009-01-19
ATE133452T1 (de) 1996-02-15
PT92758B (pt) 1996-01-31
NL300213I2 (nl) 2006-07-03
DE10075038I1 (de) 2001-03-01
IL162181A (en) 2006-04-10
JPH04502408A (ja) 1992-05-07
EP0682040B1 (en) 1999-08-25
DE122005000007I2 (de) 2009-06-25
JP2003245091A (ja) 2003-09-02
DE10075005I2 (de) 2005-06-23
JP2003245090A (ja) 2003-09-02
DK119191D0 (da) 1991-06-19
CA2328851A1 (en) 1990-06-28
EP0682040A1 (en) 1995-11-15
EP0451216A4 (en) 1992-01-02

Similar Documents

Publication Publication Date Title
CN1057013C (zh) 新的白细胞介素－２受体特异性免疫球蛋白
AU631545B2 (en) Il-2 receptor-specific chimeric antibodies
US6521230B1 (en) CD25 binding molecules
US6569430B1 (en) Antibodies to the antigen Campath-1
CA1339198C (en) Antibodies to the antigen campath-1
TWI338009B (en) Antibodies for inhibiting blood coagulation and methods of use thereof
KR20040074587A (ko) 감소된 면역원성을 갖는 인공 단백질
CN1357009A (zh) 人源化的特异于人4－1bb的抗体和含有它的药物组合物
CN1617888A (zh) 用于肌内给药的双特异性抗体dna的构建
JP4044733B2 (ja) ベロ毒素ｉｉを認識するヒト型化抗体、および該抗体を産生する細胞株
CN110054700A (zh) 长效治疗性融合蛋白
CN110573531B (zh) 经修饰的Cκ和CH1结构域
WO1993001289A1 (en) Humanized interleukin-2 receptors antibodies

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
C15 Extension of patent right duration from 15 to 20 years for appl. with date before 31.12.1992 and still valid on 11.12.2001 (patent law change 1993)
OR01 Other related matters
C56 Change in the name or address of the patentee

Owner name: PDL BIOPHARMACEUTICAL COMPANY

Free format text: FORMER NAME OR ADDRESS: PROTEIN DESIGN LABS, INC A DELAWARE CORPORATION

CP01 Change in the name or title of a patent holder

Address after: American California

Patentee after: Pdl Biopharma Inc.

Address before: American California

Patentee before: Protein Design Labs, Inc a Delaware Corporation

C17 Cessation of patent right
CX01 Expiry of patent term

Granted publication date: 20001004