公开(公告)号：US20090092579A1

公开(公告)日：2009-04-09

申请号：US12108478

申请日：2008-04-23

申请人： Martin Roland Jensen ,  Peter Birk ,  Klaus Gregorius Nielsen

发明人： Martin Roland Jensen ,  Peter Birk ,  Klaus Gregorius Nielsen

IPC分类号： A61K38/20 ,  A61K39/00 ,  C07K14/00 ,  C12N15/11 ,  C12N15/00 ,  C12N1/21 ,  A61K38/21 ,  C07K16/18 ,  C12N1/19 ,  C12N1/10 ,  C12N5/06 ,  A61K38/16 ,  C12N15/87

CPC分类号： A61K39/385 ,  A61K38/00 ,  A61K38/1709 ,  A61K39/0007 ,  A61K47/646 ,  A61K2039/53 ,  A61K2039/6037 ,  A61K2039/6087 ,  A61K2039/64 ,  C07K14/4711 ,  C07K2319/00 ,  G01N33/6896 ,  G01N2333/4709 ,  G01N2500/04

摘要： Disclosed are novel methods for combating diseases characterized by deposition of amyloid. The methods generally rely on immunization against amyloidogenic proteins (proteins contributing to formation of amyloid) such as beta amyloid (Aβ). Immunization is preferably effected by administration of analogues of autologous amyloidogenic polypeptides, said analogues being capable of inducing antibody production against the autologous amyloidogenic polypeptides. Especially preferred as an immunogen is autologous Aβ which has been modified by introduction of one single or a few foreign, immunodominant and promiscuous T-cell epitopes while substantially preserving the majority of Aβ's B-cell epitopes. Also disclosed are nucleic acid vaccination against amyloidogenic polypeptides and vaccination using live vaccines as well as methods and means useful for the vaccination. Such methods and means include methods for identification of useful immunogenic analogues of the amyloidogenic proteins, methods for the preparation of analogues and pharmaceutical formulations, as well as nucleic acid fragments, vectors, transformed cells, polypeptides and pharmaceutical formulations.

摘要翻译： 公开了用于对抗以沉淀淀粉样蛋白为特征的疾病的新方法。 所述方法通常依赖于抗淀粉样变蛋白（有助于形成淀粉样蛋白的蛋白质）如β淀粉样蛋白（Abeta）的免疫。 免疫优选通过施用自体淀粉样蛋白多肽的类似物来实现，所述类似物能够诱导针对自体淀粉样蛋白多肽的抗体产生。 作为免疫原特别优选的是通过引入一个或几个外来的免疫显性和混杂的T细胞表位而修饰的自体Abeta，同时基本上保留了大部分的Abeta的B细胞表位。 还公开了针对淀粉样变性多肽的核酸接种和使用活疫苗的疫苗接种以及可用于疫苗接种的方法和装置。 这样的方法和手段包括用于鉴定淀粉样蛋白形成蛋白质的有用的免疫原性类似物的方法，用于制备类似物和药物制剂的方法，以及核酸片段，载体，转化细胞，多肽和药物制剂。

公开(公告)号：US07285273B1

公开(公告)日：2007-10-23

申请号：US09980916

申请日：2000-04-19

申请人： Steen Klysner

发明人： Steen Klysner

IPC分类号： A61K39/00 ,  A61K45/00 ,  C12P21/04 ,  C07K1/00

CPC分类号： C07K14/5409 ,  A61K39/00 ,  A61K39/0005 ,  A61K2039/51 ,  A61K2039/53 ,  C07K2319/55

摘要： Improvements in therapy and prevention of conditions characterized by an elevated level of eosinophil leukocytes, i.e. conditions such as asthma and other chronic allergic diseases are disclosed. A method is provided for down-regulating interleukin 5 (IL5) by enabling the production of antibodies against IL5 thereby reducing the level of activity of eosinophils.

摘要翻译： 公开了治疗和预防以嗜酸性粒细胞白细胞水平升高为特征的病症的改善，即哮喘和其它慢性过敏性疾病等疾病。 提供了一种通过使抗IL5抗体产生降低白细胞介素5（IL5）的下调方法，从而降低嗜酸性粒细胞活性的水平。

公开(公告)号：US07056512B1

公开(公告)日：2006-06-06

申请号：US09620586

申请日：2000-07-20

申请人： Steen Klysner ,  Soren Mouritsen ,  Torben Halkier

发明人： Steen Klysner ,  Soren Mouritsen ,  Torben Halkier

IPC分类号： A61K39/00 ,  A61K39/38

CPC分类号： C07K14/475 ,  A61K38/00 ,  A61K39/00 ,  A61K39/0005 ,  A61K48/00 ,  A61K2039/523 ,  A61K2039/53 ,  A61K2039/55516 ,  A61K2039/55522 ,  C07K2319/00

摘要： Disclosed are novel methods for increasing muscle mass by means of immunization against Growth Differentiation Factor 8 (GDF-8, myostatin). Immunization is preferably effected by administration of analogues of GDF-8 which are capable of inducing antibody production against homologous GDF-8. Especially preferred as an immunogen is homologous GDF-8 which has been modified by introduction of one single or a few foreign, immunodominant and promiscuous T-cell epitopes while substantially preserving the tertiary structure of the homologous GDF-8. Also disclosed are nucleic acid vaccination against GDF-8 and vaccination using live vaccines as well as methods and means useful for the vaccination. Such methods and means include methods for identification of useful immunogenic GDF-8 analogues, methods for the preparation of analogues and pharmaceutical formulations, as well as nucleic acid fragments, vectors, transformed cells, polypeptides and pharmaceutical formulations.

摘要翻译： 公开了通过免疫接种生长分化因子8（GDF-8，肌生成抑制素）来增加肌肉质量的新方法。 免疫优选通过施用能够诱导针对同源GDF-8的抗体产生的GDF-8的类似物来实现。 特别优选的是作为免疫原的同源GDF-8，其通过引入一个或多个外来的免疫显性和混杂的T细胞表位而被修饰，同时基本上保留了同源的GDF-8的三级结构。 还公开了针对GDF-8的核酸疫苗接种和使用活疫苗的疫苗接种以及用于疫苗接种的方法和装置。 这些方法和手段包括鉴定有用的免疫原性GDF-8类似物的方法，制备类似物和药物制剂的方法，以及核酸片段，载体，转化细胞，多肽和药物制剂。

公开(公告)号：US20020172673A1

公开(公告)日：2002-11-21

申请号：US09949375

申请日：2001-09-06

申请人： Pharmexa A/S

发明人： Steen Klysner ,  Paul von Hoegen ,  Bjorn Voldborg ,  Anand Gautam

IPC分类号： A61K039/395

CPC分类号： A61K39/0008 ,  A61K2039/6037

摘要： The present invention discloses methods for immunizing against autologous (self) Immunoglobulin E (IgE). In particular, the invention discloses methods for inducing cytotoxic T-lymphocytes that will specifically down-regulate B-cells producing autologous IgE, notably by means of nucleic acid vaccination or live vaccination. Also disclosed are methods for inducing antibodies reactive with autologous IgE as well as methods for inducing a combined antibody and CTK response specific for IgE. The invention also discloses specific immunogenic protein constructs, nucleic acids encoding these as well as various formulations and tools for preparing the vaccines, including vectors and transformed host cells.

摘要翻译： 本发明公开了免疫自体免疫球蛋白E（IgE）免疫的方法。 特别地，本发明公开了诱导细胞毒性T淋巴细胞的方法，其特别是通过核酸接种或活疫苗接种来特异性地下调产生自体IgE的B细胞。 还公开了诱导与自体IgE反应的抗体的方法以及用于诱导IgE特异性的组合抗体和CTK应答的方法。 本发明还公开了特异性免疫原性蛋白质构建体，编码这些蛋白质的核酸以及用于制备疫苗的各种制剂和工具，包括载体和转化的宿主细胞。

公开(公告)号：US20070184023A1

公开(公告)日：2007-08-09

申请号：US10577489

申请日：2004-10-28

申请人： Peter Rasmussen ,  Florence Dal Degan ,  Valery Renard ,  Steen Klysner ,  Birgitte Volck

发明人： Peter Rasmussen ,  Florence Dal Degan ,  Valery Renard ,  Steen Klysner ,  Birgitte Volck

IPC分类号： A61K39/385 ,  A61K38/21 ,  C07H21/04 ,  C07K14/475 ,  C12N1/15 ,  C12N1/21 ,  C12N15/63 ,  C12N15/74 ,  C12N15/79 ,  C12N5/04 ,  C12N5/06

CPC分类号： C07K14/52 ,  A61K38/00 ,  A61K39/00 ,  A61K47/61 ,  A61K47/6415 ,  A61K47/642 ,  Y02A50/412

摘要： The present invention provides for novel immunogenic variants of VEGF (vascular endothelial growth factor) which are useful in active specific immunotherapy against diseases that are characterized by overexpression of VEGF. The invention also relates to methods of treating such diseases (for instance cancer) as well as to various tools in molecular biology that assist in the provision of the immunogenic variants.

摘要翻译： 本发明提供VEGF（血管内皮生长因子）的新型免疫原性变体，其可用于针对以VEGF过表达为特征的疾病的活性特异性免疫疗法。 本发明还涉及治疗这些疾病（例如癌症）的方法以及有助于提供免疫原性变体的分子生物学中的各种工具。

公开(公告)号：US07097837B2

公开(公告)日：2006-08-29

申请号：US10080101

申请日：2002-02-19

申请人： Klaus Gregorius Nielsen ,  Peter Koefoed

发明人： Klaus Gregorius Nielsen ,  Peter Koefoed

IPC分类号： A61K39/00 ,  A61K39/385 ,  A61K38/00 ,  C07K4/00 ,  C07K17/00

CPC分类号： A61K39/0007 ,  A61K9/19 ,  A61K39/385 ,  A61K47/61 ,  A61K2039/53 ,  A61K2039/6037 ,  A61K2039/6068 ,  A61K2039/6087 ,  A61K2039/6093 ,  A61K2039/64 ,  C07K14/4711 ,  C07K2319/00

摘要： The present invention provides for novel immungens that are comprised of an activated polyhydroxypolymer backbone to which is attached 2 separate antigenic determinants. The 1st antigenic determinant includes a B-cell or CTL epitope and the 2nd antigenic determinant includes a T-helper epitope. In preferred embodiments, the antigenic determinants are derived from different molecules and species. Exemplary immunogens of the invention are constituted of a linear tresyl-activated dextran backbone to which is coupled B-cell or CTL epitopes of an antigen and to which is also coupled universal T-helper epitopes. Also disclosed are immunogenic compositions comprising the immunogens, methods of immunization and a method for identification of suitable immunogens of the invention.

公开(公告)号：US20030082514A1

公开(公告)日：2003-05-01

申请号：US10178045

申请日：2002-06-20

申请人： Pharmexa A/S

发明人： Martin Roland Jensen ,  Finn Skou Pedersen ,  Soren Mouritsen ,  Peter Hindersson ,  Mogens Duch ,  Michael Schandorf Sorensen ,  Iben Dalum ,  Anders Henrik Lund

IPC分类号： C12Q001/00 ,  C12Q001/68 ,  C12P019/34 ,  C12N015/85

CPC分类号： C40B30/04 ,  C12N15/1034 ,  C12Q1/6811 ,  G01N33/5005 ,  G01N33/6845

摘要： Biologically active peptides and nucleic acids are identified by a method comprising the following steps: (a) production of a pool of appropriate vectors each containing totally or partly random DNA sequences, (b) efficient transduction of said vectors into a number of identical eukaryotic cells in such a way that a single ribonucleic acid and possibly peptide is expressed or a limited number of different random ribonucleic acids and peptides are expressed by each cell, (c) screening of said transduced cells to see whether some of them have changed a certain phenotypic trait, (d) selection and cloning of said changed cells, (e) isolation and sequencing of the vector DNA in said phenotypically changed cells, and (f) deducing the ribonucleic acid and peptide sequences from the DNA sequence. The peptide sequences may be introduced into or fused to a larger protein, preferably an antibody molecule or a fragment thereof. This may be obtained by introducing the random DNA sequences into or fusing them to a DNA sequence encoding such larger protein.

摘要翻译： 通过包括以下步骤的方法鉴定生物活性肽和核酸：（a）制备各自含有完全或部分随机DNA序列的合适载体池，（b）将所述载体有效转导到多个相同的真核细胞中 以这样一种方式，单个核糖核酸和可能的肽被表达，或者有限数目的不同的随机核糖核酸和肽被每个细胞表达，（c）筛选所述转导的细胞，看看它们中有些是否已经改变了某种表型 特征，（d）所述改变的细胞的选择和克隆，（e）在所述表型改变的细胞中分离和测序载体DNA，和（f）从DNA序列推导核糖核酸和肽序列。 肽序列可以被引入或融合到较大的蛋白质，优选抗体分子或其片段中。 这可以通过将随机DNA序列引入或将其融合到编码这种较大蛋白质的DNA序列而获得。

公开(公告)号：US20080253993A1

公开(公告)日：2008-10-16

申请号：US11909983

申请日：2006-03-30

申请人： Lucilla Steinaa ,  Valery Renard

发明人： Lucilla Steinaa ,  Valery Renard

IPC分类号： A61K45/00 ,  A61K39/00 ,  A61K38/21 ,  A61K9/127 ,  C07K14/00 ,  C12N15/11 ,  C12N15/00 ,  C12N1/20 ,  C12N15/74 ,  A61P37/00

CPC分类号： C07K14/71 ,  A61K9/0019 ,  A61K38/00 ,  A61K39/0011 ,  A61K48/00 ,  A61K2039/53 ,  A61K2039/55522 ,  A61K2039/55527 ,  A61K2039/6037 ,  A61K2039/6043 ,  A61K2039/6075 ,  Y02A50/412

摘要： Disclosed is a method for inducing an immune response against autologous Epidermal Growth Factor Receptor (EGFR) in humans. The method comprises effecting uptake by antigen presenting cells of epitopes (preferably all) from the extracellular portion of human EGFR and of at least one non-human T helper epitope (TH epitope) so as to induce antibodies against EGFR. Immunization may be accomplished by protein vaccination, nucleic acid vaccination and live or viral vaccination. The immune response is useful in treatment of malignancies. Also disclosed are modified EGFR proteins and expression plasmids useful for the immunization method as well as recombinant gene technology tools such as nucleic acids, vectors and host cells.

摘要翻译： 公开了一种在人体中诱导针对自体表皮生长因子受体（EGFR）的免疫应答的方法。 该方法包括通过来自人EGFR细胞外部分和至少一个非人T辅助表位（T H H H表位）的表位（优选全部）的抗原呈递细胞进行摄取，以诱导抗体 针对EGFR。 免疫可以通过蛋白质接种，核酸接种和活的或病毒接种来完成。 免疫反应可用于治疗恶性肿瘤。 还公开了可用于免疫方法的修饰的EGFR蛋白和表达质粒以及重组基因技术工具，例如核酸，载体和宿主细胞。

公开(公告)号：US07135181B2

公开(公告)日：2006-11-14

申请号：US09785215

申请日：2001-02-20

申请人： Martin Roland Jensen ,  Peter Birk Rasmussen ,  Klaus Gregorius Nielsen

发明人： Martin Roland Jensen ,  Peter Birk Rasmussen ,  Klaus Gregorius Nielsen

IPC分类号： A61K39/00 ,  A61K38/19 ,  A61K38/20

CPC分类号： A61K39/385 ,  A61K38/00 ,  A61K38/1709 ,  A61K39/0007 ,  A61K47/646 ,  A61K2039/53 ,  A61K2039/6037 ,  A61K2039/6087 ,  A61K2039/64 ,  C07K14/4711 ,  C07K2319/00 ,  G01N33/6896 ,  G01N2333/4709 ,  G01N2500/04

摘要： A method for in vivo down-regulation of amyloid protein in an animal, including a human being, the method comprising effecting presentation to the animal's immune system of an immunogenically effective amount of at least one amyloidogenic polypeptide or subsequence thereof which has been formulated so that immunization of the animal with the amyloidgenic polypeptide or subsequence thereof induces production of antibodies against the amyloidogenic polypeptide, and/or at least one analogue of the amyloidogenic polypeptide wherein is introduced at least one modification in the amino acid sequence of the amyloidogenic polypeptide which has as a result the immunization of the animal with the analogue induces production of antibodies against the amyloidogenic polypeptide.

摘要翻译： 一种用于动物体内下调淀粉样蛋白的方法，包括人，所述方法包括向动物的免疫系统呈递免疫有效量的至少一种淀粉样变性多肽或其子序列，其被配制成使得 用淀粉样蛋白生成多肽或其子序列免疫动物诱导针对淀粉样变性多肽和/或淀粉样变性多肽的至少一种类似物的抗体的产生，其中引入淀粉样变性多肽的氨基酸序列中的至少一个修饰，其具有如 结果，用该类似物的动物的免疫诱导产生针对淀粉样变性多肽的抗体。

公开(公告)号：US20060240511A1

公开(公告)日：2006-10-26

申请号：US10560961

申请日：2004-06-24

申请人： Marie Eskling ,  Klaus Nielsen

发明人： Marie Eskling ,  Klaus Nielsen

IPC分类号： C07K14/71 ,  C12P21/06

CPC分类号： C07K14/71

摘要： The present invention provides for a novel method for purification of EGFR family proteins obtained from cultures of insect cells. The process comprises subsequent steps of a) diafiltration and exchange of culture medium with buffer, b) immobilized metal affinity chromatography (IMAC), c) size exclusion chromatography (SEC), and d) anion exchange chromatography (AIE). The method also provides for an immunogenic variant of HER-2 protein which for which the purification process has been especially adapted, as well as means for the preparation of the variant.

摘要翻译： 本发明提供了从昆虫细胞培养物获得的EGFR家族蛋白的纯化的新方法。 该方法包括以下步骤：a）将缓冲液进行渗滤和培养基交换，b）固定化金属亲和层析（IMAC），c）尺寸排阻层析（SEC）和d）阴离子交换层析（AIE）。 该方法还提供了HER-2蛋白的免疫原性变体，其纯化方法已被特别适用，以及制备该变体的方法。