公开(公告)号：US20100215666A1

公开(公告)日：2010-08-26

申请号：US12707934

申请日：2010-02-18

Applicant: FRANCO E. DI PADOVA ,  HERMANN GRAM ,  HANS HOFSTETTER ,  MARGIT JESCHKE ,  JEAN-MICHEL RONDEAU ,  WIM VAN DEN BERG

Inventor： FRANCO E. DI PADOVA ,  HERMANN GRAM ,  HANS HOFSTETTER ,  MARGIT JESCHKE ,  JEAN-MICHEL RONDEAU ,  WIM VAN DEN BERG

IPC: A61K39/395 ,  C07K16/24 ,  C07H21/04 ,  A61P29/00 ,  A61P27/02 ,  C12N15/63 ,  C12N1/21 ,  C12N1/19 ,  C12N5/10 ,  C12P21/04

CPC classification number: C07K16/244 ,  C07K2317/21 ,  C07K2317/55 ,  C07K2317/76 ,  C07K2317/92

Abstract: An IL-17 binding molecule, in particular an antibody to human IL-17, more preferably a human antibody to human IL-17 is provided, wherein the hypervariable regions of the heavy and light chains have amino acid sequences as defined, for use in the treatment of an IL-17 mediated disease or disorder, e.g. rheumatoid arthritis.

Abstract translation: 提供IL-17结合分子，特别是人IL-17的抗体，更优选人IL-17的人抗体，其中重链和轻链的高变区具有如所定义的氨基酸序列，用于 治疗IL-17介导的疾病或病症，例如 类风湿关节炎。

公开(公告)号：US20090232803A1

公开(公告)日：2009-09-17

申请号：US12351007

申请日：2009-01-09

Applicant: Hermann Gram ,  Franco E. Di Padova

Inventor： Hermann Gram ,  Franco E. Di Padova

IPC: A61K39/395 ,  C07H21/00 ,  C12N15/63 ,  C12N5/10 ,  C12N1/21 ,  C12P21/02 ,  C07K16/24

CPC classification number: C07K16/245 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/565

Abstract: An IL-1β binding molecule, in particular an antibody to human IL-1β, especially a human antibody to human IL-1β is provided, wherein the CDRs of the heavy and light chains have amino acid sequences as defined, for use in the treatment of an IL-1 mediated disease or disorder, e.g. osteoarthritis, osteoporosis and other inflammatory arthritides.

Abstract translation: 提供IL-1β结合分子，特别是人IL-1β的抗体，特别是人IL-1β的人抗体，其中重链和轻链的CDR具有如定义的氨基酸序列，用于治疗 的IL-1介导的疾病或病症，例如 骨关节炎，骨质疏松症和其他炎症性关节炎。

公开(公告)号：US07491392B2

公开(公告)日：2009-02-17

申请号：US11484472

申请日：2006-07-11

Applicant: Hermann Gram ,  Franco E Di Padova

Inventor： Hermann Gram ,  Franco E Di Padova

IPC: A61K39/40 ,  C07K16/00

CPC classification number: C07K16/245 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/565

Abstract: An IL-1β binding molecule, in particular an antibody to human IL-1β, especially a human antibody to human IL-1β is provided, wherein the CDRs of the heavy and light chains have amino acid sequences as defined, for use in the treatment of an IL-1 mediated disease or disorder, e.g. osteoarthritis, osteroporosis and other inflammatory arthritides.

Abstract translation: 提供IL-1β结合分子，特别是人IL-1β的抗体，特别是人IL-1β的人抗体，其中重链和轻链的CDR具有如定义的氨基酸序列，用于治疗 的IL-1介导的疾病或病症，例如 骨关节炎，骨质疏松症和其他炎症性关节炎。

公开(公告)号：US07446175B2

公开(公告)日：2008-11-04

申请号：US10362082

申请日：2001-08-20

Applicant: Hermann Gram ,  Franco E. Di Padova

Inventor： Hermann Gram ,  Franco E. Di Padova

IPC: C07K16/00 ,  A61K39/395

CPC classification number: C07K16/245 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/34

Abstract: An IL-1β binding molecule, in particular an antibody to human IL-1β, especially a human antibody to human IL-1β is provided, wherein the CDRs of the heavy and light chains having amino acid sequences as defined, for use in the treatment of an IL-1 mediated disease or disorder, e.g. osteoarthritis, osteoporosis and other inflammatory arthritides.

Abstract translation: 提供IL-1β结合分子，特别是人IL-1β的抗体，特别是人IL-1β的人抗体，其中具有如定义的氨基酸序列的重链和轻链的CDR用于治疗 的IL-1介导的疾病或病症，例如 骨关节炎，骨质疏松症和其他炎症性关节炎。

公开(公告)号：US20050009147A1

公开(公告)日：2005-01-13

申请号：US10848279

申请日：2004-05-18

Applicant: Wilfried Bauer ,  Robin Breckenridge ,  Francois Cardinaux ,  Frank Gombert ,  Hermann Gram ,  Paul Ramage ,  Helmut Schneider ,  Rudolf Waelchli ,  Rainer Albert ,  Ian Lewis

Inventor： Wilfried Bauer ,  Robin Breckenridge ,  Francois Cardinaux ,  Frank Gombert ,  Hermann Gram ,  Paul Ramage ,  Helmut Schneider ,  Rudolf Waelchli ,  Rainer Albert ,  Ian Lewis

IPC: C07K9/00 ,  A61K38/00 ,  A61K38/22 ,  A61K38/29 ,  A61P3/00 ,  A61P3/14 ,  A61P19/08 ,  A61P43/00 ,  C07K20060101 ,  C07K14/01 ,  C07K14/195 ,  C07K14/41 ,  C07K14/635 ,  C07K19/00 ,  C12N1/20 ,  C12N1/21 ,  C12N5/10 ,  C12N15/09 ,  C12N15/16 ,  C12N15/62 ,  C12P21/02 ,  C12R1/19 ,  C07H21/04

CPC classification number: C07K14/005 ,  A61K38/00 ,  C07K14/635 ,  C07K2319/00 ,  C07K2319/50 ,  C07K2319/75 ,  C12N2795/10222

Abstract: PTH compounds having PTH-like activity and comprising at least one modification, said modification being either 1. at least one radical selected from a L- or D-α-amino acid, C2-6alcoxycarbonyl and optionally substituted C1-8alkyl, C2-8alkenyl, C2-8alkynyl, aralkyl, aralkenyl or C3-6cycloalkyl-C1-4alkyl and attached to the terminal amino group of the PTH compound, and/or at least one radical selected from C2-6alcoxycarbonyl and optionally substituted C1-8alkyl, C2-8alkenyl, C2-8alkynyl, aralkyl, aralkenyl or C3-6cycloalkyl-C1-4alkyl and attached to one or more side chain amino groups of the PTH compound, or 2. at least one α-amino acid unit in the positions 1 to 38 of a naturally occurring PTH sequence being replaced by a natural or unnatural amino acid unit optionally in protected form, whereby the α-amino acid units present in positions 1 and 2 at the amino terminus of the PTH sequence may be replaced by a pseudo-peptide, or a combination of such modifications, in free form or in salt form, have pharmacological activity, e.g. for preventing or treating all bone conditions which are associated with increased calcium depletion or resorption or in which calcium fixation in the bone is desirable.

Abstract translation: 具有PTH样活性并且包含至少一个修饰的PTH化合物，所述修饰是1.至少一个选自L-或D-α-氨基酸，C2-6羰基和任选取代的C 1-8烷基的基团，C 2-8烯基 ，C 2-8炔基，芳烷基，芳烯基或C 3-6环烷基-C 1-4烷基，并且连接到PTH化合物的末端氨基，和/或至少一个选自C 2-6烷氧基羰基和任选取代的C 1-8烷基基团，C 2-8烯基 ，C 2-8炔基，芳烷基，芳烯基或C 3-6环烷基-C 1-4烷基，并且连接到PTH化合物的一个或多个侧链氨基，或2个至少一个α-氨基酸单元的位置1至38 天然存在的PTH序列被任选以保护形式的天然或非天然氨基酸单元替代，由此存在于PTH序列的氨基末端的位置1和2中的α-氨基酸单元可被假肽替代，或 这些修改的组合，免费的 m或盐形式，具有药理活性，例如。 用于预防或治疗与增加的钙耗竭或吸收相关的所有骨骼状况或其中期望骨中的钙固定。

公开(公告)号：US5858728A

公开(公告)日：1999-01-12

申请号：US647144

申请日：1996-05-09

Applicant: Hermann Gram ,  Franco Di Padova ,  George Robin Barclay ,  Ian Raymond Poxton

Inventor： Hermann Gram ,  Franco Di Padova ,  George Robin Barclay ,  Ian Raymond Poxton

IPC: C07K16/12 ,  C12P21/08 ,  C12P21/04 ,  C07K16/00 ,  C12N5/06

CPC classification number: C07K16/1203 ,  C07K2319/00 ,  G01N2400/50

Abstract: The invention provides monoclonal antibodies (Mabs) which are cross-protective against endotoxemia caused by at least two different Gram-negative bacterial strains having different core structures; and methods of production of these antibodies. By use of the Kohler/Milstein procedure involving immunization of mice with a number of different rough strains of heat-killed Gram-negative bacteria, followed by fusion and proper screening of the resulting hybridomas, such murine MAbs are obtained. The murine MAbs may be chimerized or humanized by known methods. For example, a chimeric MAb of IgG isotype is provided in which the hypervariable regions of the heavy chain have the amino acid sequences: Asp Tyr Tyr Met Thr; Leu Ile Arg Asn Lys Arg Asn Gly Asp Thr Ala Glu Tyr Ser Ala Ser Val Lys; and Gln Gly Arg Gly Tyr Thr Leu Asp Tyr; the hypervariable regions of the light chain have the amino acid sequences: Arg Ala Ser Gln Asn Ile Asn Ile Trp Leu Ser; Lys Ala Ser Asn Leu His Thr; and Leu Gln Gly Gln Ser Tyr Pro Arg Thr; the framework regions in the variable domains are murine and the constant domains are human.

Abstract translation: 本发明提供对具有不同核心结构的至少两种不同革兰氏阴性细菌菌株引起的针对内毒素血症的交叉保护的单克隆抗体（Mabs） 和这些抗体的生产方法。 通过使用K + E，uml o + EE hler / Milstein程序，其涉及具有许多不同的热灭活革兰氏阴性细菌粗糙株的小鼠的免疫接种，然后融合并适当筛选得到的杂交瘤， 获得。 鼠MAb可以通过已知方法嵌合或人源化。 例如，提供IgG同种型的嵌合MAb，其中重链的高变区具有氨基酸序列：Asp Tyr Tyr Met Thr; Leu Ile Arg Asn Lys Arg Asn Gly Asp Thr Ala Glu Tyr Ser Ala Ser Val Lys; 和Gln Gly Arg Gly Tyr Thr Leu Asp Tyr; 轻链的高变区具有氨基酸序列：Arg Ala Ser Gln Asn Ile Asn Ile Trp Leu Ser; Lys Ala Ser Asn Leu His Thr; 和Leu Gln Gly Gln Ser Tyr Pro Arg Thr; 可变结构域中的框架区是鼠，恒定结构域是人。

公开(公告)号：US09168298B2

公开(公告)日：2015-10-27

申请号：US13955673

申请日：2013-07-31

Applicant: Hermann Gram ,  Thomas Jung

Inventor： Hermann Gram ,  Thomas Jung

IPC: A61K39/395 ,  C07K16/24 ,  C07K16/00

CPC classification number: C07K16/245 ,  A61K39/3955 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92

Abstract: This invention relates to a novel use of IL-1□-ligand/IL-1 receptor disrupting compounds (herein referred to as “IL-1beta Compounds”); such as small molecular compounds disrupting IL-1□ ligand—IL-1 receptor interaction, IL-1□ antibodies or IL-1 receptor antibodies, e.g. IL-1□ binding molecules described herein, e.g. antibodies disclosed herein, e.g. IL-1□ binding compounds or IL-1 receptor binding compounds, and/or RNA compounds decreasing either IL-1□ ligands or IL-1 receptor protein levels, in the treatment and/or prevention of auto-inflammatory syndromes, e.g. Juvenile rheumatoid arthritis or adult rheumatoid arthritis syndrome and to methods of treating and/or preventing auto-inflammatory syndromes, e.g. Juvenile rheumatoid arthritis or adult rheumatoid arthritis syndrome, in mammals, particularly humans.

Abstract translation: 本发明涉及IL-1□配体/ IL-1受体破坏性化合物（本文中称为“IL-1β化合物”）的新用途。 例如破坏IL-1□配体-IL-1受体相互作用的小分子化合物，IL-1□抗体或IL-1受体抗体，例如。 本文所述的IL-1β结合分子，例如 本文公开的抗体，例如 IL-1β结合化合物或IL-1受体结合化合物和/或降低IL-1配体或IL-1受体蛋白水平的RNA化合物在治疗和/或预防自身炎症综合征中的作用。 少年类风湿性关节炎或成人类风湿性关节炎综合征以及治疗和/或预防自身炎症综合征的方法，例如， 少年类风湿关节炎或成人类风湿关节炎综合征，在哺乳动物，特别是人类。

公开(公告)号：US20120321642A1

公开(公告)日：2012-12-20

申请号：US13587978

申请日：2012-08-17

Applicant: Hermann Gram ,  Thomas Jung

Inventor： Hermann Gram ,  Thomas Jung

IPC: A61K39/395 ,  A61P19/02

CPC classification number: C07K16/245 ,  A61K39/3955 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92

Abstract: This invention relates to a novel use of IL-1β-ligand/IL-1 receptor disrupting compounds (herein referred to as “IL-1beta Compounds”); such as small molecular compounds disrupting IL-1β ligand-IL-1 receptor interaction, IL-1β antibodies or IL-1 receptor antibodies, e.g. IL-1β binding molecules described herein, e.g. antibodies disclosed herein, e.g. IL-1β binding compounds or IL-1 receptor binding compounds, and/or RNA compounds decreasing either IL-1β ligands or IL-1 receptor protein levels, in the treatment and/or prevention of auto-inflammatory syndromes, e.g. Juvenile rheumatoid arthritis or adult rheumatoid arthritis syndrome and to methods of treating and/or preventing auto-inflammatory syndromes, e.g. Juvenile rheumatoid arthritis or adult rheumatoid arthritis syndrome, in mammals, particularly humans.

Abstract translation: 本发明涉及IL-1和bIG - 配体/ IL-1受体破坏化合物（本文中称为IL-1β化合物）的新用途; 例如破坏IL-1和bgr的小分子化合物; 配体-IL-1受体相互作用，IL-1和bgr; 抗体或IL-1受体抗体。 IL-1和bgr 本文所述的结合分子，例如。 本文公开的抗体，例如 IL-1和bgr 结合化合物或IL-1受体结合化合物，和/或降低IL-1和bgr的RNA化合物; 配体或IL-1受体蛋白水平，用于治疗和/或预防自身炎症综合征，例如， 少年类风湿性关节炎或成人类风湿性关节炎综合征以及治疗和/或预防自身炎症综合征的方法，例如， 少年类风湿关节炎或成人类风湿关节炎综合征，在哺乳动物，特别是人类。

公开(公告)号：US08282922B2

公开(公告)日：2012-10-09

申请号：US12601280

申请日：2008-05-28

Applicant: Hermann Gram ,  Thomas Jung

Inventor： Hermann Gram ,  Thomas Jung

IPC: A61K39/395 ,  C07K16/00 ,  C12P21/08

CPC classification number: C07K16/245 ,  A61K39/3955 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92

Abstract: This invention relates to a novel use of IL-1β-ligand/IL-1 receptor disrupting compounds (herein referred to as “IL-1beta Compounds”); such as small molecular compounds disrupting IL-1β ligand-IL-1 receptor interaction, IL-1β antibodies or IL-1 receptor antibodies, e.g. IL-1β binding molecules described herein, e.g. antibodies disclosed herein, e.g. IL-1β binding compounds or IL-1 receptor binding compounds, and/or RNA compounds decreasing either IL-1β ligands or IL-1 receptor protein levels, in the treatment and/or prevention of auto-inflammatory syndromes, e.g. Juvenile rheumatoid arthritis or adult rheumatoid arthritis syndrome and to methods of treating and/or preventing auto-inflammatory syndromes, e.g. Juvenile rheumatoid arthritis or adult rheumatoid arthritis syndrome, in mammals, particularly humans.

Abstract translation: 本发明涉及IL-1和bIG - 配体/ IL-1受体破坏化合物（本文中称为IL-1β化合物）的新用途; 例如破坏IL-1和bgr的小分子化合物; 配体-IL-1受体相互作用，IL-1和bgr; 抗体或IL-1受体抗体。 IL-1和bgr 本文所述的结合分子，例如。 本文公开的抗体，例如 IL-1和bgr 结合化合物或IL-1受体结合化合物，和/或降低IL-1和bgr的RNA化合物; 配体或IL-1受体蛋白水平，用于治疗和/或预防自身炎症综合征，例如， 少年类风湿性关节炎或成人类风湿性关节炎综合征以及治疗和/或预防自身炎症综合征的方法，例如， 少年类风湿关节炎或成人类风湿关节炎综合征，在哺乳动物，特别是人类。

公开(公告)号：US08119131B2

公开(公告)日：2012-02-21

申请号：US12707934

申请日：2010-02-18

Applicant: Franco E Di Padova ,  Hermann Gram ,  Hans Hofstetter ,  Margit Jeschke ,  Jean-Michel Rondeau ,  Wim Van Den Berg

Inventor： Franco E Di Padova ,  Hermann Gram ,  Hans Hofstetter ,  Margit Jeschke ,  Jean-Michel Rondeau ,  Wim Van Den Berg

IPC: A61K39/395 ,  C07K16/46 ,  C07K16/24 ,  C12P21/08

CPC classification number: C07K16/244 ,  C07K2317/21 ,  C07K2317/55 ,  C07K2317/76 ,  C07K2317/92

Abstract: An IL-17 binding molecule, in particular an antibody to human IL-17, more preferably a human antibody to human IL-17 is provided, wherein the hypervariable regions of the heavy and light chains have amino acid sequences as defined, for use in the treatment of an IL-17 mediated disease or disorder, e.g. rheumatoid arthritis.

Abstract translation: 提供IL-17结合分子，特别是人IL-17的抗体，更优选人IL-17的人抗体，其中重链和轻链的高变区具有如所定义的氨基酸序列，用于 治疗IL-17介导的疾病或病症，例如， 类风湿关节炎。