公开(公告)号：US09012195B2

公开(公告)日：2015-04-21

申请号：US13944427

申请日：2013-07-17

Applicant: Syntaxin Ltd. ,  Allergan Inc.

Inventor： Keith Foster ,  John Chaddock ,  Charles Penn ,  Kei Roger Aoki ,  Joseph Francis ,  Lance Steward

IPC: C07K14/665 ,  C12N9/96 ,  A61K47/48 ,  A61K38/48

CPC classification number: C12N9/96 ,  A61K38/482 ,  A61K38/4893 ,  A61K47/48246 ,  A61K47/64 ,  C07K14/665 ,  C07K2319/00

Abstract: The present invention is directed to non-cytotoxic protein conjugates for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell. The protein conjugates comprise: (i) a dynorphin Targeting Moiety (TM), wherein the TM is an agonist of a receptor present on a nociceptive sensory afferent cell, and wherein the receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of the nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell. Nucleic acid sequences encoding the protein conjugates, methods of preparing same and uses thereof are also described.

Abstract translation: 本发明涉及用于抑制或减少伤害性感觉传入细胞中的胞外融合的非细胞毒性蛋白质缀合物。 所述蛋白质缀合物包含：（i）强啡肽靶向剂量（TM），其中所述TM是感受伤害感觉传入细胞上存在的受体的激动剂，并且其中所述受体经受内吞作用以掺入伤害性感觉传入物内的内体 细胞; （ii）非细胞毒性蛋白酶或其片段，其中所述蛋白酶或蛋白酶片段能够切割伤害性感觉传入细胞的胞外融合装置的蛋白质; 易位结构域（Translocation Domain），其中易位域将位于内体内的蛋白酶或蛋白酶片段穿过内体膜并转移到伤害性感觉传入细胞的胞质溶胶中。 还描述了编码蛋白质缀合物的核酸序列，其制备方法及其用途。

公开(公告)号：US20130330807A1

公开(公告)日：2013-12-12

申请号：US13969174

申请日：2013-08-16

Applicant: Allergan, Inc.

Inventor： Lance E. Steward ,  Sanjiv Ghanshani ,  Ester Fernandez-Salas ,  Marcella A. Gilmore ,  Joseph Francis ,  Kei Roger Aoki

IPC: C12N9/52

CPC classification number: C12N9/52 ,  A61K38/4893 ,  C07K14/33 ,  C12Y304/24069

Abstract: The specification discloses Clostridial toxins or Clostridial toxin chimeras comprising an inactivation cleavage site, polynucleotide molecules encoding such toxins or chimeras, compositions comprising such toxins or chimeras, and method of producing such toxins or chimeras.

公开(公告)号：US20130330806A1

公开(公告)日：2013-12-12

申请号：US13969148

申请日：2013-08-16

Applicant: Allergan, Inc.

Inventor： Lance E. Steward ,  Sanjiv Ghanshani ,  Ester Fernandez-Salas ,  Marcella A. Gilmore ,  Joseph Francis ,  Kei Roger Aoki

IPC: C12N9/52

CPC classification number: C12N9/52 ,  A61K38/4893 ,  C07K14/33 ,  C12Y304/24069

Abstract: The specification discloses Clostridial toxins or Clostridial toxin chimeras comprising an inactivation cleavage site, polynucleotide molecules encoding such toxins or chimeras, compositions comprising such toxins or chimeras, and method of producing such toxins or chimeras.

Abstract translation: 本说明书公开了包含灭活切割位点的梭菌毒素或梭菌毒素嵌合体，编码这种毒素或嵌合体的多核苷酸分子，包含这种毒素或嵌合体的组合物，以及产生此类毒素或嵌合体的方法。

公开(公告)号：US20130224178A1

公开(公告)日：2013-08-29

申请号：US13768665

申请日：2013-02-15

Applicant: ALLERGAN, INC.

Inventor： Birgitte P.S. Jacky ,  Patton E. Garay ,  Yanira Molina ,  Dean G. Stathakis ,  Joseph Francis ,  Kei Roger Aoki ,  Ester Fernandez-Salas ,  Lance E. Steward ,  Sanjiv Ghanshani ,  Terrence J. Hunt

IPC: A61K38/48

CPC classification number: A61K38/48 ,  A61K38/00 ,  C07K14/33 ,  C07K2319/033 ,  C07K2319/55

Abstract: The present specification discloses TVEMPs, compositions comprising such TVEMPs and methods of treating cancer in a mammal using such TVEMP compositions.

Abstract translation: 本说明书公开了TVEMP，包含这样的TVEMP的组合物和使用这种TVEMP组合物治疗哺乳动物癌症的方法。

公开(公告)号：US20230256063A1

公开(公告)日：2023-08-17

申请号：US17946447

申请日：2022-09-16

Applicant: Allergan, Inc.

Inventor： Eric A. Forssen ,  Patrick M. Hughes ,  David C. Rupp ,  Terrence J. Hunt ,  Gary Shimizu ,  Joseph Francis ,  Ron S. Broide ,  Ester Fernandez-Salas ,  Catherine Rheaume

IPC: A61K38/48 ,  A61K47/34 ,  A61K38/16 ,  A61K9/00 ,  A61K47/10 ,  A61K47/36

CPC classification number: A61K38/4893 ,  A61K47/34 ,  A61K38/164 ,  A61K9/0034 ,  A61K47/10 ,  A61K47/36 ,  C12Y304/24069

Abstract: Pharmaceutical formulations comprising a clostridial derivative and a permeabilizing agent for intravesical instillation are disclosed.

公开(公告)号：US11248219B2

公开(公告)日：2022-02-15

申请号：US16416435

申请日：2019-05-20

Applicant: IPSEN BIOINNOVATION LIMITED ,  ALLERGAN, INC.

Inventor： Peter James ,  Keith Foster ,  John Chaddock ,  Roger Aoki ,  Lance Steward ,  Joseph Francis

IPC: C12N9/52 ,  A61K47/65 ,  A61K38/00 ,  C07K14/575 ,  A61K47/64 ,  C12N15/62

Abstract: Single chain polypeptide fusion protein, comprising: a non-cytotoxic protease capable of cleaving a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a galanin targeting moiety; a protease cleavage site; a translocation domain; a first spacer located between the non-cytotoxic protease and the protease cleavage site; and a second spacer located between the galanin targeting moiety and the translocation domain.

公开(公告)号：US20180119126A1

公开(公告)日：2018-05-03

申请号：US15845572

申请日：2017-12-18

Applicant: Allergan, Inc.

Inventor： Lance E. Steward ,  Sanjiv Ghanshani ,  Ester Fernandez-Salas ,  Marcella A. Gilmore ,  Joseph Francis ,  Kei Roger Aoki

IPC: C12N9/52 ,  A61K38/48 ,  C07K14/33

CPC classification number: C12N9/52 ,  A61K38/4893 ,  C07K14/33 ,  C12Y304/24069

Abstract: The specification discloses Clostridial toxins or Clostridial toxin chimeras comprising an inactivation cleavage site, polynucleotide molecules encoding such toxins or chimeras, compositions comprising such toxins or chimeras, and method of producing such toxins or chimeras.

公开(公告)号：US09474807B2

公开(公告)日：2016-10-25

申请号：US14300746

申请日：2014-06-10

Applicant: IPSEN BIOINNOVATION LTD. ,  Allergan Inc.

Inventor： Keith Foster ,  John Chaddock ,  Charles Penn ,  Kei Roger Aoki ,  Joseph Francis ,  Lance Steward

IPC: A61K47/48 ,  A61K38/48 ,  C12N15/62 ,  C07K14/665 ,  A61K38/22

CPC classification number: C12N9/6432 ,  A61K38/00 ,  A61K38/22 ,  A61K38/48 ,  A61K47/48246 ,  A61K47/48338 ,  A61K47/48361 ,  A61K47/64 ,  A61K47/65 ,  A61K47/67 ,  C07K14/665 ,  C07K2319/00 ,  C07K2319/01 ,  C07K2319/21 ,  C07K2319/55 ,  C12N9/96 ,  C12N15/62 ,  C12Y304/00 ,  C12Y304/21006

Abstract: The present invention is directed to non-cytotoxic protein conjugates for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell. The protein conjugates comprise: (i) a Targeting Moiety (TM), wherein the TM is an agonist of a receptor present on a nociceptive sensory afferent cell, and wherein the receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of the nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell wherein the Targeting Moiety is selected from the group consisting of BAM, β-endorphin, bradykinin, substance P, dynorphin and/or nociceptin.

Abstract translation: 本发明涉及用于抑制或减少伤害性感觉传入细胞中的胞外融合的非细胞毒性蛋白质缀合物。 所述蛋白质缀合物包含：（i）靶向部分（TM），其中所述TM是存在于伤害性感觉传入细胞上的受体的激动剂，并且其中所述受体经受内吞作用以掺入伤害性感觉传入细胞内的内体 ; （ii）非细胞毒性蛋白酶或其片段，其中所述蛋白酶或蛋白酶片段能够切割伤害性感觉传入细胞的胞外融合装置的蛋白质; 易位结构域，其中易位域将内体内的蛋白酶或蛋白酶片段转移穿过内体膜，并转移到伤害性感觉传入细胞的胞质溶胶中，其中靶向部分选自BAM ，β-内啡肽，缓激肽，物质P，强啡肽和/或伤害感受肽。

公开(公告)号：US20150313973A1

公开(公告)日：2015-11-05

申请号：US14700390

申请日：2015-04-30

Applicant: Allergan, Inc.

Inventor： Eric A. Forssen ,  Patrick M. Hughes ,  David C. Rupp ,  Terrence Hunt ,  Gary Shimizu ,  Joseph Francis ,  Ron S. Broide ,  Ester Fernandez-Salas

IPC: A61K38/48 ,  A61K47/36 ,  A61K47/10 ,  A61K47/34

CPC classification number: A61K38/4893 ,  A61K9/0034 ,  A61K38/164 ,  A61K47/10 ,  A61K47/34 ,  A61K47/36 ,  C12Y304/24069

Abstract: Pharmaceutical formulations comprising a clostridial derivative and a permeabilizing agent for intravesical instillation are disclosed.

Abstract translation: 公开了包含梭菌衍生物和膀胱内滴注渗透剂的药物制剂。

公开(公告)号：US08841111B2

公开(公告)日：2014-09-23

申请号：US13846364

申请日：2013-03-18

Applicant: Allergan, Inc.

Inventor： Lance E. Steward ,  Sanjiv Ghanshani ,  Ester Fernandez-Salas ,  Marcella A. Gilmore ,  Joseph Francis ,  Kei Roger Aoki

IPC: C12N9/52 ,  C12N9/50 ,  C12N9/96 ,  C07H21/04

CPC classification number: C12N9/52 ,  A61K38/4893 ,  C07K14/33 ,  C12Y304/24069

Abstract: The specification discloses Clostridial toxins or Clostridial toxin chimeras comprising an inactivation cleavage site, polynucleotide molecules encoding such toxins or chimeras, compositions comprising such toxins or chimeras, and method of producing such toxins or chimeras.