公开(公告)号：US10087432B2

公开(公告)日：2018-10-02

申请号：US14423222

申请日：2012-11-21

Applicant: Ipsen BioInnovation, Ltd.

Inventor： Andreas Rummel

IPC: C12N9/50 ,  C07K14/33 ,  C12Q1/37

Abstract: The present invention relates to a novel proteolytically active polypeptide and various uses of the polypeptide (and others) in screening and manufacturing methods.

公开(公告)号：US20160369257A1

公开(公告)日：2016-12-22

申请号：US15258282

申请日：2016-09-07

Applicant: Ipsen Bioinnovation Ltd. ,  Allergan Inc.

Inventor： Keith FOSTER ,  John CHADDOCK ,  Charles PENN ,  Kei Roger AOKI ,  Joseph FRANCIS ,  Lance STEWARD

IPC: C12N9/64 ,  C12N9/96 ,  C07K14/665 ,  A61K47/48 ,  A61K38/48

CPC classification number: C12N9/6432 ,  A61K38/00 ,  A61K38/22 ,  A61K38/48 ,  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：US20210163924A1

公开(公告)日：2021-06-03

申请号：US16641630

申请日：2018-08-27

Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGE ,  IPSEN BIOINNOVATION LTD ,  IPSEN BIOPHARM LTD

Inventor： Michael S. Packer ,  Travis R. Blum ,  David R. Liu ,  Keith A. Foster ,  Matthew Brian Beard

IPC: C12N15/10 ,  C12N9/52

Abstract: The disclosure provides amino acid sequence variants of Botulinum neurotoxin (BoNT) proteases that cleave (VAMP1, VAMP2, VAMP7, VAMP8, SNAP25, SNAP23, PTEN, etc.) and methods of evolving the same. In some embodiments, proteases described by the disclosure are useful for cleaving proteins found in a cell, that is in an intracellular environment. In some embodiments, proteases described by the disclosure are useful for treating diseases associated with increased or aberrant VAMP7, VAMP8, SNAP23 or PTEN expression or activity, for example, cancer and neurological disorders. Some aspects of this disclosure provide methods for generating BoNT protease variants by continuous directed evolution.

公开(公告)号：US10030238B2

公开(公告)日：2018-07-24

申请号：US14427234

申请日：2013-10-31

Applicant: Ipsen Bioinnovation Ltd.

Inventor： Aimee Cossins ,  Matthew Beard ,  Philip Marks

IPC: C12N9/52 ,  A61K38/00

Abstract: The invention provides a nucleic acid sequence comprising a sequence of contiguous nucleotides, wherein said sequence of contiguous nucleotides has at least 90% sequence identity to the nucleic acid sequence of SEQ ID NO: 1, and wherein said sequence of contiguous nucleotides encodes a single-chain BoNT/E1 protein. The present invention also provides methods for producing soluble single-chain BoNT/E1 protein in an E. coli host cell, together with methods for producing soluble di-chain BoNT/E1 protein.

公开(公告)号：US09650622B2

公开(公告)日：2017-05-16

申请号：US14451984

申请日：2014-08-05

Applicant: Ipsen Bioinnovation, Ltd.

Inventor： Andreas Rummel ,  Tanja Weil ,  Aleksandrs Gutcaits

IPC: A61K39/08 ,  C12N9/52 ,  C07K14/33 ,  A61K38/00

CPC classification number: C12N9/52 ,  A61K38/00 ,  C07K14/33 ,  C12Y304/24069 ,  Y02A50/469 ,  Y02A50/473

Abstract: The present invention relates to a transport protein which can be obtained by modifying the heavy chain of the neurotoxin formed by Clostridium botulinum wherein (i) the protein binds specifically to nerve cells with a higher or lower affinity as the native neurotoxin; (ii) the protein has an increased or reduced neurotoxicity compared to the native neurotoxin, the neurotoxicity being preferably determined in the hemidiaphragm assay; and/or (iii) the protein comprises a lower affinity against neutralizing antibodies compared to the native neurotoxin. The invention also relates to methods for producing the same and the use thereof in cosmetic and pharmaceutical compositions.

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。