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1. 发明授权

US10619146B2 Non-cytotoxic protein conjugates 有权
公开(公告)号：US10619146B2
公开(公告)日：2020-04-14
申请号：US15258282
申请日：2016-09-07
申请人： Ipsen Bioinnovation Ltd. , Allergan Inc.
发明人： Keith Foster , John Chaddock , Charles Penn , Kei Roger Aoki , Joseph Francis , Lance Steward
IPC分类号： C12N9/64 , C12N15/62 , A61K38/48 , C07K14/665 , A61K47/66 , A61K47/65 , A61K47/64 , A61K38/22 , C12N9/96 , A61K38/00
CPC分类号： C12N9/6432 , A61K38/22 , A61K38/48 , A61K47/64 , A61K47/65 , A61K47/67 , C07K14/665 , C12N9/96 , C12N15/62 , C12Y304/00 , C12Y304/21006 , A61K38/00 , C07K2319/00 , C07K2319/01 , C07K2319/21 , C07K2319/55
摘要： 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.

2. 发明申请

US20180305406A1 Melanocortin Receptor Ligands 审中-公开
公开(公告)号：US20180305406A1
公开(公告)日：2018-10-25
申请号：US16029837
申请日：2018-07-09
申请人： Ipsen Pharma S.A.S.
发明人： Zheng Xin Dong , Jacques-Pierre Moreau
IPC分类号： C07K7/06 , C07K14/665 , C07K7/08 , A61K38/00
CPC分类号： C07K7/06 , A61K38/00 , C07K7/08 , C07K14/665
摘要： The present invention is directed to compounds according to formula, (R2R3)-A1-c(A2-A3-A4-A5-A6-A7-A8-A9)-A10-R1, and pharmaceutically-acceptable salts thereof that act as ligands for one or more of the melanocortin receptors, to methods of using such compounds to treat mammals and to pharmaceutical compositions comprising said compounds.

3. 发明申请

US20180222940A1 MU OPIOID RECEPTOR AGONIST ANALOGS OF THE ENDOMORPHINS 审中-公开
公开(公告)号：US20180222940A1
公开(公告)日：2018-08-09
申请号：US15704730
申请日：2017-09-14
申请人： The Administrators of the Tulane Educational Fund , United States Department of Veterans Affairs
发明人： James E. ZADINA , Laszlo HACKLER
IPC分类号： C07K7/06 , C07K14/665 , A61K38/12 , A61K45/06 , C07K5/12 , G01N33/94 , C07K7/64 , A61K38/00
CPC分类号： C07K7/06 , A61K38/00 , A61K38/12 , A61K45/06 , C07K5/126 , C07K7/64 , C07K14/665 , G01N33/9486 , G01N2333/70571 , G01N2333/726 , G01N2500/04
摘要： The invention relates to cyclic peptide agonists that bind to the mu (morphine) opioid receptor and their use in the treatment of acute and/or chronic pain. Embodiments of the invention are directed to cyclic pentapeptide and hexapeptide analogs of endomorphin that have (i) a carboxy-terminal extension with an amidated hydrophilic amino acid and (ii) a substitution in amino acid position 2. These peptide analogs exhibit decreased tolerance relative to morphine, increased solubility compared to similar tetrapeptide analogs, while maintaining favorable or improved therapeutic ratios of analgesia to side effects.

4. 发明申请

US20170369531A1 MU OPIOID RECEPTOR AGONIST ANALOGS OF THE ENDOMORPHINS 审中-公开
公开(公告)号：US20170369531A1
公开(公告)日：2017-12-28
申请号：US15450259
申请日：2017-03-06
申请人： The Administrators of the Tulane Educational Fund , Department of Veterans Affairs (US)
发明人： James E. ZADINA , Laszlo HACKLER
IPC分类号： C07K7/64 , C07K5/12 , G01N33/566 , G01N33/94 , C07K14/665 , C07K7/56 , A61K38/00 , C07K5/107
CPC分类号： C07K7/64 , A61K38/00 , C07K5/1016 , C07K5/126 , C07K7/56 , C07K14/665 , G01N33/566 , G01N33/9486 , G01N2333/70571 , G01N2500/04
摘要： The invention relates to cyclic peptide agonists that bind to the mu (morphine) opioid receptor and their use in the treatment of acute and/or chronic pain. Embodiments of the invention are directed to cyclic pentapeptide and hexapeptide analogs of endomorphin that have (i) a carboxy-terminal extension with an amidated hydrophilic amino acid and (ii) a substitution in amino acid position 2, and in some embodiments, a 2′,6′-dimethyltyrosine (Dmt) residue in place of the N-terminal tyrosine residue a position 1. These peptide analogs exhibit increased solubility compared to similar tetrapeptide analogs while maintaining favorable or improved therapeutic ratios of analgesia to side effects.

5. 发明授权

US09322829B2 Stabilized bioactive peptides and methods of identification, synthesis, and use 有权
标题翻译：稳定的生物活性肽和鉴定，合成和使用的方法
公开(公告)号：US09322829B2
公开(公告)日：2016-04-26
申请号：US13861732
申请日：2013-04-12
申请人： Peptide BioSciences, Inc.
发明人： Elliot Altman
IPC分类号： C12N15/63 , A61K38/46 , G01N33/68 , C07K7/06 , C07K7/08 , C07K7/14 , C07K14/195 , C07K14/245 , C07K14/425 , C07K14/585 , C07K14/59 , C07K14/605 , C07K14/61 , C07K14/62 , C07K14/645 , C12N15/10 , C12N15/62 , C12N15/67 , C12N15/72 , C40B40/02 , G01N33/50 , A61K38/00
CPC分类号： G01N33/5008 , C07K7/06 , C07K7/08 , C07K7/14 , C07K14/195 , C07K14/245 , C07K14/425 , C07K14/435 , C07K14/43536 , C07K14/43568 , C07K14/43572 , C07K14/463 , C07K14/575 , C07K14/58 , C07K14/585 , C07K14/59 , C07K14/605 , C07K14/61 , C07K14/62 , C07K14/63 , C07K14/645 , C07K14/655 , C07K14/665 , C07K2319/00 , C12N15/1037 , C12N15/62 , C12N15/635 , C12N15/67 , C12N15/72 , C40B40/02 , G01N33/5011 , G01N33/5014 , G01N33/502 , G01N33/68 , G01N33/6845
摘要： An intracellular selection system allows screening for peptide bioactivity and stability. Randomized recombinant peptides are screened for bioactivity in a tightly regulated expression system, preferably derived from the wild-type lac operon. Bioactive peptides thus identified are inherently protease- and peptidase-resistant. Also provided are bioactive peptides stabilized by a stabilizing group at the N-terminus, the C-terminus, or both. The stabilizing group can be a small stable protein, such as the Rop protein, glutathione sulfotransferase, thioredoxin, maltose binding protein, or glutathione reductase, an α-helical moiety, or one or more proline residues.
摘要翻译：细胞内选择系统允许筛选肽的生物活性和稳定性。在紧密调节的表达系统中筛选随机重组肽的生物活性，优选衍生自野生型lac操纵子。因此鉴定的生物活性肽本身就是蛋白酶和肽酶抗性。还提供了在N末端，C末端或两者均由稳定基团稳定的生物活性肽。稳定基团可以是小的稳定蛋白质，例如Rop蛋白质，谷胱甘肽磺基转移酶，硫氧还蛋白，麦芽糖结合蛋白或谷胱甘肽还原酶，α-螺旋部分或一个或多个脯氨酸残基。

6. 发明授权

US09296809B2 Albumin fusion proteins 有权
公开(公告)号：US09296809B2
公开(公告)日：2016-03-29
申请号：US14818972
申请日：2015-08-05
申请人： Human Genome Sciences, Inc.
发明人： Craig A. Rosen , William A. Haseltine , Steven M. Ruben
IPC分类号： C07K14/765 , C07K14/505 , C07K14/535 , C07K14/61 , C07K14/62 , C07K14/56 , C07K14/585 , C07K14/565 , C07K14/60 , C07K14/55 , C07K14/635 , C07K14/575 , C07K14/525 , C07K14/555 , C07K14/50 , C07K7/06 , C07K14/475 , C07K14/51 , C07K14/605 , C07K14/54 , C07K16/26 , A61K38/00 , C07K16/24 , C07K14/52 , C07K14/47 , C07K14/655 , C12N9/02
CPC分类号： C07K14/765 , A61K31/155 , A61K31/426 , A61K31/4439 , A61K31/4965 , A61K38/00 , A61K38/04 , A61K38/17 , A61K38/28 , A61K39/21 , C07K7/06 , C07K14/005 , C07K14/435 , C07K14/4713 , C07K14/4723 , C07K14/475 , C07K14/50 , C07K14/505 , C07K14/51 , C07K14/521 , C07K14/525 , C07K14/535 , C07K14/54 , C07K14/5406 , C07K14/55 , C07K14/555 , C07K14/56 , C07K14/565 , C07K14/575 , C07K14/57563 , C07K14/5759 , C07K14/585 , C07K14/59 , C07K14/60 , C07K14/605 , C07K14/61 , C07K14/62 , C07K14/635 , C07K14/65 , C07K14/655 , C07K14/665 , C07K14/705 , C07K14/7151 , C07K14/82 , C07K16/00 , C07K16/241 , C07K16/26 , C07K2317/622 , C07K2317/76 , C07K2319/00 , C07K2319/20 , C07K2319/30 , C07K2319/31 , C12N7/00 , C12N9/0006 , C12N9/0008 , C12N15/62 , C12N2501/335 , C12N2740/16111 , C12N2740/16122 , C12N2740/16134 , C12N2740/16171 , C12Y101/01105 , C12Y102/01 , C12Y207/01095
摘要： The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disorders or conditions using albumin fusion proteins of the invention.

7. 发明授权

US09243301B2 Fusion proteins 有权
标题翻译：融合蛋白
公开(公告)号：US09243301B2
公开(公告)日：2016-01-26
申请号：US13419381
申请日：2012-03-13
申请人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
发明人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
IPC分类号： A61K38/00 , C12N9/52 , C12N15/62 , C07K14/665
CPC分类号： C12Y304/24069 , A61K38/00 , A61K38/1709 , A61K38/482 , A61K38/4886 , A61K38/4893 , A61K47/6415 , A61K47/65 , C07K14/665 , C07K2319/055 , C07K2319/06 , C07K2319/50 , C12N9/52 , C12N15/62
摘要： A single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, or a fragment thereof, which protease or protease fragment can cleave a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a Targeting Moiety that can bind to a Binding Site on the nociceptive sensory afferent, which Binding Site can undergo endocytosis to be incorporated into an endosome within the nociceptive sensory afferent; a protease cleavage site at which site the fusion protein is cleavable by a protease, which is located between the non-cytotoxic protease and the Targeting Moiety; and a translocation domain that can translocate the protease or protease fragment from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent; wherein the Targeting Moiety is BAM, β-endorphin, bradykinin, substance P, dynorphin and/or nociceptin. Nucleic acid sequences encoding the fusion proteins, methods of preparing same and uses thereof are also described.
摘要翻译：一种单链多肽融合蛋白，其包含：非细胞毒性蛋白酶或其片段，所述蛋白酶或蛋白酶片段可以切割伤害性感觉传入的胞外融合装置的蛋白质; 可以结合伤害性感觉传入物上的结合位点的靶向物质，其结合位点可以进行内吞作用以掺入伤害性感觉传入体内的内体; 蛋白酶切割位点，位于融合蛋白可被位于非细胞毒性蛋白酶和靶向部位之间的蛋白酶切割; 以及易位区域，其可以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物的胞质溶胶中; 其中靶向部分是BAM，β-内啡肽，缓激肽，物质P，强啡肽和/或伤害感受肽。还描述了编码融合蛋白的核酸序列，其制备方法及其用途。

8. 发明授权

US09012195B2 Non-cytotoxic protein conjugates 有权
标题翻译：非细胞毒性蛋白偶联物
公开(公告)号：US09012195B2
公开(公告)日：2015-04-21
申请号：US13944427
申请日：2013-07-17
申请人： Syntaxin Ltd. , Allergan Inc.
发明人： Keith Foster , John Chaddock , Charles Penn , Kei Roger Aoki , Joseph Francis , Lance Steward
IPC分类号： C07K14/665 , C12N9/96 , A61K47/48 , A61K38/48
CPC分类号： C12N9/96 , A61K38/482 , A61K38/4893 , A61K47/48246 , A61K47/64 , C07K14/665 , C07K2319/00
摘要： 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.
摘要翻译：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。

9. 发明申请

US20140294797A1 NON-CYTOTOXIC PROTEIN CONJUGATES 有权
标题翻译：非细胞毒素蛋白结合
公开(公告)号：US20140294797A1
公开(公告)日：2014-10-02
申请号：US14300746
申请日：2014-06-10
申请人： Syntaxin Ltd. , Allergan Inc.
发明人： Keith FOSTER , John CHADDOCK , Charles PENN , Kei Roger AOKI , Joseph FRANCIS , Lance STEWARD
IPC分类号： A61K47/48 , A61K38/22 , A61K38/48
CPC分类号： 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
摘要： 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.
摘要翻译：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 ，内啡肽，缓激肽，物质P，强啡肽和/或伤害感受肽。

10. 发明申请

US20130202584A1 STABILIZED IMMUNE MODULATORY RNA (SIMRA) COMPOUNDS FOR TLR7 AND TLR8 有权
标题翻译：稳定的免疫调节剂RNA（SIMRA）化合物用于TLR7和TLR8
公开(公告)号：US20130202584A1
公开(公告)日：2013-08-08
申请号：US13353905
申请日：2012-01-19
申请人： Ekambar R. Kandimalla , Tao Lan , Yukui Li , Dong Yu , Daqing Wang , Mallikarjuna Reddy Putta , Sudhir Agrawal
发明人： Ekambar R. Kandimalla , Tao Lan , Yukui Li , Dong Yu , Daqing Wang , Mallikarjuna Reddy Putta , Sudhir Agrawal
IPC分类号： A61K39/395 , A61K39/00
CPC分类号： C07K14/665 , A61K31/713 , A61K39/0005 , A61K39/395 , A61K39/3955 , C12N15/117 , C12N2310/17 , C12N2310/315 , C12N2310/318 , C12N2310/3183 , C12N2310/321 , C12N2310/33 , C12N2310/331 , C12N2310/336 , C12N2310/3521
摘要： The invention relates to the therapeutic use of stabilized oligoribonucleotides as immune modulatory agents for immune therapy applications. Specifically, the invention provides RNA based oligoribonucleotides with improved nuclease and RNase stability and that have immune modulatory activity through TLR7 and/or TLR8.
摘要翻译：本发明涉及稳定的寡核糖核苷酸作为免疫治疗应用的免疫调节剂的治疗用途。具体地，本发明提供具有改进的核酸酶和核糖核酸酶稳定性的基于RNA的寡核糖核苷酸，并且通过TLR7和/或TLR8具有免疫调节活性。

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