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序号	专利名	申请号	申请日	公开（公告）号	公开（公告）日	发明人
1	使用细菌毒素衍生的转运序列递送生物活性剂的系统和方法	CN201180053563.1	2011-09-15	CN103249401B	2016-01-20	兰德尔·J·米斯尼; 塔希尔·玛穆德
本发明提供了霍乱弧菌Cholix基因的一种无毒突变体形式（ntCholix）、一种在氨基酸A386处截短的Cholix变体（Cholix386）、以及其他不同的Cholix衍生的多肽序列用来增强生物活性药物、治疗剂的肠递送的用途。在此所述的这些系统和方法提供了以下项：在没有注射的情况下递送大分子剂量的能力；将负荷例如（但不限于）siRNA或反义分子递送至其中需要它们的活性的细胞内区室中的能力；以及使基于纳米颗粒和树枝状化合物的载体的穿过生物膜的递送，要不然该递送会由于大多数这种膜的屏障特性而将会受到阻碍。
2	使用细菌毒素衍生的转运序列递送生物活性剂的系统和方法	CN201180053563.1	2011-09-15	CN103249401A	2013-08-14	兰德尔·J·米斯尼; 塔希尔·玛穆德
本发明提供了霍乱弧菌Cholix基因的一种无毒突变体形式（ntCholix）、一种在氨基酸A386处截短的Cholix变体（Cholix386）、以及其他不同的Cholix衍生的多肽序列用来增强生物活性药物、治疗剂的肠递送的用途。在此所述的这些系统和方法提供了以下项：在没有注射的情况下递送大分子剂量的能力；将负荷例如（但不限于）siRNA或反义分子递送至其中需要它们的活性的细胞内区室中的能力；以及使基于纳米颗粒和树枝状化合物的载体的穿过生物膜的递送，要不然该递送会由于大多数这种膜的屏障特性而将会受到阻碍。
3	EXOSOME SECRETION INHIBITOR	US15758600	2016-08-30	US20190185851A1	2019-06-20	Takahiro OCHIYA; Yusuke YOSHIOKA; Nobuyoshi KOSAKA
An exosome secretion inhibitor containing a substance suppressing expression of NAPG, HINT3 or GXYLT1 gene, or a substance suppressing activity of NAPG, HINT3 or GXYLT1 protein. It is possible to suppress secretion of exosome, thereby making it possible to suppress proliferation or metastasis of cancer cells, so that the substance suppressing expression of the gene or activity of the protein can be used as an active ingredient of a pharmaceutical composition suitably used in treatment of cancer or suppression of cancer metastasis, and also the substance can provide a carcinostatic agent having a new action mechanism which specifically suppresses expression of the gene or activity of the protein.
4	TRANSGENIC PLANTS HAVING ALTERED EXPRESSION OF A XYLAN XYLOSYLTRANSFERASE AND METHODS OF USING SAME	US15299123	2016-10-20	US20170107542A1	2017-04-20	Debra Mohnen; Ajaya Biswal
Provided herein are plants having altered expression of an IRX10 or an IRX10-L protein. Such plants have phenotypes that may include decreased recalcitrance, increased growth, decreased lignin content, or a combination thereof. Also provided herein are methods of making and using such plants.
5	選択細胞への分子送達に適用する遺伝子操作したボツリヌス菌毒素	JP2017559588	2016-05-14	JP2018515542A	2018-06-14	ベンジャミン・ジェイ・パヴリク; ポール・ブルーム; ケヴィン・ヴァン・コット
遺伝子操作したペイロード送達システムは、孔形成ユニットに共有結合した標的細胞結合ユニット、および孔形成ユニットに非共有結合しうる領域を用いて適合させたペイロード部分を含む。孔形成ユニットはクロストリジウム毒素の特定の血清亜型由来であり、他方、ペイロード領域はクロストリジウム毒素の別の血清亜型由来である。本開示のキメラタンパク質ベースの組成物は、ペイロードを神経細胞に特異的に送達することができる。
6	Engineered Clostridium Botulinum Toxin Adapted To Deliver Molecules Into Selected Cells	US15574151	2016-05-14	US20180127734A1	2018-05-10	Benjamin J. Pavlik; Paul Blum; Kevin Van Cott
An engineered payload-delivery system includes a target cell binding unit, covalently bound to a pore forming unit, and a payload portion adapted with a region capable of non-covalently binding to the pore forming unit. The pore forming unit is derived from a particular sub-serotype of Clostridium toxin, while the payload region is derived from a different sub-serotype of Clostridium toxin. The disclosed chimeric protein-based composition is capable of specifically delivering payload to neural cells.
7	Inhibition of methane production during anaerobic reductive dechlorination	US13785840	2013-03-05	US09221699B2	2015-12-29	Michael Scalzi; Antonis Karachalios
This method of restricting methane production in methanogenic bacteria, by the use of the enzyme and coenzyme inhibitors, works during anaerobic reductive dechlorination. Various compounds such as, but not limited to, red yeast rice, vitamin B10 derivatives, and ethanesulfonates are utilized to disrupt these different enzyme and coenzyme systems responsible for the production of methane. This method affects the competition of the methanogen and halo bacteria for the organic hydrogen donors that are injected in the soil and groundwater system during the remediation process.
8	SYSTEMS AND METHODS OF DELIVERY OF BIOACTIVE AGENTS USING BACTERIAL TOXIN-DERIVED TRANSPORT SEQUENCES	US14733946	2015-06-08	US20150265719A1	2015-09-24	Randall Mrsny; Tahir Mahmood
The field of the present invention relates, in part, to a strategy for novel pharmaceutical applications. More specifically, the present invention relates to a non-toxic mutant form of the Vibrio cholera Cholix gene (ntCholix), a variant of Cholix truncated at amino acid A386 (Cholix386) and the use of other various Cholix-derived polypeptide sequences to enhance intestinal delivery of biologically-active therapeutics. Importantly, the systems and methods described herein provide for the following: the ability to deliver macromolecule doses without injections; the ability to deliver cargo, such as (but not limited to) siRNA or antisense molecules into intracellular compartments where their activity is required; and the delivery of nanoparticles and dendrimer-based carriers across biological membranes, which otherwise would have been impeded due to the barrier properties of most such membranes.
9	INHIBITION OF METHANE PRODUCTION DURING ANAEROBIC REDUCTIVE DECHLORINATION	US13785840	2013-03-05	US20140251900A1	2014-09-11	Michael Scalzi; Antonis Karachalios
This method of restricting methane production in methanogenic bacteria, by the use of the enzyme and coenzyme inhibitors, works during anaerobic reductive dechlorination. Various compounds such as, but not limited to, red yeast rice, vitamin B10 derivatives, and ethanesulfonates are utilized to disrupt these different enzyme and coenzyme systems responsible for the production of methane. This method affects the competition of the methanogen and halo bacteria for the organic hydrogen donors that are injected in the soil and groundwater system during the remediation process.
10	SYSTEMS AND METHODS OF DELIVERY OF BIOACTIVE AGENTS USING BACTERIAL TOXIN-DERIVED TRANSPORT SEQUENCES	US15837256	2017-12-11	US20180353610A1	2018-12-13	Randall Mrsny; Tahir Mahmood
The field of the present invention relates, in part, to a strategy for novel pharmaceutical applications. More specifically, the present invention relates to a non-toxic mutant form of the Vibrio cholera Cholix gene (ntCholix), a variant of Cholix truncated at amino acid A386 (Cholix386) and the use of other various Cholix-derived polypeptide sequences to enhance intestinal delivery of biologically-active therapeutics. Importantly, the systems and methods described herein provide for the following: the ability to deliver macromolecule doses without injections; the ability to deliver cargo, such as (but not limited to) siRNA or antisense molecules into intracellular compartments where their activity is required; and the delivery of nanoparticles and dendrimer-based carriers across biological membranes, which otherwise would have been impeded due to the barrier properties of most such membranes.
11	Botulinum Chimera Compositions for Axonal Regenerative Therapy During Spinal Cord Injury	US14761373	2014-01-16	US20160051644A1	2016-02-25	Bal Ram Singh; Nagarajan Thirunavukkarasu
The present invention relates to the isolation of polypeptides derived from the Clostridium botulinum neurotoxin and the use thereof as treatment for neuronal injury such as spinal cord injury. Botulinum neurotoxin binds to neural cells and are translocated into the cytosol and therefore is useful as a target specific therapeutic delivery system. Non-toxic botulinum toxin may be created by light chain mutagenesis and/or removal of the endopeptidase domain.
12	SYSTEMS AND METHODS OF DELIVERY OF BIOACTIVE AGENTS USING BACTERIAL TOXIN-DERIVED TRANSPORT SEQUENCES	US14733940	2015-06-08	US20150265718A1	2015-09-24	Randall Mrsny; Tahir Mahmood
The field of the present invention relates, in part, to a strategy for novel pharmaceutical applications. More specifically, the present invention relates to a non-toxic mutant form of the Vibrio cholera Cholix gene (ntCholix), a variant of Cholix truncated at amino acid A386 (Cholix386) and the use of other various Cholix-derived polypeptide sequences to enhance intestinal delivery of biologically-active therapeutics. Importantly, the systems and methods described herein provide for the following: the ability to deliver macromolecule doses without injections; the ability to deliver cargo, such as (but not limited to) siRNA or antisense molecules into intracellular compartments where their activity is required; and the delivery of nanoparticles and dendrimer-based carriers across biological membranes, which otherwise would have been impeded due to the barrier properties of most such membranes.
13	Systems and methods of delivery of bioactive agents using bacterial toxin-derived transport sequences	US13822435	2011-09-15	US09090691B2	2015-07-28	Randall J. Mrsny; Tahir Mahmood
The field of the present invention relates, in part, to a strategy for novel pharmaceutical applications. More specifically, the present invention relates to a genetically detoxified form of Vibrio cholera exotoxin (cholix) and the use of cholix-derived polypeptide sequences to enhance intestinal delivery of biologically-active therapeutics. Importantly, the systems and methods described herein provide for the following: the ability to deliver macromolecule doses without injections; the ability to deliver cargo, such as (but not limited to) siRNA or antisense molecules into intracellular compartments where their activity is required; and the delivery of nanoparticles and dendrimer-based carriers across biological membranes, which otherwise would have been impeded due to the barrier properties of most such membranes.
14	SYSTEMS AND METHODS OF DELIVERY OF BIOACTIVE AGENTS USING BACTERIAL TOXIN-DERIVED TRANSPORT SEQUENCES	US13822435	2011-09-15	US20130172229A1	2013-07-04	Randall J. Mrsny; Tahir Mahmood
The field of the present invention relates, in part, to a strategy for novel pharmaceutical applications. More specifically, the present invention relates to a genetically detoxified form of Vibrio cholera exotoxin (cholix) and the use of cholix-derived polypeptide sequences to enhance intestinal delivery of biologically-active therapeutics. Importantly, the systems and methods described herein provide for the following: the ability to deliver macromolecule doses without injections; the ability to deliver cargo, such as (but not limited to) siRNA or antisense molecules into intracellular compartments where their activity is required; and the delivery of nanoparticles and dendrimer-based carriers across biological membranes, which otherwise would have been impeded due to the barrier properties of most such membranes.
15	細菌毒素由来輸送配列を使用する生物活性剤の送達の系および方法	JP2016250581	2016-12-26	JP2017093449A	2017-06-01	マースニー,ランドル,ジェイ; マームード,タヒール
【課題】コレラ菌Cholix遺伝子の非毒性突然変異体形態(ntCholix)、アミノ酸A386においてトランケートされたCholixのバリアント(Cholix386)および生物活性薬学的治療剤の腸送達を向上させるための他の種々のCholix由来ポリペプチド配列の使用。【解決手段】巨大分子用量を注射なしで送達する能力を有する、積み荷、例えば(限定されるものではないが)siRNA又はアンチセンス分子を、活性が要求される細胞内区画中に送達する能力、ならびに他の場合においてほとんどの生物膜の障壁特性に起因して妨害されている、生物膜を越えるCholix由来のポリペプチド配列を含むナノ粒子およびデンドリマーベースの担体。【選択図】図1
16	EXOSOME SECRETION INHIBITOR	EP16844231.7	2016-08-30	EP3348278A1	2018-07-18	OCHIYA, Takahiro; YOSHIOKA, Yusuke; KOSAKA, Nobuyoshi
An exosome secretion inhibitor containing a substance suppressing expression of NAPG, HINT3 or GXYLT1 gene, or a substance suppressing activity of NAPG, HINT3 or GXYLT1 protein. It is possible to suppress secretion of exosome, thereby making it possible to suppress proliferation or metastasis of cancer cells, so that the substance suppressing expression of the gene or activity of the protein can be used as an active ingredient of a pharmaceutical composition suitably used in treatment of cancer or suppression of cancer metastasis, and also the substance can provide a carcinostatic agent having a new action mechanism which specifically suppresses expression of the gene or activity of the protein.
17	INHIBITION OF METHANE PRODUCTION DURING ANAEROBIC REDUCTIVE DECHLORINATION	EP14770315	2014-05-02	EP2969977A4	2017-03-15	SCALZI MICHAEL; KARACHALIOS ANTONIS

18	SYSTEMS AND METHODS OF DELIVERY OF BIOACTIVE AGENTS USING BACTERIAL TOXIN-DERIVED TRANSPORT SEQUENCES	EP11825567	2011-09-15	EP2616045A4	2014-12-24	MRSNY RANDALL J; MAHMOOD TAHIR
The field of the present invention relates, in part, to a strategy for novel pharmaceutical applications. More specifically, the present invention relates to a genetically detoxified form of Vibrio cholera exotoxin (cholix) and the use of cholix-derived polypeptide sequences to enhance intestinal delivery of biologically-active therapeutics. Importantly, the systems and methods described herein provide for the following: the ability to deliver macromolecule doses without injections; the ability to deliver cargo, such as (but not limited to) siRNA or antisense molecules into intracellular compartments where their activity is required; and the delivery of nanoparticles and dendrimer-based carriers across biological membranes, which otherwise would have been impeded due to the barrier properties of most such membranes.
19	SYSTEMS AND METHODS OF DELIVERY OF BIOACTIVE AGENTS USING BACTERIAL TOXIN-DERIVED TRANSPORT SEQUENCES	EP11825567.8	2011-09-15	EP2616045A1	2013-07-24	Mrsny, Randall J.; Mahmood, Tahir
The field of the present invention relates, in part, to a strategy for novel pharmaceutical applications. More specifically, the present invention relates to a genetically detoxified form of Vibrio cholera exotoxin (cholix) and the use of cholix-derived polypeptide sequences to enhance intestinal delivery of biologically-active therapeutics. Importantly, the systems and methods described herein provide for the following: the ability to deliver macromolecule doses without injections; the ability to deliver cargo, such as (but not limited to) siRNA or antisense molecules into intracellular compartments where their activity is required; and the delivery of nanoparticles and dendrimer-based carriers across biological membranes, which otherwise would have been impeded due to the barrier properties of most such membranes.
20	SYSTEMS AND METHODS OF DELIVERY OF BIOACTIVE AGENTS USING BACTERIAL TOXIN-DERIVED TRANSPORT SEQUENCES	EP11825567.8	2011-09-15	EP2616045B1	2017-10-25	Mrsny, Randall J.; Mahmood, Tahir
The field of the present invention relates, in part, to a strategy for novel pharmaceutical applications. More specifically, the present invention relates to a genetically detoxified form of Vibrio cholera exotoxin (cholix) and the use of cholix-derived polypeptide sequences to enhance intestinal delivery of biologically-active therapeutics. Importantly, the systems and methods described herein provide for the following: the ability to deliver macromolecule doses without injections; the ability to deliver cargo, such as (but not limited to) siRNA or antisense molecules into intracellular compartments where their activity is required; and the delivery of nanoparticles and dendrimer-based carriers across biological membranes, which otherwise would have been impeded due to the barrier properties of most such membranes.

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