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1. 发明授权

US09068184B2 Compositions and methods for inhibition of expression of protein C (PROC) genes 有权
标题翻译：抑制蛋白C（PROC）基因表达的组合物和方法
公开(公告)号：US09068184B2
公开(公告)日：2015-06-30
申请号：US14127090
申请日：2012-06-21
申请人： Ivanka Toudjarska , John M. Maraganore , Brian Bettencourt , Stuart Milstein , Martin A. Maier , Klaus Charisse , Kallanthottathil Rajeev , Satyanarayana Kuchimanchi
发明人： Ivanka Toudjarska , John M. Maraganore , Brian Bettencourt , Stuart Milstein , Martin A. Maier , Klaus Charisse , Kallanthottathil Rajeev , Satyanarayana Kuchimanchi
IPC分类号： A61K48/00 , C12N15/11 , C07H21/02 , C07H21/04 , C12N15/113
CPC分类号： C12N15/113 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2310/3515 , C12N2310/3521
摘要： The invention relates to double-stranded ribonucleic acid (dsRNA) targeting a PROC gene, and methods of using the dsRNA to inhibit expression of PROC. At least one nucleotide of the dsRNA can be a modified nucleotide, e.g., a 2-0-methyl modified nucleotide, a nucleotide comprising a 5′-phosphorothioate group, and a terminal nucleotide linked to a cholesteryl derivative or dodecanoic acid bisdecylamide group. Other examples of modified nucleotides include a 2′-deoxy-2′-fluoro modified nucleotide, a 2′-deoxymodified nucleotide, a locked nucleotide, an abasic nucleotide, 2′-amino-modified nucleotide, 2′-alkyl-modified nucleotide, morpholino nucleotide, a phosphoramidate, and a non-natural base comprising nucleotide. A dsRNA of the invention can include one or more of any of these modified nucleotides.
摘要翻译：本发明涉及靶向PROC基因的双链核糖核酸（dsRNA）以及使用dsRNA抑制PROC表达的方法。 dsRNA的至少一个核苷酸可以是修饰的核苷酸，例如2-0-甲基修饰的核苷酸，包含5'-硫代磷酸酯基团的核苷酸，以及与胆固醇衍生物或十二烷酸双癸酰胺基团连接的末端核苷酸。修饰的核苷酸的其它实例包括2'-脱氧-2'-氟修饰的核苷酸，2'-脱氧改性的核苷酸，锁定的核苷酸，脱碱核苷酸，2'-氨基修饰的核苷酸，2'-烷基修饰的核苷酸，吗啉代核苷酸，氨基磷酸酯和包含核苷酸的非天然碱基。本发明的dsRNA可以包括这些修饰的核苷酸中的一种或多种。

2. 发明申请

US20140142162A1 Compositions and Methods for Inhibition of Expression of Protein C (PROC) Genes 有权
标题翻译：抑制蛋白C（PROC）基因表达的组成和方法
公开(公告)号：US20140142162A1
公开(公告)日：2014-05-22
申请号：US14127090
申请日：2012-06-21
申请人： Ivanka Toudjarska , John M. Maraganore , Brian Bettencourt , Stuart Milstein , Martin A. Maier , Klaus Charisse , Kallanthottathil Rajeev , Satyanarayana Kuchimanchi
发明人： Ivanka Toudjarska , John M. Maraganore , Brian Bettencourt , Stuart Milstein , Martin A. Maier , Klaus Charisse , Kallanthottathil Rajeev , Satyanarayana Kuchimanchi
IPC分类号： C12N15/113
CPC分类号： C12N15/113 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2310/3515 , C12N2310/3521
摘要： The invention relates to double-stranded ribonucleic acid (dsRNA) targeting a PROC gene, and methods of using the dsRNA to inhibit expression of PROC. At least one nucleotide of the dsRNA can be a modified nucleotide, e.g., a 2-0-methyl modified nucleotide, a nucleotide comprising a 5′-phosphorothioate group, and a terminal nucleotide linked to a cholesteryl derivative or dodecanoic acid bisdecylamide group. Other examples of modified nucleotides include a 2′-deoxy-2′-fluoro modified nucleotide, a 2′-deoxymodified nucleotide, a locked nucleotide, an abasic nucleotide, 2′-amino-modified nucleotide, 2′-alkyl-modified nucleotide, morpholino nucleotide, a phosphoramidate, and a non-natural base comprising nucleotide. A dsRNA of the invention can include one or more of any of these modified nucleotides.
摘要翻译：本发明涉及靶向PROC基因的双链核糖核酸（dsRNA）以及使用dsRNA抑制PROC表达的方法。 dsRNA的至少一个核苷酸可以是修饰的核苷酸，例如2-0-甲基修饰的核苷酸，包含5'-硫代磷酸酯基团的核苷酸，以及与胆固醇衍生物或十二烷酸双癸酰胺基团连接的末端核苷酸。修饰的核苷酸的其它实例包括2'-脱氧-2'-氟修饰的核苷酸，2'-脱氧改性的核苷酸，锁定的核苷酸，脱碱核苷酸，2'-氨基修饰的核苷酸，2'-烷基修饰的核苷酸，吗啉代核苷酸，氨基磷酸酯和包含核苷酸的非天然碱基。本发明的dsRNA可以包括这些修饰的核苷酸中的一种或多种。

3. 发明申请

US20140099666A1 COMPOSITIONS AND METHODS FOR ENHANCING PRODUCTION OF A BIOLOGICAL PRODUCT 审中-公开
标题翻译：用于增强生物产品生产的组合物和方法
公开(公告)号：US20140099666A1
公开(公告)日：2014-04-10
申请号：US13379511
申请日：2010-07-06
申请人： Anthony Rossomando , John M. Maraganore , Stuart Pollard , David Kocisko , Muthiah Manoharan , Gregory Hinkle , Brian Bettencourt , Shannon Hogan
发明人： Anthony Rossomando , John M. Maraganore , Stuart Pollard , David Kocisko , Muthiah Manoharan , Gregory Hinkle , Brian Bettencourt , Shannon Hogan
IPC分类号： C07K16/00
CPC分类号： C07K16/00 , C12N15/111 , C12N2310/14 , C12N2310/3515
摘要： The invention provides compositions and methods for producing a biological product from a host cell. In various embodiments, the biological product is a polypeptide, a metabolite, a nutraceutical, a chemical intermediate, a biofuel, a food additive, or an antibiotic. In one aspect, the invention provides for a method for producing a biological product from a host cell. The method generally comprises contacting the cell with a RNA effector molecule, a portion of which is complementary to a target gene, maintaining the cell in a large-scale bioreactor for a time sufficient to modulate expression of the target gene, wherein the modulation enhances production of the biological product from the cell, and isolating the biological product from the cell.
摘要翻译：本发明提供了用于从宿主细胞生产生物制品的组合物和方法。在各种实施方案中，生物产物是多肽，代谢物，营养保健品，化学中间体，生物燃料，食品添加剂或抗生素。一方面，本发明提供从宿主细胞产生生物制品的方法。该方法通常包括使细胞与RNA效应分子接触，其一部分与靶基因互补，将细胞维持在大规模生物反应器中足以调节靶基因表达的时间，其中调节增强生产的来自细胞的生物产物，并从细胞中分离生物产物。

4. 发明授权

US5446131A Thrombin receptor antagonists 失效
标题翻译：凝血酶受体拮抗剂
公开(公告)号：US5446131A
公开(公告)日：1995-08-29
申请号：US328388
申请日：1994-10-24
申请人： John M. Maraganore
发明人： John M. Maraganore
IPC分类号： C12N15/09 , A61K38/00 , A61K38/55 , A61P3/00 , A61P7/02 , A61P9/00 , A61P11/00 , A61P25/00 , A61P29/00 , A61P43/00 , C07K7/06 , C07K14/46 , C12N9/74 , C12N15/62 , C12P21/02 , C12R1/91 , C07K7/00 , C07K7/08
CPC分类号： C12N9/6429 , C07K14/46 , C12N15/62 , C12Y304/21005 , A61K38/00 , C07K2319/00 , C07K2319/02 , C07K2319/55 , C07K2319/74
摘要： This invention relates to novel, biologically active molecules which bind to and inhibit the thrombin receptor. These thrombin receptor antagonists are further characterized by their ability to inhibit thrombin-induced platelet aggregation and their inability to inhibit platelet aggregation induced by an internal peptide fragment of the platelet thrombin receptor. More specifically, the thrombin receptor antagonist of this invention comprises the formula: A.sub.1 -X-X-X-A.sub.2 -X-A.sub.3 -X-A.sub.4 -B-X-A.sub.5 -C-X-A.sub.6 ; wherein each of A.sub.1 and A.sub.6, either the same or different, are selected from the group consisting of a positively charged amino acid and an acyl or alkyl chain comprising from 1 to 10 backbone atoms and a positively charged side group; each of A.sub.2, A.sub.3, A.sub.4 and A.sub.5, is a positively charged amino acid, either the same or different; each X is any amino acid, either the same or different; B is an amino acid containing an aryl side chain; and C is a polar amino acid. This invention also relates to compositions and methods which employ these molecules for therapeutic and prophylactic purposes.
摘要翻译：本发明涉及结合并抑制凝血酶受体的新型生物活性分子。这些凝血酶受体拮抗剂的特征还在于其抑制凝血酶诱导的血小板聚集和不能抑制由血小板凝血酶受体的内部肽片段诱导的血小板聚集的能力。更具体地，本发明的凝血酶受体拮抗剂包含式：A1-X-X-X-A2-X-A3-X-A4-B-X-A5-C-X-A6; 其中A1和A6各自相同或不同，选自带正电荷的氨基酸和包含1至10个骨架原子和带正电的侧基的酰基或烷基链; A2，A3，A4和A5中的每一个是带正电荷的氨基酸，相同或不同; 每个X是任何相同或不同的氨基酸; B是含有芳基侧链的氨基酸; C是极性氨基酸。本发明还涉及使用这些分子用于治疗和预防目的的组合物和方法。

5. 发明授权

US5433940A Inhibitors of thrombin 失效
标题翻译：凝血酶抑制剂
公开(公告)号：US5433940A
公开(公告)日：1995-07-18
申请号：US834259
申请日：1992-02-10
申请人： John M. Maraganore , John W. Fenton, II , Toni Kline
发明人： John M. Maraganore , John W. Fenton, II , Toni Kline
IPC分类号： A61K38/55 , A61K38/00 , A61K51/00 , A61L33/00 , A61P7/02 , A61P29/00 , A61P35/00 , C07K7/02 , C07K7/06 , C07K7/08 , C07K14/00 , C07K14/81 , C07K14/815 , C12N9/99 , G01N33/60 , G01N33/68 , C07K7/00
CPC分类号： C07K7/02 , C07K14/815 , A61K38/00 , Y10S436/804 , Y10S623/92
摘要： This invention relates to novel biologically active molecules which bind to and inhibit thrombin. Specifically, these molecules are characterized by a thrombin anion-binding exosite association moiety (ABEAM); a linker portion of at least 18.ANG. in length; and a thrombin catalytic site-directed moiety (CSDM). This invention also relates to compositions, combinations and methods which employ these molecules for therapeutic, prophylactic and diagnostic purposes.
摘要翻译： PCT No.PCT / US90 / 04642 Sec。 371日期：1992年2月10日 102（e）日期1992年2月10日PCT 1990年8月17日PCT PCT。出版物WO91 / 02750 1991年3月7日。本发明涉及结合并抑制凝血酶的新型生物活性分子。具体地，这些分子的特征在于凝血酶阴离子结合外部位点结合部分（ABEAM）; 长度为至少18个ANGSTROM的接头部分; 和凝血酶催化位点定向部分（CSDM）。本发明还涉及使用这些分子用于治疗，预防和诊断目的的组合物，组合和方法。

6. 发明授权

US5182260A DNA sequences encoding snake venom inhibitors of platelet activation processes for producing those inhibitors and compositions using them 失效
标题翻译：用于生产这些抑制剂和组合物的片剂活化方法的编码SNAKE VENOM抑制剂的DNA序列
公开(公告)号：US5182260A
公开(公告)日：1993-01-26
申请号：US430313
申请日：1989-11-01
申请人： John M. Maraganore , Joseph A. Jakubowski
发明人： John M. Maraganore , Joseph A. Jakubowski
IPC分类号： A61K35/12 , A61K35/58 , A61K35/62 , A61K38/00 , A61P7/02 , C07K1/14 , C07K14/46 , C07K14/78 , C07K19/00 , C12N1/21 , C12N15/09 , C12N15/12 , C12P21/02 , C12R1/19
CPC分类号： C07K14/78 , C07K14/46 , A61K38/00 , Y10S530/856
摘要： The present invention relates to polypeptide inhibitors of platelet activation and derivatives thereof, purified from the venom of the North American Water Moccasin and to methods for their purification. This invention also relates to DNA sequences and recombinant DNA molecules which code for these polypeptide inhibitors of platelet activation. And this invention relates to recombinant DNA molecules which code for fusion proteins comprising both a polypeptide inhibitor of platelet activation and an anti-thrombin polypeptide. This invention also relates to pharmaceutically acceptable compositions and methods characterized by at least one of these natural or recombinant inhibitors of platelet activation, alone or in combination with anti-thrombin compounds. The compositions, combinations and methods of this invention are particularly useful in the treatment of thrombotic diseases.
摘要翻译：本发明涉及从北美水性马可卡因的毒液中纯化的血小板活化多肽抑制剂及其衍生物及其纯化方法。本发明还涉及编码这些多肽抑制剂血小板活化的DNA序列和重组DNA分子。本发明涉及编码包含血小板活化多肽抑制剂和抗凝血酶多肽的融合蛋白的重组DNA分子。本发明还涉及药学上可接受的组合物和方法，其特征在于这些天然或重组的血小板活化抑制剂中的至少一种，单独或与抗凝血酶化合物组合。本发明的组合物，组合和方法特别可用于治疗血栓形成疾病。

7. 发明授权

US4985541A Novel cytotoxic protein 失效
标题翻译：新型细胞毒性蛋白
公开(公告)号：US4985541A
公开(公告)日：1991-01-15
申请号：US36840
申请日：1987-04-10
申请人： John M. Maraganore , Wayne R. Kindsvogel
发明人： John M. Maraganore , Wayne R. Kindsvogel
IPC分类号： A61K36/428 , A61K47/48
CPC分类号： A61K47/48469 , A61K36/428
摘要： Purified cytotoxic proteins for use within therapeutic compositions are disclosed. The proteins inhibit protein synthesis in vitro, exhibit abortifacient activity in mice, and contain proline residues with equivalent positions at residue 43 and residue 46 in ricin A-chain. A method for preparing such a cytotoxic protein from the tissue of Trichosanthes kirilowii is also disclosed. The proteins may also be used within a method for inhibiting protein synthesis in selected cells.

8. 发明申请

US20140154783A1 BIOPROCESSING 审中-公开
标题翻译：生物学
公开(公告)号：US20140154783A1
公开(公告)日：2014-06-05
申请号：US13379797
申请日：2010-07-06
申请人： Anthony Rossomando , John M. Maraganore , Stuart Pollard , David Kocisko , Muthiah Manogaran , Todd Borland , Shannon Hogan
发明人： Anthony Rossomando , John M. Maraganore , Stuart Pollard , David Kocisko , Muthiah Manogaran , Todd Borland , Shannon Hogan
IPC分类号： C12N7/00
CPC分类号： C12N7/00 , C12N15/113 , C12N15/1131 , C12N2310/14
摘要： The present invention relates to molecular biology, molecular genetics, and bioprocessing. The embodiments provide for compositions and methods for producing a biological product, such as an immunogenic agent, in an embryonated egg by introducing into the egg a RNA effector molecule capable of modulating expression of a target gene, wherein the modulation enhances production of the biological product in the egg. These methods provide for RNAi-based approaches to optimize the production of biologics from embryonated eggs, such as the production of viral vaccines including seasonal and pandemic flu vaccines. The invention also relates to molecules, reagents, cells, and kits useful for carrying out the methods, and biological products produced by the methods.
摘要翻译：本发明涉及分子生物学，分子遗传学和生物处理。这些实施方案提供了通过向蛋中引入能够调节靶基因表达的RNA效应分子来生产在胚胎卵中的生物产物如免疫原性试剂的组合物和方法，其中所述调节增强了生物产物的产生在蛋里这些方法提供了基于RNAi的方法来优化来自胚胎卵的生物制品的生产，例如生产包括季节性和大流行性流感疫苗的病毒疫苗。本发明还涉及可用于实施方法的分子，试剂，细胞和试剂盒，以及通过该方法生产的生物制品。

9. 发明申请

US20100069461A1 COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF FACTOR V LEIDEN MUTANT GENE 审中-公开
标题翻译：抑制因子V诱导突变基因表达的组合物和方法
公开(公告)号：US20100069461A1
公开(公告)日：2010-03-18
申请号：US12093235
申请日：2006-11-07
申请人： Hans-Peter Vornlocher , John M. Maraganore
发明人： Hans-Peter Vornlocher , John M. Maraganore
IPC分类号： A61K31/7105 , C07H21/02 , C12N5/10 , C12N15/74 , A61P9/00
CPC分类号： C12N15/113 , A61K47/554 , A61K48/00 , C12N2310/14 , C12N2320/30
摘要： The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of the Factor V Leiden mutant gene (Factor V Leiden mutant gene), comprising an antisense strand having a nucleotide sequence which is less that 25 nucleotides in length and which is substantially complementary to at least a part of the Factor V Leiden mutant gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of the Factor V Leiden mutant gene using the pharmaceutical composition; and methods for inhibiting the expression of the Factor V Leiden mutant gene in a cell.
摘要翻译：本发明涉及用于抑制因子V莱顿突变基因（因子V莱顿突变基因）表达的双链核糖核酸（dsRNA），其包含具有长度小于25个核苷酸的核苷酸序列的反义链，其中与至少一部分因子V Leiden突变基因互补。本发明还涉及包含dsRNA与药学上可接受的载体的药物组合物; 用于使用该药物组合物治疗由因子V莱顿突变基因表达引起的疾病的方法; 以及用于抑制细胞中因子V Leiden突变基因表达的方法。

10. 发明授权

US5545615A A method of inhibiting fertilization by alpha-1-antitrypsin or antithrombin III 失效
标题翻译：抑制α-1-抗胰蛋白酶或抗凝血酶III受精的方法
公开(公告)号：US5545615A
公开(公告)日：1996-08-13
申请号：US312010
申请日：1994-09-22
申请人： John M. Maraganore
发明人： John M. Maraganore
IPC分类号： A61K9/00 , A61K38/00 , A61K38/57 , C07K14/81 , A61K37/02
CPC分类号： A61K9/0034 , A61K38/57 , C07K14/8125 , Y10S424/14 , Y10S514/843
摘要： Methods for inhibiting fertilization in warm-blooded animals are disclosed. The methods generally comprise administering to the animal an effective amount of a composition comprising a protein that forms a covalent complex with acrosin, and a physiologically acceptable carrier or diluent. Suitable proteins for use in the methods include members of the serpin family of proteins, such as alpha-1-antitrypsin.
摘要翻译：公开了抑制温血动物受精的方法。所述方法通常包括向动物施用有效量的包含与顶体蛋白形成共价复合物的蛋白质和生理学上可接受的载体或稀释剂的组合物。用于该方法的合适的蛋白质包括蛋白质丝氨酸蛋白酶家族的成员，例如α-1-抗胰蛋白酶。

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