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1. 发明申请

WO2004083427A3 LIGATIONAL ENCODING OF SMALL MOLECULES 审中-公开
标题翻译：小分子的编码
公开(公告)号：WO2004083427A3
公开(公告)日：2005-02-17
申请号：PCT/DK2004000195
申请日：2004-03-22
申请人： NUEVOLUTION AS , FRANCH THOMAS , JACOBSEN SOEREN NYBOE , RASMUSSEN TORBEN , NEVE SOEREN , PEDERSEN HENRIK , GOULIAEV ALEX HAAHR
发明人： FRANCH THOMAS , JACOBSEN SOEREN NYBOE , RASMUSSEN TORBEN , NEVE SOEREN , PEDERSEN HENRIK , GOULIAEV ALEX HAAHR
IPC分类号： C12N15/10 , C12P21/02
CPC分类号： C07H21/04 , C12N15/1068 , C12P21/02 , C40B40/06 , C40B50/04
摘要： The invention relates to a method for synthesising a bifunctional complex comprising an encoded molecule and an identifier polynucleotide identifying the chemical entities having participated in the synthesis of the encoded molecule, said method comprising the steps of i) providing a) at least one template comprising one or more codons capable of hybridising to an anti-codon, wherein said template is optionally associated with one or more chemical entities, and b) a plurality of building blocks each comprising an anti-codon associated with one or more chemical entities, and ii) hybridising the anti-codon of one or more of the provided building blocks to the template, iii) covalently linking said anti-codons and/or linking the at least one template with the anti-codon of at least one building block, thereby generating an identifier polynucleotide capable of identifying chemical entities having participated in the synthesis of the encoded molecule, iv) separating the template from one or more of the anti-codons hybridised thereto, thereby generating an at least partly single stranded identifier polynucleotide associated with a plurality of chemical entities, v) generating a bifunctional complex comprising an encoded molecule and an identifier polynucleotide identifying the chemical entities having participated in the synthesis of the encoded molecule, wherein said encoded molecule is generated by reacting at least two of said plurality of chemical entities associated with the identifier polynucleotide, and wherein said at least two chemical entities are provided by separate building blocks.
摘要翻译：本发明涉及一种合成双功能复合物的方法，所述双功能复合物包含编码分子和识别已经参与编码分子合成的化学实体的标识多核苷酸，所述方法包括以下步骤：i）提供a）至少一个包含一个或更多能够与抗密码子杂交的密码子，其中所述模板任选地与一个或多个化学实体相关联，以及b）多个结构单元，每个结构单元包含与一个或多个化学实体相关联的抗密码子，和ii）将一个或多个所提供的构建块的抗密码子与模板杂交，iii）共价连接所述抗密码子和/或将至少一个模板与至少一个构建块的抗密码子连接，由此产生能够识别已经参与编码分子的合成的化学实体的标识符多核苷酸，iv）将模板从一个或多个分离出来更多的与其杂交的抗密码子，从而产生与多个化学实体相关联的至少部分单链标识多核苷酸，v）产生包含编码分子的双功能复合物和识别参与合成的化学实体的标识符多核苷酸的编码分子，其中所述编码的分子通过使与所述标识多核苷酸相关联的所述多个化学实体中的至少两个反应而产生，并且其中所述至少两个化学实体由单独的构建块提供。

2. 发明申请

WO2004039825A3 METHOD FOR THE SYNTHESIS OF A BIFUNCTIONAL COMPLEX 审中-公开
标题翻译：双功能复合物的合成方法
公开(公告)号：WO2004039825A3
公开(公告)日：2004-10-28
申请号：PCT/DK0300739
申请日：2003-10-30
申请人： NUEVOLUTION AS , FRESKGAARD PER-OLA , FRANCH THOMAS , GOULIAEV ALEX HAAHR , LUNDORF MIKKEL DYBRO , FELDING JAKOB , OLSEN EVA KAMPMANN , HOLTMANN ANETTE , JAKOBSEN SOEREN NYBOE , SAMS CHRISTIAN , GLAD SANNE SCHROEDER , JENSEN KIM BIRKEBAEK , PEDERSEN HENRIK
发明人： FRESKGAARD PER-OLA , FRANCH THOMAS , GOULIAEV ALEX HAAHR , LUNDORF MIKKEL DYBRO , FELDING JAKOB , OLSEN EVA KAMPMANN , HOLTMANN ANETTE , JAKOBSEN SOEREN NYBOE , SAMS CHRISTIAN , GLAD SANNE SCHROEDER , JENSEN KIM BIRKEBAEK , PEDERSEN HENRIK
IPC分类号： C12N15/10 , C12P19/34 , C07B61/00
CPC分类号： C12N15/1065 , C12N15/1068 , C12Q1/6806 , C12Q2521/101 , C12Q2521/501 , C40B50/10 , C40B50/16
摘要： A method for synthesising a bifunctional complex which comprises a reaction product and an encoding region. The complex is a hybridisation product between a nascent bifunctional complex and a building block. The nascent bifunctional complex comprises an attachment entity linked to an oligonucleotide identifier region and the building block comprises a fuctional entity attached to an oligonucleotide which is sufficiently complementary to the identifier region to allow for hybridisation . The functional entity may then be transferred to the attachment entity by a chemical reaction.The complementary identifier region further comprises a unique codon, which identifies the functional entity unequivocally. This codon functions as a template for forming a unique codon as an extention of the identifier region by use of an enzime, such as a polymerase. The unique codon may be used to decode the synthetic history of the reaction product after several cycles of transfer of functional entities.
摘要翻译：一种合成双功能复合物的方法，其包括反应产物和编码区。该复合物是新生的双功能复合物和构建块之间的杂交产物。新生的双功能复合物包含与寡核苷酸识别器区域连接的连接实体，并且构建单元包含连接于寡核苷酸的功能实体，其与识别符区域充分互补以允许杂交。然后可以通过化学反应将功能实体转移到附着实体。补充标识符区域还包括唯一的密码子，其明确地标识功能实体。该密码子用作用于通过使用酶，如聚合酶形成唯一密码子作为标识符区域扩展的模板。独特的密码子可以用于在功能实体的几个转移周期之后解码反应产物的合成历史。

3. 发明申请

WO2004056994A3 QUASIRANDOM STRUCTURE AND FUNCTION GUIDED SYNTHESIS METHODS 审中-公开
标题翻译：准共形结构和功能指导综合方法
公开(公告)号：WO2004056994A3
公开(公告)日：2004-08-12
申请号：PCT/DK0300921
申请日：2003-12-19
申请人： NUEVOLUTION AS , GOULIAEV ALEX HAAHR , HOLTMANN ANETTE , PEDERSEN HENRIK , FRANCH THOMAS
发明人： GOULIAEV ALEX HAAHR , HOLTMANN ANETTE , PEDERSEN HENRIK , FRANCH THOMAS
IPC分类号： C12N15/10 , C07B61/00 , C07K1/04 , C12P1/00 , C12Q1/68
CPC分类号： C40B30/04 , C12N15/1068 , C40B20/04 , C40B40/06 , C40B50/04 , C40B50/08 , Y10T436/145555
摘要： The present invention is directed to the synthesis of molecules guided b connector polynucleotides (CPNs capable of hybridizing to complementory connector ploynucleotides (CCPNs) harbouring at least one functional entity comprising at least one reactive group. At least one of said CCPNs capable of hybridize to at least two CPNs. Each CPN will "call" for one or more CCPNs capable of hybridization to the CPN. Following the formation of a supramolecular hybridization complex comprising a plurality of CPNs and a plurality of CCPNs, the reaction of functional entity reactive groups result I the formation of a molecule comprising covalently linked functional entities. The formation of the molecule involves the transfer of functional entities from one or more "donor CCPNs" to at least on "acceptor CCPN" with which the transferred functional entities were not associated prior to the transfer.
摘要翻译：本发明涉及合成分子引导的b连接多核苷酸（能够与互补连接体多核苷酸（CCPN）杂交的CPN，所述互补连接体多核苷酸携带至少一个包含至少一个反应性基团的功能实体，至少一个所述CCPN能够与至少两个CPN，每个CPN将“呼叫”一个或多个能够与CPN杂交的CCPN，形成包含多个CPN和多个CCPN的超分子杂交复合物后，功能实体反应基团的反应导致I 形成包含共价连接的功能实体的分子，分子的形成涉及将功能实体从一个或多个“供体CCPN”转移到至少一个“受体CCPN”上，转让。

4. 发明申请

WO2004110964A3 ENCODED MOLECULES BY TRANSLATION (EMT) 审中-公开
标题翻译：编码分子通过翻译（EMT）
公开(公告)号：WO2004110964A3
公开(公告)日：2005-03-31
申请号：PCT/DK2004000416
申请日：2004-06-15
申请人： NUEVOLUTION AS , PEDERSEN HENRIK , FRANCH THOMAS
发明人： PEDERSEN HENRIK , FRANCH THOMAS
IPC分类号： C07B61/00 , C12N15/10 , C12N15/67
CPC分类号： C12N15/1062 , C12N15/1068 , C12N15/67
摘要： The present invention is directed to methods for the synthesis, selection, amplification and isolation of templated molecules having desirable properties. The invention makes it possible to synthesise a variety of different templated molecules other than alpha-peptides and modified alpha-peptides. In particular, the present invention enables synthesis of templated molecules such as beta -, ϒ -, ϖ peptides, carbopeptoids, vinylogous peptides, oligoanthrilamides, oligoureas, azapeptides (azatides), oligocarbamates, PNA, oligopyrrolinones, vinylogous sulfonamidopeptide, peptoids, azapeptoids and hydrazino peptides. It is possible in accordance with the methods of the invention to synthesise templated molecules comprising heterocyclic components, such as coumarins and quinolones, pyrazolone, isoxazolone, pyrimidiones, phtalhydrazides, diketopiperazines, hydantoins, and benzodiazepines.
摘要翻译：本发明涉及用于合成，选择，扩增和分离具有所需性质的模板分子的方法。本发明使得可以合成除α-肽和修饰的α-肽以外的各种不同的模板分子。特别地，本发明能够合成模板分子，例如β - ，Υ-，π肽，卡皮派，血液肽，寡聚甲酰胺，寡聚脲，azapeptides（azatides），oligocarbamates，PNA，oligopyrrolinones，vinylogous sulfamidopeptide，peptoids，azapeptoids和hydrazino 肽。可以根据本发明的方法合成包含杂环成分的模板分子，例如香豆素和喹诺酮类，吡唑啉酮，异恶唑酮，嘧啶，邻苯二甲酰肼，二酮哌嗪，乙内酰脲和苯并二氮杂。

5. 发明申请

WO2007062664A2 ENZYMATIC ENCODING METHODS FOR EFFICIENT SYNTHESIS OF LARGE LIBRARIES 审中-公开
标题翻译：用于大型图书馆有效合成的酶编码方法
公开(公告)号：WO2007062664A2
公开(公告)日：2007-06-07
申请号：PCT/DK2006000685
申请日：2006-12-01
申请人： NUEVOLUTION AS , FRANCH THOMAS , LUNDORF MIKKEL DYBRO , JAKOBSEN SOEREN NYBOE , OLSEN EVA KAMPMANN , ANDERSEN ANNE LEE , HOLTMANN ANETTE , HANSEN ANDERS HOLM , SOERENSEN ANDERS MALLING , GOLDBECH ANNE , DE LEON DAEN , KALDOR DITTE KIVSMOSE , SLOEK FRANK ABILGAARD , HUSEMOEN GITTE NYSTRUP , DOLBERG JOHANNES , JENSEN KIM BIRKEBAEK , PETERSEN LENE , NOERREGAARD-MADSEN MADS , GODSKESEN MICHAEL ANDERS , GLAD SANNE SCHROEDER , NEVE SOEREN , THISTED THOMAS , KRONBORG TINE TITILOLA AKINLEM , SAMS CHRISTIAN , FELDING JAKOB , FRESKGAARD PER-OLA , GOULIAEV ALEX HAAHR , PEDERSEN HENRIK
发明人： FRANCH THOMAS , LUNDORF MIKKEL DYBRO , JAKOBSEN SOEREN NYBOE , OLSEN EVA KAMPMANN , ANDERSEN ANNE LEE , HOLTMANN ANETTE , HANSEN ANDERS HOLM , SOERENSEN ANDERS MALLING , GOLDBECH ANNE , DE LEON DAEN , KALDOR DITTE KIVSMOSE , SLOEK FRANK ABILGAARD , HUSEMOEN GITTE NYSTRUP , DOLBERG JOHANNES , JENSEN KIM BIRKEBAEK , PETERSEN LENE , NOERREGAARD-MADSEN MADS , GODSKESEN MICHAEL ANDERS , GLAD SANNE SCHROEDER , NEVE SOEREN , THISTED THOMAS , KRONBORG TINE TITILOLA AKINLEM , SAMS CHRISTIAN , FELDING JAKOB , FRESKGAARD PER-OLA , GOULIAEV ALEX HAAHR , PEDERSEN HENRIK
IPC分类号： C12N15/10 , C12Q1/68 , C40B40/06 , C40B50/06
CPC分类号： C12N15/1068 , C12N15/1089 , C40B40/08 , C40B50/04 , C40B50/06
摘要： Disclosed is a method for obtaining a bifunctional complex comprising a molecule linked to a single stranded identifier oligonucleotide, wherein a nascent bifunctional complex comprising a chemical reaction site and a priming site for enzymatic addition of a tag is a) reacted at the chemical reaction site with one or more reactants, and b) reacted enzymatically at the priming site with one or more tag(s) identifying the reactant(s).
摘要翻译：公开了一种获得包含与单链标识符寡核苷酸连接的分子的双功能复合物的方法，其中包含化学反应位点的新生双功能复合物和用于酶标添加的引发位点是a）在化学反应位点与一种或多种反应物，和b）在起始位点用一种或多种标记反应物的标签进行酶促反应。

6. 发明专利

IL207672A Method of generating a library of bifunctional complexes 未知
公开(公告)号：IL207672A
公开(公告)日：2015-05-31
申请号：IL20767210
申请日：2010-08-18
申请人： NUEVOLUTION AS , FRESKGARD PER-OLA , FRANCH THOMAS , GOULIAEV ALEX HAAHR , LUNDORF MIKKEL DYBRO , FELDING JAKOB , OLSEN EVA KAMPMANN , HOLTMANN ANETTE , SAMS CHRISTIAN , GLAD SANNE SCHRODER , JENSEN KIM BIRKEBAEK , PEDERSEN HENRIK , JAKOBSEN SOREN NYBOE
发明人： FRESKGARD PER-OLA , FRANCH THOMAS , GOULIAEV ALEX HAAHR , LUNDORF MIKKEL DYBRO , FELDING JAKOB , OLSEN EVA KAMPMANN , HOLTMANN ANETTE , SAMS CHRISTIAN , GLAD SANNE SCHRODER , JENSEN KIM BIRKEBAEK , PEDERSEN HENRIK , JAKOBSEN SOREN NYBOE
IPC分类号： C07H20060101 , C12N20060101 , C12N15/10 , C40B20060101
摘要： Disclosed is a method for obtaining a bifunctional complex comprising a display molecule part and a coding part wherein a nascent bifunctional complex comprising a chemical reaction site and priming site for enzymatic addition of a tag is reacted at the chemical reaction site with one or more reactants, and provided with respective tag(s) identifying the reactant(s) at the priming site using one or more enzymes.

7. 发明申请

WO2005078122A3 METHOD FOR ENRICHMENT INVOLVING ELIMINATION BY MISMATCH HYBRIDISATION 审中-公开
标题翻译：通过MISMATCH混合来增强消除消除的方法
公开(公告)号：WO2005078122A3
公开(公告)日：2005-10-20
申请号：PCT/DK2005000106
申请日：2005-02-17
申请人： NUEVOLUTION AS , FRESKAARD PER-OLA , LUNDORF MIKKEL DYBRO , FRANCH THOMAS
发明人： FRESKAARD PER-OLA , LUNDORF MIKKEL DYBRO , FRANCH THOMAS
IPC分类号： C07B61/00 , C12N15/10 , C12Q1/68
CPC分类号： C12N15/1068 , Y10T436/143333
摘要： The present invention relates to a method for selecting a molecule from a library of such molecules associated with identifier oligonucleotides, said molecule having affinity towards a target. The method involves contacting library with a target to allow for an interaction between the molecules and the target and partitioning a fraction enriched in identifier oligonucleotides of molecules interacting with the target. After an optional nucleic acid amplification of the partitioned fraction, the fraction is subjected to conditions at which hetero-duplexes and homo-duplexes are formed. The homo-duplexes are subsequently recovered and decoded to identify the identity of the molecule interacting with the target.
摘要翻译：本发明涉及从与标识符寡核苷酸相关的这种分子的文库中选择分子的方法，所述分子对靶具有亲和力。该方法包括使文库与靶接触以允许分子和靶之间的相互作用并且分配富含与靶标相互作用的分子的标识符寡核苷酸的级分。在分配级分的任选的核酸扩增后，使该级分经受形成异双链体和同双链体的条件。随后将同双链体恢复和解码，以鉴定与靶标相互作用的分子的身份。

8. 发明申请

WO2004024929A3 PROXIMITY-AIDED SYNTHESIS OF TEMPLATED MOLECULES 审中-公开
标题翻译：近模助分解模板分子的合成
公开(公告)号：WO2004024929A3
公开(公告)日：2004-05-06
申请号：PCT/DK0300590
申请日：2003-09-12
申请人： NUEVOLUTION AS , FRANCH THOMAS , THISTED THOMAS
发明人： FRANCH THOMAS , THISTED THOMAS
IPC分类号： C12N15/10 , C07B61/00 , C12P19/34 , C12Q1/68
CPC分类号： C12N15/1068
摘要： Disclosed is a method for synthesising a bifunctional complex. The complex comprises a template as well as a molecule, the synthesis of which being directed by the template. The synthesis of he complex requires initially a) a template comprising two or more codons in sequence, a first pair of a molecular affinity pair, and a reactive group; and b) two or more building blocks, each building block comprises i) an anti-codon capable of recognising a codon of the template, ii) a functional entity comprising at least one reactive group, and iii) a linker connecting the anti-codon and the functional entity, wherein building blocks having anti-codons intended to interact with codons of the template distal to the reactive group comprise as a section of the linker a second part of the molecular affinity pair. The synthesis proceeds by c) contacting the template with a building block under conditions which allow specific hybridisation of the anti-codon of the building block to the codon of the template, and under conditions ensuring assembling of the parts of the molecule pair, if present; d) obtaining a connection between the functional entity of the building block and the template by a reaction involving the template reactive group and the functional entity reactive group, e) cleaving a linkage to obtaining a nascent templated molecule, f) separating the parts of the molecular affinity pair, and g) repeating, for a building block having an anti-codon capable of hybridising to a new codon, steps c) to f) one or more times. The complexes obtainable according the invention may be used in the generation of a library which may be enriched with regard to preferred complexes using molecular evolution techniques.
摘要翻译：公开了用于合成双功能复合物的方法。该复合物包含模板以及分子，其合成由模板引导。 he复合物的合成首先需要a）包含两个或更多个序列密码子的模板，第一对分子亲和对和反应基团; 和b）两个或更多个构件，每个构件包含i）能够识别模板密码子的反密码子，ii）包含至少一个反应基团的功能实体，以及iii）连接反密码子以及功能实体，其中具有意欲与反应性基团远端的模板的密码子相互作用的反密码子的构建块包含分子亲和对的第二部分作为接头的一部分。通过c）进行合成，c）使模板与构建模块在允许结构单元的反密码子与模板的密码子特异性杂交的条件下和在确保分子对的部分（如果存在的话）的组装 ; d）通过涉及模板反应性基团和功能性实体反应性基团的反应，获得构件的功能实体与模板之间的连接，e）裂解键以获得新生模板化分子，f）分离分子亲和对，和g）对于具有能够与新密码子杂交的反密码子的结构单元，重复步骤c）至f）一次或多次。根据本发明可获得的复合物可用于产生可利用分子进化技术就优选复合物而言富集的文库。

9. 发明申请

WO2011127933A1 BI-FUNCTIONAL COMPLEXES AND METHODS FOR MAKING AND USING SUCH COMPLEXES 审中-公开
标题翻译：双功能复合物和制备和使用这种复合物的方法
公开(公告)号：WO2011127933A1
公开(公告)日：2011-10-20
申请号：PCT/DK2011000031
申请日：2011-04-16
申请人： NUEVOLUTION AS , GOULIAEV ALEX HAAHR , FRANCH THOMAS , GODSKESEN MICHAEL ANDERS , JENSEN KIM BIRKEVAEK
发明人： GOULIAEV ALEX HAAHR , FRANCH THOMAS , GODSKESEN MICHAEL ANDERS , JENSEN KIM BIRKEVAEK
IPC分类号： C12N15/10
CPC分类号： C12N15/1065 , C12N15/1068
摘要： The present invention is directed to a method for the synthesis of a bi-functional complex comprising a molecule part and an identifier oligonucleotide part identifying the molecule part. A part of the synthesis method according to the present invention is preferably conducted in one or more organic solvents when a nascent bi-functional complex comprising an optionally protected tag or oligonucleotide identifier is linked to a solid support, and another part of the synthesis method is preferably conducted under conditions suitable for enzymatic addition of an oligonucleotide tag to a nascent bi-functional complex in solution.
摘要翻译：本发明涉及一种双官能复合物的合成方法，其包括分子部分和识别分子部分的识别寡核苷酸部分。当包含任选保护的标签或寡核苷酸识别符的新生双功能复合物与固体支持物连接时，根据本发明的合成方法的一部分优选在一种或多种有机溶剂中进行，另一部分合成方法为优选在适合于向溶液中的新生双功能复合物酶促添加寡核苷酸标签的条件下进行。

10. 发明专利

SI2348125T1 POSTOPEK ZA SINTEZO BIFUNKCIONALNEGA KOMPLEKSA 未知
公开(公告)号：SI2348125T1
公开(公告)日：2017-10-30
申请号：SI200332547
申请日：2003-10-30
申请人： NUEVOLUTION AS
发明人： FRESKGARD PER-OLA , FRANCH THOMAS , GOULIAEV ALEX HAAHR , LUNDORF MIKKEL DYBRO , FELDING JAKOB , OLSEN EVA KAMPMANN , HOLTMANN ANETTE , JAKOBSEN SOREN NYBOE , SAMS CHRISTIAN , GLAD SANNE SCHRODER , JENSEN KIM BIRKEBAEK , PEDERSEN HENRIK
IPC分类号： C12N15/00 , C07B61/00 , C12N15/10 , C12P19/00 , C40B40/00

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