公开(公告)号：EP2638146A1

公开(公告)日：2013-09-18

申请号：EP11779450.3

申请日：2011-11-09

申请人： LEK Pharmaceuticals d.d.

发明人： OBRSTAR, Darja

IPC分类号： C12N5/00 ,  C12N5/10 ,  C12N5/16

CPC分类号： C12Q1/68 ,  C12N15/67 ,  C12P21/00

摘要： The present invention relates to a method for selecting for cells or cell lines that produce a recombinant protein/polypeptide in high yields, the method allowing for the selection of high producer cells or cell lines in an early phase of cell line development, the method comprising the step of determining the nuclear DNA content of the cells or cell lines, wherein the level of the nuclear DNA content of the cells or cell lines positively correlates with the capacity of the cells or cell lines to produce the recombinant protein/polypeptide.

公开(公告)号：EP1907375B1

公开(公告)日：2013-07-24

申请号：EP06754185.4

申请日：2006-06-07

申请人： LEK Pharmaceuticals d.d.

发明人： VRANICAR SAVANOVIC, Lidija ,  HAM, Zoran ,  RZEN, Janez

IPC分类号： C07D401/12

CPC分类号： C07D401/12

公开(公告)号：EP2615080A1

公开(公告)日：2013-07-17

申请号：EP12150892.3

申请日：2012-01-12

申请人： LEK Pharmaceuticals d.d.

发明人： The designation of the inventor has not yet been filed

IPC分类号： C07C211/27 ,  C07C231/06 ,  C07C239/20 ,  C07F5/02 ,  C07C227/34 ,  C07C269/06 ,  C07C303/40 ,  C07C67/31

CPC分类号： C07C231/06 ,  C07B53/00 ,  C07B2200/07 ,  C07C67/31 ,  C07C211/27 ,  C07C227/34 ,  C07C239/20 ,  C07C269/06 ,  C07C303/40 ,  C07F5/02 ,  C07F7/0892 ,  C07F7/10 ,  C07C233/47 ,  C07C229/34 ,  C07C271/22 ,  C07C311/19 ,  C07C69/732

摘要： The present invention relates to the preparation of optically resolved chiral compounds of β-amino acid type active pharmaceutical ingredients (API), more specifically to β-aminobutyryl substituted compounds and especially β-aminobutyryl compounds having γ-bound aryl groups. The present invention more particularly relates to the preparation of enantiomerically enriched chiral compounds useful as intermediates for the preparation of anti-diabetic agents, preferably sitagliptin.

摘要翻译： 本发明涉及的²氨基酸类活性药物成分旋光拆分的手性化合物（API），更具体地涉及²氨基丁substituiertem化合物的制备和爱尤其具有³结合的芳基²氨基丁化合物。 本发明尤其涉及对映体富集的手性化合物的制备有用的中间体用于抗糖尿病剂的制备中，优选西他列汀。

公开(公告)号：EP2594260A1

公开(公告)日：2013-05-22

申请号：EP11189759.1

申请日：2011-11-18

申请人： LEK Pharmaceuticals d.d.

发明人： The designation of the inventor has not yet been filed

IPC分类号： A61K9/28 ,  A61K31/436

CPC分类号： A61K9/2866 ,  A61K9/146 ,  A61K9/2018 ,  A61K9/2054 ,  A61K9/2095 ,  A61K31/436

摘要： The present invention relates to a pharmaceutical composition in a solid final dosage form comprising sirolimus exhibiting sufficient bioavailability and therapeutic effect, and a method for preparation thereof. A formulation with suitable therapeutic effect provides benefits in regard of cost reduction, process optimization and reduction in undesired effects regarding the formulation and its behavior in vivo

摘要翻译： 本发明涉及一种药物组合物中的固体剂型的最终包含西罗莫司表现出足够的生物利用度和治疗效果，以及用于制备它们的方法。 与合适的治疗效果的制剂在降低成本，工艺优化和减少不希望的效果的方面提供好处关于制剂和其在体内的行为

公开(公告)号：EP1711489B1

公开(公告)日：2012-12-26

申请号：EP04809253.0

申请日：2004-12-27

申请人： LEK Pharmaceuticals d.d.

发明人： ANTONCIC, Ljubomir ,  SORSAK, Gorazd

IPC分类号： C07D405/06 ,  C07D207/34

CPC分类号： C07D405/06 ,  C07D207/34

公开(公告)号：EP2515884A1

公开(公告)日：2012-10-31

申请号：EP10790577.0

申请日：2010-12-20

申请人： LEK Pharmaceuticals d.d.

发明人： BELE, Marjan ,  GABERSCEK, Miran ,  JAMNIK, Janko ,  ZORKO, Milena ,  MAVER, Uros ,  KOCEVAR, Klemen

IPC分类号： A61K9/50 ,  A61K31/192 ,  A61K31/501 ,  A61K31/519 ,  A61K31/7048

CPC分类号： A61J3/005 ,  A61K9/501 ,  A61K9/5089 ,  A61K31/192 ,  A61K31/501 ,  A61K31/519 ,  A61K31/7048

摘要： The present invention belongs to the field of pharmaceutical industry and relates to a process for coating a particle comprising a pharmaceutically active ingredient (API) comprising the steps of providing a composition comprising carbonate ions, phosphate ions, or a mixture thereof, providing a particle comprising an API, and precipitating a carbonate salt, a phosphate salt or a mixture thereof onto said particles. The present invention is also directed to a particle comprising an API, wherein the particle is coated with a coating comprising a carbonate salt, phosphate salt, or mixture thereof, and to a pharmaceutical composition comprising said particles. Moreover, the present invention is also directed to the use of said particles for preparing a medicament.

公开(公告)号：EP2511293A1

公开(公告)日：2012-10-17

申请号：EP11162193.4

申请日：2011-04-13

申请人： LEK Pharmaceuticals d.d.

发明人： Stojkovic, Sasa ,  Spudic, Vatroslav ,  Tisu, Matjaz ,  Koncilja, Matjaz

IPC分类号： C07K14/435 ,  C12N5/00 ,  C07K14/43

CPC分类号： C07K16/2887 ,  C07K16/22 ,  C07K16/241 ,  C07K16/2863 ,  C12N1/38 ,  C12P21/02

摘要： The present invention relates to a method of controlling quality and quantity of posttranslational modification of a recombinantly produced polypeptide/protein (glycoprotein), wherein the posttranslational modification affects the glycosylation profile and/or the acidic variants profile, as manifested in CEX profiles, wherein the polypeptide/protein (glycoprotein) production is in eukaryotic host cells, the method comprising the following steps:
a) cultivating the eukaryotic cells in a suitable medium under conditions which allow the expression of the polypeptide/protein, wherein the content of the dissolved CO 2 (pCO 2 ) in the medium is at a first value during the initial growth phase of the eukaryotic cells, allowing the eukaryotic cells to grow, and
b) increasing or decreasing the content of the dissolved CO 2 (pCO 2 ) in the medium during the production phase of the eukaryotic cells to a second value.

摘要翻译： 本发明涉及一种控制重组产生的多肽/蛋白质（糖蛋白）的翻译后修饰的质量和数量，worin翻译后修饰的方法会影响糖基化特征和/或所述酸性变体轮廓，如在CEX轮廓表现出来，worin的 多肽/蛋白质（糖蛋白）的生产是在真核宿主细胞，所述方法包括以下步骤：a）培养在合适的培养基中的真核细胞的条件，其允许所述多肽/蛋白质的表达下，worin溶解的含量的CO 2 （PCO 2）在介质中是在过程中的真核细胞的初始生长阶段的第一值，允许所述真核细胞生长，和b）增加或期间在培养基中降低的溶解的CO 2（二氧化碳分压）的含量 所述真核细胞的生产阶段到第二值。

公开(公告)号：EP2501799A1

公开(公告)日：2012-09-26

申请号：EP10781888.2

申请日：2010-11-19

申请人： LEK Pharmaceuticals d.d.

发明人： FICKO TRCEK, Tanja

IPC分类号： C12N5/00 ,  C12P21/00

CPC分类号： C07K14/47 ,  C12N5/0018 ,  C12N2500/20 ,  C12N2500/30 ,  C12N2500/34 ,  C12N2500/62 ,  C12P21/005

摘要： The present invention relates to a medium for the cultivation of eukaryotic cells, the medium comprising as (an) additive(s) DMSO, N-acetylmannosamine (NAcMan), N-acetylglucosamine (NAcGlc), or any combination of two or more of these additives, including the combination of NAcMan and NAcGlc.

公开(公告)号：EP2084158B1

公开(公告)日：2012-07-25

申请号：EP07821835.1

申请日：2007-10-25

申请人： LEK Pharmaceuticals d.d.

发明人： HAM, Zoran ,  CRNUGELJ, Martin

IPC分类号： C07D457/06

CPC分类号： C07D457/06

摘要： The present invention relates to a process for producing cabergoline crystal forms. The process comprises preparation of the desired solvate of cabergoline from a solution of cabergoline in chloroaromatic solvents. Afterwards cabergoline crystal form is prepared by recovery from a solvate of cabergoline by drying or with desolvating in a solvent media.

公开(公告)号：EP2441442A1

公开(公告)日：2012-04-18

申请号：EP10013439.4

申请日：2010-10-08

申请人： LEK Pharmaceuticals d.d.

发明人： The designation of the inventor has not yet been filed

IPC分类号： A61K9/16 ,  A61K9/20 ,  A61K9/28 ,  A61K31/155 ,  A61K31/4439

CPC分类号： A61K9/28 ,  A61K9/2054 ,  A61K9/2077 ,  A61K9/2095 ,  A61K9/2866 ,  A61K31/155 ,  A61K31/4439 ,  A61K45/06 ,  A61K2300/00

摘要： A pharmaceutical composition comprises a combination of thiazolidinedione or a pharmaceutically acceptable salt thereof as a first pharmaceutically active ingredient and a second pharmaceutically active ingredient different from thiazolidinedione, wherein the amount of said second pharmaceutically ingredient is larger than that of the first pharmaceutically active ingredient, and wherein the combination of said first and second pharmaceutically active ingredients are provided by a first granulate comprising the first and second pharmaceutically active ingredients and optionally at least one excipient, said first granulate being present in a second granulate comprising a further pharmaceutical excipient.

摘要翻译： 药物组合物包含噻唑烷二酮或其药学上可接受的盐作为第一药学活性成分和不同于噻唑烷二酮的第二药物活性成分的组合，其中所述第二药物成分的量大于第一药物活性成分的量，以及 其中所述第一和第二药物活性成分的组合由包含第一和第二药物活性成分和任选的至少一种赋形剂的第一颗粒提供，所述第一颗粒存在于包含另外的药物赋形剂的第二颗粒中。