公开(公告)号：US20210252125A1

公开(公告)日：2021-08-19

申请号：US17049245

申请日：2019-04-25

申请人： Patrick Leonard AHL ,  Akhilesh BHAMBHANI ,  Christopher Jon FARRELL ,  Patrick MCHUGH ,  Morrisa C. JONES ,  Daniel D. ROTH ,  Jessica R. SINACOLA ,  Justin STANBRO ,  Matthew P. WATSON ,  Emily WEN ,  Michael A. WINTERS ,  Merck Sharp & Dohme Corp.

发明人： Patrick Leonard Ahl ,  Akhilesh Bhambhani ,  Christopher Jon Farrell ,  Patrick McHugh ,  Morrisa C. Jones ,  Daniel D. Roth ,  Jessica R. Sinacola ,  Justin Stanbro ,  Matthew P. Watson ,  Emily Wen ,  Michael A. Winters

IPC分类号： A61K39/09 ,  A61K47/62 ,  A61K47/61

摘要： A method is described for producing a pneumococcal capsular polysaccharide protein conjugate in which one or more activated pneumococcal polysaccharides of particular pneumococcal serotypes and carrier protein are separately lyophilized, the separately lyophilized polysaccharides and carrier protein are separately reconstituted in an organic solvent, and the reconstituted polysaccharide and carrier protein are then combined together by Tee-mixing and conjugated together to produce polysaccharide carrier protein conjugates. A plurality of conjugates, each comprising polysaccharides of a particular serotype, may be used to produce multivalent pneumococcal immunogenic compositions having a combination of conjugates for use in vaccines.

公开(公告)号：US20160250319A1

公开(公告)日：2016-09-01

申请号：US15029064

申请日：2014-10-13

申请人： Akhilesh BHAMBHANI ,  Rober K. EVANS ,  Lynne A. ISOPL ,  MERCK SHARP & DOHME CORP

发明人： Akhilesh Bhambhani ,  Robert K. Evans ,  Lynne A. Isopi

IPC分类号： A61K39/155 ,  A61K47/26 ,  C12N7/00

CPC分类号： A61K39/155 ,  A61K9/19 ,  A61K39/12 ,  A61K47/26 ,  A61K2039/5254 ,  C12N7/00 ,  C12N2760/18521 ,  C12N2760/18534 ,  C12N2760/18551

摘要： Methods for improving the drying yield and stability of RSV vaccines comprising a highly thermolabile enveloped live virus and/or one or more RSV protein subunits, are described. Methods for rapid drying of RSV formulations containing between 17.5% and 60% w/w of a non-polymeric sugar and using either conduction or radiation dominant drying mechanisms, are disclosed. The disclosed methods provide for; 1) a dried RSV formulation with improved stability profile; 2) faster drying; and 3) integration of dried RSV into a primary device (such as dual chamber cartridges, foil-pouch devices etc.), pre- as well as post-drying.

摘要翻译： 描述了改善包含高度不耐热的包膜活病毒和/或一个或多个RSV蛋白亚基的RSV疫苗的干燥产率和稳定性的方法。 公开了用于快速干燥含有17.5％至60％w / w的非聚糖的RSV制剂的方法，并且使用传导或辐射优势的干燥机理。 所公开的方法规定; 1）具有改善的稳定性特征的干燥的RSV制剂; 2）干燥速度更快; 以及3）将干燥的RSV整合到主要装置（例如双室筒，箔袋装置等）中，以及干燥后。

公开(公告)号：US20220265558A1

公开(公告)日：2022-08-25

申请号：US17628711

申请日：2020-07-23

申请人： Akhilesh | Bhambhani ,  Morrisa Jones ,  Derrick M. Smith ,  David S. Thiriot ,  Joseph M. Rock ,  Merck Sharp & Dohme Corp.

发明人： Akhilesh Bhambhani ,  Morrisa Jones ,  Derrick M. Smith ,  David S. Thiriot ,  Joseph M. Rock

IPC分类号： A61K9/19 ,  F26B25/06 ,  F26B5/06 ,  A61J3/00

摘要： Disclosed herein are methods for preparing and/or dispensing lyospheres of pharmaceutical compositions of biologics (e.g., vaccines, therapeutic proteins such as monoclonal antibodies) or small molecules (e.g., chemical compounds). Also described are assemblies and systems for preparing and/or dispensing the lyospheres.

公开(公告)号：US20150307606A1

公开(公告)日：2015-10-29

申请号：US14650605

申请日：2013-12-09

申请人： Ashwin BASARKAR ,  Akhilesh BHAMBHANI ,  Ramesh KASHI ,  Shona P. MEHTA ,  MERCK SHARP & DOHME CORP.

发明人： Ashwin Basarkar ,  Akhilesh Bhambhani ,  Ramesh Kashi ,  Shona P. Mehta

IPC分类号： C07K16/24 ,  F26B5/06 ,  A61K9/19

CPC分类号： C07K16/244 ,  A61K9/0019 ,  A61K9/1688 ,  A61K9/19 ,  A61K39/39591 ,  C07K2317/565 ,  C07K2317/94 ,  F26B5/06

摘要： Methods for preparing lyophilized pellets of antibodies that specifically bind to human IL-23 are described. The pellets have a substantially spherical shape and are prepared by freezing droplets of a liquid composition of a desired biological material on a flat, solid surface, in particular, a surface that does not have any cavities, followed by lyophilizing the frozen droplets. These methods are useful for preparing lyophilized pellets having a high concentration of anti-IL-23 antibody, and which have a faster reconstitution time than lyophilized powder cakes prepared in vials. Also provided are improved formulations for use in preparing lyophilized forms of antibodies that specifically bind to human IL-23.

摘要翻译： 描述了制备特异性结合人IL-23的抗体冻干颗粒的方法。 颗粒具有基本上球形的形状，并且通过在平坦的固体表面，特别是没有任何空腔的表面上冷冻所需生物材料的液体组合物的液滴，然后冻结冷冻液滴来制备。 这些方法可用于制备具有高浓度抗IL-23抗体的冻干颗粒，并且比在小瓶中制备的冻干粉饼具有更快的重构时间。 还提供了用于制备特异性结合人IL-23的抗体的冻干形式的改进制剂。

公开(公告)号：US20210236646A1

公开(公告)日：2021-08-05

申请号：US17049208

申请日：2019-04-25

申请人： Patrick Leonard AHL ,  Akhilesh BHAMBHANI ,  Christopher Jon FARRELL, ,  Patrick MHUGH ,  Morrisa C. JONES ,  Daniel D. ROTH ,  Jessica R. SINACOLA ,  Justin STANBRO ,  Matthew P. WATSON ,  Emily WEN ,  Michael A. WINTERS ,  MERCK SHARP & DOHME CORP.

发明人： Patrick Leonard AHL ,  Akhilesh BHAMBHANI ,  Christopher Jon FARRELL ,  Patrick McHUGH ,  Morrisa C. JONES ,  Daniel D. ROTH ,  Jessica R. SINACOLA ,  Justin STANBRO ,  Matthew P. WATSON ,  Emily WEN ,  Michael A. WINTERS

IPC分类号： A61K47/61 ,  A61K39/09

摘要： A method is described for producing a pneumococcal capsular polysaccharide protein conjugate in which one or more activated pneumococcal polysaccharides of particular pneumococcal serotypes and carrier protein are separately lyophilized in the form of lyospheres of carrier protein and lyospheres of the one or more polysaccharides. A predetermined amount of carrier protein lyospheres and activated polysaccharide lyospheres are mixed together and the mixture reconstituted in an organic solvent to produce polysaccharide carrier protein conjugates. A plurality of conjugates, each comprising polysaccharides of a particular serotype, may be used to produce multivalent pneumococcal immunogenic compositions having a combination of conjugates for use in vaccines.

公开(公告)号：US20160252300A1

公开(公告)日：2016-09-01

申请号：US15029062

申请日：2014-10-13

申请人： Akhilesh BHAMBHANI ,  Robert K. EVANS ,  Rebecca LIZZANO ,  Jessica Sinacola ,  MERCK SHARP & DOHME CORP.

发明人： Akhilesh Bhambhani ,  Robert K. Evans ,  Jessica Sinacola ,  Rebecca Lizzano

IPC分类号： F26B5/04 ,  A61K39/15 ,  C12N7/00

CPC分类号： F26B5/048 ,  A61K9/0014 ,  A61K39/15 ,  A61K2039/525 ,  C07K1/00 ,  C12N7/00 ,  C12N2720/12334 ,  F26B2200/08

摘要： Methods for preparing dried pellets of biological materials are described. The pellets can have a substantially spherical shape and are prepared by freezing droplets of a liquid composition of a desired biological material on a solid surface followed by microwave vacuum drying the frozen droplets. These methods are useful for preparing dried pellets having a high concentration of a desired biological material, in particular a therapeutic protein or vaccine, and which have a faster reconstitution time than lyophilized powder cakes prepared in vials.

摘要翻译： 描述了制备生物材料干颗粒的方法。 颗粒可以具有基本上球形的形状，并且通过将所需生物材料的液体组合物的液滴冷冻在固体表面上，然后微波真空干燥冷冻液滴来制备。 这些方法可用于制备具有高浓度所需生物材料，特别是治疗性蛋白质或疫苗的干燥颗粒，并且其比在小瓶中制备的冻干粉饼具有更快的重构时间。

公开(公告)号：US20120121580A1

公开(公告)日：2012-05-17

申请号：US13387268

申请日：2010-07-27

申请人： Akhilesh Bhambhani ,  Brian K. Meyer ,  Jeffrey T. Blue

发明人： Akhilesh Bhambhani ,  Brian K. Meyer ,  Jeffrey T. Blue

IPC分类号： A61K39/395 ,  A61K38/02

CPC分类号： A61K39/39591 ,  A61K9/08 ,  A61K9/19 ,  A61K47/02 ,  A61K47/183 ,  A61K47/26 ,  C07K16/18 ,  C07K2317/24 ,  C07K2317/56 ,  C07K2317/565

摘要： The present invention relates to methods of producing lyophilized pharmaceutical compositions comprising a high concentration of therapeutic protein or antibody prior to lyophilization, wherein the lyophilized formulation can be reconstituted with a diluent in about 15 minutes or less. The invention also relates to the high concentration lyophilized formulations produced by the methods described herein. The lyophilized formulations produced by the methods of the invention are stable and are suitable for veterinary and human medical use and are suitable for modes of administration including oral, pulmonary and parenteral, such as intravenous, intramuscular, intraperitoneal, or subcutaneous injection. Also provided by the invention are high concentration pharmaceutical compositions that have long term stability and can be reconstituted, following lyophilization, in a short period of time, preferably 15 minutes or less.

摘要翻译： 本发明涉及在冷冻干燥之前生产包含高浓度治疗性蛋白质或抗体的冻干药物组合物的方法，其中所述冻干制剂可在约15分钟或更短时间内用稀释剂重建。 本发明还涉及通过本文所述方法制备的高浓度冻干制剂。 通过本发明方法制备的冻干制剂是稳定的并且适用于兽医和人类医学用途，并且适合于包括口服，肺和肠胃外（例如静脉内，肌肉内，腹膜内或皮下注射）的给药方式。 本发明还提供了具有长期稳定性并可以在短时间内优选15分钟或更短时间内冻干后重构的高浓度药物组合物。

公开(公告)号：US20210223262A1

公开(公告)日：2021-07-22

申请号：US15734346

申请日：2019-06-03

申请人： Akhilesh BHAMBHANI ,  Thorsten VERCH ,  Morrisa C. JONES ,  Mary RETZLAFF ,  Jessica R. SINACOLA ,  Silikhone L. BOUARAPHAN ,  Merck Sharp & Dohme Corp.

发明人： Akhilesh Bhambhani ,  Thorsten Verch ,  Morrisa C. Jones ,  Mary Retzlaff ,  Jessica R. Sinacola ,  Silikhone L. Bouaraphan

IPC分类号： G01N33/68 ,  G01N33/58

摘要： The present invention provides lyophilized pellets of low concentrations of antibodies in the form of lyospheres. These lyospheres provide pre-measured antibody concentrations suitable for diagnostic and quality control assays.

公开(公告)号：US20200325020A1

公开(公告)日：2020-10-15

申请号：US16759167

申请日：2018-10-22

申请人： Akhilesh BHAMBHANI ,  Muneeswara Babu MEDI ,  Maya SALNIKOVA ,  James William SMITH ,  David S. THIRIOT ,  Merck Sharp & Dohme Corp.

发明人： Akhilesh Bhambhani ,  Muneeswara Babu Medi ,  Maya Salnikova ,  William James Smith ,  David S. Thiriot

IPC分类号： C01B25/36 ,  A61K39/39 ,  A61K47/52

摘要： Vaccine formulations are described comprising physically separated, lyophilized antigens and adjuvant components, which may be in lyoparticle form, as well as methods of using and making such formulations. Reconstituted formulations are also described.

公开(公告)号：US20140127260A1

公开(公告)日：2014-05-08

申请号：US14126992

申请日：2012-06-22

申请人： Ramesh V. Chintala ,  Akhilesh Bhambhani

发明人： Ramesh V. Chintala ,  Akhilesh Bhambhani

IPC分类号： A61K39/12

摘要： The invention provides human papillomavirus (HPV) antigen formulations which show increased antigen stability. More specifically, the invention provides stable HPV formulations comprising HPV virus-like particles (VLPs) bound to an aluminum salt adjuvant and further comprise a combination of sucrose and mannitol. The vaccine formulations of the invention are stable following freeze-thaw and freeze-drying. Also provided are lyophilized and frozen HPV vaccine formulations comprising HPV VLPs of at least one HPV type adsorbed onto an aluminum salt adjuvant, sucrose, and mannitol. Methods of making the stable vaccine formulations of the invention are also provided.

摘要翻译： 本发明提供了显示增加的抗原稳定性的人乳头状瘤病毒（HPV）抗原制剂。 更具体地，本发明提供了包含与铝盐佐剂结合的HPV病毒样颗粒（VLP）的稳定的HPV制剂，并且还包含蔗糖和甘露醇的组合。 本发明的疫苗制剂在冻融和冷冻干燥后是稳定的。 还提供了包含吸附在铝盐佐剂，蔗糖和甘露醇上的至少一种HPV类型的HPV VLP的冻干和冷冻的HPV疫苗制剂。 还提供了制备本发明稳定的疫苗制剂的方法。