公开(公告)号：US08871201B2

公开(公告)日：2014-10-28

申请号：US11203367

申请日：2005-08-12

Applicant: Li Li ,  Angela Kantor ,  Shannon B. MacMillan

Inventor： Li Li ,  Angela Kantor ,  Shannon B. MacMillan

IPC: A61K39/395 ,  C07K16/06 ,  C07K16/28 ,  A61K9/28 ,  C07K16/30 ,  A61K39/00

CPC classification number: A61K9/2886 ,  C07K16/065 ,  C07K16/2803 ,  C07K16/2896 ,  C07K16/30 ,  C07K2317/24

Abstract: Formulations are described that are suitable for storage of proteins, such as antibodies, over a relatively broad range of protein concentrations, pH, and buffer types. Also described are methods of storing a protein and methods of identifying a suitable formulation for storage of a specific protein. In general, a formulation contains low to no surfactant, no to relatively low salt concentrations, and requires a relatively low buffer concentration.

Abstract translation: 描述了适合于在相对宽的蛋白质浓度，pH和缓冲液类型范围内存储蛋白质（例如抗体）的制剂。 还描述了存储蛋白质的方法和鉴定用于储存特定蛋白质的合适制剂的方法。 通常，制剂含有低至无表面活性剂，不含相对较低的盐浓度，并且需要相对较低的缓冲液浓度。

公开(公告)号：US07883704B2

公开(公告)日：2011-02-08

申请号：US11645287

申请日：2006-12-22

Applicant: Jochen G. Salfeld ,  Michael Roguska ,  Michael Paskind ,  Subhashis Banerjee ,  Daniel Edward Tracey ,  Michael White ,  Zehra Kaymakcalan ,  Boris Labkovsky ,  Paul Sakorafas ,  Geertruida M. Veldman ,  Amy Venturini ,  Angela Widom ,  Stuart Friedrich ,  Nicholas W. Warne ,  Angela Kantor ,  John Gawain Elvin ,  Alexander Robert Duncan ,  Elaine Joy Derbyshire ,  Sara Carmen ,  Stephen Smith ,  Thor Las Holtet ,  Sarah Leila Du Fou

Inventor： Jochen G. Salfeld ,  Michael Roguska ,  Michael Paskind ,  Subhashis Banerjee ,  Daniel Edward Tracey ,  Michael White ,  Zehra Kaymakcalan ,  Boris Labkovsky ,  Paul Sakorafas ,  Geertruida M. Veldman ,  Amy Venturini ,  Angela Widom ,  Stuart Friedrich ,  Nicholas W. Warne ,  Angela Kantor ,  John Gawain Elvin ,  Alexander Robert Duncan ,  Elaine Joy Derbyshire ,  Sara Carmen ,  Stephen Smith ,  Thor Las Holtet ,  Sarah Leila Du Fou

IPC: A61K38/20 ,  A61K39/395 ,  C07K16/24 ,  C12P21/08

CPC classification number: C07K16/244 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/30 ,  C07K2317/33 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/73 ,  C07K2317/76 ,  C07K2317/92

Abstract: Human antibodies, preferably recombinant human antibodies, that specifically bind to human interleukin-12 (hIL-12 ) are disclosed. Preferred antibodies have high affinity for hIL-12 and neutralize hIL-12 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hIL-12 and for inhibiting hIL-12 activity, e.g., in a human subject suffering from a disorder in which hIL-12 activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies of the invention, and methods of synthesizing the recombinant human antibodies, are also encompassed by the invention.

Abstract translation: 公开了特异性结合人白细胞介素-12（hIL-12）的人抗体，优选重组人抗体。 优选的抗体对hIL-12具有高亲和力，并在体外和体内中和hIL-12活性。 本发明的抗体可以是全长抗体或其抗原结合部分。 本发明的抗体或抗体部分可用于检测hIL-12和抑制hIL-12活性，例如在患有hIL-12活性有害的病症的人类受试者中。 用于表达本发明的重组人抗体的核酸，载体和宿主细胞以及合成重组人抗体的方法也包括在本发明中。

公开(公告)号：US20100172862A1

公开(公告)日：2010-07-08

申请号：US12625057

申请日：2009-11-24

Applicant: Ivan R. Correia ,  Czeslaw H. Radziejewski ,  Wolfgang Fraunhofer ,  Nicholas W. Warne ,  Angela Kantor

Inventor： Ivan R. Correia ,  Czeslaw H. Radziejewski ,  Wolfgang Fraunhofer ,  Nicholas W. Warne ,  Angela Kantor

IPC: A61K38/20 ,  C07K16/18 ,  A61K39/395 ,  A61K38/19 ,  A61K38/21 ,  A61P37/04

CPC classification number: C07K16/244 ,  A61K9/0019 ,  A61K39/3955 ,  A61K39/39591 ,  A61K47/183 ,  A61K47/22 ,  A61K47/26 ,  A61K2039/505 ,  C07K16/065 ,  C07K2317/21 ,  C07K2317/41 ,  C07K2317/52 ,  C07K2317/55 ,  C07K2317/76 ,  C07K2317/94

Abstract: The invention provides compositions and methods for inhibiting fractionation of immunoglobulins comprising a lambda light chain based on the observation that iron, in the presence of histidine, results in increased fragmentation of a recombinant fully human IgG molecule containing a lambda light chain due to cleavage in the hinge region. The invention further provides an aqueous pharmaceutical formulation comprising an antibody, or antigen-binding portion thereof, that binds the p40 subunit of IL-12/IL-23 and a buffer system comprising histidine, wherein the formulation has enhanced stability, including enhanced resistance to fragmentation.

Abstract translation: 本发明提供了用于抑制包含λ轻链的免疫球蛋白分级分离的组合物和方法，基于以下观察结果：在组氨酸存在下，铁导致包含λ轻链的重组完全人IgG分子由于在 铰链区域。 本发明还提供了包含结合IL-12 / IL-23的p40亚基的抗体或其抗原结合部分的水性药物制剂和包含组氨酸的缓冲体系，其中所述制剂具有增强的稳定性，包括增强的抗性 碎片化

公开(公告)号：US20060115472A1

公开(公告)日：2006-06-01

申请号：US11203367

申请日：2005-08-12

Applicant: Li Li ,  Angela Kantor ,  Shannon MacMillan

Inventor： Li Li ,  Angela Kantor ,  Shannon MacMillan

IPC: A61K39/395

CPC classification number: A61K9/2886 ,  C07K16/065 ,  C07K16/2803 ,  C07K16/2896 ,  C07K16/30 ,  C07K2317/24

Abstract: Formulations are described that are suitable for storage of proteins, such as antibodies, over a relatively broad range of protein concentrations, pH, and buffer types. Also described are methods of storing a protein and methods of identifying a suitable formulation for storage of a specific protein. In general, a formulation contains low to no surfactant, no to relatively low salt concentrations, and requires a relatively low buffer concentration.

Abstract translation: 描述了适合于在相对宽的蛋白质浓度，pH和缓冲液类型范围内存储蛋白质（例如抗体）的制剂。 还描述了存储蛋白质的方法和鉴定用于储存特定蛋白质的合适制剂的方法。 通常，制剂含有低至无表面活性剂，不含相对较低的盐浓度，并且需要相对较低的缓冲液浓度。

公开(公告)号：US20120114646A1

公开(公告)日：2012-05-10

申请号：US13378751

申请日：2010-06-18

Applicant: Serguei Tchessalov ,  Angela Kantor ,  Li Li ,  Nicholas Luksha ,  Nicholas Warne

Inventor： Serguei Tchessalov ,  Angela Kantor ,  Li Li ,  Nicholas Luksha ,  Nicholas Warne

IPC: A61K39/395 ,  A61P37/00

CPC classification number: A61K39/39591 ,  A61K9/0014 ,  A61K9/19 ,  A61K47/183 ,  A61K47/26 ,  C07K16/2887 ,  C07K2317/24 ,  C07K2317/52 ,  C07K2317/56 ,  C07K2317/622 ,  C07K2319/00

Abstract: The present invention provides, among other things, stable formulations for small modular immunopharmaceutical (SMIP™) proteins. In some embodiments, the present invention provides a formulation containing a lyophilized mixture of a small modular immunopharmaceutical protein, wherein less than 7% of the lyophilized small modular immunopharmaceutical protein exists in aggregated form. Formulations according to the invention may contain buffering agents, stabilizers, bulking agents, surfactants and/or other excipients. The present invention also provides formulations for lyophilization, reconstitution and methods of use thereof.

Abstract translation: 本发明尤其提供了用于小型模块化免疫药物（SMIP TM）蛋白质的稳定制剂。 在一些实施方案中，本发明提供含有小模块化免疫药物蛋白质的冻干混合物的制剂，其中小于7％的冻干小模块化免疫药物蛋白以聚集形式存在。 根据本发明的制剂可以含有缓冲剂，稳定剂，填充剂，表面活性剂和/或其它赋形剂。 本发明还提供了用于冻干，重构和其使用方法的制剂。

公开(公告)号：US20110123544A1

公开(公告)日：2011-05-26

申请号：US12910461

申请日：2010-10-22

Applicant: Jochen G. Salfeld ,  Michael Roguska ,  Michael Paskind ,  Subhashis Banerjee ,  Daniel Edward Tracey ,  Michael White ,  Zehra Edward Kaymakcalan ,  Boris Labkovsky ,  Paul Sakorafas ,  Geertuida M. Veldman ,  Amy Venturini ,  Angela Widom ,  Stuart Friedrich ,  Nicholas W. Warne ,  Angela Kantor ,  John Gawain Elvin ,  Alexander Robert Duncan ,  Elaine Joy Derbyshire ,  Sara Carmen ,  Stephen Smith ,  Thor Las Holtet ,  Sarah Leila Du Fou

Inventor： Jochen G. Salfeld ,  Michael Roguska ,  Michael Paskind ,  Subhashis Banerjee ,  Daniel Edward Tracey ,  Michael White ,  Zehra Edward Kaymakcalan ,  Boris Labkovsky ,  Paul Sakorafas ,  Geertuida M. Veldman ,  Amy Venturini ,  Angela Widom ,  Stuart Friedrich ,  Nicholas W. Warne ,  Angela Kantor ,  John Gawain Elvin ,  Alexander Robert Duncan ,  Elaine Joy Derbyshire ,  Sara Carmen ,  Stephen Smith ,  Thor Las Holtet ,  Sarah Leila Du Fou

IPC: C07K16/24 ,  A61K39/395 ,  G01N33/566 ,  C07K14/54 ,  A61P19/02 ,  A61P37/00 ,  A61P9/10 ,  A61P13/12 ,  A61P25/28 ,  A61P25/16 ,  A61P31/00 ,  A61P7/06 ,  A61P3/10 ,  A61P9/00 ,  A61P35/04 ,  A61P17/06

CPC classification number: C07K16/244 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/30 ,  C07K2317/33 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/73 ,  C07K2317/76 ,  C07K2317/92

Abstract: Human antibodies, preferably recombinant human antibodies, that specifically bind to human interleukin-12 (hIL-12) are disclosed. Preferred antibodies have high affinity for hIL-12 and neutralize hIL-12 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hIL-12 and for inhibiting hIL-12 activity, e.g., in a human subject suffering from a disorder in which hIL-12 activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies of the invention, and methods of synthesizing the recombinant human antibodies, are also encompassed by the invention.

Abstract translation: 公开了特异性结合人白细胞介素-12（hIL-12）的人抗体，优选重组人抗体。 优选的抗体对hIL-12具有高亲和力，并在体外和体内中和hIL-12活性。 本发明的抗体可以是全长抗体或其抗原结合部分。 本发明的抗体或抗体部分可用于检测hIL-12和抑制hIL-12活性，例如在患有hIL-12活性有害的病症的人类受试者中。 用于表达本发明的重组人抗体的核酸，载体和宿主细胞以及合成重组人抗体的方法也包括在本发明中。

公开(公告)号：US20080064856A1

公开(公告)日：2008-03-13

申请号：US11725534

申请日：2007-03-19

Applicant: Nicholas Warne ,  Angela Kantor ,  Thomas Crowley ,  Erin Soley ,  Li Li ,  Nicholas Luksha ,  Edie Neidhardt

Inventor： Nicholas Warne ,  Angela Kantor ,  Thomas Crowley ,  Erin Soley ,  Li Li ,  Nicholas Luksha ,  Edie Neidhardt

IPC: C07K14/755 ,  C07K1/14 ,  C07K14/00

CPC classification number: A61K39/39591 ,  A61K9/0019 ,  A61K9/19 ,  A61K38/00 ,  A61K47/183 ,  A61K47/26 ,  C07K2319/30

Abstract: Methods of reducing aggregation of a protein or proteins in a formulation, and protein formulations having reduced aggregation properties are provided. The methods and formulations described herein maintain the biological activity of a protein and increase the shelf life of protein formulations.

Abstract translation: 提供了减少制剂中蛋白质或蛋白质聚集的方法，以及具有降低的聚集性质的蛋白质制剂。 本文描述的方法和制剂维持蛋白质的生物活性并增加蛋白质制剂的保质期。

公开(公告)号：US20080063634A1

公开(公告)日：2008-03-13

申请号：US11645287

申请日：2006-12-22

Applicant: Jochen Salfeld ,  Michael Roguska ,  Michael Paskind ,  Subhashis Banerjee ,  Daniel Tracey ,  Michael White ,  Zehra Kaymakcalan ,  Boris Labkovsky ,  Paul Sakorafas ,  Geertruida Veldman ,  Amy Venturini ,  Angela Widom ,  Stuart Friedrich ,  Nicholas Warne ,  Angela Kantor ,  John Elvin ,  Alexander Duncan ,  Elaine Derbyshire ,  Sara Carmen ,  Stephen Smith ,  Thor Holtet ,  Sarah Du Fou

Inventor： Jochen Salfeld ,  Michael Roguska ,  Michael Paskind ,  Subhashis Banerjee ,  Daniel Tracey ,  Michael White ,  Zehra Kaymakcalan ,  Boris Labkovsky ,  Paul Sakorafas ,  Geertruida Veldman ,  Amy Venturini ,  Angela Widom ,  Stuart Friedrich ,  Nicholas Warne ,  Angela Kantor ,  John Elvin ,  Alexander Duncan ,  Elaine Derbyshire ,  Sara Carmen ,  Stephen Smith ,  Thor Holtet ,  Sarah Du Fou

IPC: A61K39/395 ,  A61P37/00 ,  C07K14/54 ,  C07K16/24 ,  G01N33/00

CPC classification number: C07K16/244 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/30 ,  C07K2317/33 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/73 ,  C07K2317/76 ,  C07K2317/92

Abstract: Human antibodies, preferably recombinant human antibodies, that specifically bind to human interleukin-12 (hIL-12) are disclosed. Preferred antibodies have high affinity for hIL-12 and neutralize hIL-12 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hIL-12 and for inhibiting hIL-12 activity, e.g., in a human subject suffering from a disorder in which hIL-12 activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies of the invention, and methods of synthesizing the recombinant human antibodies, are also encompassed by the invention.

Abstract translation: 公开了特异性结合人白细胞介素-12（hIL-12）的人抗体，优选重组人抗体。 优选的抗体对hIL-12具有高亲和力，并在体外和体内中和hIL-12活性。 本发明的抗体可以是全长抗体或其抗原结合部分。 本发明的抗体或抗体部分可用于检测hIL-12和抑制hIL-12活性，例如在患有hIL-12活性有害的病症的人类受试者中。 用于表达本发明的重组人抗体的核酸，载体和宿主细胞以及合成重组人抗体的方法也包括在本发明中。

公开(公告)号：US20060210557A1

公开(公告)日：2006-09-21

申请号：US11342252

申请日：2006-01-27

Applicant: Donna Luisi ,  Nicholas Warne ,  Angela Kantor

Inventor： Donna Luisi ,  Nicholas Warne ,  Angela Kantor

IPC: A61K39/395 ,  A61K31/4172 ,  A61K31/198

CPC classification number: A61K47/26 ,  A61K9/0019 ,  A61K9/08 ,  A61K31/198 ,  A61K31/4172 ,  A61K39/39591 ,  A61K47/02 ,  A61K47/183 ,  A61K47/22 ,  A61K2039/505 ,  C07K16/18 ,  C07K2317/24 ,  C07K2317/56

Abstract: The present invention provides formulations for maintaining the stability of polypeptides, in particular, therapeutic antigen-binding polypeptides such as antibodies and the like, for example, anti-Aβ antibodies. The formulations generally include an antioxidant in a sufficient amount as to inhibit by-product formation, for example, the formation of high molecular weight polypeptide aggregates, low molecular weight polypeptide degradation fragments, and mixtures thereof. The formulations of the invention optionally comprise a tonicity agent, such as mannitol, and a buffering agent or amino acid such as histidine, and thus, the formulations are suitable for several different routes of administration.

Abstract translation: 本发明提供用于维持多肽的稳定性，特别是治疗性抗原结合多肽如抗体等的抗体，例如抗Aβ抗体的制剂。 制剂通常包括足够量的抗氧化剂以抑制副产物形成，例如形成高分子量多肽聚集体，低分子量多肽降解片段及其混合物。 本发明的制剂任选地包含张度剂，例如甘露糖醇，缓冲剂或氨基酸，例如组氨酸，因此，该制剂适合于几种不同的给药途径。

公开(公告)号：US08318164B2

公开(公告)日：2012-11-27

申请号：US12637508

申请日：2009-12-14

Applicant: Nicholas W. Warne ,  Donna Luisi ,  Angela Kantor

Inventor： Nicholas W. Warne ,  Donna Luisi ,  Angela Kantor

IPC: A61K39/395

CPC classification number: A61K47/26 ,  A61K9/0019 ,  A61K9/19 ,  A61K31/198 ,  A61K31/4172 ,  A61K39/39591 ,  A61K47/02 ,  A61K47/183 ,  C07K16/18 ,  C07K2317/24

Abstract: The present invention provides formulations for maintaining the stability of Aβ binding polypeptides, for example, Aβ antibodies. Exemplary formulations include a tonicity agent such as mannitol and a buffering agent or amino acid such as histidine. Other exemplary formulations include an antioxidant in a sufficient amount as to inhibit by-product formation, for example, the formation of high molecular weight polypeptide aggregates, low molecular weight polypeptide degradation fragments, and mixtures thereof. The formulations of the invention optionally comprise a tonicity agent, such as mannitol, and a buffering agent or amino acid such as histidine. The formulations are suitable for several different routes of administration.

Abstract translation: 本发明提供用于维持A＆Bgr的稳定性的制剂; 结合多肽，例如A＆bgr; 抗体。 示例性制剂包括张力剂如甘露醇和缓冲剂或氨基酸如组氨酸。 其它示例性制剂包括足够量的抗氧化剂以抑制副产物形成，例如形成高分子量多肽聚集体，低分子量多肽降解片段及其混合物。 本发明的制剂任选地包含张力剂，例如甘露醇，缓冲剂或氨基酸，例如组氨酸。 该制剂适用于几种不同的给药途径。