公开(公告)号：US20200031895A1

公开(公告)日：2020-01-30

申请号：US16468347

申请日：2017-12-15

Applicant: Biogen MA Inc.

Inventor： R. Blake Pepinsky ,  Andreas Lehmann ,  Dingyi Wen

IPC: C07K14/51 ,  C12P21/02

Abstract: Methods of activating GDF11 proteins in vitro as well as formulations of mature GDF11 polypeptides with enhanced solubility at neutral pH are provided.

公开(公告)号：US10308706B2

公开(公告)日：2019-06-04

申请号：US14638215

申请日：2015-03-04

Applicant: BIOGEN MA INC.

Inventor： David Evans ,  R. Blake Pepinsky ,  Dingyi Wen ,  Rashmi Rohit Kshirsagar ,  Karin Lucas

IPC: C07K16/00 ,  C07K1/113

Abstract: The present invention pertains to methods of preventing and eliminating trisulfide bonds in proteins such as antibodies. In one embodiment, trisulfide bonds in proteins are converted to disulfide bonds as part of chromatographic purification procedures. In another embodiment, the formation of trisulfide bonds in proteins is inhibited by implementation of methods described herein during the cell culture production of such proteins. In another embodiment, monoclonal antibodies are produced by the methods described herein.

公开(公告)号：US20160002329A1

公开(公告)日：2016-01-07

申请号：US14734144

申请日：2015-06-09

Applicant: Biogen MA Inc.

Inventor： Sha Mi ,  R. Blake Pepinsky ,  John McCoy

IPC: C07K16/28 ,  C07K16/40

CPC classification number: C07K16/28 ,  A01K67/0275 ,  A01K67/0276 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0393 ,  A61K2039/505 ,  C07K14/4702 ,  C07K16/18 ,  C07K16/2863 ,  C07K16/32 ,  C07K16/40 ,  C07K2317/74 ,  C07K2317/75 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2319/30 ,  C12N15/8509

Abstract: The invention provides methods of treating diseases, disorders or injuries involving demyelination and dysmyelination, including multiple sclerosis, by the administration of an Sp35 antagonist. Additional methods include methods for inhibiting the binding of the Sp35 polypeptide with the ErbB2 polypeptide and a method for increasing ErbB2 phosphorylation by contacting oligodendrocytes with an effective amount of a composition comprising an Sp35 antagonist of the invention. Further embodiments of the invention include methods of inhibiting the binding of the Sp35 polypeptide with the ErbB2, increasing ErbB2 phosphorylation and promoting oligodendrocyte differentiation comprising contacting oligodendrocyte or oligodendrocyte progenitor cells with an ErbB2 binding agent.

Abstract translation: 本发明提供了通过施用Sp35拮抗剂治疗涉及脱髓鞘和髓鞘脱离（包括多发性硬化）的疾病，病症或损伤的方法。 另外的方法包括用于抑制Sp35多肽与ErbB2多肽的结合的方法以及通过使少突胶质细胞与有效量的包含本发明的Sp35拮抗剂的组合物接触来增加ErbB2磷酸化的方法。 本发明的其它实施方案包括抑制Sp35多肽与ErbB2结合的方法，增加E​​rbB2磷酸化和促进少突胶质细胞分化，包括使少突胶质细胞或少突胶质细胞祖细胞与ErbB2结合剂接触。

公开(公告)号：US20150315273A1

公开(公告)日：2015-11-05

申请号：US14677521

申请日：2015-04-02

Applicant: Biogen MA Inc.

Inventor： Sha Mi ,  R. Blake Pepinsky ,  Zhaohui Shao ,  Ellen A. Garber ,  Steven D. Miklasz ,  Christilyn Graff

IPC: C07K16/28

CPC classification number: C07K16/2803 ,  A61K2039/505 ,  C07K16/28 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2317/41 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/75 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2319/30

Abstract: Endogenous Sp35 is a negative regulator for neuronal survival, axon regeneration, oligodendrocyte differentiation and myelination. Molecules that block endogenous Sp35 function, such anti-Sp35 antibodies can be used as therapeutics for the treatment of neuron and oligodendrocyte dysfunction. The present invention provides antibodies specific for Sp35, and methods of using such antibodies as antagonists of endogenous Sp35 function. The invention further provides specific hybridoma and phage library-derived monoclonal antibodies, nucleic acids encoding these antibodies, and vectors and host cells comprising these antibodies. The invention further provides methods of promoting oligodendrocyte survival and myelination in a vertebrate, comprising administering to a vertebrate in need of such treatment an effective amount of an anti-Sp35 antibody.

Abstract translation: 内源性Sp35是神经元存活，轴突再生，少突胶质细胞分化和髓鞘形成的负调节因子。 阻断内源性Sp35功能的分子，这种抗Sp35抗体可以用作治疗神经元和少突胶质细胞功能障碍的治疗剂。 本发明提供对Sp35特异性的抗体，以及使用抗体作为内源性Sp35功能拮抗剂的方法。 本发明还提供特异性杂交瘤和源自噬菌体文库的单克隆抗体，编码这些抗体的核酸，以及包含这些抗体的载体和宿主细胞。 本发明还提供了在脊椎动物中促进少突胶质细胞存活和髓鞘形成的方法，其包括对需要这种治疗的脊椎动物施用有效量的抗Sp35抗体。