Universal glycoform compositions and methods for enhancing antibody efficacy
一种医药组合物、抗体的技术,应用在抗体、药物组合、化学仪器和方法等方向,能够解决缩短药物循环寿命、诱导免疫原性、改变蛋白质折迭等问题
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[0666] The following examples are included to demonstrate preferred embodiments of the present invention. Those skilled in the art will appreciate that the techniques disclosed in the following examples represent techniques discovered by the inventors to function well in the practice of the present invention, and are therefore considered to constitute preferred embodiments thereof. However, those of ordinary skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments that are disclosed and still obtain a like or similar result without departing from the spirit and scope of the present disclosure.
example 1
[0667] Example 1: Optimizing an exemplary structure of a universal Fc glycan
[0668] The glycan structure of an optimized universal Fc glycan for therapeutic antibodies is Sia 2 (α2-6)Gal 2 GlcNAc 2 Man 3 GlcNAc 2 ( figure 1 ).
[0669] figure 1 . Structure of the optimized generic Fc glycan for therapeutic antibodies.
example 2
[0670] Example 2: Exemplary general procedure for making homogenous antibodies with optimized general glycans in the Fc region.
[0671] The present invention provides an exemplary improved method for preparing a homogeneous population of antibodies with optimized universal glycans in the Fc region, the method comprising the steps of: (a) combining a monoclonal antibody with alpha-trehalosidase and at least one endo Glycosidase contact, thereby producing a detrehalosylated antibody with a single N-acetylglucosamine (GlcNAc), and (b) adding a universal glycan to the GlcNAc in the Fc region of the antibody to form a figure 1 Homogeneous antibodies in the optimized glycan form shown ( figure 2 ).
[0672] see figure 2 . A general strategy for making homogeneous antibodies in which a general glycan is optimized in the Fc region in order to improve its therapeutic activity.
[0673] Endoglycosidases are used to cleave the variable portion of oligosaccharides in N-glycans. Ex...
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