mRNA display antibody library and methods
A library and antibody technology, applied in chemical instruments and methods, biochemical equipment and methods, libraries, etc., can solve problems such as low affinity, high diversity libraries are difficult to obtain, and low cross-reactivity conjugates
Pending Publication Date: 2021-09-07
NANTBIOSCI
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However, such a process requires iterative analysis and is not effective for all antigens
[0007] Therefore, even though methods for creating and identifying candidate binders using mRNA display and other methods are known, high diversity libraries of binders with high structural integrity / stability, low affinity, and / or low cross-reactivity remain difficult. get
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[0087] While any suitable diversification scheme can be envisaged to identify one or more regions of targeted diversification in order to maximize diversity while maintaining efficiency, the inventors have found that VH3 / Vk1 can be various domains of immunoglobulins One of the good candidate regions for randomization in , VH3 is considered to be the most stable and soluble VH domain to date, and Vk1 of the light chain is stable and soluble. Therefore, it is envisaged that VH3 / Vk1 randomized pairs will be more efficiently converted to full-size immunoglobulins. Therefore, the inventors developed a preselection strategy using the VH3 and Vk1 frameworks. figure 1 An exemplary randomization strategy using the VH3 / Vk1 pair is shown. The protein sequences of at least 14 immunoglobulin molecules specific for an antigen are compared and analyzed. The most stable and conserved sequence among the 14 immunoglobulin molecules was used as the frame, and the positions of the variable sequ...
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Abstract
Compositions, methods and uses of a recombinant virus and / or recombinant viral vector encoding a distinct antibody or antibody fragment generated from high-diversity nucleic acid library are presented. Preferably, the recombinant virus is genetically modified, low immunogenic virus, for example, an E2b-deleted adenovirus. The high-diversity nucleic acid library comprises or is derived from (1) a VH-CDR1 / 2 sub-library, (2) a plurality of VH-CDR3 sub-libraries, and (3) a VL sub-library, each of which comprises a plurality of members. Preferably, each member of the sub-libraries comprises at least one random cassette that has a plurality of degenerate base positions. In an especially preferred embodiment, at least portions of at least two members of the VH-CDR1 / 2 sub-library, the plurality of VH-CDR3 sub-libraries, and the VL sub-library are recombined to form an expression library member in an expression library, wherein each member of the expression library encodes a distinct antibody or antibody fragment.
Description
technical field [0001] The field of the invention is compositions and methods for ultra-high diversity antibody libraries, in particular as it relates to mRNA display libraries and to the use of mRNA display libraries for the generation of recombinant high affinity binders. Background technique [0002] The Background Description includes information useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, nor is any publication specifically or implicitly referenced to be prior art. [0003] All publications and patent applications herein are incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. Where a definition or usage of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, ...
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IPC IPC(8): C12N15/10C12N7/00C07K16/00C40B30/04C40B40/02
CPCC07K16/00C12N15/1062C07K16/005C07K2317/565C07K2317/622C07K2317/92C07K16/2827C07K16/244C07K16/2878C07K16/248C07K16/2803C07K16/2818C12N2710/10343C12N15/1037C12N7/00C40B30/04C40B40/02C12N2710/10011C07K2319/01
Inventor 克利福德·安德斯·奥尔森卡伊万·尼亚兹
Owner NANTBIOSCI