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Non-immunogenic single domain antibodies

A single-domain antibody, antibody recognition technology, used in immunoglobulins, non-central analgesics, anti-inflammatory agents, etc.

Inactive Publication Date: 2018-01-02
INHIBRX INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, even fully human antibodies and antibody fragments carry the risk of immunogenicity

Method used

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  • Non-immunogenic single domain antibodies
  • Non-immunogenic single domain antibodies
  • Non-immunogenic single domain antibodies

Examples

Experimental program
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Effect test

Embodiment

[0096] A direct anti-single domain antibody (ASDA) detection assay can be used to determine pre-existing ASDA in sera from human donors. In general, pre-existing antibodies in human serum can be identified by ELISA in which sdAbs are immobilized on plates and blocked with BSA. Human serum (neat or diluted in PBS + 0.01% Tween-20) was then incubated with plate-bound sdAbs. Unbound serum IgG was washed away, and any remaining antibody against the sdAb was detected using both anti-human Igκ and anti-human Igλ HRP-conjugated antibodies.

[0097] The indirect ASDA assay can be used to analyze multiple variants of a given sdAb in order to measure sdAb-specific serum antibody reactivity. Indirect ASDA involves immobilization of sdAb and blocking with BSA. Human serum (pure or diluted in PBS + 0.01% Tween-20) was then pre-incubated with soluble sdAb (either the same sdAb or a variant of the parental sdAb with a modification of the invention [mutation, truncation or extension]) , an...

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Abstract

The invention provides modifications within human or humanized single domain antibody fragments (sdAbs) that prevent recognition by pre-existing antibodies, to isolated polypeptides that include thesemodifications, and to methods and uses thereof.

Description

[0001] related application [0002] This application claims the benefit of US Provisional Application No. 62 / 106,035, filed January 21, 2015, the contents of which are hereby incorporated by reference in their entirety. field of invention [0003] The present invention relates generally to modifications within human or humanized single domain antibody fragments (sdAbs) that prevent recognition by pre-existing antibodies, to isolated polypeptides comprising these modifications and to methods and uses thereof. [0004] Introduction of Sequence Listing [0005] The contents of the text file named "INHI018001WO_ST25" created on January 20, 2016 and having a size of 10.0 KB are hereby incorporated by reference in its entirety. Background of the invention [0006] Clinical immunogenicity of biotherapeutics can limit efficacy and contribute to adverse events. Both cellular and humoral immunogenicity can be problematic in the clinical setting. Most commonly observed immunogenicit...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/00C07K16/42
CPCC07K16/00C07K16/4283C07K2317/569C07K2317/567C07K2317/56C07K2317/24A61P29/00A61P37/06
Inventor B.P.埃克尔曼J.C.蒂默Q.德弗劳瓦
Owner INHIBRX INC
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