Anti-fc epsilon-r1 alpha (fcer1a) antibodies, bispecific antigen-binding molecules that bind fcer1a and cd3, and uses thereof

An antigen-binding molecule, bispecific technology, applied to anti-Fcε-R1α (FCER1A) antibody, which can solve problems such as unreported effects

Pending Publication Date: 2021-06-01
REGENERON PHARM INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The α chain of FcεR1 binds to a single IgE antibody molecule, while the roles of β and γ chains in ligand binding have not been reported

Method used

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  • Anti-fc epsilon-r1 alpha (fcer1a) antibodies, bispecific antigen-binding molecules that bind fcer1a and cd3, and uses thereof
  • Anti-fc epsilon-r1 alpha (fcer1a) antibodies, bispecific antigen-binding molecules that bind fcer1a and cd3, and uses thereof
  • Anti-fc epsilon-r1 alpha (fcer1a) antibodies, bispecific antigen-binding molecules that bind fcer1a and cd3, and uses thereof

Examples

Experimental program
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preparation example Construction

[0197] Preparation of antigen-binding domains and construction of bispecific molecules

[0198] Antigen-binding domains specific for a particular antigen can be prepared by any antibody production technique known in the art. Once obtained, two different antigen-binding domains specific for two different antigens (eg, CD3 and FcεR1α) can be appropriately aligned relative to each other using conventional methods to generate bispecific antigen-binding molecules of the invention. (A discussion of exemplary bispecific antibody formats that can be used to construct bispecific antigen binding molecules of the invention is provided elsewhere herein). In certain embodiments, one or more of the individual components (e.g., heavy and light chains) of a multispecific antigen-binding molecule of the invention are derived from chimeric antibodies, humanized antibodies, or fully humanized antibodies. antibodies. Methods for preparing such antibodies are well known in the art. For example,...

example

[0245] The following examples are presented to provide those of ordinary skill in the art with a complete disclosure and description of how to make and use the methods and compositions of the invention, and are not intended to limit the scope of what the inventors believe to be their invention. Efforts have been made to ensure accuracy with respect to numbers used (eg, amounts, temperature, etc.), but some experimental errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, molecular weight is average molecular weight, temperature is in degrees Centigrade, and pressure is at or near atmospheric.

example 1

[0246] Example 1: Production of Antibodies

[0247] Generation of anti-FcεR1α antibody

[0248] By immunizing genetically modified mice with human FcεR1α antigen (e.g., hFcεR1α, SEQ ID NO:63), or by immunizing human FcεR1α antigens with human FcεR1α antigens engineered to contain DNA encoding human immunoglobulin heavy chain and kappa light chain variable regions. mice to obtain anti-FcεR1α antibodies.

[0249] After immunization, splenocytes were harvested from each mouse and either (1) fused with mouse myeloma cells to maintain their viability and form hybridomas and screened for FcεR1α specificity, or (2) using human FcεR1α fragments as binding B cells are sorted with a sorting reagent that identifies reactive antibodies (antigen positive B cells) (as described in US 2007 / 0280945A1).

[0250] Chimeric antibodies against FcεR1α were originally isolated with human variable regions and mouse constant regions. Antibodies are characterized and selected for desired propertie...

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Abstract

The present invention provides novel full-length human antibodies that bind to human Fc epsilon-R1 alpha (monospecific antibodies). The present invention also provides novel bispecific antibodies (bsAbs) that bind to both Fc epsilon-R1 alpha and CD3 and activate T cells via the CD3 complex in the presence of Fc epsilon-R1 alpha-expressing cells. The bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an up regulated or induced Fc epsilon-R1 alpha-targeted immune response is desired and / or therapeutically beneficial. For example, the bispecific antibodies of the invention are useful for the treatment of allergies, including anaphylaxis.

Description

[0001] related application [0002] This application is related to and claims priority from U.S. Provisional Application No. 62 / 721,921, filed August 23, 2018. The entire contents of the aforementioned applications are expressly incorporated herein by reference. [0003] Reference Sequence Listing [0004] This application incorporates by reference the Sequence Listing, filed in computer readable form as file 10480WO01_118003-45320_SL.txt, created on August 21, 2019, and containing 67,307 bytes. technical field [0005] The present invention relates to antibodies specific for FcεR1α, antigen-binding fragments thereof, and methods of use thereof. The invention also relates to bispecific antigen-binding molecules that bind FcεR1α and CD3 and methods of use thereof. Background technique [0006] FcεR1 is a high-affinity Fc receptor for immunoglobulin E (IgE), and FcεR1 is expressed in about 10 -10 The equilibrium dissociation constant of M (K D ) value combined with IgE. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61P37/08C07K16/28
CPCC07K16/283C07K16/2803C07K2317/31C07K2317/92C07K2317/73A61P37/08A61K2039/505C07K16/2809C07K2317/565
Inventor J·M·奥伦戈A·林南德J·H·金A·J·墨菲
Owner REGENERON PHARM INC
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