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EGFRxCD28 MULTISPECIFIC ANTIBODIES

A multi-specific and bi-specific technology, applied in the direction of antibodies, antibody medical components, specific peptides, etc., can solve the problem of insufficient tumor clearance and anti-tumor response

Pending Publication Date: 2021-11-16
REGENERON PHARM INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Interruption of T cell activation by blocking PD-1 release, but its efficacy as a single agent is often insufficient for tumor clearance and durable antitumor responses

Method used

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  • EGFRxCD28 MULTISPECIFIC ANTIBODIES
  • EGFRxCD28 MULTISPECIFIC ANTIBODIES
  • EGFRxCD28 MULTISPECIFIC ANTIBODIES

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0353] Preparation of antigen-binding domains and construction of bispecific molecules

[0354] 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, CD28 and EGFR) can be suitably arranged relative to each other to generate bispecific antigen-binding molecules of the invention using conventional methods. (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 the multispecific antigen binding molecules of the invention are derived from chimeric antibodies, humanized antibodies, or Fully human antibody. Methods for preparing such antibodies are well known in the art. For example, VELOCIMMUNE can be ...

example

[0414] 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 regard as their invention.

example 1

[0415] Example 1: Construction of anti-EGFRxCD28 antibody

[0416] Production of anti-EGFR antibodies

[0417] By directly administering an EGFR-expressing cell line (A431) with an adjuvant to stimulate an immune response to a DNA encoding a human immunoglobulin heavy-chain variable region and a universal light-chain variable region mice to obtain anti-EGFR antibodies. That is, antibodies produced in this mouse have different heavy chain variable regions but substantially identical light chain variable regions.

[0418] Antibody immune responses were monitored by EGFR-specific immunoassay. When the desired immune response is achieved, anti-EGFR antibodies are isolated directly from antigen-positive B cells without fusion with myeloma cells, as described in US7,582,298.

[0419] Table 1 shows the amino acid sequence identifiers of the heavy and light chain variable regions and CDRs of selected anti-EGFR antibodies of the invention. The corresponding nucleic acid sequence ...

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Abstract

The present invention provides multispecific antibodies that bind to EGFR and CD28 (EGFRxCD28) as well as anti-EGFR antibodies. Such antibodies may be combined with a further therapeutic agent such as an anti-PD1 antibody. Methods for treating cancers (e.g., EGFR-expressing cancer) by administering the antibodies (e.g., and combinations thereof with anti-PD1 ) are also provided. The EGFRxCD28 antibodies of the present invention embody a tumor-targeted immunotherapeutic modality combined with PD-1 inhibition. These bispecific antibodies bind a tumor-specific antigen (TSA) (EGFR) with one arm and the co-stimulatory receptor, CD28, on T -cells with the other arm. Combination therapy with PD-1 inhibitors specifically potentiated intra-tu moral T cell activation, promoting an effector memory-like T cell phenotype without systemic cytokine secretion in a variety of syngeneic and human tumor xenograft models. Combining this class of CD28-co-stimulatory bispecific antibodies with the clinically validated anti-PD-1 treatment provides a well-tolerated antibody therapy with markedly enhanced anti-tumor efficacy.

Description

[0001] related application [0002] This application is related to and claims priority to U.S. Provisional Application No. 62 / 822,124, filed March 22, 2019. The entire contents of the aforementioned applications are expressly incorporated herein by reference. technical field [0003] The present invention relates to antibodies that bind to EGF receptor and CD28 and methods of use thereof, eg, for the treatment or prevention of cancer. [0004] sequence listing [0005] This application contains a Sequence Listing that has been filed electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy was created on March 19, 2020, is named 118003-10620_SL.txt and is 63,481 bytes in size. Background technique [0006] The ability of T cells to recognize and kill their cellular targets—such as virus-infected cells or tumor cells—depends on a series of coordinated interactions. Foremost among these is the recognition and binding of targ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/28C07K16/30A61P35/00C07K16/40
CPCC07K16/2818C07K16/2863C07K16/3092C07K16/2809A61P35/00C07K2317/31C07K2317/33C07K2317/34C07K2317/73C07K2317/75C07K2317/76C07K16/40C07K2317/92C07K2317/52A61K2039/505A61K2039/507A61K2039/572C07K2317/24C07K2317/35C07K16/3069A61K9/0019A61K39/3955A61K45/06C07K2317/565C12N5/0682
Inventor D·思科科斯A·J·墨菲G·D·扬科普洛斯L·哈伯林家杨
Owner REGENERON PHARM INC
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