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Bispecific Anti-psma x Anti-cd28 antibodies and uses thereof

A bispecific and specific technology, applied in the field of bispecific antigen-binding molecules, can solve problems such as unpredictable cytokine responses

Pending Publication Date: 2021-02-09
REGENERON PHARM INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Toxicology studies in cynomolgus monkeys fail to predict cytokine responses observed in humans

Method used

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  • Bispecific Anti-psma x Anti-cd28 antibodies and uses thereof
  • Bispecific Anti-psma x Anti-cd28 antibodies and uses thereof
  • Bispecific Anti-psma x Anti-cd28 antibodies and uses thereof

Examples

Experimental program
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Effect test

preparation example Construction

[0185] Preparation of antigen-binding domains and construction of bispecific molecules

[0186] 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 PSMA) 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 individual components (eg, heavy and light chains) of a multispecific antigen binding molecule of the invention are derived from chimeric, humanized, or fully human antibodies. Methods for making such antibodies are well known in the art. For example, VELOCIMMUNE can be used TM Techniques One or more heav...

example

[0233] 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. 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.

[0234] Summary

[0235] Recent clinical success of tumor-specific antigen (TSA) or tumor-associated antigen (TAA)-CD3 bispecific antibodies (such as anti-PSMAxCD3 bispecific antibodies) is transforming cancer immunotherapy. The TAA-CD3 antibody provides a relatively safe and ready-to-use therapeutic solution that may prove to be an important...

example 1

[0246] Example 1. Construction of anti-PSMAxCD28 antibodies

[0247] Production of anti-CD28 antibodies

[0248] By using human CD28 protein fused to the Fc portion of mouse IgG2a, or using cells expressing CD28, or using DNA encoding CD28 Mice (ie, engineered mice comprising DNA encoding human immunoglobulin heavy chain and kappa light chain variable regions) were immunized to obtain anti-CD28 antibodies. Antibody immune responses were monitored by a CD28-specific immunoassay. When the desired immune response is achieved, splenocytes are harvested and fused with mouse myeloma cells to maintain their viability and form hybridoma cell lines. Hybridoma cell lines were screened and selected to identify cell lines producing CD28-specific antibodies. Several anti-CD28 chimeric antibodies (ie, antibodies with human variable domains and mouse constant domains) were obtained using this technique. Additionally, several fully human anti-CD28 antibodies were isolated directly from a...

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PUM

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Abstract

The present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD28, and a second antigen-binding molecule that specifically binds human PSMA. In certain embodiments, the bispecific antigen- binding molecules of the present invention are capable of inhibiting the growth of tumors expressing PSMA, such as prostate tumors.The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an up-regulated or induced targeted immune response is desiredand / or therapeutically beneficial.

Description

[0001] Cross References to Related Applications [0002] This application relates to and claims U.S. Provisional Application No. 62 / 688,227, filed June 21, 2018, U.S. Provisional Application No. 62 / 781,930, filed December 19, 2018, filed December 19, 2018 Priority to U.S. Provisional Application No. 62 / 781,980 and U.S. Provisional Application No. 62 / 815,878, filed March 8, 2019. The entire contents of the aforementioned applications are expressly incorporated herein by reference. [0003] sequence listing [0004] This application contains a Sequence Listing that has been filed electronically in ASCII format and is hereby incorporated by reference in its entirety. The ASCII copy, created on June 20, 2019, is named 10367WO01_118003-45220_SL.TXT and is 48,690 bytes in size. technical field [0005] The present invention relates to bispecific antigen binding molecules that bind CD28 and a target molecule such as PSMA and methods of use thereof. Background technique [00...

Claims

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Application Information

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IPC IPC(8): A61P35/00C07K16/28C07K16/30A61K39/00
CPCC07K16/2818C07K16/3069C07K2317/31C07K2317/92C07K2317/76C07K2317/75A61K2039/507A61K2039/57A61P35/00A61K2039/505C07K2317/565C07K2317/732C07K2317/734C07K2317/74C07K2317/94
Inventor A·J·墨菲D·斯科克斯J·韦特E·乌尔曼A·赫尔曼E·史密斯L·哈伯G·D·扬科普洛斯
Owner REGENERON PHARM INC
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