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Anti-ly6g6d antibodies and methods of use

An antibody, multispecific antibody technology, applied in the direction of antibodies, antibody medical components, chemical instruments and methods, etc.

Active Publication Date: 2022-08-05
GENENTECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] There is an unmet need in the field to develop effective bispecific antibody-based immunotherapies (e.g., bispecific anti-LY6G6D antibody-based immunotherapies) for the treatment of cancer (e.g., CRC)

Method used

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  • Anti-ly6g6d antibodies and methods of use
  • Anti-ly6g6d antibodies and methods of use
  • Anti-ly6g6d antibodies and methods of use

Examples

Experimental program
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Effect test

example 1

[0537] Example 1. LY6G6D is a surface marker of colorectal cancer cells and has restricted expression in normal tissues

[0538] Expression of lymphocyte antigen 6 family member G6D (LY6G6D) (SEQ ID NO:75) in human normal and tumor tissues using The Cancer Genome Atlas (TCGA) (Grossman et al., New England Journal of Medicine, 375(12):1109 -1112) and Genotype-Tissue Expression Project (GTEx) data (Pierson et al., PLoS ComputBiol, 11, e1004220, 2015) and immunohistochemistry (IHC).

[0539] A. Expression of LY6G6D

[0540] Figure 1A Expression of LY6G6D and lymphocyte antigen 6 family member G6F (LY6G6F) in normal and tumor tissues in human tissues from TCGA data is shown. Among tumor tissues, the colon with the highest indication of LY6G6D expression was the colon, and LY6G6D was significantly overexpressed only in colon tumor tissues. Normal colon tissue also showed some degree of LY6G6D expression, but at much lower levels. Interestingly, LY6G6F expression (>1 nRPKM) was ...

example 2

[0545] Example 2. Manufacturing responsibility for anti-LY6G6D 1G4 arm, anti-LY6G6D clone generation, epitope mapping and humanization

[0546] A. Manufacturing responsibility for the anti-LY6G6D 1G4 arm

[0547] Anti-LY6G6D TDB containing a chimeric anti-LY6G6D 1G4 arm and an anti-CD3 38E4.v1 arm demonstrated in vitro killing of HT55 cells (a human colon cancer cell line) ( Figure 3A ) and targeting xenografts LS1034 and HT55 tumors in NSG TM In vivo activity in mice ( Figure 3B ). 1G4 is a mouse hybridoma antibody; chimeric 1G4 (ch1G4) is a mouse / human chimeric antibody in which the mouse variable domains (VH and VL) of 1G4 are respectively associated with a N297G amino acid substitution mutation in CH2 And human heavy chain constant domains (CH1, CH2 and CH3) and human light chain constant domains (CL) comprising "hole" regions are genetically fused. A humanized version of the 1G4 arm was generated and demonstrated in vitro and in vivo efficacy ( Figure 3C and 3D )...

example 3

[0585] Example 3. Sequence and crystal structure of anti-LY6G6D antibody hu.20A12.QNTv12

[0586] As described in Example 2, the humanized rabbit antibody 20A12.QNTv12 (Example 2) with overlapping epitopes with 1G4 was identified as a potent anti-LY6G6D antibody. 20A12.QNTv12 as a TDB exhibits high binding affinity for human Ly6G6D at 37°C (K D is about 2 nM for 1G4 and about 16 nM for 1G4), has comparable binding affinity to human and cynomolgus LY6G6D, and exhibits good results in BV ELISA assays, expression tests and molecular assessment (MA) thermal and oxidation tests. The amino acid sequence of 20A12.QNTv12, including variants modified to contain charge pairs for single cell preparation, and the crystal structure of 20A12.QNTv12 bound to LY6G6D are described below.

[0587] A.20A12.Amino acid sequence of QNTv12

[0588] The amino acid sequences of the heavy and light chain variable regions of 20A12.QNTv12 are in Figure 5A and 5B shown in (SEQ ID NOs: 22 and 23). 20...

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Abstract

Provided herein are anti-Ly6G6D (lymphocyte antigen 6 complex, locus G61) antibodies and methods of use thereof.

Description

[0001] sequence listing [0002] This application contains a Sequence Listing, which has been submitted electronically in ASCII format and is incorporated herein by reference in its entirety. The ASCII copy was created on December 10, 2020, named 50474-184WO2_Sequence_Listing_12.10.20_ST25, and is 146,127 bytes in size. technical field [0003] Provided herein are anti-Ly6G6D (lymphocyte antigen 6 complex, locus G61) antibodies and methods of use thereof. Background technique [0004] Cancer remains one of the deadliest threats to human health. Cancer affects more than 1.7 million new patients each year in the United States and is the second leading cause of death after heart disease, accounting for about a quarter of all deaths. Colorectal cancer (CRC), in particular, is the third leading cause of cancer death in the United States, and the five-year survival rate for patients with advanced CRC is poor. Cancers, such as CRC, represent a significant and increasing societal...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61P35/00C07K14/725C07K16/28C07K16/30C07K16/46A61K39/00
CPCC07K16/28C07K16/3046C07K16/2809A61P35/00G01N33/57419G01N33/57492C07K2317/565C07K2317/567C07K2317/56C07K2317/92C07K2317/31C07K2317/73C07K2317/24C07K2317/33C07K2299/00A61K2039/505G01N2333/705C07K16/30A61K39/39558C07K2317/71C07K2317/72C07K2317/90C07K2317/41C07K16/468C07K14/70539C07K16/2824A61K2039/507C07K2317/30
Inventor W·林C·施皮斯L·孙吴雁C·P.C.·邱W·C·达博恩M·A·狄龙
Owner GENENTECH INC
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