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Anti-human vista antibodies and use thereof

An antibody and antibody fragment technology, applied in the field of anti-human VISTA antibody and antibody fragment, anti-human VISTA antibody and antibody fragment, can solve the problem that anti-human VISTA antibody or antibody fragment has not been identified yet

Active Publication Date: 2019-05-21
IMMUNEXT INC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, as far as the inventors are aware, no anti-human VISTA antibody or antibody fragment that can elicit the effect of human VISTA has been identified before

Method used

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  • Anti-human vista antibodies and use thereof
  • Anti-human vista antibodies and use thereof
  • Anti-human vista antibodies and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0592] Example 1: Assay to screen for immunosuppressive anti-mouse VISTA antibodies

[0593] The inventors developed various assays for screening putative agonistic anti-mouse VISTA antibodies. like figure 1 In vitro and in vivo screening assays were used to identify immunosuppressive anti-VISTA monoclonal antibodies as shown in . exist figure 1 In experiments in A, purified T cells were plated on anti-CD3 in the presence of the indicated monoclonal antibodies for 72 hours. Proliferation was measured by H3 incorporation. exist figure 1 In the experiments of B, purified DO11.10T cells were stimulated by ISQ-pulsed APCs in the presence of the indicated antibodies for 6 days. Proliferation was measured by diluting the dye with CTV. exist figure 1 In the experiments in C, GVHD was induced by transferring C57BL / 6 cells into irradiated BALB / c recipients. Mice were injected intraperitoneally with 200 μg of antibody on days 0, 2, and 4 post-transfer and analyzed for survival...

Embodiment 2

[0598] Example 2: Identification of anti-VISTA antibodies that suppress autoimmunity in different autoimmune disease models

[0599] exist figure 2 In the experiments in A-F, the effects of different anti-mouse VISTA antibodies were again compared in different disease models. exist figure 2 In the experiment in A, NZB / WF1 mice were treated with Ab1 or hamster Ig (200 μg) 3 times / week from week 25 until the end of the experiment. "X" indicates the time point at which the control treatment group was all sacrificed. exist figure 2 In the experiment in B, mice were treated with 200 μg of antibody 3 hours before administration of 15 mg / kg (mpk) ConA for 3 hours and followed for survival for 80 hours. exist figure 2 In the experiments in C, mice were sequentially treated with Collagen II mAb followed by LPS, and arthritis was measured by measuring foot swelling. In these experiments, Ab1 and hamster Ig (200 μg) were administered 3 times every other day. exist figure 2...

Embodiment 3

[0605] Example 3: Development of human VISTA knock-in mice for screening of agonistic anti-human VISTA antibodies

[0606] The previous examples relate to the isolation and characterization of agonistic anti-mouse VISTA antibodies. To date, agonistic anti-human VISTA antibodies have never been reported in the literature. Although the present assignee and other groups have identified a very large number of antagonistic anti-human VISTA antibodies. Therefore, prior to the present invention, it was uncertain whether agonistic anti-human VISTA antibodies would be identified.

[0607] Such antibodies would be very beneficial as there are currently no approved human therapeutics that exploit the natural function of the NCR to suppress immune responses. Although Orencia (CTLA4-Ig) is potent, it works only by blocking the CD28-B7 interaction and pathway, and not by stimulating the down-regulated pathway. The involvement of this pathway may prove to be a revolution in the manageme...

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Abstract

The invention provides agonistic anti-human VISTA antibodies and antibody fragments. These agonist antibodies and antibody fragments may be used to potentiate or enhance or mimic VISTA's suppressive effects on T cell immunity and thereby suppress T cell immunity. These agonist antibodies and antibody fragments are especially useful in the treatment of autoimmunity, allergy, inflammatory conditions, GVHD, sepsis and transplant recipients. Screening assays for identifying these agonists are also provided.

Description

[0001] Related applications [0002] This application claims US Provisional Application No. 62 / 323,193, filed on April 15, 2016, US Provisional Application No. 62 / 343,355, filed on May 31, 2016, and US Provisional Application No. 62 / 343,355, filed on August 9, 2016. 62 / 372,362, US Provisional Application No. 62 / 385,627, filed September 9, 2016, US Provisional Application No. 62 / 425,184, November 22, 2016, US Provisional Application No. July 19, 2016 .62 / 363,929, U.S. Provisional Application No. 62 / 365,085, filed July 21, 2016, U.S. Provisional Application No. 62 / 385,805, filed September 9, 2016, U.S. Provisional Application No. 62 / 385,805, filed July 19, 2016 No. 62 / 363,931, US Provisional Application No. 62 / 365,102, filed July 21, 2016, US Provisional Application No. 62 / 385,871, filed September 9, 2016, US Provisional Application No. 62 / 385,871, filed July 19, 2016 Application No. 62 / 363,917, US Provisional Application No. 62 / 365,081, filed July 21, 2016, US Provisional Applic...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K45/06C07K16/28C07K16/30
CPCC07K16/2827A61P37/02A61P37/08A61P29/00C07K2317/565C07K2317/76C07K2317/75C07K2317/74C07K2317/92C07K2317/33A61K2039/505A61P35/00A61P35/02A61P31/00C07K2317/24C07K2317/522C07K2317/73C07K2317/52C07K2317/53A61K38/17C07K2317/21C07K2317/34A61P1/00A61P1/16A61P11/00A61P13/02A61P13/12A61P17/00A61P17/06A61P17/14A61P19/02A61P25/00A61P31/14A61P31/20A61P37/06A61P39/02A61P43/00A61P9/10Y02A50/30A61K38/16A61K39/00A61K39/395C07K14/705C07K16/42C07K16/46A61K39/3955A61K45/06C07K16/2803C07K16/2896C07K2317/31
Inventor M·莫里J·罗斯坦C·卡里尔R·J·诺勒S·德龙I·勒梅西埃
Owner IMMUNEXT INC
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