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Anti-human pd-l2 antibodies

A PD-L2, CDR-L2 technology, applied in the field of anti-human PD-L2 antibodies or their antigen-binding parts, can solve the problems of unmet medical needs and the absence of therapeutic antibodies

Pending Publication Date: 2020-10-09
アバセラピューティクスアーゲー
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, there are no therapeutic antibodies known to bind to PD-L2
There is a large unmet medical need as the optimal therapy for PD-L2 has not been discovered

Method used

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  • Anti-human pd-l2 antibodies

Examples

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example

[0806] The following are examples of methods and compositions of the invention. It is understood that various other embodiments may be practiced, given the general description provided above.

example 1

[0807] Example 1: Production and purification of human anti-PD-L2 antibodies

[0808] Antibodies were produced using transgenic rats expressing human immunoglobulin loci (by replacing the endogenous rat immunoglobulin loci ), which has been reported in detail (Osborn et al., J Immunol 190:1481-1490, 2013 and WO 14 / 093908). Six rats were immunized by genetic immunization with a synthetic cDNA encoding the extracellular domain of human PD-L2 (Aldevron, Freiburg). Lymph nodes were collected from the three rats with the best immune responses and used to generate hybridomas. Supernatants from individual hybridoma clones were screened for their ability to bind to human PD-L2 expressed on the cell surface and subsequently block the PD-1 / PD-L2 interaction in a cell-based bioassay. Corresponding fusionomas exhibiting higher function-blocking activity were subcloned, and individual clones were re-examined for biological activity and sequenced. Several chimeric anti-PD-L2 antibodies ...

example 2

[0810] Example 2: Nucleotide and Amino Acid Sequences of Heavy and Light Chain Variable Regions

[0811] Human heavy and light chain variable regions were sequenced using next-generation sequencing methods (Absolute Antibodies Ltd, Oxford, UK). Table 3 presents the DNA sequence identifiers of the heavy and light chain variable regions and CDRs of human anti-PD-L2 antibodies. The corresponding amino acid sequence identifiers are shown in Table 4. Antibody has rat IgG2b Fc and human VH and fully human light chains (kappa or lambda). An antibody with a particular Fc isotype can be converted to an antibody with a different Fc isotype (eg, an antibody with rat IgG2b can be converted to an antibody with human IgG1, etc.). The variable domains (including CDRs) will be the same as indicated by the sequence identifiers in Tables 3 and 4, and thus the binding properties to the antigen are considered to be the same regardless of the nature of the Fc domain.

[0812] table 3

[0813] ...

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PUM

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Abstract

The present invention relates to anti-human PD-L2 antibodies, or the antigen binding parts thereof, which specifically bind human PD-L2 such that PD-L2 binding to PD-1 is blocked, wherein preferably said antibodies or antigen binding parts do not bind to mouse PD-L2 and human PD-L1 but bind to cyno PD-L2, preferably as determined by FACS analysis. The present invention also relates to nucleotide sequences encoding the anti-human PD-L2 antibodies, vectors and cells containing the nucleotide sequences. The antibodies and / or compositions of the invention are useful in human therapy, e.g., cancertherapy, and / or in cell-line based bioassays for determining T cell signalling.

Description

[0001] The present invention relates to an anti-human PD-L2 antibody or an antigen-binding portion thereof, which specifically binds to human PD-L2 such that PD-L2 is blocked from binding to PD-1, wherein preferably the antibody or antigen-binding portion does not bind Binding to mouse PD-L2 and human PD-L1 but to cynomolgus PD-L2 is preferably determined by FACS analysis. The present invention also relates to a nucleotide sequence encoding an anti-human PD-L2 antibody, a vector and a cell containing the nucleotide sequence. Antibodies and / or compositions of the invention are suitable for use in human therapy, such as cancer therapy, and / or in cell line-based bioassays to determine T cell signaling. Background technique [0002] The development of immune checkpoint pathway inhibitors has been the subject of intense research and drug development efforts aimed at cancer treatment. The programmed death-1 receptor (PD-1) and its ligands PD-L1 and PD-L2 represent a class of inhibi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/28
CPCC07K16/2827C07K2317/21C07K2317/24C07K2317/33C07K2317/565C07K2317/76C07K2317/92C07K2317/56
Inventor R·S·科勒薛公达L·克龙
Owner アバセラピューティクスアーゲー
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