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Isolation of therapeutic target specific VNAR domains to ICOSL

A specific, targeted analyte technology, applied in the field of neoantigen receptor domains, which can solve the problems of diversity limitation and achieve high affinity effect

Inactive Publication Date: 2016-04-27
THE UNIV COURT OF THE UNIV OF ABERDEEN REGENT WALK
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Studies in juvenile nurse sharks have shown that the isotype lineage and the resulting diversity of IgNAR domains that increase response to any external challenge is restricted to the D-region fusion isoform known as type III

Method used

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  • Isolation of therapeutic target specific VNAR domains to ICOSL
  • Isolation of therapeutic target specific VNAR domains to ICOSL
  • Isolation of therapeutic target specific VNAR domains to ICOSL

Examples

Experimental program
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Embodiment Construction

[0072] In one embodiment of the present invention, an antigen-specific antigen-binding molecule is provided, which contains the amino acid sequence shown in formula (I)

[0073] A-X-B-Y-C(I)

[0074] in,

[0075] A- is SEQ ID NO: 1 or SEQ ID NO: 4

[0076] X is a CDR1 region of 5, 6 or 7 amino acid residues

[0077] B - for SEQ ID NO: 2 or SEQ ID NO: 5

[0078] Y is a CDR3 region of 8, 9, 10, 11, 12, 13, 14, 15, 16 or 17 amino acid residues

[0079] C- is SEQ ID NO: 3 or SEQ ID NO: 6

[0080] or sequences at least 50% homologous to them,

[0081] Among them, SEQ ID NO: 1 is TRVDQTPRTATKETGESLTINCVLTDT, TRVDQTPRTATKETGESLTINCVVTGA

[0082] SEQ ID NO: 2 is TSWFRKNPGTTDWERMSIGGRYVESVNKGAKSFSLRIKDLTVADSATYYCKA or TSWFRKNPGTTDWERMSIGGRYVESVNKGAKSFSLRIKDLTVADSATYICRA

[0083] SEQ ID NO: 3 is DGAGTVLTVN

[0084] SEQ ID NO: 4 is ASVNQTPRTATKETGESLTINCVLTDT

[0085] SEQ ID NO: 5 is TYWYRKNPGSSNQERISISGRYVESVNKRTMSFSLRIKDLTVADSATYYCKA or TYWYRKNPGSSNQERISISGRYVESVNKRTMSFSLRIKDL...

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Abstract

The present invention provides ICOSL specific antigen binding molecules which are isolated from immunized and synthetic Elasmobranchii derived libraries. In particular, the present invention relates to shark Variable New Antigen Receptor (VNAR) domains that specifically bind and neutralize the activity of human Induced Co-Stimulatory Ligand (ICOSL). The neutralizing VNAR domains are isolated from two independent sources; an immunized nurse shark library and a synthetic spiny dogfish framework fusion library. The molecules may be formulated as pharmaceutical compositions and used in medicine.

Description

technical field [0001] The present invention relates to the isolation and characterization of natural and non-natural binding molecules with high affinity antigen specificity isolated from immunized and synthetic elasmobranch derived libraries. In particular, the present invention relates to specifically binding and neutralizing inducible co-stimulatory ligand (InducedCo-StimulatoryLigand, ICOSL) (as an important regulator of immune function molecules) active shark variable neoantigen receptor (VNAR) structure area. Neutralizing VNAR domains were isolated from two independent sources; one from an immunized nurse shark library and one from a synthetic squalid framework fusion library. Background technique [0002] Biologics-based monoclonal antibodies (mAbs) have several advantages over small molecules, such as their continued clinical success and subsequent economic value to biotech and biopharmaceutical companies. The inherent ability to specifically bind to a target and ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/13C07K16/00C07K16/18
CPCC07K16/18C07K2317/20C07K2317/565C07K2317/567C07K2317/569C07K2317/73C07K2317/76C07K2317/92C07K16/005C07K16/2827A61P37/02A61P43/00A61K49/0002C07K2317/24G01N33/6872G01N2333/70532A61K2039/505C07K16/28C07K16/2803C07K16/40C07K2317/14C12N15/1037
Inventor C·J·巴雷勒W·J·J·芬莱A·达尔马宁-希恩
Owner THE UNIV COURT OF THE UNIV OF ABERDEEN REGENT WALK
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