Isolation of therapeutic target specific VNAR domains to ICOSL
AssigneeThe University Court of the University of Aberdeen
InventorsCaroline Jane Barelle, William James Jonathan Finlay, Alfredo Darmanin-Sheehan
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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.
Claims6
An ICOSL specific antigen binding molecule comprising an amino acid sequence represented by the formula (I)
- A-X-B-Y-C (I);
- wherein:
- A is SEQ ID NO:
- 1, SEQ ID NO:
- 4 or SEQ ID NO:
- 7, or a sequence at least 87% identical to SEQ ID NO:
- 1, SEQ ID NO:
- 4 or SEQ ID NO:
- 7,
- X is a CDR1 region of SEQ ID NO:
- 95,
- B is SEQ ID NO:
- 2, SEQ ID NO:
- 5 or SEQ ID NO:
- 8, or a sequence at least 87% identical to SEQ ID NO:
- 2, SEQ ID NO:
- 5 or SEQ ID NO:
- 8,
- Y is a CDR3 region of SEQ ID NO:
- 122, and
- C is SEQ ID NO:
- 3, SEQ ID NO:
- 6, or SEQ ID NO:
- 9, or a sequence at least 87% identical to SEQ ID NO:
- 3, SEQ ID NO:
- 6, or SEQ ID NO:
- 9,
- in which:
- SEQ ID NO:
- 1 is
- TRVDQTPRTATKETGESLTINCVLTDT,
- TRVDQTPRTATKETGESLTINCWTGA
- SEQ ID NO:
- 2 is
- TSWFRKNPGTTDWERMSIGGRYVESVNKGAKSFSLRIKDLTVADSATYY
- CKA
- or
- TSWFRKNPGTTDWERMSIGGRYVESVNKGAKSFSLRIKDLTVADSATYI
- CRA
- SEQ ID NO:
- 3 is
- DGAGTVLTVN
- SEQ ID NO:
- 4 is
- ASVNQTPRTATKETGESLTINCVLTDT
- SEQ ID NO:
- 5 is
- TYWYRKNPGSSNQERISISGRYVESVNKRTMSFSLRIKDLTVADSATYY
- CKA
- or
- TYWYRKNPGSSNQERISISGRYVESVNKRTMSFSLRIKDLTVADSATYI
- CRA
- SEQ ID NO:
- 6 is
- YGAGTVLTVN
- SEQ ID NO:
- 7 is
- ARVDQTPRSVTKETGESLTINCVLRDP
- or
- ARVDQTPRSVTKETGESLTINCVLRDA
- or
- ARVDQTPRSVTKETGESLTINCVLRDG
- or
- ARVDQTPRSVTKETGESLTINCVLRES
- SEQ ID NO:
- 8 is
- TCWYRKKSGSTNEESISKGGRYVETVNSGSKSFSLRINDLTVEDGGTYR
- CGA
- or
- TCWSRKKSGSTNEESISKGGRYVETVNSGSKSFSLRINDLTVEDGGTYR
- CGL,
- TCWTRKKSGSTNEESISKGGRYVETVNSGSKSFSLRINDLTVEDGGTYR
- CAL,
- TCWYRKKSGSTNEESISKGGRYVETVNSGSKSFSLRINDLTVEDGGTYR
- CGV,
- TCWYRKKSGSTNEESISKGGRYVETVNSGSKSFSLRINDLTVEDGGTYR
- CGH,
- TCWYRKKSGSTNEESISKGGRYVETVNSGSKSFSLRISDLTVEDGGTYR
- CGH,
- SEQ ID NO:
- 9 is
- CGGGTVVTVN, CGGGTAVTVN, CGDGTAVTVN,
- or
- CGDGTAVTVN,
- SEQ ID NO:
- 95 is DYGLFS, and
- SEQ ID NO:
- 122 is FTWPWEWPDRWFRPWY.
Dependencies are inferred from the claim text.