Polypeptides antagonizing Wnt signaling in tumor cells
AssigneeAblynx N.V.
InventorsVittoria Zinzalla, Klaus-Peter Kuenkele, Marie-Ange Buyse, Karen Cromie, Stephanie Staelens, Beatrijs Strubbe
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Abstract
The invention provides LRP5-binding polypeptides, and more specifically LRP5-binding immunoglobulin single variable domain constructs which can inhibit Wnt signaling pathways. The invention also relates to specific sequences of such polypeptides, methods of their production, and methods of using them, including methods of treatment of diseases such as cancer.
Claims8
A nucleic acid molecule encoding a biparatopic polypeptide comprising a first low-density lipoprotein receptor-like 5 protein (LRP5) epitope-binding domain, which binds a Wnt3a binding region of LRP5, wherein said first LRP5 epitope binding domain comprises a first immunoglobulin single variable domain (ISVD), and a second LRP5 epitope-binding domain, which binds a Wnt1 binding region of LRP5, wherein said second LRP5 epitope-binding domain comprises an ISVD, wherein said polypeptide comprising said first and said second ISVD are each selected from the group consisting of ISVDs (i) to (iv):
- (i) an ISVD comprising the following complementarity-determining region (CDR) sequences:
- (SEQ ID NO:
- 1)
- CDR1:
- TYVMG,
- (SEQ ID NO:
- 2)
- CDR2:
- AISWSGGSTYYADSVKG,
- (SEQ ID NO:
- 3)
- CDR3:
- SRGTSTPSRASGVSRYDY,
- (ii) an ISVD comprising the following CDR sequences:
- (SEQ ID NO:
- 4)
- CDR1:
- RYAVA,
- (SEQ ID NO:
- 5)
- CDR2:
- AITWSSGRIDYADSVKG,
- (SEQ ID NO:
- 6)
- CDR3:
- DRRPRSTGRSGTGSPSTYDY,
- (iii) an ISVD comprising the following CDR sequences:
- (SEQ ID NO:
- 7)
- CDR1:
- IGAMG,
- (SEQ ID NO:
- 8)
- CDR2:
- AVSSGGSTYYVDSVKG,
- (SEQ ID NO:
- 9)
- CDR3:
- ETGPYGPPKRDY,
- (iv) an ISVD comprising the following CDR sequences:
- (SEQ ID NO:
- 10)
- CDR1:
- INAMG,
- (SEQ ID NO:
- 8)
- CDR2:
- AVSSGGSTYYVDSVKG,
- (SEQ ID NO:
- 9)
- CDR3:
- ETGPYGPPKRDY.
A method for the inhibition of tumor growth in a human being or an animal in need thereof comprising administrating a therapeutic agent comprising a biparatopic polypeptide comprising a first low-density lipoprotein receptor-like 5 protein (LRP5) epitope-binding domain, which binds a Wnt3a binding region of LRP5, wherein said first LRP5 epitope binding domain comprises a first immunoglobulin single variable domain (ISVD), and a second LRP5 epitope-binding domain, which binds a Wnt1 binding region of LRP5, wherein said second LRP5 epitope-binding domain comprises an ISVD, wherein said polypeptide comprising said first and said second ISVD are each selected from the group consisting of ISVDs (i) to (iv):
- (i) an ISVD comprising the following complementarity-determining region (CDR) sequences:
- (SEQ ID NO:
- 1)
- CDR1:
- TYVMG,
- (SEQ ID NO:
- 2)
- CDR2:
- AISWSGGSTYYADSVKG,
- (SEQ ID NO:
- 3)
- CDR3:
- SRGTSTPSRASGVSRYDY,
- (ii) an ISVD comprising the following CDR sequences:
- CDR1:
- (SEQ ID NO:
- 4)
- RYAVA,
- CDR2:
- (SEQ ID NO:
- 5)
- AITWSSGRIDYADSVKG,
- CDR3:
- (SEQ ID NO:
- 6)
- DRRPRSTGRSGTGSPSTYDY,
- (iii) an ISVD comprising the following CDR sequences:
- (SEQ ID NO:
- 7)
- CDR1:
- IGAMG,
- (SEQ ID NO:
- 8)
- CDR2:
- AVSSGGSTYYVDSVKG,
- (SEQ ID NO:
- 9)
- CDR3:
- ETGPYGPPKRDY,
- and
- (iv) an ISVD comprising the following CDR sequences:
- CDR1:
- (SEQ ID NO:
- 10)
- INAMG,
- CDR2:
- (SEQ ID NO:
- 8)
- AVSSGGSTYYVDSVKG,
- CDR3:
- (SEQ ID NO:
- 9)
- ETGPYGPPKRDY.
Dependencies are inferred from the claim text.