Engineering multifunctional and multivalent molecules with collagen xv trimerization domain
AssigneeLeadartis, S.L.
InventorsLuis Álvarez Vallina, Ángel Cuesta-Martínez, Noelia Sainz Pastor, Laura Sanz Alcober
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Abstract
The invention relates generally to a new trimerization domain useful for developing multifunctional and multivalent complexes. Particularly, the invention relates to the design of trimeric polypeptide complexes using polypeptide structural elements derived from the collagen XV protein, and their use in diagnostic and therapeutic systems in vivo and in vitro. The invention also relates to nucleic acids and vectors useful for producing said trimeric complexes.
Claims22
A trimeric polypeptide complex comprising three monomer polypeptides, wherein:
- (i) each of said monomer polypeptides comprises a collagen XV trimerizing structural element (XVTSE), wherein said XVTSE comprises:
- a) a polypeptide having the amino acid sequence shown in SEQ ID NO:
- 1, or
- b) a polypeptide having at least 60% amino acid sequence identity with the sequence shown in SEQ ID NO:
- 1, and maintains the ability to form trimers;
- and
- (ii) at least one of said monomer polypeptides is covalently linked to at least one heterologous moiety (HM),
- with the proviso that at least one of said three monomer polypeptides does not contain an endostatin domain or a restin domain.
A polypeptide selected from the group consisting of:
- (i) a polypeptide consisting of the amino acid sequence shown in SEQ ID NO:
- 1,
- (ii) a polypeptide comprising the amino acid sequence shown in SEQ ID NO:
- 1 wherein said polypeptide does not contain an endostatin domain or a restin domain and
- (iii) a polypeptide having at least 60% amino acid sequence identity with the sequence shown in SEQ ID NO:
- 1, wherein said polypeptide has the ability to form trimers and wherein said polypeptide does not contain an endostatin domain or a restin domain.
A polynucleotide encoding a fusion protein, said fusion protein comprising (i) a collagen XV trimerizing structural element (XVTSE) and (ii) at least one heterologous moiety (HM),
- wherein said XVTSE comprises:
- a) a polypeptide having the amino acid sequence shown in SEQ ID NO:
- 1, or
- b) a polypeptide having at least 60% amino acid sequence identity with the sequence shown in SEQ ID NO:
- 1, and maintains the ability to form trimers;
- and
- wherein said heterologous moiety is a polypeptide other than endostatin or restin.
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Dependencies are inferred from the claim text.