Protein scaffolds and uses thereof
AssigneeAvidia Research Institute
InventorsWillem Stemmer, Martin Vogt, Joost Kolkman, Josh Silverman
Life of this patent
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Abstract
The present invention provides thrombospondin, thyroglobulin and trfoil/PD monomer domains and multimers comprising the monomer domains are provided. Methods, compositions, libraries and cells that express one or more library member, along with kits and integrated systems, are also included in the present invention.
Claims28
A method for identifying a monomer domain that binds to a target molecule, the method comprising,
- a) providing a library of non-naturally-occurring monomer domains, wherein the monomer domain is selected from the group consisting of:
- a thrombospondin monomer domain, a trefoil monomer domain, and a thyroglobulin monomer domain,
- wherein the thrombospondin monomer domain comprises the following sequence:
- (wxxWxx)C1sxtC2xxGxx(x)xRxrxC3xxxx(Px
- (SEQ ID NO:2)
- x)xxxxxC4xxxxxx(x)xxxC5(x)xxxxC6;
- the trefoil monomer domain comprises the following sequence:
- C1(xx)xxxpxxRxnC2gx(x)pxitxxxC3xxxgC4
- (SEQ ID NO:8)
- C5fdxxx(x)xxxpwC6f;
- and
- the thyroglobulin monomer domain comprises the following sequence:
- C1xxxxxxxxxxxxxxx(xxxxxxxxxx)xxxxxxxy
- (SEQ ID NO:3)
- xPxC2xxxGxyxxxQC3x(x)s(xxx)xxgxC4WC5V
- dxx(x)GxxxxGxxxxxgxx(xx)xC6;
- wherein “x” is any amino acid;
- b) screening the library of monomer domains for affinity to a first target molecule;
- and
- c) identifying at least one monomer domain that binds to at least one target molecule.
A protein, comprising a non-naturally occurring monomer domain that specifically binds to a target molecule
- wherein the target molecule is not bound by a naturally-occurring monomer domain at least 90% identical to the non-naturally occurring monomer domain,
- wherein the non-naturally occurring monomer domain is selected from the group consisting of:
- a thrombospondin monomer domain, a trefoil monomer domain, and a thyroglobulin monomer domain.
A library of proteins comprising non-naturally-occurring monomer domains, wherein the monomer domain is selected from the group consisting of:
- a thrombospondin monomer domain, a trefoil monomer domain, and a thyroglobulin monomer domain,
- wherein the thrombospondin monomer domain comprises the following sequence:
- (wxxWxx)C1sxtC2xxGxx(x)xRxrxC3xxxx(Px
- (SEQ ID NO:2)
- x)xxxxxC4xxxxxx(x)xxxC5(x)xxxxC6;
- the trefoil monomer domain comprises the following sequence:
- C1(xx)xxxpxxRxnC2gx(x)pxitxxxC3xxxgC4
- (SEQ ID NO:8)
- C5fdxxx(x)xxxpwC6f;
- and
- the thyroglobulin monomer domain comprises the following sequence:
- C1xxxxxxxxxxxxxxx(xxxxxxxxxx)xxxxxxxy
- (SEQ ID NO:3)
- xPxC2xxxGxyxxxQC3x(x)s(xxx)xxgxC4WC5V
- dxx(x)GxxxxGxxxxxgxx(xx)xC6;
- wherein “x” is any amino acid.
Dependencies are inferred from the claim text.