Collagen-binding agent compositions and methods of using the same
The invention generally relates to collagen-binding agent compositions and methods of using the same. More specifically, the invention relates in part to new collagen-binding agent compositions and methods that may be used to treat damaged collagen within tissues or used to specifically target therapeutics to tissues containing undamaged or damaged collagen.
1. A collagen-binding agent comprising a first collagen-binding domain and a second collagen-binding domain linked by a domain linker and a therapeutic agent linked to at least one of the collagen-binding domains by a therapeutic agent linker,
wherein the collagen-binding agent lacks collagenase activity;
wherein the therapeutic agent is fibroblast growth factor (FGF);
wherein the two collagen-binding domains bind to collagen with a K D of between 100 μM and 0.1 nM;
wherein the first collagen-binding domain is selected from the group consisting of the polypeptides of SEQ ID NOs: 1-14, and the second collagen-binding domain is selected from the group consisting of the polypeptides of SEQ ID NOs: 15-30; and
wherein the C-terminus of the first collagen-binding domain is linked to the N-terminus of the second collagen-binding domain by the domain linker.
2. The collagen-binding agent of claim 1 , wherein the domain linker comprises a polypeptide.
3. The collagen-binding agent of claim 1 , wherein the domain linker comprises a polypeptide selected from the group consisting of the polypeptides of SEQ ID NOs: 48-55 or a polypeptide having at least 80% sequence identity to any one of the polypeptides of SEQ ID NOs: 48-55.
4. The collagen-binding agent of claim 1 , wherein the therapeutic agent linker comprises a polypeptide.
5. The collagen-binding agent of claim 4 , wherein the C-terminus of the therapeutic agent is linked to the N-terminus of the collagen-binding domains by the therapeutic agent linker.
6. A pharmaceutical composition comprising the collagen-binding agent of claim 1 and a pharmaceutical carrier.
7. A method of stimulating bone formation in a subject having a bone condition comprising administering to the subject a therapeutically effective amount of the collagen-binding agent of claim 1 .
8. The method of claim 7 , wherein the subject is a mammal.
9. The method of claim 8 , wherein the mammal is a human.