Bibliographic Details
| Title: |
FUSION PROTEINS FORMING TRIMERS |
| Document Number: |
20120041181 |
| Publication Date: |
February 16, 2012 |
| Appl. No: |
13/143531 |
| Application Filed: |
January 09, 2009 |
| Abstract: |
The present invention refers to fusion proteins comprising a neck region and carbohydrate recognition domain of a collectin trimerization domain, a linker element and an effector polypeptide. Further the invention refers to a nucleic acid encoding the said fusion protein. The fusion proteins, the nucleic acid, and the cell are suitable as pharmaceutical composition or for therapeutic, diagnostic and/or research applications as described herein. |
| Inventors: |
Hill, Oliver (Neckarsteinach, DE); Branschaedel, Marcus (Laupheim, DE); Gieffers, Christian (Dossenheim, DE); Thiemann, Meinolf (Schriesheim, DE) |
| Claim: |
1. A fusion protein comprising (i) a collectin family trimerization domain comprising a. a collectin family Carbohydrate Recognition Domain; and b. a collection family neck region; (ii) a linker element; and (iii) an effector polypeptide, wherein the effector polypeptide is located N-terminally of the collectin family neck region. |
| Claim: |
2. The fusion protein of claim 1, wherein the Carbohydrate Recognition Domain is the Carbohydrate Recognition Domain of surfactant protein-D, surfactant protein-A 1, surfactant protein-A 2, mannan-binding-protein-C, collectin liver 1, collectin placenta 1, or collectin-11. |
| Claim: |
3. The fusion protein claim 1, wherein the Carbohydrate Recognition Domain comprises one or more amino acid mutations or substitutions. |
| Claim: |
4. The fusion protein of claim 3, wherein the Carbohydrate Recognition Domain is the Carbohydrate Recognition Domain of surfactant protein D, and the substitution is a substitution of phenylalanin 355 in SEQ ID NO: 21 mutated to a polar amino acid selected from aspartic acid, glutamic acid, asparagine and glutamine. |
| Claim: |
5. The fusion protein claim 1, wherein the collectin family neck region is the neck region of surfactant protein-D, surfactant protein-A 1, surfactant protein-A 2, mannan-binding-protein-C, collectin liver 1, collectin placenta 1, or collectin-11. |
| Claim: |
6. The fusion protein claim 1, wherein the linker element has a length of 25 or less amino acids. |
| Claim: |
7. The fusion protein claim 1, wherein the linker element is built from amino acids selected from alanine, threonine, glycine and serine. |
| Claim: |
8. The fusion protein claim 1, wherein the effector polypeptide is a cytokine of the TNF superfamily, a receptor binding domain thereof or a receptor for a cytokine. |
| Claim: |
9. The fusion protein claim 1, wherein the effector polypeptide is a mutant of a cytokine of the TNF superfamily, of a receptor binding domain thereof or of a receptor for a cytokine. |
| Claim: |
10. The fusion protein of claim 8, wherein the effector protein is a cytokine of the TNF superfamily, a receptor binding domain or a mutant thereof, and wherein the N-terminal stalk region of such cytokine is not included in the fusion protein. |
| Claim: |
11. The fusion protein claim 1, wherein the cytokine of the TNF superfamily or the receptor binding domain thereof is selected from TRAIL, CD95L, APRIL, LIGHT and RANK-L or the respective receptor binding domain thereof. |
| Claim: |
12. The fusion protein claim 1, wherein the receptor for a cytokine is selected from TRAIL-R1, TRAIL-R2, LTbetaR, TNFRSF13B, TNFRSF17 and IL-4R-alpha. |
| Claim: |
13. The fusion protein claim 1, wherein the effector polypeptide is an antibody, a single chain antibody or a fragment of an antibody or a single chain antibody. |
| Claim: |
14. The fusion protein of claim 13, wherein the antibody, a single chain antibody or a fragment of an antibody or a single chain antibody is directed against a cytokine of the TNF superfamily, a receptor binding domain thereof or a receptor for a cytokine. |
| Claim: |
15. The fusion protein of claim 14, wherein the receptor for a cytokine is IL4R-alpha. |
| Claim: |
16. The fusion protein of claim 1, comprising at the C-terminal end of the collectin family Carbohydrate Recognition Domain an antibody, a single chain antibody, or a fragment of an antibody or a single chain antibody. |
| Claim: |
17. (canceled) |
| Claim: |
18. The fusion protein of claim 1, for treatment of proliferative disorders associated with dysfunction of TNF cytokines comprising tumors, infectious diseases, inflammatory diseases, metabolic diseases, autoimmune disorders, degenerative diseases, and transplant rejections. |
| Current U.S. Class: |
5303/873 |
| Current International Class: |
07; 07 |
| Accession Number: |
edspap.20120041181 |
| Database: |
USPTO Patent Applications |
