Claims
- 1. A non-naturally occurring variant TNF-α protein comprising an amino acid sequence that has at least one amino acid substitution as compared to the wild-type TNF-α sequence, wherein said variant TNF-α protein will preferentially interact with the wild-type-TNF-α to form mixed trimers incapable of activating receptor signaling.
- 2. A non-naturally occurring TNF-α protein according to claim 1 wherein said TNF-α protein has from 3 to 5 amino acid substitutions as compared to wild-type TNF-α sequence.
- 4. The non-naturally occurring TNF-α protein according to claim 1, wherein said substitutions are selected from the group of substitutions consisting of K112D, Y115T, D143K, D143R AND Y1151.
- 5. A recombinant nucleic acid encoding the non-naturally occurring TNF-α protein of claim 1.
- 6. An expression vector comprising the recombinant nucleic acid of claim 5.
- 7. A host cell comprising the recombinant nucleic acid of claim 5.
- 8. A host cell comprising the expression vector of claim 6.
- 9. A method of producing a non-naturally occurring TNF-α protein comprising culturing the host cell of claim 7 under conditions suitable for expression of said nucleic acid.
- 10. The method according to claim 9 further comprising recovering said TNF-α protein.
- 11. A pharmaceutical composition comprising a non-naturally occurring TNF-α protein according to claim 1 and a pharmaceutical carrier.
- 12. A method for treating a TNF-α related disorder comprising administering a non-naturally occurring TNF-α protein to a patient.
- 13. The method according to claim 12, wherein said condition is rheumatoid arthritis.
Parent Case Info
[0001] This application is a continuing application of U.S. Ser. No. 09/945,150, filed Aug. 31, 2001, and U.S. Ser. No. 09/798,789, filed Mar. 2, 2001, which claims the benefit of the filing date of U.S. Ser. No. 60/186,427, filed Mar. 2, 2000.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60186427 |
Mar 2000 |
US |
Continuation in Parts (2)
|
Number |
Date |
Country |
Parent |
09945150 |
Aug 2001 |
US |
Child |
09981289 |
Oct 2001 |
US |
Parent |
09798789 |
Mar 2001 |
US |
Child |
09981289 |
Oct 2001 |
US |