Claims
- 1. A method for generating, from a parent protein, a variant protein having desired immunological and functional properties, said method comprising:
a) inputting the coordinates of a structure of a parent protein into a computer; b) identifying the amino acid positions of at least a first immunogenic sequence in said parent protein; c) generating one or more variant sequences comprising at least one amino acid substitution of at least one position of said first immunogenic sequence in said parent protein; d) applying, in any order:
i) at least one computational protein design algorithm that analyzes the compatibility of said variant sequence with the structure or function of said parent protein; and ii) at least one computational immunogenicity filter that analyzes the immunological properties of said variant sequence; and e) identifying at least one variant protein having desired immunological and functional properties.
- 2. A method according to claim 1, wherein said desired immunological property is enhanced uptake by antigen presenting cells (APCs).
- 3. A method according to claim 1, wherein said desired immunological property is reduced immunogenicity.
- 4. A method according to claim 1, wherein said desired immunological property is enhanced immunogenicity.
- 5. A method according to claim 1, wherein said immunogenic sequence is selected from the group consisting of: an antigen processing cleavage site, a class I MHC agretope, a class II MHC agretope, and an antibody epitope.
- 6. A method according to claim 1, wherein said immunogenicity filter comprises a function that predicts antigen processing cleavage sites.
- 7. A method according to claim 1, wherein said immunogenicity filter comprises a function that predicts class I MHC agretopes.
- 8. A method according to claim 1, wherein said immunogenicity filter comprises a function that predicts class II MHC agretopes.
- 9. A method according to claim 1, wherein said immunogenicity filter comprises a matrix method calculation.
- 10. A method according to claim 1, wherein said immunogenicity filter comprises a function that predicts antibody epitopes.
- 11. A method according to claim 1, wherein said computational protein design algorithm comprises a scoring function with two or more terms selected from the list: van der Waals, hydrogen bonding, electrostatics, solvation, and secondary structure propensity.
- 12. A method according to claim 1, wherein said computational protein design algorithm is used to assess the stability of said variant protein.
- 13. A method according to claim 1, wherein said computational protein design algorithm is used to assess the affinity of said variant protein for one or more receptor or ligand molecules.
- 14. A method according to claim 1, wherein said computational protein design algorithm is PDA® technology.
- 15. A method according to claim 1, further comprising experimentally generating said variant protein.
- 16. A method according to claim 15, further comprising recovering said variant protein.
- 17. A method according to claim 15, further comprising administering said variant protein to a patient.
- 18. A variant protein with reduced immunogenicity made using the method of claim 1.
- 19. A variant protein with enhanced immunogenicity made using the method of claim 1.
- 20. A nucleic acid encoding the variant protein of claim 18.
- 21. A nucleic acid encoding the variant protein of claim 19.
Parent Case Info
[0001] This application claims the benefit under §§119/120 of the filing date of U.S. Ser. No. 10/339,788, filed Jan. 8, 2003, which claims the benefit of the filing date of U.S. Ser. No. 60/432,909, filed Dec. 11, 2002, and is a Continuation-in-Part of U.S. Ser. No. 10/039,170, filed Jan. 4, 2002, and a U.S. Ser. No. 09/903,378, filed Jul. 10, 2001, which claims the benefit of the filing date of U.S. Ser. No. 60/416,305 filed Oct. 3, 2002, all of which are incorporated by reference in entirety.
Provisional Applications (1)
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Number |
Date |
Country |
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60432909 |
Dec 2002 |
US |
Continuation in Parts (2)
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Number |
Date |
Country |
Parent |
10339788 |
Jan 2003 |
US |
Child |
10754296 |
Jan 2004 |
US |
Parent |
10039170 |
Jan 2002 |
US |
Child |
10754296 |
Jan 2004 |
US |