التفاصيل البيبلوغرافية
| العنوان: |
VIRUS COAT PROTEIN/RECEPTOR CHIMERAS AND METHODS OF USE |
| Document Number: |
20090081124 |
| تاريخ النشر: |
March 26, 2009 |
| Appl. No: |
11/940445 |
| Application Filed: |
November 15, 2007 |
| مستخلص: |
The invention relates to chimeric molecules comprising a virus coat sequence and a receptor sequence that can inter-act with each other to form a complex that is capable of binding a co-receptor. Such chimeric molecules therefore exhibit functional properties characteristic of a receptor-coat protein complex and are useful as agents that inhibit virus infection of cells due to occn-panty of co-receptor present on the cell, for example. In particular aspects, the chimeric polypeptide includes an immunodeficiency virus envelope polypeptide, such as that of HIV, SIV, FIV, FeLV, FPV and herpes virus. Receptor sequences suitable for use in a chimeric polypeptide include, for example, CCR5 and CXCR4 sequences. |
| Inventors: |
DeVico, Anthony Louis (Alexandria, VA, US); Fouts, Timothy R. (Columbia, MD, US); Tuskan, Robert G. (Woodsboro, MD, US) |
| Claim: |
1. A chimeric polypeptide comprising: a virus coat polypeptide sequence, a viral cell surface receptor polypeptide and an amino acid sequence spacer, wherein the amino acid sequence of the chimeric polypeptide is a full length reference sequence, a truncated sequence or modified sequences thereof, wherein the modified sequences have at least 95% identity to the full length reference sequence or truncated sequence, and wherein the full length reference sequence, truncated sequence and modified sequences have the functionality of forming an intramolecular interacting complex between the virus coat polypeptide and viral cell surface receptor, wherein the amino acid spacer is of sufficient length to allow the virus coat polypeptide sequence and the viral cell surface receptor polypeptide sequence to form the intramolecular interacting complex, wherein the virus is an immunodeficiency virus selected from the group consisting of retroviruses HIV, SIV, FIV, and FeLV, and wherein the chimeric polypeptide further comprising a heterologous domain. |
| Claim: |
2. The chimeric polypeptide of claim 1, wherein the heterologous domain is selected from the group consisting of: a tag, an adhesin, and an immunopotentiating agent. |
| Claim: |
3. The chimeric polypeptide of claim 2, wherein the heterologous domain comprises an amino acid sequence. |
| Claim: |
4. The chimeric polypeptide of claim 3, wherein said amino acid sequence is a c-myc polypeptide sequence. |
| Claim: |
5. The chimeric polypeptide of claim 2, wherein said immunopotentiating agent is an immunoglobulin polypeptide sequence. |
| Claim: |
6. The chimeric polypeptide of claim 5, wherein said immunoglobulin polypeptide sequence is a heavy-chain polypeptide sequence. |
| Claim: |
7. A polynucleotide sequence comprising a nucleic acid sequence encoding the chimeric polypeptide of claim 1. |
| Claim: |
8. The polynucleotide sequence of claim 7, further comprising an expression vector. |
| Claim: |
9. A host cell containing the expression vector of claim 8. |
| Claim: |
10. The polynucleotide sequence of claim 7, further comprising a pharmaceutically acceptable carrier. |
| Claim: |
11. A method for identifying an agent that reduces an interaction between a virus and a virus receptor or co-receptor comprising the steps of: contacting the chimeric polypeptide of claim 1 with a virus receptor or co-receptor under conditions allowing the chimeric polypeptide and the virus receptor or virus co-receptor to bind, in the presence and absence of a test agent; and detecting binding in the presence and absence of the test agent, wherein decreased binding in the presence of the test agent thereby identifies an agent that reduces binding between the virus and the virus receptor or virus co-receptor. |
| Claim: |
12. The method of claim 11, wherein the immunodeficiency virus is HIV. |
| Claim: |
13. The method of claim 12, wherein the test agent is added after or before contacting the chimeric polypeptide with the virus receptor or virus co-receptor. |
| Claim: |
14. The method of claim 11, wherein the test agent is selected from the group consisting of a peptide, an organic molecule, an antibody, an antiviral, a chimeric polypeptide comprising an HIV virus polypeptide and a virus receptor polypeptide, an immunodeficiency virus co-receptor or functional fragment thereof. |
| Claim: |
15. The method of claim 11, wherein the immunodeficiency virus co-receptor is a CCR5 or CXCR4 polypeptide sequence. |
| Claim: |
16. The method of claim 11, wherein the virus receptor or virus co-receptor is present on the surface of an intact cell. |
| Claim: |
17. The method of claim 16, wherein the intact cell is present in an animal. |
| Claim: |
18. The method of claim 11, wherein the test agent is a library of agents. |
| Claim: |
19. The method of claim 11, wherein the virus receptor is CD4. |
| Claim: |
20. The method of claim 14, wherein the virus receptor polypeptide is a CD4 polypeptide sequence or fragment thereof. |
| Claim: |
21. An antibody or functional fragment thereof that binds to the chimeric polypeptide of claim 1. |
| Claim: |
22. The antibody of claim 21, wherein the antibody neutralizes the virus in vitro. |
| Claim: |
23. The antibody of claim 21, wherein the antibody inhibits virus infection. |
| Claim: |
24. The antibody of claim 21, wherein the antibody binds to an epitope produced by the binding of the virus coat polypeptide sequence and the receptor polypeptide sequence. |
| Claim: |
25. The antibody of claim 24, wherein the epitope is present on an envelope polypeptide sequence. |
| Current U.S. Class: |
424/91 |
| Current International Class: |
61; 07; 07; 07; 12; 61; 12; 61; 12 |
| رقم الانضمام: |
edspap.20090081124 |
| قاعدة البيانات: |
USPTO Patent Applications |