Claims for Patent: 8,916,159
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Summary for Patent: 8,916,159
Title: | Selenocysteine mediated hybrid antibody molecules |
Abstract: | The invention provides methods and compositions employing hybrid molecules of a synthetic molecule and antibody or antibody fragment comprising a selenocysteine residue, wherein the synthetic molecule is covalently linked to the antibody or antibody fragment at the selenocysteine residue. The invention also provides a composition comprising a hybrid molecule as described above and a pharmaceutically acceptable carrier. The invention further provides for methods of making the hybrid molecules, and methods of using the hybrid molecule described above to inhibit cell surface receptor binding. |
Inventor(s): | Rader; Christoph (Olney, MD), Hofer; Thomas (Zurich, CH), Burke, Jr.; Terrence (Bethesda, MD), Thomas; Joshua (Frederick, MD) |
Assignee: | The United States of America, as represented by the Secretary, Department of Health and Human Services (Washington, DC) |
Application Number: | 12/570,796 |
Patent Claims: | 1. A composition comprising (a) a hybrid molecule comprising a synthetic molecule and an antibody or antibody fragment selected from the group consisting of Fc,
F(ab')2, Fab, scFv, IgG.DELTA.CH2, scFv2CH3, scFv4, scFv3, scFv2, dsFv, and scFv-Fc, wherein the antibody or antibody fragment comprises at least one selenocysteine residue, wherein the at least one selenocysteine residue is located within 10 amino acids
of a C-terminus of the antibody or antibody fragment, wherein the at least one selenocysteine residue is cotranslationally incorporated at a UGA stop codon of the antibody or antibody fragment that was recoded from termination to selenocysteine
insertion, and wherein the synthetic molecule is covalently linked to the antibody or antibody fragment at the at least one selenocysteine residue, and (b) a pharmaceutically acceptable carrier.
2. The composition of claim 1, wherein the antibody is selected from the group consisting of IgA, IgD, IgE, IgG, and IgM. 3. The composition of claim 1, wherein the antibody is rituximab. 4. The composition of claim 1, wherein the antibody fragment is an Fc domain. 5. The composition of claim 1, wherein the antibody fragment is an Fab domain. 6. The composition of claim 1, wherein the antibody or antibody fragment comprises only one selenocysteine residue. 7. The composition of claim 1, wherein the antibody or antibody fragment comprises more than one selenocysteine residue. 8. The composition of claim 1, wherein the at least one selenocysteine residue is located within 5 amino acids of the C-terminus of the antibody or antibody fragment. 9. The composition of claim 1, wherein the at least one selenocysteine residue is located at the C terminus of the antibody or antibody fragment. 10. The composition of claim 1, wherein the antibody or antibody fragment is produced using a eukaryotic expression system. 11. The composition of claim 10, wherein the antibody or antibody fragment is produced using a mammalian expression system. 12. The composition of claim 1, wherein the synthetic molecule comprises an iodoacetamide, bromoacetamide, chloroacetamide, maleimide, or acrylamide moiety. 13. The composition of claim 1, wherein the synthetic molecule comprises a binding moiety for an integrin selected from the group consisting of .alpha.4.beta.1, .alpha.4.beta.7, .alpha.v.beta.3, .alpha.v.beta.5, .alpha.V.beta.6, .alpha.5.beta.1, and .alpha.IIB.beta.3. 14. The composition of claim 13, wherein the synthetic molecule comprises both an .alpha.4.beta.1 and an .alpha.4.beta.7 integrin binding moiety. 15. The composition of claim 1, wherein the synthetic molecule comprises a binding moiety for a receptor selected from the group consisting of CCR5, LHRH, CXCR4, TPO, folate, endothelin, and vitamin B12. 16. The composition of claim 1, wherein the synthetic molecule comprises a biotin moiety. 17. The composition of claim 1, wherein the synthetic molecule comprises an .alpha.4.beta.1 integrin binding moiety, a biotin moiety, and a maleimide moiety. 18. The composition of claim 1, wherein the synthetic molecule comprises a radioisotope. 19. The composition of claim 1, wherein the synthetic molecule comprises a cytotoxic agent. 20. The composition of claim 19, wherein the cytotoxic agent is selected from the group consisting of doxorubicin, calicheamicin, maytansinoid, and auristatin. 21. The composition of claim 1, wherein the synthetic molecule is covalently linked to the selenocysteine residue by a polyethylene glycol (PEG) linker. 22. The composition of claim 21, wherein the PEG linker comprises poly(ethylene glycol)-succinamide-lysine-lysine-maleimide. |
Details for Patent 8,916,159
Applicant | Tradename | Biologic Ingredient | Dosage Form | BLA | Approval Date | Patent No. | Expiredate |
---|---|---|---|---|---|---|---|
Genentech, Inc. | RITUXAN | rituximab | Injection | 103705 | 11/26/1997 | ⤷ Try a Trial | 2027-04-02 |
Idec Pharmaceuticals Corp. | RITUXAN | rituximab | Injection | 103737 | 02/19/2002 | ⤷ Try a Trial | 2027-04-02 |
Genentech, Inc. | RITUXAN HYCELA | rituximab and hyaluronidase human | Injection | 761064 | 06/22/2017 | ⤷ Try a Trial | 2027-04-02 |
>Applicant | >Tradename | >Biologic Ingredient | >Dosage Form | >BLA | >Approval Date | >Patent No. | >Expiredate |
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