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Last Updated: April 19, 2024

Claims for Patent: 7,786,273

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Summary for Patent: 7,786,273

Title:	Macromolecules comprising a thioether cross-link
Abstract:	The present invention provides macromolecules comprising at least one thioether cross-link. A thioether cross-link comprising a single thioether bond between two residues of a macromolecule. The macromolecules of the invention can display enhanced stability, pharmaceutical properties and functional properties. In particular, the invention provides an isolated antibodies comprising at least one thioether cross-link that specifically bind to particular antigens. The present invention also provides a composition comprising a macromolecule substantially free of a denaturing reagent, wherein the macromolecule comprises at least one thioether cross-link. In addition, the present invention provides a method for producing the macromolecules and compositions of the invention.
Inventor(s):	Tous; Guillermo I. (East Windsor, NJ), Schenerman; Mark (Reisterstown, MD), Wei; Ziping (North Potomac, MD)
Assignee:	Medimmune, LLC (Gaithersburg, MD)
Application Number:	11/375,810
Patent Claims:	1. A composition substantially free of a denaturing reagent comprising a monoclonal antibody population and a carrier, wherein each monoclonal antibody in the population comprises the same amino acid sequence, wherein about 0.05%-4% of said population comprises one or multiple thioether cross-link, wherein the thioether cross-link links a heavy chain of the monoclonal antibody and a light chain of the monoclonal antibody, wherein the monoclonal antibody is capable of specifically binding to a respiratory syncytial virus (RSV) antigen provided that the monoclonal antibody is not palivizumab, and wherein said monoclonal antibody population is an IgG.sub.1. 2. The composition of claim 1, wherein less than 2%, 1%, 0.75%, 0.5%, 0.25%, or 0.1% of said population comprises at least one thioether cross-link. 3. The composition of claim 1, wherein the monoclonal antibody population is a population of a human antibody, a chimeric antibody, and/or a humanized antibody. 4. The composition of claim 1, wherein said about 0.05%-4% of said population comprises multiple thioether cross-links. 5. The composition of claim 1, wherein the thioether cross-link is in the Fab portion or the Fc portion of the antibody. 6. The composition of claim 1, wherein the thioether cross-link links a cysteine residue of the heavy chain and a residue of the light chain. 7. The composition of claim 1, wherein the thioether links a residue of the heavy chain and a cysteine residue of the light chain of the antibody. 8. The composition of claim 1, wherein the thioether cross-link links a cysteine residue of the heavy chain and a cysteine residue of the light chain. 9. The composition of claim 7, wherein the thioether cross-link links a cysteine residue in the C.sub.H1 region of the heavy chain and a cysteine residue in the C.sub.L region of the light chain. 10. The composition of claim 9, wherein the cysteine residue in the C.sub.H1 region of the heavy chain is at the amino acid position 223 according to the Kabat numbering system. 11. The composition of claim 9, wherein the cysteine residue in the C.sub.L region of the light chain is at the amino acid position 213 according to the Kabat numbering system. 12. The composition of claim 1, wherein the carrier is water. 13. The composition of claim 1, wherein the monoclonal antibody is motavizumab. 14. The composition of claim 1, wherein the thioether crosslink is lanthionine. 15. The composition of claim 8, wherein the cysteine residue in the C.sub.H1 region of the heavy chain is at the amino acid position 223 according to the Kabat numbering system, and the cysteine residue in the C.sub.L region of the heavy chain is at the amino acid position 213 according to the Kabat numbering system. 16. The composition of claim 15, wherein the monoclonal antibody is motavizumab.

Details for Patent 7,786,273

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Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Swedish Orphan Biovitrum Ab (publ)	SYNAGIS	palivizumab	For Injection	103770	06/19/1998	⤷ Try a Trial	2025-03-14
Swedish Orphan Biovitrum Ab (publ)	SYNAGIS	palivizumab	Injection	103770	07/23/2004	⤷ Try a Trial	2025-03-14
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

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