Claims for Patent: 10,059,936

Summary for Patent: 10,059,936

Title:	Multi-chain eukaryotic display vectors and uses thereof
Abstract:	A eukaryotic expression vector capable of displaying a multi-chain polypeptide on the surface of a host cell is provided, such that the biological activity of the multi-chain polypeptide is exhibited at the surface of the host cell. Such a vector allows for the display of complex biologically active polypeptides, e.g., biologically active multi-chain polypeptides such as immunoglobulin Fab fragments. The present invention describes and enables the successful display of a multi-chain polypeptide on the surface of a eukaryotic host cell. Preferred vectors are described for expressing the chains of a multi-chain polypeptide in a host cell separately and independently (e.g., under separate vector control elements, and/or on separate expression vectors, thus forming a matched vector set). The use of such matched vector sets provides flexibility and versatility in the generation of eukaryotic display libraries, for example the ability to generate and to display multi-chain polypeptides by combining and recombining vectors that express variegations of the individual chains of a multi-chain polypeptide. Entire repertoires of novel chain combinations can be devised using such vector sets.
Inventor(s):	Hufton; Simon E. (Clitheroe Lane, GB), Hoogenboom; Hendricus Renerus Jacobus Mattheus (Maastricht, NL)
Assignee:	Dyax Corp. (Lexington, MA)
Application Number:	15/377,846
Patent Claims:	1. A method for selecting a multi-chain antibody that binds to a target antigen, the method comprising: (i) providing a plurality of host yeast cells, which collectively displays a plurality of multi-chain antibodies; (ii) contacting a target antigen with the plurality of host yeast cells; and (iii) isolating a host yeast cell that displays a multi-chain antibody binding to the target antigen; and (iv) identifying the antibody that binds the target antigen. 2. The method of claim 1, wherein the plurality of multi-chain antibodies is fully human. 3. The method of claim 1, wherein the plurality of multi-chain antibodies is a plurality of full length antibodies. 4. The method of claim 3, wherein the full length antibodies are immunoglobulin G molecules. 5. The method of claim 1, wherein the plurality of multi-chain antibodies is a plurality of Fab molecules. 6. The method of claim 1, wherein the diversity of the plurality of multi-chain antibodies is at least 1.times.10.sup.6. 7. The method of claim 6, wherein the diversity of the plurality of multi-chain antibodies is at least 1.times.10.sup.7. 8. The method of claim 1, wherein the plurality of host yeast cells are diploid yeast cells. 9. The method of claim 8, wherein the multi-chain antibodies are linked to a surface anchor protein of the yeast cells. 10. The method of claim 9, wherein the multi-chain antibodies are linked indirectly to the surface anchor protein via an intermediate association. 11. The method of claim 10, wherein the surface anchor protein is Aga1p-Aga2p pair. 12. A method of making a library of yeast cells displaying multi-chain antibodies, the method comprising: (i) providing a first plurality of haploid yeast cells each comprising a first polynucleotide encoding a heavy chain of a multi-chain antibody; (ii) providing a second plurality of haploid yeast cell each comprising a second polynucleotide encoding a light chain of a multi-chain antibody, wherein the first plurality of haploid yeast cells and the second plurality of haploid yeast cells are of opposite mating types; and (iii) contacting the first plurality of haploid yeast cells with the second plurality of haploid yeast cells under conditions sufficient to permit the cells to fuse, thereby producing a plurality of diploid eukaryotic cells that collectively produce a library of multi-chain antibodies. 13. The method of claim 12, wherein multi-chain antibodies of the library are displayed on the surface of the plurality of the diploid yeast cells. 14. The method of claim 13, wherein the multi-chain antibodies are linked to a surface anchor protein of the yeast cells. 15. The method of claim 14, wherein the multi-chain antibodies are linked indirectly to the surface anchor protein via an intermediate association. 16. The method of claim 15, wherein the surface anchor protein is Aga1p-Aga2p pair.

Details for Patent 10,059,936

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Octapharma Pharmazeutika Produktionsges.m.b.h.	CUTAQUIG	immune globulin subcutaneous (human)-hipp	Solution	125668	December 12, 2018		2036-12-13