Claims for Patent: 7,070,959

Summary for Patent: 7,070,959

Title:	Modified chimeric polypeptides with improved pharmacokinetic properties
Abstract:	Modified chimeric polypeptides with improved pharmacokinetics are disclosed. Specifically, modified chimeric Flt1 receptor polypeptides that have been modified in such a way as to improve their pharmacokinetic profile are disclosed. Also disclosed are methods of making and using the modified polypeptides including but not limited to using the modified polypeptides to decrease or inhibit plasma leakage and/or vascular permeability in a mammal.
Inventor(s):	Papadopoulos; Nicholas J. (Lagrangeville, NY), Davis; Samuel (New York, NY), Yancopoulos; George D. (Yorktown Heights, NY)
Assignee:	Regeneron Pharmaceuticals, Inc. (Tarrytown, NY)
Application Number:	10/009,852
Patent Claims:	1. An isolated nucleic acid molecule encoding a fusion protein capable of binding vascular endothelial growth factor (VEGF), consisting of (a) a (VEGF) receptor component having immunoglobulin-like (Ig) domains consisting of an Ig domain 2 of a first VEGF receptor human Flt1 and Ig domain 3 of a second VEGF receptor human Flk1; and (b) a multimerizing component. 2. The isolated nucleic acid molecule of claim 1, wherein the nucleotide sequence encoding a first VEGF receptor component is upstream of the nucleotide sequence encoding a second VEGF receptor component. 3. The isolated nucleic acid molecule of claim 1, wherein the nucleotide sequence encoding a first VEGF receptor component is downstream of the nucleotide sequence encoding a second VEGF receptor component. 4. The isolated nucleic acid of claim 1, wherein the multimerizing component comprises an immunoglobulin domain. 5. The isolated nucleic acid of claim 4, wherein the immunoglobulin domain is selected from the group consisting of the Fc domain of IgG, and the heavy chain of IgG. 6. The isolated nucleic acid molecule of claim 1, comprising a nucleic acid sequence selected from: (a) SEQ ID NO: 15; and (b) nucleic acid sequences which, as a result of the degeneracy of the genetic code, differ from the nucleic acid sequence of SEQ ID NO: 15. 7. An expression vector comprising a nucleic acid molecule encoding a fusion protein capable of binding vascular endothellal growth factor (VEGF), wherein the fusion protein consists of immunoglobulin-like (Ig) domain 2 of VEGF receptor human Flt1, Ig domain 3 of VEGF receptor human Flk1, and a multimerizing component. 8. A host-vector system for the production of a fusion polypeptide comprising an expression vector encoding a fusion protein capable of binding vascular endothelial growth factor (VEGF), wherein the fusion protein consists of immunoglobulin-like (Ig) domain 2 of VEGF receptor human Flt1, Ig domain 3 of VEGF receptor human Flk1, and a multimerizing component, In a suitable isolated host cell. 9. The host-vector system of claim 8, wherein the host cell is a bacterial cell, yeast cell, insect cell, or mammalian cell. 10. The host-vector system of claim 9, wherein the host cell is selected from the group consisting of E. coli and CHO. 11. A method of producing a fusion polypeptide, comprising growing cells of the host-vector system of claim 8, under conditions permitting production of the fusion polypeptide and recovering the fusion polypeptide so produced. 12. An isolated nucleic acid molecule encoding a fusion protein capable of binding vascular endothelial growth factor (VEGF), consisting of (a) a VEGF receptor component having immunoglobulin-like (Ig) domains consisting of an Ig domain 2 of a first VEGF receptor human Flt1 and Ig domain 3 of a second VEGF receptor human Flt-4: and (b) a multimerizing component. 13. The isolated nucleic acid molecule of claim 12, wherein the multimerizing component is chosen from the Fc domain of IgG and the heavy chain of IgG. 14. An isolated nucleic acid molecule consisting of a nucleotide sequence encoding immunoglobulin-like (Ig) domain 2 of a first vascular endothelial growth factor (VEGF) receptor upstream of a nucleotide sequence encoding Ig domain 3 of a second VEGF receptor and a nucleotide sequence encoding a multimerizing component, wherein the nucleic acid sequence is SEQ ID NO:15. 15. The isolated nucleic acid molecule of claim 14 encoding a fusion protein comprising the amino acid sequence of SEQ ID NO:16.

Details for Patent 7,070,959

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Regeneron Pharmaceuticals, Inc.	EYLEA	aflibercept	Injection	125387	November 18, 2011	7,070,959	2019-06-08
Regeneron Pharmaceuticals, Inc.	EYLEA	aflibercept	Injection	125387	August 16, 2018	7,070,959	2019-06-08

International Patent Family for US Patent 7,070,959

Country	Patent Number	Estimated Expiration
South Africa	200600157
South Africa	200110068
Yugoslavia	86901