Coagulation factor IX compositions and methods of making and using same

• US 9,758,776 B2
• Filed: 05/24/2016
• Issued: 09/12/2017
• Est. Priority Date: 08/24/2009
• Status: Active Grant

• Current Assignee: Amunix Pharmaceuticals, Inc. (Sanofi )
• Original Assignee: Amunix Operating Inc.
• Inventors: Schellenberger, Volker, Stemmer, Willem P., Geething, Nathan C., To, Wayne, Silverman, Joshua, Wang, Chia-wei, Spink, Benjamin
• Primary Examiner(s): Beane, Randall L
• Application Number:
  US15/163,603
• Publication Number:
  US 20160362672A1
• Time in Patent Office: 476 Days
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: C07K 14/001 by chemical synthesis
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/31 fusions, other than Fc, for prolonged plasma life, e.g. albumin
• CPC Class Codes: C07K 2319/50 containing protease site
• CPC Class Codes: C12N 15/70 Vectors or expression systems specially adapted for E. coli
• CPC Class Codes: C12N 9/6437 Coagulation factor VIIa (3.4.21.21)
• CPC Class Codes: C12N 9/644 Coagulation factor IXa (3.4.21.22)
• CPC Class Codes: C12Y 304/21022 Coagulation factor IXa (3.4.21.22)

Abstract

The present invention relates to compositions comprising factor IX coagulation factors linked to extended recombinant polypeptide (XTEN), isolated nucleic acids encoding the compositions and vectors and host cells containing the same, and methods of making and using such compositions in treatment of coagulation factor-related diseases, disorders, and conditions.

Claims

1. A polynucleotide encoding a factor IX fusion protein, which comprises a factor IX polypeptide and an extended recombinant polypeptide (XTEN), wherein the XTEN comprises an amino acid sequence having at least 90% sequence identity to a sequence selected from SEQ ID NOs:

35, 36, 37, 38, 43, 44, 45, and 46 and wherein the XTEN is capable of extending a half-life of the factor IX polypeptide.

2. The polynucleotide of claim 1, wherein the XTEN comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:

36.

3. The polynucleotide of claim 1, wherein the XTEN comprises the amino acid sequence set forth in SEQ ID NO:

36.

4. The polynucleotide of claim 1, wherein the XTEN comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:

37.

5. The polynucleotide of claim 1, wherein the XTEN comprises the amino acid sequence set forth in SEQ ID NO:

37.

6. The polynucleotide of claim 1, wherein the XTEN is fused to the C-terminus of the factor IX polypeptide.

7. The polynucleotide of claim 1, wherein the XTEN is inserted within the factor IX polypeptide.

8. The polynucleotide of claim 1, wherein the factor IX polypeptide comprises an activation peptide and wherein the XTEN is inserted at the C-terminus or N-terminus of the activation peptide in the factor IX polypeptide.

9. The polynucleotide of claim 1, which comprises more than one XTEN.

10. The polynucleotide of claim 7, wherein the XTEN is incorporated between any two adjacent domains contained in the factor IX polypeptide and wherein the two adjacent domains are selected from the group consisting of a Gla domain, an EGF1 domain, an EGF2 domain, an activation peptide, and a peptidase S1 domain (Pro).

11. The polynucleotide of claim 1, wherein the XTEN is encoded by a polynucleotide comprising a nucleic acid sequence having at least 90% sequence identity to a sequence selected from SEQ ID NOs:

226, 228, 230, 232, 234, 236, 238, 240, 242, 244, 246, 248, 250, 252, 254, 256, 258, 260, 262, 264, 266, 268, 270, 272, 274, 276, 278, 280, 282, 284, 286, 288, 290, 292, 294, 296, 298, 342, 404, 406, 408, 410, 412, 414, 416, 418, 420, 422, 424, 426, 428, 430, 432, 434, 436, 438, 440, 442, 444, 446, 448, 450, 452, 454, 456, 458, 460, 462, 464, 466, 468, 470, 472, 474, 476, 478, 480, 482, 484, 486, 488, and 490.

12. The polynucleotide of claim 1, wherein the XTEN is encoded by a polynucleotide comprising a nucleic acid sequence having at least 90% sequence identity to a sequence selected from SEQ ID NOs:

111, 112, 113, 115, 116, 118, 119, 120, 121, 122, 123, 124, 125, 491, 493, 495, 497, 499, 501, 503, 505, 507, 509, 511, 513, 515, 517, 519, 521, 523, 525, 527, 529, 531, 533, 535, 537, 539, 541, 543, 545, 547, 549, 551, 553, and 555.

13. The polynucleotide of claim 1 comprising a nucleic acid sequence having at least 90% sequence identity to a sequence selected from SEQ ID NOs:

603, 605, 607, 609, 613, 615, 617, and 619.

14. A vector comprising the polynucleotide of claim 1.

15. The polynucleotide of claim 1, wherein the XTEN comprises an amino acid sequence having at least 90% sequence identity to a sequence selected from SEQ ID NOs:

225, 227, 229, 231, 233, 235, 237, 239, 241, 243, 245, 247, 249, 251, 253, 255, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 341, 403, 405, 407, 409, 411, 413, 415, 417, 419, 421, 423, 425, 427, 429, 431, 433, 435, 437, 439, 441, 443, 445, 447, 449, 451, 453, 455, 457, 459, 461, 463, 465, 467, 469, 471, 473, 475, 477, 479, 481, 483, 485, 487, and 489.

16. The polynucleotide of claim 15, wherein the XTEN comprises an amino acid sequence having at least 95% sequence identity to a sequence selected from SEQ ID NOs:

225, 227, 229, 231, 233, 235, 237, 239, 241, 243, 245, 247, 249, 251, 253, 255, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 341, 403, 405, 407, 409, 411, 413, 415, 417, 419, 421, 423, 425, 427, 429, 431, 433, 435, 437, 439, 441, 443, 445, 447, 449, 451, 453, 455, 457, 459, 461, 463, 465, 467, 469, 471, 473, 475, 477, 479, 481, 483, 485, 487, and 489.

17. The polynucleotide of claim 15, wherein the XTEN comprises an amino acid sequence selected from SEQ ID NOs:

225, 227, 229, 231, 233, 235, 237, 239, 241, 243, 245, 247, 249, 251, 253, 255, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 341, 403, 405, 407, 409, 411, 413, 415, 417, 419, 421, 423, 425, 427, 429, 431, 433, 435, 437, 439, 441, 443, 445, 447, 449, 451, 453, 455, 457, 459, 461, 463, 465, 467, 469, 471, 473, 475, 477, 479, 481, 483, 485, 487, and 489.

18. The polynucleotide of claim 1, wherein the XTEN comprises an amino acid sequence having at least 90% sequence identity to a sequence selected from SEQ ID NOs:

61, 62, 63, 65, 66, 69, 71, 73, 74, 75, 76, 77, 78, 79, 492, 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524, 526, 528, 530, 532, 534, 536, 538, 540, 542, 544, 546, 548, 550, 552, 554, and 556.

19. The polynucleotide of claim 1, wherein the XTEN comprises an amino acid sequence having at least 95% sequence identity to a sequence selected from SEQ ID NOs:

61, 62, 63, 65, 66, 69, 71, 73, 74, 75, 76, 77, 78, 79, 492, 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524, 526, 528, 530, 532, 534, 536, 538, 540, 542, 544, 546, 548, 550, 552, 554, and 556.

20. The polynucleotide of claim 1, wherein the XTEN comprises an amino acid sequence selected from SEQ ID NOs:

61, 62, 63, 65, 66, 69, 71, 73, 74, 75, 76, 77, 78, 79, 492, 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524, 526, 528, 530, 532, 534, 536, 538, 540, 542, 544, 546, 548, 550, 552, 554, and 556.

21. The polynucleotide of claim 1, wherein the XTEN comprises an amino acid sequence having at least 90% sequence identity to a sequence selected from SEQ ID NO:

63 or 65.

22. The polynucleotide of claim 1, wherein the XTEN comprises an amino acid sequence having at least 95% sequence identity to a sequence selected from SEQ ID NO:

63 or 65.

23. The polynucleotide of claim 1, wherein the XTEN comprises an amino acid sequence selected from SEQ ID NO:

63 or 65.