Coagulation factor IX compositions and methods of making and using same
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-038/36
C07K-014/745
C12N-009/64
C07K-014/00
C12N-015/70
출원번호
US-0163603
(2016-05-24)
등록번호
US-9758776
(2017-09-12)
발명자
/ 주소
Schellenberger, Volker
Stemmer, Willem P.
Geething, Nathan C.
To, Wayne
Silverman, Joshua
Wang, Chia-wei
Spink, Benjamin
출원인 / 주소
Amunix Operating Inc.
대리인 / 주소
Sterne, Kessler, Golstein & Fox P.L.L.C.
인용정보
피인용 횟수 :
1인용 특허 :
206
초록▼
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
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.
대표청구항▼
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,
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.
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