Extended recombinant polypeptides and compositions comprising same
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-038/16
C07K-014/47
C07K-014/00
C07K-014/605
C07K-014/61
C07K-014/745
C07K-014/545
C12N-009/64
출원번호
US-0154223
(2016-05-13)
등록번호
US-9926351
(2018-03-27)
발명자
/ 주소
Schellenberger, Volker
Silverman, Joshua
Wang, Chia-wei
Spink, Benjamin
Stemmer, Willem P.
Geething, Nathan
To, Wayne
Cleland, Jeffrey L.
출원인 / 주소
Amunix Operating Inc.
대리인 / 주소
Wilson Sonsini Goodrich & Rosati
인용정보
피인용 횟수 :
1인용 특허 :
130
초록▼
The present invention relates to compositions comprising biologically active proteins linked to extended recombinant polypeptide (XTEN), isolated nucleic acids encoding the compositions and vectors and host cells containing the same, and methods of using such compositions in treatment of glucose-rel
The present invention relates to compositions comprising biologically active proteins linked to extended recombinant polypeptide (XTEN), isolated nucleic acids encoding the compositions and vectors and host cells containing the same, and methods of using such compositions in treatment of glucose-related diseases, metabolic diseases, coagulation disorders, and growth hormone-related disorders and conditions.
대표청구항▼
1. An isolated extended recombinant polypeptide (XTEN) comprising an amino acid sequence which has at least 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOS: 207, 215, 216, 217, 218, 219, 563-606, 684, 685, 686, 687, 688, 692, 693, 694, 695, 696, 697, 698, 701, 70
1. An isolated extended recombinant polypeptide (XTEN) comprising an amino acid sequence which has at least 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOS: 207, 215, 216, 217, 218, 219, 563-606, 684, 685, 686, 687, 688, 692, 693, 694, 695, 696, 697, 698, 701, 702, 704, 706, 708-711, 714-716, 773, 776, 777-780, 794, and 797-799, wherein the XTEN comprises a motif selected from the group consisting of SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, and SEQ ID NO: 197. 2. The isolated XTEN of claim 1, wherein the XTEN is further characterized in that: (a) the sum of asparagine and glutamine residues is less than 10% of the total amino acid sequence of the XTEN; and/or(b) the sum of methionine and tryptophan residues is less than 2% of the total amino acid sequence of the XTEN. 3. The isolated XTEN of claim 1, wherein the XTEN is further characterized in that: (a) no one type of amino acid constitutes more than 30% of the XTEN sequence; and(b) the XTEN comprises a sequence in which no three contiguous amino acids are identical unless the amino acid is serine, in which case no more than three contiguous amino acids are serine residues. 4. The isolated XTEN of claim 1, wherein the XTEN is further characterized in that the XTEN enhances pharmacokinetic properties of a biologically active protein (BP) when linked to the BP as a fusion protein wherein the pharmacokinetic properties are ascertained by measuring the blood concentration of the fusion protein after administration of a therapeutically effective dose to a subject in comparison to the corresponding BP not linked to XTEN and administered to a subject at a comparable dose. 5. The isolated XTEN of claim 4, wherein the enhanced pharmacokinetic property is selected from an increase in terminal half-life of at least three-fold and blood concentrations that remain within the therapeutic window for the fusion protein for a period at least about three-fold longer compared to the corresponding BP not linked to XTEN. 6. The isolated XTEN of claim 1, wherein the XTEN comprises an amino acid sequence at least 95% identical to a sequence selected from the group consisting of SEQ ID NOS: 207, 215, 216, 217, 218, 219, 563-606, 684, 685, 686, 687, 688, 692, 693, 694, 695, 696, 697, 698, 701, 702, 704, 706, 708-711, 714-716, 773, 776, 777-780, 794, and 797-799. 7. An isolated fusion protein, comprising the XTEN of claim 1 linked to a BP selected from the group consisting of glucose regulating peptide, metabolic protein, coagulation protein, and growth hormone. 8. The isolated fusion protein of claim 7, wherein the BP is glucose regulating peptide. 9. The isolated fusion protein of claim 8, wherein the glucose regulating peptide comprises an amino acid sequence at least 95% identical to a sequence selected from the group consisting of SEQ ID NOS: 11-24, 30, and 37-39. 10. The isolated fusion protein of claim 7, wherein the BP is metabolic protein. 11. The isolated fusion protein of claim 10, wherein the BP comprises an amino acid sequence at least 95% identical to a sequence selected from the group consisting of SEQ ID NOS: 1729-1734. 12. The isolated fusion protein of claim 7, wherein the BP is a coagulation factor. 13. The isolated fusion protein of claim 12, wherein the BP is factor IX. 14. The isolated fusion protein of claim 12, wherein the BP is factor VII or factor VIIa. 15. The isolated fusion protein of claim 7, wherein the BP is a growth hormone sequence at least 95% identical to SEQ ID NO: 1750. 16. An isolated fusion protein, comprising the XTEN of claim 1 linked to a BP exhibiting at least 90% sequence identity to a sequence selected from SEQ ID NOS: 1-42, 48-179, 1723-1747, and 1750-1777. 17. The isolated fusion protein of claim 7, further comprising a second XTEN sequence. 18. The isolated fusion protein of claim 7, further comprising a spacer sequence between the BP and XTEN, wherein the spacer sequence comprises between 1 to about 50 amino acid residues that optionally comprises a cleavage sequence. 19. The isolated fusion protein of claim 18, wherein the cleavage sequence is susceptible to cleavage by a protease selected from FXIa, FXIIa, kallikrein, FVIIa, FIXa, FXa, thrombin, elastase-2, granzyme B, MMP-12, MMP-13, MMP-17 or MMP-20, TEV, enterokinase, rhinovirus 3C protease, and sortase A. 20. An isolated fusion protein comprising a sequence that has at least 90% sequence identity to a sequence selected from SEQ ID NOS: 809, 816-819, 829, 836-841, 847, 854-857, 863, 870-875, 881, 889-892, 898, 906-911, 917, 924-927, 933, 940-945, 951, 958-961, 967, 974-979, 985, 992-995, 1001, 1008-1010, 1019, 1026-1028, 1035, 1042-1044, 1053, 1060-1062, 1069, 1076-1081, 1087, 1094-1097, 1102, 1109-1114, 1120, 1127-1130, 1135, 1142-1147, 1153, 1160-1163, 1169, 1176-1181, 1187, 1194-1197, 1203, 1210-1212, 1221, 1228-1231, 1237, 1244-1247, 1255, 1262-1265, 1271, 1278-1283, 1289, 1296-1299, 1305, 1312-1317, 1323, 1330-1333, 1339, 1346-1351, 1357, 1364-1367, 1373, 1380-1385, 1391, 1398-1401, 1407, 1414-1419, 1425, 1432-1435, 1441, 1448-1453, 1459, 1469, 1476-1479, 1485, 1492-1499, 1505, 1512-1517, 1523, 1530-1533, 1539, 1546-1551, 1557, 1564-1567, 1573, 1580-1585, 1591, 1598-1601, 1607, 1614-1619, 1625, 1632-1635, 1641, 1648-1653, 1659, 1666-1669, 1675, 1682-1687, 1780, and 1782-1784. 21. A pharmaceutical composition comprising the fusion protein of claim 7 or claim 20 and at least one pharmaceutically acceptable carrier. 22. An isolated nucleic acid comprising a polynucleotide sequence selected from (a) a polynucleotide encoding the XTEN of claim 1 or the fusion protein of claim 7 or claim 20, or (b) the complement of the polynucleotide of (a). 23. An expression vector comprising the polynucleotide sequence of claim 22. 24. The expression vector of claim 23, further comprising a recombinant regulatory sequence operably linked to the polynucleotide sequence. 25. The expression vector of claim 23, wherein the polynucleotide sequence is fused in frame to a polynucleotide encoding a secretion signal sequence. 26. The expression vector of claim 25, wherein the secretion signal sequence is a prokaryotic signal sequence. 27. A host cell, comprising the expression vector of claim 24. 28. The host cell of claim 27, wherein the host cell is E. coli. 29. The host cell of claim 27, wherein the host cell is a CHO cell. 30. A kit, comprising packaging material, at least a first container comprising the pharmaceutical composition of claim 21, a label identifying the pharmaceutical composition and storage and handling conditions, and a sheet of instructions for the reconstitution and/or administration of the pharmaceutical compositions to a subject. 31. A method of treating a disease, disorder or condition, comprising administering a therapeutically effective dose of the pharmaceutical composition of claim 21 to a subject in need thereof, wherein the disease, disorder or condition is selected from type 1 diabetes, type 2 diabetes, obesity, hyperglycemia, hyperinsulinemia, decreased insulin production, insulin resistance, syndrome X, excessive appetite, insufficient satiety, glucagonomas, dyslipidemia, retinal neurodegenerative processes, Factor VII deficiency, Factor X deficiency, Factor XII deficiency, hemophilia A, hemophilia B, Von Willebrand's disease, hypertension, acute coronary syndrome, rheumatoid arthritis, reperfusion injury following ischemia, growth-hormone deficiency, Turner's Syndrome, Prader-Willi Syndrome, idiopathic short stature, AIDS wasting, multiple sclerosis, Crohn's disease, ulcerative colitis, muscular dystrophy, and surgical bleeding. 32. The method of claim 31, wherein the pharmaceutical composition is administered subcutaneously, intramuscularly, or intravenously. 33. The method of claim 31, wherein the therapeutically effective dose results in maintaining blood concentrations of the fusion protein within a therapeutic window for the fusion protein at least three-fold longer compared to the corresponding BP not linked to the fusion protein and administered at a comparable dose to a subject. 34. The method of claim 31, wherein multiple consecutive doses of the pharmaceutical composition are administered using a therapeutically effective dose regimen. 35. The method of claim 34, wherein the therapeutically effective dose regimen results in a gain in time of at least four-fold between at least two consecutive Cmax peaks and/or Cmin, troughs for blood levels of the fusion protein compared to the corresponding BP not linked to the fusion protein and administered using a comparable dose regimen to a subject. 36. The method of claim 35, wherein the therapeutically effective dose regimen results in an improvement in at least one measured parameter in a subject using less frequent dosing or a lower total dosage in moles of the fusion protein of the pharmaceutical composition administered to the subject compared to the corresponding BP not linked to the fusion protein and administered to a subject. 37. The method of claim 36, wherein the one measured parameter is selected from fasting glucose level, response to oral glucose tolerance test, peak change of postprandial glucose from baseline, HbA1c, caloric intake, satiety, rate of gastric emptying, insulin secretion, peripheral insulin sensitivity, response to insulin challenge, beta cell mass, body weight, prothrombin time, bleeding time, thrombin-antithrombin III complex (TAT), D-dimer, incidence of bleeding episodes, erythrocyte sedimentation rate (ESR), C-reactive protein, bone density, muscle mass, blood pressure, plasma triglycerides, HDL, cholesterol, LDL cholesterol, incidence of angina, and cardiac output.
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Curtis Joseph E. (Glendora CA) Helgerson Sam L. (Pasadena CA) Lundblad Roger L. (Chapel Hill NC) Liu Shu-Len (Cerritos CA), Activated factor VIII as a therapeutic agent and method of treating factor VIII deficiency.
Silverman, Joshua; Schellenberger, Volker; Stemmer, Willem P.; Wang, Chia-Wei; Brennan, Ian M., Alpha 1-antitrypsin compositions and methods of making and using same.
Schellenberger, Volker; Silverman, Joshua; Wang, Chia-wei; Spink, Benjamin; Stemmer, Willem P.; Geething, Nathan, Binding fusion proteins, binding fusion protein-drug conjugates, XTEN-drug conjugates and methods of making and using same.
Lillicrap David,CAX ; Cameron Cherie,CAX ; Notley Colleen,CAX ; Hoyle Horrocks L. Suzanne,CAX ; Hough Christine,CAX, Canine factor VIII gene, protein and methods of use.
Schellenberger, Volker; Silverman, Joshua; Stemmer, Willem; Wang, Chia-wei; Spink, Benjamin; Geething, Nathan; To, Wayne, Coagulation factor VII compositions and methods of making and using same.
Osterberg Thomas,SEX ; Fatouros Angelica,SEX, Composition comprising coagulation factor VIII formulation, process for its preparation and use of a surfactant as stabi.
Tice Thomas R. ; Gilley Richard M. ; Eldridge John H. ; Staas Jay K., Composition for delivering bioactive agents for immune response and its preparation.
Qiu, Yihong; Bollinger, J. Daniel; Cheskin, Howard S.; Dutta, Sandeep; Engh, Kevin R.; Poska, Richard P., Controlled release formulation of divalproex sodium.
Prausnitz, Mark R.; Allen, Mark G.; Henry, Sebastien; McAllister, Devin V.; Ackley, Donald E.; Jackson, Thomas, Devices and methods for enhanced microneedle penetration of biological barriers.
Ladner Robert C. (Ijamsville MD) Guterman Sonia K. (Belmont MA) Roberts Bruce L. (Milford MA) Markland William (Milford MA) Ley Arthur C. (Newton MA) Kent Rachel B. (Boxborough MA), Directed evolution of novel binding proteins.
Lenting, Petrus Johannes; Van Mourik, Jan Aart; Mertens, Koenraad; Pannekoek, Hans; Turecek, Peter; Schwarz, Hans-Peter; Scheiflinger, Friedrich, Factor VII polypeptide having factor VII:C activity.
Meulien Pierre (Strasbourg FRX) Pavirani Andrea (Strasbourg FRX), Factor VIII analog, preparation process, and pharmaceutical composition containing it.
Schellenberger, Volker; Silverman, Joshua; Stemmer, Willem P.; Wang, Chia-wei; Geething, Nathan; Cleland, Jeffrey L., Glucose-regulating polypeptides and methods of making and using same.
Schellenberger, Volker; Silverman, Joshua; Wang, Chia-wei; Stemmer, Willem P.; Geething, Nathan; Cleland, Jeffrey L., Growth hormone polypeptides and methods of making and using same.
Schellenberger, Volker; Silverman, Joshua; Stemmer, Willem P.; Wang, Chia-Wei; Geething, Nathan; Cleland, Jeffrey L., Growth hormone polypeptides fused to extended recombinant polypeptides and methods of making and using same.
Cunningham Brian C. (Piedmont CA) Lowman Henry (Hercules CA) Wells James A. (Burlingame CA), Human growth hormone variants having greater affinity for human growth hormone receptor at site 1.
Tice, Thomas R.; Lewis, Danny H.; Cowsar, Donald R.; Beck, Lee R., Injectable, long-acting microparticle formulation for the delivery of anti-inflammatory agents.
Turner Terry L. (Charlottesville VA) Howards Stuart S. (Charlottesville VA), Intraorgan injection of biologically active compounds contained in slow-release microcapsules or microspheres.
Woiszwillo James E. ; Brown Larry R. ; Scott Terrence L. ; Di Jie ; Sudhalter Judith ; Blizzard Charles D., Macromolecular microparticles and methods of production and use.
Woiszwillo James E. ; Brown Larry R. ; Scott Terrence L. ; Di Jie ; Sudhalter Judith ; Blizzard Charles D. ; Riske Frank J., Macromolecular microparticles and methods of production and use.
Woiszwillo James E. ; Brown Larry R. ; Scott Terrence L. ; Di Jie ; Sudhalter Judith ; Blizzard Charles D. ; Riske Frank J., Macromolecular microparticles and methods of production and use.
Kuo George (San Francisco CA) Masiarz Frank (San Francisco CA) Truett Martha (Oakland CA) Valenzuela Pablo (San Francisco CA), Method and composition for preparation of factor VIIIC.
Tice Thomas R. ; Gilley Richard M. ; Eldridge John H. ; Staas Jay K., Method for delivering bioactive agents into and through the mucosally-associated lymphoid tissues and controlling their.
D\Arrigo Joseph S. (Farmington CT), Method for the production of medical-grade lipid-coated microbubbles, paramagnetic labeling of such microbubbles and the.
Spira Jack,SEX ; Widlund Lars,SEX ; Osterberg Thomas,SEX, Method for treatment of hemophilia by extravascular administration of factor VIII deletion derivatives.
Jolly, Douglas J.; Chang, Stephen; Respess, James G.; DePolo, Nicholas J.; Hsu, David Chi-Tang; Ibanez, Carlos E.; Greengard, Judith; Will, Lee, Methods for administration of recombinant gene delivery vehicles for treatment of hemophilia and other disorders.
Schellenberger, Volker; Stemmer, Willem P.; Wang, Chia-wei; Scholle, Michael D.; Popkov, Mikhail; Gordon, Nathaniel C.; Crameri, Andreas, Methods for production of unstructured recombinant polymers and uses thereof.
Andrew S. Janoff ; Thomas D. Madden CA; Pieter R. Cullis CA; John J. Kearns ; Anthony G. Durning, Methods of preparing low-toxicity drug-lipid complexes.
Tice, Thomas R.; Dillon, Deborah L.; Mason, David W.; McRae-McFarlane, Amanda; Dahlstrom, Annica B., Microcapsules for administration of neuroactive agents.
Harrison Juan M. E. (Mountain View CA) Barclay Brian L. (Sunnyvale CA) Childers Jerry D. (Menlo Park CA) Wright Jeri D. (Dublin CA) Place Virgil A. (Kawaihae HI) Wong Patrick S. (Palo Alto CA), Oral osmotic device with hydrogel driving member.
Popescu Mircea C. ; Weiner Alan L. ; Recine Marie S. ; Janoff Andrew S. ; Estis Leonard ; Keyes Lynn D. ; Alving Carl R., Peptide-containing liposomes, immunogenic liposomes and methods of preparation and use.
Capon Daniel J. (San Mateo CA) Lawn Richard M. (San Francisco CA) Levinson Arthur D. (Hillsborough CA) Vehar Gordon A. (San Carlos CA) Wood William I. (San Mateo CA), Preparation of functional human factor VIII in mammalian cells using methotrexate based selection.
Chapman Barbara ; Burke Rae Lyn ; Rasmussen Mirella Ezban,DKX ; Mikkelson Jan Moller,DKX, Protein complexes having Factor VIII:C activity and production thereof.
Van Ooyen Albert Johannes Joseph,NLX ; Pannekoek Hans,NLX ; Verbeet Martinus Philippus,NLX ; Van Leen Robert Willem,NLX, Proteins with Factor VIII activity: process for their preparation using genetically-engineered cells and pharmaceutical compositions containing them.
van Ooyen Albert J. J. (Voorburg NLX) Pannekoek Hans (Aalsmeer NLX) Verbeet Martinus P. (Amsterdam NLX) van Leen Robert W. (Nijmegen NLX), Proteins with factor VIII activity: process for their preparation using genetically-engineered cells and pharmaceutical.
Albert Johannes Joseph Van Ooyen NL; Hans Pannekoek NL; Martinus Philippus Verbeet NL; Robert Willem Van Leen NL, Proteins with factor VIII activity: process for their preparation using genetically-engineered cells and pharmaceutical compositions containing them.
Edward M. Rudnic ; Beth A. Burnside ; Henry H. Flanner ; Sandra E. Wassink ; Richard A. Couch ; Jill E. Pinkett, Soluble form osmotic dose delivery system.
Rudnic Edward M. ; Burnside Beth A. ; Flanner Henry H. ; Wassink Sandra E. ; Couch Richard A. ; Pinkett Jill E., Soluble form osmotic dose delivery system.
Rudnic, Edward M.; Burnside, Beth A.; Flanner, Henry H.; Wassink, Sandra E.; Couch, Richard A.; Pinkett, Jill E., Soluble form osmotic dose delivery system.
D\Arrigo Joseph S. (23A Brickyard Rd. Farmington CT 06032), Surfactant mixtures, stable gas-in-liquid emulsions, and methods for the production of such emulsions from said mixtures.
Wheatley Margaret A. (Norristown PA) Langer Robert S. (Somerville MA) Eisen Herman N. (Waban MA), System for controlled release of biologically active compounds.
Adler-Moore Jill ; Gamble Ronald C. ; Proffitt Richard T., Treatment of systemic fungal infections with phospholipid particles encapsulating polyene antibiotics.
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