LISTADO DE SECUENCIAS <110> Loxo Oncology, Inc. <120> FORMULACIONES LÍQUIDAS DE (S)-N-(5-((R)-2-(2,5-DIFLUOROFENIL) -PIRROLIDIN-1-IL)-PIRAZOLO[1,5-A]PIRIMIDIN-3-IL) -3-HIDROXIPIRROLIDINA-1-CARBOXAMIDA <130> 42001-0005WO1 <150> 62/329,561 <151> 2016-04-29 <150> 62/323,452 <151> 2016-04-15 <150> 62/318,041 <151> 2016-04-04 <160> 3 <170> PatentIn version 3.5 <210> 1 <211> 796 <212> PRT <213> Homo sapiens <400> 1 Met Leu Arg Gly Gly Arg Arg Gly Gln Leu Gly Trp His Ser Trp Ala 1 5 10 15 Ala Gly Pro Gly Ser Leu Leu Ala Trp Leu Ile Leu Ala Ser Ala Gly 20 25 30 Ala Ala Pro Cys Pro Asp Ala Cys Cys Pro His Gly Ser Ser Gly Leu 35 40 45 Arg Cys Thr Arg Asp Gly Ala Leu Asp Ser Leu His His Leu Pro Gly 50 55 60 Ala Glu Asn Leu Thr Glu Leu Tyr Ile Glu Asn Gln Gln His Leu Gln 65 70 75 80 His Leu Glu Leu Arg Asp Leu Arg Gly Leu Gly Glu Leu Arg Asn Leu 85 90 95 Thr Ile Val Lys Ser Gly Leu Arg Phe Val Ala Pro Asp Ala Phe His 100 105 110 Phe Thr Pro Arg Leu Ser Arg Leu Asn Leu Ser Phe Asn Ala Leu Glu 115 120 125 Ser Leu Ser Trp Lys Thr Val Gln Gly Leu Ser Leu Gln Glu Leu Val 130 135 140 Leu Ser Gly Asn Pro Leu His Cys Ser Cys Ala Leu Arg Trp Leu Gln 145 150 155 160 Arg Trp Glu Glu Glu Gly Leu Gly Gly Val Pro Glu Gln Lys Leu Gln 165 170 175 Cys His Gly Gln Gly Pro Leu Ala His Met Pro Asn Ala Ser Cys Gly 180 185 190 Val Pro Thr Leu Lys Val Gln Val Pro Asn Ala Ser Val Asp Val Gly 195 200 205 Asp Asp Val Leu Leu Arg Cys Gln Val Glu Gly Arg Gly Leu Glu Gln 210 215 220 Ala Gly Trp Ile Leu Thr Glu Leu Glu Gln Ser Ala Thr Val Met Lys 225 230 235 240 Ser Gly Gly Leu Pro Ser Leu Gly Leu Thr Leu Ala Asn Val Thr Ser 245 250 255 Asp Leu Asn Arg Lys Asn Val Thr Cys Trp Ala Glu Asn Asp Val Gly 260 265 270 Arg Ala Glu Val Ser Val Gln Val Asn Val Ser Phe Pro Ala Ser Val 275 280 285 Gln Leu His Thr Ala Val Glu Met His His Trp Cys Ile Pro Phe Ser 290 295 300 Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser 305 310 315 320 Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Ala 325 330 335 Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr 340 345 350 His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Phe Gly 355 360 365 Gln Ala Ser Ala Ser Ile Met Ala Ala Phe Met Asp Asn Pro Phe Glu 370 375 380 Phe Asn Pro Glu Asp Pro Ile Pro Val Ser Phe Ser Pro Val Asp Thr 385 390 395 400 Asn Ser Thr Ser Gly Asp Pro Val Glu Lys Lys Asp Glu Thr Pro Phe 405 410 415 Gly Val Ser Val Ala Val Gly Leu Ala Val Phe Ala Cys Leu Phe Leu 420 425 430 Ser Thr Leu Leu Leu Val Leu Asn Lys Cys Gly Arg Arg Asn Lys Phe 435 440 445 Gly Ile Asn Arg Pro Ala Val Leu Ala Pro Glu Asp Gly Leu Ala Met 450 455 460 Ser Leu His Phe Met Thr Leu Gly Gly Ser Ser Leu Ser Pro Thr Glu 465 470 475 480 Gly Lys Gly Ser Gly Leu Gln Gly His Ile Ile Glu Asn Pro Gln Tyr 485 490 495 Phe Ser Asp Ala Cys Val His His Ile Lys Arg Arg Asp Ile Val Leu 500 505 510 Lys Trp Glu Leu Gly Glu Gly Ala Phe Gly Lys Val Phe Leu Ala Glu 515 520 525 Cys His Asn Leu Leu Pro Glu Gln Asp Lys Met Leu Val Ala Val Lys 530 535 540 Ala Leu Lys Glu Ala Ser Glu Ser Ala Arg Gln Asp Phe Gln Arg Glu 545 550 555 560 Ala Glu Leu Leu Thr Met Leu Gln His Gln His Ile Val Arg Phe Phe 565 570 575 Gly Val Cys Thr Glu Gly Arg Pro Leu Leu Met Val Phe Glu Tyr Met 580 585 590 Arg His Gly Asp Leu Asn Arg Phe Leu Arg Ser His Gly Pro Asp Ala 595 600 605 Lys Leu Leu Ala Gly Gly Glu Asp Val Ala Pro Gly Pro Leu Gly Leu 610 615 620 Gly Gln Leu Leu Ala Val Ala Ser Gln Val Ala Ala Gly Met Val Tyr 625 630 635 640 Leu Ala Gly Leu His Phe Val His Arg Asp Leu Ala Thr Arg Asn Cys 645 650 655 Leu Val Gly Gln Gly Leu Val Val Lys Ile Gly Asp Phe Gly Met Ser 660 665 670 Arg Asp Ile Tyr Ser Thr Asp Tyr Tyr Arg Val Gly Gly Arg Thr Met 675 680 685 Leu Pro Ile Arg Trp Met Pro Pro Glu Ser Ile Leu Tyr Arg Lys Phe 690 695 700 Thr Thr Glu Ser Asp Val Trp Ser Phe Gly Val Val Leu Trp Glu Ile 705 710 715 720 Phe Thr Tyr Gly Lys Gln Pro Trp Tyr Gln Leu Ser Asn Thr Glu Ala 725 730 735 Ile Asp Cys Ile Thr Gln Gly Arg Glu Leu Glu Arg Pro Arg Ala Cys 740 745 750 Pro Pro Glu Val Tyr Ala Ile Met Arg Gly Cys Trp Gln Arg Glu Pro 755 760 765 Gln Gln Arg His Ser Ile Lys Asp Val His Ala Arg Leu Gln Ala Leu 770 775 780 Ala Gln Ala Pro Pro Val Tyr Leu Asp Val Leu Gly 785 790 795 <210> 2 <211> 822 <212> PRT <213> Homo sapiens <400> 2 Met Ser Ser Trp Ile Arg Trp His Gly Pro Ala Met Ala Arg Leu Trp 1 5 10 15 Gly Phe Cys Trp Leu Val Val Gly Phe Trp Arg Ala Ala Phe Ala Cys 20 25 30 Pro Thr Ser Cys Lys Cys Ser Ala Ser Arg Ile Trp Cys Ser Asp Pro 35 40 45 Ser Pro Gly Ile Val Ala Phe Pro Arg Leu Glu Pro Asn Ser Val Asp 50 55 60 Pro Glu Asn Ile Thr Glu Ile Phe Ile Ala Asn Gln Lys Arg Leu Glu 65 70 75 80 Ile Ile Asn Glu Asp Asp Val Glu Ala Tyr Val Gly Leu Arg Asn Leu 85 90 95 Thr Ile Val Asp Ser Gly Leu Lys Phe Val Ala His Lys Ala Phe Leu 100 105 110 Lys Asn Ser Asn Leu Gln His Ile Asn Phe Thr Arg Asn Lys Leu Thr 115 120 125 Ser Leu Ser Arg Lys His Phe Arg His Leu Asp Leu Ser Glu Leu Ile 130 135 140 Leu Val Gly Asn Pro Phe Thr Cys Ser Cys Asp Ile Met Trp Ile Lys 145 150 155 160 Thr Leu Gln Glu Ala Lys Ser Ser Pro Asp Thr Gln Asp Leu Tyr Cys 165 170 175 Leu Asn Glu Ser Ser Lys Asn Ile Pro Leu Ala Asn Leu Gln Ile Pro 180 185 190 Asn Cys Gly Leu Pro Ser Ala Asn Leu Ala Ala Pro Asn Leu Thr Val 195 200 205 Glu Glu Gly Lys Ser Ile Thr Leu Ser Cys Ser Val Ala Gly Asp Pro 210 215 220 Val Pro Asn Met Tyr Trp Asp Val Gly Asn Leu Val Ser Lys His Met 225 230 235 240 Asn Glu Thr Ser His Thr Gln Gly Ser Leu Arg Ile Thr Asn Ile Ser 245 250 255 Ser Asp Asp Ser Gly Lys Gln Ile Ser Cys Val Ala Glu Asn Leu Val 260 265 270 Gly Glu Asp Gln Asp Ser Val Asn Leu Thr Val His Phe Ala Pro Thr 275 280 285 Ile Thr Phe Leu Glu Ser Pro Thr Ser Asp His His Trp Cys Ile Pro 290 295 300 Phe Thr Val Lys Gly Asn Pro Lys Pro Ala Leu Gln Trp Phe Tyr Asn 305 310 315 320 Gly Ala Ile Leu Asn Glu Ser Lys Tyr Ile Cys Thr Lys Ile His Val 325 330 335 Thr Asn His Thr Glu Tyr His Gly Cys Leu Gln Leu Asp Asn Pro Thr 340 345 350 His Met Asn Asn Gly Asp Tyr Thr Leu Ile Ala Lys Asn Glu Tyr Gly 355 360 365 Lys Asp Glu Lys Gln Ile Ser Ala His Phe Met Gly Trp Pro Gly Ile 370 375 380 Asp Asp Gly Ala Asn Pro Asn Tyr Pro Asp Val Ile Tyr Glu Asp Tyr 385 390 395 400 Gly Thr Ala Ala Asn Asp Ile Gly Asp Thr Thr Asn Arg Ser Asn Glu 405 410 415 Ile Pro Ser Thr Asp Val Thr Asp Lys Thr Gly Arg Glu His Leu Ser 420 425 430 Val Tyr Ala Val Val Val Ile Ala Ser Val Val Gly Phe Cys Leu Leu 435 440 445 Val Met Leu Phe Leu Leu Lys Leu Ala Arg His Ser Lys Phe Gly Met 450 455 460 Lys Gly Pro Ala Ser Val Ile Ser Asn Asp Asp Asp Ser Ala Ser Pro 465 470 475 480 Leu His His Ile Ser Asn Gly Ser Asn Thr Pro Ser Ser Ser Glu Gly 485 490 495 Gly Pro Asp Ala Val Ile Ile Gly Met Thr Lys Ile Pro Val Ile Glu 500 505 510 Asn Pro Gln Tyr Phe Gly Ile Thr Asn Ser Gln Leu Lys Pro Asp Thr 515 520 525 Phe Val Gln His Ile Lys Arg His Asn Ile Val Leu Lys Arg Glu Leu 530 535 540 Gly Glu Gly Ala Phe Gly Lys Val Phe Leu Ala Glu Cys Tyr Asn Leu 545 550 555 560 Cys Pro Glu Gln Asp Lys Ile Leu Val Ala Val Lys Thr Leu Lys Asp 565 570 575 Ala Ser Asp Asn Ala Arg Lys Asp Phe His Arg Glu Ala Glu Leu Leu 580 585 590 Thr Asn Leu Gln His Glu His Ile Val Lys Phe Tyr Gly Val Cys Val 595 600 605 Glu Gly Asp Pro Leu Ile Met Val Phe Glu Tyr Met Lys His Gly Asp 610 615 620 Leu Asn Lys Phe Leu Arg Ala His Gly Pro Asp Ala Val Leu Met Ala 625 630 635 640 Glu Gly Asn Pro Pro Thr Glu Leu Thr Gln Ser Gln Met Leu His Ile 645 650 655 Ala Gln Gln Ile Ala Ala Gly Met Val Tyr Leu Ala Ser Gln His Phe 660 665 670 Val His Arg Asp Leu Ala Thr Arg Asn Cys Leu Val Gly Glu Asn Leu 675 680 685 Leu Val Lys Ile Gly Asp Phe Gly Met Ser Arg Asp Val Tyr Ser Thr 690 695 700 Asp Tyr Tyr Arg Val Gly Gly His Thr Met Leu Pro Ile Arg Trp Met 705 710 715 720 Pro Pro Glu Ser Ile Met Tyr Arg Lys Phe Thr Thr Glu Ser Asp Val 725 730 735 Trp Ser Leu Gly Val Val Leu Trp Glu Ile Phe Thr Tyr Gly Lys Gln 740 745 750 Pro Trp Tyr Gln Leu Ser Asn Asn Glu Val Ile Glu Cys Ile Thr Gln 755 760 765 Gly Arg Val Leu Gln Arg Pro Arg Thr Cys Pro Gln Glu Val Tyr Glu 770 775 780 Leu Met Leu Gly Cys Trp Gln Arg Glu Pro His Met Arg Lys Asn Ile 785 790 795 800 Lys Gly Ile His Thr Leu Leu Gln Asn Leu Ala Lys Ala Ser Pro Val 805 810 815 Tyr Leu Asp Ile Leu Gly 820 <210> 3 <211> 839 <212> PRT <213> Homo sapiens <400> 3 Met Asp Val Ser Leu Cys Pro Ala Lys Cys Ser Phe Trp Arg Ile Phe 1 5 10 15 Leu Leu Gly Ser Val Trp Leu Asp Tyr Val Gly Ser Val Leu Ala Cys 20 25 30 Pro Ala Asn Cys Val Cys Ser Lys Thr Glu Ile Asn Cys Arg Arg Pro 35 40 45 Asp Asp Gly Asn Leu Phe Pro Leu Leu Glu Gly Gln Asp Ser Gly Asn 50 55 60 Ser Asn Gly Asn Ala Ser Ile Asn Ile Thr Asp Ile Ser Arg Asn Ile 65 70 75 80 Thr Ser Ile His Ile Glu Asn Trp Arg Ser Leu His Thr Leu Asn Ala 85 90 95 Val Asp Met Glu Leu Tyr Thr Gly Leu Gln Lys Leu Thr Ile Lys Asn 100 105 110 Ser Gly Leu Arg Ser Ile Gln Pro Arg Ala Phe Ala Lys Asn Pro His 115 120 125 Leu Arg Tyr Ile Asn Leu Ser Ser Asn Arg Leu Thr Thr Leu Ser Trp 130 135 140 Gln Leu Phe Gln Thr Leu Ser Leu Arg Glu Leu Gln Leu Glu Gln Asn 145 150 155 160 Phe Phe Asn Cys Ser Cys Asp Ile Arg Trp Met Gln Leu Trp Gln Glu 165 170 175 Gln Gly Glu Ala Lys Leu Asn Ser Gln Asn Leu Tyr Cys Ile Asn Ala 180 185 190 Asp Gly Ser Gln Leu Pro Leu Phe Arg Met Asn Ile Ser Gln Cys Asp 195 200 205 Leu Pro Glu Ile Ser Val Ser His Val Asn Leu Thr Val Arg Glu Gly 210 215 220 Asp Asn Ala Val Ile Thr Cys Asn Gly Ser Gly Ser Pro Leu Pro Asp 225 230 235 240 Val Asp Trp Ile Val Thr Gly Leu Gln Ser Ile Asn Thr His Gln Thr 245 250 255 Asn Leu Asn Trp Thr Asn Val His Ala Ile Asn Leu Thr Leu Val Asn 260 265 270 Val Thr Ser Glu Asp Asn Gly Phe Thr Leu Thr Cys Ile Ala Glu Asn 275 280 285 Val Val Gly Met Ser Asn Ala Ser Val Ala Leu Thr Val Tyr Tyr Pro 290 295 300 Pro Arg Val Val Ser Leu Glu Glu Pro Glu Leu Arg Leu Glu His Cys 305 310 315 320 Ile Glu Phe Val Val Arg Gly Asn Pro Pro Pro Thr Leu His Trp Leu 325 330 335 His Asn Gly Gln Pro Leu Arg Glu Ser Lys Ile Ile His Val Glu Tyr 340 345 350 Tyr Gln Glu Gly Glu Ile Ser Glu Gly Cys Leu Leu Phe Asn Lys Pro 355 360 365 Thr His Tyr Asn Asn Gly Asn Tyr Thr Leu Ile Ala Lys Asn Pro Leu 370 375 380 Gly Thr Ala Asn Gln Thr Ile Asn Gly His Phe Leu Lys Glu Pro Phe 385 390 395 400 Pro Glu Ser Thr Asp Asn Phe Ile Leu Phe Asp Glu Val Ser Pro Thr 405 410 415 Pro Pro Ile Thr Val Thr His Lys Pro Glu Glu Asp Thr Phe Gly Val 420 425 430 Ser Ile Ala Val Gly Leu Ala Ala Phe Ala Cys Val Leu Leu Val Val 435 440 445 Leu Phe Val Met Ile Asn Lys Tyr Gly Arg Arg Ser Lys Phe Gly Met 450 455 460 Lys Gly Pro Val Ala Val Ile Ser Gly Glu Glu Asp Ser Ala Ser Pro 465 470 475 480 Leu His His Ile Asn His Gly Ile Thr Thr Pro Ser Ser Leu Asp Ala 485 490 495 Gly Pro Asp Thr Val Val Ile Gly Met Thr Arg Ile Pro Val Ile Glu 500 505 510 Asn Pro Gln Tyr Phe Arg Gln Gly His Asn Cys His Lys Pro Asp Thr 515 520 525 Tyr Val Gln His Ile Lys Arg Arg Asp Ile Val Leu Lys Arg Glu Leu 530 535 540 Gly Glu Gly Ala Phe Gly Lys Val Phe Leu Ala Glu Cys Tyr Asn Leu 545 550 555 560 Ser Pro Thr Lys Asp Lys Met Leu Val Ala Val Lys Ala Leu Lys Asp 565 570 575 Pro Thr Leu Ala Ala Arg Lys Asp Phe Gln Arg Glu Ala Glu Leu Leu 580 585 590 Thr Asn Leu Gln His Glu His Ile Val Lys Phe Tyr Gly Val Cys Gly 595 600 605 Asp Gly Asp Pro Leu Ile Met Val Phe Glu Tyr Met Lys His Gly Asp 610 615 620 Leu Asn Lys Phe Leu Arg Ala His Gly Pro Asp Ala Met Ile Leu Val 625 630 635 640 Asp Gly Gln Pro Arg Gln Ala Lys Gly Glu Leu Gly Leu Ser Gln Met 645 650 655 Leu His Ile Ala Ser Gln Ile Ala Ser Gly Met Val Tyr Leu Ala Ser 660 665 670 Gln His Phe Val His Arg Asp Leu Ala Thr Arg Asn Cys Leu Val Gly 675 680 685 Ala Asn Leu Leu Val Lys Ile Gly Asp Phe Gly Met Ser Arg Asp Val 690 695 700 Tyr Ser Thr Asp Tyr Tyr Arg Leu Phe Asn Pro Ser Gly Asn Asp Phe 705 710 715 720 Cys Ile Trp Cys Glu Val Gly Gly His Thr Met Leu Pro Ile Arg Trp 725 730 735 Met Pro Pro Glu Ser Ile Met Tyr Arg Lys Phe Thr Thr Glu Ser Asp 740 745 750 Val Trp Ser Phe Gly Val Ile Leu Trp Glu Ile Phe Thr Tyr Gly Lys 755 760 765 Gln Pro Trp Phe Gln Leu Ser Asn Thr Glu Val Ile Glu Cys Ile Thr 770 775 780 Gln Gly Arg Val Leu Glu Arg Pro Arg Val Cys Pro Lys Glu Val Tyr 785 790 795 800 Asp Val Met Leu Gly Cys Trp Gln Arg Glu Pro Gln Gln Arg Leu Asn 805 810 815 Ile Lys Glu Ile Tyr Lys Ile Leu His Ala Leu Gly Lys Ala Thr Pro 820 825 830 Ile Tyr Leu Asp Ile Leu Gly 835