1 N N O O N FIG. 1 AJAporksio4pektiewil Arousal EEG Airflow Effort {Rib Cage) Effort (Abdomen) Effort (Pes) Sa0 2 10 sec (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 01 November 2018 (01.11.2018) WIPO I PCT omit VIII °nolo Holollomoinno oimIE (10) International Publication Number WO 2018/200775 Al (51) International Patent Classification: A61K 31/137 (2006.01) A61K 31/551 (2006.01) A61K 31/42 (2006.01) A61K 31/7008 (2006.01) A61K 31/506 (2006.01) A61K 45/06 (2006.01) (21) International Application Number: PCT/US2018/029518 (22) International Filing Date: 26 April 2018 (26.04.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/491,504 28 April 2017 (28.04.2017) US 62/558,814 14 September 2017 (14.09.2017) US (71) Applicant: THE BRIGHAM AND WOMEN'S HOSPI- TAL, INC. [US/US]; 75 Francis Street, Boston, Massachu- setts 02115 (US). (72) Inventors: WELLMAN, D. Andrew; 57 Clubhouse Lane, Wayland, Massachusetts 01778 (US). TARANTO-MON- TEMURRO, Luigi; 55 Sherman Road, Chestnut Hill, Massachusetts 02467 (US). (74) Agent: DEYOUNG, Janice Kugler et al.; Fish & Richardson P.C., P.O. Box 1022, Minneapolis, Minnesota 55440-1022 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, (54) Title: METHODS AND COMPOSITIONS FOR TREATING SLEEP APNEA 1-1 (57) : Methods and compositions for the treatment of conditions associated with pharyngeal airway muscle collapse while the subject is in a non-fully conscious state, e.g., sleep apnea and snoring, comprising administration of a norepinephrine reuptake inhibitor C (NRI) and a muscarinic receptor antagonist. [Continued on next page] WO 2018/200775 Al MIDEDIMOMMIDIREIDIHNONIFIEMOMOVOIMIE TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Published: with international search report (Art. 21(3)) before the expiration of the time limit for amending the claims and to be republished in the event of receipt of amendments (Rule 48.2(h))
METHODS AND COMPOSITIONS FOR TREATING SLEEP APNEA