Claims for Patent: 10,183,029

Summary for Patent: 10,183,029

Title:	Oxytocin receptor antagonist therapy in the luteal phase for implantation and pregnancy in women undergoing assisted reproductive technologies
Abstract:	The present invention relates to the use of an oxytocin receptor antagonist in females undergoing embryo transfer as part of an assisted reproductive technology. In particular, methods are provided for increasing ongoing implantation rate, increasing ongoing pregnancy rate, increasing clinical pregnancy rate, and/or increasing live birth rate in a female subject undergoing embryo transfer. Specifically, the antagonists are released in the luteal phase when the endometrium is receptive for embryo implantation and/or when the embryo has reached the blastocyst-stage.
Inventor(s):	Arce; Joan-Carles (Parsippany, NJ)
Assignee:	Ferring B.V. (Hoofddorp, NL)
Application Number:	15/408,256
Patent Claims:	1. A method of treating a female undergoing embryo transfer, comprising: administering to the female luteal phase support, and administering to the female an oxytocin receptor antagonist: (1) only during a time a) between day 6 following luteinizing hormone (LH) surge (LH+6) and day 9 following LH surge (LH+9) of a natural ovulation cycle; b) between day 6 following human chorionic gonadotropin (hCG) administration (hCG+6) and day 9 following hCG administration (hCG+9) of an induced ovulation cycle; c) between day 6 and day 7 of a luteal phase support following oocyte retrieval; or d) between day 6 and day 9 of a luteal phase support; or (2) only on the day of transfer of an embryo, wherein the transferred embryo is a blastocyst-stage embryo. 2. The method of claim 1, wherein the luteal phase support comprises progesterone. 3. The method of claim 2, wherein the luteal phase support comprises about 100 mg progesterone. 4. The method of claim 2, wherein the luteal phase support comprises administration of progesterone at least twice daily. 5. The method of claim 2, further comprising transferring an embryo into the uterus, the uterine cavity, or the fallopian tubes of the female. 6. The method of claim 5, wherein the luteal phase support comprises progesterone administration at least 3 hours before the embryo transfer or at least 3 hours after the embryo transfer. 7. The method of claim 5, wherein the antagonist is administered to the female between 2 hours prior to and 2 hours after embryo transfer. 8. The method of claim 2, wherein the progesterone is administered intramuscularly or vaginally. 9. The method of claim 1, wherein the transferred embryo is a cleavage-stage embryo and the antagonist is administered to the female only during a time a) between day 6 following luteinizing hormone (LH) surge (LH+6) and day 9 following LH surge (LH+9) of a natural ovulation cycle; b) between day 6 following human chorionic gonadotropin (hCG) administration (hCG+6) and day 9 following hCG administration (hCG+9) of an induced ovulation cycle; c) between day 6 and day 7 of a luteal phase support following oocyte retrieval; or d) between day 6 and day 9 of a luteal phase support. 10. The method of claim 9, wherein the cleavage-stage embryo is a day 2 or day 3 post-fertilization embryo. 11. The method of claim 1, wherein the blastocyst-stage embryo has an expansion and hatching status of 3, 4, 5, or 6. 12. The method of claim 1, wherein a blastocyst-stage embryo is transferred to the female, and wherein the antagonist is administered to the female on the same day as the embryo transfer. 13. A method of treating a female undergoing embryo transfer, comprising administering to the female: (i) luteal phase support; and (ii) an oxytocin receptor antagonist only during a time a) between day 6 and day 7 of the luteal phase support following oocyte retrieval; or b) between day 6 and day 9 of the luteal phase support. 14. A method of treating a female undergoing embryo transfer comprising administering to the female an oxytocin receptor antagonist (1) only during a time a) between day 6 following luteinizing hormone (LH) surge (LH+6) and day 9 following LH surge (LH+9) of a natural ovulation cycle; b) between day 6 following human chorionic gonadotropin (hCG) administration (hCG+6) and day 9 following hCG administration (hCG+9) of an induced ovulation cycle; c) between day 6 and day 7 of a luteal phase support following oocyte retrieval; or d) between day 6 and day 9 of a luteal phase support; or (2) only on the day of transfer of an embryo, wherein the transferred embryo is a blastocyst-stage embryo, and wherein the antagonist is barusiban, atosiban, OBE001/AS-602305, TT-235, Epelsiban ((3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-1-[(1R)-1-(2,6-dimethylp- yridin-3-yl)-2-(morpholin-4-yl)-2-oxoethyl]-6-[(1S)-1-methylpropyl]piperaz- ine-2,5-dione); Retosiban ((3R,6R)-6-[(2S)-butan-2-yl]-3-(2,3-dihydro-1H-inden-2-yl)-1-[(1R)-1-(2-m- ethyl-1,3-oxazol-4-yl)-2-(morpholin-4-yl)-2-oxoethyl]piperazine-2,5-dione)- ; PF-3274167 (5-(3-(3-(2-chloro-4-fluorophenoxy)azetidin-1-yl)-5-(methoxymethyl)-4H-1,- 2,4-triazol-4-yl)-2-methoxypyridine); L-368,899 hydrochloride; or L-371,257 (1-[1-[4-(1-acetylpiperidin-4-yl)oxy-2-methoxybenzoyl]piperidin- -4-yl]-4H-3,1-benzoxazin-2-one). 15. The method of claim 14, further comprising transferring an embryo into the uterus, the uterine cavity or the fallopian tubes of the female. 16. The method of claim 14, wherein the antagonist is administered to the female at day 5 post oocyte retrieval. 17. The method of claim 14, wherein the antagonist is administered to the female between 2 hours prior to and 2 hours after the embryo transfer.

Details for Patent 10,183,029

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	January 15, 1974	10,183,029	2037-01-17
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	December 27, 1984	10,183,029	2037-01-17
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	February 15, 1985	10,183,029	2037-01-17
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	February 16, 1990	10,183,029	2037-01-17
Bel-mar Laboratories, Inc.	CHORIONIC GONADOTROPIN	chorionic gonadotropin	Injection	017054	March 26, 1974	10,183,029	2037-01-17
Fresenius Kabi Usa, Llc	CHORIONIC GONADOTROPIN	chorionic gonadotropin	For Injection	017067	March 05, 1973	10,183,029	2037-01-17