IP Library Granted Patent US 12,329,740
Granted Patent B2
US 12,329,740 · App. 18/653,318 · Granted Jun 17, 2025

Rescue treatment of post operative nausea and vomiting

Inventors: Julian Clive Gilbert (Duxford, GB); Robert William Gristwood (Duxford, GB); Gabriel Fox (Duxford, GB)
Assignee: Acacia Pharma Limited
A61K31/40A61K9/0019A61K31/4178A61K31/438A61K31/439A61K31/496A61K31/5377A61K31/573A61P1/08
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,329,740
App. No.
18/653,318
Granted
Jun 17, 2025
Kind
B2
Abstract

Amisulpride is useful in the treatment of postoperative nausea and/or vomiting in a patient, wherein the patient has already been administered a prophylaxis drug for postoperative nausea and/or vomiting, and wherein the dose of amisulpride is 7.5 to 15 mg.

Claims (17)

1. A method for treating postoperative nausea and/or vomiting (PONV) in a patient, comprising administering to the patient amisulpride at a dose of 9.5 mg to 10.5 mg, wherein the patient has been administered a non-amisulpride prophylaxis drug at the time of induction of anaesthesia, and wherein the amisulpride is administered by IV infusion over a time period of from about 20 seconds up to about 20 minutes.

2. The method of claim 1 , wherein the prophylaxis drug is not a dopamine-2 (D 2 ) antagonist.

3. The method of claim 1 , wherein the prophylaxis drug is an anti-emetic selected from a 5HT 3 -antagonist, a corticosteroid, an anti-histamine (H1), an anti-cholinergic, a H 2 -antagonist and a NK 1 -antagonist.

4. The method of claim 1 , wherein the amisulpride is administered in combination with another anti-emetic, either sequentially or simultaneously.

5. The method of claim 4 , wherein the another anti-emetic is a 5HT 3 antagonist, an NK 1 antagonist or a steroid.

6. The method of claim 5 , wherein the another anti-emetic is dexamethasone, ondansetron, granisetron, palonosetron, aprepitant, netupitant or rolapitant.

7. The method of claim 1 , wherein the amisulpride is substantially in the form of a racemate.

8. The method of claim 1 , wherein the amisulpride is administered within 1 hour following a first emetic episode and/or following a first nausea episode.

9. The method of claim 8 , wherein the amisulpride is administered within 30 minutes following the first emetic episode and/or following the first nausea episode.

10. The method of claim 9 , wherein the amisulpride is administered within 15 minutes following the first emetic episode and/or following the first nausea episode.

11. The method of claim 1 , wherein the amisulpride is administered by IV infusion over about 1 to 15 minutes.

12. The method of claim 11 , wherein the amisulpride is administered by IV infusion over about 1 to 10 minutes.

13. The method of claim 11 , wherein the amisulpride is administered by IV infusion over about 1 to 5 minutes.

14. The method of claim 11 , wherein the amisulpride is administered by IV infusion over about 1 to 2 minutes.

15. The method of claim 1 , wherein the amisulpride is administered at a dose of 10 mg.

16. The method of claim 1 , wherein the amisulpride is administered as a single daily dose.

17. A method for treating postoperative nausea and/or vomiting (PONV) in a patient, comprising administering to the patient racemic amisulpride at a dose of 9.5 to 10.5 mg, wherein the patient has been administered a non-amisulpride prophylaxis drug at the time of induction of anaesthesia, and wherein the racemic amisulpride is administered by IV infusion over a time period of from about 20 seconds up to about 20 minutes.

Assignments (5)
SECURITY INTEREST Recorded Apr 27, 2026
From: LXO IRELAND DESIGNATED ACTIVITY COMPANY
To: KROLL TRUSTEE SERVICES LIMITED, AS SECURITY AGENT
Reel/Frame 074483/0163 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 4, 2026
From: ACACIA PHARMA LIMITED; ACACIA PHARMA, INC.; EAGLE PHARMACEUTICALS, INC.
To: LXO IRELAND DESIGNATED ACTIVITY COMPANY; LXO US, INC.
Reel/Frame 073967/0303 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 3, 2026
From: GILBERT, JULIAN CLIVE; GRISTWOOD, ROBERT WILLIAM; FOX, GABRIEL
To: ACACIA PHARMA LTD
Reel/Frame 073958/0622 →
RELEASE OF SECURITY INTEREST Recorded Apr 1, 2025
From: JPMORGAN CHASE BANK, N.A., AS ADMINISTRATIVE AGENT
To: ACACIA PHARMA LIMITED
Reel/Frame 070698/0351 →
SECURITY INTEREST Recorded Oct 11, 2024
From: ACACIA PHARMA LIMITED
To: JPMORGAN CHASE BANK, N.A.
Reel/Frame 068873/0911 →
Priority Claims (1)
GB 1702250 · Feb 10, 2017 · national
Continuity (3)
Continuation 17746032 · May 17, 2022
Continuation 16485008
Related Publication 20240285579A1 · Aug 29, 2024
References Cited (101)
US 4294828A · Thominet et al. · 1981 [cited by applicant]
US 4401822A · Thominet et al. · 1983 [cited by applicant]
US 5952340A · Sanger et al. · 1999 [cited by applicant]
US 6169094B1 · Perrault et al. · 2001 [cited by applicant]
US 8686019B2 · Gilbert et al. · 2014 [cited by applicant]
US 8691836B2 · Luehr et al. · 2014 [cited by applicant]
US 9119836B2 · Gilbert et al. · 2015 [cited by applicant]
US 9545426B2 · Gilbert et al. · 2017 [cited by applicant]
US 9889118B2 · Gilbert et al. · 2018 [cited by applicant]
US 10085970B2 · Gilbert et al. · 2018 [cited by applicant]
US 10525033B2 · Gilbert et al. · 2020 [cited by applicant]
US 11357753B2 · Gilbert · 2022 [cited by examiner]
US 12005042B2 · Gilbert · 2024 [cited by examiner]
US 20060074101A1 · Baroni et al. · 2006 [cited by applicant]
US 20070190145A1 · Venkatesh et al. · 2007 [cited by applicant]
US 20080188537A1 · Azorin · 2008 [cited by applicant]
US 20090163544A1 · Rigby et al. · 2009 [cited by applicant]
US 20090175939A1 · Bosse et al. · 2009 [cited by applicant]
US 20110003005A1 · Venkatesh et al. · 2011 [cited by applicant]
US 20130022688A1 · Gilbert et al. · 2013 [cited by applicant]
US 20140350005A1 · Luehr et al. · 2014 [cited by applicant]
US 20150099004A1 · Toti et al. · 2015 [cited by applicant]
US 20190262310A1 · Gilbert et al. · 2019 [cited by applicant]
US 20200038369A1 · Gilbert et al. · 2020 [cited by applicant]
US 20200093792A1 · Gilbert et al. · 2020 [cited by applicant]
US 20210228543A1 · Gilbert et al. · 2021 [cited by applicant]
US 20220296570A1 · Gilbert et al. · 2022 [cited by applicant]
US 20230263799A1 · Trento et al. · 2023 [cited by applicant]
AU 2002361185A1 · 2003 [cited by applicant]
DE 102005013726A1 · 2006 [cited by applicant]
GB 10040202 · 2010 [cited by applicant]
WO 0003740A2 · 2000 [cited by applicant]
WO 2006106358A2 · 2006 [cited by applicant]
WO 2007067714A2 · 2007 [cited by applicant]
WO 2007090082A2 · 2007 [cited by applicant]
WO 2007093909A1 · 2007 [cited by applicant]
WO 2009126931A2 · 2009 [cited by applicant]
WO 2011110854A2 · 2011 [cited by applicant]
WO 2016162695A1 · 2016 [cited by applicant]
Acacia Pharma: “Acacia Pharma Announces Positive Results from Second Pivotal Phase 3 Study of Baremsis tm (APD421) in Prevention of Post-operative Nausea & Vomiting”, 8 pages, (2016), Retrieved from the Internet URL: ht… [cited by applicant]
Castelli et al.“(−} S amisulpride binds with high affinity to cloned dopamine 03 and 02 receptors”, European Journal of Pharmacology 432 (2001) 143-147. [cited by applicant]
Chen and Ensor, “The Influence of Diphenhydramine.cndot. HC1 (Benadryl) on Apomorphine-Induced Emesis in Dogs”, Journal of Pharmacology and Experimental Therapeutics, 98:245-250 (1950). [cited by applicant]
Chinese Office Action issued in CN 201780068552.8 dated Feb. 16, 2022. [cited by applicant]
Cook-Sather et al., “Cisapride Does Not Prevent Postoperative Vomiting in Children”, Anesth Analg, vol. 94, No. 1, 2002, pp. 50-54. [cited by applicant]
Depoortere et al. “Apomorphine-Induced Emesis in Dogs: Differential Sensitivity to Established and Novel Dopamine D2/5-HT1A Antipsychotic Compounds.” Eur. J. Pharmcol. 597.1-3(2008):34-38. [cited by applicant]
Dopaminergic receptors, New Pharmacology (New Yakuri-gaku) 3rd Edition, Japan, Nankodo, Nov. 2, 19965, p. 112-113. [cited by applicant]
Elwood, et al., Emesis in dogs: a review, Journal of Small Animal Practice, vol. 51, Jan. 2010, 4-22. [cited by applicant]
F'ernanoez-Gonzalez, “Tissue and plasma distribution of exogenous growth hormone-releasing factor analogue (GRF1-29NH2) after intravenous, subcutaneous and intraperitoneal injection in the rat”, General Pharmacology: Th… [cited by applicant]
Gan et al. “Consensus Guidelines for the Management of Postoperative Nausea and Vomiting”, Anesthesia & Analgesia, vol. 118, No. 1, pp. 85-113, 2014. [cited by applicant]
Gan et al., “Fourth Consensus Guidelines for the Management of Postoperative Nausea and Vomiting”, Anesth Analg, Aug. 2020, vol. 131, No. 2, pp. 411-448. [cited by applicant]
Gan TJ. et al., “Intravenous Amisulpride for the Prevention of Postoperative Nausea and Vomiting: Two Concurrent, Randomized, Double-blind, Placebo-controlled Trials”, Anesthesiology, vol. 126, No. 2, pp. 268-275 (2017). [cited by applicant]
Gardner et al., “The broad-spectrum anti-emetic activity of the novel non-peptide tachykinin NK1 receptor antagonist GR203040”, British Journal of Pharmacology, 1995, vol. 116, pp. 3158-3163. [cited by applicant]
Grant et al., “Dose-ranging evaluation of the substituted benzamide dazopride when used as an antiemteic in patients receiving anticanceer chemotherapy”, Cancer Chemother. Pharmacol., 1993, vol. 31, Issue 6, pp. 442-444. [cited by applicant]
Guslandi M. “The Clinical Use of Levosulpiride”, Current Therapeutic Research, vol. 53, No. 5, pp. 484-501, 1993. [cited by applicant]
Guslandi M: “Antiemetic properties of levo-sulpiride”, Minerva Medica, Edizioni Minerva Medica, Torino, IT, vol. 81, No. 12, Dec. 1, 1990 (Dec. 1, 1990), pp. 855-860. [cited by applicant]
Habib et al., “Amisulpride for the Rescue Treatment of Postoperative Nausea or Vomiting in Patients Failing Prophylaxis, A Randomized, Placebo-controlled Phase III Trial”, Anesthesiology, Feb. 2019, vol. 130, No. 2, pp.… [cited by applicant]
Hesketh, “Chemotherapy-induced nausea and vomiting,” The New England Journal of Medicine, vol. 358, No. 23, Jun. 5, 2008, pp. 2482-2494. [cited by applicant]
Hesketh, P.J., “Defining the Emetogenicity of Cancer Chemotherapy Regimens: Relevance to Clinical Practice”, The Oncologist, 4:191-196 (1999). [cited by applicant]
Hirokawa et al., “Synthesis and Structure-Affinity Relationships of Novel N-(1-Ethyl-4-methylhexahydro-1.4-diazepin-6-yl)pyridine-3-carboxamides with Potent Serotonin 5-HT3 and Dopamine 02 Receptor Antagonistic Activity… [cited by applicant]
Hooper et al., “SAMBA Consensus Guidelines for the Management of Postoperative Nausea and Vomiting: An Executive Summary for Perianesthesia Nurses”, Oct. 2015, vol. 30, No. 5, pp. 377-382. [cited by applicant]
International Preliminary Report on Patentability issued in PCT/GB2011/050472 dated Jun. 6, 2012. [cited by applicant]
International Search Report and Written Opinion issued in Application No. PCT/GB2017/053288 dated Jan. 23, 2018. [cited by applicant]
International Search Report and Written Opinion issued in Application No. PCT/GB2018/050374 dated Apr. 30, 2018. [cited by applicant]
International Search Report and Written Opinion issued in PCT/GB2011/050472 dated Sep. 21, 2011. [cited by applicant]
Jordan et al. “Neue antiemetische Strategien—nicht nur in der Onkologie.” Der Internist. 50.7(2009):887-894. (German Original and English Abstract). [cited by applicant]
Kranke et al., “Intravenous Buspirone for the Prevention of Postoperative Nausea and Vomiting”, Eur. J. Clin. PharmacoL 68: 1465-1472 (2012). [cited by applicant]
Kranke et al., “I.V. APD421 (amisulpride) prevents postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled, multicentre trial”, BJA: British Journal of Anaesthesia, 2013, vol. 111, Issue 6, pp.… [cited by applicant]
Kranke P. et al. “I.V. APD421 (amisulpride) prevents postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled, multicentre trial”, British Journal of Anaesthesia, vol. 111, No. 6, pp. 938-945 (2… [cited by applicant]
Lefebvre et al., “Gastric relaxation and vomiting by apomorphine, morphine and fentanyl in the conscious dog”, European Journal of Pharmacology, 1981, vol. 69, pp. 139-145. [cited by applicant]
Maggi et al., “Controlled Study of the Bioavailability of a Naproxen Salt by Various Routes of Administration in Healthy Volunteers”, 1987, pp. 303-310. [cited by applicant]
Magnani, M., “Amisulpride: Pharmacological and biochemical aspects”, Farmacia E Clinica, 33(3):91-97 (1994). [cited by applicant]
Makita, K., Practical Anesthesia Series “Countermeasure to PONY and Anesthesia”, Anet. (quarterly journal), Maruishi Pharmaceutical, vol. 8, No. 2, pp. 18-24 (2004). [cited by applicant]
McCracken et al., “Guideline for the Management of Postoperative Nausea and Vomiting”, SOGC Clinical Practice Guideline, No. 209, pp. 600-607 (2008). [cited by applicant]
Metoclopramide and haloperidol for the prophylaxis and treatment of nausea or vomiting induced by epidural injection of morphine for pain relief, Chinese Journal of Pain Medicine, vol. 4, No. 3, p. 167, 1998. [cited by applicant]
Minami et al., “Role of serotonin in emesis,” Folia Pharmacal., pp. 233-242, vol. 108 (1996). [cited by applicant]
Modem Surgical Anesthesia and perioperative treatment, Genetics et al. Eds. Guillin Scientific, 1st edition publication date 20160930 pp. 337-338. [cited by applicant]
Murakuni, “Mechanism of action of morphine in nausea/vomiting and countermeasures”, Palliative Medicine, vol. 3, No. 1: pp. 72-78 (2001). [cited by applicant]
NCT0150704, Clinicaltrials''gov archive, History of Changes for Study: NCT01510704, Submitted Date: May 15, 2013 (v4), https://clinicaltrials.gov/ct2/history/nct01510704?V_4=View#StudyPageTop[Search Date: Jul. 28, 2021]… [cited by applicant]
NCT02646566, Study of APD421 as PONV Treatment (Prior Prophylaxis), 2017, Clinicaltrials.gov, 5 pages. [cited by applicant]
Office Action issued in JP 2012-556586 mailed Nov. 27, 2014. [cited by applicant]
Office Action issued in JP 2015-187057 dated Jul. 27, 2016. [cited by applicant]
Office Action issued in JP 2019-523638 dated Aug. 25, 2021. [cited by applicant]
Pizzo et al., “Oral cisapride for the control of delayed vomiting following high-dose cisplatin”, Supportive Care in Cancer, vol. 7, No. 1, 1999, pp. 44-46. [cited by applicant]
Porreca et al. “Nausea and Vomiting Side Effects with Opioid Analgesics During Treatment of Chronic Pain: Mechanisms, Implications, and Management Options.” Pain Med. 10.4(2009):654-662. [cited by applicant]
Puech et al. “Pharmacological Classification of Benzamides.” Acta Psyhciatr. Scand. Suppl. 311(1984):139-143. [cited by applicant]
Research progress in antiemetic drugs for chemotherapy, Journal of Shantou University Medical College, vol. 21, No. 2, pp. 123-125, 2008. [cited by applicant]
RN: 71675-85-9, Database Registry on STN, 1984, 1 page. [cited by applicant]
RN: 71675-90-6, Database Registry on STN, 1984, 1 page. [cited by applicant]
RN: 71675-92-8, Database Registry on STN, 1984, 1 page. [cited by applicant]
Roila et al., “Prevention of chemotherapy- and radiotherapy-induced emesis: Results of the 2004 Perugia International Antiemetic Consensus Conference”, Annals of Oncology, vol. 17, No. i, Jan. 2006, pp. 20-28. [cited by applicant]
Rosenmayr-Templeton et al., “Industry Update”, Therapeutic Delivery, 2015, vol. 6, No. 2, pp. 109-114. [cited by applicant]
Ruiz et al., “Routes of Drug Administration: Dosage, Design, and Pharmacotherapy Success”, ADME Processes in Pharmaceutical Sciences, Jan. 2018, pp. 1-43. [cited by applicant]
Schoemaker et al., Neurochemical Characteristics of Amisulpride, an Atypical Dopamine 02/03 Receptor Antagonist with Both Presynaptic and Limbic Selectivity, The Journal of Pharmacology and Experimental Therapeutics, 19… [cited by applicant]
Shaikh et al., “Postoperative nausea and vomiting: A simple yet complex problem”, Anesth. Essays Res., 2016, vol. 10, No. 3, pp. 388-396. [cited by applicant]
Spano: “Sulpiride and other benzamides”, Jan. 1, 1978 (Jan. 1, 1978) pp. 48-49. [cited by applicant]
Sulpiride, Wikipedia: The Free Encyclopedia. Wikimedia Foundation, Inc., Jun. 6, 2009. Web. Jun. 25, 2009. http://web.archive.org/web/20090729132126/http://en.wikipedia.org/wiki/Sulpiride. [cited by applicant]
Takei, D. et al., “Drug Therapy for Nausea and Vomiting”, J. Pharm. Palliat. Care Sci., pp. 111-117, vol. 2 (2009}. [cited by applicant]
Taube et aL “Thorough QT study of the effect of intravenous amisulpride on QTc interval in Caucasian and Japanese healthy subjects”, British Journal of Clinical Pharmacology, vol. 83, pp. 339-348, 2017. [cited by applicant]
Tonini et al., “Prevention of Radiotherapy-Induced Emesis”, J. Exp. Clin. Cancer Res. 22.1:17-22 (2003) (Abstract only). [cited by applicant]
Torta et al. “Amisulpride in the short-term treatment of depressive and physical symptoms in cancer patients during chemotherapies”, Support Care Cancer, No. 15, pp. 539-546, 2007. [cited by applicant]
Verhoef et al., “Des-enkephalin-y-endorphin: bioavailability in rats following the subcutaneous and intramuscular route of administration”, Regulatory Peptides, vol. 14, Jan. 13, 1986, pp. 113-124. [cited by applicant]