Granted Patent
B2
US 12,478,633 · App. 18/908,587 · Granted Nov 25, 2025
Compositions of grapiprant and methods for using the same
Inventors:
Lesley Rausch-Derra (Parkville, MO); Tamara Newbold (Martinsville, NJ); Gopinath Devaraj (Auckland, NZ); Akemi Shiraishi (Auckland, NZ)
Assignee:
ARATANA THERAPEUTICS, INC.
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Abstract
The present disclosure provides a method for treating pain or inflammation in a non-human animal in need thereof. The method comprises administering to a non-human animal a pharmaceutical composition comprising a therapeutically effective amount of grapiprant. Also provided herein are pharmaceutical compositions for treating pain or inflammation in a non-human animal in need thereof. The pharmaceutical compositions comprise a therapeutically effective amount of grapiprant and an excipient, including flavorants.
Claims (16)
1 . A method for treating pain and inflammation in a dog, the method comprising administering to the dog an oral pharmaceutical composition comprising a therapeutically effective amount of grapiprant and one or more excipients;
wherein the therapeutically effective amount of grapiprant is administered at a dosage rate of 2 mg per kilogram bodyweight of the dog once per day; and
wherein the oral pharmaceutical composition is administered with or without food.
2 . The method of claim 1 , wherein the administering achieves a C max of grapiprant of 375 ng/ml to 10000 ng/ml at a T max of 0.4 to 3.4 hours.
3 . The method of claim 2 , wherein the administering achieves a C max of grapiprant of 750 ng/ml to 4000 ng/ml.
4 . The method of claim 3 , wherein the administering achieves a C max of grapiprant of 1300 ng/ml to 4000 ng/ml.
5 . The method of claim 2 , wherein the administering achieves the C max of grapiprant at a T max of 0.7 to 1.7 hours.
6 . The method of claim 3 , wherein the administering achieves the C max of grapiprant at a T max of 0.5 to 1.0 hours.
7 . The method of claim 1 , wherein the pharmaceutical composition further comprises 1% to 30% flavorant (w/w of the total composition).
8 . The method of claim 7 , wherein the pharmaceutical composition comprises 5% to 15% flavorant (w/w of the total composition).
9 . The method of claim 1 , wherein the pharmaceutical composition is administered for 6 days to 9 months.
10 . The method of claim 9 , wherein the pharmaceutical composition is administered for 9 to 21 days.
11 . The method of claim 10 , wherein the pharmaceutical composition is administered for 12 to 14 days.
12 . The method of claim 1 , wherein the administering occurs from about 10 hours to about 18 hours before a surgery is performed on the dog.
13 . The method of claim 1 , wherein the pharmaceutical composition comprises sodium lauryl sulfate.
14 . The method of claim 1 , wherein the composition after administering causes no clinically significant adverse gastrointestinal event or changes in liver, kidney, and coagulation parameters in the dog.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Oct 8, 2024
From: RAUSCH-DERRA, LESLEY; NEWBOLD, TAMARA; DEVARAJ, GOPINATH; SHIRAISHI, AKEMI
To: ARATANA THERAPEUTICS, INC.
Reel/Frame 068825/0317 →
Continuity (6)
Provisional Application
62089713
· Dec 9, 2014
Provisional Application
61948957
· Mar 6, 2014
References Cited (113)
US 6710054B2
· Nakao et al.
· 2004
[cited by applicant]
US 6861441B1
· Clayton
· 2005
[cited by applicant]
US 7141580B2
· Nakao
· 2006
[cited by applicant]
US 7479564B2
· Nakao
· 2009
[cited by applicant]
US 7960407B2
· Haruta
· 2011
[cited by examiner]
US 9265756B2
· Newbold
· 2016
[cited by applicant]
US 20020107273A1
· Nakao et al.
· 2002
[cited by applicant]
US 20080206309A1
· Jabbour
· 2008
[cited by applicant]
US 20080242713A1
· Guilford
· 2008
[cited by applicant]
US 20090036495A1
· Audoly
· 2009
[cited by applicant]
US 20130225609A1
· Nickolaus
· 2013
[cited by applicant]
CN 1477960A
· 2004
[cited by applicant]
CN 101137656A
· 2008
[cited by applicant]
CN 101967146A
· 2011
[cited by applicant]
JP 2006249089A
· 2006
[cited by applicant]
WO 9850033A1
· 1998
[cited by applicant]
WO 0232422A2
· 2002
[cited by applicant]
WO 2002032900A2
· 2002
[cited by applicant]
WO 0308637A2
· 2003
[cited by applicant]
WO 2006095268A1
· 2006
[cited by applicant]
WO 2011102149A1
· 2011
[cited by applicant]
WO 2012048854A2
· 2012
[cited by applicant]
WO 2012048854A3
· 2012
[cited by applicant]
WO 2012122279A1
· 2012
[cited by applicant]
WO 2012157288A1
· 2012
[cited by applicant]
WO 2013017928A1
· 2013
[cited by applicant]
WO 2014148053A1
· 2014
[cited by applicant]
U.S. Appl. No. 18/887,856, filed Sep. 17, 2024, Rausch-Derra; Lesley.
[cited by examiner]
Notice of Opposition on European Patent Application 15758877.3, dated Sep. 28, 2022—KRKA Opposition.
[cited by applicant]
Notice of Opposition on European Patent Application 15758877.3, dated Oct. 28, 2022, VIRBAC Opposition, machine translation of Opposition.
[cited by applicant]
Communication of Notices of Opposition (R.79.91) Epc) on European Patent Application 15758877.3, dated Aug. 11, 2022.
[cited by applicant]
Response to Oppositions on European Patent Application 15758877.3, filed Mar. 17, 2023.
[cited by applicant]
L. Rausch-Derra et al., “Safety of the EP4 Receptor Antagonist, Grapiprant, Administered Daily to Beagle Dogs for 9 Months at 1,6 and 50 mg/kg”, presented at ACVIM, Nashville, TN—Jun. 2014.
[cited by applicant]
J Vet Intern Med 2014, 28, 976-1134, 2014 ACVIM Forum Research Abstracts Program, published online 2014.
[cited by applicant]
Nakao. K et al., “CJ-023,423, a Novel, Potent and Selective Prostaglandin EP4 Receptor Antagonist with Antihyperagesic Properties”, JPET 322(2), pp. 686-694, 2007.
[cited by applicant]
C. K. Cassel et al., “Geriatric Medicine: An Evidence-Based Approach”, Springer 2003, pp. 71-75.
[cited by applicant]
J. K. Aronson, “Meyler's Side Effects of Analgesics and Anti-inflammatory Drugs”, Elsevier B. V. 2010, pp. 237-239.
[cited by applicant]
R. S. Sinatra et al., “The Essence of Analgesia and Analgesics”, Cambridge University Press 2011, pp. 66-70.
[cited by applicant]
WHO Drug Information, vol. 27, No. 4, 2013, Proposed INN: List 110, pp. 399-458.
[cited by applicant]
The Wayback Machine, www.aratana.investorroom.com, archive date Jan. 18, 2014 (printed version followed by screenshots).
[cited by applicant]
Press Release Aratana Therapeutics Announces Positive Top-Line Results from AT-001 Dose-Ranging Field Study in Client-Owned Dogs with Osteoarthritis, provided by Aratana Therapeutics, Inc., Nov. 20, 2013.
[cited by applicant]
Press Release Why Aratana Therapeutics Inc. Shares Jumped, Dec. 23, 2013.
[cited by applicant]
M. Boriello et al., “Prostaglandin EP4 antagonists”, Pharm. Pat. Analyst (2013) 2(3), pp. 387-397.
[cited by applicant]
S. F. Crowley et al., “Aratana Therapeutics, Inc., Alpha Select List”, Institutional Research, Craig-Hallum Capital Group LLC 2013, pp. 1-17.
[cited by applicant]
G. Sinha, “Companion therapeutics”, Nature Biotechnology, vol. 6, No. 3, Jan. 2014, pp. 12-14.
[cited by applicant]
S. A. Khan et al., “Toxicology of Frequently Encountered Nonsteroidal Anti-Inflammatory Drugs in Dogs and Cats”, Vet Clin Small Anim 42 (2012) pp. 289-306.
[cited by applicant]
B. D. X. Lascelles, “Guidelines for Safe and Effective Use of NSAIDs in Dogs”, Veterinary Therapeutics, vol. 6, No. 3, Fall 2005, pp. 237-251.
[cited by applicant]
M. G. Papich, “An Update on Nonsteroidal Anti- Inflammatory Drugs (NSAIDs) in Small Animals”, Vet Clin Small Anim 38 (2008) pp. 1243-1266.
[cited by applicant]
Dugdale et al., “Veterinary Anaesthesia: Principles to Practice”, Blackwell Publishing Ltd. 2010, pp. 19-24.
[cited by applicant]
M. Kahn et al., “The Merck/Merial Manual for Pet Health”, Merck & Co., Inc. 2007, p. 1140.
[cited by applicant]
D. F. Woodward, “International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress”, Pharmacol Rev 63: pp. 471-538, 2011.
[cited by applicant]
V. Konya et al., “E-type prostanoid receptor 4 (EP4) in disease and therapy”, Pharmacology & Therapeutics, 138 (2013), pp. 485-502.
[cited by applicant]
ClinicalTrials.gov, NCT00392080, Mar. 18, 2008.
[cited by applicant]
RaQualia innovators for life, 2012, http://www.raqualia.co.jp—machine translation.
[cited by applicant]
R. Schmidt, “Dose-Finding Studies in Clinical Drug Development”, Eur J Clin Pharmacol (1988) 34:15-19.
[cited by applicant]
D. M. Boothe, Veterinary Compounding in Small Animals: A Clinical Pharmacologist's Perspective, Vet Clin Small Anim 36 (2006) pp. 1129-1173.
[cited by applicant]
N. Ting et al., Dose Finding in Drug Development, Springer Science+Business Media, Inc.2006, pp. 18-29.
[cited by applicant]
V. Sharma et al., “To scale or not to scale: the principles of dose extrapolation”, British Journal of Pharmacology (2009), 157, pp. 907-921.
[cited by applicant]
G.E. Hardee et al., “Development and Formulation of Veterinary Dosage Forms”, 2nd ed., 1998, Marcel Dekker, pp. 474-477.
[cited by applicant]
Guidance for Industry, 185, 2009, Target Animal Safety for Veterinary Pharmaceutical Products, VICH GL43.
[cited by applicant]
R.C. Gupta et al., Veterinary Toxicology, Basic and Clinical Principles, Elsevier In. 2012, pp. 119-120.
[cited by applicant]
T. Vaughan-Scott et al., “The pathophysiology and medical management of canine osteoarthritis”, JI. S.Afr.vet.Ass. (1997) 68(1): pp. 21-25.
[cited by applicant]
D. C. Plumb, “Veterinary Drug Handbook”, 7th edition, PharmaVet Inc. 2011, pp. 2929-2936.
[cited by applicant]
R. C. Gupta, “Veterinary Toxicology: Basic and Clinical Principals”, Elsevier Inc. 2007, pp. 368-373.
[cited by applicant]
H. Wen et al., “Oral Controlled Release Formulation Design and Drug Delivery”, John Wiley & Sons, Inc. 2010, pp. 257-258.
[cited by applicant]
J. Zheng, “Formulation and analytical development for low-dose oral drug products”, John Wiley & Sons, Inc. 2009, pp. 331-333.
[cited by applicant]
J. K. H. Ma et al., “Basic Physical Pharmacy”, 2013 Jones & Bartlett Learning, LLC, pp. 248-252.
[cited by applicant]
L. L. Augsburger et al., “Pharmaceutical Dosage Forms: Tablets”, 3rd edition, Informa Healthcare, 2008, Chapter 13, pp. 383-431.
[cited by applicant]
Rausch-Derra et al., “Evaluation of the safety of long-term, daily oral administration of grapiprant, a novel drug for treatment of osteoarthritic pain and inflammation, in heatly dogs,” American Journal of Veterinary R…
[cited by applicant]
Jones et al., “Prostanoid receptor antagonists: development strategies and therapeutic applications, British Journal of Pharmacology”, 2009, 158, 104-145.
[cited by applicant]
Maubach et al., “BGC20-1531, a novel, otent and selective prostanoid EP4 receptor antagonist: a putative new treatment for migrain headache”, British Journal of Pharmacology, 2009, 156, 316-327.
[cited by applicant]
Castleberry et al., “Molecular cloning and functional characterization of the canine prostaglandin E2, receptor EP4 subtype”, Prostaglandins & other Lipid Mediators, 2001, vol. 65, pp. 167-187.
[cited by applicant]
Papich Handbook of Veterinary Drugs, Fifth Edition, Elsevier, Mar. 30, 2020, 13 first pages presentation p. and pp. 418-420 only.
[cited by applicant]
I. Sartini et al., “Grapiprant: A Snapshot of the current knowledge”, Journal of Veterinary Pharmacology and Therapeutics, 2021, published online May 31, 2021.
[cited by applicant]
Heather K. Knych et al., “Detection and pharmacokinetics of grapiprant following oral administration to exercised Thoroughbred horses”, Drug Test Anal., 2018, vol. 10, pp. 1237-1243, published online Mar. 25, 2018.
[cited by applicant]
A. Nagahisa & T. Okumura, “Pharmacology of grapiprant, a novel EP4 antagonist: receptor binding, efficacy in a rodent postoperative pain model, and a dose estimation for controlling pain in dogs”, J. vet. Pharmacol. The…
[cited by applicant]
S. Cox et al., “Determination of grapiprant plasma and urine concentrations in horses”, Veterinary Anaesthesia and Analgesia, 2020, vol. 47, pp. 705-709, published online Mar. 25, 2018.
[cited by applicant]
Communication de Aratana Therapeutics, published on Jan. 19, 2015, www.prnewswire.com/news-releases/aratana-therapeutics-awarded-best-pipeline-2014-byanimal-pharm-300022144. html.
[cited by applicant]
Communication from Aratana Therapeutics, published on May 2, 2014 regarding their attendance at the ACVIM 2014 conference scheduled for Jun. 4-7, 2014 in Nashville, Tennessee for three oral presentations and three poste…
[cited by applicant]
Communication from Aratana Therapeutics, published on Jun. 9, 2014 and relating to their attendance at the ACVIM 2014 conference which took place on Jun. 4-7, 2014 in Nashville, Tennessee, describing a summary of the th…
[cited by applicant]
“A Study of the Effect of CJ-023,423 on the Incidence of Stomach Ulcers”, ClinicalTrials.gov, Identifier: NCT00392080, clinicaltrials.gov/ct2/show/NCT00392080, first posted Oct. 25, 2006.
[cited by applicant]
Okumura, T. et al., “Effects of the selective EP4 antagonist, CJ-023,423 on chronic inflammation and bone destruction in rat adjuvant-induced arthritis”, Journal of Pharmacy and Pharmacology, vol. 60, pp. 723-730. Jun. …
[cited by applicant]
Form 8-K, filing date Jan. 16, 2014, SEC Accession No. 0001193125-14-013272, Aratana Therapeutics, Inc., CIK:0001509190.
[cited by applicant]
Murase, Akio, et al. “Characterization of Binding Affinity of CJ-023,423 for Human Prostanoid EP4 Receptor” Pharmacology, vol. 82, No. 1, pp. 10-14, Apr. 11, 2008.
[cited by applicant]
“VICH Topic GL9 (GCP)—Step 7 Consensus Guideline”, Guideline on Good Clinical Practices, CVMP/VICH/595/98—Final, The European Agency for the Evaluation of Medicinal Products, Veterinary Medicines and information Technol…
[cited by applicant]
“A Placebo-Controlled, Dose Ranging, Field Study To Evaluate the Safety and Effectiveness of AT-001, Administered Daily as an Oral Tablet, for the Control of Pain and Inflammation Associated With Osteoarthritis in Dogs”…
[cited by applicant]
Amendment No. 5 to Form S-1 Registration Statement under the securities act of 1933, Aratana Therapeutics, Inc., Registration No. 333-187372.
[cited by applicant]
“CVMP assessment report for Galliprant (EMEA/V/C/004222/0000)—International non-proprietary name: grapiprant”, Committee for Medicinal Products for Veterinary Use, Nov. 9, 2017, European Medicines Agency, Science Medici…
[cited by applicant]
“The Committee for Veterinary Medicinal Products (CVMP) is the European Medicines Agency's (EMA) committee responsible for veterinary medicines.”, Committee for Veterinary Medicinal Products (CVMP), 2023.
[cited by applicant]
Cunningham et al., “Interspecies Allometric Scaling”, Comparative and Veterinary Pharmacology, Springer Heidelberg Dordrecht, pp. 149-152, DOI 10.2007/978-3-642-10324-7.
[cited by applicant]
Antonova, Met al., “The pharmacological effect of BGC20-1531, a novel prostanoid EP4 receptor antagonist, in the Prostaglandin E2 human model of headache”, J Headache Pain, 12, pp. 551-559, 2011.
[cited by applicant]
Chinese Office Action mailed Dec. 27, 2017 for corresponding Chinese Patent Application No. 201580006168.6.
[cited by applicant]
European Search report mailed Sep. 22, 2017 for corresponding European Application No. 15758877.3.
[cited by applicant]
Final Office Action, related to U.S. Appl. No. 14/639,898 dated Feb. 7, 2017, 13 pages.
[cited by applicant]
Goodman & Gilman's the Pharmacological Basis of Therapeutics. Tenth Edition (2001), Appendix II, pp. 1917-1923, McGraw Hill Medical Publishing Division, USA.
[cited by applicant]
International Search Report and the Witten Opinion of the International Searching Authority, or the Declaration, PCT/US2015/019037, mailing date Jun. 8, 2015.
[cited by applicant]
Japanese Office Action mailed Oct. 17, 2017 for corresponding Japanese Patent Application No. 2016-573691.
[cited by applicant]
Johnston, Spencer A, “Osteoarthritis: Joint Anatomy, Physiology, and Pathobiology”, Vet Clin North Am Small Anim Pract., 27(4). Jul. 1997, pp. 699-723.
[cited by applicant]
Murase, A., “Effect of prostanoid EP4 receptor antagonist, CO-042, 794, in rat models of pain and inflammation”, Eur J. Pharmacol., Feb. 2, 2008, N 580(1-2), c. 116-21, PMIO: 18031725.
[cited by applicant]
Office Action, related to U.S. Appl. No. 14/639,898 dated Aug. 2, 2016, 14 pages.
[cited by applicant]
Taiwan Office Action related to Application No. 104107084, dated Apr. 25, 2016, 11 pages.
[cited by applicant]
PR Newswire, “Aratana, Elanco Announce Global Strategic Collaboration”, http//www.prnewswire.com/news-releases/aratana-elanco-announce-global-strategic-collaboration-300256859.html, Apr. 25, 2016.
[cited by applicant]
PR Newswire. “Calliprant (grapiprant tablets) Now Available for Canine Osteoarthritis”, http://www.prnewswire.com/news-releases/gailiprant-grapiprant-tablets-now-available-for-canine-osteoarthritis-300396003.html, Jan. …
[cited by applicant]
Rausch-Derra, Lesley C. et al., “Evaluation of the safety of long-term, daily oral administration of grapiprant, a novel drug for treatment of osteoarthritic pain and inflammation, in healthy dogs”, American Journal of …
[cited by applicant]
Roush. James K. et al.. “Multicenter veterinary practice assessment of the effects of omega-3 fatty acids on osteoarthritis in dogs”, J. of the American Medical Association, vol. 236, No. 1. Jan. 1, 2010, pp. 59-66.
[cited by applicant]
Search Report issued Apr. 8, 2018 and English translation from Gorodissky and Partners for corresponding RU Application No. 2016137926.
[cited by applicant]
Shaw. Kristin Kirby et al., “Grapiprant: an EP4 prostaglandin receptor antagonist and novel therapy for pain and inflammation”, Veterinary Medicine and Science (2016), 10.1002/vms3.13 pp. 3-9.
[cited by applicant]