IP Library › Granted Patent US 12,285,460
Granted Patent B2
US 12,285,460 · App. 17/401,929 · Granted Apr 29, 2025

Pharmaceutical compositions

Inventors: Shubh Sharma (Cranbury, NJ); Leonardus H. T. Van Der Ploeg (Newton, MA); Bart T. Henderson (Belmont, MA)
Assignee: RHYTHM PHARMACEUTICALS, INC.
A61K38/12A61K9/08A61K9/10A61K9/146A61K38/08A61K45/06A61K47/10A61K47/12A61K47/24A61K47/38A61K47/541A61K47/542A61K47/544
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Quick Facts
Patent No.
US 12,285,460
App. No.
17/401,929
Granted
Apr 29, 2025
Kind
B2
Abstract

The present invention relates to an ionic complex comprising a cationic polypeptide and an anionic excipient selected from: a PEG-carboxylic acid; a fatty acid having 10 or more carbon atoms; an anionic phospholipid; and a combination thereof. The invention also relates to a pharmaceutical composition comprising the ionic complex of the invention and a pharmaceutically acceptable carrier. The cationic polypeptide of the ionic complex has pharmacological activity and the complex can provide a more desirable pharmacokinetic profile for the cationic polypeptide of the complex as compared to the cationic polypeptide alone following administration. As such, the invention also relates to the use of the ionic complex and pharmaceutical composition comprising same to treat a subject suffering from a disease or disorder that is responsive to the cationic polypeptide of the ionic complex.

Claims (15)

1. An ionic complex comprising:

(i) a cationic polypeptide represented by the following structural formula:

or a pharmaceutically acceptable salt thereof; and

(ii) a 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) conjugated polyethylene glycol,

wherein the molar ratio of the cationic polypeptide to the 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) conjugated polyethylene glycol ranges from about 1:1 to about 1:10.

2. The ionic complex of claim 1 , wherein the molar ratio of the cationic peptide to the 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) conjugated polyethylene glycol ranges from about 1:2 to about 1:8.

3. The ionic complex of claim 1 , wherein the molar ratio of the cationic peptide to the 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) conjugated polyethylene glycol ranges from about 1:3 to about 1:6.

4. The ionic complex of claim 1 , further comprising an anionic excipient selected from carboxymethylcellulose (CMC), stearic acid, and DPPA.

5. The ionic complex of claim 4 , wherein the anionic excipient is CMC.

6. The ionic complex of claim 1 , wherein the 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) conjugated polyethylene glycol is selected from mPEG-2,000-DSPE and mPEG-5,000-DSPE.

7. The ionic complex of claim 6 , wherein the 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) conjugated polyethylene glycol is mPEG-2,000-DSPE.

8. The ionic complex of claim 1 , further comprising a combination of anionic excipients.

9. The ionic complex of claim 8 , wherein the combination of anionic excipients is selected from: stearic acid and mPEG-2,000-DSPE; DPPA and mPEG-2,000-DSPE; mPEG-2,000-DSPE and CMC; and mPEG-2,000-DSPE.

10. The ionic complex of claim 1 , wherein the ionic complex has the property that it forms a drug depot in a physiological environment.

11. The ionic complex of claim 1 , wherein the ionic complex has the property that it forms a drug depot when delivered subcutaneously.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 8, 2023
From: SHARMA, SHUBH; VAN DER PLOEG, LEONARDUS H.T.; HENDERSON, BART T.
To: RHYTHM METABOLIC, INC.
Reel/Frame 064852/0617 →
CHANGE OF NAME Recorded Sep 8, 2023
From: RHYTHM METABOLIC, INC.
To: RHYTHM PHARMACEUTICALS, INC.
Reel/Frame 064852/0625 →
Continuity (3)
Continuation 14775911
Provisional Application 61792440 · Mar 15, 2013
Related Publication 20220160818A1 · May 26, 2022
References Cited (71)
US 5731408A · Hadley et al. · 1998 [cited by applicant]
US 5849704A · Sørensen et al. · 1998 [cited by applicant]
US 7655468B2 · Huang · 2010 [cited by examiner]
US 8039435B2 · Dong et al. · 2011 [cited by applicant]
US 8349797B2 · Dong et al. · 2013 [cited by applicant]
US 8563000B2 · Dong et al. · 2013 [cited by applicant]
US 9155777B2 · Alem et al. · 2015 [cited by applicant]
US 11129869B2 · Sharma · 2021 [cited by examiner]
US 20050267147A1 · Poitout et al. · 2005 [cited by applicant]
US 20060173036A1 · Poitout et al. · 2006 [cited by applicant]
US 20060281784A1 · Poitout et al. · 2006 [cited by applicant]
US 20090209531A1 · Poitout et al. · 2009 [cited by applicant]
US 20100173834A1 · Dong · 2010 [cited by applicant]
US 20120135923A1 · Halem et al. · 2012 [cited by applicant]
US 20120225816A1 · Dong et al. · 2012 [cited by applicant]
US 20120226018A1 · Dong · 2012 [cited by applicant]
US 20140127303A1 · Richard et al. · 2014 [cited by applicant]
US 20150157719A1 · Baronnet et al. · 2015 [cited by applicant]
CN 101257916A · 2008 [cited by applicant]
CN 101439182A · 2009 [cited by applicant]
JP 2005504715A · 2005 [cited by applicant]
JP 2007517023A · 2007 [cited by applicant]
WO 9426251A1 · 1994 [cited by applicant]
WO 9825642A2 · 1998 [cited by applicant]
WO 03006620A2 · 2003 [cited by applicant]
WO 2004045633A2 · 2004 [cited by applicant]
WO 2005000339A2 · 2005 [cited by applicant]
WO 2005014617A2 · 2005 [cited by applicant]
WO 2007008704A2 · 2007 [cited by applicant]
WO 2007022254A2 · 2007 [cited by applicant]
WO 2008147556A2 · 2008 [cited by applicant]
WO 2009151383A1 · 2009 [cited by applicant]
WO 2009158415A1 · 2009 [cited by applicant]
WO 2010144344A2 · 2010 [cited by applicant]
WO 2010144038A1 · 2010 [cited by applicant]
WO 2011060355A1 · 2011 [cited by applicant]
WO 2012172433A2 · 2012 [cited by applicant]
WO 2013032028A1 · 2013 [cited by applicant]
WO 2013033838A1 · 2013 [cited by applicant]
WO 2013182653A1 · 2013 [cited by applicant]
WO 2014144260A1 · 2014 [cited by applicant]
WO 2014144842A2 · 2014 [cited by applicant]
Al-Obeidi et al., “Potent and Prolonged Acting Cyclic Lactam Analogues of a-Melanotropin: Design Based on Molecular Dynamics” J. Med. Chem (1989) vol. 32 pp. 2555-2561. [cited by applicant]
Bednarek et al., “Analogs of MTII, Lactam Derivatives of a-Melanotropin, Modified at the N-Terminus, and Their Selectivity at Human Melanocortin Receptors 3, 4 and 5” Biochem. and Biophys. Research Communications (1999)… [cited by applicant]
Bednarek et al., “Structure-function studies on the cyclic peptide MT-II, lactam derivative of a-melanotropin” Peptides (1999) vol. 20 pp. 401-409. [cited by applicant]
Grieco et al., “Further structure-activity studies of lactam derivatives of MT-II and SHU-9119: Their activity and selectivity at human melanocortin receptors 3, 4 and 5” Peptides (2007) vol. 28 pp. 1191-1196. [cited by applicant]
Grieco et al., “Structure-Activity Studies of the Melanocortin Peptides: Discovery of Potent and Selective Affinity Antagonists for the hMC3 and hMC4 Receptors” J. Med. Chem. (2002) vol. 45 pp. 5287-5294. [cited by applicant]
International Preliminary Report on Patentability and Written Opinion for PCT/US2014/029421 mailed Sep. 15, 2015. [cited by applicant]
International Search Report from PCT/US2014/029421 mailed Feb. 23, 2015. [cited by applicant]
Macedo et al., “Estimation of average depth of penetration of melanotropins in dimyristoylphosphatidylglycerol vesicles” Biophysical Chemistry (1999) vol. 59 pp. 193-202. [cited by applicant]
Vogt & Bechinger, “The Interactions of Histidine-containing Amphipathic Helical Peptide Antibiotics with Lipid Bilayers” The Journal of Biological Chemistry (1999) vol. 274 No 41 pp. 29115-29121. [cited by applicant]
Farooqi et al. “Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency”, The Journal of Clinical Investigation (2000) vol. 106, No. 2, pp. 271-279. [cited by applicant]
Vaisse et al. “Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity”, The Journal of Clinical Investigation (2000) vol. 106, No. 2, pp. 253-262. [cited by applicant]
Xiang et al. “Pharmacological characterization of 30 human melanocortin-4 receptor polymorphisms with the endogenous proopiomelanocortin-derived agonists, synthetic agonists, and the endogenous agouti-related protein an… [cited by applicant]
Farooqi et al. “Clinical and Molecular Genetic Spectrum of Congenital Deficiency of the Leptin Receptor” The New England Journal of Medicine (2007) vol. 356, No. 3, pp. 237-247. [cited by applicant]
Lee “The Role of Leptin-Melanocortin System and Human Weight Regulation: Lessons from Experiments of Nature” Annals Academy of Medicine, Jan. 2009, vol. 38 No. 1, pp. 34-44. [cited by applicant]
Krude et al. “Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans” Nature Genetics, 1998 vol. 19, pp. 155-157. [cited by applicant]
Lee et al, “A POMC variant implicates ?-melanocyte-stimulating hormone in the control of human energy balance” Cell Metabolism (2006) vol. 3, Issue 2, pp. 135-140. [cited by applicant]
Brennan et al., “Drug Insight: the role of leptin in human physiology and pathophysiology-emerging clinical applications” Nature Reviews Endocrinology (2006) vol. 2, pp. 318-327. [cited by applicant]
European Search Report for European Application No. 14 724 574.0 dated Nov. 18, 2016. [cited by applicant]
Kievit et al. “Chronic Treatment With a Melanocortin-4 Receptor Agonist Causes Weight Loss, Reduces Insulin Resistence, and Improves Cardiovascular Function in Diet-Induced Obese Rhesus Macaques” Diabetes (2013) vol. 62… [cited by applicant]
Blume et al. “Liposomes for the sustained drug release in vivo” Biochimica et Biophysica Acta (1990) vol. 1029, No. 1, pp 91-97. [cited by applicant]
Mufamadi et al., “A Review on Composite Liposomal Technologies for Specialized Drug Delivery” J. Drug Delivery (2011) vol. 2011, Article ID: 939851, pp. 1-19. [cited by applicant]
Katdare, et al., Chap. 17. “Excipients for Protein Drugs,” Excipient Development for Pharmaceutical, Biotechnology, and Drug Delivery Systems, Taylor & Francis Group LLC, pp. 291-332 (2006). [cited by applicant]
Sigma Aldrich, “Polyethylene glycol,” Product Information available online at https://www.sigmaaldrich.com/content!dam/sigmaaldrich/docs/Sigma/Product_I nformation_Sheet/1 /p3390pis.pdf, 2 pages (2003). [cited by applicant]
European Examination Report for Application No. 14724574.0 dated Jul. 16, 2018. [cited by applicant]
Lotz, “PEGylation for Improving the Properties of Peptide-Based APIs,” available at https://www.biocompare.com/Bench-Tips/ 344638-PEGylation-for-Improving-the-Properties-of-Peptide-Based-APIs/, 13 pages (2017) (Year: 20… [cited by applicant]
Peptu et al., “Release of liposome-encapsulated calcein from liposome entrapping gelatin-carboxymethylcellulose films: A presentation of differnt possibilities” Journal of Nanoscience and Nanotechnology, 2008, vol. 8, p… [cited by applicant]
“Precipitating”, Merriam-Webster Dictionary, available online at https://www.merriam-webster.com/dictionary/precipitate, 17 pages (accessed on Jun. 10, 2018) (Year: 2018). [cited by applicant]
M.E. Aulton, “Pharmaceutics: The Science of Dosage Form Design”, Churchill Livingstone, Second Edition 2002, Chapter 20, 289-305. [cited by applicant]
Wikipedia: “Setmelanotide”, (accessed 2021). [cited by applicant]