IP Library › Granted Patent US 12,208,135
Granted Patent B2
US 12,208,135 · App. 18/530,421 · Granted Jan 28, 2025

Formulations of dengue virus vaccine compositions

Inventors: Michael S. Ryan (Allentown, PA); Sherrie-Ann P. Martin (Paoli, PA); Morrisa Jones (Upper Darby, PA); Justin Stanbro (Sellersville, PA); Akhilesh Bhambhani (Doylestown, PA); Jeffrey Thomas Blue (Telford, PA); Heidi Joanne Pixley (Glenside, PA); Erin J. Green-Trexler (Green Lane, PA); Lynne Ann Isopi (Quakertown, PA)
Assignee: Merck Sharp & Dohme LLC
A61K39/12A61K9/19A61K39/39A61K47/10A61K47/26A61K47/32A61K47/36A61K47/42A61K2039/5254A61K2039/55505A61K2039/70
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 12,208,135
App. No.
18/530,421
Granted
Jan 28, 2025
Kind
B2
Abstract

The present invention relates to formulations of dengue virus vaccine comprising at least one live, attenuated dengue virus or live, attenuated chimeric flavivirus, a buffer, a sugar, a cellulose derivative, a glycol or sugar alcohol, optionally an alkali or alkaline salt and an amino acid; and formulations of dengue virus vaccine comprising at least one live, attenuated dengue virus or live, attenuated chimeric flavivirus, a buffer, a sugar of at least 150 mg/ml, a carrier, and optionally an alkali or alkaline salt and an amino acid.

Claims (12)

1. A formulation comprising:

a) a live attenuated tetravalent dengue vaccine comprising i) 100-10,000,000 pfu/ml rDEN1430 virus, ii) 100-10,000,000 pfu/ml rDEN2/4430 virus, iii) 100-10,000,000 pfu/ml rDEN3Δ30/31 virus, and iv) 100-10,000,000 pfu/ml rDEN4Δ30 virus,

b) 5-300 mM potassium phosphate buffer at pH 7.0 to 8.0,

c) 60-120 mg/ml sucrose or trehalose or a combination thereof,

d) 3-7 mg/ml propylene glycol or glycerol, and

e) 3-7 mg/ml carboxymethylcellulose,

f) optionally 30-90 mM NaCl, and

g) optionally 10-75 mM amino acid Leu, Lys or Glu, or a combination thereof.

2. The formulation of claim 1 further comprising an aluminum adjuvant.

3. The formulation of claim 1 that is frozen or lyophilized.

4. The formulation of claim 1 that is reconstituted in solution.

5. The formulation of claim 1 that is in an aqueous solution prior to lyophilization or microwave vacuum drying.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 11, 2023
From: RYAN, MICHAEL S.; MARTIN, SHERRIE-ANN P.; JONES, MORRISA C.; STANBRO, JUSTIN; BHAMBHANI, AKHILESH; BLUE, JEFFREY THOMAS; PIXLEY, HEIDI JOANNE; GREEN-TREXLER, ERIN J.; ISOPI, LYNNE ANN
To: MERCK SHARP & DOHME CORP.
Reel/Frame 065825/0076 →
MERGER Recorded Dec 11, 2023
From: MERCK SHARP & DOHME CORP .
To: MERCK SHARP & DOHME LLC
Reel/Frame 065825/0884 →
Continuity (4)
Continuation 17815037 · Jul 26, 2022
Continuation 16769837
Provisional Application 62595842 · Dec 7, 2017
Related Publication 20240131144A1 · Apr 25, 2024
References Cited (66)
US 6190859B1 · Putnak et al. · 2001 [cited by applicant]
US 6254873B1 · Putnak et al. · 2001 [cited by applicant]
US 6432411B1 · Ivy et al. · 2002 [cited by applicant]
US 11883480B2 · Ryan · 2024 [cited by examiner]
US 20030180352A1 · Patel · 2003 [cited by applicant]
US 20040022760A1 · Mckenna et al. · 2004 [cited by applicant]
US 20120219588A1 · Thompson et al. · 2012 [cited by applicant]
US 20150017191A1 · Fox · 2015 [cited by examiner]
US 20150246114A1 · Qiao et al. · 2015 [cited by applicant]
US 20160158248A1 · Gizurarson · 2016 [cited by applicant]
US 20160199496A1 · Jezek et al. · 2016 [cited by applicant]
US 20160296616A1 · Croyle et al. · 2016 [cited by applicant]
US 20160310412A1 · Tanoue et al. · 2016 [cited by applicant]
US 20160324783A1 · Fox et al. · 2016 [cited by applicant]
US 20160354460A1 · Poon et al. · 2016 [cited by applicant]
US 20230061673A1 · Ryan et al. · 2023 [cited by applicant]
CN 1119414A · 1996 [cited by applicant]
CN 101115472A · 2008 [cited by applicant]
CN 101128216A · 2008 [cited by applicant]
CN 101296705A · 2008 [cited by applicant]
CN 101679954A · 2010 [cited by applicant]
EP 2143440A1 · 2010 [cited by applicant]
EP 2687229A1 · 2014 [cited by applicant]
WO 1993006214A1 · 1993 [cited by applicant]
WO 02095075 · 2002 [cited by applicant]
WO 03092592A2 · 2003 [cited by applicant]
WO 2005016239A2 · 2005 [cited by applicant]
WO 2006074303A2 · 2006 [cited by applicant]
WO 2007002470A2 · 2007 [cited by applicant]
WO 2007038926A1 · 2007 [cited by applicant]
WO 2008022196 · 2008 [cited by applicant]
WO 2009014774A1 · 2009 [cited by applicant]
WO 2010037402A1 · 2010 [cited by applicant]
WO 2010105251A2 · 2010 [cited by applicant]
WO 2011098837A1 · 2011 [cited by applicant]
WO 2012154202A1 · 2012 [cited by applicant]
WO 2012160199A1 · 2012 [cited by applicant]
WO 2014204892A1 · 2014 [cited by applicant]
WO 2015057541A1 · 2015 [cited by applicant]
WO 2015059284A1 · 2015 [cited by applicant]
WO 2015093452A1 · 2015 [cited by applicant]
WO 2015130157A1 · 2015 [cited by applicant]
WO 2016106107A2 · 2016 [cited by applicant]
WO 2016203025A1 · 2016 [cited by applicant]
WO 2017041156A2 · 2017 [cited by applicant]
WO 2017056101A1 · 2017 [cited by applicant]
WO WO2017056101 · 2017 [cited by examiner]
WO 2017109698A1 · 2017 [cited by applicant]
WO 2017165736A1 · 2017 [cited by applicant]
WO 2017179017A1 · 2017 [cited by applicant]
WO 2018027075A1 · 2018 [cited by applicant]
WO 2018053524A1 · 2018 [cited by applicant]
WO 2018183429A1 · 2018 [cited by applicant]
WO 2019077622A1 · 2019 [cited by applicant]
WO 2019112921A1 · 2019 [cited by applicant]
Tlaxca, Jose L. et al., Live attenuated and inactivated viral vaccine formulation and nasal delivery: Potential and challenges, Advanced Drug Delivery Reviews, 93, 56-78, 2014. [cited by applicant]
Duane J. Gubler, Dengue and Dengue Hemorrhagic Fever, Clinical Microbiology Reviews, 11-3, 480-496, Jul. 1998. [cited by applicant]
Erik A. Henchal, The Dengue Viruses, Clinical Microbiology Reviews, 3-4, 376-396, 1990. [cited by applicant]
Hansen, L.J.J. et al., Freeze-drying of live virus vaccines: A review, Vaccine, 33(42), 5507-5519, 2015. [cited by applicant]
Heinz, Franz et al., Flaviviruses and flavivirus vaccines, Vaccine;, 30, 4301-4306, 2012. [cited by applicant]
J. Robert Putnak et al., An evaluation of dengue type-2 inactivated, recombinant subunit, and live-attenuated vaccine candidates in the rhesus macaque model, Vaccine, 23, 4442-4452, 2005. [cited by applicant]
L.J. Braun et al., Characterization of a thermostable hepatitis B vaccine formulation, Vaccine, 27, 4609-4614, 2009. [cited by applicant]
Robert V. Gibbons, Dengue: an escalating problem, British Medical Journal, -, 1563-1566, 2002. [cited by applicant]
Tang, Roderick S. et al., Development of a PIV-vectored RSV vaccine: Preclinical evaluation of safety, toxicity, and enhanced disease and initial clinical testing in healthy adults, Vaccine, 26, 6373-6382, 2008. [cited by applicant]
Thomas J. Chambers, Flavivirus Genome Organization, Expression, and Replication Annu. Rev. Microbiol, Annu. Rev. Microbiol., 44, 649-88, 1990. [cited by applicant]
U.S. Appl. No. 17/815,037, filed Jul. 26, 2022. [cited by applicant]