IP Library › Granted Patent US 12,653,829
Granted Patent B2
US 12,653,829 · App. 17/803,220 · Granted Jun 16, 2026

Formulated and/or co-formulated compositions containing A2aR antagonist prodrugs useful in the treatment of cancer and methods thereof

Inventors: David Stover (Encino, CA); Dhruba Bharali (Sherman Oaks, CA); Bruce A Hay (Niskayuna, NY); Tahmineh Safaie (Los Angeles, CA)
Assignee: Nammi Therapeutics, Inc.
A61K31/53A61K47/543A61K47/6911B82Y5/00
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 12,653,829
App. No.
17/803,220
Granted
Jun 16, 2026
Kind
B2
Abstract

Formulated and/or co-formulated nanocarriers (e.g., LNPs and/or SLNPs) comprising AR Prodrugs and methods of making the nanocarriers are disclosed herein. The AR prodrug compositions comprise a drug moiety, a lipid moiety, and linkage unit that inhibit A2aR. The AR Prodrugs can be formulated and/or co-formulated into a nanocarrier to provide a method of treating cancer, immunological disorders, and other disease by utilizing a targeted drug delivery vehicle.

Claims (8)

1 . A nanocarrier comprising, an AR prodrug whereby the nanocarrier releases an active A2aR inhibitor and wherein the AR prodrug has the following chemical structure:

and wherein the nanocarrier is a liposome and wherein the liposome has a Zav size of 87.29 nm and a Zeta potential of −18.6 m V.

2 . The nanocarrier of claim 1 , further comprising a helper lipid, whereby the helper lipid is selected from the group consisting of 1,2-dioleoyl-3-trimethylammonium-propane (chloride salt), 1,2-dioleyloxy-3-dimethylaminopropane, 1,2-dilinoleyloxy-3-dimethylaminopropane, 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane, 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine, 1,2-dioleoyl-sn-glycero-3-phosphocholine, cholesterol, N-[(methoxy poly(ethylene glycol) 2000) carbamyl]-1,2-dimyristyloxlpropyl-3-amine, cholesteryl hemisuccinate, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-distearoyl-sn-glycero-3-phosphocholine, 4-(2-aminoethyl)-morpholino-cholesterolhemisuccinate, (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol), L-α-phosphatidylcholine, and hydrogenated (Soy) powder.

3 . The nanocarrier of claim 1 , whereby the liposome is further co-formulated with one or more immune modulating agents or a lipid-prodrug thereof, wherein the immune modulating agent is selected from the group consisting of immunogenic-cell death (ICD) inducing chemotherapeutics, toll-like receptor (TLR) agonists, Stimulator of Interferon Gene (STING) agonists, Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) inhibitors, indoleamine 2,3-dioxygenase (IDO) inhibitors, programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors, and cluster of differentiation 1 (CDID) agonists and/or prodrugs thereof.

4 . The nanocarrier of claim 1 , whereby the liposome is further co-formulated with an ICD-inducing chemotherapeutic, wherein the ICD-inducing chemotherapeutic is selected from the group consisting of doxorubicin (DOX), mitoxanthrone (MTO), oxaliplatin (OXA), cyclophosphamide (CP), Bortezomib, Carfilzomib, or Paclitaxel.

5 . A kit comprising the nanocarrier of claim 1 .

6 . A kit comprising the nanocarrier of claim 3 .

7 . A kit comprising the nanocarrier of claim 4 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 18, 2022
From: STOVER, DAVID; BHARALI, DHRUBA; HAY, BRUCE A.; SAFAIE, TAHMINEH
To: NAMMI THERAPEUTICS, INC.
Reel/Frame 059624/0736 →
Continuity (2)
Provisional Application 63207749 · Mar 18, 2021
Related Publication 20220401451A1 · Dec 22, 2022
References Cited (74)
US 5726164A · Wder et al. · 1998 [cited by applicant]
US 6664252B2 · Castelhano et al. · 2003 [cited by applicant]
US 6673802B2 · Castelhano et al. · 2004 [cited by applicant]
US 7429574B2 · Castelhano et al. · 2008 [cited by applicant]
US 7504407B2 · Castelhano et al. · 2009 [cited by applicant]
US 8232313B2 · Munn et al. · 2012 [cited by applicant]
US 8883177B2 · Wu · 2014 [cited by applicant]
US 8912162B2 · Ahrabi et al. · 2014 [cited by applicant]
US 9017974B2 · Zheng et al. · 2015 [cited by applicant]
US 9526787B2 · Ko et al. · 2016 [cited by applicant]
US 9598422B2 · Beck et al. · 2017 [cited by applicant]
US 9732035B2 · Mautino et al. · 2017 [cited by applicant]
US 10004694B2 · Park et al. · 2018 [cited by applicant]
US 10022365B2 · Tong et al. · 2018 [cited by applicant]
US 10028913B2 · Li et al. · 2018 [cited by applicant]
US 10287606B2 · Valamehr et al. · 2019 [cited by applicant]
US 10392405B2 · Malathong et al. · 2019 [cited by applicant]
US 10399962B2 · Beatty et al. · 2019 [cited by applicant]
US 10428083B2 · Harter et al. · 2019 [cited by applicant]
US 10568868B2 · Slusher et al. · 2020 [cited by applicant]
US 10702526B2 · Webster et al. · 2020 [cited by applicant]
US 10781189B2 · Sasikkumar et al. · 2020 [cited by applicant]
US 10995101B2 · Crosignani et al. · 2021 [cited by applicant]
US 11034708B2 · Asai et al. · 2021 [cited by applicant]
US 11045472B2 · Leleti et al. · 2021 [cited by applicant]
US 11096964B2 · Rosen et al. · 2021 [cited by applicant]
US 11246906B2 · Losey et al. · 2022 [cited by applicant]
US 11376255B2 · Crosignani et al. · 2022 [cited by applicant]
US 11400155B2 · Coric · 2022 [cited by applicant]
US 11413244B2 · Kasagi et al. · 2022 [cited by applicant]
US 11433143B2 · Nel et al. · 2022 [cited by applicant]
US 20030165568A1 · Colombo et al. · 2003 [cited by applicant]
US 20080070936A1 · Castelhano et al. · 2008 [cited by applicant]
US 20100178299A1 · Sitkovsky et al. · 2010 [cited by applicant]
US 20110178164A1 · Cunha Dias Real Oliveira et al. · 2011 [cited by applicant]
US 20150071990A1 · Longnecker · 2015 [cited by applicant]
US 20180044304A1 · Sasikumar et al. · 2018 [cited by applicant]
US 20180303949A1 · Zhang · 2018 [cited by applicant]
US 20180339044A1 · Gutierrez · 2018 [cited by examiner]
US 20190099413A1 · Tanaka et al. · 2019 [cited by applicant]
US 20190358343A1 · Wang et al. · 2019 [cited by applicant]
US 20200102319A1 · Crosignani · 2020 [cited by applicant]
US 20200197534A1 · Mei et al. · 2020 [cited by applicant]
US 20210137930A1 · Fardis · 2021 [cited by applicant]
US 20210161898A1 · Leleti et al. · 2021 [cited by applicant]
US 20210163418A1 · Stover et al. · 2021 [cited by applicant]
US 20210251995A1 · Bell et al. · 2021 [cited by applicant]
US 20210315912A1 · Karp et al. · 2021 [cited by applicant]
US 20210332055A1 · Sun et al. · 2021 [cited by applicant]
US 20220025015A1 · Wang · 2022 [cited by applicant]
US 20220211701A1 · Anderson et al. · 2022 [cited by applicant]
US 20220267350A1 · Yu et al. · 2022 [cited by applicant]
US 20220339160A1 · Yu et al. · 2022 [cited by applicant]
WO WO2017147407A1 · 2017 [cited by applicant]
WO WO2018175473A1 · 2018 [cited by examiner]
WO WO2018213631A1 · 2018 [cited by applicant]
WO WO2022119531A1 · 2022 [cited by applicant]
Jorg et al.; Novel adenosine A2A receptor ligands: A synthetic, functional and computational investigation of selected literature adenosine A2A receptor antagonists for extending into extracellular space; Elsevier; Bioo… [cited by examiner]
Jacobson et al; Adenosine analogs with covalently attached lipids have enhanced potency at AI-adenosine receptors; Elsevier; vol. 225, No. 1,2, 97-102 FEBS Letters 1987 (Year: 1987). [cited by examiner]
Langmead et al.; Identification of Novel Adenosine A2A Receptor Antagonists by Virtual Screening; ACS Publications; J. Med. Chem. 2012, 55, 1904-1909 (Year: 2012). [cited by examiner]
Vecchio, et al., Ligand-Independent Adenosine A2B Receptor Constitutive Activity as a Promotor of Prostate Cancer . . . , J. Pharmacol Exp. Ther. 357:36-44 (Apr. 2016). [cited by applicant]
Jaakola, et al., The 2.6 A Crystal Strcuture of a Human A2a Adenosine Receptor Bound to an Antagonist, Science, 322(5905): pp. 1211-1217 (Nov. 21, 2008). [cited by applicant]
Carpenter, et al., Structure of the Adeonsine A2a Receptor Bound to an Engineered G Protein, Nature 536(7614): 104-107 (Aug. 4, 2016). [cited by applicant]
Jacobson, et al., Adenosine Analogs with Covalently Attached Lipids have Enhanced Potency at A1-Adeonosine Receptors, FEBS Letters (1987), 225(1-2), pp. 97-102. [cited by applicant]
Jacobson, et al., Adenosine Analogs with Covalently Attached Lipids have Enhanced Potency at A1-Adenosine Receptors, FEBS Lett. 225(0): pp. 97-102 (Dec. 10, 1987). [cited by applicant]
Jorg, et al., Novel Adenosine A2a Receptor Ligands: A Synthetic, Functional and Computational Investigation of Selected . . . , Bioorg. Med. Chem. Lett. 23 (2013) pp. 3427-3433. [cited by applicant]
Maillard, et al., Adenosine Receptor Prodrugs: Synthesis and Biological Activity of Derivatives of Potent A1- . . . , J. Pharm. Sci., vol. 83, nb. 1, pp. 46-53 (1994)—Abstract. [cited by applicant]
Maillard, et al., Adenosine Receptor Prodrugs: Synthesis and Biological Activity of Derivatives of Potent A1- . . . , J. Pharm. Sci., vol. 83, nb. 1, pp. 46-53 (1994). [cited by applicant]
Ohta, et al., The Role of G-Coupled Adenosine Receptors in Downregulation of Inflammation and Protection From Tissue Damage, Nature, vol. 414, pp. 916-920 (Dec. 2001). [cited by applicant]
Helms, et al., Rethinking the Adenosine-A2aR Checkpoint: Implications for Enhancing Anti-Tumor Immunotherapy, Curr. Opin. in Pharmac. 53: pp. 77-83 (2020). [cited by applicant]
Willingham, et al., Targeting the A2aR in Cancer; Early Lessons from the Clinic, Curr. Opin. in Pharmac., 53: pp. 126-133 (2020). [cited by applicant]
Schiffman, et al., Adenosine A2a Receptors and Basal Ganglia Physiology, Prog. Neurobiol.; 83(5) pp. 277-292 (Dec. 2007). [cited by applicant]
Ongini, et al., Selective Adenosine A2aR Receptors Antagonists, II Farmaco, 56(2001) pp. 87-90. [cited by applicant]
Dore, et al., Structure of the Adenosine A2a Receptor in Complex with ZM241385 and the Xanthines XAC and Caffeine, Structure; 19(9) pp. 1283-1293 (Sep. 7, 2011). [cited by applicant]