IP Library › Granted Patent US 12,616,712
Granted Patent B2
US 12,616,712 · App. 17/754,177 · Granted May 5, 2026

Sting agonist comprising exosomes for treating neuroimmunological disorders

Inventor: Ajay Verma (Cambridge, MA)
Assignee: LONZA SALES AG
A61K31/7084A61K9/127A61K38/208A61K47/6425A61P25/00A61P35/00
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 12,616,712
App. No.
17/754,177
Granted
May 5, 2026
Kind
B2
Abstract

Provided herein are compositions comprising EV, e.g., exosome, which comprises STING agonists and methods of using such compositions for the treatment of neuroimmunological disorders. Methods of producing the compositions (e.g., EVs comprising a STING agonist) described herein are also provided.

Claims (23)

1 . A method of treating a glioblastoma multiforme in a subject in need thereof comprising administering to the subject a composition comprising an extracellular vesicle EV and a stimulator of interferon genes protein STING agonist, wherein the EV overexpresses a Scaffold X protein selected from the group consisting of: prostaglandin F2 receptor negative regulator PTGFRN, basigin BSG, immunoglobulin superfamily member 2 IGSF2, immunoglobulin superfamily member 3 IGSF3, immunoglobulin superfamily member 8 IGSF8, integrin beta-1 ITGB1, integrin alpha-4 ITGA4, 4F2 cell-surface antigen heavy chain SLC3A2, ATP transporter protein, and wherein the Scaffold X protein is a whole protein or a fragment thereof.

2 . The method of claim 1 , wherein the composition is administered intrathecally or intratumorally.

3 . The method of claim 1 , wherein the extracellular vesicle is an exosome.

4 . The method of claim 1 , wherein the STING agonist is associated with the extracellular vesicle.

5 . The method of claim 1 , wherein the Scaffold X protein is prostaglandin F2 receptor negative regulator PTGFRN or a fragment thereof.

6 . The method of claim 5 , wherein the STING agonist is linked to the PTGFRN protein or fragment thereof, optionally by a linker.

7 . The method of claim 1 , wherein the extracellular vesicle is produced by a cell that overexpresses a PTGFRN protein.

8 . The method of claim 1 , wherein the extracellular vesicle further comprises a ligand, a cytokine, or an antibody.

9 . The method of claim 8 , wherein the antibody comprises an antagonistic antibody and/or an agonistic antibody.

10 . The method of claim 1 , wherein the STING agonist is a cyclic dinucleotide or a non-cyclic dinucleotide.

11 . The method of claim 1 , wherein the STING agonist comprises a lipid-binding tag.

12 . The method of claim 1 , wherein the concentration of the STING agonist associated with the extracellular vesicle is about 0.01 μM to 100 μM.

13 . The method of claim 1 , wherein the STING agonist is selected from the group consisting of:

and a pharmaceutically acceptable salt thereof.

14 . The method of claim 13 , wherein the STING agonist is in the lumen of the extracellular vesicle and is not linked to a scaffold moiety.

15 . The method of claim 14 , wherein the composition further comprises a pharmaceutically acceptable carrier.

16 . The method of claim 1 , wherein the administering induces or modulates an immune response and/or an inflammatory response in the subject.

17 . The method of claim 1 , further comprising administering an additional therapeutic agent.

18 . The method of claim 17 , wherein the additional therapeutic agent is an antibody or antigen-binding fragment thereof or an IL-12 moiety.

19 . A kit comprising a composition which comprises an extracellular vesicle and a STING agonist and instructions for use according to the method of claim 1 .

20 . The method of claim 1 , wherein the extracellular vesicle further comprises one or more antisense oligonucleotides ASO.

21 . The method of claim 1 , wherein the EV comprises an anti-phagocytic signal on the exterior surface of the EV.

22 . The method of claim 1 , wherein the EV further comprises one or more tropism moieties that alters the distribution of the EV in a particular cell, tissue or organ.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 5, 2023
From: VERMA, AJAY
To: CODIAK BIOSCIENCES, INC.
Reel/Frame 065766/0969 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 11, 2023
From: CODIAK BIOSCIENCES, INC.
To: LONZA SALES AG
Reel/Frame 064251/0794 →
Continuity (4)
Provisional Application 62704986 · Jun 5, 2020
Provisional Application 62989528 · Mar 13, 2020
Provisional Application 62906002 · Sep 25, 2019
Related Publication 20230241089A1 · Aug 3, 2023
References Cited (103)
US 6268490B1 · Imanishi et al. · 2001 [cited by applicant]
US 7335765B2 · Masakatsu et al. · 2008 [cited by applicant]
US 8821943B2 · Kompella et al. · 2014 [cited by applicant]
US 9056892B2 · Sun et al. · 2015 [cited by applicant]
US 9757470B2 · Narasimhaswamy et al. · 2017 [cited by applicant]
US 10195290B1 · Dooley et al. · 2019 [cited by applicant]
US 20120322851A1 · Hardee et al. · 2012 [cited by applicant]
US 20170348416A1 · Häsler et al. · 2017 [cited by applicant]
US 20180193270A1 · Bolen · 2018 [cited by examiner]
US 20190202936A1 · Dennis et al. · 2019 [cited by applicant]
US 20190300513A1 · Altman · 2019 [cited by examiner]
US 20200254028A1 · Goodman · 2020 [cited by examiner]
WO 1998039352A1 · 1998 [cited by applicant]
WO 1999014226A2 · 1999 [cited by applicant]
WO 2000047599A1 · 2000 [cited by applicant]
WO 2000066604A2 · 2001 [cited by applicant]
WO 2001023613A1 · 2001 [cited by applicant]
WO 2004046160A2 · 2004 [cited by applicant]
WO 2007090071A2 · 2007 [cited by applicant]
WO 2007134181A2 · 2007 [cited by applicant]
WO 2007146511A2 · 2007 [cited by applicant]
WO 2008150729A2 · 2008 [cited by applicant]
WO 2008154401A2 · 2008 [cited by applicant]
WO 2009006478A2 · 2009 [cited by applicant]
WO 2009067647A1 · 2009 [cited by applicant]
WO 2010036698A1 · 2010 [cited by applicant]
WO 2010077578A1 · 2010 [cited by applicant]
WO 2011017521A2 · 2011 [cited by applicant]
WO 2011156202A1 · 2011 [cited by applicant]
WO 2013036868A1 · 2013 [cited by applicant]
WO 2013154798A1 · 2013 [cited by applicant]
WO 2013185052A1 · 2013 [cited by applicant]
WO 2014179335A1 · 2014 [cited by applicant]
WO 2014179760A1 · 2014 [cited by applicant]
WO 2014189805A1 · 2014 [cited by applicant]
WO 2014189806A1 · 2014 [cited by applicant]
WO 2015017652A1 · 2015 [cited by applicant]
WO 2015077354A1 · 2015 [cited by applicant]
WO 2015185565A1 · 2015 [cited by applicant]
WO 2016096577A1 · 2016 [cited by applicant]
WO 2016120305A1 · 2016 [cited by applicant]
WO 2016096174A1 · 2016 [cited by applicant]
WO 2016145102A1 · 2016 [cited by applicant]
WO 2017027645A1 · 2017 [cited by applicant]
WO WO2017027646A1 · 2017 [cited by examiner]
WO 2017075477A1 · 2017 [cited by applicant]
WO 2017175147A1 · 2017 [cited by applicant]
WO 2017175156A1 · 2017 [cited by applicant]
WO 2018100558A1 · 2018 [cited by applicant]
WO 2019099942A1 · 2019 [cited by applicant]
WO 2019183578A1 · 2019 [cited by applicant]
WO 2020101740A1 · 2020 [cited by applicant]
WO 2020191361A2 · 2020 [cited by applicant]
Aguila, B. et al., “The IG superfamily protein PTGFRN coordinates survival signaling in glioblastoma multiforme”, Cancer Letters, 462:33-42 (2019). [cited by applicant]
Bergstrom, D.E., “Unnatural Nucleosides With Unusual Base Pairing Properties,” Current Protocols in Nucleic Acid Chemistry 37(1):1.4.1-1.4.32 (2009). [cited by applicant]
Besse, B. et al., “Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC”, Oncoimmunology 5(4):e107108 (2016). [cited by applicant]
“Codiak Biosciences, Inc., form S-1”, (Apr. 2019), pp. 1-254. [cited by applicant]
Deleavey, G.F. and Damha, M.J., “Designing Chemically Modified Oligonucleotides for Targeted Gene Silencing,” Chemistry & Biology 19(8):937-954 (2012). [cited by applicant]
“Development of the engExTM Platform for Engineered Exosomes and Therapeutic Potential of Codiak's exoSTING Highlighted at the 2019 American Association for Cancer Research Annual Meeting” BusinessWire, Apr. 1, 2019, ac… [cited by applicant]
Dobeli, H. et al., “Role of the carboxy-terminal sequence on the biological activity of human immune interferon (IFN-y)”, Journal of Biotechnology 7(3):199-216 (1988). [cited by applicant]
Dooley, K., et al., “Abstract 2150: engEx: A novel exosome engineering platform enabling targeted transfer of pharmacological molecules”, Cancer Research, 79(13 Supplement): Abstract 2150 (2019). [cited by applicant]
Ernfors, P., et al., “Developmental and Regional Expression of Beta-nerve Growth Factor Receptor mRNA in the Chick and Rat,” Neuron 1(10):983-996, Cell Press, United States (Dec. 1988). [cited by applicant]
Freier, S.M. and Altmann, K.H., “The Ups and Downs of Nucleic Acid Duplex Stability: Structure-stability Studies on Chemically-modified DNA: RNA Duplexes,” Nucleic Acids Research 25(22):4429-4443 (1997). [cited by applicant]
Gayle, R.B. et al., “Identification of regions in interleukin-I alpha important for activity”, Journal of Biological Chemistry 268(29):22105-22111 (1993). [cited by applicant]
GenBank, “ [cited by applicant]
GenBank, “ [cited by applicant]
GenBank, “ [cited by applicant]
GenBank, “ [cited by applicant]
GenBank, “ [cited by applicant]
GenBank, “ [cited by applicant]
GenBank, “Mus musculus melanotransferrin (Meltf), mRNA,” Accession No. NM_013900, accessed at URL:[https://www.ncbi.nlm.nih.gov/nuccore/NM_013900.2/], 6 pages. [cited by applicant]
GenBank, “ [cited by applicant]
GenBank, “ [cited by applicant]
GenBank, “ [cited by applicant]
Hirao, I., et al., “Natural Versus Artificial Creation of Base Pairs in DNA: Origin of Nucleobases From the Perspectives of Unnatural Base Pair Studies,” Accounts of Chemical Research 45(12):2055-2065 (2012). [cited by applicant]
Ibáñez, C.F., et al., “Chimeric Molecules With Multiple Neurotrophic Activities Reveal Structural Elements Determining the Specificities of NGF and BDNF,” The EMBO Journal 10(8):2105-2110, Wiley Blackwell, United Kingdo… [cited by applicant]
Jafari, B. et al., “Peptide-mediated drug delivery across the blood-brain barrier for targeting brain tumors”, Expert Opinion on Drug Delivery 16(6):583-605 (2019). [cited by applicant]
Jang, S.C. et al., “Abstract 944: exoSTING: An engineered exosome therapeutic that selectively delivers STING agonist to the tumor resident antigen-presenting cells resulting in improved tumor antigenspecific adaptive i… [cited by applicant]
Kamerkar, S. et al., “Genetic reprogramming of TAMS by engineered exosomes results in potent single agent anti-tumor activity”, 80(60 Supplement): Abstract 5696 (2020). [cited by applicant]
Kramer, K. et al., “Monoclonal Antibody to Human Trk-A: Diagnostic and Therapeutic Potential in Neuroblastoma”, European Journal of Cancer 33(12):2090-2091 (1997). [cited by applicant]
Leibrock, J., et al., “Molecular Cloning and Expression of Brain-derived Neurotrophic Factor,” Nature 341(6238):149-152 (1989). [cited by applicant]
Lesauteur, L. et al. “Small Peptide Mimics of Nerve Growth Factor Bind TrkA Receptors and Affect Biological Responses”, The Journal of Biological Chemistry 270(12):6564-6569 (1995). [cited by applicant]
Longo, F.M. et al., “Synthetic NGF Peptide Derivatives Prevent Neuronal Death Via a p75 Receptor-Dependent Mechanism”, Journal of Neuroscience Research 48:1-17 (1997). [cited by applicant]
Mei, B. et al., “Rational design of a fully active, long-acting PEGylated factor VIII for hemophilia A treatment”, Blood 116(2):270-279 (2010). [cited by applicant]
Mitsuoka, Y., et al., “A Bridged Nucleic Acid, 2′,4′-BNA COC: Synthesis of Fully Modified Oligonucleotides Bearing Thymine, 5-Methylcytosine, Adenine and Guanine 2′,4′-BNA COC Monomers and RNA-Selective Nucleic-Acid Rec… [cited by applicant]
Morita, K., et al., “2′-O,4′-C-Ethylene-Bridged Nucleic Acids (ENA): Highly Nuclease-Resistant and Thermodynamically Stable Oligonucleotides for Antisense Drug,” Bioorganic and Medicinal Chemistry Letters 12(1):73-76 (2… [cited by applicant]
Oh, T. et al., “Immunocompetent murine models for the study of glioblastoma immunotherapy”, Journal of Translational Medicine 29(12):107 (2014). [cited by applicant]
Ohkuri, T. et al., “STING contributes to anti-glioma immunity via triggering type-I IFN signals in the tumor microenvironment”, Cancer Immunology Research 2(12):1199-1208 (2014). [cited by applicant]
Ohkuri, T. et al., “Protective role of STING against gliomagenesis: Rational use of STING agonist in anti-glioma immunotherapy”, Oncoimmunology 4(4):e999523 (2015). [cited by applicant]
Oller-Salvia, B. et al., “Blood-brain barrier shuttle peptides: an emerging paradigm for brain delivery”, Chemical Society Reviews 45(7):4690-4707 (2016). [cited by applicant]
Papapetrou, E.P. et al., “Genetic Modification of Hematopoietic Stem Cells With Nonviral Systems: Past Progress and Future Prospects”, Gene Therapy 12(Supplement 1):S118-S130 (2005). [cited by applicant]
Rodriguez, P.L. et al., “Minimal “Self” peptides that inhibit phagocytic clearance and enhance delivery of nanoparticles”, Science 339(6122):971-975 (2013). [cited by applicant]
Ron, D. et al., “Expression of biologically active recombinant keratinocyte growth factor. Structure/function analysis of amino-terminal tnmcation mutants”, Journal of Biological Chemistry 268(4):2984-2988 (1993). [cited by applicant]
Sellers, D.L., et al., “Targeted Axonal Import (TAxI) Peptide Delivers Functional Proteins Into Spinal Cord Motor Neurons After Peripheral Administration,” Proceedings of the National Academy of Sciences of the United S… [cited by applicant]
Seth, P.P., et al., “Synthesis and Biophysical Evaluation of 2′,4′-constrained 2′O-methoxyethyl and 2′,4′-constrained 2′O-ethyl Nucleic Acid Analogues,” Journal of Organic Chemistry 75(5):1569-1581 (2010). [cited by applicant]
Spengler, J., et al., “Abbreviated nomenclature for cyclic and branched homo- and hetero-detic peptides,” Peptide Research 65(6):550-555 (2005). [cited by applicant]
Ubah, O.C., et al., “Next-generation Flexible Formats of VNAR Domains Expand the Drug Platform's Utility and Developability,” Biochemical Society Transactions 46(6):1559-1565 (2018). [cited by applicant]
Uhlmann, E., “Recent Advances in the Medicinal Chemistry of Antisense Oligonucleotides,” Current Opinion in Drug Discovery and Development 3(2):203-213 (2000). [cited by applicant]
UniProtKB, “CEBPB_HUMAN,” Accession No. P17676, accessed at URL:[https://www.uniprot.org/uniprotkb/P17676/entry], 16 pages. [cited by applicant]
UniProtKB, “TFR1_HUMAN,” Accession No. P20786, accessed at URL:[https://www.uniprot.org/uniprotkb/P02786/entry], 11 pages. [cited by applicant]
UniProtKb, “STAT6_HUMAN,” Accession No. P42226, accessed at URL:[https://www.uniprot.org/uniprotkb/P42226/entry], 13 pages. [cited by applicant]
Verma, A., et al., “Intrathecal 99mTc-DTPA imaging of molecular passage from lumbar cerebrospinal fluid to brain and periphery in humans,” Alzheimer's & Dementia 12(1):e12030 (2020). [cited by applicant]
“33rd Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2018)” Journal for ImmunoTherapy of Cancer 6(Supplement 1):115, pp. 1-192 (2018). [cited by applicant]