IP Library › Granted Patent US 12,398,377
Granted Patent B2
US 12,398,377 · App. 19/043,304 · Granted Aug 26, 2025

Pseudotyped viral particles, compositions comprising the same, and uses thereof

Inventors: Ronnie M. Russell (Philadelphia, PA); Philip R. Johnson (Sarasota, FL); Bruce Schnepp (Philadelphia, PA)
Assignee: Interius Biotherapeutics, Inc.
C12N7/00C07K14/005C07K16/2896C12N15/113C12N15/86C12N2740/15023C12N2740/15043C12N2760/20222
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Quick Facts
Patent No.
US 12,398,377
App. No.
19/043,304
Granted
Aug 26, 2025
Kind
B2
Abstract

Provided for herein are mutant VSV-G polypeptides, compositions comprising the same, and methods of using the same. Also provided for herein are polypeptides and compositions that bind to CD7 and uses thereof. Also provided for herein are polypeptides and compositions that bind to CD8 and uses thereof.

Claims (24)

1. A pseudotyped lentivirus comprising:

i) a mutant VSV-G polypeptide comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 2;

ii) a targeting moiety on the surface of the pseudotyped lentivirus comprising an antibody that binds to CD7; and

iii) a nucleic acid molecule encoding a heterologous molecule of interest;

wherein the mutant VSV-G polypeptide is not linked or conjugated to the targeting moiety.

2. The pseudotyped lentivirus of claim 1 , wherein the mutant VSV-G polypeptide is at least 97% identical to the amino acid sequence of SEQ ID NO: 2.

3. The pseudotyped lentivirus of claim 1 , wherein the mutant VSV-G polypeptide is at least 99% identical to the amino acid sequence of SEQ ID NO: 2.

4. The pseudotyped lentivirus of claim 1 , wherein the VSV-G polypeptide comprises a T214N mutation or a T352A mutation.

5. The pseudotyped lentivirus of claim 2 , wherein the VSV-G polypeptide comprises a T214N mutation or a T352A mutation.

6. The pseudotyped lentivirus of claim 3 , wherein the VSV-G polypeptide comprises a T214N mutation or a T352A mutation.

7. The pseudotyped lentivirus of claim 1 , wherein the VSV-G polypeptide comprises a T214N mutation and a T352A mutation.

8. The pseudotyped lentivirus of claim 2 , wherein the VSV-G polypeptide comprises a T214N mutation and a T352A mutation.

9. The pseudotyped lentivirus of claim 3 , wherein the VSV-G polypeptide comprises a T214N mutation and a T352A mutation.

10. The pseudotyped lentivirus of claim 1 , wherein the antibody is an scFv antibody, a VHH domain antibody, or a single domain antibody.

11. The pseudotyped lentivirus of claim 1 , wherein the lentivirus does not comprise a targeting moiety that binds to CD3.

12. The pseudotyped lentivirus of claim 1 , wherein the heterologous molecule of interest is a chimeric antigen receptor (“CAR”).

13. The pseudotyped lentivirus of claim 1 , wherein the heterologous molecule of interest is an siRNA, an shRNA, a non-coding RNA, a peptide, a polypeptide, a viral payload, a viral genome, or a combination thereof.

14. A pharmaceutical composition comprising the pseudotyped lentivirus of claim 1 .

15. A pharmaceutical composition comprising the pseudotyped lentivirus of claim 4 .

16. A pharmaceutical composition comprising the pseudotyped lentivirus of claim 5 .

17. A pharmaceutical composition comprising the pseudotyped lentivirus of claim 6 .

18. A pharmaceutical composition comprising the pseudotyped lentivirus of claim 8 .

19. The pseudotyped lentivirus of claim 1 , wherein the targeting moiety is attached to the viral surface through an IgG Fc stalk.

20. The pseudotyped lentivirus of claim 19 , wherein the stalk comprises a transmembrane domain.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 13, 2025
From: RUSSELL, RONNIE M.; JOHNSON, PHILIP R.; ANDORKO, JAMES I.; SACHDEVA, MOHIT; SCHNEPP, BRUCE; MARINELLI, MICAHEL; FOSS, JEFFERY; BORAL, DEBASISH
To: INTERIUS BIOTHERAPEUTICS, INC.
Reel/Frame 070505/0368 →
Continuity (8)
Continuation 18647283 · Apr 26, 2024
Continuation 18157421 · Jan 20, 2023
Continuation 18066420 · Dec 15, 2022
Provisional Application 63267039 · Jan 21, 2022
Provisional Application 63266044 · Dec 27, 2021
Provisional Application 63289977 · Dec 15, 2021
Provisional Application 63289888 · Dec 15, 2021
Related Publication 20250171746A1 · May 29, 2025
References Cited (109)
US 4439196A · Higuchi · 1984 [cited by applicant]
US 4447224A · DeCant, Jr. et al. · 1984 [cited by applicant]
US 4447233A · Mayfield · 1984 [cited by applicant]
US 4487603A · Harris · 1984 [cited by applicant]
US 4596556A · Morrow et al. · 1986 [cited by applicant]
US 4790824A · Morrow et al. · 1988 [cited by applicant]
US 4816567A · Cabilly et al. · 1989 [cited by applicant]
US 4941880A · Burns · 1990 [cited by applicant]
US 4946778A · Ladner et al. · 1990 [cited by applicant]
US 5064413A · McKinnon et al. · 1991 [cited by applicant]
US 5260203A · Ladner et al. · 1993 [cited by applicant]
US 5312335A · McKinnon et al. · 1994 [cited by applicant]
US 5383851A · McKinnon, Jr. et al. · 1995 [cited by applicant]
US 5399163A · Peterson et al. · 1995 [cited by applicant]
US 6005079A · Casterman et al. · 1999 [cited by applicant]
US 6096002A · Landau · 2000 [cited by applicant]
US 6620135B1 · Weston et al. · 2003 [cited by applicant]
US 11767366B1 · Russell et al. · 2023 [cited by applicant]
US 20080227736A1 · Chen et al. · 2008 [cited by applicant]
US 20180036429A1 · Acharjee · 2018 [cited by applicant]
US 20180371064A1 · Fusil et al. · 2018 [cited by applicant]
US 20190055568A1 · Pulé et al. · 2019 [cited by applicant]
US 20200216502A1 · Albertini et al. · 2020 [cited by applicant]
US 20200371088A1 · Birnbaum et al. · 2020 [cited by applicant]
US 20210106632A1 · Kim et al. · 2021 [cited by applicant]
US 20230279363A1 · Russell et al. · 2023 [cited by applicant]
EP 0404097A2 · 1990 [cited by applicant]
WO WO1988001649A1 · 1988 [cited by applicant]
WO WO1993011161A1 · 1993 [cited by applicant]
WO WO1994004678A1 · 1994 [cited by applicant]
WO WO1994025591A1 · 1994 [cited by applicant]
WO WO1997009433A1 · 1997 [cited by applicant]
WO WO2004041862A2 · 2004 [cited by applicant]
WO WO2016065323A2 · 2016 [cited by applicant]
WO WO2020223240A1 · 2020 [cited by applicant]
WO WO2022183072A1 · 2022 [cited by applicant]
WO WO2023107593A2 · 2023 [cited by applicant]
WO WO2023114884A2 · 2023 [cited by applicant]
WO WO2023170681A1 · 2023 [cited by applicant]
WO 2024067870A1 · 2024 [cited by applicant]
WO 2024213019A1 · 2024 [cited by applicant]
WO 2024213153A1 · 2024 [cited by applicant]
Andorko, J. et al., Blood, 2023, vol. 142: pp. 763-764. [cited by examiner]
Zeller, S. et al., Mol. Ther., May 2012, vol. 20 Supplement 1: p. S135. [cited by examiner]
U.S. Appl. No. 63/154,639, filed Feb. 26, 2021, ViraLogic Therapeutics, Inc. [cited by applicant]
50YL Albertini, A.A. et al., “5OYL, VSV G CR2”, RCSB PDB, Mar. 21, 2018, last revised Apr. 18, 2018, available at https://www.rcsb.org/structure/5OYL (last accessed Jan. 3, 2024), 6 pages. [cited by applicant]
50Y9—Albertini, A.A. et al., “5OY9, VSV G CR3”, RCSB PDB, Mar. 21, 2018, last revised Apr. 18, 2018, available at https://www.rcsb.org/structure/5OY9 (last accessed Jan. 3, 2024), 6 pages. [cited by applicant]
Albertini et al., “Molecular and Cellular Aspects of Rhabdovirus Entry,” Viruses (2012) 4:117-129. [cited by applicant]
Baert et al., “Influence of Immunogenicity on the Long-Term Efficacy of Infliximab in Crohn's Disease,” (2003) New Engl. J. Med. 348:601-608. [cited by applicant]
Beniaminovitz et al., “Prevention of Rejection in Cardiac Transplantation by Blockade of the Interleukin-2 Receptor with a Monoclonal Antibody,” (2000) New Engl. J. Med. 342(9):613-619. [cited by applicant]
C. Dunbar et al, “Gene therapy comes of age”, 359 Science 1 (2018). [cited by applicant]
Chothia et al., “Canonical Structures for the Hypervariable Regions of Immunoglobulins,” (1987) J. Mol. Biol. 196:901-917. [cited by applicant]
Chothia et al., “Conformations of Immunoglobulin Hypervariable Regions,” (1989) Nature 342: 877-883. [cited by applicant]
Clackson et al., “Making Antibody Fragments Using Phage Display Libraries,” (1991) Nature 352:624-628. (Abstract Only). [cited by applicant]
Donald J. Voet et al, “Fundamentals of biochemistry” (2008), chapters 3 and 4, 39-82. [cited by applicant]
Duverge and M. Negroni, “Pseudotyping lentiviral vectors: when the clothes make the virus”, 12 Viruses 1311 (2020). [cited by applicant]
E. Pettersen et al., “UCSF Chimera—A visualization system for exploratory research and analysis”, 25 J. Comp. Chem. 1605 (2004). [cited by applicant]
F. Amirache et al, “Mystery solved: VSV-G-LVs do not allow efficient gene transfer into unstimulated T cells, B cells, and HSCs cause they lack the LDL receptor”, 123 Blood 1422 (2014). [cited by applicant]
Finkelshtein et al., “LDL Receptor and its Family Members Serve as the Cellular Receptors for Vesicular Stomatitis Virus,” PNAS (2013) 110(18): 7306-7311. [cited by applicant]
Ghosh et al., “Natalizumab for Active Crohn's Disease,” (2003) New Engl. J. Med. 348:24-32. [cited by applicant]
Herold et al., “Anti-CD3 Monoclonal Antibody in New-Onset Type 1 Diabetes Mellitus,” (2002) New Engl. J. Med. 346(22):1692-1698. [cited by applicant]
Holliger et al., “Diabodies: Small Bivalent and Bispecific Antibody Fragments,” (1993) Proc. Natl. Acad. Sci. USA 90: 6444-6448. [cited by applicant]
Holliger et al., “Engineered Antibody Fragments and the Rise of Single Domains,” (2005) Nat. Biotechnol. 23(9): 1126-1136. [cited by applicant]
Hwang et al., “Engineering a Serum-Resistant and Thermostable Vesicular Stomatitis Virus G Glycoprotein for Pseudotyping Retroviral and Lentiviral Vectors,” Gene Ther. (Aug. 2013) 20(8):807-815. [cited by applicant]
International Search Report and Written Opinion for PCT/US2022/081616, dated Jun. 15, 2023, 14 pages. [cited by applicant]
J. Rose and C. Gallione, “Nucleotide Sequences of the mRNAs Encoding the Vesicular Stomatitis Virus G and M Proteins Determined from cDNA Clones Containing the Complete Coding Regions”, 39 J. Virology 519 (1981). [cited by applicant]
Kabat et al., “Unusual Distributions of Amino Acids in Complementarity-Determining (Hypervariable) Segments of Heavy and Light Chains of Immunoglobulins and Their Possible Roles in Specificity of Antibody-Combining Site… [cited by applicant]
Kabat, “The Structural Basis for Antibody Complementary,” Adv. Prot. Chem. (1978) 32:1-75. (Abstract Only). [cited by applicant]
L. Naldini et al, “In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector”, 272 Science 263 (1996). [cited by applicant]
Lathe, “Synthetic Oligonucleotide Probes Deduced from Amino Acid Sequence Data,” J. Molec. Biol. (1985) 183:1-12. [cited by applicant]
Lee et al., “ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells,” Biol. Blood Marrow Transplant (2019) 25:625-638. [cited by applicant]
Lipsky et al., “Infliximab and Methotrexate in the Treatment of Rheumatoid Arthritis,” (2000) New Engl. J. Med. 343(22):1594-1602. [cited by applicant]
Liu et al., “Chimeric Mouse-Human IgG1 Antibody that can Mediate Lysis of Cancer Cells,” Proc Natl. Acad. Sci., USA (1987) 84:3439-3443. [cited by applicant]
Liu et al., “Production of a Mouse-Human Chimeric Monoclonal Antibody to CD20 with Potent Fc-Dependent Biologic Activity,” J. Immunology (1987) 139(10):3521-3526. [cited by applicant]
Liu et al., “Randomised, Double Blind, Placebo Controlled Study of Interferon Beta-1a in Relapsing-Remitting Multiple Sclerosis Analysed by Area under Disability/Time Curves,” J. Neurol. Neurosurg. Psych. (1999) 67:451-… [cited by applicant]
Marks et al., “By-Passing Immunization,” J. Mol. Biol. (1991) 222: 581-597. [cited by applicant]
Michaels et al., “Preclinical proof of concept for VivoVec, a lentiviral-based platform for in vivo CAR T-cell engineering”, J Immunother Cancer 2023;11:e006292. doi:10.1136/jitc-2022-006292, 40 pages. [cited by applicant]
Milgrom et al., “Treatment of Allergic Asthma with Monoclonal Anti-IgE Antibody,” New Engl. J. Med. (1999) 341:1966-1973. [cited by applicant]
Muller, “[43] Determination of Affinity and Specificity of Anti-Hapten Antibodies by Competitive Radioimmunoassay,” Meth. Enzymol. (1983) 92:589-601. (Abstract Only). [cited by applicant]
Muyldermans et al., “Recognition of Antigens by Single-Domain Antibody Fragments: the Superfluous Luxury of Paired Domains,” (2001) Trends Biochem. Sci. 26(4):230-235. [cited by applicant]
N. Depolo et al., “VSV-G Pseudotyped lentiviral vector produced in human cells are inactivated by human serum”, 2 Molecular therapy 218 (2000). [cited by applicant]
Neelapu et al., “Chimeric Antigen Receptor T-Cell Therapy—Assessment and Management of Toxicities,” Nat. Rev. Clin. Oncology (Jan. 2018) 15(1):47-62. [cited by applicant]
Nikolic et al., “Structural Basis for the Recognition of LDL-Receptor Family Members by VSV Glycoprotein,” Nature Comm. (2018) 9(1029): 1-12. [cited by applicant]
Notice of Allowance for U.S. Appl. No. 18/066,420 dated Jul. 26, 2023. [cited by applicant]
Notice of Allowance for U.S. Appl. No. 18/157,421 dated Aug. 25, 2023. [cited by applicant]
Pluckthun, “Antibodies from [cited by applicant]
Portielji et al., “IL-12: A Promising Adjuvant for Cancer Vaccination,” Cancer Immunol. Immunother. (2003) 52:133-144. [cited by applicant]
Presta, “Selection, Design, and Engineering of Therapeutic Antibodies,” J. Allergy Clin. Immunol. (2005) 116(4):731-736. [cited by applicant]
R. Florkiewicz and J. Rose, “A Cell Line Expressing Vesicular Stomatitis Virus Glycoprotein fuses at low ph”, 225 Science 721 (1984). [cited by applicant]
Reichmann et al., “Reshaping Human Antibodies for Therapy,” Nature (1988) 332(6162):323-327. [cited by applicant]
Roche et al., “Crystal Structure of the Low-pH Form of the Vesicular Stomatitis Virus Glycoprotein G,” Science (Jul. 14, 2006) 313:187-191. [cited by applicant]
Roche et al., “Structure of the Prefusion Form of the Vesicular Stomatitis Virus Glycoprotein G,” Science (Feb. 9, 2007) 315:843-848. [cited by applicant]
S. P. J. Whelan, “Vesicular stomatis Virus”, Encyclopedia of virology 291 (Elsevier ltd) (2008). [cited by applicant]
S. Roche et al, “Structures of vesicular stomatitis virus glycoprotein: membrane fusion revisited”, 65 Cell Mol. Life Sci. 1716 (2008). [cited by applicant]
Slamon et al., “Use of Chemotherapy Plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer that Overexpresses HER2,” (2001) New Engl. J. Med. 344(11):783-792. [cited by applicant]
Teachey et al., “Identification of Predictive Biomarkers for Cytokine Release Syndrome after Chimeric Antigen Receptor T-cell Therapy for Acute Lymphoblastic Leukemia,” Cancer Discov. (Jun. 2016) 6(6):664-679. [cited by applicant]
Tsurushita et al., “Humanization of a Chicken Anti-IL-12 Monoclonal Antibody,” J. Immuno. Methods (2004) vol. 295, pp. 9-19. [cited by applicant]
Yang et al., “A Randomized Trial of Bevacizumab, an Anti-Vascular Endothelial Growth Factor Antibody, for Metastatic Renal Cancer,” (2003) New Engl. J. Med. 349(5):427-434. [cited by applicant]
Zardecki et al, “RCSB Protein Data Bank: A Resource for Chemical, Biochemical, and Structural Explorations of large and small biomolecules”, 93 J. Chem. Educ. 569(2016). [cited by applicant]
INH-014USCI—USPTO Before the Patent Trial and Appeal Board [cited by applicant]
INH-014USCI—SPTO Before the Patent Trial and Appeal Board [cited by applicant]
Ammayappan, et al “Characteristics of Oncolytic Vesicular Stomatitis Virus Displaying Tumor-Targeting Ligands”, Journal of Virology, vol. 87, No. 24, Dec. 2013, pp. 13543-13555. [cited by applicant]
Petition for Post-Grant Review of U.S. Pat. No. 11,767,366, Before the Patent Trial and Appeal Board, [cited by applicant]
Declaration of Professor John K. Rose, PHD, in Support of Petition for Post-Grant Review of U.S. Pat. No. 11,767,366, Before the Patent Trial and Appeal Board, [cited by applicant]
[cited by applicant]
U.S. Appl. No. 63/154,639, filed Feb. 26, 2021, Applicant ViraLogic Therapeutics, Inc. [cited by applicant]
5OY9—Albertini, A.A. et al., “5OY9, VSV G CR3”, RCSB PDB, Mar. 21, 2018, last revised Apr. 18, 2018, available at https://www.rcsb.org/structure/5OY9 (last accessed Jan. 3, 2024), 6 pages. [cited by applicant]
INH-014USCI—USPTO Before the Patent Trial and Appeal Board [cited by applicant]
Notice of Allowance for U.S. Appl. No. 18/157,421 dated Jul. 26, 2023. [cited by applicant]