IP Library Granted Patent US 12,403,194
Granted Patent B2
US 12,403,194 · App. 18/919,103 · Granted Sep 2, 2025

Compositions for treating cancer

Inventors: Kevin M. Friedman (Boston, MA); Molly R. Perkins (Milton, MA); Connor S. Dobson (Washington, DC); Stephen L. Sazinsky (Winchester, MA); Shannon G. Contrastano (Auburndale, MA); Emily Thompson Beura (Mansfield, MA); Cory Ahonen (Lebanon, NH); Andrew Avery (Lebanon, NH)
Assignee: Kelonia Therapeutics, Inc.
A61K40/4215A61K40/11A61K40/15A61K40/31A61K48/005A61P35/00C07K14/7051C07K16/2809C07K16/2878C12N15/86A61K2239/13C07K2317/622C12N2740/15022C12N2740/15023C12N2740/15043C12N2830/48C12N2830/50
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Quick Facts
Patent No.
US 12,403,194
App. No.
18/919,103
Granted
Sep 2, 2025
Kind
B2
Abstract

The present disclosure provides compositions and methods comprising recombinant particles suitable for specifically delivering one or more chimeric antigen receptors to immune effector cells in vivo.

Claims (31)

1. A recombinant lentiviral particle comprising:

(a) a viral envelope comprising (i) a vesicular stomatitis Indiana virus envelope glycoprotein (VSIV-G) comprising amino acid substitutions selected from the group consisting of: K47A and R354A; K47A and R354Q; K47Q and R354A; and K47Q and R354Q; and (ii) a non-viral membrane-bound tropism polypeptide comprising an anti-CD3ε scFv and a human CD8α hinge and transmembrane domain; and

(b) a recombinant lentiviral vector comprising a polynucleotide encoding a myeloproliferative sarcoma virus enhancer, negative control region deleted, d1587rev primer-binding site substituted (MND) U3 promoter or an EF1α promoter operably linked to a polynucleotide encoding a signal peptide and an anti-BCMA chimeric antigen receptor comprising an anti-BCMA scFv comprising a heavy chain variable region (VH) comprising a CDRH1, a CDRH2, and a CDRH3 comprising the amino acid sequences of SEQ ID NOs: 82, 83, and 84, and a light chain variable region (VL) comprising a CDRL1, a CDRL2, and a CDRL3 comprising the amino acid sequences of SEQ ID NOs: 86, 87, and 88; a CD8α hinge and transmembrane domain; a CD137 costimulatory domain; and a CD3ζ primary signaling domain.

2. The particle of claim 1 , wherein the anti-CD3ε scFv is isolated from TR66.

3. The particle of claim 1 , wherein the anti-CD3ε scFv comprises the amino acid sequence of any one of SEQ ID NOs: 153, 154, 163, 164, 173, 174, 183, 184, 193, 194, 203, 204, 213, 214, 223, and 224.

4. An isolated immune effector cell transduced with the particle of claim 1 .

5. A composition comprising the immune effector cell of claim 4 .

6. A composition comprising the particle of claim 1 .

7. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the particle of claim 1 .

8. A kit comprising the particle of claim 1 , a pharmaceutically acceptable carrier, and instructions for use.

9. A recombinant lentiviral particle comprising:

(a) a viral envelope comprising (i) a mutated viral envelope glycoprotein comprising the amino acid sequence of any one of SEQ ID NOs: 332, 333, 334, and 335 and (ii) a non-viral membrane-bound tropism polypeptide comprising the amino acid sequence of any one of SEQ ID NOs: 324, 325, 326, 327, 328, 329, 330, and 331; and

(b) a recombinant lentiviral vector comprising a 5′ long terminal repeat (LTR) comprising R and U5 regions; a Psi (Ψ) packaging signal; a cPPT/FLAP; a rev response element (RRE); a polynucleotide encoding an MND promoter or an EF1α promoter operably linked to a polynucleotide encoding a signal peptide and an anti-BCMA chimeric antigen receptor (CAR) comprising the amino acid sequence of SEQ ID NO: 270; optionally a WPRE; a 3′ LTR comprising U3 and R regions; a polyadenylation signal; and a poly(A) tail.

10. The particle of claim 9 , wherein the mutated viral envelope glycoprotein comprises the amino acid sequence of SEQ ID NO: 335.

11. The particle of claim 9 , wherein the non-viral membrane-bound tropism polypeptide comprises the amino acid sequence of SEQ ID NO: 324.

12. An isolated immune effector cell transduced with the particle of claim 9 .

13. A composition comprising the particle of claim 9 .

14. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the particle of claim 9 .

15. A kit comprising the particle of claim 9 , a pharmaceutically acceptable carrier, and instructions for use.

16. A recombinant lentiviral particle comprising:

(a) a viral envelope comprising (i) a mutated viral envelope glycoprotein comprising the amino acid sequence of SEQ ID NO: 335 and (ii) a non-viral membrane-bound tropism polypeptide comprising the amino acid sequence of SEQ ID NO: 324; and

(b) a recombinant lentiviral vector comprising a 5′ LTR comprising R and U5 regions; a Ψ packaging signal; a cPPT/FLAP; a rev response element (RRE); a polynucleotide encoding an EF1α promoter operably linked to a polynucleotide encoding a signal peptide and an anti-BCMA CAR comprising the amino acid sequence of SEQ ID NO: 270; optionally a WPRE; a 3′ LTR comprising U3 and R regions; a polyadenylation signal; and a poly(A) tail.

17. The particle of claim 16 , wherein the EF1α promoter comprises the polynucleotide sequence of SEQ ID NO: 319.

18. The particle of claim 16 , wherein the recombinant lentiviral vector is a recombinant HIV-1 lentiviral vector or a recombinant HIV-2 lentiviral vector.

19. The particle of claim 16 , wherein the polynucleotide encoding the anti-BCMA CAR comprises the polynucleotide sequence of SEQ ID NO: 302.

20. The particle of claim 16 , wherein the signal peptide is isolated from a polypeptide selected from the group consisting of: CD8α, mIgGκ, hIgGk, CD33, tPA, SEAP, hGM-CSF, CSF2R, and B2M.

21. The particle of claim 16 , wherein the lentiviral vector further comprises a WPRE operably linked to the 3′ end of the polynucleotide encoding the anti-BCMA CAR.

22. An isolated immune effector cell transduced with the particle of claim 16 .

23. The immune effector cell of claim 22 , wherein the immune effector cell is a T cell or natural killer (NK) cell.

24. A composition comprising the particle of claim 16 .

25. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the particle of claim 16 .

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 27, 2025
From: FRIEDMAN, KEVIN M.; DOBSON, CONNOR S.; SAZINSKY, STEPHEN L.; CONTRASTANO, SHANNON G.; BEURA, EMILY THOMPSON
To: KELONIA THERAPEUTICS, INC.
Reel/Frame 070012/0149 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 27, 2025
From: PERKINS, MOLLY R.
To: KELONIA THERAPEUTICS, INC.
Reel/Frame 070012/0188 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 27, 2025
From: AHONEN, CORY; AVERY, ANDREW
To: ADIMAB, LLC
Reel/Frame 070012/0239 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 27, 2025
From: ADIMAB, LLC
To: KELONIA THERAPEUTICS, INC.
Reel/Frame 070012/0249 →
Continuity (4)
Continuation PCTUS2024048301 · Sep 25, 2024
Provisional Application 63618878 · Jan 8, 2024
Provisional Application 63540336 · Sep 25, 2023
Related Publication 20250099615A1 · Mar 27, 2025
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