BCMA chimeric antigen receptors

• US 10,383,929 B2
• Filed: 12/07/2015
• Issued: 08/20/2019
• Est. Priority Date: 12/12/2014
• Status: Active Grant

• Current Assignee: 2seventy Bio, Inc. (bluebird bio, Inc.)
• Original Assignee: bluebird bio, Inc.
• Inventors: Morgan, Richard, Friedman, Kevin
• Primary Examiner(s): Babic, Christopher M
• Assistant Examiner(s): Aron, Kimberly A.
• Application Number:
  US15/535,365
• Publication Number:
  US 20180085444A1
• Time in Patent Office: 1,352 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/5156 expressing foreign proteins
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 2039/585 wherein the target is cancer
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4631 Chimeric Antigen Receptors [CAR]
• CPC Class Codes: A61K 39/464417 Receptors for tumor necrosis factors [TNF], e.g. lymphotoxin receptor [LTR], CD30
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/7051 : T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 14/70517 : CD8
• CPC Class Codes: C07K 14/70578 : NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 NGF-receptor C07K14/71, TNF-receptor C07K14/7151
• CPC Class Codes: C07K 16/2878 : against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C07K 2317/622 : Single chain antibody (scFv)
• CPC Class Codes: C07K 2319/32 : fusions with soluble part of a cell surface receptor, "decoy receptors"
• CPC Class Codes: C12N 15/86 : Viral vectors
• CPC Class Codes: C12N 2740/15043 : viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2830/15 : chimeric enhancer/promoter combination
• CPC Class Codes: C12N 5/0636 : T lymphocytes
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention provides improved compositions for adoptive T cell therapies for B cell related conditions.

Claims

1. A polynucleotide encoding a chimeric antigen receptor (CAR) comprising the polynucleotide sequence set forth in SEQ ID NO:

10.

2. A vector comprising the polynucleotide of claim 1.

3. The vector of claim 2, wherein the vector is an expression vector.

4. The vector of claim 2, wherein the vector is an episomal vector.

5. The vector of claim 2, wherein the vector is a viral vector.

6. The vector of claim 2, wherein the vector is a retroviral vector.

7. The vector of claim 2, wherein the vector is a lentiviral vector.

8. The vector of claim 2, wherein the lentiviral vector is selected from the group consisting essentially of:

human immunodeficiency virus 1 (HIV-1);

human immunodeficiency virus 2 (HIV-2), visna-maedi virus (VMV) virus;

caprine arthritis-encephalitis virus (CAEV);

equine infectious anemia virus (EIAV);

feline immunodeficiency virus (FIV);

bovine immune deficiency virus (BIV); and

simian immunodeficiency virus (SIV).

9. The vector of claim 8, comprising a left (5′

) retroviral LTR, a Psi (Ψ

) packaging signal, a central polypurine tract/DNA flap (cPPT/FLAP), a retroviral export element;

a promoter operably linked to the polynucleotide encoding the CAR; and

a right (3′

) retroviral LTR.

10. The vector of claim 9, further comprising a heterologous polyadenylation sequence.

11. The vector of claim 10, wherein the polyadenylation sequence is a bovine growth hormone polyadenylation or signal rabbit β

-globin polyadenylation sequence.

12. The vector of claim 9, wherein the promoter of the 5′

LTR is replaced with a heterologous promoter.

13. The vector of claim 12, wherein the heterologous promoter is a cytomegalovirus (CMV) promoter, a Rous Sarcoma Virus (RSV) promoter, or a Simian Virus 40 (SV40) promoter.

14. The vector of claim 9, wherein the 5′

LTR or 3′

LTR is a lentivirus LTR.

15. The vector of claim 9, wherein the 3′

LTR comprises one or more modifications.

16. The vector of claim 9, wherein the 3′

LTR comprises one or more deletions.

17. The vector of claim 9, wherein the 3′

LTR is a self-inactivating (SIN) LTR.

18. The vector of claim 9, wherein the promoter operably linked to the polynucleotide encoding the CAR is selected from the group consisting of:

a cytomegalovirus immediate early gene promoter (CMV), an elongation factor 1 alpha promoter (EF1-α

), a phosphoglycerate kinase-1 promoter (PGK), a ubiquitin-C promoter (UBQ-C), a cytomegalovirus enhancer/chicken beta-actin promoter (CAG), polyoma enhancer/herpes simplex thymidine kinase promoter (MC1), a beta actin promoter (β

-ACT), a simian virus 40 promoter (SV40), and a myeloproliferative sarcoma virus enhancer, negative control region deleted, dl587rev primer-binding site substituted (MND) promoter.

19. An immune effector cell comprising the vector of any one of claims 2 to 18.

20. The immune effector cell of claim 19, wherein the immune effector cell is selected from the group consisting of:

a T lymphocyte and a natural killer (NK) cell.

21. A composition comprising the immune effector cell of claim 20 and a physiologically acceptable excipient.