MND PROMOTER CHIMERIC ANTIGEN RECEPTORS

• US 20170051308A1
• Filed: 04/24/2015
• Published: 02/23/2017
• Est. Priority Date: 04/25/2014
• Status: Active Grant

• Current Assignee: 2seventy Bio, Inc. (bluebird bio, Inc.)
• Original Assignee: bluebird bio, Inc.
• Inventors: Morgan, Richard, Friedman, Kevin, Ryu, Byoung
• Granted Patent: US 10,774,343 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/001104 Epidermal growth factor receptors [EGFR]
• CPC Class Codes: A61K 39/001106 Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ErbB4
• CPC Class Codes: A61K 39/001109 Vascular endothelial growth factor receptors [VEGFR]
• CPC Class Codes: A61K 39/001112 CD19 or B4
• CPC Class Codes: A61K 39/001113 CD22, BL-CAM, siglec-2 or sialic acid- binding Ig-related lectin 2
• CPC Class Codes: A61K 39/001119 Receptors for interleukins [IL]
• CPC Class Codes: A61K 39/001122 Ephrin Receptors [Eph]
• CPC Class Codes: A61K 39/001124 CD20
• CPC Class Codes: A61K 39/001128 CD44 not IgG
• CPC Class Codes: A61K 39/001129 Molecules with a "CD" designation not provided for elsewhere
• CPC Class Codes: A61K 39/001138 Tumor necrosis factors [TNF] or CD70
• CPC Class Codes: A61K 39/00115 Apoptosis related proteins, e.g. survivin or livin
• CPC Class Codes: A61K 39/001166 Adhesion molecules, e.g. NRCAM, EpCAM or cadherins
• CPC Class Codes: A61K 39/001168 Mesothelin [MSLN]
• CPC Class Codes: A61K 39/00117 Mucins, e.g. MUC-1
• CPC Class Codes: A61K 39/001171 Gangliosides, e.g. GM2, GD2 or GD3
• CPC Class Codes: A61K 39/001174 Proteoglycans, e.g. glypican, brevican or CSPG4
• CPC Class Codes: A61K 39/00118 : from embryonic or fetal origin
• CPC Class Codes: A61K 39/001182 : Carcinoembryonic antigen [CEA]
• CPC Class Codes: A61K 39/001184 : Cancer testis antigens, e.g. SSX, BAGE, GAGE or SAGE
• CPC Class Codes: A61K 39/001186 : MAGE
• CPC Class Codes: A61K 39/001188 : NY-ESO
• CPC Class Codes: A61K 39/001189 : PRAME
• CPC Class Codes: A61K 39/001193 : Prostate associated antigens e.g. Prostate stem cell antigen [PSCA]; Prostate carcinoma tumor antigen [PCTA]; PAP or PSGR
• CPC Class Codes: A61K 39/001195 : Prostate specific membrane antigen [PSMA]
• 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 39/464412 : CD19 or B4
• CPC Class Codes: A61K 39/464417 : Receptors for tumor necrosis factors [TNF], e.g. lymphotoxin receptor [LTR], CD30
• CPC Class Codes: A61K 48/00 : Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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 16/2803 : against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/30 : from tumour cells
• CPC Class Codes: C07K 2317/622 : Single chain antibody (scFv)
• CPC Class Codes: C07K 2319/00 : Fusion polypeptide
• CPC Class Codes: C07K 2319/02 : containing a signal sequence
• CPC Class Codes: C07K 2319/03 : containing a transmembrane segment
• 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 5/0636 : T lymphocytes
• CPC Class Codes: C12N 7/00 : Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

Abstract

Vector compositions comprising a myeloproliferative sarcoma virus enhancer, negative control region deleted, dl587rev primer-binding site substituted (MND) promoter operably linked to a chimeric antigen receptor (CAR) are provided.

Claims

1. A polynucleotide comprising a myeloproliferative sarcoma virus enhancer, negative control region deleted, dl587rev primer-binding site substituted (MND) promoter operably linked to a nucleic acid encoding a chimeric antigen receptor (CAR).

2. The polynucleotide of claim 1, wherein the CAR comprises:

a) an extracellular domain that binds an antigen selected from the group consisting of;

alpha folate receptor, 5T4, α

_vβ

₆ integrin, BCMA, B7-H3, B7-H6, CAIX, CD19, CD20, CD22, CD30, CD33, CD44, CD44v6, CD44v7/8, CD70, CD79a, CD79b, CD123, CD138, CD171, CEA, CSPG4, EGFR, EGFR family including ErbB2 (HER2), EGFRvIII, EGP2, EGP40, EPCAM, EphA2, EpCAM, FAP, fetal AchR, FRα

, GD2, GD3, ‘

Glypican-3 (GPC3), HLA-A1+MAGE1, HLA-A2+MAGE1, HLA-A3+MAGE1, HLA-A1+NY-ESO-1, HLA-A2+NY-ESO-1, HLA-A3+NY-ESO-1, IL-11Rα

, IL-13Rα

2, Lambda, Lewis-Y, Kappa, Mesothelin, Muc1, Muc16, NCAM, NKG2D Ligands, NY-ESO-1, PRAME, PSCA, PSMA, ROR1, SSX, Survivin, TAG72, TEMs, and VEGFR2;

b) a transmembrane domain derived from a polypeptide selected from the group consisting of;

CD8α

;

CD4, CD28, CD45, PD1, and CD152;

c) one or more intracellular co-stimulatory signaling domains selected from the group consisting of;

CD28, CD54 (ICAM), CD134 (OX40), CD137 (41BB), CD152 (CTLA4), CD273 (PD-L2), CD274 (PD-L), and CD278 (ICOS); and

d) a CD3ζ

primary signaling domain.

3. The polynucleotide of claim 2, wherein:

a) the extracellular domain comprises an antibody or antigen binding fragment that binds the antigen;

b) the extracellular domain comprises an antibody or antigen binding fragment that binds the antigen is selected from the group consisting of;

a Camel Ig, Ig NAR, Fab fragments, Fab′

fragments, F(ab)′

2 fragments, F(ab)′

3 fragments, Fv, single chain Fv antibody (“

scFv”

), bis-scFv, (scFv)2, minibody, diabody, triabody, tetrabody, disulfide stabilized Fv protein (“

dsFv”

), and single-domain antibody (sdAb, Nanobody);

c) the extracellular domain comprises an antibody or antigen binding fragment that binds the antigen is an scFv;

or

d) the extracellular domain comprises a human antibody, a murine antibody, or a humanized antibody.

7. The polynucleotide claim 2, wherein the transmembrane domain is derived from CD8α

.

8. The polynucleotide of claim 2, wherein the one or more co-stimulatory signaling domains selected from the group consisting of:

CD28, CD134, and CD137.

13. The polynucleotide of claim 2, wherein the CAR further comprises a hinge region polypeptide, a spacer region, or a signal peptide.

19. The polynucleotide of claim 1, wherein the polynucleotide encodes a CAR as set forth in any one of SEQ ID NOs:

2-3.

20. A vector comprising the polynucleotide of claim 1.

21. The vector of claim 20, wherein:

a) the vector is an expression vector;

b) the vector is a viral vector;

c) the vector is a retroviral vector;

d) the vector is a lentiviral vector;

or

e) the vector is a lentiviral vector selected from the group consisting of;

human immunodeficiency virus (HIV);

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).

26. The vector of claim 21, comprising a left (5′

) retroviral LTR, a Psi (Ψ

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

a MND promoter operably linked to the CAR of claim 1; and

a right (3′

) retroviral LTR.

27. The vector of claim 26, further comprising:

a) a heterologous polyadenylation sequence;

b) a heterologous polyadenylation sequence that is a bovine growth hormone polyadenylation or signal rabbit β

-globin polyadenylation sequence;

or

c) a hepatitis B virus posttranscriptional regulatory element (HPRE) or woodchuck post-transcriptional regulatory element (WPRE).

30. The vector of claim 26, wherein:

a) the promoter of the 5′

LTR is replaced with a heterologous promoter;

b) the promoter of the 5′

LTR is replaced with a heterologous promoter selected from the group consisting of;

a cytomegalovirus (CMV) promoter, a Rous Sarcoma Virus (RSV) promoter, or an Simian Virus 40 (SV40) promoter.

32. The vector of claim 26, wherein:

a) the 5′

LTR or 3′

LTR is a lentivirus LTR;

b) the 3′

LTR comprises one or more modifications;

c) the 3′

LTR comprises one or more deletions;

d) the 3′

LTR is a self-inactivating (SIN) LTR.

37. An immune effector cell comprising the vector of claim 21.

38. The immune effector cell of claim 37, wherein the immune effector cell is a T lymphocyte.

39. A composition comprising the immune effector cell of claim 37 and a physiologically acceptable excipient.

40. A composition comprising the immune effector cell of claim 38 and a physiologically acceptable excipient.

43. A method of making an immune effector cell comprising isolating CD34+ cells from bone marrow, cord blood or mobilized peripheral blood from a subject, and introducing the vector of claim 21 into the isolated CD34+ cells.

45. A method of treating a cancer in a subject in need thereof, comprising administering to the subject a therapeutically effect amount of the composition of claim 39.

53. A method of treating a hematological malignancy in a subject in need thereof, comprising administering to the subject a therapeutically effect amount of the composition of claim 39.

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54-56. -56. (canceled)