NZ782857B2 - Compositions and methods for immunooncology - Google Patents

Compositions and methods for immunooncology

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Publication number
NZ782857B2
NZ782857B2 NZ782857A NZ78285716A NZ782857B2 NZ 782857 B2 NZ782857 B2 NZ 782857B2 NZ 782857 A NZ782857 A NZ 782857A NZ 78285716 A NZ78285716 A NZ 78285716A NZ 782857 B2 NZ782857 B2 NZ 782857B2
Authority
NZ
New Zealand
Prior art keywords
nucleic acid
molecule
grna
grna molecule
car
Prior art date
Application number
NZ782857A
Other versions
NZ782857A (en
Inventor
Ming Wei Chen
Melissa Deck
Glenn Dranoff
Reynald Lescarbeau
Craig Mickanin
Celeste Richardson
Morag Stewart
Yi Yang
Original Assignee
Intellia Therapeutics Inc
Novartis Ag
Filing date
Publication date
Application filed by Intellia Therapeutics Inc, Novartis Ag filed Critical Intellia Therapeutics Inc
Publication of NZ782857A publication Critical patent/NZ782857A/en
Publication of NZ782857B2 publication Critical patent/NZ782857B2/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2121/00—Preparations for use in therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
    • A—HUMAN NECESSITIES
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    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
    • A61K38/1774—Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)
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    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
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    • A61K40/10—Cellular immunotherapy characterised by the cell type used
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    • A61K40/31—Chimeric antigen receptors [CAR]
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    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0009—Galenical forms characterised by the drug release technique; Application systems commanded by energy involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
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    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/7051—T-cell receptor (TcR)-CD3 complex
    • C—CHEMISTRY; METALLURGY
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    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
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    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1135—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against oncogenes or tumor suppressor genes
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    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1138—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against receptors or cell surface proteins
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    • C12N15/09—Recombinant DNA-technology
    • C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • C12N15/90—Stable introduction of foreign DNA into chromosome
    • C12N15/902—Stable introduction of foreign DNA into chromosome using homologous recombination
    • C12N15/907—Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian cells
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/20—Type of nucleic acid involving clustered regularly interspaced short palindromic repeats [CRISPR]
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
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    • C12N2320/35—Special therapeutic applications based on a specific dosage / administration regimen
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    • C12N2510/00—Genetically modified cells
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    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0636—T lymphocytes
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    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
    • C12N9/22—Ribonucleases [RNase]; Deoxyribonucleases [DNase]
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention is directed to genome editing systems, reagents and methods for immunooncology.

Claims (16)

THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS:
1. A gRNA molecule comprising a tracr and a crRNA, wherein the crRNA comprises a targeting domain that is complementary to a target sequence of class II major histocompatibility transactivator ), wherein the targeting domain comprises SEQ ID NO: 7771.
2. The gRNA molecule of claim 1, wherein the targeting domain and the tracr are ed on separate nucleic acid molecules, or wherein the targeting domain and the tracr are ed on a single nucleic acid molecule, wherein the tracr is disposed 3’ to the targeting domain.
3. The gRNA molecule of claim 1 or claim 2, comprising: (a) one or more phosphorothioate modification(s) at the 3’ end of a nucleic acid molecule; (b) one or more phosphorothioate modification(s) at the 5’ end of a c acid molecule; (c) one or more 2’-O-methyl modification(s) at the 3’ end of a nucleic acid molecule; (d) one or more 2’-O-methyl modification(s) at the 5’ end of a nucleic acid molecule; (e) one or more 2’ O-methyl modification at each of the 4th -to-terminal, 3rd -toterminal , and 2nd -to-terminal 3’ es of a nucleic acid molecule; or (f) any ation thereof.
4. A composition comprising a first gRNA molecule of any one of claims 1 to 3 and a Cas9 le or a nucleic acid encoding a Cas9 molecule, wherein the gRNA molecule and the Cas9 molecule are present in a ribonuclear protein x (RNP).
5. The composition of claim 4, wherein the Cas9 molecule comprises any one of SEQ ID NO: 6611 or SEQ ID NO: 7821 to SEQ ID NO: 7831, or a sequence having at least 95% homology thereto.
6. The composition of claim 4 or claim 5, further comprising a second gRNA molecule; a second gRNA molecule and a third gRNA le; or a second gRNA molecule, a third gRNA molecule, and a fourth gRNA molecule, wherein each gRNA molecule is complementary to a different target ce.
7. The composition of claim 4, further comprising a template nucleic acid.
8. The ition of claim 7, wherein the template nucleic acid encodes a chimeric antigen receptor (CAR).
9. The composition of claim 8, n the CAR is selected from: (a) a CD19 CAR; (b) a BCMA CAR; (c) a CD20 CAR; (d) a CD22 CAR; (e) a CD123 CAR; (f) an EGFRvIII CAR; and (g) a mesothelin CAR.
10. A nucleic acid comprising a sequence that encodes the gRNA molecule of any one of claims 1 to 3.
11. A vector comprising the nucleic acid of claim 10.
12. An ex-vivo method of altering a target sequence of a cell, comprising contacting said cell with: (a) the gRNA molecule of any one of claims 1 to 3 and a Cas9 molecule; (b) the gRNA molecule of any one of claims 1 to 3 and a nucleic acid encoding a Cas9 molecule; (c) a nucleic acid encoding the gRNA le any one of claims 1 to 3 and a Cas9 molecule; (d) a nucleic acid encoding the gRNA molecule of any one of claims 1 to 3 and a nucleic acid encoding a Cas9 molecule; (e) any of a) to d), above, and a template nucleic acid; (f) any of a) to d) above, and a nucleic acid comprising sequence encoding a te nucleic acid; or (g) the composition of any one of claims 4 to 9.
13. The ex-vivo method of claim 12, wherein the gRNA molecule or the nucleic acid encoding the gRNA le, and the Cas9 molecule or the c acid encoding the Cas9 molecule, are formulated in a single ition or more than one composition.
14. An o method of preparing cells for immunotherapy comprising modifying cells to reduce or eliminate expression of CIITA by introducing into said cells a gRNA molecule of any one of claims 1 to 3, and wherein the method further comprises expanding said cells.
15. The ex-vivo method of claim 14, wherein the method further comprises introducing a template nucleic acid to the cells, wherein the template nucleic acid comprises a nucleic acid sequence encoding a chimeric antigen receptor (CAR).
16. Use of the gRNA molecule of any one of claims 1 to 3, the composition of any one of claims 4 to 9, the nucleic acid of claim 10, or the vector of claim 11 in the manufacture of a medicament for treating a disease associated with expression of a tumor antigen or providing an anti-tumor ty in a subject. o k m g Q & 03°" .Q ®@.®§a. W E m m m g *2“ m! 69% g? gm E? w £3 E ' :3 “ 3? a ”E g...“ as: 3%,. m mum E .“ 5m WNW ‘3 EELS“ m g E a; N ?g? ? 3 Wa‘ g 100 C3 C3 C3 C3 C23 GD (0 '6' N {gm} a?muemaa M32951 HEW SUBSTITUTE SHEET (RULE 26) ma?a; Maze: \\\\\\\\\\\\\\\\\\\\\g m?hmw gated Mém‘sms?asamg ________ _____ _____ SUBSTITUTE SHEET (RULE 26) E 1.3 Day 3322*; 74 74 \
NZ782857A 2016-12-02 Compositions and methods for immunooncology NZ782857B2 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201562263169P 2015-12-04 2015-12-04
US201662316784P 2016-04-01 2016-04-01
US201662394290P 2016-09-14 2016-09-14
NZ758480A NZ758480B2 (en) 2016-12-02 Compositions and methods for immunooncology

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