NZ782849B2 - Compositions and methods for immunooncology - Google Patents

Compositions and methods for immunooncology

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Publication number
NZ782849B2
NZ782849B2 NZ782849A NZ78284916A NZ782849B2 NZ 782849 B2 NZ782849 B2 NZ 782849B2 NZ 782849 A NZ782849 A NZ 782849A NZ 78284916 A NZ78284916 A NZ 78284916A NZ 782849 B2 NZ782849 B2 NZ 782849B2
Authority
NZ
New Zealand
Prior art keywords
nucleic acid
molecule
grna molecule
grna
composition
Prior art date
Application number
NZ782849A
Other versions
NZ782849A (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 NZ782849A publication Critical patent/NZ782849A/en
Publication of NZ782849B2 publication Critical patent/NZ782849B2/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
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    • 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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    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A—HUMAN NECESSITIES
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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
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K38/1774—Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)
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    • 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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    • A61K40/31—Chimeric antigen receptors [CAR]
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    • A61K9/00—Medicinal preparations characterised by special physical form
    • 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
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • 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
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    • C07K14/7051—T-cell receptor (TcR)-CD3 complex
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • 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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    • C12N15/113—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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    • C12N15/09—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
    • C12N15/1138—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
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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 (15)

THE CLAIMS DEFINING THE ION ARE AS FOLLOWS:
1. A gRNA molecule comprising a tracr and a crRNA, wherein the crRNA ses a targeting domain that is complementary to a target sequence of T Cell Receptor Alpha Constant (TRAC), wherein the targeting domain comprises SEQ ID NO: 5569 and the tracr comprises SEQ ID NO: 6660.
2. The gRNA molecule of claim 1, wherein the targeting domain and the tracr are disposed on separate nucleic acid molecules.
3. The gRNA molecule of claim 1 or claim 2, wherein the targeting domain and the tracr are disposed on a single nucleic acid le, and wherein the tracr is disposed 3’ to the targeting .
4. The gRNA molecule of any one of claims 1 to 3, comprising: (a) one or more orothioate modification(s) at the 3’ end of a nucleic acid molecule; (b) one or more phosphorothioate cation(s) at the 5’ end of a nucleic 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 combination thereof.
5. A composition comprising a first gRNA molecule of any one of claims 1 to 4 and a Cas9 molecule or a nucleic acid encoding a Cas9 molecule, wherein the gRNA molecule and the Cas9 molecule are present in a ribonuclear protein complex (RNP).
6. The composition of claim 5, 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.
7. The composition of claim 5 or claim 6, further comprising a second gRNA molecule; a second gRNA molecule and a third gRNA molecule; or a second gRNA molecule, a third gRNA molecule, and a fourth gRNA molecule, wherein each gRNA le is complementary to a different target sequence.
8. The composition of any one of claims 5 to 7, further comprising a template nucleic acid.
9. The composition of claim 8, n the template nucleic acid encodes a chimeric n receptor (CAR).
10. A nucleic acid sing a sequence that encodes the gRNA molecule of any one of claims 1 to 4.
11. A vector comprising the nucleic acid of claim 10.
12. An o 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 4 and a Cas9 molecule; (b) the gRNA molecule of any one of claims 1 to 4 and a nucleic acid encoding a Cas9 molecule; (c) a nucleic acid encoding the gRNA molecule of any one of claims 1 to 4 and a Cas9 molecule; (d) a nucleic acid encoding the gRNA molecule of any one of claims 1 to 4 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 5 to 9.
13. The ex-vivo method of claim 12, wherein the gRNA molecule or the nucleic acid encoding the gRNA molecule, and the Cas9 molecule or the nucleic acid encoding the Cas9 le, and, if present, the template nucleic acid, are formulated in a single composition or more than one composition.
14. An ex-vivo method of preparing cells for immunotherapy comprising ing cells by reducing or eliminating expression of TRAC by introducing into said cells the gRNA le of any one of claims 1 to 4, wherein the method further comprises expanding said cells.
15. Use of the gRNA molecule of any one of claims 1 to 4, the composition of any one of claims 5 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 immunity 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 wags...“ 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 s?asamg ________ _____ _____ SUBSTITUTE SHEET (RULE 26) E 1.3 Day 3322*; 74 74 \
NZ782849A 2016-12-02 Compositions and methods for immunooncology NZ782849B2 (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

Publications (2)

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NZ782849A NZ782849A (en) 2025-08-29
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