SG11201906161VA - Microorganisms programmed to produce immune modulators and anti-cancer therapeutics in tumor cells - Google Patents

Microorganisms programmed to produce immune modulators and anti-cancer therapeutics in tumor cells

Info

Publication number
SG11201906161VA
SG11201906161VA SG11201906161VA SG11201906161VA SG11201906161VA SG 11201906161V A SG11201906161V A SG 11201906161VA SG 11201906161V A SG11201906161V A SG 11201906161VA SG 11201906161V A SG11201906161V A SG 11201906161VA SG 11201906161V A SG11201906161V A SG 11201906161VA
Authority
SG
Singapore
Prior art keywords
street
international
january
pct
microorganisms
Prior art date
Application number
SG11201906161VA
Inventor
Dean Falb
Jonathan Kotula
Vincent Isabella
Paul Miller
Suman Machinani
Saurabh Saha
Adam Fisher
Yves Millet
Ning Li
Jose Lora
Original Assignee
Synlogic Operating Co Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from PCT/US2017/013072 external-priority patent/WO2017123675A1/en
Application filed by Synlogic Operating Co Inc filed Critical Synlogic Operating Co Inc
Publication of SG11201906161VA publication Critical patent/SG11201906161VA/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4995—Pyrazines or piperazines forming part of bridged ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/745—Bifidobacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/521—Chemokines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/525—Tumour necrosis factor [TNF]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/53—Colony-stimulating factor [CSF]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/53—Colony-stimulating factor [CSF]
    • C07K14/535—Granulocyte CSF; Granulocyte-macrophage CSF
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/54—Interleukins [IL]
    • C07K14/5434—IL-12
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/54—Interleukins [IL]
    • C07K14/5443—IL-15
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/555—Interferons [IFN]
    • C07K14/57—IFN-gamma
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • 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
    • C07K14/70575—NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • 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
    • C07K14/70596—Molecules with a "CD"-designation not provided for elsewhere
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62—DNA sequences coding for fusion proteins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/74—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
    • C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
    • C12N9/2405—Glucanases
    • C12N9/2408—Glucanases acting on alpha -1,4-glucosidic bonds
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
    • C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
    • C12N9/2474—Hyaluronoglucosaminidase (3.2.1.35), i.e. hyaluronidase
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y307/00—Hydrolases acting on carbon-carbon bonds (3.7)
    • C12Y307/01—Hydrolases acting on carbon-carbon bonds (3.7) in ketonic substances (3.7.1)
    • C12Y307/01003—Kynureninase (3.7.1.3)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A61K2039/507—Comprising a combination of two or more separate antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/243—Platinum; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
    • C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
    • C07K2319/21—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2840/00—Vectors comprising a special translation-regulating system
    • C12N2840/002—Vectors comprising a special translation-regulating system controllable or inducible
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
    • C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
    • C12Y302/01003—Glucan 1,4-alpha-glucosidase (3.2.1.3), i.e. glucoamylase
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
    • C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
    • C12Y302/01035—Hyaluronoglucosaminidase (3.2.1.35), i.e. hyaluronidase
    • 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

INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 12 July 2018 (12.07.2018) WIPO I PCT ill mu °million °nolo Oil Oil mo Ho IIIII m 111110 oimIE (10) International Publication Number WO 2018/129404 Al (51) International Patent Classification: A61K 35/74 (2015.01) Cl 2N 15/74 (2006.01) C12N 15/70 (2006.01) (21) International Application Number: PCT/US2018/012698 (22) International Filing Date: 05 January 2018 (05.01.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/443,639 06 January 2017 (06.01.2017) US 62/443,634 06 January 2017 (06.01.2017) US PCT/US2017/013072 11 January 2017 (11.01.2017) US 62/531,784 12 July 2017 (12.07.2017) US 62/543,322 09 August 2017 (09.08.2017) US 62/552,319 30 August 2017 (30.08.2017) US 62/592,317 29 November 2017 (29.11.2017) US 62/607,210 18 December 2017 (18.12.2017) US (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Published: with international search report (Art. 21(3)) before the expiration of the time limit for amending the claims and to be republished in the event of receipt of amendments (Rule 48.2(h)) with sequence listing part of description (Rule 5.2(a)) W O 20 18/ 129 40 4 Al (71) Applicant: SYNLOGIC, INC. [US/US]; 200 Sidney Street, #320, Cambridge, MA 02139 (US). (72) Inventors: FALB, Dean; 180 Lake Street, Sherborn, MA 01770 (US). KOTULA, Jonathan, W.; 345 Washington Street, Somerville, MA 02143 (US). ISABELLA, Vincent, M.; 465 Putnam Avenue, Unit 1, Cambridge, MA 02139 (US). MILLER, Paul, F.; 39 Emerald Glen Lane, Salem, CT 06420 (US). FISHER, Adam; 240 Sidney Street, Apt. 306, Cambride, MA 02139 (US). MILLET, Yves; 15 Fred- erick Street, Newton, MA 02460 (US). LI, Ning; 322 Cam- bridge Street, Winchester, MA 01890 (US). LORA, Jose, M.; 45 Province Street, Apt. 902, Boston, MA 02108 (US). MACHINANI, Suman; 18 Centre Street, Apt. 302, Cam- bridge, MA 02139 (US). SAHA, Saurabh; 44 Carisbrooke Road, Wellesley Hills, MA 02481 (US). (74) Agent: HANLEY, Elizabeth, A. et al.; McCarter & Eng- lish, LLP, 265 Franklin Street, Boston, MA 02110 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (54) Title: MICROORGANISMS PROGRAMMED TO PRODUCE IMMUNE MODULATORS AND ANTI-CANCER THERA- PEUTICS IN TUMOR CELLS (57) : Genetically programmed microorganisms, such as bacteria or virus, pharmaceutical compositions thereof, and methods of modulating and treating cancers are disclosed.
SG11201906161VA 2017-01-06 2018-01-05 Microorganisms programmed to produce immune modulators and anti-cancer therapeutics in tumor cells SG11201906161VA (en)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
US201762443634P 2017-01-06 2017-01-06
US201762443639P 2017-01-06 2017-01-06
PCT/US2017/013072 WO2017123675A1 (en) 2016-01-11 2017-01-11 Microorganisms programmed to produce immune modulators and anti-cancer therapeutics in tumor cells
US201762531784P 2017-07-12 2017-07-12
US201762543322P 2017-08-09 2017-08-09
US201762552319P 2017-08-30 2017-08-30
US201762592317P 2017-11-29 2017-11-29
US201762607210P 2017-12-18 2017-12-18
PCT/US2018/012698 WO2018129404A1 (en) 2017-01-06 2018-01-05 Microorganisms programmed to produce immune modulators and anti-cancer therapeutics in tumor cells

Publications (1)

Publication Number Publication Date
SG11201906161VA true SG11201906161VA (en) 2019-08-27

Family

ID=62790899

Family Applications (1)

Application Number Title Priority Date Filing Date
SG11201906161VA SG11201906161VA (en) 2017-01-06 2018-01-05 Microorganisms programmed to produce immune modulators and anti-cancer therapeutics in tumor cells

Country Status (11)

Country Link
US (2) US11471494B2 (en)
EP (1) EP3565566A1 (en)
JP (1) JP2020505016A (en)
CN (1) CN110913875A (en)
AU (1) AU2018205276A1 (en)
BR (1) BR112019013863A2 (en)
CA (1) CA3049579A1 (en)
IL (1) IL267830A (en)
MX (1) MX2019008196A (en)
SG (1) SG11201906161VA (en)
WO (1) WO2018129404A1 (en)

Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017123675A1 (en) 2016-01-11 2017-07-20 Synlogic, Inc. Microorganisms programmed to produce immune modulators and anti-cancer therapeutics in tumor cells
EP3565566A1 (en) * 2017-01-06 2019-11-13 Synlogic Operating Company, Inc. Microorganisms programmed to produce immune modulators and anti-cancer therapeutics in tumor cells
JP7097438B2 (en) 2017-07-11 2022-07-07 アクティム・セラピューティクス・インコーポレイテッド Genetically engineered immunostimulatory bacterial strains and their use
KR20200064980A (en) * 2017-07-12 2020-06-08 신로직 오퍼레이팅 컴퍼니, 인코포레이티드 Microorganisms programmed to produce immunomodulators and anti-cancer drugs in tumor cells
BR112021000315A2 (en) 2018-07-11 2021-08-03 Actym Therapeutics, Inc. Genetically modified immunostimulant bacterial strains and their uses
WO2020018989A1 (en) * 2018-07-20 2020-01-23 The Trustees Of Columbia University In The City Of New York Programmable bacteria for the treatment of cancer
CN112513276B (en) * 2018-07-30 2024-03-15 张晋宇 Protein heterodimers and uses thereof
EP3844276A2 (en) 2018-08-28 2021-07-07 Actym Therapeutics, Inc. Engineered immunostimulatory bacterial strains and uses thereof
US20220023358A1 (en) * 2018-11-08 2022-01-27 Synlogic Operating Company, Inc. Combination therapies of microorganisms and immune modulators for use in treating cancer
CN109750054B (en) * 2019-02-21 2021-07-02 华中农业大学 Mycoplasma bovis protein gene MbovGdpp and application thereof
CA3131017A1 (en) 2019-02-27 2020-09-03 Actym Therapeutics, Inc. Immunostimulatory bacteria engineered to colonize tumors, tumor-resident immune cells, and the tumor microenvironment
CN110055188A (en) * 2019-03-07 2019-07-26 南京师范大学 One plant of Paenibacillus polymyxa XW4 for producing bacteriostatic peptide and its separation screening and application
KR20220003030A (en) 2019-04-29 2022-01-07 신로직 오퍼레이팅 컴퍼니, 인코포레이티드 Counting of genetically engineered microorganisms by living cell counting technology
EP3969601A4 (en) * 2019-05-13 2022-12-28 Synlogic Operating Company, Inc. Synergistic combinations of arginine-producing bacteria and/or ammonia-consuming bacteria and checkpoint inhibitors and methods of use thereof
CN110734888B (en) * 2019-09-17 2021-08-03 广州维生君生物科技有限公司 TIM3 human single-chain antibody fusion gene transformed lactic acid bacteria and application thereof
CA3161450A1 (en) 2019-11-12 2021-05-20 Actym Therapeutics, Inc. Immunostimulatory bacteria delivery platforms and their use for delivery of therapeutic products
CN111254087B (en) * 2019-12-27 2021-12-17 杭州娃哈哈科技有限公司 Lactobacillus helveticus with high adhesion performance and function of enhancing immunity and application thereof
CA3167223A1 (en) * 2020-02-13 2021-08-19 William R. Bishai Recombinant therapeutic interventions for cancer
WO2021163490A1 (en) * 2020-02-14 2021-08-19 University Of Washington Targeted depletion of bacteria from mixed populations through programmable cell-cell adhesion
EP4135733A2 (en) * 2020-04-17 2023-02-22 University of Cincinnati Engineered probiotics for treatment and immunity against viruses
WO2021252519A1 (en) * 2020-06-08 2021-12-16 University Of Florida Research Foundation, Inc. Materials and methods for the diagnosis and treatment of cancer
CN111849805B (en) * 2020-06-17 2022-04-22 天津科技大学 Pediococcus acidilactici with cervical cancer resistance effect and application thereof
CN116113425A (en) * 2020-07-07 2023-05-12 丹麦科技大学 Bacterial vectors for engineering non-phagocytic immune cells
AU2021324883A1 (en) 2020-08-12 2023-03-23 Actym Therapeutics, Inc. Immunostimulatory bacteria-based vaccines, therapeutics, and rna delivery platforms
CN114073777A (en) * 2020-08-18 2022-02-22 中国科学院深圳先进技术研究院 Bacterial targeting vector carrying cytokine or polynucleotide thereof and application thereof in tumor treatment
EP4232069A1 (en) * 2020-10-26 2023-08-30 Cytune Pharma Il-2/il-15rbetagamma agonist for treating squamous cell carcinoma
EP4232068A1 (en) * 2020-10-26 2023-08-30 Cytune Pharma IL-2/IL-15RBetaGamma AGONIST FOR TREATING NON-MELANOMA SKIN CANCER
CN112342233B (en) * 2020-11-10 2022-08-26 上海陶宇晟生物技术有限责任公司 Polynucleotide for increasing c-di-AMP production when bacteria express DacA
CA3200887A1 (en) 2020-12-02 2022-06-09 Michael James Engineered microorganisms
KR102287114B1 (en) * 2021-01-25 2021-08-06 씨제이제일제당 주식회사 Novel cytosine permease variant and a method for producing L-tryptophan using the same
CN112877271B (en) * 2021-02-05 2023-03-14 江西师范大学 Method for improving L-arginine production of corynebacterium crenatum through anaerobic fermentation
WO2022221273A1 (en) * 2021-04-13 2022-10-20 Synlogic Operating Company, Inc. Bacteria engineered to secrete active proteins
US20240139280A1 (en) * 2021-04-14 2024-05-02 OncoC4, Inc. Use of hif-1-alpha inhibitors in cancer immunotherapy
CA3235418A1 (en) 2021-11-09 2023-05-19 Actym Therapeutics, Inc. Immunostimulatory bacteria for converting macrophages into a phenotype amenable to treatment, and companion diagnostic for identifying subjects for treatment
CN114181863B (en) * 2021-12-15 2023-06-23 安徽师范大学 Violet bacillus strain E1, preparation method thereof and application thereof in degradation of phthalate
WO2023161371A1 (en) * 2022-02-25 2023-08-31 Danmarks Tekniske Universitet Engineered bacteria secreting cytokines for use in cancer immunotherapy
CN116836283B (en) * 2022-05-17 2024-05-07 苏州万灏生物科技有限公司 Enhanced oncolytic virus with multiple immune regulatory factors, and preparation method and application thereof
CN114958891B (en) * 2022-05-24 2023-04-14 郑州大学 Escherichia coli recombinant expression vector and application thereof
WO2024075067A1 (en) * 2022-10-06 2024-04-11 Centro Di Riferimento Oncologico Cancer vaccine composition that comprises a host cell expressing glypican-1 (gpc-1)

Family Cites Families (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4946778A (en) 1987-09-21 1990-08-07 Genex Corporation Single polypeptide chain binding molecules
GB9107305D0 (en) 1991-04-08 1991-05-22 Unilever Plc Probiotic
US6203797B1 (en) 1998-01-06 2001-03-20 Stephen C. Perry Dietary supplement and method for use as a probiotic, for alleviating the symptons associated with irritable bowel syndrome
EP1034787A1 (en) 1999-03-11 2000-09-13 Société des Produits Nestlé S.A. Lactobacillus strains preventing diarrhea caused by pathogenic bacteria
US6962696B1 (en) * 1999-10-04 2005-11-08 Vion Pharmaceuticals Inc. Compositions and methods for tumor-targeted delivery of effector molecules
AU783714B2 (en) * 1999-10-04 2005-12-01 Vion Pharmaceuticals, Inc. Compositions and methods for tumor-targeted delivery of effector molecules
ES2528384T3 (en) 2001-12-12 2015-02-09 The Government Of The United States Of America, As Represented By The Secretary Department Of Healt Methods of using adenosine receptor inhibitors to enhance the immune response and inflammation
US7731976B2 (en) 2003-08-29 2010-06-08 Cobb And Company, Llp Treatment of irritable bowel syndrome using probiotic composition
AU2007241023B2 (en) 2006-03-30 2013-11-28 University Of California Methods and compositions for localized secretion of anti-CTLA-4 antibodies
TW200819540A (en) 2006-07-11 2008-05-01 Genelux Corp Methods and compositions for detection of microorganisms and cells and treatment of diseases and disorders
US20080057034A1 (en) 2006-07-19 2008-03-06 North Carolina State University Attenuated FNR Deficient Enterobacteria
US9061048B2 (en) * 2010-12-15 2015-06-23 The Regents Of The University Of California Cyclic di-AMP induction of type I interferon
US9409950B2 (en) 2010-12-23 2016-08-09 Biogen Ma Inc. Linker peptides and polypeptides comprising same
CN102604949A (en) 2011-04-12 2012-07-25 南京大学 Anaerobic tissue selective gene expression method driven by alcohol dehydrogenase promoter and application thereof
HUE050875T2 (en) 2012-01-17 2021-01-28 Univ Leland Stanford Junior High affinity sirp-alpha reagents
US9127284B2 (en) 2012-05-04 2015-09-08 The University Of Hong Kong Modified bacteria and their uses thereof for the treatment of cancer or tumor
CA2884816A1 (en) 2012-09-13 2014-03-20 Massachusetts Institute Of Technology Programmable drug delivery profiles of tumor-targeted bacteria
EP2916854A4 (en) * 2012-11-06 2016-06-22 Aduro Biotech Inc Facultatively attenuated bacterial species and methods of preparation and use thereof
US9539290B2 (en) 2012-12-24 2017-01-10 Anticancer Inc. Individualized bacterial treatment of pancreatic cancer
WO2014198002A1 (en) 2013-06-14 2014-12-18 Ottawa Hospital Research Institute A bacterium producing an interferon binding protein and uses thereof
US20160287623A1 (en) 2013-11-19 2016-10-06 The University Of Chicago Use of sting agonist as cancer treatment
WO2015078840A1 (en) 2013-11-26 2015-06-04 Boehringer Ingelheim International Gmbh Full and partial protein secretion and cell surface display using type iii secretion system
CN107002090B (en) * 2014-05-01 2021-09-10 阿苏萨医药科学有限公司 Heterologous polypeptide expression cassette
JP7080053B2 (en) 2014-08-29 2022-06-03 ボード オブ リージェンツ，ザ ユニバーシティ オブ テキサス システム Administration of kynurenine-depleting enzymes for the treatment of tumors
SG11201704543XA (en) 2014-12-05 2017-07-28 Synlogic Inc Bacteria engineered to treat diseases associated with hyperammonemia
US9688967B2 (en) 2014-12-05 2017-06-27 Synlogic, Inc. Bacteria engineered to treat diseases associated with hyperammonemia
US10617729B2 (en) 2014-12-24 2020-04-14 The Uab Research Foundation Multitargeting onocolytic adenovirus, methods of use, and methods of making
US20160220652A1 (en) * 2015-02-03 2016-08-04 Advaxis, Inc. Methods of using recombinant listeria vaccine strains in disease immunotherapy
CA3013713A1 (en) * 2015-02-11 2016-08-18 The Johns Hopkins University Bacteria over-expressing c-di-amp and therapeutic methods
EP3294757B1 (en) * 2015-05-13 2023-12-27 Synlogic Operating Company, Inc. Bacteria engineered to treat a disease or disorder
WO2016191283A2 (en) 2015-05-22 2016-12-01 University Of Houston System Enzymatic immunomodulation of solid tumors and user thereof
WO2016210373A2 (en) * 2015-06-24 2016-12-29 Synlogic, Inc. Recombinant bacteria engineered for biosafety, pharmaceutical compositions, and methods of use thereof
WO2017123675A1 (en) 2016-01-11 2017-07-20 Synlogic, Inc. Microorganisms programmed to produce immune modulators and anti-cancer therapeutics in tumor cells
EP3565566A1 (en) 2017-01-06 2019-11-13 Synlogic Operating Company, Inc. Microorganisms programmed to produce immune modulators and anti-cancer therapeutics in tumor cells
KR20200064980A (en) 2017-07-12 2020-06-08 신로직 오퍼레이팅 컴퍼니, 인코포레이티드 Microorganisms programmed to produce immunomodulators and anti-cancer drugs in tumor cells
BR112021000315A2 (en) 2018-07-11 2021-08-03 Actym Therapeutics, Inc. Genetically modified immunostimulant bacterial strains and their uses
EP3844276A2 (en) 2018-08-28 2021-07-07 Actym Therapeutics, Inc. Engineered immunostimulatory bacterial strains and uses thereof
US20220023358A1 (en) 2018-11-08 2022-01-27 Synlogic Operating Company, Inc. Combination therapies of microorganisms and immune modulators for use in treating cancer

Also Published As

Publication number Publication date
US20190336544A1 (en) 2019-11-07
JP2020505016A (en) 2020-02-20
CA3049579A1 (en) 2018-07-12
AU2018205276A1 (en) 2019-07-18
BR112019013863A2 (en) 2020-03-03
WO2018129404A8 (en) 2019-06-13
MX2019008196A (en) 2019-12-16
US11471494B2 (en) 2022-10-18
US20230226122A1 (en) 2023-07-20
IL267830A (en) 2019-09-26
CN110913875A (en) 2020-03-24
WO2018129404A1 (en) 2018-07-12
EP3565566A1 (en) 2019-11-13

Similar Documents

Publication Publication Date Title
SG11201906161VA (en) Microorganisms programmed to produce immune modulators and anti-cancer therapeutics in tumor cells
SG11201805888SA (en) Cyclic dinucleotides for treating conditions associated with sting activity such as cancer
SG11201901126UA (en) Combination therapy for cancer
SG11201808622SA (en) Chimeric receptors to flt3 and methods of use thereof
SG11201804375WA (en) Compositions and methods for internalizing enzymes
SG11201811432WA (en) Rna for cancer therapy
SG11201803703UA (en) Anti-complement factor c1q fab fragments and uses thereof
SG11201909322VA (en) Treatment of asthma with anti-tslp antibody
SG11201407486PA (en) Compositions and methods for modulating utrn expression
SG11201907299XA (en) Multi-specific binding proteins for activation of natural killer cells and therapeutic uses thereof to treat cancer
SG11201805645QA (en) Lsd1 inhibitors
SG11201811290VA (en) Compositions and methods for the depletion of cd117+cells
SG11201805300QA (en) Heterocyclic compounds as immunomodulators
SG11201804814YA (en) Materials and methods for delivering nucleic acids to cochlear and vestibular cells
SG11201807025SA (en) Crispr/cas systems for c-1 fixing bacteria
SG11201901628XA (en) Methods and compositions for spinal cord cells
SG11201807279QA (en) Binding proteins and methods of use thereof
SG11201908179UA (en) Aryl cyclopropyl-amino-isoquinolinyl amide compounds
SG11201407580YA (en) Composition comprising two antibodies engineered to have reduced and increased effector function
SG11201907646YA (en) Proteins binding her2, nkg2d and cd16
SG11201406903SA (en) Cell culture compositions and methods for polypeptide production
SG11201906853QA (en) Anti-rsv monoclonal antibody formulation
SG11201805052YA (en) Therapeutic methods using erythrocytes
SG11201808525UA (en) Anti-complement factor bb antibodies and uses thereof
SG11201909419XA (en) Hydrogel for cell culture and biomedical applications