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WO2019023555A1 - Compositions polymères - Google Patents

Compositions polymères Download PDF

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Publication number
WO2019023555A1
WO2019023555A1 PCT/US2018/044053 US2018044053W WO2019023555A1 WO 2019023555 A1 WO2019023555 A1 WO 2019023555A1 US 2018044053 W US2018044053 W US 2018044053W WO 2019023555 A1 WO2019023555 A1 WO 2019023555A1
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WIPO (PCT)
Prior art keywords
bacillus
clostridium
carcinoma
composition
protein
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PCT/US2018/044053
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English (en)
Inventor
Brian Goodman
Jason HUDAK
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Evelo Biosciences Inc
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Evelo Biosciences Inc
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Publication of WO2019023555A1 publication Critical patent/WO2019023555A1/fr
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    • 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
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • 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
    • C12N11/00—Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
    • C12N11/02—Enzymes or microbial cells immobilised on or in an organic carrier
    • C12N11/08—Enzymes or microbial cells immobilised on or in an organic carrier the carrier being a synthetic polymer
    • C12N11/089—Enzymes or microbial cells immobilised on or in an organic carrier the carrier being a synthetic polymer obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61K35/742—Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
    • 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
    • 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
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • A61K38/38—Albumins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/61—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
    • A61K49/0069—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
    • A61K49/0097—Cells, viruses, ghosts, red blood cells, viral vectors, used for imaging or diagnosis in vivo
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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

Definitions

  • compositions comprising a bacterium and a polymer (e.g., in which the polymer coats the bacterium).
  • the polymer can be a natural polymer or a synthetic polymer.
  • the polymer coating protects the bacteria following administration to a human subject (e.g., from acid, bile, oxygen, enzymatic degradation, mechanical force, etc.).
  • the polymer enhances delivery of the bacteria to a therapeutic target in a subject, for example, by facilitating adherence and/or penetration to a mucus layer, such as the mucus layer in the stomach, small intestine or colon.
  • the polymer layer improves therapeutic efficacy of the bacterium, such as by adding or enhancing immunological function.
  • the polymer coating is functionalized with one or more functional residues.
  • the polymer can be functionalized with a therapeutic agent (e.g., an immune modulatory agent, a cytotoxic agent, a cell signaling agent, a
  • the polymer is functionalized with an agent that enhances bacterial delivery and/or targeting. In some embodiments, the polymer is functionalized with an agent that enhances bacterial survival (e.g., nutrients or microbial signaling molecules).
  • a disease or condition comprising administering to a subject (e.g., a human subject) a composition provided herein.
  • the disease or condition is a cancer.
  • the disease or condition is an inflammatory and/or autoimmune condition.
  • the disease or condition is an infectious disease (e.g., a bacterial infection, a viral infection, a parasitic infection).
  • Figure 1 shows two FACS histograms demonstrating the coating of
  • Bifidobacterium with PEI or chitosan polymers Bifidobacterium with PEI or chitosan polymers.
  • Figure 2 is a graph that shows that PEI-NAc polymer-coated Lactococcus lactis ssp. cremoris (Strain A) retains in vivo efficacy as compared to the powdered bacteria in a delayed-type hypersensitivity (DTH) model. The significance is p value of ⁇ 0.05 in a t- test. The number of dots at each dosage amount is equal to the number of mice surveyed in the experiment.
  • Figure 3 is a graph that shows that PEI-NAc polymer increases the retention of Lactococcus lactis ssp. cremoris (Strain A) at 24 h after administration. In the absence of a polymer coating, peak expulsion for Strain A occurs between 4-8 h. At 24 h after administration, uncoated Strain A (indicated in the graph as "powder") is completely excreted. The PEI-NAc polymer coating increases retention at 24 h.
  • administering broadly refers to a route of administration of a composition to a subject.
  • routes of administration include oral administration, rectal administration, topical administration, inhalation (nasal) or injection.
  • Administration by injection includes intravenous (IV), intramuscular (IM), intratumoral (IT) and subcutaneous (SC) administration.
  • compositions described herein can be administered in any form by any effective route, including but not limited to intratumoral, oral, parenteral, enteral, intravenous, intraperitoneal, topical, transdermal ⁇ e.g., using any standard patch), intradermal, ophthalmic, (intra)nasally, local, non-oral, such as aerosol, inhalation, subcutaneous, intramuscular, buccal, sublingual, (trans)rectal, vaginal, intra-arterial, and intrathecal, transmucosal ⁇ e.g., sublingual, lingual, (trans)buccal, (trans)urethral, vaginal ⁇ e.g., trans- and perivaginally), intravesical, intrapulmonary, intraduodenal, intragastrical, and intrabronchial.
  • the pharmaceutical compositions described herein are administered intratumorally, topically, intravesically, by injection into or adjacent to a draining lymph node, intravenously, by inhalation or aero
  • the term "antibody” may refer to both an intact antibody and an antigen binding fragment thereof.
  • Intact antibodies are glycoproteins that include at least two heavy (H) chains and two light (L) chains inter-connected by disulfide bonds.
  • Each heavy chain includes a heavy chain variable region (abbreviated herein as VH) and a heavy chain constant region.
  • Each light chain includes a light chain variable region (abbreviated herein as VL) and a light chain constant region.
  • the VH and VL regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with regions that are more conserved, termed framework regions (FR).
  • CDR complementarity determining regions
  • Each VH and VL is composed of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.
  • the variable regions of the heavy and light chains contain a binding domain that interacts with an antigen.
  • the term "antibody” includes, for example, monoclonal antibodies, polyclonal antibodies, chimeric antibodies, humanized antibodies, human antibodies, multispecific antibodies (e.g., bispecific antibodies), single-chain antibodies and antigen-binding antibody fragments.
  • antigen binding fragment and "antigen-binding portion" of an antibody, as used herein, refers to one or more fragments of an antibody that retain the ability to bind to an antigen.
  • binding fragments encompassed within the term "antigen- binding fragment” of an antibody include Fab, Fab', F(ab') 2 , Fv, scFv, disulfide linked Fv, Fd, diabodies, single-chain antibodies, NANOBODIES®, isolated CDRH3, and other antibody fragments that retain at least a portion of the variable region of an intact antibody. These antibody fragments can be obtained using conventional recombinant and/or enzymatic techniques and can be screened for antigen binding in the same manner as intact antibodies.
  • carcinomas which are cancers of the epithelial tissue (e.g., skin, squamous cells); sarcomas which are cancers of the connective tissue (e.g., bone, cartilage, fat, muscle, blood vessels, etc.); leukemias which are cancers of blood forming tissue (e.g., bone marrow tissue); lymphomas and myelomas which are cancers of immune cells; and central nervous system cancers which include cancers from brain and spinal tissue.
  • carcinomas which are cancers of the epithelial tissue (e.g., skin, squamous cells)
  • sarcomas which are cancers of the connective tissue (e.g., bone, cartilage, fat, muscle, blood vessels, etc.)
  • leukemias which are cancers of blood forming tissue (e.g., bone marrow tissue)
  • lymphomas and myelomas which are cancers of immune cells
  • central nervous system cancers which include cancers from brain and spinal tissue.
  • cancer refers to all types of cancer or neoplasm or malignant tumors including leukemias, carcinomas and sarcomas, whether new or recurring. Specific examples of cancers are: carcinomas, sarcomas, myelomas, leukemias, lymphomas and mixed type tumors.
  • Non-limiting examples of cancers are new or recurring cancers of the brain, melanoma, bladder, breast, cervix, colon, head and neck, kidney, lung, non-small cell lung, mesothelioma, ovary, prostate, sarcoma, stomach, uterus and medulloblastoma.
  • a "combination" of two or more microbial strains includes the physical coexistence of the two strains, either in the same material or product or in physically connected products, as well as the temporal co-administration or co-localization of the two strains.
  • the term “decrease” or “deplete” means a change, such that the difference is, depending on circumstances, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 1/100, 1/1000, 1/10,000, 1/100,000, 1/1,000,000 or undetectable after treatment when compared to a pre-treatment state.
  • epitope means a protein determinant capable of specific binding to an antibody.
  • Epitopes usually consist of chemically active surface groupings of molecules such as amino acids or sugar side chains. Certain epitopes can be defined by a particular sequence of amino acids to which an antibody is capable of binding.
  • genomic is used broadly to refer to any nucleic acid associated with a biological function.
  • gene applies to a specific genomic sequence, as well as to a cDNA or an mRNA encoded by that genomic sequence.
  • nucleic acid sequences of two nucleic acid molecules can be determined as a percentage of identity using known computer algorithms such as the "FASTA” program, using for example, the default parameters as in Pearson et al. (1988) Proc. Natl. Acad. Sci. USA 85:2444 (other programs include the GCG program package (Devereux, J., et al, Nucleic Acids Research 12(I):387 (1984)), BLASTP, BLASTN, FASTA Atschul, S. F., et al, J Molec Biol 215:403 (1990); Guide to Huge Computers, Mrtin J.
  • Immunotherapy is treatment that uses a subject's immune system to treat cancer or another dieseas or disorder and includes, for example, checkpoint inhibitors, cancer vaccines, cytokines, cell therapy, CAR-T cells, and dendritic cell therapy.
  • the term "increase” means a change, such that the difference is, depending on circumstances, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 2-fold, 4-fold, 10- fold, 100-fold, 10 ⁇ 3 fold, 10 ⁇ 4 fold, 10 ⁇ 5 fold, 10 ⁇ 6 fold, and/or 10 ⁇ 7 fold greater after treatment when compared to a pre-treatment state.
  • Properties that may be increased include immune cells, metabolites, and cytokines.
  • "Innate immune agonists" or “immuno-adjuvants” are small molecules, proteins, or other agents that specifically target innate immune receptors including Toll-Like Receptors, NOD receptors, STING Pathway components.
  • LPS is a TLR-4 agonist that is bacterially derived or synthesized and aluminum can be used as an immune stimulating adjuvant
  • immuno-adjuvants are a specific class of broader adjuvant or adjuvant therapy.
  • isolated encompasses a microbe or other entity or substance that has been (1) separated from at least some of the components with which it was associated when initially produced (whether in nature or in an experimental setting), and/or (2) produced, prepared, purified, and/or manufactured by the hand of man. Isolated microbes may be separated from at least about 10%, about 20%, about 30%>, about 40%, about 50%, about 60%), about 70%, about 80%, about 90%, or more of the other components with which they were initially associated.
  • isolated microbes are more than about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%o, about 97%, about 98%, about 99%, or more than about 99% pure.
  • a substance is "pure” if it is substantially free of other components.
  • the terms "purify,” “purifying” and “purified” refer to a microbe or other material that has been separated from at least some of the components with which it was associated either when initially produced or generated (e.g. , whether in nature or in an experimental setting), or during any time after its initial production.
  • a microbe or a microbial population may be considered purified if it is isolated at or after production, such as from a material or environment containing the microbe or microbial population, and a purified microbe or microbial population may contain other materials up to about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%), about 80%), about 90%, or above about 90% and still be considered "isolated.”
  • purified microbes or microbial population are more than about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%o, about 98%, about 99%, or more than about 99% pure.
  • the one or more microbial types present in the composition can be independently purified from one or more other microbes produced and/or present in the material or environment containing the microbial type.
  • Microbial compositions and the microbial components thereof are generally purified from residual habitat products.
  • Merobe refers to any natural or engineered organism characterized as a bacterium, fungus, microscopic alga, protozoan, and the stages of development or life cycle stages (e.g., vegetative, spore (including sporulation, dormancy, and germination), latent, biofilm) associated with the organism.
  • gut microbes examples include: Actinomyces graevenitzii, Actinomyces odontolyticus, Akkermansia muciniphila, Bacteroides caccae, Bacteroides fragilis, Bacteroides putredinis, Bacteroides thetaiotaomicron, Bacteroides vultagus, Bifidobacterium adolescentis, Bifidobacterium bifidum, Bilophila wadsworthia, Blautia, Butyrivibrio, Campylobacter gracilis, Clostridia cluster III, Clostridia cluster IV, Clostridia cluster IX (Acidaminococcaceae group), Clostridia cluster XI, Clostridia cluster XIII (Peptostreptococcus group), Clostridia cluster XIV, Clostridia cluster XV, Collinsella aerofaciens, Coprococcus, Coryne
  • Microbiome broadly refers to the microbes residing on or in body site of a subject or patient.
  • Microbes in a microbiome may include bacteria, viruses, eukaryotic microorganisms, and/or viruses.
  • Individual microbes in a microbiome may be metabolically active, dormant, latent, or exist as spores, may exist planktonically or in biofilms, or may be present in the microbiome in sustainable or transient manner.
  • the microbiome may be a commensal or healthy-state microbiome or a disease-state microbiome.
  • the microbiome may be native to the subject or patient, or components of the microbiome may be modulated, introduced, or depleted due to changes in health state (e.g., precancerous or cancerous state) or treatment conditions (e.g., antibiotic treatment, exposure to different microbes).
  • the microbiome occurs at a mucosal surface.
  • the microbiome is a gut microbiome.
  • the microbiome is a tumor microbiome.
  • polynucleotide and “nucleic acid” are used interchangeably.
  • Polynucleotides refer to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or analogs thereof.
  • Polynucleotides may have any three-dimensional structure, and may perform any function.
  • polynucleotides coding or non-coding regions of a gene or gene fragment, loci (locus) defined from linkage analysis, exons, introns, messenger RNA (mRNA), transfer RNA, ribosomal RNA, ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes, and primers.
  • a polynucleotide may comprise modified nucleotides, such as methylated nucleotides and nucleotide analogs.
  • nucleotide structure may be imparted before or after assembly of the polymer.
  • a polynucleotide may be further modified, such as by conjugation with a labeling component.
  • U nucleotides are interchangeable with T nucleotides.
  • telomere binding refers to the ability of an antibody to bind to a predetermined antigen or the ability of a polypeptide to bind to its predetermined binding partner.
  • an antibody or polypeptide specifically binds to its predetermined antigen or binding partner with an affinity corresponding to a KD of about 10 "7 M or less, and binds to the predetermined antigen/binding partner with an affinity (as expressed by KD) that is at least 10 fold less, at least 100 fold less or at least 1000 fold less than its affinity for binding to a non-specific and unrelated antigen/binding partner (e.g., BSA, casein).
  • a non-specific and unrelated antigen/binding partner e.g., BSA, casein
  • subject refers to any animal.
  • a subject or a patient described as “in need thereof refers to one in need of a treatment for a disease.
  • Mammals i.e., mammalian animals
  • mammals include humans, laboratory animals (e.g. , primates, rats, mice), livestock (e.g. , cows, sheep, goats, pigs), and household pets (e.g. , dogs, cats, rodents).
  • the subject or patient may be healthy, or may be suffering from a neoplasm at any developmental stage, wherein any of the stages are either caused by or opportunistically supported of a cancer associated or causative pathogen, or may be at risk of developing a neoplasm, or transmitting to others a cancer associated or cancer causative pathogen.
  • any of the stages are either caused by or opportunistically supported of a cancer associated or causative pathogen, or may be at risk of developing a neoplasm, or transmitting to others a cancer associated or cancer causative pathogen.
  • patients have lung cancer, bladder cancer, prostate cancer, ovarian cancer, and/or melanoma.
  • the patients may have tumors that show enhanced macropinocytosis with the underlying genomics of this process including Ras activation.
  • patients suffer from other cancers.
  • the subject has undergone a cancer therapy.
  • strain refers to a member of a bacterial species with a genetic signature such that it may be differentiated from closely-related members of the same bacterial species.
  • the genetic signature may be the absence of all or part of at least one gene, the absence of all or part of at least on regulatory region (e.g.
  • a promoter, a terminator, a riboswitch, a ribosome binding site the absence ("curing") of at least one native plasmid, the presence of at least one recombinant gene, the presence of at least one mutated gene, the presence of at least one foreign gene (a gene derived from another species), the presence at least one mutated regulatory region (e.g., a promoter, a terminator, a riboswitch, a ribosome binding site), the presence of at least one non-native plasmid, the presence of at least one antibiotic resistance cassette, or a combination thereof.
  • strains may be identified by PCR amplification optionally followed by DNA sequencing of the genomic region(s) of interest or of the whole genome.
  • strains may be differentiated by selection or counter-selection using an antibiotic or nutrient/metabolite, respectively.
  • treating refers to subjecting the subject to a pharmaceutical treatment, e.g., the administration of one or more agents, such that at least one symptom of the disease is decreased or prevented from worsening.
  • a pharmaceutical treatment e.g., the administration of one or more agents, such that at least one symptom of the disease is decreased or prevented from worsening.
  • “treating” refers inter alia to delaying progression, expediting remission, inducing remission, augmenting remission, speeding recovery, increasing efficacy of or decreasing resistance to alternative therapeutics, or a combination thereof.
  • a polymer coating on the microbe offers numerous advantages over existing microbial therapeutics.
  • the polymeric coatings protect the microbial compositions, by, for example, offering a barrier to
  • the polymeric coatings in the compositions provided herein can aid in the delivery and targeting of a therapeutic agent.
  • the compositions may adhere to or penetrate mucus layer, or alternatively may target a host cell surface (e.g., M cells, epithelial cells).
  • compositions provided herein may enhance or add immunological functionality.
  • the polymer coating in the compositions described herein may be functionalized with proteins, drugs, and metabolites (e.g., antigens, immune stimulants) that enhance the therapeutic effect of the composition.
  • compositions enable maintenance or control of activity by, e.g., providing nutrients or signaling molecules to the bacteria.
  • the compositions can be administered with prebiotics or host bidning factors.
  • a compostion comprising a bacterium and a polymer.
  • the polymer partially coats the bacterium.
  • the polymer fully coats the bacterium.
  • the composition comprises a plurality of bacteria.
  • the polymer partially coats a plurality of bacteria.
  • the polymer may fully coat a plurality of bacteria.
  • the polymer is bound to a surface of the bacterium.
  • the polymer may be bound to a surface of the bacterium through electrostatic interactions.
  • it may be bound to a surface of the bacterium through one or more covalent bonds.
  • the polymer is positively charged.
  • the bacterium is negatively charged.
  • electrostatic interactions may bind the polymer to the bacterium.
  • the polymer is selected from the group consisting of polycarbonates, polysaccharides, polyurethanes, polyamides, polyesters, polyethers, polyimides, polyimines, polyorganosiloxanes, polysulfides, polysulfones,
  • polytetrafluoroethylene polysiloxanes, polyvinylarenes, polyacrylates, and oligosaccharides (e.g., cyclic oligosaccharides).
  • the polymer is selected from the group consisting of chitosan, alginate, polyethyleneimine, poly-y-glutamic acid, poly(beta-amino ester), polyglycolic acid, polylysine, cyclodextrin, collagen, polybrene, diethylaminoethyl-dextran, polyamidoamine, polyethylene glycol, propylene glycol, polystyrene, and polyvinylacetate.
  • the polymer may be selected from the group consisting of chitosan, alginate, polyethyleneimine, poly-y-glutamic acid, poly(beta-amino ester), polyglycolic acid, polylysine, cyclodextrin, collagen, polybrene, diethylaminoethyl-dextran, and polyamidoamine; more preferably the polymer is selected from the group consisting of chitosan, alginate, polyethyleneimine, polyglycolic acid, and poly(beta-amino ester).
  • the polymer is selected from the group consisting of chitosan, alginate, and polyethyleneimine.
  • the polymer may be chitosan.
  • the polymer may be alginate.
  • the polymer may be polyethyleneimine.
  • the polymer may comprise two or more crosslinked polymers.
  • each crosslinked polymer is selected from the group consisting of polyurethanes, polyamides, polyesters, polyethers, polyorganosiloxanes, polysulfones, polytetrafluoroethylene, polysiloxanes, polyvinylarenes, and polyacrylates.
  • each crosslinked polymer may be selected from the group consisting of chitosan, alginate, polyethyleneimine, poly-y-glutamic acid, poly(beta-amino ester), polyglycolic acid, polylysine, cyclodextrin, collagen, polybrene, diethylaminoethyl-dextran, polyamidoamine, polyethylene glycol, propylene glycol, polystyrene, and polyvinylacetate.
  • the crosslinked polymers are polyethyleneimine and
  • PEI-NAc N-acetyl cysteine
  • polymer is covalently attached to a residue of a therapeutic agent.
  • the polymer described herein is modified (either before, during or after administration to a subject) such that it is linked to a target-specific moiety.
  • the target-specific moiety is a cancer-specific moiety that has binding specificity for a cancer cell (e.g., has binding specificity for a cancer-specific antigen).
  • the target-specific moiety comprises an antibody or antigen binding fragment thereof.
  • the target-specific moiety comprises a T cell receptor or a chimeric antigen receptor (CAR).
  • the target-specific moiety comprises a ligand for a receptor expressed on the surface of a cell (e.g., a cancer cell) or a receptor-binding fragment thereof.
  • the target-specific moiety is a bipartite fusion protein that has two parts: a first part that binds to and/or is linked to the polymer and a second part that is capable of binding to a target cell, such as a cancer cell (e.g., by having binding specificity for a target-specific antigen, such as a cancer-specific antigen).
  • the first and/or second part comprises an antibody or antigen binding fragment thereof.
  • the first and/or second part comprises a T cell receptor or a chimeric antigen receptor (CAR). In some embodiments, the first and/or second part comprises a ligand for a receptor expressed on the surface of a cancer cell or a receptor-binding fragment thereof. In certain embodiments, co-administration of the target- specific moiety with the bacteria (either in combination or in separate administrations) increases the targeting of the bacteria to the cancer cells.
  • CAR chimeric antigen receptor
  • the polymer causes the coated bacteria to acquire an infection profile wherein they localize to and/or infect certain cells, tissues and/or organs.
  • the polymer-coated bacteria have an infection profile in which they localize to tumors and/or cancer cells.
  • the polymer-coated bacteria have an infection profile where they localize to a particular organ and/or tissue (e.g., skeletal muscles, cardiac muscles, smooth muscles, bones, joints, ligaments, tendons, salivary glands, stomach, small intestine, large intestine, liver, gallbladder, pancreas, pharynx, larynx, bronchi, lungs, kidneys, ureters, bladder, urethra, ovaries, uterus, vagina, placenta, testes, prostate, brain, spinal cord, peripheral nerves, pituitary gland, pineal gland, thyroid gland, parathyroid gland, adrenal gland, pancreas, heart, arteries, veins, capillaries, lymph nodes, thymus, spleen, bone marrow, eyes and skin).
  • tissue e.g., skeletal muscles, cardiac muscles, smooth muscles, bones, joints, ligaments, tendons, salivary glands, stomach, small intestine, large intestine, liver, gallbla
  • the polymer-coated bacteria have an infection profile wherein they infect and/or bind to particular cell types. In some embodiments, the polymer-coated bacteria have an infection profile wherein they infect and/or bind to cancer and/or tumor cells. In some embodiments, the bacteria have an infection profile wherein they infect and/or bind to antigen presenting cells (e.g., dendritic cells, macrophages, B cells). In some embodiments, the polymer-coated bacteria have an infection profile wherein they infect and/or bind to tumor-associated macrophages and/or myeloid- derived suppressor cells.
  • antigen presenting cells e.g., dendritic cells, macrophages, B cells.
  • the polymers provided herein are bound to a therapeutic agent by a cross-linker.
  • cross-linker broadly refers to compositions that can be used to join various molecules, including proteins, together.
  • cross-linkers include, but are not limited to, l,5-difluoro-2,4-dinitrobenzene, 3,3'-dithiobis(succinimidyl propionate), bis(2-succinimidooxycarbonyloxy)ethyl)sulfone, bis(sulfosuccinimidyl)suberate, dimethyl 3,3'-dithiobispropionimidate, dimethyl adipimidate, dimethyl pimelimidate, dimethyl suberimidate, disuccinimidyl glutarate, disuccinimidyl suberate, disuccinimidyl tartrate, dithiobis(succinimidyl propionate), ethylene glycosl bis(succinimidyl succinate) , ethylene glycosl bis(sulfosuccinimidyl succinate) , PEGylated bis(sulfosuccinimidyl)suberate (with PEG5),
  • the polymer described herein is linked to a therapeutic agent through a nucleic acid linker.
  • the polymers described herein are covalently bonded to a first single-stranded nucleic acid oligonucleotide (e.g., an oligonucleotide of at least 10, 1 1, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 nucleotides in length and/or no more than 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 nucleotides in length) that can serve binding site for an agent that comprises and/or is linked to second nucleic acid oligonucleotide (e.g., an oligonucleotide of at least 10, 1 1, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 nucleotides in length and/or no more than 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85,
  • the first oligonucleotide has a sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to a sequence of the second oligonucleotide.
  • a cancer therapeutic is covalently linked to a single-stranded nucleic acid oligonucleotide that specifically hybridizes to a single-stranded nucleic acid oligonucleotide covalently attached to a polymer described herein.
  • the hybridized oligonucleotides hybridize and the resulting double-stranded nucleic acid duplex is stable for days.
  • the stability of the duplex is improved by incorporating phosphorothioate bonds (e.g., 1, 2, 3, 4, 5, 6, 7 or more phosphorothioate bonds) on the 5' and/or 3 ' ends of one or both oligonucleotides.
  • phosphorothioate bonds e.g., 1, 2, 3, 4, 5, 6, 7 or more phosphorothioate bonds
  • polynucleotide and “nucleic acid” are used interchangeably and refer to a polymeric form of nucleotides, whether deoxyribonucleotides, ribonucleotides, or analogs thereof, in any combination and of any length.
  • a polynucleotide may comprise modified nucleotides, such as methylated nucleotides and nucleotide analogs. If present, modifications to the nucleotide structure may be imparted before or after assembly of the polymer.
  • a polynucleotide may be further modified, such as by conjugation with a labeling component.
  • U nucleotides are interchangeable with T nucleotides.
  • a polynucleotide "specifically hybridizes" to a target sequence if the oligomer hybridizes to the target under physiological conditions, with a Tm substantially greater than 45 °C, or at least 50 °C, or at least 60 °C-80° C or higher. Such hybridization corresponds to stringent hybridization conditions.
  • the Tm is the temperature at which 50% of a target sequence hybridizes to a
  • complementary polynucleotide Such hybridization may occur with “near” or “substantial” complementarity of the oligonucleotide to the target sequence, as well as with exact complementarity.
  • the polymers described herein are linked to a therapeutic agent through a biotin/streptavidin interaction.
  • the polymers described herein are linked to biotin or to a cancer therapeutic using amine-reactive N-hydroxysuccinimide (NHS) esters or N-hydroxysulfosuccinimide (Sulfo-NHS) esters.
  • NHS esters or Sulfo-NHS esters can be made of virtually any carboxyl- containing molecule of interest by mixing the NHS or Sulfo-NHS with the carboxyl- containing molecule of interest and a dehydrating agent such as the carbodimide EDC using methods available in the art.
  • functional groups such as ketones, azides, alkynes or other functional groups functionalize the polymers described herein and are used to link the polymer to a therapeutic agent.
  • Methods for producing the microbial compositions of the invention may include three main processing steps. The steps are: organism banking, organism production, and preservation. [0055]
  • organism banking the strains included in the microbial composition may be (1) isolated directly from a specimen or taken from a banked stock, (2) optionally cultured on a nutrient agar or broth that supports growth to generate viable biomass, and (3) the biomass optionally preserved in multiple aliquots in long-term storage.
  • the agar or broth may contain nutrients that provide essential elements and specific factors that enable growth.
  • An example would be a medium composed of 20 g/L glucose, 10 g/L yeast extract, 10 g/L soy peptone, 2 g/L citric acid, 1.5 g/L sodium phosphate monobasic, 100 mg/L ferric ammonium citrate, 80 mg/L magnesium sulfate, 10 mg/L hemin chloride, 2 mg/L calcium chloride, 1 mg/L menadione.
  • Another examples would be a medium composed of 10 g/L beef extract, 10 g/L peptone, 5 g/L sodium chloride, 5 g/L dextrose, 3 g/L yeast extract, 3 g/L sodium acetate, 1 g/L soluble starch, and 0.5 g/L L-cysteine HC1, at pH 6.8.
  • a variety of microbiological media and variations are well known in the art (e.g., R.M. Atlas, Handbook of Microbiological Media (2010) CRC Press). Culture media can be added to the culture at the start, may be added during the culture, or may be intermittently/continuously flowed through the culture.
  • the strains in the bacterial composition may be cultivated alone, as a subset of the microbial composition, or as an entire collection comprising the microbial composition.
  • a first strain may be cultivated together with a second strain in a mixed continuous culture, at a dilution rate lower than the maximum growth rate of either cell to prevent the culture from washing out of the cultivation.
  • the inoculated culture is incubated under favorable conditions for a time sufficient to build biomass.
  • microbial compositions for human use this is often at 37°C temperature, pH, and other parameter with values similar to the normal human niche.
  • the environment may be actively controlled, passively controlled (e.g., via buffers), or allowed to drift.
  • an anoxic/reducing environment may be employed. This can be accomplished by addition of reducing agents such as cysteine to the broth, and/or stripping it of oxygen.
  • composition may be grown at 37°C, pH 7, in the medium above, pre-reduced with 1 g/L cysteine-HCl.
  • the culture When the culture has generated sufficient biomass, it may be preserved for banking.
  • the organisms may be placed into a chemical milieu that protects from freezing (adding 'cryoprotectants'), drying ('lyoprotectants'), and/or osmotic shock
  • Containers are generally impermeable and have closures that assure isolation from the environment.
  • Cryopreservation treatment is accomplished by freezing a liquid at ultra-low temperatures (e.g., at or below - 80°C).
  • Dried preservation removes water from the culture by evaporation (in the case of spray drying or 'cool drying') or by sublimation (e.g., for freeze drying, spray freeze drying). Removal of water improves long-term microbial composition storage stability at temperatures elevated above cryogenic.
  • the final composition may be purified by additional means such as density gradient centrifugation preserved using the techniques described above.
  • Microbial composition banking may be done by culturing and preserving the strains individually, or by mixing the strains together to create a combined bank.
  • a microbial composition culture may be harvested by centrifugation to pellet the cells from the culture medium, the supernatant decanted and replaced with fresh culture broth containing 15% glycerol. The culture can then be aliquoted into 1 mL cryotubes, sealed, and placed at -80°C for long-term viability retention. This procedure achieves acceptable viability upon recovery from frozen storage.
  • Microbial production may be conducted using similar culture steps to banking, including medium composition and culture conditions. It may be conducted at larger scales of operation, especially for clinical development or commercial production. At larger scales, there may be several subcultivations of the microbial composition prior to the final cultivation. At the end of cultivation, the culture is harvested to enable further formulation into a dosage form for administration. This can involve concentration, removal of undesirable medium components, and/or introduction into a chemical milieu that preserves the microbial composition and renders it acceptable for administration via the chosen route. For example, a microbial composition may be cultivated to a concentration of 10 10 CFU/mL, then
  • the spent medium may be exchanged by diafiltering with a preservative medium consisting of 2% gelatin, 100 mM trehalose, and 10 mM sodium phosphate buffer.
  • the suspension can then be freeze-dried to a powder and titrated.
  • the powder may be blended to an appropriate potency, and mixed with other cultures and/or a filler such as microcrystalline cellulose for consistency and ease of handling, and the bacterial composition formulated as provided herein.
  • a filler such as microcrystalline cellulose for consistency and ease of handling, and the bacterial composition formulated as provided herein.
  • formulations for administration to subjects are combined with additional active and/or inactive materials in order to produce a final product, which may be in single dosage unit or in a multi-dose format.
  • the composition comprises at least one carbohydrate.
  • Carbohydrate refers to a sugar or polymer of sugars.
  • saccharide refers to a sugar or polymer of sugars.
  • saccharide refers to a sugar or polymer of sugars.
  • polysaccharide “carbohydrate,” and “oligosaccharide” may be used interchangeably.
  • Most carbohydrates are aldehydes or ketones with many hydroxyl groups, usually one on each carbon atom of the molecule.
  • Carbohydrates generally have the molecular formula CnEhnOn.
  • a carbohydrate may be a monosaccharide, a disaccharide, trisaccharide, oligosaccharide, or polysaccharide.
  • the most basic carbohydrate is a monosaccharide, such as glucose, sucrose, galactose, mannose, ribose, arabinose, xylose, and fructose.
  • Disaccharides are two joined monosaccharides.
  • Exemplary disaccharides include sucrose, maltose, cellobiose, and lactose.
  • an oligosaccharide includes between three and six monosaccharide units (e.g., raffinose, stachyose), and polysaccharides include six or more monosaccharide units.
  • Exemplary polysaccharides include starch, glycogen, and cellulose.
  • Carbohydrates may contain modified saccharide units such as 2'-deoxyribose wherein a hydroxyl group is removed, 2'-fluororibose wherein a hydroxyl group is replaced with a fluorine, or N- acetylglucosamine, a nitrogen-containing form of glucose (e.g., 2'-fluororibose, deoxyribose, and hexose).
  • Carbohydrates may exist in many different forms, for example, conformers, cyclic forms, acyclic forms, stereoisomers, tautomers, anomers, and isomers.
  • the composition comprises at least one lipid.
  • a "lipid” includes fats, oils, triglycerides, cholesterol, phospholipids, fatty acids in any form including free fatty acids. Fats, oils and fatty acids can be saturated, unsaturated (cis or trans) or partially unsaturated (cis or trans).
  • the lipid comprises at least one fatty acid selected from lauric acid (12:0), myristic acid (14:0), palmitic acid (16:0), palmitoleic acid (16: 1), margaric acid (17:0), heptadecenoic acid (17: 1), stearic acid (18:0), oleic acid (18: 1), linoleic acid (18:2), linolenic acid (18:3), octadecatetraenoic acid (18:4), arachidic acid (20:0), eicosenoic acid (20: 1), eicosadienoic acid (20:2), eicosatetraenoic acid (20:4), eicosapentaenoic acid (20:5) (EPA), docosanoic acid (22:0), docosenoic acid (22: 1), docosapentaenoic acid (22:5), docosahexaenoic acid (22:6) (DHA), and t
  • the composition comprises at least one supplemental mineral or mineral source.
  • supplemental mineral or mineral source examples include, without limitation: chloride, sodium, calcium, iron, chromium, copper, iodine, zinc, magnesium, manganese, molybdenum, phosphorus, potassium, and selenium.
  • Suitable forms of any of the foregoing minerals include soluble mineral salts, slightly soluble mineral salts, insoluble mineral salts, chelated minerals, mineral complexes, non-reactive minerals such as carbonyl minerals, and reduced minerals, and combinations thereof.
  • the composition comprises at least one supplemental vitamin.
  • the at least one vitamin can be fat-soluble or water soluble vitamins.
  • Suitable vitamins include but are not limited to vitamin C, vitamin A, vitamin E, vitamin B12, vitamin K, riboflavin, niacin, vitamin D, vitamin B6, folic acid, pyridoxine, thiamine, pantothenic acid, and biotin.
  • Suitable forms of any of the foregoing are salts of the vitamin, derivatives of the vitamin, compounds having the same or similar activity of the vitamin, and metabolites of the vitamin.
  • the composition comprises an excipient.
  • suitable excipients include a buffering agent, a preservative, a stabilizer, a binder, a compaction agent, a lubricant, a dispersion enhancer, a disintegration agent, a flavoring agent, a sweetener, and a coloring agent.
  • the excipient is a buffering agent.
  • suitable buffering agents include sodium citrate, magnesium carbonate, magnesium bicarbonate, calcium carbonate, and calcium bicarbonate.
  • the excipient comprises a preservative.
  • suitable preservatives include antioxidants, such as alpha-tocopherol and ascorbate, and antimicrobials, such as parabens, chlorobutanol, and phenol.
  • the composition comprises a binder as an excipient.
  • Suitable binders include starches, pregelatinized starches, gelatin, polyvinylpyrolidone, cellulose, methylcellulose, sodium carboxymethylcellulose,
  • ethylcellulose polyacrylamides, polyvinyloxoazolidone, polyvinylalcohols, C12-C18 fatty acid alcohol, polyethylene glycol, polyols, saccharides, oligosaccharides, and combinations thereof.
  • the composition comprises a lubricant as an excipient.
  • Non-limiting examples of suitable lubricants include magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, sterotex, polyoxyethylene monostearate, talc, polyethyleneglycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, and light mineral oil.
  • the composition comprises a dispersion enhancer as an excipient.
  • suitable dispersants include starch, alginic acid, polyvinylpyrrolidones, guar gum, kaolin, bentonite, purified wood cellulose, sodium starch glycolate, isoamorphous silicate, and microcrystalline cellulose as high HLB emulsifier surfactants.
  • the composition comprises a disintegrant as an excipient.
  • the disintegrant is a non-effervescent disintegrant.
  • suitable non-effervescent disintegrants include starches such as corn starch, potato starch, pregelatinized and modified starches thereof, sweeteners, clays, such as bentonite, micro-crystalline cellulose, alginates, sodium starch glycolate, gums such as agar, guar, locust bean, karaya, pectin, and tragacanth.
  • the disintegrant is an effervescent disintegrant.
  • suitable effervescent disintegrants include sodium bicarbonate in combination with citric acid, and sodium bicarbonate in combination with tartaric acid.
  • the composition is a food product (e.g., a food or beverage) such as a health food or beverage, a food or beverage for infants, a food or beverage for pregnant women, athletes, senior citizens or other specified group, a functional food, a beverage, a food or beverage for specified health use, a dietary supplement, a food or beverage for patients, or an animal feed.
  • a food product e.g., a food or beverage
  • a food or beverage such as a health food or beverage, a food or beverage for infants, a food or beverage for pregnant women, athletes, senior citizens or other specified group, a functional food, a beverage, a food or beverage for specified health use, a dietary supplement, a food or beverage for patients, or an animal feed.
  • the foods and beverages include various beverages such as juices, refreshing beverages, tea beverages, drink preparations, jelly beverages, and functional beverages; alcoholic beverages such as beers; carbohydrate-containing foods such as rice food products, noodles, breads, and pastas; paste products such as fish hams, sausages, paste products of seafood; retort pouch products such as curries, food dressed with a thick starchy sauces, and Chinese soups; soups; dairy products such as milk, dairy beverages, ice creams, cheeses, and yogurts; fermented products such as fermented soybean pastes, yogurts, fermented beverages, and pickles; bean products; various confectionery products, including biscuits, cookies, and the like, candies, chewing gums, gummies, cold desserts including jellies, cream caramels, and frozen desserts; instant foods such as instant soups and instant soy-bean soups; microwavable foods; and the like. Further, the examples also include health foods and beverages prepared in the forms of powders, granules, tablets, carb
  • compositions provided herein include a polymer that is covalently attached to a residue of a therapeutic agent.
  • the therapeutic agent is an anti-cancer therapeutic agent.
  • the therapeutic agent is an anti-inflammatory therapeutic agent.
  • the anti-cancer therapeutic agent is a chemotherapy agent.
  • chemotherapeutic agents include, but are not limited to, alkylating agents such as thiotepa and cyclosphosphamide; alkyl sulfonates such as busulfan, improsulfan and piposulfan; aziridines such as benzodopa, carboquone, meturedopa, and uredopa; ethylenimines and methylamelamines including altretamine, triethylenemelamine, trietylenephosphoramide, triethiylenethiophosphoramide and trimethylolomelamine;
  • acetogenins especially bullatacin and bullatacinone
  • a camptothecin including the synthetic analogue topotecan
  • bryostatin cally statin; CC-1065 (including its adozelesin, carzelesin and bizelesin synthetic analogues); cryptophycins (particularly cryptophycin 1 and cryptophycin 8); dolastatin; duocarmycin (including the synthetic analogues, KW-2189 and CB 1-TM1); eleutherobin; pancrati statin; a sarcodictyin; spongistatin; nitrogen mustards such as chlorambucil, chlornaphazine, cholophosphamide, estramustine, ifosfamide,
  • calicheamicin omegal l dynemicin, including dynemicin A; bisphosphonates, such as clodronate; an esperamicin; as well as neocarzinostatin chromophore and related
  • authrarnycin azaserine, bleomycins, cactinomycin, carabicin, caminomycin, carzinophilin, chromomycinis, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, doxorubicin (including morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino- doxorubicin and deoxydoxorubicin), epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins such as mitomycin C, mycophenolic acid, nogalamycin, olivomycins, peplomycin, potfiromycin, puromycin, quelamycin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; anti -
  • elliptinium acetate an epothilone; etoglucid; gallium nitrate; hydroxyurea; lentinan;
  • lonidainine lonidainine
  • maytansinoids such as maytansine and ansamitocins
  • mitoguazone lonidainine
  • mitoxantrone mopidanmol; nitraerine; pentostatin; phenamet; pirarubicin; losoxantrone; podophyllinic acid; 2-ethylhydrazide; procarbazine; PSK polysaccharide complex); razoxane; rhizoxin; sizofuran; spirogermanium; tenuazonic acid; triaziquone; 2,2',2"- trichlorotriethylamine; trichothecenes (especially T-2 toxin, verracurin A, roridin A and anguidine); urethan; vindesine; dacarbazine; mannomustine; mitobronitol; mitolactol;
  • pipobroman gacytosine; arabinoside ("Ara-C”); cyclophosphamide; thiotepa; taxoids, e.g., paclitaxel and doxetaxel; chlorambucil; gemcitabine; 6-thioguanine; mercaptopurine;
  • methotrexate platinum coordination complexes such as cisplatin, oxaliplatin and carboplatin; vinblastine; platinum; etoposide (VP- 16); ifosfamide; mitoxantrone; vincristine; vinorelbine; novantrone; teniposide; edatrexate; daunomycin; aminopterin; xeloda; ibandronate; irinotecan (e.g., CPT-11); topoisomerase inhibitor RFS 2000; difluoromethylomithine (DMFO);
  • DMFO difluoromethylomithine
  • retinoids such as retinoic acid; capecitabine; and pharmaceutically acceptable salts, acids or derivatives of any of the above.
  • the anti-cancer therapeutic agent is a cancer immunotherapy agent.
  • Immunotherapy refers to a treatment that uses a subject's immune system to treat cancer, e.g., checkpoint inhibitors, cancer vaccines, cytokines, cell therapy, CAR-T cells, and dendritic cell therapy.
  • checkpoint inhibitors include Nivolumab (BMS, anti-PD-1), Pembrolizumab (Merck, anti- PD-1), Ipilimumab (BMS, anti-CTLA-4), MEDI4736 (AstraZeneca, anti-PD-Ll), and MPDL3280A (Roche, anti-PD-Ll).
  • Other immunotherapies may be tumor vaccines, such as Gardail, Cervarix, BCG, sipulencel-T, Gpl00:209-217, AGS-003, DCVax-L, Algenpantucel- L, Tergenpantucel-L, TG4010, ProstAtak, Prostvac-V/R-TRICOM, Rindopepimul, E75 peptide acetate, IMA901, POL-103A, Belagenpumatucel-L, GSK1572932A, MDX-1279, GV1001, and Tecemotide.
  • tumor vaccines such as Gardail, Cervarix, BCG, sipulencel-T, Gpl00:209-217, AGS-003, DCVax-L, Algenpantucel- L, Tergenpantucel-L, TG4010, ProstAtak, Prostvac-V/R-TRICOM, Rindopepimul, E75
  • Immunotherapy may be administered via injection (e.g., intravenously, intratumorally, subcutaneously, or into lymph nodes), but may also be administered orally, topically, or via aerosol.
  • Immunotherapies may comprise adjuvants such as cytokines.
  • the immunotherapy agent is an immune checkpoint inhibitor.
  • Immune Checkpoint inhibition broadly refers to inhibiting the checkpoints that cancer cells can produce to prevent or downregulate an immune response.
  • immune checkpoint proteins include, but are not limited to, CTLA4, PD-1, PD-L1, PD-L2, A2AR, B7-H3, B7-H4, BTLA, KIR, LAG3, TIM-3 or VISTA.
  • Immune checkpoint inhibitors can be antibodies or antigen binding fragments thereof that bind to and inhibit an immune checkpoint protein.
  • immune checkpoint inhibitors include, but are not limited to, nivolumab, pembrolizumab, pidilizumab, AMP-224, AMP-514, STI-A1110, TSR-042, RG- 7446, BMS-936559, MEDI-4736, MSB-0020718C, AUR-012 and STI-A1010.
  • the immunotherapy agent is an immunostimulatory agent.
  • the immunostimulatory agent is an adjuvant.
  • the adjuvant is selected from immune modulatory protein, Adjuvant 65, a- GalCer, aluminum phosphate, aluminum hydroxide, calcium phosphate, ⁇ -Glucan Peptide, CpG DNA, GPI-0100, lipid A, lipopoly saccharide, Lipovant, Montanide, N-acetyl-muramyl- L-alanyl-D-isoglutamine, Pam3CSK4, quil A and trehalose dimycolate.
  • the immunostimulatory agent is an immune modulatory protein, such as a cytokine.
  • the immunotherapy agent is an antibody or antigen binding fragment thereof that, for example, binds to a cancer-associated antigen.
  • cancer-associated antigens include, but are not limited to, adipophilin, AIM-2, ALDHlAl, alpha-actinin-4, alpha-fetoprotein ("AFP"), ARTCl, B-RAF, BAGE-1, BCLX (L), BCR- ABL fusion protein b3a2, beta-catenin, BING-4, CA-125, CALCA, carcinoembryonic antigen ("CEA”), CASP-5, CASP-8, CD274, CD45, Cdc27, CDK12, CDK4, CDKN2A, CEA, CLPP, COA-1, CPSF, CSNK1A1, CTAG1, CTAG2, cyclin Dl, Cyclin-Al, dek-can fusion protein, DKK1, EFTUD2, Elongation factor 2, ENAH (hMena), Ep-CAM,
  • the immunotherapy agent is a cancer vaccine and/or a component of a cancer vaccine (e.g., an antigenic peptide and/or protein).
  • the cancer vaccine can be a protein vaccine, a nucleic acid vaccine or a combination thereof.
  • the cancer vaccine comprises a polypeptide comprising an epitope of a cancer-associated antigen.
  • the cancer vaccine comprises a nucleic acid (e.g., DNA or RNA, such as mRNA) that encodes an epitope of a cancer-associated antigen.
  • cancer-associated antigens include, but are not limited to, adipophilin, AIM-2, ALDHIAI, alpha-actinin-4, alpha-fetoprotein ("AFP"), ARTCl, B-RAF, BAGE-1, BCLX (L), BCR-ABL fusion protein b3a2, beta-catenin, BING-4, CA-125, CALCA,
  • CEA carcinoembryonic antigen
  • CASP-5 CASP-8
  • CD274, CD45 Cdc27, CDK12, CDK4, CDKN2A
  • CEA carcinoembryonic antigen
  • CLPP COA-1, CPSF, CS K1A1, CTAG1, CTAG2, cyclin Dl, Cyclin-Al, dek-can fusion protein, DKK1, EFTUD2, Elongation factor 2, ENAH (hMena), Ep-CAM, EpCAM, EphA3, epithelial tumor antigen ("ETA”), ETV6-AML1 fusion protein, EZH2, FGF5, FLT3-ITD, FN1, G250/MN/CAIX, GAGE-1,2,8, GAGE-3,4,5,6,7, GAS7, glypican-3, GnTV, gpl00/Pmel l7, GP MB, HAUS3, Hepsin, HER-2/neu, HERV-K-MEL, HLA-Al
  • the antigen is a neo-antigen.
  • the cancer vaccine is administered with an adjuvant.
  • adjuvants include, but are not limited to, an immune modulatory protein, Adjuvant 65, a-GalCer, aluminum phosphate, aluminum hydroxide, calcium phosphate, ⁇ -Glucan Peptide, CpG DNA, GPI-0100, lipid A, lipopoly saccharide, Lipovant, Montanide, N-acetyl-muramyl-L- alanyl-D-isoglutamine, Pam3CSK4, quil A and trehalose dimycolate.
  • the immunotherapy agent is an immune modulating protein to the subject.
  • the immune modulatory protein is a cytokine.
  • immune modulating proteins include, but are not limited to, B lymphocyte chemoattractant ("BLC"), C-C motif chemokine 11 (“Eotaxin-1 "), Eosinophil chemotactic protein 2 (“Eotaxin-2”), Granulocyte colony-stimulating factor (“G-CSF”), Granulocyte macrophage colony-stimulating factor (“GM-CSF”), 1-309, Intercellular Adhesion Molecule 1 (“ICAM-l "), Interferon gamma ("IFN-gamma”), Interlukin-1 alpha (“IL-l alpha”), Interlukin-1 beta (“IL-l beta”), Interleukin 1 receptor antagonist (“IL-l ra”), Interleukin-2 (“IL-2”), Interleukin-4 (“IL-4"), Interleukin-5 (“IL-5"), Inter
  • IL-17 Interleukin- 17
  • MCP-1 Chemokine (C-C motif) Ligand 2
  • MCP-2 Macrophage colony- stimulating factor
  • MIG Monokine induced by gamma interferon
  • MIG Chemokine (C-C motif) ligand 2
  • MIP-1 beta Chemokine (C-C motif) ligand 4
  • MIP-1 delta Macrophase inflammatory protein- 1 -delta
  • PDGF-BB Platelet-derived growth factor subunit B
  • RANTES TIMP metallopeptidase inhibitor 1
  • TIMP-2 TIMP metallopeptidase inhibitor 2
  • TNF alpha Tumor necrosis factor
  • TNF beta Tumor necrosis factor-alpha
  • TNF beta Tumor necrosis factor
  • TNF beta Tumor necrosis factor
  • TNF alpha Tumor necrosis factor
  • TNF beta Tumor necrosis factor-beta
  • GD F Growth Hormone, Heparin-binding EGF-like growth factor
  • FIB-EGF Hepatocyte growth factor
  • HGF Hepatocyte growth factor
  • IGFBP-1 Insulin-like growth factor binding protein 1
  • IGFBP-2 Insulin-like growth factor binding protein 2
  • IGFBP-3 Insulin-like growth factor binding protein 3
  • IGFBP-4 Insulin-like growth factor binding protein 4
  • IGFBP-6 Insulinlike growth factor binding protein 6
  • TGFalpha Transforming growth factor beta-1
  • TGF beta 3 Transforming growth factor beta 3
  • VEGF Vascular endothelial growth factor
  • VEGFR2 Vascular endothelial growth factor receptor 2
  • VEGFR3 Vascular endothelial growth factor receptor 3
  • VEGF-D 6Ckine Tyrosine-protein kinase receptor UFO (“Axl”)
  • BTC Betacellulin
  • CCL28 Chemokine (C- C motif) ligand 27
  • CXCL16 Chemokine (C-X-C motif) ligand 16
  • CX-C motif chemokine 5 ENA-78
  • Chemokine (C-C motif) ligand 26 Eotaxin-3
  • Granulocyte chemotactic protein 2 ("GCP-2"), GRO, Chemokine (C-C motif) ligand 14 ("HCC-l”), Chemokine (C-C motif) ligand 16 (“HCC-4"), Interleukin-9 ("IL-9”), Interleukin- 17 F (“IL-17F”), Interleukin- 18-binding protein (“IL-18 BPa”), Interleukin-28 A (“IL-28A”), Interleukin 29 (“IL-29”), Interleukin 31 (“IL-31 “), C-X-C motif chemokine 10 (“IP-10”), Chemokine receptor CXCR3 (“I-TAC”), Leukemia inhibitory factor (“LIF”), Light,
  • GCP-2 Granulocyte chemotactic protein 2
  • HCC-l Chemokine (C-C motif) ligand 14
  • Chemokine (C-C motif) ligand 16 (“HCC-4")
  • Interleukin-9 Interleukin- 17 F
  • Chemokine (C motif) ligand (“Lymphotactin”), Monocyte chemoattractant protein 2 (“MCP- 2”), Monocyte chemoattractant protein 3 (“MCP-3”), Monocyte chemoattractant protein 4 (“MCP-4"), Macrophage-derived chemokine (“MDC”), Macrophage migration inhibitory factor (“MIF”), Chemokine (C-C motif) ligand 20 (“MIP-3 alpha”), C-C motif chemokine 19 (“MIP-3 beta”), Chemokine (C-C motif) ligand 23 (“MPIF-1 "), Macrophage stimulating protein alpha chain (“MSPalpha”), Nucleosome assembly protein 1-like 4 (“NAP-2”), Secreted phosphoprotein 1 (“Osteopontin”), Pulmonary and activation-regulated cytokine (“PARC”), Platelet factor 4 ("PF4"), Stroma cell-derived factor- 1 alpha (“SDF-1 alpha”), Chemokine (C-C motif
  • Trappin-2 Urokinase receptor
  • VCAM-1 Vascular cell adhesion protein 1
  • XEDARActivin A Agouti-related protein
  • AgRP Agouti-related protein
  • Angiogenin Ribonuclease 5
  • Angiopoietin 1 Angiostatin
  • Catheprin S CD40
  • Cryptic family protein IB Cryptic family protein IB
  • DAN Dickkopf-related protein 1
  • E-Cadherin Epithelial cell adhesion molecule
  • EpCAM Fas Ligand (FasL or CD95L)
  • Fcg RIIB/C FoUistatin
  • Galectin-7 Intercellular adhesion molecule 2
  • IAM-2 Intercellular adhesion molecule 2
  • IAM-2 Intercellular adhesion molecule 2
  • IL-13 Rl Intercellular adhesion molecule 2
  • IL-13R2 Intercellular adhesion molecule 2
  • IL-17B Intercellular adhesion molecule 2
  • Triggering receptor expressed on myeloid cells 1 ("TREM-1 "), Vascular endothelial growth factor C (“VEGF-C”), VEGFRlAdiponectin, Adipsin ("AND”), Alpha-fetoprotein (“AFP”), Angiopoietin-like 4 (“ANGPTL4"), Beta-2-microglobulin (“B2M”), Basal cell adhesion molecule (“BCAM”), Carbohydrate antigen 125 (“CA125”), Cancer Antigen 15-3 (“CA15- 3"), Carcinoembryonic antigen (“CEA”), cAMP receptor protein (“CRP”), Human Epidermal Growth Factor Receptor 2 (“ErbB2”), FoUistatin, Follicle-stimulating hormone (“FSH”), Chemokine (C-X-C motif) ligand 1 (“GRO alpha”), human chorionic gonadotropin (“beta HCG”), Insulin-like growth factor 1 receptor (“IGF-l sR”), IL-1 sRII
  • the immunotherapy agent is an adjuvant.
  • the adjuvant is selected from immune modulatory protein, Adjuvant 65, a-
  • GalCer aluminum phosphate, aluminum hydroxide, calcium phosphate, ⁇ -Glucan Peptide,
  • the anti-cancer therapeutic agent is an angiogenesis inhibitor.
  • the angiogenesis inhibitor is selected from the group consisting of Bevacizumab (Avastin®), Ziv-aflibercept (Zaltrap®), Sorafenib
  • the anti-cancer therapeutic agent is a radioactive agent.
  • the radioactive agent comprises a radionuclide selected from the group consisting of Cr-51, Cs-131, Ce-134, Se-75, Ru-97, 1-125, Eu-149, Os-189m, Sb-119, 1-123, Ho-161, Sb-117, Ce-139, In-I l l, Rh-103m, Ga-67, Tl-201, Pd-103, Au-195, Hg-197, Sr-87m, Pt-191, P-33, Er-169, Ru-103, Yb-169, Au-199, Sn-121, Tm-167, Yb-175, In-113m, Sn-113, Lu-177, Rh-105, Sn-117m, Cu-67, Sc-47, Pt-195m, Ce-141, 1- 131, Tb-161, As-77, Pt-197, Sm-153, Gd-159, Tm-173, Pr-143, Au-198, Tm-170, Re-186
  • a radionuclide
  • the anti-cancer therapeutic agent is an anti-cancer compound.
  • anti-cancer compounds include, but are not limited to, Alemtuzumab (Campath®), Alitretinoin (Panretin®), Anastrozole (Arimidex®), Bevacizumab (Avastin®), Bexarotene (Targretin®), Bortezomib (Velcade®), Bosutinib (Bosulif®), Brentuximab vedotin (Adcetris®), Cabozantinib (CometriqTM), Carfilzomib (KyprolisTM), Cetuximab (Erbitux®), Crizotinib (Xalkori®), Dasatinib (Sprycel®), Denileukin diftitox (Ontak®), Erlotinib hydrochloride (Tarceva®), Everolimus (Afinitor®),
  • Exemplary anti-cancer compounds that modify the function of proteins that regulate gene expression and other cellular functions are Vorinostat (Zolinza®), Bexarotene (Targretin®) and Romidepsin (Istodax®), Alitretinoin (Panretin®), and Tretinoin (Vesanoid®).
  • Exemplary anti-cancer compounds that induce apoptosis are Bortezomib (Velcade®), Carfilzomib (KyprolisTM), and
  • Pralatrexate (Folotyn®).
  • anti CD20 e.g., anti CD20, anti CD52; anti-cytotoxic T-lymphocyte-associated antigen-4) are examples of anti CD20, anti CD52; anti-cytotoxic T-lymphocyte-associated antigen-4) are examples of anti CD20, anti CD52; anti-cytotoxic T-lymphocyte-associated antigen-4) are examples of anti CD20, anti CD52; anti-cytotoxic T-lymphocyte-associated antigen-4) are examples of CD20, anti CD52; anti-cytotoxic T-lymphocyte-associated antigen-4) are examples of CD20, anti CD52; anti-cytotoxic T-lymphocyte-associated antigen-4) are examples of anti CD20, anti CD52; anti-cytotoxic T-lymphocyte-associated antigen-4) are examples of anti CD52, anti CD52; anti-cytotoxic T-lymphocyte-associated antigen-4) are examples of anti CD52, anti CD52; anti-cytotoxic T-lymphocyte-associated antigen-4) are examples of anti CD52, anti CD52; anti-cytotoxic T
  • Rituximab (Rituxan®), Alemtuzumab (Campath®), Ofatumumab (Arzerra®), and
  • anti-CD20-radionuclide fusions e.g., anti-CD20-radionuclide fusions; IL-2-diphtheria toxin fusions; anti-CD30- monomethylauristatin E (MMAE)-fusions
  • MMAE monomethylauristatin E
  • exemplary anti-cancer compounds are small molecule inhibitors and conjugates thereof of, e.g., Janus kinase, ALK, Bcl-2, PARP, PI3K, VEGF receptor, Braf, MEK, CDK, and HSP90.
  • Exemplary platinum-based anti-cancer compounds include, for example, cisplatin, carboplatin, oxaliplatin, satraplatin, picoplatin, Nedaplatin, Triplatin, and
  • Lipoplatin Other metal-based drugs suitable for treatment include, but are not limited to ruthenium-based compounds, ferrocene derivatives, titanium-based compounds, and gallium- based compounds.
  • the anti-cancer therapeutic agent is a radioactive moiety that comprises a radionuclide.
  • radionuclides include, but are not limited to Cr-51, Cs-131, Ce-134, Se-75, Ru-97, 1-125, Eu-149, Os-189m, Sb-1 19, 1-123, Ho-161, Sb- 1 17, Ce-139, In-1 1 1, Rh-103m, Ga-67, Tl-201, Pd-103, Au-195, Hg-197, Sr-87m, Pt-191, P- 33, Er-169, Ru-103, Yb-169, Au-199, Sn-121, Tm-167, Yb-175, In-1 13m, Sn-1 13, Lu-177, Rh-105, Sn-1 17m, Cu-67, Sc-47, Pt-195m, Ce-141 , 1-131, Tb-161, As-77, Pt-197, Sm-153, Gd-159, Tm-173, Pr-143,
  • the cancer therapeutic is an antibiotic.
  • antibiotics broadly refers to compounds capable of inhibiting or preventing a bacterial infection. Antibiotics can be classified in a number of ways, including their use for specific infections, their mechanism of action, their bioavailability, or their spectrum of target microbe (e.g., Gram-negative vs. Gram-positive bacteria, aerobic vs. anaerobic bacteria, etc.) and these may be used to kill specific bacteria in specific areas of the host (“niches”) (Leekha, et al 201 1. General
  • antibiotics can be used to selectively target bacteria of a specific niche.
  • antibiotics known to treat a particular infection that includes a cancer niche may be used to target cancer-associated microbes, including cancer-associated bacteria in that niche.
  • antibiotics can be selected based on their bactericidal or bacteriostatic properties.
  • Bactericidal antibiotics include mechanisms of action that disrupt the cell wall (e.g., ⁇ -lactams), the cell membrane (e.g., daptomycin), or bacterial DNA (e.g., fluoroquinolones).
  • Bacteriostatic agents inhibit bacterial replication and include
  • sulfonamides tetracyclines, and macrolides, and act by inhibiting protein synthesis.
  • bactericidal and bacteriostatic antibiotics inhibit the activity of bactericidal antibiotics.
  • bactericidal and bacteriostatic antibiotics inhibit the activity of bactericidal antibiotics.
  • Antibiotics include, but are not limited to aminoglycosides, ansamycins, carbacephems, carbapenems, cephalosporins, glycopeptides, lincosamides, lipopeptides, macrolides, monobactams, nitrofurans, oxazolidonones, penicillins, polypeptide antibiotics, quinolones, fluoroquinolone, sulfonamides, tetracyclines, and anti-mycobacterial compounds, and combinations thereof.
  • Aminoglycosides include, but are not limited to Amikacin, Gentamicin,
  • Kanamycin, Neomycin, Netilmicin, Tobramycin, Paromomycin, and Spectinomycin are examples of the compounds listed in the following paragraphs.
  • Aminoglycosides are effective, e.g., against Gram -negative bacteria, such as Escherichia coli, Klebsiella, Pseudomonas aeruginosa, and Francisella tularensis, and against certain aerobic bacteria but less effective against obligate/facultative anaerobes. Aminoglycosides are believed to bind to the bacterial 30S or 50S ribosomal subunit thereby inhibiting bacterial protein synthesis.
  • Ansamycins include, but are not limited to, Geldanamycin, Herbimycin,
  • Carbacephems include, but are not limited to, Loracarbef. Carbacephems are believed to inhibit bacterial cell wall synthesis.
  • Carbapenems include, but are not limited to, Ertapenem, Doripenem,
  • Carbapenems are bactericidal for both Gram-positive and Gram-negative bacteria as broad-spectrum antibiotics. Carbapenems are believed to inhibit bacterial cell wall synthesis.
  • Cephalosporins include, but are not limited to, Cefadroxil, Cefazolin,
  • Cefalotin Cefalothin, Cefalexin, Cefaclor, Cefamandole, Cefoxitin, Cefprozil, Cefuroxime, Cefixime, Cefdinir, Cefditoren, Cefoperazone, Cefotaxime, Cefpodoxime, Ceftazidime, Ceftibuten, Ceftizoxime, Ceftriaxone, Cefepime, Ceftaroline fosamil,and Ceftobiprole.
  • Cephalosporins are effective, e.g., against Gram-negative bacteria and against Gram-positive bacteria, including Pseudomonas, certain Cephalosporins are effective against methicillin-resistant Staphylococcus aureus (MRSA). Cephalosporins are believed to inhibit bacterial cell wall synthesis by disrupting synthesis of the peptidoglycan layer of bacterial cell walls.
  • MRSA methicillin-resistant Staphylococcus aureus
  • Glycopeptides include, but are not limited to, Teicoplanin, Vancomycin, and
  • Glycopeptides are effective, e.g., against aerobic and anaerobic Gram-positive bacteria including MRSA and Clostridium difficile. Glycopeptides are believed to inhibit bacterial cell wall synthesis by disrupting synthesis of the peptidoglycan layer of bacterial cell walls.
  • Lincosamides include, but are not limited to, Clindamycin and Lincomycin.
  • Lincosamides are effective, e.g., against anaerobic bacteria, as well as Staphylococcus, and Streptococcus. Lincosamides are believed to bind to the bacterial 50S ribosomal subunit thereby inhibiting bacterial protein synthesis.
  • Lipopeptides include, but are not limited to, Daptomycin. Lipopeptides are effective, e.g., against Gram -positive bacteria. Lipopeptides are believed to bind to the bacterial membrane and cause rapid depolarization.
  • Macrolides include, but are not limited to, Azithromycin, Clarithromycin,
  • Macrolides are effective, e.g., against Streptococcus and Mycoplasma.
  • Macrolides are believed to bind to the bacterial or 50S ribosomal subunit, thereby inhibiting bacterial protein synthesis.
  • Monobactams include, but are not limited to, Aztreonam. Monobactams are effective, e.g., against Gram -negative bacteria. Monobactams are believed to inhibit bacterial cell wall synthesis by disrupting synthesis of the peptidoglycan layer of bacterial cell walls.
  • Nitrofurans include, but are not limited to, Furazolidone and Nitrofurantoin.
  • Oxazolidonones include, but are not limited to, Linezolid, Posizolid,
  • Oxazolidonones are believed to be protein synthesis inhibitors.
  • Penicillins include, but are not limited to, Amoxicillin, Ampicillin, Azlocillin,
  • Penicillins are effective, e.g., against Gram-positive bacteria, facultative anaerobes, e.g., Streptococcus, Borrelia, and Treponema. Penicillins are believed to inhibit bacterial cell wall synthesis by disrupting synthesis of the peptidoglycan layer of bacterial cell walls.
  • Penicillin combinations include, but are not limited to,
  • Polypeptide antibiotics include, but are not limited to, Bacitracin, Colistin, and
  • Polymyxin B and E. Polypeptide Antibiotics are effective, e.g., against Gram-negative bacteria. Certain polypeptide antibiotics are believed to inhibit isoprenyl pyrophosphate involved in synthesis of the peptidoglycan layer of bacterial cell walls, while others destabilize the bacterial outer membrane by displacing bacterial counter-ions.
  • Quinolones and Fluoroquinolone include, but are not limited to, Ciprofloxacin,
  • Quinolones/Fluoroquinolone are effective, e.g., against Streptococcus and Neisseria. Quinolones/Fluoroquinolone are believed to inhibit the bacterial DNA gyrase or topoisomerase IV, thereby inhibiting DNA replication and transcription.
  • Sulfonamides include, but are not limited to, Mafenide, Sulfacetamide,
  • Sulfadiazine Silver sulfadiazine, Sulfadimethoxine, Sulfamethizole, Sulfamethoxazole, Sulfanilimide, Sulfasalazine, Sulfisoxazole, Trimethoprim-Sulfamethoxazole (Co- trimoxazole), and Sulfonamidochrysoidine.
  • Sulfonamides are believed to inhibit folate synthesis by competitive inhibition of dihydropteroate synthetase, thereby inhibiting nucleic acid synthesis.
  • Tetracyclines include, but are not limited to, Demeclocycline, Doxycycline,
  • Tetracyclines are effective, e.g., against Gram-negative bacteria. Tetracyclines are believed to bind to the bacterial 30S ribosomal subunit thereby inhibiting bacterial protein synthesis.
  • Anti-mycobacterial compounds include, but are not limited to, Clofazimine,
  • Suitable antibiotics also include arsphenamine, chloramphenicol, fosfomycin, fusidic acid, metronidazole, mupirocin, platensimycin, quinupristin/dalfopristin, tigecycline, tinidazole, trimethoprim amoxicillin/clavulanate, ampicillin/sulbactam, amphomycin ristocetin, azithromycin, bacitracin, buforin II, carbomycin, cecropin PI, clarithromycin, erythromycins, furazolidone, fusidic acid, Na fusidate, gramicidin, imipenem, indolicidin, josamycin, magainan II, metronidazole, nitroimidazoles, mikamycin, mutacin B-Ny266, mutacin B-JHl 140, mutacin J-T8, nisin, nisin A, novobiocin, ole
  • the therapeutic agent is a prodrug enzyme, such as purine nucleoside phosphorylase.
  • composition of the invention further comprises a prodrug, such as 6-methylpurine 2'-deoxyriboside (6MePdR).
  • a prodrug such as 6-methylpurine 2'-deoxyriboside (6MePdR).
  • composition of the invention further comprises a prebiotic.
  • the prebiotic may be a fructooligosaccharide, a
  • galactooligosaccharide a trans-galactooligosaccharide, a xylooligosaccharide, a chitooligosaccharide, a soy oligosaccharide, a gentiooligosaccharide, an
  • isomaltooligosaccharide a mannooligosaccharide, a maltooligosaccharide, a
  • mannanoligosaccharide lactulose, lactosucrose, palatinose, glycosyl sucrose, guar gum, gum Arabic, tagalose, amylose, amylopectin, pectin, xylan, or a cyclodextrin.
  • the therapeutic agent is an anti-inflammatory agent.
  • the anti-inflammatory agent may be selected from the group consisting of corticosteroids, mesalazine, mesalamine, sulfasalazine, sulfasalazine derivatives,
  • immunosuppressive drugs cyclosporin A, mercaptopurine, azathiopurine, prednisone, methotrexate, antihistamines, glucocorticoids, epinephrine, theophylline, cromolyn sodium, anti-leukotrienes, anti-cholinergic drugs for rhinitis, anti-cholinergic decongestants, mast-cell stabilizers, monoclonal anti-IgE antibodies, and cytokine inhibitors.
  • the cytokine inhibitor is selected from anti-IL-6 antibodies and TNF inhibitors.
  • TNF inhibitors include infliximab, adalimumab, certolizumab pegol, golimumab, and etanercept.
  • the anti-inflammatory agent is a vaccine (e.g., a vaccine used for vaccination where the amount of an allergen is gradually increased).
  • the therapeutic agent is N-acetyl cysteine, polyethylene glycol, a lectin, a protein antigen, a vitamin, curcumin, quercetin, bromelain, zinc, glutamine, a TLR agonist, a TDO/IDO metabolite, a TDO/IDO inhibitor, a DNA fragment, a prebiotic, or a quorum sensing molecule.
  • the therapeutic agent is N-acetyl cysteine (NAC).
  • NAC may adhere to or facilitate breaking up or penetrating a mucus layer. Loosening a mucus layer may confer a positive therapeutic effect in disorders such as cystic fibrosis, chronic obstructive pulmonary disorder, or Tylenol overdose.
  • the therapeutic agent is polyethylene glycol (PEG).
  • PEG is commonly used for protection and delivery, and can function to protect and/or penetrate mucus. In some embodiments, PEG is useful for penetrating mucus and extracellular matrix for cellular uptake.
  • the therapeutic agent is a lectin, and the lectin is Ulex europaeus agglutinin I, Aleuria aurantia lectin, or wheat germ agglutinin.
  • Ulex europaeus agglutinin is useful for targeting M cells and/or Peyer' s patches. Ulex europaeus agglutinin-I lectin binds to fucose glycan, which is commonly found on M cells. This agent may target delivery of particles and/or vaccines to Peyer's patches.
  • the therapeutic agent may be a protein antigen and the protein antigen is a peanut allergen or ovalbumin.
  • the therapeutic agent may be a vitamin, and the vitamin is retinoic acid, vitamin D3, vitamin B6, biotin, or folic acid.
  • the therapeutic agent is a TLR agonist
  • the TLR agonist is selected from the group consisting of R848/imiquimod, polyinosinic-polycytidylic acid, Pam3CSK4, and zymosan.
  • the therapeutic agent is a TDO inhibitor
  • TDO inhibitor is selected from the group consisting of tryptophan kynurenine and indole-3- aldehyde.
  • compositions provided herein comprise a bacterium.
  • bacteria broadly refers to the domain of prokaryotic organisms, including Gram positive and Gram negative organisms. Examples of specific bacteria useful in the compositions and methods provided herein are provided in Table 1 and/or Table 2. In certain embodiments, the bacterial strain used and/or detected in the methods provided herein is a bacterial strain listed in Table 1 and/or Table 2.
  • the bacterial strain is a bacterial strain having a genome that has at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8% or 99.9% sequence identity to a strain listed in Table 1 and/or Table 2.
  • a combination of bacterial strains are used and/or detected in the methods provided herein.
  • the combination is a combination of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45 or 50 bacterial strains.
  • combination includes bacterial strains listed in Table 1 and/or Table 2 and/or bacterial strains having a genome that has at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8% or 99.9% sequence identity to a strain listed in Table 1 and/or Table 2.
  • Coprococcus catus EU266552 Coprococcus comes ABVRO 1000038

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Abstract

L'invention concerne des procédés et des compositions associés à des bactéries enrobées de polymère.
PCT/US2018/044053 2017-07-28 2018-07-27 Compositions polymères Ceased WO2019023555A1 (fr)

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Non-Patent Citations (57)

* Cited by examiner, † Cited by third party
Title
"Guide to Huge Computers", 1994, ACADEMIC PRESS
"Handbook of Microbiological Media", 2010, THE MANUAL OF CLINICAL MICROBIOLOGY ASM PRESS
"Mouse Models of Innate Immunity: Methods and Protocols, Methods in Molecular Biology", vol. 1031, 2013
ADAMOPOULOU E. ET AL.: "Exploring the MHC-peptide matrix of central tolerance in the human thymus", NAT. COMMUN., vol. 4, 2013, pages 2039
ATSCHUL, S. F. ET AL., J MOLEC BIOL, vol. 215, 1990, pages 403
B. EWING; L. HILLIER; M. WENDL; P. GREEN, GENOME RES., vol. 8, 1998, pages 175 - 185
B. EWING; P. GREEN, GENOME RES., vol. 8, 1998, pages 186 - 194
BETTENCOURT, P. ET AL.: "Application of Confocal Microscopy for Quantification of Intracellular Mycobacteria in Macrophages", MICROSCOPY: SCIENCE, TECHNOLOGY, APPLICATIONS AND EDUCATION, vol. 1, 2010, pages 614 - 621, ISBN: 978-84-614-6189-9
BOBEK V. ET AL.: "Syngeneic lymph-node-targeting model of green fluorescent protein-expressing Lewis lung carcinoma", CLIN. EXP. METASTASIS, vol. 21, no. 8, 2004, pages 705 - 8, XP019235796, DOI: doi:10.1007/s10585-004-8118-8
CARILLO ET AL., SIAM J APPLIED MATH, vol. 48, 1988, pages 1073
CATHERINE TOMARO-DUCHESNEAU ET AL: "Microencapsulation for the Therapeutic Delivery of Drugs, Live Mammalian and Bacterial Cells, and Other Biopharmaceutics: Current Status and Future Directions", JOURNAL OF PHARMACEUTICS, 4 December 2012 (2012-12-04), XP055519958, Retrieved from the Internet <URL:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4595965/pdf/JPHAR2013-103527.pdf> [retrieved on 20181030] *
CHANDRA D. ET AL.: "Myeloid-derived suppressor cells have a central role in attenuated Listeria monocytogenes-based immunotherapy against metastatic breast cancer in young and old mice", BR. J. CANCER, vol. 108, no. 11, 2013, pages 2281 - 90
CHANDRA D. ET AL.: "Myeloid-derived suppressor cells have a central role in attenuated Listeria monocytogenes-based immunotherapy against metastatic breast cancer in young and old mice", BR. J. CANCER., vol. 108, no. 11, 2013, pages 2281 - 90
D. GORDON; C. ABAJIAN; P. GREEN, GENOME RES., vol. 8, 1998, pages 195 - 202
D. GORDON; C. DESMARAIS; P. GREEN, GENOME RES., vol. 11, 2001, pages 614 - 625
DAINIAK M.B. ET AL.: "Chromatography of living cells using supermacroporous hydrogels, cryogels", ADV. BIOCHEM. ENG. BIOTECHNOL., vol. 106, 2007, pages 101 - 27, XP055408103, DOI: doi:10.1007/10_2006_044
DAINIAK, M.B. ET AL.: "Macroporous monolithic hydrogels in a 96-minicolumn plate format for cell surface-analysis and integrated binding/quantification of cells", ENZYME MICROB. TECHNOL., vol. 40, no. 4, 2007, pages 688 - 695, XP005892486, DOI: doi:10.1016/j.enzmictec.2006.05.027
DAUBEUF, F.; FROSSARD, N.: "Performing Bronchoalveolar Lavage in the Mouse", CURR. PROTOC. MOUSE BIOL., vol. 2, no. 2, 2012, pages 167 - 75
DAVID A. RUSLING; KEITH R. FOX: "Small Molecule-Oligonucleotide Conjugates", DNA CONJUGATES AND SENSORS, 2012, pages 75 - 102, XP009186921, DOI: doi:10.1039/9781849734936-00075
DEPETERS E.J.; HOVEY R.C.: "Methods for collecting milk from mice", J. MAMMARY. GLAND. BIOL. NEOPLASIA, vol. 14, no. 4, 2009, pages 397 - 400, XP019771441, DOI: doi:10.1007/s10911-009-9158-0
DEVEREUX, J. ET AL., NUCLEIC ACIDS RESEARCH, vol. 12, no. I, 1984, pages 387
ELSINGHORST E. A.: "Measurement of invasion by gentamicin resistance", METHODS ENZYMOL., vol. 236, 1994, pages 405 - 20
FARDINI Y. ET AL.: "Fusobacterium nucleatum adhesin FadA binds vascular endothelial cadherin and alters endothelial integrity", MOL. MICROBIOL., vol. 82, no. 6, 2011, pages 1468 - 80
FUSS I. ET AL.: "Curr Protoc Immunol.", April 2009, article "Isolation of whole mononuclear cells from peripheral blood and cord blood"
GABITASS R.F. ET AL.: "Elevated myeloid-derived suppressor cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13", CANCER IMMUNOL. IMMUNOTHER., vol. 60, no. 10, 2011, pages 1419 - 30, XP019954939, DOI: doi:10.1007/s00262-011-1028-0
GARCIA-GARCERA M. ET AL.: "A new method for extracting skin microbes allows metagenomic analysis of whole-deep skin", PLOS ONE, vol. 8, no. 9, 2013, pages e74914
INABA, K. ET AL.: "Current Protocols in Immunology", 2001, article "Isolation of dendritic cells"
IRWIN M.H. ET AL.: "Identification of transgenic mice by PCR analysis of saliva", NAT. BIOTECHNOL., vol. 14, no. 9, 1996, pages 1146 - 8, XP002463190
KOWALEWSKI D. ET AL.: "HLA ligandome analysis identifies the underlying specificities of spontaneous antileukemia immune responses in chronic lymphocytic leukemia (CLL", PROC. NATL. ACAD. SCI. USA, vol. 112, no. 2, 2015, pages E166 - 75, XP055207429, DOI: doi:10.1073/pnas.1416389112
KOWALEWSKI D.J.; STEVANOVIC S.: "Biochemical large-scale identification of MHC class I ligands", METHODS MOL. BIOL., vol. 960, 2013, pages 145 - 57
KRAPF MARIE-EVE M ET AL: "Deciphering the aggregation mechanism of bacteria (Shewanella oneidensisMR1) in the presence of polyethyleneimine: Effects of the exopolymeric superstructure and polymer molecular weight", COLLOIDS AND SURFACES. B, BIOINTERFACES, ELSEVIER, AMSTERDAM, NL, vol. 139, 8 December 2015 (2015-12-08), pages 285 - 293, XP029400322, ISSN: 0927-7765, DOI: 10.1016/J.COLSURFB.2015.12.015 *
KUMAR A.; SRIVASTAVA A.: "Cell separation using cryogel-based affinity chromatography", NAT. PROTOC., vol. 5, no. 11, 2010, pages 1737 - 47, XP009170682, DOI: doi:10.1038/nprot.2010.135
LAMPERT I.; BERLYNE G.M.: "Bacterial excretion-rates in the diagnosis of urinary-tract infections", LANCET, vol. 1, no. 7689, 1971, pages 51 - 2
LAOUI, D. ET AL.: "Purification of Tumor-Associated Macrophages (TAM) and Tumor-Associated Dendritic Cells (TADC", BIO-PROTOCOL, vol. 4, no. 22, 2014, pages el294, XP055297718, DOI: doi:10.21769/BioProtoc.1294
LEEKHA ET AL.: "General Principles of Antimicrobial Therapy", MAYO CLIN PROC., vol. 86, no. 2, 2011, pages 156 - 167, XP055372896, DOI: doi:10.4065/mcp.2010.0639
LETOURNEAU J. ET AL.: "In vitro assay of bacterial adhesion onto mammalian epithelial cells", J. VIS. EXP., vol. 51, 2011
M. BOETZER; W. PIROVANO, GENOME BIOL., vol. 13, no. 6, 2012, pages R56
MATSUDA K. ET AL.: "Sensitive quantitative detection of commensal bacteria by rRNA-targeted reverse transcription-PCR", APPL. ENVIRON. MICROBIOL., vol. 73, no. 1, 2007, pages 32 - 9, XP002549226, DOI: doi:10.1128/AEM.01917-07
MENCK K. ET AL.: "Isolation of human monocytes by double gradient centrifugation and their differentiation to macrophages in teflon-coated cell culture bags", J. VIS. EXP., vol. 91, 2014, pages e51554
NEBE-VON-CARON, G. ET AL.: "Analysis of bacterial function by multi-color fluorescence flow cytometry and single cell sorting", JOURNAL OF MICROBIOLOGICAL METHODS, vol. 42, no. 1, 2000, pages 97 - 114, XP002405917, DOI: doi:10.1016/S0167-7012(00)00181-0
OVERWIJK W. ET AL.: "Tumor regression and autoimmunity after reversal of a functionally tolerant state of self-reactive CD8+ T cells", J. EXP. MED., vol. 198, 2003, pages 569 - 80, XP002416108, DOI: doi:10.1084/jem.20030590
PALMER, A. ET AL.: "Chemical decay of an antibiotic inverts selection for resistance", NAT. CHEM. BIOL., vol. 6, no. 2, 2010, pages 105 - 107
PEARSON ET AL., PROC. NATL. ACAD. SCI. USA, vol. 85, 1988, pages 2444
PETERSEN ET AL.: "In vivo pharmacological disease models for psoriasis and atopic dermatitis in drug discovery", BASIC & CLINICAL PHARM & TOXICOLOGY, vol. 99, no. 2, 2006, pages 104 - 115, XP055360626, DOI: doi:10.1111/j.1742-7843.2006.pto_298.x
R.M. ATLAS: "Handbook of Microbiological Media", 2010, CRC PRESS
RINTTILA, T. ET AL.: "Development of an extensive set of 16S rDNA-targeted primers for quantification of pathogenic and indigenous bacteria in faecal samples by real-time PCR", JOURNAL OF APPLIED MICROBIOLOGY, vol. 97, no. 6, 2004, pages 1166 - 77, XP008128526, DOI: doi:10.1111/j.1365-2672.2004.02409.x
ROHDE, K. H. ET AL.: "Mycobacterium tuberculosis Invasion of Macrophages: Linking Bacterial Gene Expression to Environmental Gene Cues", CELL HOST & MICROBE, vol. 2, no. 5, 2007, pages 352 - 364
SCHMID M.C.; VARNER J.A.: "Myeloid cells in the tumor microenvironment: modulation of tumor angiogenesis and tumor inflammation", J. ONCOL., vol. 2010, 2010, pages 201026
STORKUS W. ET AL.: "Identification of T-cell epitopes: rapid isolation of class I-presented peptides from viable cells by mild acid elution", J. IMMUNOTHER. EMPHASIS. TUMOR IMMUNOL., vol. 14, no. 2, 1993, pages 94 - 103, XP009009060
VANKELECOM H.: "Fixation and paraffin-embedding of mouse tissues for GFP visualization", vol. 2009, 2009, COLD SPRING HARB. PROTOC., pages: 10
VREMEC D.; SHORTMAN K.: "The isolation and identification of murine dendritic cell populations from lymphoid tissues and their production in culture", METHODS MOL. BIOL., vol. 415, 2008, pages 163 - 78
WANG E.C. ET AL.: "Cell sorting using immunomagnetic beads", METHODS MOL. BIOL., vol. 80, 1992, pages 347 - 57
WANG N. ET AL.: "Measuring bacterial load and immune responses in mice infected with Listeria monocytogenes", J. VIS. EXP., vol. 54, 2011
WEI ET AL: "Bacterial targeted tumour therapy-dawn of a new era", CANCER LETTERS, NEW YORK, NY, US, vol. 259, no. 1, 11 December 2007 (2007-12-11), pages 16 - 27, XP022385470, ISSN: 0304-3835, DOI: 10.1016/J.CANLET.2007.10.034 *
XU M. ET AL.: "FadA from Fusobacterium nucleatum utilizes both secreted and nonsecreted forms for functional oligomerization for attachment and invasion of host cells", J. BIOL. CHEM., vol. 282, no. 34, 2007, pages 25000 - 9
YUNG ET AL., FEMS, 2007
ZHANG, G. ET AL.: "Anti-melanoma activity of T cells redirected with a TCR-like chimeric antigen receptor", SCI. REP., vol. 4, 2014, pages 3571

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