COMPOSITIONS COMPRISING ANIMAL HEMOGLOBIN
Methods and compositions related to pharmaceutical agents, pharmaceutical compositions, and solid dosage forms comprising animal hemoglobin and bacteria or agents of bacterial origin are provided herein.
1 . A bacterial composition comprising:
(a) bacteria and/or microbial extracellular vesicles (mEVs); and
(b) animal hemoglobin.
2 . The bacterial composition of claim 1 , wherein the animal hemoglobin is porcine hemoglobin.
3 . The bacterial composition of claim 1 or 2 , wherein the bacterial composition comprises bacteria.
4 . The bacterial composition of claim 3 , wherein the bacteria are hemoglobin-dependent bacteria.
5 . The bacterial composition of claim 3 or 4 , wherein the bacteria are of the genus Actinomyces, Alistipes , Anaerobutyricum, Bacillus, Bacteroides, Cloacibacillus, Clostridium, Collinsella , Cutibacterium, Eisenbergiella, Erysipelotrichaceae, Eubacterium/Mogibacterium, Faecalibacterium, Fournierella, Fusobacterium, Megasphaera, Parabacteroides, Peptoniphilus, Peptostreptococcus, Porphyromonas, Prevotella, Propionibacterium , Rarimicrobium, Shuttleworthia, Turicibacter , or Veillonella.
6 . The bacterial composition of claim 5 , wherein the bacteria are of the genus Prevotella.
7 . The bacterial composition of claim 6 , wherein the bacteria are Prevotella albensis, Prevotella amnii, Prevotella bergensis, Prevotella bivia, Prevotella brevis, Prevotella bryantii, Prevotella buccae, Prevotella buccalis, Prevotella copri, Prevotella dentalis, Prevotella denticola, Prevotella disiens, Prevotella histicola, Prevotella intermedia, Prevotella maculosa, Prevotella marshii, Prevotella melaninogenica, Prevotella micans, Prevotella multiformis, Prevotella nigrescens, Prevotella oralis, Prevotella oris, Prevotella oulorum, Prevotella pallens, Prevotella salivae, Prevotella stercorea, Prevotella tannerae, Prevotella timonensis, Prevotella jejuni, Prevotella aurantiaca, Prevotella baroniae, Prevotella colorans, Prevotella corporis, Prevotella dentasini, Prevotella enoeca, Prevotella falsenii, Prevotella fusca, Prevotella heparinolytica, Prevotella loescheii, Prevotella multisaccharivorax, Prevotella nanceiensis, Prevotella oryzae, Prevotella paludivivens, Prevotella pleuritidis, Prevotella ruminicola, Prevotella saccharolytica, Prevotella scopos, Prevotella shahii, Prevotella zoogleoformans , or Prevotella veroralis.
8 . The bacterial composition of claim 6 , wherein the bacteria are of the species Prevotella histicola.
9 . The bacterial composition of claim 6 , wherein the Prevotella comprise at least 99% genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of the Prevotella Strain B 50329 (NRRL accession number B 50329).
10 . The bacterial composition of claim 6 , wherein the Prevotella comprise at least 99% genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of the Prevotella Strain C (ATTC Deposit Number PTA-126140).
11 . The bacterial composition of claim 6 , wherein the Prevotella are Prevotella Strain B 50329 (NRRL accession number B 50329).
12 . The bacterial composition of claim 6 , wherein the Prevotella are Prevotella Strain C (ATTC Deposit Number PTA-126140).
13 . The bacterial composition of claim 6 , wherein the Prevotella bacteria (i) comprise one or more proteins listed in Table 3, and/or (ii) are substantially free of a protein listed in Table 4.
14 . The bacterial composition of any one of claims 3 to 13 , wherein the bacterial are live, attenuated, or dead.
15 . The bacterial composition of any one of claims 3 to 14 , wherein the bacteria are lyophilized bacteria.
16 . The bacterial composition of any one of claims 1 - 15 , wherein the bacterial composition comprises mEVs.
17 . The bacterial composition of claim 16 , wherein the mEVs are secreted mEVs (smEVs).
18 . The bacterial composition of claim 16 , wherein the mEVs are processed mEVs (pmEVs).
19 . The bacterial composition of any one of claims 16 to 18 , wherein the mEVs are from hemoglobin-dependent bacteria.
20 . The bacterial composition of any one of claims 16 to 19 , wherein the mEVs are from bacteria of the genus Actinomyces, Alistipes , Anaerobutyricum, Bacillus, Bacteroides, Cloacibacillus, Clostridium, Collinsella , Cutibacterium, Eisenbergiella, Erysipelotrichaceae, Eubacterium/Mogibacterium, Faecalibacterium, Fournierella, Fusobacterium, Megasphaera, Parabacteroides, Peptoniphilus, Peptostreptococcus, Porphyromonas, Prevotella, Propionibacterium , Rarimicrobium, Shuttleworthia, Turicibacter , or Veillonella.
21 . The bacterial composition of claim 20 , wherein the mEVs are from bacteria of the genus Prevotella.
22 . The bacterial composition of claim 21 , wherein the bacteria are Prevotella albensis, Prevotella amnii, Prevotella bergensis, Prevotella bivia, Prevotella brevis, Prevotella bryantii, Prevotella buccae, Prevotella buccalis, Prevotella copri, Prevotella dentalis, Prevotella denticola, Prevotella disiens, Prevotella histicola, Prevotella intermedia, Prevotella maculosa, Prevotella marshii, Prevotella melaninogenica, Prevotella micans, Prevotella multiformis, Prevotella nigrescens, Prevotella oxalis, Prevotella oris, Prevotella oulorum, Prevotella pallens, Prevotella salivae, Prevotella stercorea, Prevotella tannerae, Prevotella timonensis, Prevotella jejuni, Prevotella aurantiaca, Prevotella baroniae, Prevotella colorans, Prevotella corporis, Prevotella dentasini, Prevotella enoeca, Prevotella falsenii, Prevotella fusca, Prevotella heparinolytica, Prevotella loescheii, Prevotella multisaccharivorax, Prevotella nanceiensis, Prevotella oryzae, Prevotella paludivivens, Prevotella pleuritidis, Prevotella ruminicola, Prevotella saccharolytica, Prevotella scopos, Prevotella shahii, Prevotella zoogleoformans , or Prevotella veroralis.
23 . The bacterial composition of claim 21 or 22 , wherein the mEVs are from bacteria of the species Prevotella histicola.
24 . The bacterial composition of claim 21 , wherein the Prevotella comprise at least 99% genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of the Prevotella Strain B 50329 (NRRL accession number B 50329).
25 . The bacterial composition of claim 21 , wherein the Prevotella comprise at least 99% genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of the Prevotella Strain C (ATTC Deposit Number PTA-126140).
26 . The bacterial composition of claim 21 , wherein the Prevotella are Prevotella Strain B 50329 (NRRL accession number B 50329).
27 . The bacterial composition of claim 21 , wherein the Prevotella are Prevotella Strain C (ATTC Deposit Number PTA-126140).
28 . The bacterial composition of claim 21 , wherein the Prevotella bacteria (i) comprise one or more proteins listed in Table 3, and/or (ii) are substantially free of a protein listed in Table 4.
29 . The bacterial composition of any one of claims 16 to 39 , wherein the mEVs are lyophilized mEVs.
30 . The bacterial composition of any one of claims 1 to 29 , further comprising a cryoprotectant.
31 . A solid dosage form comprising:
(i) a pharmaceutical agent, wherein the pharmaceutical agent comprises
(a) bacteria and/or microbial extracellular vesicles (mEVs); and
(b) animal hemoglobin; and
(ii) at least one diluent, at least one lubricant, at least one glidant, and/or at least one disintegration agent.
32 . A solid dosage form comprising:
(i) a pharmaceutical agent, wherein the pharmaceutical agent comprises
(a) bacteria and/or microbial extracellular vesicles (mEVs); and
(b) animal hemoglobin; and
(ii) at least one diluent, at least one lubricant, and/or at least one glidant.
33 . A method of preventing or treating a disease in a subject comprising administering to the subject a pharmaceutical composition of any one of claims 1 to 30 .
34 . A method of preventing or treating a disease in a subject comprising administering to the subject a solid dosage form of claim 31 .
35 . Use of a pharmaceutical composition of any one of claims 1 to 30 for the treatment or prevention of a disease in a subject.
36 . Use of a solid dosage form of claim 31 for the treatment or prevention of a disease in a subject.
37 . A method of preparing a solid dosage form, the method comprising:
(A) combining into a pharmaceutical composition:
(i) a pharmaceutical agent, wherein the pharmaceutical agent comprises
(a) bacteria and/or microbial extracellular vesicles (mEVs); and
(b) animal hemoglobin; and
(ii) at least one diluent, at least one lubricant, at least one glidant, and/or at least one disintegration agent.
(B) compressing the pharmaceutical composition into a solid dosage form.
38 . A method of preparing a solid dosage form, the method comprising combining into a pharmaceutical composition:
(i) a pharmaceutical agent, wherein the pharmaceutical agent comprises
(a) bacteria and/or microbial extracellular vesicles (mEVs); and
(b) animal hemoglobin; and
(ii) at least one diluent, at least one lubricant, and/or at least one glidant.
39 . A method of testing a pharmaceutical composition comprising bacteria and/or microbial extracellular vesicles (mEVs), the method comprising performing an assay to detect the presence of an animal hemoglobin in the pharmaceutical composition.
40 . The method of claim 39 , wherein the animal hemoglobin is porcine hemoglobin.
41 . The method of claim 39 or 40 , wherein the animal hemoglobin protein is detected using an antibody specific for the animal hemoglobin protein, HPLC or UPLC.
42 . The method of any one of claims 39 to 41 , wherein the pharmaceutical composition comprises bacteria.
43 . The method of claim 42 , wherein the bacteria are hemoglobin-dependent bacteria.
44 . The method of claim 42 or 43 , wherein the bacteria are of the genus Actinomyces, Alistipes , Anaerobutyricum, Bacillus, Bacteroides, Cloacibacillus, Clostridium, Collinsella , Cutibacterium, Eisenbergiella, Erysipelotrichaceae, Eubacterium/Mogibacterium, Faecalibacterium, Fournierella, Fusobacterium, Megasphaera, Parabacteroides, Peptoniphilus, Peptostreptococcus, Porphyromonas, Prevotella, Propionibacterium , Rarimicrobium, Shuttleworthia, Turicibacter , or Veillonella.
45 . The method of claim 44 , wherein the bacteria are of the genus Prevotella.
46 . The method of claim 45 , wherein the bacteria are Prevotella albensis, Prevotella amnii, Prevotella bergensis, Prevotella bivia, Prevotella brevis, Prevotella bryantii, Prevotella buccae, Prevotella buccalis, Prevotella copri, Prevotella dentalis, Prevotella denticola, Prevotella disiens, Prevotella histicola, Prevotella intermedia, Prevotella maculosa, Prevotella marshii, Prevotella melaninogenica, Prevotella micans, Prevotella multiformis, Prevotella nigrescens, Prevotella oxalis, Prevotella oris, Prevotella oulorum, Prevotella pallens, Prevotella salivae, Prevotella stercorea, Prevotella tannerae, Prevotella timonensis, Prevotella jejuni, Prevotella aurantiaca, Prevotella baroniae, Prevotella colorans, Prevotella corporis, Prevotella dentasini, Prevotella enoeca, Prevotella falsenii, Prevotella fusca, Prevotella heparinolytica, Prevotella loescheii, Prevotella multisaccharivorax, Prevotella nanceiensis, Prevotella oryzae, Prevotella paludivivens, Prevotella pleuritidis, Prevotella ruminicola, Prevotella saccharolytica, Prevotella scopos, Prevotella shahii, Prevotella zoogleoformans , or Prevotella veroralis.
47 . The method of claim 45 or 46 , wherein the bacteria are of the species Prevotella histicola.
48 . The method of claim 45 , wherein the Prevotella bacteria comprise at least 99% genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of the Prevotella Strain B 50329 (NRRL accession number B 50329).
49 . The method of claim 45 , wherein the Prevotella comprise at least 99% genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of the Prevotella Strain C (ATTC Deposit Number PTA-126140).
50 . The method of claim 45 , wherein the Prevotella are Prevotella Strain B 50329 (NRRL accession number B 50329).
51 . The method of claim 45 , wherein the Prevotella are Prevotella Strain C (ATTC Deposit Number PTA-126140).
52 . The method of claim 45 , wherein the Prevotella bacteria (i) comprise one or more proteins listed in Table 3, and/or (ii) are substantially free of a protein listed in Table 4.
53 . The method of any one of claims 39 to 52 , wherein the bacteria are live, attenuated, or dead.
54 . The method of any one of claims 39 to 53 , wherein the bacteria are lyophilized bacteria.
55 . The method of any one of claims 39 to 54 , wherein the pharmaceutical composition comprises mEVs.
56 . The method of claim 55 , wherein the mEVs are secreted mEVs (smEVs).
57 . The method of claim 55 , wherein the mEVs are processed mEVs (pmEVs).
58 . The method of any one of claims 55 to 57 , wherein the mEVs are from hemoglobin-dependent bacteria.
59 . The method of any one of claims 55 to 58 , wherein the mEVs are from bacteria of the genus Actinomyces, Alistipes , Anaerobutyricum, Bacillus, Bacteroides, Cloacibacillus, Clostridium, Collinsella , Cutibacterium, Eisenbergiella, Erysipelotrichaceae, Eubacterium/Mogibacterium, Faecalibacterium, Fournierella, Fusobacterium, Megasphaera, Parabacteroides, Peptoniphilus, Peptostreptococcus, Porphyromonas, Prevotella, Propionibacterium , Rarimicrobium, Shuttleworthia, Turicibacter , or Veillonella.
60 . The method of claim 59 , wherein the mEVs are from bacteria of the genus Prevotella.
61 . The method of claim 60 , wherein the bacteria are Prevotella albensis, Prevotella amnii, Prevotella bergensis, Prevotella bivia, Prevotella brevis, Prevotella bryantii, Prevotella buccae, Prevotella buccalis, Prevotella copri, Prevotella dentalis, Prevotella denticola, Prevotella disiens, Prevotella histicola, Prevotella intermedia, Prevotella maculosa, Prevotella marshii, Prevotella melaninogenica, Prevotella micans, Prevotella multiformis, Prevotella nigrescens, Prevotella ovalis, Prevotella oris, Prevotella oulorum, Prevotella pallens, Prevotella salivae, Prevotella stercorea, Prevotella tannerae, Prevotella timonensis, Prevotella jejuni, Prevotella aurantiaca, Prevotella baroniae, Prevotella colorans, Prevotella corporis, Prevotella dentasini, Prevotella enoeca, Prevotella falsenii, Prevotella fusca, Prevotella heparinolytica, Prevotella loescheii, Prevotella multisaccharivorax, Prevotella nanceiensis, Prevotella oryzae, Prevotella paludivivens, Prevotella pleuritidis, Prevotella ruminicola, Prevotella saccharolytica, Prevotella scopos, Prevotella shahii, Prevotella zoogleoformans , or Prevotella veroralis.
62 . The method of claim 60 or 61 , wherein the mEVs are from bacteria of the species Prevotella histicola.
63 . The method of claim 60 , wherein the Prevotella comprise at least 99% genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of the Prevotella Strain B 50329 (NRRL accession number B 50329).
64 . The method of claim 60 , wherein the Prevotella comprise at least 99% genomic, 16S and/or CRISPR sequence identity to the nucleotide sequence of the Prevotella Strain C (ATTC Deposit Number PTA-126140).
65 . The method of claim 60 , wherein the Prevotella are Prevotella Strain B 50329 (NRRL accession number B 50329).
66 . The method of claim 60 , wherein the Prevotella are Prevotella Strain C (ATTC Deposit Number PTA-126140).
67 . The method of claim 60 , wherein the Prevotella bacteria (i) comprise one or more proteins listed in Table 3, and/or (ii) are substantially free of a protein listed in Table 4.