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Compositions and methods against pseudomonas aeruginosa infections

A technology of Pseudomonas aeruginosa and composition, applied in the field of affinity peptides, can solve serious, immunocompromised, infection and other problems

Pending Publication Date: 2020-07-03
ARIDIS PHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, infection can be serious if the individual also has an underlying disease or condition that renders them immune-compromised

Method used

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  • Compositions and methods against pseudomonas aeruginosa infections
  • Compositions and methods against pseudomonas aeruginosa infections
  • Compositions and methods against pseudomonas aeruginosa infections

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0095] Example 1 - Antibacterial MAb / Antibiotic Combinations in Pneumonia

[0096] Anti-Pseudomonas aeruginosa MEP-binding antibody (called or F429 or erubumab) are effective against acute pneumonia in neutropenic mice and may have cumulative (or compensatory) effects with antibiotics. Aerucin was discovered from a screen of B cells from highly immune patient individuals and selected based on their ability to bind complement to result in complement-dependent killing of Pseudomonas aeruginosa. But we found that for many Pa strains, killing was also observed in the absence of complement.

[0097] preparation:

[0098] 1. Aerucin storage preparation: 29 mg / ml in 10 mM histidine, 150 mM NaCl, 0.02% PS20, pH6.

[0099] 2. Control IgG stock solution: Human IgG1λ (Sigma I5029) from myeloma plasma, 1 mg / mL, dissolved in tris-buffered saline with water-in-oil preservative.

[0100] 3. Tobramycin stock solution: tobramycin sulfate (Sigma T1783).

[0101] 4. Meropenem stock solutio...

Embodiment 2

[0113] Example 2 - Antibacterial MAbs in Opsonophagocytosis Assay (OPA)

[0114] Show Aerucin with OPA TM Induced killing of Pseudomonas aeruginosa by human neutrophils. Design trials to closely mimic Aerucin TM Immune response elicited in vivo by neutrophils to Aerucin TM Complement-mediated opsonophagocytosis of bound Pseudomonas.

[0115] Assays were performed in 96-well microtiter plates supplemented with 1% BSA in MEM solution as assay diluent. The leukemia-derived human cell line HL-60 was used as a source of neutrophils. HL-60 were induced to differentiate into neutrophils by adding 100 mM dimethylformamide (DMF). Neutrophil morphology was verified by FACS by the expression of the Cd11b / Mac-1 marker. Neutrophils were washed, resuspended in assay diluent, counted and diluted to a density of 2.5x10 7 cells / ml. Opsonization was mediated with rabbit serum complement (diluted to a final dilution factor of 1:60 in assay diluent). Resuspend freshly cultured log-phase ...

Embodiment 3

[0118] Example 3 - Testing various antibacterial mAb / antibiotic combinations in opsonophagocytosis assay (OPA)

[0119] The synergistic effect of Aerucin and five antibiotics (ciprofloxacin, colistin, piperacillin, cefepime, aztreonam) was tested in vitro. The assay was performed as described above except that equal volumes (50 [mu]l) of each component were added to the assay wells in the following order: antibody, antibiotic, complement, neutrophils, then bacteria. Bacterial titers (CFU / ml) were measured directly after mixing all components and after 90 min incubation. The readout (% kill) of the test is the extent to which the drug or combination of drugs was able to kill the bacteria during these 90 minutes.

[0120] The test concentrations of Aerucin and antibiotics were chosen such that each component alone showed little to no killing activity in the OPA assay. Means of three independent experiments are shown.

[0121] In the no drug control (Aerucin or antibiotics), a...

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Abstract

A combination of an antibody and other therapeutic that work together in vivo against a pathogenic microbe. The combination can include the antibody with an antibiotic, and / or a therapeutic against adisease. The combination can attack the pathogenic microbe with an efficiency more than either of the components alone, with a synergistic effect, or an effect moderated by one or more modes of actionnot existing with administration of either the antibody or therapeutic alone.

Description

[0001] field of invention [0002] The present invention relates to the prevention and treatment of microbial (such as Pseudomonas aeruginosa) infections and related diseases using affinity polypeptides, including human monoclonal antibodies, in combination with antibiotics that bind microorganisms, such as Pseudomonas aeruginosa (eg cystic fibrosis). Background technique [0003] Pathogenic microorganisms are often the ultimate cause of death in many disease states. Resistance to antibiotics often develops, especially in Pseudomonas bacteria. Antibodies are a surrogate but have also been shown to be insufficient in stopping chronic bacterial infections, even long after secondary humoral immune and cellular responses have matured. [0004] For example, Pseudomonas aeruginosa is an important hospital-acquired pathogen that causes diverse severe acute and chronic infections. Pseudomonas aeruginosa infection is a major health problem for immunocompromised patients and individu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/02C07K16/12
CPCA61K39/40A61K31/496C07K16/1214A61K2039/505A61K31/43A61K31/427A61K31/7036A61K31/47A61K31/545A61K31/407A61K31/546A61K45/06A61P27/00A61P17/00A61P31/00A61P7/00A61K38/12A61K2300/00
Inventor V·L·特鲁翁
Owner ARIDIS PHARMA INC
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