Patents on antivirulence therapies

Table 4 Patents concerning the inhibition of multidrug resistance systems

Patent title	Description	Application date	Inventors	Publication number
Method for screening for non-tetracycline efflux pump inhibitors	Provides screening methods for inhibitors of microbial efflux pumps and pharmaceutical compositions containing such efflux pump inhibitors as well as methods for treating microbial infections by use of these compositions	1995	Trias; Joaquim Chamberland; Suzanne Hecker; Scott J Lee; Ving J	US5989832 A
Efflux pump inhibitors	Provides screening methods for inhibitors of microbial efflux pumps and pharmaceutical compositions containing such efflux pump inhibitors. Also provides methods for treating microbial infections using those compositions	1996	Trias Joaquim; Hecker Scott J; Chamberland Suzanne; Lee Ving J	CA2217865
Methods and compositions for reducing bacterial tolerance of disinfectants and organic solvents	Methods and compositions useful for manipulating bacterial resistance to non-antibiotic antibacterial compositions, disinfectants and organic solvents, and for rendering bacterial cells susceptible to non-antibiotic antibacterial compositions	1997	Levy Stuart B	WO9917607 (A2)
Methods and compositions for reducing bacterial tolerance to antibacterials, disinfectants and organic solvents	Methods and compositions useful for manipulating bacterial resistance to non-antibiotic antibacterial compositions, disinfectants and organic solvents, and methods for rendering bacterial cells susceptible to non-antibiotic antibacterial compositions	1997	Levy Stuart B	US6068972 (A)
Inhibitors of cellular efflux pumps of microbes	Describes compounds that are inhibitors of efflux pump in bacteria. Also describes methods of preparing and using such compounds and the pharmaceutical compositions that include such compounds	2001	De Souza Noel John; Patel Mahesh Vithalbhai; Gupte Shrikant V; Upadhyay Dilip J; Shukla Milind Chintaman; Chaturvedi Nishith C; Bhawsar Satish B; Nair Sheela Chandresekharan; Jafri Mohammed A; Khorakiwala Habil Fakhruddin	US2002177559 (A1)
Drug discovery and increased potency of antiseptics and disinfectants based on high extracellular pH, the disablement of cellular efflux pumps, and the unexpected synergism therebetween	Methods for increasing the therapeutic potency of amphipathic compounds, e.g., antiseptics and disinfectants, and the exploitation of these discoveries in the screening of small molecules, and libraries thereof, for biological activity in prokaryotes and eukaryotes	2002	Lewis Kim; Hsieh Peichung	US2003118541 (A1)
Methods to study and mechanisms of biofilm-related antibiotic resistance	Discloses various genes that encode proteins shown to play a role in microbial resistance of an organism in a biofilm and homologs thereof. Describes methods of identifying a compound that modulates microbial resistance of an organism in a biofilm and also genes encoding proteins that play a role in biofilm resistance	2002	O'Toole George A; Mah Thien-Fah	US2003166030 (A1)
Minicell-based gene therapy	Provides compositions and methods for the production of achromosomal and anucleate cells useful for applications such as diagnostic and therapeutic uses, as well as research tools and agents for drug discovery	2002	Sabbadini Roger A; Berkley Neil; Surber Mark W	US2003199088 (A1)
Potentiators of antibacterial activity	The invention relates to compounds that potentiate the activity of antibacterials, compositions useful in treating bacterial infection, and related methods. Also relates to a method of inhibiting bacterial efflux of an antibiotic, thereby increasing its efficacy	2004	Grossman Trudy H	US20040887719 20040709
Substituted polyamines as inhibitors of bacterial efflux pumps	Methods of treating bacterial infections, including those caused by multidrug resistant bacteria, by using polyamine efflux pump inhibiting compounds, optionally in combination with other drugs such as antibiotics. The pharmaceutical compositions of the polyamines are also reported	2004	Nelson Mark L; Alekshun Michael N	US2004204378 (A1)
Essential and important genes of Pseudomonas aeruginosa and the use thereof to design or identify antibacterial agents	Database of candidate essential genes in Pseudomonas aeruginosa, and other important genes that, when mutated, produce a growth attenuated phenotype. The invention includes methods for confirming the need for or importance of candidate genes, methods for using those genes to screen for new antibacterial drugs, the antibacterial agents identified using the disclosed methods, and also methods of using the same for treating and preventing Pseudomonas infection	2005	Bruce Kim F; Warrener Paul; Hou Kevin	US2007196829 (A1)
Method for increasing the susceptibility of peptide deformylase inhibitors by using efflux pump inhibitors	Provides methods and compositions for increasing the susceptibility of PDF inhibitors against Gram-negative organisms by using efflux pump inhibitors	2005	Dean Charles Richard; Ryder Neil Stewart	CA2569681
Products and methods for in vivo secretion of monatin	Provides products and methods for the in vivo production of monatin sweetener. The products include microorganisms that are genetically modified to secrete or to improve secretion of monatin, to produce monatin, and to both secrete/ improve secretion and produce monatin	2006	Laplaza Jose; Anderson James C; Desouza Mervyn L; Hicks Paula M; Kollmann Sherry R	WO2006113897
Rhamnose-inducible expression systems and methods	Describes rhamnose-inducible expression constructs which may include at least one rhamnose-inducible regulatory element expressing a regulatory protein and one promoter that is inducible by the regulatory protein. An open reading frame expressing a protein of interest may be placed under control of the promoter. Also describes optimized Shine-Dalgarno sequences for use with the promoter	2006	Surber Mark W	US2007122881 (A1)
Enhancement of tigecycline potency using efflux pump inhibitors	Discloses Efflux Pump Inhibitor (EPI) compounds that can be co-administered with antimicrobial agents for the treatment of infections caused by drug resistant pathogens and methods of treatment and pharmaceutical compositions for co-administering tigecylcine with an EPI	2007	Glinka Tomasz; Bostian Keith; Lomovskaya Olga; Surber Mark; Sun Dongxu	US20070832626 20070801
Method or agent for inhibiting the function of efflux pump of Pseudomonas aeruginosa	Discloses a method comprised of modifying any amino acid residue selected from 100th to 109th and 311th to 320th amino acid residues in an amino acid sequence for mature OprM protein, as well as an agent for inhibiting the function of an efflux pump of Pseudomonas aeruginosa with good efficiency. Further disclosed is a method for screening the agent	2007	Yoshihara Eisaku; Inoko Hidatoshi	CA2641988
Method or agent for inhibiting the function of efflux pump of Pseudomonas aeruginosa	Provides a method for inhibiting the function of the drug efflux pump of Pseudomonas aeruginosa, comprising modification of any amino acid residue selected from 100th to 109th or 311th to 320th amino acid residues in the amino acid sequence of mature OprM protein. Also reports an agent with such inhibitory effect, as well as a screening method	2007	Yoshihara Eisaku; Inoko Hidatoshi	WO2007/091395
Microbial production of aromatic acids	Method for the microbial production of aromatic acids from a fermentable carbon substrate using a host cell capable of producing said aromatic acid, and comprising an efflux pump for said aromatic acid. A preferred host cell comprises a member of the proton-dependent resistance/nodulation/cell division (RND) family of efflux pumps	2007	Wery Jan	US2007259409 (A1)
Near-infrared electromagnetic modification of cellular steady-state membrane potentials	Discloses systems and methods for applying near-infrared optical energies and dosimetries to alter the bioenergetic steady-state trans-membrane and mitochondrial potentials (DeltaPsi-steady) of all irradiated cells through an optical depolarization effect. This membrane depolarization provides the ability to potentiate antimicrobial, antifungal and/or antineoplastic drugs against only targeted undesirable cells	2007	Bornstein Eric	US2008139992
In vivo gene sensors	Describes methods and compositions for the detection of target genes that permit the selective expression of an effector gene in those cells expressing the target gene, thus selectively targeting these cells for treatment or elimination. The methods and compositions described may also permit the selective expression of an agent such as a therapeutic gene product, in a targeted population of cells	2009	Collins James J; Lu Timothy Kuan-Ta	WO2009/137136
Methods of reducing microbial resistance to drugs	Provides methods of treating infection, screening for inhibitors of AcrAB-like efflux pumps, and enhancing antimicrobial activity of drugs. Pharmaceutical composition comprising an inhibitor of an AcrAB-like efflux pump and an antimicrobial agent are also provided	2009	Oethinger Margaret; Levy Stuart B	US2009298873
Minicells displaying antibodies or derivatives thereof and comprising biologically active compounds1	Minicells are used to deliver biologically active compounds, including polypeptides, nucleic acids, small molecules, drug molecules, and chemotherapeutic agents. In some cases, the minicell displays ligands or binding moieties that target the minicell to a desired host cell	2011	Sabbadini Roger A; Berkley Neil; Surber Mark W; Klepper Robert	US20070725196 20070316

¹Those published from 2010 onwards are highlighted.