Methods for the treatment of an infectious bacterial disease with an anti-lactone or lactone derived signal molecules antibody
| Title: | Methods for the treatment of an infectious bacterial disease with an anti-lactone or lactone derived signal molecules antibody |
|---|---|
| Patent Number: | 8,168,397 |
| Publication Date: | May 01, 2012 |
| Appl. No: | 12/791927 |
| Application Filed: | June 02, 2010 |
| Abstract: | The present invention relates to methods for the control of virulence of infectious bacteria by modulating the extra-cellular concentration of bacterial cell signalling molecules. Derivatives of cell signalling molecules are conjugated to suitable carrier proteins and used to isolate high affinity receptors recognizing the native signal molecule(s). By binding to signalling molecules, the receptors reduce and maintain extra-cellular concentrations of signal molecules below the threshold level that would otherwise result in certain opportunistic pathogens adopting a virulent form, and can transform virulent organisms to non-virulent states. These receptors have applications for the treatment of individuals with susceptibility to infection, the treatment of patients with existing infections, in disease monitoring and management, and in related applications where the host for infection is an animal or plant. |
| Inventors: | Charlton, Keith Alan (Aberdeen, GB); Porter, Andrew Justin Radcliffe (Aberdeen, GB) |
| Assignees: | Haptogen Ltd. (Aberdeen, GB) |
| Claim: | 1. A method of screening a naive human phage display library for an anti-bacterial monoclonal antibody, comprising: conjugating a bacterial lactone or lactone-derived signal molecule to a first carrier molecule to generate an enriched library; and screening said enriched library against the bacterial lactone or lactone-derived signal molecule conjugated to a second, different, carrier molecule to identify a monoclonal antibody that specifically binds to the free soluble form of the bacterial lactone or lactone-derived signal molecule from the enriched library in the presence of conjugated derivatives thereof. |
| Claim: | 2. A method as claimed in claim 1 in which the lactone signal molecule is a homoserine molecule or a peptide thiolactone molecule. |
| Claim: | 3. A method as claimed in claim 2 in which the homoserine lactone molecule has a general formula selected from the group consisting of: [chemical expression included] where n =0 to 12. |
| Claim: | 4. A method as claimed in claim 3 in which the homoserine lactone molecule of general formula I is N-butanoly-L-homoserine lactone (BHL) where n =0, N-dodecanoyl-L-homoserine lactone (dDHL) where n =8, or n-tetradecanoyl-L-homoserine lactone (tDHL) where n =10. |
| Claim: | 5. A method as claimed in claim 3 in which the homoserine lactone molecule of general formula II is N-(-3-oxohexanoyl)-L-homoserine lactone (OHHL) where n =2 or N-(-3-oxododecanoyl)-L-homoserine lactone (OdDHL) where n = 8 . |
| Claim: | 6. A method as claimed in claim 3 in which the homoserine lactone molecule of general formula III is N-(- 3 -hydroxybutanoyl)-L-homoserine lactone (HBHL) where n =0. |
| Claim: | 7. A method as claimed in claim 2 in which the peptide thiolactone has a general formula (IV) as follows: [chemical expression included] where X is any amino acid and n =1 to 10. |
| Claim: | 8. A method as claimed in claim 7 in which the peptide thiolactone molecule is: [chemical expression included] |
| Claim: | 9. A method as claimed in claim 1 in which the lactone-derived signal molecule is a furanosyl borate diester. |
| Claim: | 10. A method as claimed in claim 9 in which the furanosyl borate diester is Auto Inducer-2 (AI-2), [chemical expression included] |
| Claim: | 11. A method as claimed in claim 1 in which the lactone-derived signal molecule is Pro-AI-2 or a C 1 -C 10 saturated or unsaturated carboxylic acid derivative thereof [chemical expression included] |
| Claim: | 12. A method as claimed in claim 1 in which the antibody is a single chain antibody (scAb). |
| Claim: | 13. A method as claimed in claim 1 in which the antibody is an antibody fragment. |
| Claim: | 14. A method as claimed in claim 13 in which the antibody fragment is a single chain variable fragment (scFv) or a single domain fragment. |
| Current U.S. Class: | 435/71 |
| Patent References Cited: | 5254671 October 1993 Chang 6090388 July 2000 Wang 6395282 May 2002 Kende et al. 6703513 March 2004 Quay 6713059 March 2004 Kende et al. 7384639 June 2008 Kende et al. 7812134 October 2010 Charlton et al. 2003/0095985 May 2003 Kende et al. 2004/0147592 July 2004 Quay 2006/0165704 July 2006 Charlton et al. 2007/0218058 September 2007 Charlton et al. 2000186042 July 2000 2002-514092 May 2002 98/58075 December 1998 99/27786 June 1999 01/94543 December 2001 2002/018342 March 2002 2004/014423 February 2004 |
| Other References: | Erickson, D. L., et al., Pseudomonas aeruginosa quorum-sensing systems may control virulence factor expression in the lungs of patients with cystic fibrosis, Infection and Immunity, Apr. 2002;70(4):1783-1790. cited by other European Search Report mailed Dec. 14, 2010. cited by other McElhiney, J., et al., Rapid isolation of a single-chain antibody against the cyanobacterial toxin microcystin-LR by phage display and its use in the immunoaffinity concentration of microcystins from water, Appl Environ Microbiol. Nov. 2002;68(11):5288-95. cited by other Non-final Office Action dated Jun. 17, 2010 in co-pending U.S. Appl. No. 11/568,673. cited by other Final Office Action dated Dec. 6, 2010 in co-pending U.S. Appl. No. 11/568,671. cited by other Non-Final Office Action dated Jul. 13, 2009 in co-pending U.S. Appl. No. 10/599,355. cited by other Final Office Action dated Jan. 19, 2010 in co-pending U.S. Appl. No. 10/599,355. cited by other D'Argenio, et al., Autolysis and autoaggregation in Pseudomonas aeruginosa colony morphology mutants, Journal of Bacteriology, 2002;184(23):6481-6489. cited by other McGrath, et al., Dueling quorum sensing systems in Pseudomonas aeruginosa control the production of the Pseudomonas quinolone signal (PQS), FEMS Microbiology Letters, 2004;230(1):27-34. cited by other Charlton, K., et al., The isolation of super-sensitive anti-hapten antibodies from combinatorial antibody libraries derived from sheep, Biosens Bioelectron., Dec. 2001;16(9-12):639-46. cited by other Chen, X., et al., Structural identification of a bacterial quorum-sensing signal containing boron, Nature, Jan. 31, 2002;415(6871):545-9. cited by other Dong, Y. H., et al., Quenching quorum-sensing-dependent bacterial infection by an N-acyl homoserine lactonase, Nature, Jun. 14, 2001;411(6839):813-7. cited by other Finch, R. G., et al., Quorum sensing: a novel target for anti-infective therapy, J Antimicrob Chemother, Nov. 1998;42(5):569-71. cited by other International Search Report dated Dec. 12, 2003 for International Application No. PCT/GB03/03529. cited by other Mayville, P., et al, Structure-activity analysis of synthetic autoinducing thiolactone peptides from Staphylococcus aureus responsible for virulence, Proc Natl Acad Sci U S A., Feb. 16, 1999;96(4):1218-23. cited by other Moghaddam, A., et al., Identification of scFv antibody fragments that specifically recognise the heroin metabolite 6-monoacetylmorphine but not morphine, J Immunol Methods., Sep. 2003;280(1-2):139-55. cited by other Moghaddam, A., et al., Selection and characterisation of recombinant single-chain antibodies to the hapten Aflatoxin-B1 from naive recombinant antibody libraries, J Immunol Methods., Aug. 1, 2001;254(1-2):169-81. cited by other Reverchon, S., et al., New synthetic analogues of N-acyl homoserine lactones as agonists or antagonists of transcriptional regulators involved in bacterial quorum sensing, Bioorg Med Chem Lett., Apr. 22, 2002;12(8):1153-7. cited by other Wu, H., et al., Detection of N-acylhomoserine lactones in lung tissues of mice infected with Pseudomonas aeruginosa, Microbiology, Oct. 2000;146 ( Pt 10):2481-93. cited by other McCafferty, J., et al., Phage antibodies: filamentous phage displaying antibody variable domains, Nature, Dec. 6, 1990;348(6301):552-4. cited by other Hartman, et al., Quorum sensing: potential means for treating gram-negative infections?, The Lancet 1998;351:848-849. cited by other Notice of Allowance dated Jun. 7, 2010 in co-pending U.S. Appl. No. 10/524,082. cited by other Advisory Action dated Dec. 10, 2008 in co-pending U.S. Appl. No. 10/524,082. cited by other Final Office Action dated Sep. 8, 2008 in co-pending U.S. Appl. No. 10/524,082. cited by other Non-Final Office Action dated Jan. 24, 2008 in co-pending U.S. Appl. No. 10/724.082. cited by other Non-Final Office Action dated Apr. 24, 2009 in co-pending U.S. Appl. No. 10/524,082. cited by other Final Office Action dated Dec. 2, 2009 in co-pending U.S. Appl. No. 10/524,082. cited by other Non-Final Office Action dated Jun. 27, 2011 in U.S. Appl. No. 12/837,588. cited by other Ikeda, Otsukasa, et al., The Control Methods of Quorum Sensing in Gram Negative Bacteria, Utsunomiya University, Department of Applied Chemistry, 2003. cited by other Final Office Action dated Nov. 8, 2011 in co-pending U.S. Appl. No. 12/837,588. cited by other |
| Primary Examiner: | Navarro, Albert |
| Attorney, Agent or Firm: | Pfizer Inc. Miller, John L. Alvarez, Raquel M. |
| Accession Number: | edspgr.08168397 |
| Database: | USPTO Patent Grants |
| Language: | English |
|---|