Novel antibiotics for the treatment of tuberculosis

The Challenge
According to the World Health Organisation (WHO) one-third of the world's population is currently infected with the tuberculosis (TB) bacillus. Each year about 1.7 million people die from tuberculosis (TB) and someone in the world is newly infected with TB bacilli every second.
However, people infected with TB bacilli will not necessarily become sick with the disease. The immune system "walls off" the TB bacilli which, protected by a thick waxy coat, can lie dormant for years. But when someone's immune system is weakened, the chances of becoming sick are higher (e. g. people infected with HIV are much more likely to develop TB).
Until 50 years ago, there were no medicines to cure TB. Now, strains that are resistant to a single drug have been documented; what is more, strains of TB resistant to all major anti-TB drugs have emerged. A particularly dangerous form of drug-resistant TB is multidrug-resistant TB (MDR-TB), which is defined as the disease caused by TB bacilli resistant to at least isoniazid and rifampicin, the two most powerful anti-TB drugs. Rates of MDR-TB are high in some countries, especially in the former Soviet Union.
In conclusion, there is an urgent demand for new alternative antibiotics to combat the tuberculosis pathogens.


	Macrophages and Tuberculosis pathogens. (Image: Max Planck Institute for Infection Biology)

The Technologies
All of the following substances are showing strong antibacterial effects against gram-positive bacteria, especially against mycobacteria.

TO 10-00006: New O-(aminoalkyle)-derivatives based on monosaccharides
This invention discloses new O-(aminoalkyle)-derivatives from monosaccharides, a method for its production, as well as their application as antibiotics. The monosaccharide scaffold allows these new substances siderophore-like functions. In addition to the anti-mycobacterial an anti-fungal effect is proven. These substances could be used for the development of a new class of antibiotics.

Patent situation: German patent application is pending (DE 199 42 864 A 1).

Further Reading: Heggemann, S. et al. 2001. New artificial siderophores based on a monosaccharide scaffold. BioMetals 14: 1-11.

TO 10-00042: Lydiamycins
This invention encloses new selectively active substances for the treatment of diseases caused by mycobacteria, a method for its production, as well as its application. These substances isolated from Streptomyces lydicus are called lydiamycins A – D and belong to the class of cyclodepsipeptides Lydiamycins are showing strong antibacterial properties without cytotoxic effects. Due to this lydiamycins are interesting drug candidates for the therapy of tuberculosis and also for leprosy.

Patent situation: German patent is granted (DE 102004046142).

Further Reading: Huang, X. et al. 2006. Lydiamycins A-D: Cyclodepsipeptides with Antimycobacterial Properties. Angew. Chem. Int. Ed. 45: 3067-3072.

TO 10-00214: Thuggacines
Thuggacines are novel macrocyclic lactones that have been isolated from different Myxobacteria belonging to the genera Sorangium and Chondromyces. The compounds are showing strong antibacterial properties especially against mycobacteria and nocardia. The multiple glycosylated macrocycles are promising lead structures for drug development.

Patent situation: German patent granted (DE 19542786), new European patent application pending (EP06125361.3).

Commercial Opportunity

New alternative antibiotics like those mentioned above are urgently needed to combat tuberculosis especially caused by an increasing number of multi-resistant pathogens and to cope with the re-increasing number of tuberculosis infections worldwide.
Advantages of the offered novel compounds are
- new lead structures for derivatisation
- patent protection extendable due to future optimized derivatives
- proven anti-mycobacterial activity, partially even against multidrug-
resistant Mycobacterium tuberculosis strains
- low cytotoxicity already shown for most of the drug candidates
- easy and cost effective biotechnological production by fermentation
A cooperation agreement with option for an exclusive or non-exclusive license or a license agreement (exclusive or non-exclusive) are possible deals.