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Heavy Chain and Domain Antibodies

a technology of immunoglobulin and heavy chain, applied in the field of heavy chain immunoglobulins, can solve the problems of large amounts of conventional immunotherapy products, prohibitive wide-scale application of immunotherapy, and inability to meet the needs of patients, so as to reduce the viral load, reduce the effect of viral load and great health benefits

Inactive Publication Date: 2012-06-07
VHSQUARED LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The system effectively reduces viral load and mitigates diarrhea in animal models, offering a cost-effective and sustainable solution for managing enteropathogenic infections by ensuring antibody stability and targeted delivery to the gut.

Problems solved by technology

Unfortunately, there are many problems associated with conventional immunotherapy.
Thus, the associated production costs, including the requirement for purification of the antibodies before administration, are expensive and make their wide scale application as immunotherapeutics prohibitive.
Furthermore, in order to treat a large part of the population, large amounts of conventional immunotherapy products would be required.
If, for example, the therapy was based on colostrum and / or immunised chicken eggs, it would be difficult to provide the required amounts of the immunotherapy products in a large volume.
However, none of these documents disclose the use of heavy chain immunoglobulins or fragments of the VHH or VNAR type or domain antibodies.
One major disadvantage of these known systems is that the use of antibodies or antibody fragments per se (i.e. a harvested protein) in the treatment of a disease in a human may result in the antibody being degraded or digested before they provide the desired health benefits and even before they reach the desired location.
In developing countries, rotavirus induced diarrhoea may cause 600,000 to 870,000 deaths each year and in developed countries, rotavirus disease accounts for immense economic loss.
However, in particular in very young, malnourished children in developing countries the efficacy of such vaccinations might be limited.
However, the high costs of production of these immunoglobulin preparations make their wide scale application as immunotherapeutics prohibitive.
To date, no specific therapy is available for the widespread management of enteropathogenic micro-organisms and viruses.

Method used

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  • Heavy Chain and Domain Antibodies
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Examples

Experimental program
Comparison scheme
Effect test

examples 1 to 3

Generation of Antibody Fragments with Subsequent In-Vitro and In-Vivo Testing

example 1

Selection of Rotavirus Specific Heavy-Chain Antibody Fragments from a Llama Immune Phage Display Library and Production in Yeast

[0216]Rhesus rotavirus strain RRV (serotype G3) was purified, amplified and concentrated as described previously (Svensson L., Finlay B. B., Bass D., Vonbonsdorff C. H., Greenberg H. B. “Symmetrical infection on polarised human intestinal epithelial (CaCo-2) cells”. J Virol. (1991) 65, 4190-4197.

[0217]A llama was immunized subcutaneously and intramuscularly at day 0, 42, 63, 97 and 153 with 5×1012 pfu of rotavirus strain RRV.

[0218]Prior to immunization, the viral particles were taken up in oil emulsion (1:9 V / V, antigen in PBS: Specol (Bokhout, B. A., Van Gaalen, C., and Van Der Heijden, Ph. J. “A selected water-in-oil emulsion: composition and usefulness as an immunological adjuvant”. Vet. Immunol. Immunopath. (1981) 2: 491-500 and Bokhout, B. A., Bianchi, A. T. J., Van Der Heijden, Ph. J., Scholten, J. W. and Stok, W. “The influence of a water-in-oil emul...

example 2

In Vitro Inhibition of Rotavirus

[0226]Bovine Rotavirus Compton CK5 was obtained from the Moredun Institute, Midlothian, Scotland and the BS-C1 cells were purchased from the European Animal Cell Culture Collection.

[0227]The BS-C1 cells were cultured in Earles Modified Essential Medium supplemented with 10% Heat inactivated foetal calf serum, 1% MEM Amino Acids solution (100×), 20 mmol l-1 L-Glutamine, 100 I.U. ml-1 penicillin, 100 μg ml-1 streptomycin and 2.5 μg ml-1 amphotericin B (all from Sigma, US).

[0228]CK5 Rotavirus stock was diluted in Serum Free Medium (SFM) EMEM supplemented with 1% MEM Amino Acids solution (100×), 20 mmol l-1 L-Glutamine and 0.54 ml crystalline trypsin and then 5 ml of diluted seed was added to confluent monolayers of BS-C1 cells in 162 cm2 tissue culture flasks (Costar, UK). The virus was adsorbed onto the cells for one hour at 37° C. then the medium was topped up to 75 ml. The bottles were incubated at 37° C. until complete cytopathic effect was observed....

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PUM

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Abstract

The present invention related to heavy chain immunoglobulins or fragments thereof of the VHH or VNAR type, or domain antibodies (dAbs) of the heavy or light chains of immunoglobulins or fragments thereof, suitable for use in the management of infections, in particular gastrointestinal tract. The present invention also relates to a delivery system comprising these heavy chain immunoglobulins or functional fragments thereof of the VHH or VNAR type, or domain antibodies (dAbs) of the heavy or light chains of immunoglobulins or fragments thereof, and hosts comprising expression vectors encoding for these heavy chain immunoglobulins or functional fragments thereof of the VHH or VNAR type, or domain antibodies (dAbs) of the heavy or light chains of immunoglobulins or fragments thereof. The invention also related to food products and pharmaceutical preparations comprising the delivery system, and method for the preparation of food products according to the invention.

Description

FIELD OF THE INVENTION[0001]The present invention relates to heavy chain immunoglobulins of the VHH or VNAR type or domain antibodies (dAbs) of the heavy or light chains of immunoglobulins or fragments thereof suitable for use in the management of infections by enteropathogenic micro-organisms. The present invention also relates to a delivery system comprising these heavy chain immunoglobulins of the VHH or VNAR type or domain antibodies (dAbs) of the heavy or light chains of immunoglobulins or fragments thereof, and hosts comprising expression vectors encoding for these heavy chain immunoglobulins of the VHH or VNAR type or domain antibodies (dAbs) of the heavy or light chains of immunoglobulins or fragments thereof. The invention further relates to food products or pharmaceutical preparations comprising a delivery system for delivering antibodies to the gastro-intestinal tract (GIT) wherein the antibodies are active in the gut.BACKGROUND OF THE INVENTION[0002]Immunoglobulins (also...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/42A61P31/12C12N15/63C12N1/21C07K16/08C07H21/04A23L33/10A23L33/17A61K39/00
CPCA23F3/14A23F3/34C07K2317/622A23G9/363A23L1/1643A23L1/24A23L1/3014A23L2/39A23L2/52A23V2002/00A23Y2220/17A61K9/0056A61K9/1652A61K2039/505C07K16/10C07K2317/22C07K2317/569A23V2250/5434A23L7/126A23L27/60A23L33/135A23L33/18A23L33/195A61P31/12A61P31/14A23V2400/125
Inventor FRENKEN, LEO GERARDUS JOSEPHHAMMARSTROM, LARS-GORAN LENNARTLEDEBOER, ADRIANUS MARINUS
Owner VHSQUARED LTD
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