Virco Bvba

Virco N.v.

Tibotec-virco Virology Bvba

Janssen Diagnostics Bvba

Brendan Larder

Kurt Hertogs

Stuart Bloor

Rudi Pauwels

Sharon Kemp

Pascale Alfons Rosa Dehertogh

Dechao Wang

Ann Brophy

Richard P Harrigan

Rudy Jean Marc Mortier

Rudi Wilfried Pauwels

The invention provides novel mutations, mutation combinations or mutational profiles of HIV-1 reverse transcriptase and/or protease genes correlated with phenotypic resistance to HIV drugs. More particularly, the present invention relates to the use of genotypic characterization of a target population of HIV and the subsequent correlation of this information to phenotypic interpretation in order to correlate virus mutational profiles with drug resistance. The invention also relates to methods of utilizing the mutational profiles of the invention in databases, drug development, i.e., drug design, and drug modification, therapy and treatment design, clinical management and diagnostic analysis.

Mutational profiles in HIV-1 reverse transcriptase correlated with phenotypic drug resistance

Mutational profiles in HIV-1 protease and reverse transcriptase correlated with phenotypic drug resistance

The present invention concerns methods and systems for improving the accuracy of predicting resistance of a disease to a therapy. In one embodiment of the invention, mean and standard deviation (SD) values of fold change in normalized sensitivity, relative to a laboratory wild type standard pathogen or malignant cell are calculated to demonstrate that the patient samples display inherently different degrees of variation in susceptibility to each therapy. In another embodiment, the 2&#xd7;SD value for each therapy is used as the cut-off between sensitive (within normal susceptible range) and resistant (above normal susceptible range).

Establishment of biological cut-off values for predicting resistance to therapy

The present invention relates to a method for mutation analysis of the HIV pol gene of HIV virions comprising amplifying virion RNA or DNA via nested PCR using outer primers as represented in SEQ ID No. 1 and 2, amplifying said PCR product via nested PCR using a 5' and 3&#x2032; primer chosen from the inner primers SEQ ID No. 3, 4, 5, and 6, and sequencing this secondary obtained PCR product using at least one sequencing primer chosen from any of SEQ ID No. 7 to 12 or variants thereof. In the alternative, at least one secondary sequencing primer may be used chosen from any of SEQ ID No. 13 to 24. The benefit of the sequences present in the invention resides in the fact that, with the aid of the oligonucleotides, the sequences of all presently known HIV subtypes and all mutations of the pol gene presently known to yield resistance towards antiretroviral therapy can be determined. The present invention also relates to kits for performing such a method as well as primers for performing the same.

Method for mutation detection in HIV-1 using pol sequencing

The present invention concerns methods for measuring drug resistance by correlating genotypic information with phenotypic profiles. In one embodiment, a method for interpreting genotypic information is described wherein a genetic code is generated from a patient sample, a list of mutations known or suspect to play a role in the development of resistance to one or more drugs is obtained from the generated genetic code, a genotype database is interrogated for previous samples with similar mutations relating to said one or more drugs, a phenotype for said sample is located in a phenotype database, the mean change in inhibition is determined based on all the examples located in said phenotype database, a distribution of sensitivities of one or more drugs suitable for treating a specific indication is determined.

Methods for measuring therapy resistance

A method and system for predicting the resistance of a disease to a therapeutic agent is provided. Further provided is a method and system for designing a therapeutic treatment agent for a patient afflicted with a disease. Specifically, the methods use a trained neural network to interpret genotypic information obtained from the disease. The trained neural network is trained using a database of known or determined genotypic mutations that are correlated with phenotypic therapeutic agent resistance. The present invention also provides methods and systems for predicting the probability of a patient developing a genetic disease. A trained neural network for making such predictions is also provided.

Method and system for predicting resistance of a disease to a therapeutic agent using a neural network

The present invention relates to a method of for mutation analysis of the HIV pol gene of HIV-1 virions comprising amplifying viral RNA or DNA via nested PCR using outer primers as represented in SEQ ID No: 1 and 2, amplifying said PCR product via nested PCR using a 5&prime; and 3&prime; primer chosen from the inner primers SEQ ID No: 3, 4, 5, and 6, and sequencing this secondary obtained PCR product using at least one sequencing primer chosen from any of SEQ ID No: 7 to 12 or variants thereof. In the alternative, at least one secondary sequencing primer may be used chosen from any of SEQ ID No: 13 to 24. The present invention also relates to kits for performing such a method as well as primers for performing the same.

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Cambridge, United Kingdom

Brendan Larder