Administration. As noted above, it was known that resistance had developed very quickly to all the NNRTIs which were under investigation. At that time, the skilled person would have been aware of three strategies to overcome the problem of HIV resistance: increase the dose of the failing drug, which can work in certain circumstances, but often has limited success due to toxicity concerns at higher doses; find a new drug with a different resistance profile; or combine two or more drugs, if possible with complementary resistance profiles. Combination therapy In August 1992, because monotherapy for HIV was failing as a result of resistance, combination therapy was also being considered. When two or more agents are given in combination there can be one of four interactions: indifferent the result is equal to the result of the most effective drug by itself; – antagonistic the result is significantly worse than the indifferent response; – additive the result is to the combined action of each drug used – separately; or synergistic the result is significantly better than the additive response. – The theory behind combination therapy for HIV was that, by targeting the replication pathway of HIV at two different steps or using drugs that had different mechanisms of action on the same enzyme, the chances of inhibiting replication are increased, and hence the chances of developing resistance are reduced. Combination therapy was also thought to have a number of other potential advantages, including the potential to allow lower doses and thus reduce toxicity and increase patient compliance. The idea of combination therapy was accepted as a basis for further investigation in August 1992, and interest in combinations of HIV drugs was growing. The motivation to combine different drugs was described by Prof Seley-Radtke in her first report in the following terms: 1992, researchers and clinicians were desperate to find “In improved treatments for HIV was essentially still a death sentence at that time. Those working in the field were trying everything in an effort to find something that worked.” The Patent The Patent was applied for on 3 August 1993 with an earliest claimed priority date of 7 August 1992. It is entitled as inhibitors of HIV reverse “Benzoxazinones transcriptase”. It was granted on 2 November 2000 and expired on 2 August 2013.
Administration. As noted above, it was known that resistance had developed very quickly to all the NNRTIs which were under investigation. At that time, the skilled person would have been aware of three strategies to overcome the problem of HIV resistance: increase the dose of the failing drug, which can work in certain circumstances, but often has limited success due to toxicity concerns at higher doses; find a new drug with a different resistance profile; or combine two or more drugs, if possible with complementary resistance profiles. Combination therapy In August 1992, because monotherapy for HIV was failing as a result of resistance, combination therapy was also being considered. When two or more agents are given in combination there can be one of four interactions: indifferent – the result is equal to the result of the most effective drug by itself; antagonistic – the result is significantly worse than the indifferent response; additive – the result is to the combined action of each drug used separately; or synergistic – the result is significantly better than the additive response. The theory behind combination therapy for HIV was that, by targeting the replication pathway of HIV at two different steps or using drugs that had different mechanisms of action on the same enzyme, the chances of inhibiting replication are increased, and hence the chances of developing resistance are reduced. Combination therapy was also thought to have a number of other potential advantages, including the potential to allow lower doses and thus reduce toxicity and increase patient compliance. The idea of combination therapy was accepted as a basis for further investigation in August 1992, and interest in combinations of HIV drugs was growing. The motivation to combine different drugs was described by Prof Seley-Radtke in her first report in the following terms: “In 1992, researchers and clinicians were desperate to find improved treatments for HIV was essentially still a death sentence at that time. Those working in the field were trying everything in an effort to find something that worked.” The Patent The Patent was applied for on 3 August 1993 with an earliest claimed priority date of 7 August 1992. It is entitled “Benzoxazinones as inhibitors of HIV reverse transcriptase”. It was granted on 2 November 2000 and expired on 2 August 2013.
UK-Hand-Down-Teva-v-MSD-judgment.docx