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Inventions are patentable according to the German Patent Law (and the European Patent Convention), if they are new, involve an inventive step and are susceptible to industrial application. Living matter and processes performed therewith are likewise patentable.
The issue of patents on inventions of genomic research is the subject of intense debate. The exchange of scientific information and access to new technologies are critical to biomedical research. Similarly, strong patent laws are necessary to encourage innovation. Thus, it is time to balance access and incentive. Patents claiming genes with purely speculative utilities should not be issued, and they possibly limit research. Reasonable access to properly patented genes should be provided for research, and exclusive positions maintained for commercial utilities. This will promote ready access to genomic information and fundamental technologies, while optimizing the discovery and disclosure of basic advances in biomedical research.
Successful transcatheter closure of a calcified patent ductus arteriosus was performed in a symptomatic 78 year old man. Cardiac catheterization revealed a left to right shunt across the patent ductus arteriosus with a pulmonary to systemic flow ratio of 2.8:1. Calcification of the ductus and severe lung disease increased the risk of surgical patent ductus arteriosus closure. A 17 mm Rashkind double umbrella was positioned in the ductus percutaneously by way of the femoral vein. After closure of the ductus there was marked hemodynamic improvement and the patient was discharged with improved exercise tolerance. Transcatheter closure of patent ductus arteriosus may be a viable option for the elderly patient too sick to withstand cardiovascular surgery.
OBJECTIVES: Evaluation of the immediate and long-term efficacy of a novel method of transvenous closure of the patent ductus arteriosus was the purpose of this study. BACKGROUND: In 1981 at the First Moscow Hospital, a new method of transvenous patent ductus arteriosus closure with the Botallooccluder was developed. METHODS: Transvenous closure of the patent ductus arteriosus with the Botallooccluder was carried out in 273 patients. All patients were regularly followed up as outpatients at intervals of 3, 6 and 12 months after intervention. A total of 171 patients were examined at a mean of 3.2 +/- 1.1 years (range 1 to 8) after the procedure. Late evaluation with cardiac catheterization was performed in 62 patients (36%); 50 (29%) of these 62 also underwent right heart catheterization. RESULTS: Successful implantation was achieved in 266 patients (97%). The late follow-up findings testify to the favorable clinical course, with disappearance of the continuous murmur and regression of the electrocardiographic signs of ventricular overloading in the vast majority of patients. In no case after complete patent ductus arteriosus closure was a late ductus recanalization observed. No patient had even a minor degree of postprocedural lower extremity venous damage. In 29 patients (24%), the femoral artery was imaged by ultrasonography at late follow-up, without evidence of any vascular abnormality. CONCLUSIONS: The clinical data suggest high long-term efficacy and reliability of this technique. Introducer sheaths (12F to 16F outer diameter) did not cause any long-term entry site sequelae.
OBJECTIVES: This study was designed to assess the safety, efficacy, medium-term outcome, and complications of patent ductus arteriosus (PDA) stenting in duct-dependent pulmonary circulation. BACKGROUND: Patent ductus arteriosus stenting has been proposed as an alternative to surgical shunt on account of postoperative morbidity and complications of surgical shunting. METHODS: Between April 2000 and February 2003, 69 patients with duct-dependent pulmonary circulation underwent cardiac catheterization with the intent of PDA stenting as first palliative procedure. Patients with critical pulmonary stenosis and pulmonary atresia with intact ventricular septum post-radiofrequency valvotomy who had PDA stenting were excluded. Thirteen more patients were excluded because of branch pulmonary artery (PA) stenosis. The follow-up was by clinical examination, echocardiography, and repeat cardiac catheterization at six to nine months following the procedure. RESULTS: Patent ductus arteriosus stenting was successful in 51 patients (91.1%) and failed in 5 patients (8.9%). The mean narrowest PDA diameter was 1.9 +/- 0.6 mm. The mean procedure and fluoroscopy time were 95.7 min and 29.4 min, respectively. In one patient the stent dislodged and migrated to the left femoral artery and another patient developed transient intravascular hemolysis. There was no procedure-related mortality. Three patients (5.9%) died one day to two months after the procedure. At follow-up (3.2 months to 2.4 years), 8 patients developed significant stent stenosis requiring reintervention. Seven patients developed worsening of preexisting branch PA stenosis. The freedom from reintervention was 89% and 55% at 6 months and 1 year, respectively. CONCLUSIONS: Patent ductus arteriosus stenting is an attractive alternative to surgical shunt in a majority of patients with duct-dependent circulation. An absolute contraindication to this technique is the presence of branch pulmonary stenosis.
The patents of the first generation of biopharmaceuticals derived from recombinant DNA such as interferons, growth hormone and epoietins are expiring, opening up the possibility for competitors to introduce biosimilar products. The concept of generics that applies to classical drugs and allows market admission on limited documentation cannot be extrapolated to these "off-patent biologics". Physicochemical characterization, bioassays and animals studies do not predict completely the efficacy and safety of therapeutic proteins. Clinical studies will nearly always be necessary to obtain marketing authorization for off-patent biologics. Immunogenicity is considered to be the main problem with therapeutic proteins. The recent upsurge of pure red cell aplasia (PRCA), a severe form of anemia associated with the use of epoietin-alpha, highlights both the unpredictability and the severe consequences of immunogenicity. A risk-based approach can be used to evaluate the potential induction of antibodies by off-patent biologics.
BACKGROUND: Despite multiple patented ideas for vascular end-to-side anastomotic devices, and the growing need for them in minimally invasive coronary bypass procedures, no device has been evaluated clinically yet. This study assessed patents of micromechanical end-to-side anastomotic devices with respect to application in coronary artery bypass grafting. METHODS: Patents were categorized with respect to their micromechanical bonding principle. Calculated values for the wall strain during the construction of an anastomosis were compared with the allowable strain for human coronary arteries. RESULTS: From 51 patents describing vascular anastomotic devices, 11 ideas, categorized into four groups (staples, clips, mounting systems, and intraluminal stent structures), are serious candidates for coronary end-to-side anastomoses. Most ideas use an anvil for proper application of the bonding elements. For small (1.5 mm) coronary arteries, the calculated wall strain was 0.87, exceeding the breaking strain (0.45) in 60- to 79-year-old patients. CONCLUSIONS: In a coronary anastomotic device, the concept of using an anvil for the application of micromechanical bonding elements is not attractive, because excessive wall strain is likely to occur.
Efficacy of surgical closure versus indomethacin for treatment of patent ductus arteriosus in symptomatic neonates is an ongoing controversy. In recent years, surgical closure has been performed in the neonatal intensive care unit rather than the operating room in some centers, creating further controversy. In a retrospective study of the charts of 115 sequential patent ductus arteriosus surgical closures performed in the neonatal intensive care unit in premature infants, we found no surgical morbidity or mortality. Ninety-nine of these infants of less than 33 weeks gestational age were evaluated for various factors that might influence outcome. All were operated on within 72 hours of diagnosis, with an extra-pleural approach and metal clips used for closure of the ductus. All infants were extubated at an average of 33 weeks in each age group studied unless they had underlying severe bronchopulmonary dysplasia. We conclude that surgical closure of the symptomatic patent ductus arteriosus in neonates is safe and 100% effective, with none of the reported complications of indomethacin therapy, and should be the treatment of choice in neonates aged less than 33 weeks (gestational age) at birth with symptomatic patent ductus arteriosus. Closure performed in the neonatal intensive care unit eliminates transport risks and is ultimately safer and easier than transport to an operating room.
BACKGROUND: Minimally invasive techniques for interruption of patent ductus arteriosus have been reported, but are in use at only a few centers. We examined our series of patients who underwent thoracoscopic patent ductus arteriosus ligation. METHODS: We reviewed 59 consecutive patients, age 6 days to 50 years, weighing 640 g to 62 kg, who underwent video-assisted placement of a stainless steel clip across the patent ductus arteriosus. RESULTS: Thirty-eight nonneonates and 21 neonates (18 were < or =1,500 g) underwent video-assisted thoracic surgery for patent ductus arteriosus closure with intraoperative echocardiographic confirmation in nonneonates. There were no residual shunts, transfusions, chylothoraces, or significant pneumothoraces. Four were converted to thoracotomy, 3 for anatomic variances, and 1 for coagulopathy. Thirty-six of 38 nonneonate patients stayed less than 24 hours; 18 were discharged the evening of the operation. Two were admitted, one after thoracotomy, and one for a small mucosal intubation injury. No others required a chest tube. There were two recurrent nerve injuries. All neonates survived, and were extubated. CONCLUSIONS: Video-assisted thoracoscopic ductus closure is a safe, reliable technique and can be performed as an outpatient procedure in nonneonate patients.
Pharmacogenomics promises to revolutionize medicine by using genetic information to guide drug therapy. Genetic tests should help doctors improve drug safety and efficacy by better matching patients and drugs. This chapter evaluates the effectiveness of patent-based incentives to create genetic tests, and considers the optimal mix of public and private sector pharmacogenomic research and development (R&D). Drug patent owners have a strong incentive to develop genetic tests that predict adverse drug reactions and allow them to market drugs that otherwise would be shelved. Incentives are also strong for genetic tests that are created as part of the drug development process. Incentives tend to be weaker for genetic tests that are used in conjunction with existing drugs. Drug patent owners might gain or lose profit from the introduction of genetic tests into existing drug markets. Profits may fall because of lost sales, or profits may rise because drugs are more valuable to appropriate patients, and because drugs become more differentiated. Public sector R&D should target genetic tests that are likely to be underprovided by the private sector because private returns are low relative to social returns, or private costs are high relative to social costs. Private returns are relatively low when the rate of adoption of a genetic test is apt to be low, when test results increase consumer heterogeneity and consumer bargaining power, and when a test reveals information relevant to the use of more than one drug. Private costs are relatively high when test innovators need to obtain costly patent and trade secret licenses.
We sought to determine the capacity of neonatal ventricular sensory nerve endings (neurites) to transduce the cardiac milieu in the presence of cardiovascular pathology. The spontaneous activity generated by nodose ganglion cardiac afferent neurons was identified in situ using extracellular recording techniques in two groups of piglets approximately 2 weeks old: (i). controls that underwent sham operations (n=19 piglets) 2 weeks earlier and (ii). a pathological model of patent ductus arteriosus stented open for about 2 weeks (n=16 piglets). The capacity of ventricular sensory neurites associated with nodose ganglion afferent neurons to transduce local mechanical (including alterations in right or left ventricular volumes) or chemical stimuli was studied in both groups. The average conduction velocity of afferent axons associated with identified neuronal somata was estimated to be 1.5+/-0.6 or 2.9+/-1.3 m s(-1). Ventricular afferent neurons transduced mechanical stimuli similarly in both groups. In control animals, ventricular afferent neurons transduced the following chemicals: the sodium channel modifier veratridine (delta 23+/-7 impulses min(-1)), the P(1)-purinoceptor agonist adenosine (Delta 24+/-8 impulses min(-1)), and the beta-adrenoceptor agonist isoproterenol (delta 18+/-7 impulses min(-1)). On the other hand, patent ductus arteriosus cardiac afferent neurons did not transduce these chemicals. It is concluded that neonatal cardiac afferent neuronal chemosensory-as opposed to mechanosensory-transduction remodels in the presence of a patent ductus arteriosus. The reduced capacity of neonatal cardiac afferent neurons to transduce chemicals in the presence of a patent ductus arteriosus should be taken into account when considering neonatal cardiovascular control in such a state.
This paper uses John Rawls' theory of justice to defend the patent system against charges that it has an unfair effect on access to medications,from the perspective of national and international justice. The paper argues that the patent system is fair in a national context because it respects intellectual property rights and it benefits the least advantaged members of society by providing incentives for inventors, investors, and entrepreneurs. The paper also argues that the patent system is fair in an international context, provided that developed nations take steps to help disease-stricken countries secure internal justice. Fairness in a national or international context also requires that the patent system should include emergency exceptions to deal with short-term inequities.
Patent protection is available for certain inventions in the field of structural genomics. A review of the patent application procedure is provided, and patentable aspects of protein structural information under US law are discussed. Strategic and international factors to consider when seeking patent protection for an invention also are presented.
Gene patenting is now a familiar commercial practice, but there is little awareness that several patents claim ownership of the complete genome sequence of a prokaryote or virus. When these patents are analysed and compared to those for other biological entities, it becomes clear that genome patents seek to exploit the genome as an information base and are part of a broader shift towards intangible intellectual property in genomics.
The prostaglandins affect smooth-muscle tone of the ductus arteriosus. Patent ductus often complicates the clinical course of prematurely born infants with respiratory-distress syndrome. In the present study, a single oral or rectal dose of a potent inhibitor of prostaglandin synthesis, indomethacin, was administered to six consecutive premature infants with the syndrome who would otherwise have undergone surgical ligation of the patent ductus. Within 24 hours all the clinical symptoms and physical, echocardiographic and radiographic signs attributable to substantial left-to-right shunting through a patent ductus arteriosus dramatically and permanently disappeared. A transient reduction in renal function was observed in two infants in whom sustained ill-effects did not occur. The observation that constriction and closure of the patent ductus arteriosus may be induced pharmacologically raises important possibilities for the improved treatment of the respiratory-distress syndrome.
We studied 170 premature infants with birth weights between 751 and 2000 g in a randomized sequential trial comparing "high" and "low" volumes of fluid intake. Beginning on the third day of life, the low-volume group received only enough water to meet average estimated requirements, and the high-volume group received an excess of at least 20 ml per kilogram of body weight per day (mean excess, 47 ml per kilogram per day). Sequential analysis showed that the risk of patent ductus arteriosus with congestive heart failure was greater in infants receiving the high-volume regimen. Thirty-five of 85 infants in the high-volume group acquired murmurs consistent with patent ductus arteriosus, and 11 of these 35 had congestive heart failure. Only nine of 85 infants in the low-volume group had murmurs consistent with patent ductus arteriosus, and two of these nine had congestive heart failure. More cases of necrotizing enterocolitis also occurred in the high-volume group. We conclude that limitation of fluid intake to amounts estimated to meet requirements for excretion, insensible loss, and growth can reduce the risks of patent ductus arteriosus and congestive heart failure in premature infants.
Furosemide stimulates the renal synthesis of prostaglandin E2, a potent dilator of the ductus arteriosus. We administered this drug to 33 premature infants with the respiratory-distress syndrome, to determine whether it increased the incidence of patent ductus arteriosus. Chlorothiazide, a diuretic that does not stimulate prostaglandin E synthesis, was used as the control drug in 33 other infants. During the study, the incidence of patent ductus arteriosus was significantly higher (P less than 0.02) in the furosemide group (18 of 33 infants) than in the chlorothiazide group (8 of 33). Eleven infants in the furosemide group and seven in the chlorothiazide group required ductal ligation (P greater than 0.2). An additional six infants (all from the furosemide group) who did not have evidence of a patent ductus during the study were later found to have one. Overall survival was 76 and 61 per cent in the furosemide and chlorothiazide groups, respectively (P greater than 0.2). Small (less than twofold) increases in the urinary excretion of prostaglandin E were seen after the initial dose of both drugs. When the analysis was repeated after the fifth day of life, prostaglandin E excretion tripled after furosemide administration, whereas no increase occurred with chlorothiazide. We conclude that furosemide increases the incidence of patent ductus arteriosus in premature infants with the respiratory-distress syndrome, probably through a prostaglandin-mediated process.
BACKGROUND: Transcatheter implantation of the Rashkind PDA occluder is an alternative to conventional surgical closure of isolated patent ductus arteriosus. Neither the clinical outcomes nor the costs of these procedures have been formally compared. METHODS: We performed a retrospective cohort study to evaluate the clinical outcomes within a seven-month period for comparable patients with patent ductus arteriosus who underwent either placement of an occluder or surgical closure. The patients were treated between 1982 and 1987 at 14 major North American centers where patent ductus arteriosus was closed predominantly by a surgical procedure or by the occluder technique. To estimate inpatient and follow-up costs, we multiplied the observed use of resources by 1989 unit costs based on hospital-accounting and physician-reimbursement data. RESULTS: On the basis of cardiac auscultation at follow-up, the initial procedure resulted in closure of the ductus arteriosus in 77.3 percent of 185 patients in whom the occluder was implanted (95 percent confidence interval, 70.6 to 83.1 percent) and 99.8 percent of 446 surgical patients (95 percent confidence interval, 98.8 to 100.0 percent). Second procedures increased the percentage of successful closures to 87.6 percent (95 percent confidence interval, 81.9 to 92.0 percent) and 100.0 percent (95 percent confidence interval, 99.3 to 100.0 percent) for patients in the occluder and surgical groups, respectively. There were no deaths. Major complications occurred in 2.7 percent of the patients in whom the occluder was implanted (95 percent confidence interval, 0.9 to 6.2 percent) and 0.2 percent of the patients who underwent surgery (95 percent confidence interval, 0.0 to 1.2 percent); moderate complications in 16.8 percent (95 percent confidence interval, 11.7 to 22.9 percent) and 15.0 percent (95 percent confidence interval, 11.8 to 18.7 percent), respectively; and minor complications in 11.4 percent (95 percent confidence interval, 7.2 to 16.8 percent) and 24.9 percent (95 percent confidence interval, 20.9 to 29.2 percent). Including the cost of follow-up care, the mean estimated cost per case treated surgically was $8,838 (in 1989 U.S. dollars), as compared with $11,466 per case treated with the occluder technique. Sensitivity analyses based on our data identified no plausible situations in which the costs of surgery and of implantation of the occluder would be equal. CONCLUSIONS: The more effective and less costly surgical procedure was superior to transcatheter placement of the occluder for closure of isolated patent ductus arteriosus. Consequently, our results do not support the wide-spread dissemination of the occluder procedure for the management of this common congenital lesion.