Case No. IP-2019-000196

12.The main function of the respiratory system is to regulate gases in the blood. Gas exchange occurs in the alveoli, very small air sacs in the lungs. Blood in the capillaries within the wall of the alveoli takes up oxygen in the inhaled air, while carbon dioxide is transferred from the capillaries to the air within the alveoli. That air is then exhaled. Meanwhile the oxygenated blood in the alveoli walls travels from the lungs to the heart where it is pumped to the organs of the body.13.Mechanical ventilation is required when a patient cannot breathe on their own, either satisfactorily or at all. This may be because they are undergoing surgery with anaesthesia or because of an illness. Some illnesses (such as covid-19, to use an example post-dating the priority date of the Patent) may lead to a life-threatening condition known as “acute respiratory distress syndrome” or “ARDS”, where the lungs cannot provide the body’s vital organs with enough oxygen. Ventilators are used to compensate.14.Ventilators consist of a mechanical pneumatic apparatus which delivers air to the patient, usually supplemented with oxygen. This mechanical function is controlled by an electronic system which also provides information to those monitoring the patient. The invention claimed in the Patent is concerned with an electronic system of that type.15.A ventilator has two functions. One is oxygenation: controlling the level of oxygen in the blood. The other is ventilation: eliminating carbon dioxide from the patient’s blood.16.The fraction of oxygen in the inspiratory gas delivered to the patient is called the “FiO2”. The lower the level of oxygen in the patient’s blood, the higher will be the FiO2, which may vary from 21%, i.e. the figure for air in its natural form, to 100% oxygen. The aim of oxygenating the patient’s blood is to increase the partial pressure of oxygen, “PaO2”, in the arterial blood. This is sometimes measured as the oxygen saturation or “SaO2”. Measuring either the PaO2 or the SaO2 of the patient may be invasive, so a proxy method can be used known as “pulse oximetry”. A pulse oximeter is a device with a probe which is clipped to a body part, usually a finger or ear lobe. The probe uses light to measure the level of oxygen in the blood, the “SpO2”. A typical SpO2 of a healthy person is in the region of 95-99%. The target SpO2 of a patient under ventilation is generally 88-95%.17.Another measure to be monitored is the level of carbon dioxide in the exhaled air. A “capnograph” is a device which measures the partial pressure of carbon dioxide at the end of an exhaled breath. Normal values are 5-6% CO2.18.The breathing of a patient using a ventilator may be “spontaneous”, meaning that the breaths are generated by the patient, albeit assisted by the ventilator. When the patient is unable to breathe spontaneously, the breaths are “mandatory”, fully controlled by the ventilator.19.A ventilator will deliver gas at a pressure higher than atmospheric pressure in order to inflate the patient’s lungs. This pressure is maintained, even at the end of the patient’s exhalation, to prevent collapse or partial collapse of the alveoli and is known as the “positive end-expiratory pressure”, or “PEEP”. Excessive PEEP is harmful so it is generally maintained within the range 5-25 cm H2O.20.The ventilator provides a prescribed volume of gas to the patient, known as the “tidal volume” or “VT”. The volume of air delivered to a patient per minute is the “minute volume”. It will vary and depends in part on the partial pressure of carbon dioxide in the patient’s blood. The rate at which gas is delivered by the ventilator is known as the “respiration frequency” or sometimes the “respiration rate”.21.When in mandatory mode, a ventilator is in control of the lengths of both inhalation and exhalation. The ratio of the two is known as the “I:E” and is typically 2. It is important to maintain an appropriate I:E to ensure that a tidal volume of gas delivered to the patient is removed before the next volume is delivered. Failure to maintain the correct I:E may lead to a build-up of trapped air in the lungs, generating pressure known as “auto-PEEP” or “intrinsic PEEP”.22.A significant balance which featured in the evidence was that between FiO2 and PEEP. Both affect the oxygen level of the patient’s blood and by the priority date it was well recognised that the balance is important to the maintenance of a satisfactory oxygen level.23.Professor Rees’ evidence was that at the priority date there were two well-known approaches to the manual adjustment of FiO2 and PEEP, i.e. adjustment by the clinician. One of these followed from what were known as the “ARDSnet studies”. These were published in the New England Journal of Medicine in 2000 in what Professor Rees called a seminal paper, which the skilled person would have read. He said that the paper generated considerable interest and discussion and had been incorporated into textbooks by the priority date. He exhibited a copy of the relevant section of one of the textbooks, Essentials of Mechanical Ventilation by Dean Hess and Robert Kacmarek, 2nd ed., pub. 2002.24.The ARDSnet studies provided a protocol for the treatment of patients with ARDS. Fixed value pairs for FiO2 and PEEP were devised. PEEP was then set according to the FiO2 required.25.Professor Rees also made the point that if either FiO2 or PEEP is adjusted, there will be a delay before any further adjustment is made because it will take time for the change to have an effect and to be monitored. He said that typically it takes about 30 seconds for a change in levels of oxygen in the mouth to be registered by a pulse oximeter on the patient’s finger and between 2 to 5 minutes for a completed change in oxygen level in the arterial blood. For that reason, manual changes in FiO2 (i.e. in a non-automated system) were not made more frequently than once every 30 seconds and generally less frequently. Changes in PEEP were made incrementally to avoid excessive PEEP, with a delay of at least 20 minutes between changes, more often one to two hours.26.At the priority date of the Patent, some ventilators used a “closed-loop system”. The concept pre-dates its use in ventilators. The operator of a closed-loop system sets a target value for a variable. The target is achieved and then maintained using feedback from a sensor. A component within the system, a controller, compares a measured value of the variable with the target value, producing an error value. The error value determines an output value, the application of which causes adjustment to the variable towards the target value.27.By the priority date closed-loop control of PEEP and FiO2 in ventilators had been developed. One known means of automatic control was by use of a proportional, integral and derivative (“PID”) controller. The details of PID controllers do not matter; it is enough to say that they helped to avoid an overshoot of the target.