1. A graphical user interface for accessing and displaying ventilatory settings, the ventilator configured with a computer having a user interface including the graphical user interface for accepting commands and for displaying information, the graphical user interface comprising:
at least one window associated with the graphical user interface;
one or more elements within the at least one window comprising:
one or more actual ventilatory settings; and
a setup icon.
2. The graphical user interface of claim 1, wherein the setup icon is selectable.
3. The graphical user interface of claim 2, wherein selection of the setup icon accesses one or more settings elements.
4. The graphical user interface of claim 3, wherein the one or more settings elements are arranged in a same configuration as the one or more actual ventilatory settings.
5. The graphical user interface of claim 3, further comprising:
receiving a selection of a setting element of the one or more settings elements; and
associating a visual indication with the selected setting element.
6. The graphical user interface of claim 5, wherein an actual setting value is associated with the selected setting element, and wherein the actual setting value is changed to a pending setting value that is different from the actual setting value.
7. The graphical user interface of claim 6, further comprising:
a visual indicator for signaling that one or more settings changes are pending.
8. The graphical user interface of claim 6, further comprising:
accepting the pending setting value, wherein the pending setting value becomes a changed actual setting value; and
populating a corresponding actual ventilatory setting of the one or more actual ventilatory settings with the changed actual setting value.
9. A ventilatory system for accessing and displaying ventilatory settings, comprising:
at least one display device;
at least one processor; and
at least one memory, communicatively coupled to the at least one processor and containing instructions that, when executed by the at least one processor, provide a graphical user interface on the at least one display, comprising:
at least one window associated with the graphical user interface; and
one or more elements within the at least one window comprising one or more actual ventilatory settings.
10. The ventilatory system of claim 9, wherein the one or more actual ventilatory settings are selectable.
11. The ventilatory system of claim 10, wherein selection of at least one of the one or more actual ventilatory settings accesses one or more settings elements.
12. The ventilatory system of claim 11, wherein the one or more settings elements are arranged in a same configuration as the one or more actual ventilatory settings.
13. The ventilatory system of claim 11, further comprising:
receiving a selection of a setting element of the one or more settings elements; and
associating a visual indication with the selected setting element.
14. The ventilatory system of claim 13, wherein an actual setting value is associated with the selected setting element, and wherein the actual setting value is changed to a pending setting value that is different from the actual setting value.
15. The ventilatory system of claim 14, further comprising:
accepting the pending setting value, wherein the pending setting value becomes a changed actual setting value; and
populating a corresponding actual ventilatory setting of the one or more actual ventilatory settings with the changed actual setting value.
16. A computer-readable storage medium having instructions that when executed provide a graphical user interface for accessing and displaying ventilatory settings, the graphical user interface comprising:
at least one window associated with the graphical user interface; and
one or more elements within the at least one window comprising one or more actual ventilatory settings.
17. The computer-readable storage medium of claim 16, wherein selection of at least one of the one or more actual ventilatory settings accesses one or more settings elements.
18. The computer-readable storage medium of claim 16, further comprising:
receiving a selection of a setting element of the one or more settings elements; and
associating a visual indication with the selected setting element.
19. The computer-readable storage medium of claim 18, wherein an actual setting value is associated with the selected setting element, and wherein the actual setting value is changed to a pending setting value that is different from the actual setting value.
20. The computer-readable storage medium of claim 19, further comprising:
accepting the pending setting value, wherein the pending setting value becomes a changed actual setting value; and
populating a corresponding actual ventilatory setting of the one or more actual ventilatory settings with the changed actual setting value.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A polyvalent or polyspecific protein complex, comprising three or more polypeptides which associate to form three or more functional target-binding regions (TBRs), and in which each individual polypeptide comprises two or more immunoglobulin-like domains which are covalently joined together, such that two Ig-like domains in a single polypeptide do not associate with each other to form a TBR.
2. A polyvalent or polyspecific protein complex according to claim 1 in which the immunoglobulin-like domains are linked by a peptide of fewer than 3 amino acid residues.
3. A polyvalent or polyspecific protein complex according to claim 2 in which the immunoglobulin-like domains are covalently joined without a linker peptide.
4. A polyvalent or polyspecific protein complex according to any one of claims 1 to 3, comprising polypeptides in which each polypeptide comprises two or more immunoglobulin-like domains, and in which the domains are covalently joined without requiring a foreign linker polypeptide.
5. A polyvalent or polyspecific protein complex according to any one of claims 1 to 4, in which the polypeptides comprise the immunoglobulin-like domains of any member of the immunoglobulin superfamily.
6. A polyvalent or polyspecific protein complex according to any one of claims 1 to 5, in which the immunoglobulin-like domain is derived from an antibody, a T-cell receptor fragment, CD4, CD8, CD80, CD86, CD28, or CTLA4.
7. A polyvalent or polyspecific protein complex according to any one of claims 1 to 6, comprising different polypeptides, each of which comprises antibody VH and VL domains or other immunoglobulin domains, which are covalently joined preferably without a polypeptide linker, and in which the polypeptides associate to form active TBRs directed against different target molecules.
8. A polyvalent or polyspecific protein complex according to claim 7, which comprises one TBR directed to a cancer cell-surface molecule and one or more TBRs directed to T-cell surface molecules.
9. A polyvalent or polyspecific protein complex according to claim 7, which comprises one TBR directed against a cancer cell surface molecule, and a second TBR directed against a different cell surface molecule on the same cancer cell.
10. A polyvalent or polyspecific protein complex according to any one of claims 1 to 6, comprising two polypeptides which may be the same or different, each polypeptide comprising two or more immunoglobulin-like domains, in which the polypeptides associate to form a trimer with three or more active TBRs directed against different molecules.
11. A polyvalent or polyspecific protein complex according to claim 8, which comprises one TBR directed to a costimulatory T-cell surface moleculeselected from the group consisting of CTLA4, CD28, CD80 and CD86.
12. A polyvalent or polyspecific protein complex according to any one of claims 1 to 11, in which one of the polypeptides is a non-antibody immunoglobulin-like molecule.
13. A polyvalent or polyspecific protein complex according to claim 12, in which the immunoglobulin-like molecule is the immunoglobulin-like molecule extracellular domain of CTLA4 or CD28, or a derivative thereof, or the immunoglobulin-like extracellular domain of B7-1 or of B7-2.
14. A polyvalent or polyspecific protein complex according to either claim 12 or claim 13, in which the immunoglobulin-like domain is an affinity-matured analogue of the natural mammalian sequence of said domain which has been selected to possess higher binding affinity to the cognate receptor than that of the natural sequence.
15. A polyvalent or polyspecific protein complex according to claim 1, comprising a non-immunoglobulin-like domain.
16. A polyvalent or polyspecific protein complex according to any one of claims 1 to 15, in which the TBRs of each of the monomer polypeptides are respectively directed to three separate targets, whereby the complex possesses a plurality of separate specifities.
17. A polyvalent or polyspecific protein complex according to any one of claims 1 to 6, comprising identical polypeptides, each of which comprises immunoglobulin VH and VL domains which are covalently joined preferably without a polypeptide linker, in which the polypeptides associate to form active TBRs specific for the same target molecule.
18. A polyvalent or polyspecific protein complex according to claim 17, comprising identical scFv molecules which are inactive as monomers, but which form active and identical antigen combining sites in the complex.
19. A polyvalent or polyspecific protein complex according to claim 16, comprising different scFv molecules which are inactive as monomers, but which form active and different antigen combining sites in the complex.
20. A polyvalent or polyspecific protein complex according to any one of claims 1 to 19, which is a trimer.
21. A polyvalent or polyspecific protein complex according to any one of claims 1 to 19, which is a tetramer.
22. A polyvalent or polyspecific protein complex according to any one of claims 1 to 21, in which one or more of the polypeptides is linked to a biologically-active substance, a chemical agent, a peptide, a protein or a drug.
23. A polyvalent or polyspecific protein complex according to claim 22, in which any of the polypeptides are linked using chemical methods.
24. A polyvalent or polyspecific protein complex according to claim 22, in which any of the polypeptides are linked using recombinant methods.
25. A pharmaceutical composition comprising a polyvalent or polyspecific protein complex according to any one of claims 1 to 24, together with a pharmaceutically-acceptable carrier.
26. A method of treatment of a pathological condition, comprising the step of administering an effective amount of a polyvalent or polyspecific protein according to any one of claims 1 to 24 to a subject in need of such treatment, wherein one or more TBRs of the protein is directed to a marker which is:
a) characteristic of an organism which causes the pathological condition, or
b) characteristic of a cell of the subject which manifests the pathological condition,
and another TBR of the protein binds specifically to a therapeutic agent suitable for treatment of the pathological condition.
27. A method according to claim 26, in which two different TBRs of the protein are directed against markers of the pathological condition, and a third is directed to the therapeutic agent.
28. A method according to claim 26, in which one TBR of the protein is directed to a marker for the pathological condition or its causative organism, and the remaining TBRs of the trimer are directed to different therapeutic agents.
29. A method according to any one of claims 26 to 28 for treatment of tumours, in which the therapeutic agent is a cytotoxic agent, a toxin, or a radioisotope.
30. A method of diagnosis of a pathological condition, comprising the steps of administering a polyvalent or polyspecific protein according to any one of claims 1 to 24 to a subject suspected of suffering from said pathological condition, and identifying a site of localisation of the polyvalent or polyspecific protein using a suitable detection method.
31. A method according to claim 30 for detection andor localisation of cancers or blood clots.
32. An imaging reagent comprising a polyvalent or polyspecific protein according to any one of claims 1 to 24.
33. An imaging reagent according to claim 32, in which all the TBRs of the polyvalent or polyspecific protein are directed to a molecular marker specific for a pathological condition, and in which the protein is either labelled with radioisotopes or is conjugated to a suitable imaging reagent.
34. An imaging reagent according to claim 32, in which two TBRs of the polyvalent or polyspecific protein are directed to two different markers specific for a pathological condition or site, and a third is directed to a suitable imaging reagent.
35. An imaging reagent according to claim 32, in which one TBR of the polyvalent or polyspecific protein is directed to a marker characteristic of a pathological condition, a second TBR is directed to a marker specific for a tissue site where the pathological condition is suspected to exist, and a third TBR is directed to a suitable imaging agent.
36. An imaging reagent according to claim 32, in which one TBR of the protein is directed to a marker characteristic of the pathological condition and the remaining TBRs are directed to different imaging agents.
37. An imaging reagent according to any one of claims 32 to 36, in which the polyvalent or polyspecific protein is a trimer or a tetramer.
38. An imaging reagent according to any one of claims 32 to 37, in which the molecular marker is specific for a tumour.