1. A method of screening for agonistic antibodies, the method comprising:
(a) providing a cell that expresses both a multimer-forming receptor and a test antibody, wherein the cell in the absence of the antibody requires a ligand of the receptor for growth;
(b) culturing the cell in the absence of the ligand; and
(c) selecting the test antibody as an agonist of the receptor if the cell grows in the absence of the ligand.
2. The method of claim 1, flirt her comprising the steps of (i) providing a cell comprising a nucleic acid encoding the light chain of the antibody and a nucleic acid encoding the receptor; and (ii) introducing into the cell a nucleic acid that encodes the heavy chain of the test antibody, thereby producing the cell of step (a).
3. The method of claim 1, wherein the receptor is a chimeric receptor that functions to transduce a cell growth signal.
4. The method of claim 1, wherein the receptor is a dimer-forming receptor.
5. The method of claim 4, wherein the dimer-forming receptor is a homo-dimer-forming receptor.
6. The method of claim 4, wherein the dimer-forming receptor is a hetero-dimer-forming receptor.
7. The method of claim 1, wherein the receptor is a G-CSF receptor.
8. The method of claim 1, further comprising a step of producing a plurality of cells expressing a library of diverse antibodies, the cell of step (a) being a member of the plurality of cells.
9. The method of claim 8, wherein the library of diverse antibodies is encoded by a retroviral antibody library introduced into the plurality of cells.
10. The method of claim 1, wherein the test antibody is a multi-specific antibody.
11. The method of claim 10, wherein the test antibody comprises heavy and light chain variable regions connected via a linker.
12. The method of claim 11, further comprising expressing the test antibody by a method that comprises:
(i) producing a first DNA encoding a single chain Fv that binds to the receptor;
(ii) producing a second DNA encoding a single chain antibody comprising the single chain Fv of step (i) linked to a CH1-hinge-CH2-CH3; and
(iii) expressing a multi-specific antibody that comprises the single chain antibody of step (ii).
13. The method of claim 11, further comprising expressing the test antibody by a method that comprises:
(i) producing a first DNA encoding a single chain Fab that binds to the receptor;
(ii) producing a second DNA encoding a single chain antibody comprising the single chain Fab of step (i) linked to an Fc; and
(iii) expressing a multi-specific antibody that comprises the single chain antibody of step (ii).
14. A method of screening for agonistic antibodies, the method comprising:
providing an antibody expression library of cells, the cells each expressing both a member of a set of diverse antibodies and a multimer-forming receptor, wherein the cells in the absence of the antibodies require a ligand of the receptor for cell growth;
culturing the library of cells in the absence of the ligand;
selecting a cell that grows in the absence of the ligand; and
identifying the antibody expressed by the selected cell as being an agonist of the receptor.
15. The method of claim 14, wherein the antibody expression library comprises a retroviral antibody library.
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 vertically oriented separator for separating liquid from a gas stream, said separator comprising
an inlet nozzle (121,221,321) arranged mainly perpendicularly to the centre axis of the separator and communicating with a circular swirl-inducing inlet device (101, 201,301) being outwardly limited by the separator wall (103, 203,303), inwardly limited by a mainly centrally arranged pipe (117, 217, 317) and upwardly limited by a sealed top cover (122,222,322);
a first separation compartment (112,212, 312) arranged below the pipe (117,217,317);
a second separator compartment (123,223,323,) arranged above the pipe (117,217,317), so the incoming fluid successively and under continuous swirl is forced to pass from the circular swirl-inducing inlet device (101,201,301) to the first separator compartment (112,212,312) and further through the pipe (117,217,317) to the second separator compartment (123,223,323);
axial flow cyclones (107, 207, 307) arranged between the second separation compartment (123,223,323) and the separator gas outlet nozzle (109,209,309); and
one or more drain pipes (104,204,304) for drainage of liquid separated from the gas in the axial flow cyclones.
2. Vertically oriented separator as claimed in claim 1, wherein the drain pipe (104,204,304) is arranged internally or externally of the separator to a liquid compartment (105,205,305) at the bottom of the separator.
3. Vertically oriented separator as claimed in claim 1, wherein the drain pipe (104,204,304) is arranged mainly concentrically with and vertically through the vertically arranged pipe (117,217,317).
4. Vertically oriented separator as claimed in claim 1, wherein the pipe (117,217,317) at its top ends with a free upper edge (120,220,320) in a vertical distance above the top cover (122,222,322), so portions of the liquid film deposited on the inner wall of the pipe (117,217,317) can pass over this free edge (120, 220,320), and be collected in the annular open void formed by the outer wall of the pipe (117,217, 317), the inner wall (103,203,303) of the separator and the top cover (122, 222, 322) of the circular swirl-inducing inlet device.
5. Vertical oriented separator as claimed in claim 4, wherein the liquid collected in the annular open void formed by the outer wall of the pipe (117,217,317), the inner wall (103,203,303) of the separator and the top cover (122,222,322) of the circular swirl-inducing inlet device, is drained down to the liquid compartment (105, 205,305) at the bottom of the separator through a separate internal drain pipe (114,214), or through a separate external drain pipe (314).