WO2005114218B1 - Cross-screening system and methods for detecting a molecule having binding affinity for a target molecule - Google Patents
Cross-screening system and methods for detecting a molecule having binding affinity for a target moleculeInfo
- Publication number
- WO2005114218B1 WO2005114218B1 PCT/US2005/016770 US2005016770W WO2005114218B1 WO 2005114218 B1 WO2005114218 B1 WO 2005114218B1 US 2005016770 W US2005016770 W US 2005016770W WO 2005114218 B1 WO2005114218 B1 WO 2005114218B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- antibody
- ecla
- target molecule
- analyte
- molecule
- Prior art date
Links
- 108090001123 antibodies Proteins 0.000 claims abstract 39
- 102000004965 antibodies Human genes 0.000 claims abstract 39
- 239000012491 analyte Substances 0.000 claims abstract 32
- 238000001514 detection method Methods 0.000 claims abstract 9
- 238000004166 bioassay Methods 0.000 claims abstract 3
- 230000001225 therapeutic Effects 0.000 claims abstract 2
- 230000004044 response Effects 0.000 claims 11
- 239000000427 antigen Substances 0.000 claims 8
- 108091007172 antigens Proteins 0.000 claims 8
- 102000038129 antigens Human genes 0.000 claims 8
- 238000002965 ELISA Methods 0.000 claims 5
- 108010005144 Bevacizumab Proteins 0.000 claims 2
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 claims 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims 2
- 238000004458 analytical method Methods 0.000 claims 2
- 108010049535 anti-IgE antibodies Proteins 0.000 claims 2
- 229960000397 bevacizumab Drugs 0.000 claims 2
- 230000028993 immune response Effects 0.000 claims 2
- 102100019442 ITGAL Human genes 0.000 claims 1
- 101710006573 ITGAL Proteins 0.000 claims 1
- 102100000165 MS4A1 Human genes 0.000 claims 1
- 101710010909 MS4A1 Proteins 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000035800 maturation Effects 0.000 claims 1
- 238000003018 immunoassay Methods 0.000 abstract 3
- 239000003814 drug Substances 0.000 abstract 1
Abstract
The invention is directed to a cross-screening system and methods of the invention utilizing a combination of an immunoassay (IA) and electrochemiluminescence assay (ECLA) to identify molecules that have binding affinities for a target molecule. The cross-screening system and methods of the invention can detect molecules that have binding affinities for the target molecule below the detection limits of the individual immunoassay or ECLA. The cross-screening system and methods of the invention are useful for generating a pool of candidate analyte molecules enriched in a desired characteristic, such as low binding affinity for a target molecule. Low affinity antibodies identified by the cross-screening system and methods of the invention are useful, for example, in assessing the safety and efficacy of biological therapeutics.
Claims
1. A method of enriching a pool of analyte molecules with candidate analyte molecules that selectively bind a target molecule, comprising:
(a) determining ECLA responses for individual members of a pool of analyte molecules binding a target molecule;
(b) determining IA responses for individual members of the pool of analyte molecules binding the target molecule; and
(c) generating a pool of candidate analyte molecules comprising: i) IA-/ECLA+, and enriched for low affinity analyte molecules; ii) IA+/ECLA+ or 1 A+/ECLA\ and enriched for high affinity analyte molecules; or iii) IA+/ECLA+, and enriched for analyte molecules that bind the target molecule at a binding site not recognized by ECLA.
2. The method of claim 1 , wherein the pool of candidate analyte molecules is IAVECLA+, and enriched for low affinity analyte molecules.
3. The method of claim 2, wherein the pool of candidate analyte molecule is IA+/ECLA+ or IA+/ECLA-, and enriched for high affinity analyte molecules.
4. The method of claim 2, wherein the pool of candidate analyte molecules is IA+/ECLA-, and enriched for analyte molecules that bind the target molecule at a binding site not recognized by ECLA.
5. A method of identifying candidate low affinity analyte molecules from a pool of analyte molecules, comprising:
(a) determining ECLA responses for individual members of the pool of analyte molecules binding a target molecule; and
(b) determining IA responses for individual members of the pool of analyte molecules binding the target molecule; wherein analyte molecules that are IA-/ECLA+ are identified as candidate low affinity molecules.
6. The method of any one of claims 1-5, further comprising:
(a) applying a detection limit to the analysis of the ECLA response, wherein an ECLA response equal to or greater than the ECLA detection limit identifies an ECLA+ analyte molecule and an ECLA response less than the ECLA detection identifies an ECLA- analyte molecule; and
(b) applying a detection limit to the analysis of the ELlSA response, wherein an ELlSA response equal to or greater than the ELISA detection limit is ELISA+ and an ELISA response less than the ELISA detection limit is ELlSA-,
7. The method of claim 6, wherein the ELISA detection limit is 0.5 O.D. at 650 nm.
8. The method of claim 6, wherein the detection limit for the ECLA response is 250 ECLU.
9. The method of any one of claims 1 -8, further comprising confirm ing specific binding affinity of an analyte molecule selected from the enriched pool of candidate
10. The method of claim 9, wherein a Kdissoc of about 10-6 1/sec or less identifies a high affinity analyte molecule.
11. The method of claim 9, wherein a Kdissoc greater than about 10-6 1 /sec identifies a low affinity analyte molecule.
12. The method of claim 9, wherein a Kdissoc greater or equal to about 10-5 1/sec identifies a low affinity analyte molecule.
13. The method of claim 9, wherein a Kdissoc greater or equal to about 10-3 1 /sec identifies a low affinity analyte molecule.
14. The method of claim 9, wherein a KD equal to or greater than about 10-8 M identifies a low affinity analyte molecule.
15. The method of claim 9, wherein a KD of about 10-6 M lo about 10-8 M identifies a low affinity aπalyte molecule.
16. The method of any one of claims 1-15, wherein the analyte molecules are antibodies or antigen binding portions thereof.
17. The method of claim 16, wherein the antibodies are anti-therapeutic antibodies.
18. The method of any one of claims 1-17, wherein the target molecule is an antigen.
19. The method of claim 18, wherein the antigen is an antibody or antigen binding portion thereof.
20. The method of any one of claims 1-17, wherein the target molecul e is an antibody or antigen binding fragment thereof.
21. The method of claim 19 or 20, wherein the antibody is a therapeutic antibody.
22. The method of claim 21, wherein the antibody binds CD20.
23. The method of claim 21, wherein the antibody binds VEGF.
24. The method of any one of claims 1 -23, wherein the analyte or target antibodies arc monoclonal.
25. The method of any one of claims 1 -24, further comprising isotyping the analyte antibodies.
26. The method of any one of claims 1 -25, wherein the analyte antibodies are IgG.
27. An antibody having a Kdissoc in the range of 10-2 to 10-6 selected by the method of any one of claims 1-26, wherein the target molecule is an anti-VEGF antibody, anti-HER2 antibody, anti-CD20 antibody, anti-ϊgE antibody, antϊ-CDl Ia antibody, or antigen binding fragment thereof.
28. An antibody having a KD in the range of 10-6 M to 10-8 M selected by the method of any one of claims 1-26, wherein the target molecule is an anti-VEGF antibody, anti-HER2 antibody, anti-CD20 antibody, anti-IgE antibody, anti-CD 1 Ia antibody, or antigen binding fragment thereof.
29. The antibody of claim 27 or 28, wherein the target molecule is 2H7 or bevacizumab.
30. Use of one or more antibody having a Kdissoc in the range of 10-2 to 10-6 for a target molecule, the one or more antibody selected by the method of any one of claims 1-26, in an assay for detecting an immune response to the target molecule.
31. Use of one or more antibody having a KD in the range of 10-6 M to 10-8 M for a target molecule, the one or more antibody selected by the method of any one of claims 1-26, in an assay for detecting an immune response to the target molecule.
32. The use according to claim 30 or 31 , wherein the target molecule is an anli- VEGF antibody, anti-HER2 antibody, anti-CD20 antibody, anti-IgE antibody, anti- CD11a antibody, or antigen binding fragment thereof.
33. The use according to claim 30, wherein the target molecule is 2H7 or bevacizumabi
34. The use according to claim 31 , wherein the target molecule is bevacizumab.
35. A method for producing a high affinity antibody to a target molecule, comprising subjecting a low affinity antibody selected by the method of any one of claims 1-26 to affinity maturation, thereby producing an affinity-matured antibody having high affinity for the target molecule,
36. The method of claim 35, wherein the low affinity antibody has a Kdissoc in the range of 10-2 to 10-6.
37. The method of claim 35, wherein the low affinity antibody has a KD in the range of 10-6M to 10-8 M.
38. The method of any one of claims 35-37, wherein the high affinity antibody has a Kdissoc of about 10-6 1/sec or less.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP05779248A EP1769243A2 (en) | 2004-05-15 | 2005-05-13 | Cross-screening system and methods for detecting a molecule having binding affinity for a target molecule |
| CA002562800A CA2562800A1 (en) | 2004-05-15 | 2005-05-13 | Cross-screening system and methods for detecting a molecule having binding affinity for a target molecule |
| AU2005246289A AU2005246289A1 (en) | 2004-05-15 | 2005-05-13 | Cross-screening system and methods for detecting a molecule having binding affinity for a target molecule |
| JP2007527314A JP2007538258A (en) | 2004-05-15 | 2005-05-13 | Cross-screening system and method for detecting molecules having binding affinity for a target molecule |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US57115704P | 2004-05-15 | 2004-05-15 | |
| US60/571,157 | 2004-05-15 | ||
| US62682704P | 2004-11-09 | 2004-11-09 | |
| US60/626,827 | 2004-11-09 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO2005114218A2 WO2005114218A2 (en) | 2005-12-01 |
| WO2005114218A3 WO2005114218A3 (en) | 2006-02-16 |
| WO2005114218B1 true WO2005114218B1 (en) | 2006-04-06 |
Family
ID=35311822
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US2005/016770 WO2005114218A2 (en) | 2004-05-15 | 2005-05-13 | Cross-screening system and methods for detecting a molecule having binding affinity for a target molecule |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US7514223B2 (en) |
| EP (1) | EP1769243A2 (en) |
| JP (1) | JP2007538258A (en) |
| AU (1) | AU2005246289A1 (en) |
| CA (1) | CA2562800A1 (en) |
| WO (1) | WO2005114218A2 (en) |
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| US8170803B2 (en) | 2004-07-13 | 2012-05-01 | Dexcom, Inc. | Transcutaneous analyte sensor |
| US20070045902A1 (en) | 2004-07-13 | 2007-03-01 | Brauker James H | Analyte sensor |
| WO2008031532A1 (en) | 2006-09-12 | 2008-03-20 | F. Hoffmann-La Roche Ag | Anti-drug antibody assay |
| AR073295A1 (en) | 2008-09-16 | 2010-10-28 | Genentech Inc | METHODS TO TREAT PROGRESSIVE MULTIPLE SCLEROSIS. MANUFACTURING ARTICLE. |
| WO2010075249A2 (en) | 2008-12-22 | 2010-07-01 | Genentech, Inc. | A method for treating rheumatoid arthritis with b-cell antagonists |
| AR078161A1 (en) | 2009-09-11 | 2011-10-19 | Hoffmann La Roche | VERY CONCENTRATED PHARMACEUTICAL FORMULATIONS OF AN ANTIBODY ANTI CD20. USE OF THE FORMULATION. TREATMENT METHOD |
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-
2005
- 2005-05-13 WO PCT/US2005/016770 patent/WO2005114218A2/en active Application Filing
- 2005-05-13 US US11/128,981 patent/US7514223B2/en active Active
- 2005-05-13 EP EP05779248A patent/EP1769243A2/en not_active Withdrawn
- 2005-05-13 CA CA002562800A patent/CA2562800A1/en not_active Abandoned
- 2005-05-13 JP JP2007527314A patent/JP2007538258A/en active Pending
- 2005-05-13 AU AU2005246289A patent/AU2005246289A1/en not_active Abandoned
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