Claims
- 1. A method of detecting and/or identifying an agent which binds to mammalian Bonzo or a ligand-binding variant thereof comprising combining:
a) a reference agent that binds mammalian Bonzo; b) a test agent; and c) a composition comprising mammalian Bonzo or a ligand-binding variant thereof under conditions suitable for binding of said reference agent to said Bonzo or ligand-binding variant thereof; and detecting or measuring the formation of a complex between said reference agent and said Bonzo or a ligand-binding variant thereof, wherein a decrease in the formation of said complex relative to a suitable control indicates that said test agent binds to said Bonzo or to a ligand-binding variant thereof, and wherein said reference agent is not platelet factor-4.
- 2. The method of claim 1, wherein said reference agent is a natural ligand for said Bonzo or a receptor-binding variant thereof.
- 3. The method of claim 1, wherein said reference agent is SExCkine or a receptor-binding variant thereof.
- 4. The method of claim 1, wherein said reference agent is an antibody which binds to said Bonzo or an antigen-binding fragment thereof.
- 5. The method of claim 1, wherein said reference agent comprises a detectable label.
- 6. The method of claim 5, wherein said label is selected from the group consisting of a radioisotope, an epitope, an affinity label, an enzyme, a fluorescent group and a chemiluminescent group.
- 7. The method of claim 1, wherein said composition comprising mammalian Bonzo or ligand-binding variant thereof is a cell that expresses mammalian Bonzo.
- 8. The method of claim 7, wherein said cell is a recombinant cell.
- 9. The method of claim 7, wherein said cell is a cell line.
- 10. The method of claim 1, wherein said composition comprising a functional mammalian Bonzo or ligand-binding variant thereof is a membrane preparation of a cell that expresses mammalian Bonzo or ligand-binding variant thereof.
- 11. A method of detecting and/or identifying an antagonist of mammalian Bonzo comprising combining:
a) a cell expressing mammalian Bonzo or a ligand-binding variant thereof; b) a ligand or promoter of said Bonzo; and c) an agent to be tested, under conditions suitable for detecting a ligand- or promoter-induced response; and determining the ability of the test compound to inhibit said response, wherein inhibition of a ligand- or promoter-induced response by the agent indicates that the agent is an antagonist, and wherein said ligand or promoter is not platelet factor-4.
- 12. The method of claim 11, wherein said cell is a recombinant cell.
- 13. The method of claim 12, wherein said recombinant cell expresses human Bonzo.
- 14. The method of claim 11, wherein said ligand or promoter is SExCkine.
- 15. The method of claim 11, wherein said response is selected from the group consisting of Ca2+ flux, chemotaxis, exocytosis and respiratory burst.
- 16. A method of detecting a mammalian Bonzo or portion thereof in a biological sample, comprising:
a) contacting a biological sample with a Bonzo binding agent, under conditions appropriate for binding of said agent to mammalian Bonzo or a portion thereof; and b) detecting binding of said agent thereto; wherein the binding of said agent indicates the presence of said Bonzo or portion thereof, and wherein said Bonzo binding agent is not platelet factor-4.
- 17. The method of claim 16, wherein the biological sample is of human origin.
- 18. The method of claim 16, wherein said binding agent is an antibody which can inhibit the binding of ligand to Bonzo or an antigen-binding fragment thereof.
- 19. The method of claim 18, wherein said antibody or antigen-binding fragment thereof is selected from the group consisting of:
a) mAb 4A11, mAb 7A2, mAb 7F3; b) an antibody which can compete with mAb 4A11, mAb 7A2 or mAb 7F3 for binding to mammalian Bonzo; c) antigen-binding fragments of (a) or (b) which bind mammalian Bonzo or a portion thereof; and d) combinations of the foregoing.
- 20. The method of claim 16, wherein said binding agent is SExCkine or a receptor-binding variant thereof.
- 21. An antibody or antigen-binding fragment thereof which binds mammalian Bonzo and inhibits the binding of ligand to said Bonzo.
- 22. The antibody or antigen-binding fragment of claim 21, wherein said mammalian Bonzo is human Bonzo.
- 23. The antibody or antigen-binding fragment of claim 21, wherein said ligand is SExCkine.
- 24. The antibody or antigen-binding fragment of claim 21, wherein said antibody or antigen-binding fragment inhibits a cellular response to binding of ligand to said Bonzo in an in vitro assay with an IC50 of less than about 8 μg/mL.
- 25. The antibody or antigen-binding fragment of claim 24, wherein said cellular response is selected from the group consisting of Ca2+ flux, chemotaxis, exocytosis and respiratory burst.
- 26. The antibody or antigen-binding fragment of claim 24, wherein said cellular response is chemotaxis.
- 27. The antibody or antigen-binding fragment of claim 21, wherein the binding of said antibody or said antigen-binding fragment to Bonzo can be inhibited by an antibody selected from the group consisting of mAb 4A11, mAb 7A2 and mAb 7F3.
- 28. An antibody produced by murine hybridoma 4A11 or an antigen-binding fragment thereof.
- 29. An antibody produced by murine hybridoma 7A2 or an antigen-binding fragment thereof.
- 30. An antibody produced by murine hybridoma 7F3 or an antigen-binding fragment thereof.
- 31. Murine hybridoma 4A11.
- 32. Murine hybridoma 7A2.
- 33. Murine hybridoma 7F3.
- 34. An isolated cell which produces an antibody or antigen-binding fragment thereof that binds to mammalian Bonzo and inhibits the binding of ligand to said Bonzo.
- 35. The isolated cell of claim 34, wherein said antibody or antigen-binding fragment inhibits a cellular response to binding of ligand to said Bonzo in an in vitro assay with an IC50 of less than about 8 μg/mL.
- 36. The isolated cell of claim 35, wherein said cellular response is selected from the group consisting of Ca2+ flux, chemotaxis, exocytosis and respiratory burst.
- 37. The isolated cell of claim 35, wherein said cellular response is chemotaxis.
- 38. The isolated cell of claim 34, wherein said mammalian Bonzo is human Bonzo.
- 39. The isolated cell of claim 34, wherein said ligand is SExCkine.
- 40. The isolated cell of claim 34, wherein said isolated cell is selected from the group consisting of an immortalized B cell, a hybridoma and a recombinant cell comprising one or more exogenous nucleic acid molecules that encode said antibody or antigen-binding fragment thereof.
- 41. An antibody or antigen-binding fragment thereof which binds mammalian Bonzo expressed on the membrane of a cell and inhibits a cellular response to binding of ligand to said Bonzo.
- 42. The antibody or antigen-binding fragment of claim 41, wherein said cellular response is selected from the group consisting of Ca2+ flux, chemotaxis, exocytosis and respiratory burst.
- 43. The antibody or antigen-binding fragment of claim 42, wherein said antibody or antigen-binding fragment thereof inhibits a cellular response in an in vitro assay with an IC50 of less than about 8 μg/mL.
- 44. The antibody or antigen-binding fragment of claim 41, wherein said cellular response is chemotaxis.
- 45. The antibody or antigen-binding fragment of claim 41, wherein said mammalian Bonzo is human Bonzo.
- 46. The antibody or antigen-binding fragment of claim 41, wherein said ligand is SExCkine
- 47. A method of treating a subject having an inflammatory disease, comprising administering to said subject an effective amount of an antagonist of mammalian Bonzo.
- 48. The method of claim 47, wherein said antagonist inhibits the binding of ligand to mammalian Bonzo.
- 49. The method of claim 48, wherein said ligand is SExCkine.
- 50. The method of claim 48, wherein said antagonist is an antibody which binds mammalian Bonzo or an antigen-binding fragment thereof.
- 51. A method of treating a subject having an inflammatory disease, comprising administering to said subject an effective amount of an antibody or antigen-binding fragment thereof which binds mammalian SExCkine and inhibits the binding of said SExCkine to receptor.
- 52. The method of claim 51, wherein said receptor is Bonzo.
- 53. The method of claim 52, wherein said Bonzo is human Bonzo.
- 54. The method of claim 51, wherein said antibody is mAb SD7 or an antigen binding fragment thereof, or an antibody or antigen-binding fragment that can compete with mAb SD7 for binding to mammalian SExCkine.
- 55. The method of claim 51, wherein said mammalian SExCkine is human SExCkine.
- 56. The method of claim 51, wherein said inflammatory disease is inflammatory arthritis.
- 57. The method of claim 56, wherein said inflammatory arthritis is rheumatoid arthritis.
- 58. A method of inhibiting a cellular response to binding of ligand to Bonzo expressed on the surface of a leukocyte in a mammal, comprising administering to said mammal an effective amount of an antagonist of Bonzo.
- 59. The method of claim 58, wherein said cellular response is selected from the group consisting of Ca2+ flux, chemotaxis, exocytosis and respiratory burst.
- 60. The method of claim 58, wherein said antagonist inhibits the binding of ligand to Bonzo.
- 61. The method of claim 60, wherein said ligand is SExCkine.
- 62. The method of claim 60, wherein said antagonist is an antibody which binds Bonzo or an antigen-binding fragment thereof.
- 63. A method of inhibiting a cellular response to binding of SExCkine to receptor expressed on the surface of a leukocyte in a mammal, comprising administering to said mammal an effective amount of an antibody or antigen-binding fragment which binds said SExCkine and inhibits the binding of said SExCkine to receptor.
- 64. The method of claim 63, wherein said receptor is Bonzo.
- 65. The method of claim 63, wherein said antibody is mAb SD7 or an antigen-binding fragment thereof, or an antibody or antigen-binding fragment that can compete with mAb SD7 for binding to mammalian SExCkine.
- 66. A method of modulating a Bonzo function comprising contacting a cell that expresses Bonzo with an agent which binds thereto, thereby modulating the function of said Bonzo.
- 67. The method of claim 66, wherein said agent can promote the function of Bonzo.
- 68. The method of claim 67, wherein said agent is SExCkine.
- 69. The method of claim 66, wherein said agent can inhibit a function of Bonzo.
- 70. The method of claim 69, wherein said agent is an antibody or antigen-binding fragment thereof.
- 71. The method of claim 70, wherein said antibody is selected from the group consisting of mAb 4A11, mAb 7A2 and mAb 7E3.
- 72. The method of claim 66, wherein said function is selected from the group consisting of ligand binding, ligand-induced chemotaxis, ligand-induced Ca2+ flux, ligand-induced exocytosis and ligand-induced respiratory burst.
- 73. A method of recruiting Bonzo+ cells to a desired location in a mammal, comprising locally administering to said mammal a therapeutically effective amount of mammalian SExCkine at said location.
- 74. The method of claim 73, wherein said desired location is a tumor or a site of infection.
- 75. A targeting molecule, comprising a first binding moiety which binds mammalian Bonzo expressed on the surface of a first cell, and a second binding moiety which binds a molecule expressed on the surface of a target cell.
- 76. The targeting molecule of claim 75, wherein said first binding moiety is SExCkine or a receptor-binding fragment thereof.
- 77. The targeting molecule of claim 76, wherein said targeting molecule is a fusion protein and the second binding moiety is an antibody or antigen-binding fragment thereof.
- 78. The targeting molecule of claim 77, wherein said antibody or antigen-binding fragment thereof binds a tumor antigen or a viral antigen.
- 79. The targeting molecule of claim 75, wherein said first binding moiety is an antibody or antigen-binding fragment thereof.
- 80. The targeting molecule of claim 75, wherein said second binding moiety binds a viral or tumor antigen.
- 81. The targeting molecule of claim 79, wherein said second binding moiety is an antibody or antigen-binding fragment thereof.
- 82. The targeting molecule of claim 75, wherein said targeting molecule is a bispecific antibody which binds Bonzo and a molecule expressed on a target cell or a bivalent antigen-binding fragment thereof.
- 83. A method of effectuating the interaction of a Bonzo+ cell with a target cell in a mammal, comprising administering to said mammal an effective amount of a targeting molecule comprising a first moiety which binds mammalian Bonzo, and a second binding moiety which binds a molecule expressed on the surface of said target cell.
- 84. The method of claim 83, wherein said target cell is infected with a virus.
- 85. The method of claim 83, wherein said target cell is a tumor cell.
- 86. A method of isolating a population of mammalian cells enriched in cytotoxic effector cells, comprising:
a) contacting a suspension of mammalian cells comprising said cytotoxic effector cells with an antibody or antigen-binding fragment thereof which binds to mammalian Bonzo or a ligand-binding variant thereof under conditions suitable for binding thereto; b) separating bound cells from unbound cells; and c) recovering the bound cells.
- 87. The method of claim 86, wherein said antibody or antigen-binding fragment is immobilized on a solid support.
- 88. The method of claim 86, wherein said antibody or antigen-binding fragment comprises a detectable label.
- 89. The method of claim 88, wherein said detectable label is selected from the group consisting of a magnetic particle, a fluorescent group, an affinity label, a radioisotope, an epitope, an enzyme and a chemiluminescent group.
- 90. A test kit for use in detecting the presence of mammalian Bonzo or portion thereof in a biological sample comprising
a) an agent which binds to mammalian Bonzo or portion of said receptor; and b) one or more ancillary reagents suitable for detecting the presence of a complex between said agent and said mammalian Bonzo or a portion thereof, wherein said agent is not platelet factor-4.
- 91. The test kit of claim 90, wherein said agent is SExCkine.
- 92. The test kit of claim 90, wherein said agent is an antibody or antigen-binding fragment thereof.
- 93. The test kit of claim 92, wherein said antibody inhibits binding of ligand to mammalian Bonzo.
- 94. The test kit of claim 93, wherein said antibody is selected from the group consisting of
a) mAb 4A11, mAb 7A2, mAb 7F3; b) an antibody which can compete with mAb 4A11, mAb 7A2 or mAb 7F3 for binding to mammalian Bonzo; c) antigen-binding fragments of (a) or (b) which bind mammalian Bonzo or a portion thereof; and d) combinations of the foregoing.
- 95. A test kit for use in detecting the presence of a mammalian SExCkine or portion thereof in a biological sample comprising
a) at least one antibody or antigen-binding fragment thereof which binds to a mammalian SExCkine or portion thereof, wherein said antibody or antigen-binding fragment thereof inhibits binding of SExCkine to receptor; and b) one or more ancillary reagents suitable for detecting the presence of a complex between said antibody or antigen-binding fragment thereof and said mammalian SExCkine or a portion thereof.
- 96. The test kit of claim 95, wherein said receptor is Bonzo.
- 97. The test kit of claim 95, wherein said antibody or antigen-binding fragment is selected from the group consisting of:
a) mAb 9B10, mAb 10B12 or mAb SD7; b) an antibody which can compete with mAb 9B10, mAb 10B12 or mAb SD7 for binding to mammalian SExCkine; c) an antigen-binding fragment of any one of (a) or (b) which binds mammalian SExCkine or a portion thereof; and d) combinations of the foregoing.
- 98. An isolated nucleic acid encoding the antibody or antigen-binding fragment of claim 28.
- 99. An isolated nucleic acid encoding the antibody or antigen-binding fragment of claim 29.
- 100. An isolated nucleic acid encoding the antibody or antigen-binding fragment of claim 30.
- 101. An isolated nucleic acid encoding the targeting molecule of claim 77.
- 102. A receptor-binding fragment of SExCkine.
- 103. The receptor-binding fragment of claim 102, wherein said fragment binds Bonzo.
- 104. The receptor-binding fragment of claim 103, wherein said fragment has an amino acid sequence consisting essentially of an amino acid sequence selected from:
the sequence of residues 1-200 of SEQ ID NO:3, the sequence of residues 30-200 of SEQ ID NO:3, the sequence of residues 1-199 of SEQ ID NO:3, the sequence of residues 30-199 of SEQ ID NO:3, the sequence of residues 1-202 of SEQ ID NO:3, the sequence of residues 30-202 of SEQ ID NO:3, the sequence of residues 1-155 of SEQ ID NO:3, the sequence of residues 30-155 of SEQ ID NO:3, the sequence of residues 1-117 of SEQ ID NO:3, the sequence of residues 30-117 of SEQ ID NO:3, and the sequence of residues 30-95 of SEQ ID NO:3.
- 105. An antibody or antigen-binding fragment thereof which binds mammalian SExCkine and can inhibit one or more functions of said mammalian SExCkine.
- 106. The antibody or antigen-binding fragment of claim 105, wherein said one or more functions are selected from the group consisting of receptor binding, signaling activity and induction of a cellular response.
- 107. The antibody or antigen-binding fragment of claim 106, wherein said antibody or fragment inhibits the binding of SExCkine to receptor.
- 108. The antibody or antigen-binding fragment of claim 106, wherein said antibody or fragment inhibits the binding of human SExCkine to receptor.
- 109. The antibody or antigen-binding fragment of claim 106, wherein said receptor is Bonzo.
- 110. The antibody or antigen-binding fragment of claim 109, wherein said Bonzo is human Bonzo.
- 111. The antibody or antigen-binding fragment of claim 107, wherein said antibody is mAb SD7 or an antigen-binding fragment thereof.
- 112. The antibody or antigen-binding fragment of claim 107, wherein said antibody or antigen-binding fragment can compete with mAb SD7 for binding to mammalian SExCkine.
- 113. The antibody or antigen-binding fragment of claim 107, wherein said antibody or antigen-binding fragment has the epitopic specificity of mAb SD7.
- 114. The antibody or antigen-binding fragment of claim 105, wherein said antibody or antigen-binding fragment is a human, humanized or chimeric antibody or a human, humanized or chimeric antigen-binding fragment.
- 115. The antibody or antigen-binding fragment of claim 105, wherein said antigen-binding fragment is selected from the group consisting of a Fab fragment, a Fab′ fragment, a F(ab)′2 fragment and a Fv fragment.
- 116. The antibody or antigen-binding fragment of claim 107, wherein said antibody or fragment inhibits a cellular response to the binding of SExCkine to said receptor in an in vitro assay.
- 117. The antibody or antigen-binding fragment of claim 116, wherein said cellular response is selected from the group consisting of Ca2+ flux, chemotaxis, exocytosis and respiratory burst.
- 118. The antibody or antigen-binding fragment of claim 117, wherein said cellular response is chemotaxis.
- 119. An antibody produced by murine hybridoma 9B10 or an antigen-binding fragment thereof.
- 120. An antibody produced by murine hybridoma 10B12 or an antigen-binding fragment thereof.
- 121. An antibody produced by murine hybridoma SD7 or an antigen-binding fragment thereof.
- 122. The antibody or antigen-binding fragment of claim 107, wherein said antibody or antigen-binding fragment is a human, humanized or chimeric antibody or a human, humanized or chimeric antigen-binding fragment.
- 123. The antibody or antigen-binding fragment of claim 107, wherein said antibody or antigen-binding fragment is a humanized immunoglobulin comprising the light chain CDRs (CDR1, CDR2 and CDR3) and the heavy chain CDRs (CDR1, CDR2 and CDR3) of monoclonal antibody SD7 and a human framework region, wherein said humanized immunoglobulin has the same or similar epitopic specificity as monoclonal antibody SD7.
- 124. Murine hybridoma 9B10.
- 125. Murine hybridoma 10B12.
- 126. Murine hybridoma SD7.
- 127. An isolated cell which produces an antibody or antigen-binding fragment thereof that binds to mammalian SExCkine and inhibits the binding of said SExCkine to receptor.
- 128. The isolated cell of claim 127, wherein said receptor is Bonzo.
- 129. The isolated cell of claim 127, wherein said antibody or antigen-binding fragment inhibits a cellular response to the binding of SExCkine to said receptor in an in vitro assay.
- 130. The isolated cell of claim 129, wherein said cellular response is selected from the group consisting of Ca2+ flux, chemotaxis, exocytosis and respiratory burst.
- 131. The isolated cell of claim 130, wherein said cellular response is chemotaxis.
- 132. The isolated cell of claim 127, wherein said mammalian SExCkine is human SExCkine.
- 133. The isolated cell of claim 127, wherein said isolated cell is selected from the group consisting of an immortalized B cell, a hybridoma and a recombinant cell comprising one or more exogenous nucleic acid molecules that encode said antibody or antigen-binding fragment thereof.
- 134. A method of detecting and/or identifying an agent which binds mammalian SExCkine or a functional variant thereof comprising combining:
a) a reference agent that binds mammalian SExCkine; b) a test agent; and c) a composition comprising mammalian SExCkine or functional variant thereof under conditions suitable for binding of said reference agent to said SExCkine or functional variant thereof; and detecting or measuring the formation of a complex between said reference agent and said SExCkine or functional variant thereof, wherein a decrease in the formation of said complex relative to a suitable control indicates that said test agent binds to said SExCkine or functional variant thereof.
- 135. The method of claim 134, wherein said reference agent is a receptor.
- 136. The method of claim 135, wherein said receptor is Bonzo.
- 137. The method of claim 134, wherein said reference agent is an antibody or antigen-binding fragment which binds SExCkine.
- 138. The method of claim 137, wherein said anti-SExCkine antibody or antigen-binding fragment is selected from the group consisting of:
a) mAb 9B10, mAb 10B12 or mAb SD7; b) an antibody that can compete with mAb 9B10, mAb 10B12 or mAb SD7 for binding to mammalian SExCkine; c) an antigen-binding fragment of any one of (a) or (b) which binds mammalian SExCkine; or d) combinations of the foregoing.
- 139. The method of claim 134, wherein said reference agent comprises a detectable label.
- 140. The method of claim 139, wherein said label is selected from the group consisting of a radioisotope, an epitope label, an affinity label, a spin label, an enzyme, a fluorescent group and a chemiluminescent group.
- 141. The method of claim 134, wherein said composition comprising mammalian SExCkine or functional variant thereof is a cell that expresses mammalian SExCkine.
- 142. The method of claim 141, wherein said cell is a recombinant cell.
- 143. The method of claim 134, wherein said composition comprising a mammalian SExCkine or functional variant thereof is a membrane preparation of a cell that expresses cell-surface SExCkine or functional variant thereof.
- 144. The method of claim 134, wherein said composition comprising a mammalian SExCkine or functional variant thereof is a supernatant from a culture comprising a cell that expresses soluble SExCkine or functional variant thereof or is recovered from said supernatant.
- 145. A method of detecting a mammalian SExCkine or portion thereof in a biological sample, comprising:
a) contacting a biological sample with a SExCkine-binding agent, under conditions appropriate for binding of said agent to mammalian SExCkine or a portion thereof; and b) detecting binding of said agent thereto; wherein the binding of said agent indicates the presence of said SExCkine or portion thereof.
- 146. The method of claim 145, wherein the biological sample is of human origin.
- 147. The method of claim 145, wherein said binding agent is an anti-SExCkine antibody or antigen-binding fragment thereof.
- 148. The method of claim 147, wherein said antibody or antigen-binding fragment is selected from the group consisting of:
a) mAb 9B10, mAb 10B12or mAb SD7; b) an antibody which can compete with mAb 9B10, mAb 10B12 or mAb SD7 for binding to mammalian SExCkine; c) an antigen-binding fragment of any one of (a) or (b) which binds mammalian SExCkine or a portion thereof; and d) combinations of the foregoing.
- 149. The method of claim 145, wherein said SExCkine-binding agent is a receptor or SExCkine-binding fragment thereof.
- 150. The method of claim 149, wherein said receptor is Bonzo or a SExCkine-binding fragment thereof.
- 151. A method of modulating the recruitment of Bonzo+ cells in a mammal, comprising administering to said mammal an antibody or antigen-binding fragment that binds SExCkine.
- 152. The method of claim 151, wherein said antibody or antigen-binding fragment is immobilized on a solid support.
- 153. The method of claim 151, wherein the recruitment of Bonzo+ cells is inhibited.
- 154. The method of claim 153, wherein said antibody is mAb SD7 or an antigen binding fragment thereof, or an antibody or antigen-binding fragment that can compete with mAb SD7 for binding to mammalian SExCkine.
- 155. The method of claim 151, wherein the recruitment of Bonzo+ cells is promoted.
- 156. The method of claim 155, wherein said antibody or antigen-binding fragment is selected from the group consisting of:
a) mAb 9B10 or mAb 10B12; b) an antibody which can compete with mAb 9B10 or mAb 10B12 for binding to mammalian SExCkine; c) an antigen-binding fragment of any one of (a) or (b) which binds mammalian SExCkine or a portion thereof; and d) combinations of the foregoing.
- 157. A method of isolating a population of mammalian cells enriched in CD19+ B lymphocytes and/or CD14+ monocytes/macrophages, comprising:
a) contacting a suspension of mammalian cells comprising said CD19+ B lymphocytes and/or CD14+ monocytes/macrophages, with an antibody or antigen-binding fragment thereof which binds to mammalian SExCkine under conditions suitable for binding thereto; b) separating bound cells from unbound cells; and c) recovering the bound cells.
- 158. The method of claim 157, wherein said antibody or antigen-binding fragment is immobilized on a solid support.
- 159. The method of claim 157, wherein said antibody or antigen-binding fragment comprises a detectable label.
- 160. The method of claim 159, wherein said detectable label is selected from the group consisting of a magnetic particle, a fluorescent group, an affinity label, a radioisotope, an epitope, an enzyme and a chemiluminescent group.
- 161. The method of claim 157, wherein said antibody or antigen-binding fragment is selected from the group consisting of:
a) mAb 9B10, mAb 10B12 or mAb SD7; b) an antibody which can compete with mAb 9B10, mAb 10B12 or mAb SD7 for binding to mammalian SExCkine; c) an antigen-binding fragment of any one of (a) or (b) which bind mammalian SExCkine or a portion thereof; and d) combinations of the foregoing.
- 162. A method of isolating a population of mammalian cells enriched in dendritic cells, comprising:
a) contacting a suspension of cells comprising said dendritic cells, with an antibody or antigen-binding fragment thereof which binds to mammalian SExCkine under conditions suitable for binding thereto; b) separating bound cells from unbound cells; and c) recovering the bound cells.
- 163. The method of claim 162, wherein said antibody or antigen-binding fragment is immobilized on a solid support.
- 164. The method of claim 162, wherein said antibody or antigen-binding fragment is selected from the group consisting of:
a) mAb 9B10, mAb 10B12 or mAb SD7; b) an antibody which can compete with mAb 9B10, mAb 10B12 or mAb SD7 for binding to mammalian SExCkine; c) an antigen-binding fragment of any one of (a) or (b) which bind mammalian SExCkine or a portion thereof; and d) combinations of the foregoing.
- 165. An isolated nucleic acid encoding the antibody or antigen-binding fragment of claim 119.
- 166. An isolated nucleic acid encoding the antibody or antigen-binding fragment of claim 120.
- 167. An isolated nucleic acid encoding the antibody or antigen-binding fragment of claim 121.
- 168. A method of detecting or identifying an agent which inhibits SExCkine binding to receptor comprising combining:
a) a composition that comprises a receptor that binds SExCkine; b) a test agent; and c) a composition comprising mammalian SExCkine or receptor-binding variant thereof under conditions suitable for binding of said SExCkine or receptor-binding variant thereof, to said receptor; and detecting or measuring the formation of a complex between said receptor and said SExCkine or receptor-binding variant thereof, wherein a decrease in the formation of said complex relative to a suitable control indicates that said test agent is an inhibitor.
- 169. The method of claim 168, wherein said receptor is Bonzo.
- 170. The method of claim 168, wherein said test agent is an antibody or antigen-binding fragment.
- 171. A method of identifying an antagonist of mammalian SExCkine function comprising combining:
a) a cell that expresses cell surface SExCkine; b) a test agent; and c) a ligand or promoter of SExCkine function under conditions suitable for detecting a promoter-induced response; and determining the ability of the test-compound to inhibit said response, wherein inhibition of said ligand or promoter-induced response by the agent indicates that the agent is an antagonist.
- 172. The method of claim 171, wherein said response is selected from the group consisting of Ca2+ flux, chemotaxis, exocytosis and respiratory burst.
- 173. The method of claim 171, wherein said test agent is an antibody or antigen-binding fragment.
RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. Ser. No. 09/449,437, filed Nov. 24, 1999, the entire teachings of which are incorporated herein by reference.
Continuations (1)
|
Number |
Date |
Country |
Parent |
09722064 |
Nov 2000 |
US |
Child |
10174293 |
Jun 2002 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
09449437 |
Nov 1999 |
US |
Child |
09722064 |
Nov 2000 |
US |