SCREENING, THERAPY AND DIAGNOSIS

• US 20100306863A1
• Filed: 07/23/2008
• Published: 12/02/2010
• Est. Priority Date: 07/23/2007
• Status: Abandoned Application

• Current Assignee: Novo Nordisk A/S
• Original Assignee: BioXell S.p.A. (Cosmo Pharmaceuticals NV)
• Inventors: Colonna, Marco, Klesney-Tait, Julia, Panina, Paola
• Application Number:
  US12/452,813
• Publication Number:
  US 20100306863A1
• Time in Patent Office: Days
• US Class Current: 800/6
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: G01N 2500/04 Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
• CPC Class Codes: G01N 2800/065 Bowel diseases, e.g. Crohn, ulcerative colitis, IBS
• CPC Class Codes: G01N 2800/26 Infectious diseases, e.g. generalised sepsis
• CPC Class Codes: G01N 33/5047 Cells of the immune system
• CPC Class Codes: G01N 33/56972 White blood cells
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

A TREM-1 ligand is identified. This allows various derivatives to be provided/identified that are capable of binding to the TREM-1 receptor. The TREM-1 ligand or the derivatives can be used in screening for drugs/drug candidates. Substances that block or reduce binding of the TREM-1 ligand/derivative to a TREM-1 receptor may be useful for treating sepsis, particularly sepsis of bacterial or fungal origin. Antibodies to the ligand may be useful in diagnosing sepsis, particularly sepsis of bacterial or fungal origin.

Claims

1-47. -47. (canceled)

48. A non human animal, wherein the animal is genetically modified for reduced expression of TREM-1 or of a TREM-1 ligand, relative to the wild type animal.

49. A non-human animal according to claim 48 that is a knock-out for a TREM-1 ligand or TREM-1 receptor.

50. A non-human animal, according to claim 48, wherein the animal is genetically engineered for reduced expression of TREM-3.

51. A non-human animal, according to claim 50 which is a TREM-1/TREM-3 double knock out rodent.

52-65. -65. (canceled)

66. An antibody that binds to a TREM-1 ligand so as to prevent the ligand binding to the TREM-1 receptor or to reduce the efficiency of such binding.

67. An antibody according to claim 66, that binds to the TREM-1 ligand, but does not bind to any other cell surface protein expressed on septic neutrophils or monocytes.

68. An antibody according to claim 66, that is specific for a TREM-1 ligand.

69. An antibody according to claim 68, that is specific for a part of the TREM-1 ligand that binds to a TREM-1 receptor.

70. An antibody according to claim 68, that binds preferentially to a mutant form of a TREM-1 ligand relative to a wild type TREM-1 ligand.

71. An antibody according to claim 68, that is specific for a mutant form of a TREM-1 ligand.

72. An antibody according to claim 68, that is specific for cells which present on their surface a TREM-1 ligand or a derivative thereof.

73. An antibody according to claim 66, wherein the TREM-1 ligand is CD177.

74-87. -87. (canceled)

88. A method for obtaining anti-TREM-1 ligand antibodies which comprises providing a TREM-1 ligand or a derivative thereof and using it to generate antibodies in a non-human host, or which comprises providing cells which present on their surface a TREM-1 ligand or a derivative thereof and using them to generate antibodies in a non-human host.

90. A method according to claim 88, further comprising the step of purifying the antibodies.

92. A method according to claim 88, wherein the TREM-1 ligand or derivative is in substantially pure form.

93. A method according to claim 88, wherein the TREM-1 ligand is CD177.

98. A non-human animal according to claim 88 wherein the TREM-1 ligand is CD177.

89. (canceled)

91. A method for obtaining a hybridoma producing anti-TREM-1 ligand antibodies comprising

a) providing a TREM-1 ligand or a derivative thereof;

b) using the ligand or derivative to generate a B cell that produces anti-TREM-1 ligand antibodies in a non-human host,

c) fusing the B cell with a tumour cell to produce the hybridoma.

99. A method according to claim 91 wherein the TREM-1 ligand is CD177.

94. A hybridoma that produces anti-TREM-1 ligand antibodies, said antibodies being antibodies that bind to a TREM-1 ligand so as to prevent the ligand binding to the TREM-1 receptor or to reduce the efficiency of such binding.

95-97. -97. (canceled)