Compositions comprising DC-SIGN blockers and methods of using DC-SIGNblockers for preventing or treating diseases of a mammal, including viral infections
First Claim
1. A method of preventing or treating a disease of a mammal, wherein at least one symptom of the disease is mediated at least in part by the binding of an effector molecule to a DC-SIGN receptor of the mammal to be treated, wherein the method comprises administering to the mammal an amount of a DC-SIGN modulator sufficient to substantially modulate the binding of the effector molecule to the DC-SIGN receptor to thereby prevent or treat the disease.
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Accused Products
Abstract
The present invention relates to methods and compositions for preventing or treating diseases of a mammal, including viral infections, wherein at least one symptom of the disease is mediated at least in part by the binding of an effector molecule to a DC-SIGN receptor present on cells of the mammal to be treated. The invention also provides methods of identifying compositions, wherein the compositions are useful for treating mammalian diseases, including viral infections, for which at least one symptom of the disease is mediated at least in part by the specific binding of an effector molecule to a DC-SIGN receptor present on the cells that express the DC-SIGN receptor, belonging to the mammal to be treated. The invention further relates to compositions and methods for targeting subject molecules to cells that express the DC-SIGN receptor.
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Citations
80 Claims
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1. A method of preventing or treating a disease of a mammal, wherein at least one symptom of the disease is mediated at least in part by the binding of an effector molecule to a DC-SIGN receptor of the mammal to be treated, wherein the method comprises administering to the mammal an amount of a DC-SIGN modulator sufficient to substantially modulate the binding of the effector molecule to the DC-SIGN receptor to thereby prevent or treat the disease.
- 2. A method of preventing or treating a disease of a mammal, wherein at least one symptom of the disease is mediated at least in part by the binding of an effector molecule to a DC-SIGN receptor of the mammal to be treated, wherein the method comprises administering to the mammal an amount of a DC-SIGN blocker sufficient to substantially inhibit the binding of the effector molecule to the DC-SIGN receptor to thereby prevent or treat the disease.
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9. A method of preventing or treating a viral infection of a mammal, wherein the viral infection is mediated at least in part by the binding of a viral effector molecule to a DC-SIGN receptor of the mammal to be treated, wherein the method comprises administering to the mammal an amount of a DC-SIGN modulator sufficient to substantially modulate the binding of the viral effector molecule to the DC-SIGN receptor to thereby prevent or treat the viral infection.
- 10. A method of preventing or treating a viral infection of a mammal, wherein the viral infection is mediated at least in part by the binding of a viral effector molecule to a DC-SIGN receptor of the mammal to be treated, wherein the method comprises administering to the mammal an amount of a DC-SIGN blocker sufficient to substantially inhibit the binding of the viral effector molecule to the DC-SIGN receptor to thereby prevent or treat the viral infection.
- 16. The method of 15, wherein the antibody is a monoclonal antibody.
- 33. The method of 32, wherein the antibody is a monoclonal antibody.
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39. A method of preventing or treating an Ebola, HIV or SIV infection of a human or a simian, wherein the method comprises administering to the human or simian an amount of a DC-SIGN modulator sufficient to substantially modulate the binding of Ebola, HIV or SIV to the DC-SIGN receptor present on dendritic cells of the human or simian to thereby prevent or treat the Ebola, HIV or SIV infection.
- 40. A method of preventing or treating an Ebola, HIV or SIV infection of a human or a simian, wherein the method comprises administering to the human or simian an amount of a DC-SIGN blocker sufficient to substantially inhibit the binding of Ebola, HIV or SIV to the DC-SIGN receptor present on dendritic cells of the human or simian to thereby prevent or treat the Ebola, HIV or SIV infection.
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43. A method of preventing or treating inflammation in a mammal caused by specific binding of ICAM-3 present on T cells of the mammal with DC-SIGN receptor present on dendritic cells of the mammal, wherein the method comprises administering to the mammal an amount of a DC-SIGN modulator sufficient to substantially modulate the binding of ICAM-3 present on T cells of the mammal with DC-SIGN receptor present on dendritic cells of the mammal to thereby prevent or treat inflammation.
- 44. A method of preventing or treating inflammation in a mammal caused by specific binding of ICAM-3 present on T cells of the mammal with DC-SIGN receptor present on dendritic cells of the mammal, wherein the method comprises administering to the mammal an amount of a DC-SIGN blocker sufficient to substantially inhibit the binding of ICAM-3 present on T cells of the mammal with DC-SIGN receptor present on dendritic cells of the mammal to thereby prevent or treat inflammation.
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47. A pharmaceutical composition comprising:
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a) A DC-SIGN modulator, and b) at least one pharmaceutically acceptable excipient;
wherein the DC-SIGN blocker is present in the composition at an achievable therapeutic concentration.
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48. A pharmaceutical composition comprising:
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a) A DC-SIGN blocker, and b) at least one pharmaceutically acceptable excipient;
wherein the DC-SIGN blocker is present in the composition at an achievable therapeutic concentration. - View Dependent Claims (49, 50, 51, 52, 53, 54, 55, 56, 57, 58)
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59. A method of identifying a DC-SIGN modulator, wherein the method comprises:
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a) determining a baseline binding value by;
i. providing cultured cells comprising a DC-SIGN receptor;
ii. exposing the cultured cells to a marked viral effector molecule binding moiety for a period of time sufficient to allow binding equilibrium to be reached; and
iii. determining the extent of binding of the marked viral effector molecule binding moiety to the cultured cells to thereby determine a baseline binding value;
b) determining a test substance binding value by;
i. providing cultured cells comprising a DC-SIGN receptor;
ii. exposing the cultured cells to a marked viral effector molecule binding moiety in the presence of a test substance for a period of time sufficient to allow binding equilibrium to be reached; and
iii. determining the extent of binding of the marked viral effector molecule binding moiety to the cultured cells to thereby determine a test substance binding value; and
c) determining a test substance binding modulation value for the test substance by dividing the test substance binding value by the baseline binding value, wherein a test substance binding modulation value representing an about 95% inhibition of binding of the viral effector molecule to dendritic cells by the test substance, indicates that the test substance is a substance that substantially modulates the binding of a viral effector molecule to the DC-SIGN receptor.
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60. A method of identifying a DC-SIGN blocker, wherein the method comprises:
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a) determining a baseline binding value by;
i. providing cultured cells comprising a DC-SIGN receptor;
ii. exposing the cultured cells to a marked viral effector molecule binding moiety for a period of time sufficient to allow binding equilibrium to be reached; and
iii. determining the extent of binding of the marked viral effector molecule binding moiety to the cultured cells to thereby determine a baseline binding value;
b) determining a test substance binding value by;
i. providing cultured cells comprising a DC-SIGN receptor;
ii. exposing the cultured cells to a marked viral effector molecule binding moiety in the presence of a test substance for a period of time sufficient to allow binding equilibrium to be reached; and
iii. determining the extent of binding of the marked viral effector molecule binding moiety to the cultured cells to thereby determine a test substance binding value; and
c) determining a test substance binding inhibition value for the test substance by dividing the test substance binding value by the baseline binding value, wherein a test substance binding inhibition value representing an about 95% inhibition of binding of the viral effector molecule to dendritic cells by the test substance, indicates that the test substance is a substance that substantially inhibits the binding of a viral effector molecule to the DC-SIGN receptor. - View Dependent Claims (61, 62, 63, 64, 65)
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- 66. A method of targeting a subject molecule to a cell expressing a DC-SIGN receptor by exposing the cell to a targeting complex, wherein the targeting complex comprises a subject molecule and a DC-SIGN blocker, wherein the exposure is under conditions which allow the DC-SIGN blocker to bind to DC-SIGN on the cell expressing the DC-SIGN receptor, thereby targeting the subject molecule to the cell expressing a DC-SIGN receptor.
- 74. An isolated antibody, wherein the isolated antibody specifically binds DC-SIGN.
- 77. An isolated monoclonal antibody, wherein the isolated monoclonal antibody specifically binds DC-SIGN.
Specification