Decoy Influenza Therapies

• US 20100004195A1
• Filed: 01/02/2009
• Published: 01/07/2010
• Est. Priority Date: 01/03/2008
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Chandrasekaran, Aarthi, Sasisekharan, Ram, Viswanathan, Karthik, Raman, Rahul, Srinivasan, Aravind, Sasisekharan, Viswanathan, Raguram, S.
• Granted Patent: US 8,815,522 B2
• Time in Patent Office: Days
• US Class Current: 514/54
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: G01N 2333/11 Orthomyxoviridae, e.g. influenza virus
• CPC Class Codes: G01N 2400/10 Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
• CPC Class Codes: G01N 33/56983 Viruses

Abstract

The present invention provides umbrella-topology glycan decoys. The present invention provides systems and methods treating influenza infection utilizing inventive umbrella-topology glycan decoys. The present invention provides methods for identifying novel umbrella-topology glycan decoys.

Claims

1. A method comprising steps of:

administering to a subject who is suffering from, exhibiting symptoms of, or susceptible to an influenza infection an umbrella-topology glycan decoy such that the decoy binds to influenza hemagglutinin (HA) and competes away an interaction between the HA and HA receptors in the subject.

8. The method of claim 1, wherein the step of administering is performed by a route of administration selected from the group consisting of intravenous injection, intramuscular injection, or oral administration.

2-7. -7. (canceled)

9-10. -10. (canceled)

11. A method of identifying agents useful in the treatment of influenza infection by:

providing an influenza HA;

providing a collection of candidate umbrella-topology decoys including at least one candidate decoy that mimics umbrella-topology glycans; and

contacting the HA with candidate decoys from the plurality, such that candidate decoys that interact with HA and compete its interaction with umbrella-topology glycans are identified.

12. An isolated umbrella-topology glycan decoy that binds to influenza hemagglutinin (HA) and competes away an interaction between HA and HA receptors.

13-46. -46. (canceled)

47. An isolated umbrella-topology glycan decoy comprising:

a carrier attached to an umbrella-topology glycan moiety, wherein the umbrella-topology glycan moiety has the structure;

Neu5Acα

2-6Sug1-Sug2-Sug3-Sug4

wherein one or more of the following conditions are met;

a. Neu5Ac α

2-6 is at the non-reducing end of the glycan;

b. Sug1, Sug2, Sug3, or Sug4 is a hexose or hexosamine in α

or β

configuration;

c. No sugars other than Neu5Acα

2-6 are attached to any of the non-reducing positions of Sug1;

d. Non-sugar moieties are attached to non-reducing positions of Sug1, Sug2, Sug3, or Sug4;

e. Linkage between any two sugars in the oligosaccharide apart from Neu5Acα

2-6 linkage are 1-2, 1-3, 1-4, and/or 1-6; and

f. The Neu5Acα

2-6Sug1-Sug2-Sug3- portion satisfies structural constraints or hemagglutinin contact constraints of the umbrella-like topology glycan.

63. The isolated umbrella-topology glycan decoy of claim 47 or 49, wherein the isolated umbrella-topology glycan decoy comprises a sialic acid analog.

68. A pharmaceutical composition comprising

the umbrella-topology glycan decoy of any one of claims 47, 49, or 63;

and

a pharmaceutically acceptable excipient.

48. (canceled)

49. An isolated umbrella-topology glycan decoy comprising a substance that interacts with one or more hemagglutinin amino acids selected from the group consisting of 131, 133, 136, 137, 143, 144, 145, 153, 155, 156, 159, 186, 187, 189, 190, 192, 193, 194, 196, 222, 225, 226, 228, and/or and combinations thereof.

50-62. -62. (canceled)

64-67. -67. (canceled)

69. A pharmaceutical composition comprising

an umbrella-topology glycan decoy that binds to influenza hemagglutinin (HA) and competes away an interaction between the HA and HA receptors;

and

a pharmaceutically acceptable excipient.

70. A method of inhibiting in a subject binding of an influenza virus to a hemagglutinin receptor having an umbrella topology glycan (an UTHAr), minimizing the risk of infection of a subject by an influenza virus which binds an UTHAr, treating a subject, inhibiting infection in a subject, inhibiting onset or progression of disease in a subject, or inhibiting transmission or spread of a virus, comprising:

administering an effective amount of glycan decoy to the subject.

71. The method of claim 70, further comprising a step of identifying a subject in need of being protected from infection by an influenza virus which binds an UTHAr.

72. The method of claim 70, further comprising a step of identifying a subject at risk of infection by an influenza virus which binds an UTHAr.

73. The method of claim 70, further comprising a step of selecting a glycan decoy that binds to an HA polypeptide.

74. The method of claim 73, wherein the HA polypeptide binds to UTHAr.

75. The method of claim 70, further comprising a step of providing a glycan decoy.