Engineered polypeptide agents for targeted broad spectrum influenza neutralization

• US 9,334,309 B2
• Filed: 01/24/2014
• Issued: 05/10/2016
• Est. Priority Date: 01/27/2010
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Sasisekharan, Ram, Viswanathan, Karthik, Soundararajan, Venkataramanan, Raguram, S., Sasisekharan, Viswanathan, Subramanian, Vidya
• Primary Examiner(s): Alstrum Acevedo, James H
• Assistant Examiner(s): DABKOWSKI, ERINNE R
• Application Number:
  US14/163,882
• Publication Number:
  US 20140206603A1
• Time in Patent Office: 837 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/162 from virus
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61P 31/12 Antivirals
• 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: C07K 14/001 by chemical synthesis
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C12N 2760/16122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2760/16133 Use of viral protein as therapeutic agent other than vaccine, e.g. apoptosis inducing or anti-inflammatory
• CPC Class Codes: C12N 7/00 Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00
• CPC Class Codes: G01N 2333/11 Orthomyxoviridae, e.g. influenza virus
• CPC Class Codes: G01N 33/56983 Viruses

Abstract

The present invention provides novel agents for broad spectrum influenza neutralization. The present invention provides agents for inhibiting influenza infection by bind to the influenza virus and/or hemagglutinin (HA) polypeptides and/or HA receptors, and reagents and methods relating thereto. The present invention provides a system for analyzing interactions between infolds and the interaction partners that bind to them.

Claims

1. A method comprising steps of:

providing a sample from a patient suspected of suffering from an influenza infection;

contacting the sample with an infold agent that binds a hemagglutinin (HA) polypeptide, wherein the infold agent comprises an infold selected from the group consisting of Infold-1, Infold-2, Infold-3, Infold-4, Infold-5, Infold-6, Infold-7, Infold-8, Infold-9, Infold-10, Infold-11, Infold-12, Infold-13, Infold-14, Infold-15, Infold-16, Infold-17, Infold-18, Infold-19, Infold-20, Infold-21, Infold-22, Infold-23, Infold-24, Infold-25, Infold-26, Infold-27, Infold-28, Infold-29, Infold-30, Infold-31, Infold-32, Infold-33, Infold-34, Infold-35, Infold-36, Infold-37, Infold-38, Infold-39, and Infold-40; and

detecting binding of the infold agent to components in the sample; and

based on the detected binding, diagnosing the patient as suffering from an influenza infection.

2. The method of claim 1, wherein prior to the step of contacting, the sample is processed by subjecting it to one or more purification steps.

3. The method of claim 1, wherein the infold agent is labeled with a detectable moiety.

4. The method of claim 3, wherein the detectable moiety is a fluorescent moiety.

5. The method of claim 3, wherein the detectable moiety is a radioactive moiety.

6. The method of claim 3, wherein the detectable moiety is a chemoluminescent moiety.

7. The method of claim 1, wherein the infold agent is detected by an immunological method.

8. The method of claim 7, wherein the immunological method is Western blotting.

9. The method of claim 7, wherein the immunological method is ELISA.

10. The method of claim 7, wherein the immunological method is immunofluorescence.

11. The method of claim 1, wherein the infold agent is immobilized.

12. The method of claim 11, wherein the infold agent is immobilized to a bead.

13. The method of claim 11, wherein the infold agent is immobilized to a microtiter dish.

14. The method of claim 11, wherein the infold agent is immobilized to an array.

15. The method of claim 14, wherein the array is a glycan array.