Specific binding agents for KSHV vIL-6 that neutralize a biological activity

• US 7,374,756 B2
• Filed: 05/14/2007
• Issued: 05/20/2008
• Est. Priority Date: 07/31/2000
• Status: Expired due to Fees

• Current Assignee: United States Department Of Health And Human Services (Government of the United States of America)
• Original Assignee: United States Department Of Health And Human Services (Government of the United States of America)
• Inventors: Aoki, Yoshiyasu, Tosato, Giovanna
• Primary Examiner(s): SALIMI, ALI REZA
• Application Number:
  US11/803,732
• Publication Number:
  US 20070243162A1
• Time in Patent Office: 372 Days
• Field of Search: 435/6, 435/345, 424/130.1, 424/141.1
• US Class Current: 424/130.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07K 16/085 Herpetoviridae, e.g. pseudorabies virus, Epstein-Barr virus
• CPC Class Codes: C07K 16/248 IL-6
• CPC Class Codes: C12Q 1/705 for herpetoviridae, e.g. herpes simplex, varicella zoster
• CPC Class Codes: C12Q 2563/131 the label being a member of a cognate binding pair, i.e. extends to antibodies, haptens, avidin
• CPC Class Codes: G01N 2333/03 Herpetoviridae, e.g. pseudorabies virus
• CPC Class Codes: G01N 2333/5412 IL-6
• CPC Class Codes: G01N 2469/10 Detection of antigens from microorganism in sample from host
• CPC Class Codes: G01N 2500/00 Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 2500/02 Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
• 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 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/56983 Viruses
• CPC Class Codes: G01N 33/56994 Herpetoviridae, e.g. cytomegalovirus, Epstein-Barr virus
• CPC Class Codes: G01N 33/6869 Interleukin

Abstract

A specific binding agent is provided, wherein the specific binding agent specifically binds Kaposi'"'"'s sarcoma-associated herpesvirus (KSHV) interleukin-6 (vIL-6), and the specific binding agent neutralizes an activity of vIL-6. In one embodiment, the specific binding agent is an antibody. Methods are provided for using a specific binding agent that binds vIL-6, and neutralizes a biological activity of vIL-6. Methods of treatment for a KSHV-associated disorder are also provided. Methods for diagnosing a KSHV-associated disorder are provided, as are kits that include a specific binding agent of the invention. A method is also provided for testing an agent for effectiveness in treating a KSHV-associated disorder. The method includes incubating the agent with a cell free system comprising a vIL-6 receptor component and vIL-6, and comparing the binding of vIL-6 and the receptor component in the presence of the agent to binding of vIL-6 to the receptor component in the absence of the agent. A decrease in the binding of vIL-6 to the receptor component in the presence of the agent indicates that the agent is effective for treating the KSHV-associated disorder.

Claims

1. An isolated functional fragment of a monoclonal antibody or a humanized form thereof, wherein the monoclonal antibody specifically binds Kaposi'"'"'s sarcoma-associated herpesvirus (KSHV) interleukin-6 (vIL-6), wherein the monoclonal antibody is produced by a hybridoma deposited as American Type Culture Collection (ATCC) Deposit No. PTA-2217, PTA-2218, PTA-2219, or PTA-2220.

2. The isolated functional fragment of claim 1, wherein the monoclonal antibody is a humanized form of the hybridoma deposited as American Type Culture Collection (ATCC) Deposit No. PTA-2217, PTA-2218, PTA-2219, or PTA-2220.

3. The isolated functional fragment of claim 1, wherein the functional fragment is labeled.

4. The isolated functional fragment of claim 3, wherein the label is a radiolabel, a fluorescent label, a colorimetric label, or a luminescent label.

5. The isolated functional fragment of claim 2, wherein the functional fragment is a Fab, Fab′

, (Fab′

)₂, Fv or a single chain fragment.

6. A method for diagnosing or determining the prognosis of an infection of a subject with a Kaposi'"'"'s sarcoma-associated herpesvirus (KSHV), comprising

contacting a sample from the subject with the isolated functional fragment of claim 1, and

detecting the binding of the monoclonal antibody with the sample,

wherein binding of the monoclonal antibody to the sample is indicative of the diagnosis or prognosis of the infection of the subject with KSHV.

7. The method of claim 6 wherein the subject has a Kaposi'"'"'s sarcoma-associated herpes virus (KSHV) associated disorder.

8. The method of claim 6 wherein the disorder is primary effusion lymphoma, Castleman'"'"'s disease, or Kaposi'"'"'s sarcoma.

9. The method of claim 6, wherein the monoclonal antibody is labeled.

10. A method of detecting Kaposi'"'"'s sarcoma-associated herpesvirus (KSHV) interleukin-6 (vIL-6) in a biological sample, comprising

contacting the biological sample with the functional fragment of the monoclonal antibody of claim 1;

and

detecting binding of the functional fragment of the monoclonal antibody to KSHV vIL-6;

thereby detecting the presence of KSHV vIL-6 in the sample.

11. The method of claim 10, wherein the functional fragment of the monoclonal antibody is labeled.

12. The method of claim 11, wherein the label is an enzyme, a radioisotope, a fluorescent compound, a colloidal metal, a chemiluminescent compound, a phosphorescent compound, or a bioluminescent compound.