Binding molecules capable of neutralizing rabies virus and uses thereof

a technology of rabies virus and binding molecules, applied in the field of biotechnology and medicine, can solve the problems of insufficient amount, inability to neutralize rabies virus, and inability to meet the needs of patients,

Inactive Publication Date: 2008-03-20
JANSSEN VACCINES & PREVENTION BV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Rabies is a viral infection with nearly worldwide distribution that affects principally wild and domestic animals but also involves humans, resulting in a devastating, almost invariably fatal encephalitis.
A disadvantage of ERIG as well as HRIG is that they are not available in sufficient amounts and, in case of HRIG, are too expensive.
In addition, the use of ERIG might lead to adverse reactions such as anaphylactic shock.
However, the use of murine antibodies in vivo is limited due to problems associated with administration of murine antibodies to humans, such as short serum half life, an inability to trigger certain human effector functions and elicitation of an unwanted dramatic immune response against the murine antibody in a human (the “human anti-mouse antibody” (HAMA) reaction).

Method used

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  • Binding molecules capable of neutralizing rabies virus and uses thereof
  • Binding molecules capable of neutralizing rabies virus and uses thereof
  • Binding molecules capable of neutralizing rabies virus and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

example 1

Epitope Recognition of Human Anti-Rabies Antibodies CR-57 and CR-J

[0121] To address whether the human monoclonal antibodies called CR-57 and CR-JB recognize non-overlapping, non-competing epitopes, escape viruses of the human monoclonal antibodies called CR-57 and CR-JB were generated. CR-57 and CR-JB were generated essentially as described (see, Jones et al., 2003), via introduction of the variable heavy and light chain coding regions of the corresponding antibody genes into a single human IgG1 expression vector named pcDNA3002(Neo). The resulting vectors pgSO57C11 and pgSOJBC11 were used for transient expression in cells from the cell line deposited at the European Collection of Cell Cultures (ECACC), CAMR, Salisbury, Wiltshire SP4 OJG, Great Britain on 29 Feb. 1996 under number 96022940 and marketed under the trademark PER.C6®. The nucleotide and amino acid sequences of the heavy and light chains of these antibodies are shown in SEQ ID NOS:122 through 129, respectively. Serial d...

example 2

Construction of a ScFv Phage Display Library Using Peripheral Blood Lymphocytes of Rabies-Vaccinated Donors

[0126] From four rabies-vaccinated human subjects, 50 ml blood was drawn from a vein one week after the last boost. Peripheral blood lymphocytes (PBL) were isolated from these blood samples using Ficoll cell density fractionation. The blood serum was saved and frozen at −20° C. The presence of anti-rabies antibodies in the sera was tested positive using a FACS staining on rabies virus glycoprotein transfected 293T cells. Total RNA was prepared from the PBL using organic phase separation (TRIZOL™) and subsequent ethanol precipitation. The obtained RNA was dissolved in DEPC-treated ultrapure water and the concentration was determined by OD 260 nm measurement. Thereafter, the RNA was diluted to a concentration of 100 ng / μl. Next, 1 μg of RNA was converted into cDNA as follows: To 10 μl total RNA, 13 μl DEPC-treated ultrapure water and 1 μl random hexamers (500 ng / μl) were added a...

example 3

Selection of Phages Carrying Single Chain Fv Fragments Specifically Recognizing Rabies Virus Glycoprotein

[0131] Antibody fragments were selected using antibody phage display libraries, general phage display technology and MAbstract® technology, essentially as described in U.S. Pat. No. 6,265,150 and in WO 98 / 15833 (both of which are incorporated by reference herein). The antibody phage libraries used were two different semi-synthetic scFv phage libraries (JK1994 and WT2000) and the immune scFv phage libraries (RAB-03-G01 and RAB-04-G01) prepared as described in Example 2 above. The first semi-synthetic scFv phage library (JK1994) has been described in de Kruif et al. (1995b), the second one (WT2000) was built essentially as described in de Kruif et al. (1995b). Briefly, the library has a semi-synthetic format whereby variation was incorporated in the heavy and light chain V genes using degenerated oligonucleotides that incorporate variation within CDR regions. Only VH3 heavy chain ...

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Abstract

Provided are binding molecules that specifically bind rabies virus and are able to neutralize the virus. Further provided are nucleic acid molecules encoding the binding molecules, compositions comprising the binding molecules and methods of identifying or producing the binding molecules. The binding molecules can be used in the diagnosis, prophylaxis and / or treatment of a condition resulting from rabies virus. In certain embodiments, they can be used in the post-exposure prophylaxis of rabies.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a divisional of U.S. patent application Ser. No. 11 / 590,126, filed Oct. 31, 2006, now U.S. Pat. No. ______, which application is a continuation of International Patent Appln. No. PCT / EP2005 / 052410 filed May 26, 2005, and published in English as PCT Internat'l Publication No. WO 2005 / 118644 A2, on Dec. 15, 2005, which application claims priority to Internat'l Patent Appln. No. PCT / EP2005 / 050953 filed Mar. 3, 2005, which application claims priority to Internat'l Patent Appln. No. PCT / EP2005 / 050310, filed Jan. 25, 2005, which application claims priority to Internat'l Patent Appln. No. PCT / EP2004 / 052772 filed Nov. 3, 2004, which application claims priority to Internat'l Patent Appln. No. PCT / EP2004 / 052286 filed Sep. 23, 2004, which application claims priority to Internat'l Patent Appln. No. PCT / EP2004 / 051661 filed Jul. 29, 2004 which application claims priority to Internat'l Patent Appln. No. PCT / EP2004 / 050943 filed May ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12Q1/70C40B30/04A61K39/395C07K16/10G01N33/569
CPCA61K2039/505A61K2039/507C07K14/005C07K16/10C07K2316/96G01N33/56983C07K2317/34C07K2317/56C07K2317/622C12N2760/20122C07K2317/21C07K2317/76A61P31/12A61P31/14A61P43/00C12N15/11C12N15/63A61K39/395
Inventor BAKKER, ALEXANDER BERTHOLD HENDRIKMARISSEN, WILLEM EGBERTKRAMER, ROBERT ARJENDE KRUIF, CORNELIS ADRIAAN
Owner JANSSEN VACCINES & PREVENTION BV
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