Human antibodies derived from immunized xenomice

a technology of human antibodies and xenomice, which is applied in the field of immunology, can solve problems such as problems in the use of human antibodies in vivo diagnostics, in particular, and in the treatment of human diseases

Inactive Publication Date: 2006-02-23
KUCHERLAPATI RAJU +4
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Those antibodies intended for human therapeutic and in vivo diagnostic use, in particular, have been problematic because prior art sources for such antibodies resulted in immunoglobulins bearing the characteristic structures of antibodies produced by nonhuman hosts.

Method used

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  • Human antibodies derived from immunized xenomice
  • Human antibodies derived from immunized xenomice
  • Human antibodies derived from immunized xenomice

Examples

Experimental program
Comparison scheme
Effect test

example 1

Human Antibodies Against Human IL-6

[0075] Three to 5 xenomice aged 8-20 weeks were age-matched and immunized intraperitoneally with 50 μg human IL-6 emulsified in complete Freund's adjuvant for primary immunization and in incomplete Freund's adjuvant for subsequent injections. The mice received 6 injections 2-3 weeks apart. Serum titers were determined after the second dose and following each dose thereafter. Bleeds were performed 6-7 days after injections from the retrobulbar plexus. The blood was allowed to clot at room temperature for about 2 hours and then incubated at 4° C. for at least 2 hours before separating and collecting the sera.

[0076] ELISAs were conducted as described above by applying 100 μl per well of recombinant human IL-6 at 2 mg / ml in coating buffer. Plates were then incubated at 4° C. overnight or at 37° C. for 2 hours and then washed three times in washing buffer. Addition of 100 μl / well blocking buffer was followed by incubation at room temperature for 2 hou...

example 2

Human Antibodies Against Human IL-8

[0079] Immunization and serum preparation were as described in Example 1 as except that human recombinant IL-8 was used as an immunogen.

[0080] ELISA assays were performed with respect to the recovered serum, also exactly as described in Example 1, except that the ELISA plates were initially coated using 100 μl / well of recombinant human IL-8 at 0.5 mg / ml in the coating buffer. The results obtained for various serum dilutions from xenomouse A260-5 after 6 injections are shown in FIG. 2. Human anti-IL-8 reactivity was again shown at serum dilutions having concentrations higher than that represented by a 1:1,000 dilution.

example 3

Human Antibodies Against Human TNFα

[0081] Immunization and serum preparation were conducted as described in Example 1 except that human recombinant TNFα was substituted for human IL-6. ELISAs were conducted as described in Example 1 except that the initial coating of the ELISA plate employed 100 μl / well recombinant human TNFα at 1 mg / ml in coating buffer.

[0082] The dilution curves for serum from xenomouse A210-8 after 6 injections obtained are shown in FIG. 3. Again significant titers of human anti-TNFα reactivity were shown.

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Abstract

Antibodies with fully human variable regions against a specific antigen can be prepared by administering the antigen to a transgenic animal which has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled. Various subsequent manipulations can be performed to obtain either antibodies per se or analogs thereof.

Description

TECHNICAL FIELD [0001] The invention relates to the field of immunology, and in particular to the production of antibodies. More specifically, it concerns producing such antibodies by a process which includes the step of immunizing a transgenic animal with an antigen to which antibodies are desired. The transgenic animal has been modified so as to produce human, as opposed to endogenous antibodies. BACKGROUND ART [0002] PCT application WO 94 / 02602, published 3 Feb. 1994 and incorporated herein by reference, describes in detail the production of transgenic nonhuman animals which are modified so as to produce antibodies with fully human variable regions rather than endogenous antibodies in response to antigenic challenge. Briefly, the endogenous loci encoding the light and heavy immunoglobulin chains are incapacitated in the transgenic hosts and loci encoding human heavy and light chain proteins are inserted into the genome. In general, the animal which provides all the desired modifi...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12P21/04C12N5/06A61K38/00C07K16/00C07K16/12C07K16/22C07K16/24C07K16/28C07K16/46C12N15/85C12N15/87C12N15/90
CPCA01K2207/15C12N2840/203A01K2217/05A01K2217/072A01K2267/01A01K2267/0381A61K38/00A61K2039/505C07K16/00C07K16/1282C07K16/22C07K16/241C07K16/244C07K16/248C07K16/2812C07K16/2854C07K16/2875C07K16/462C07K2317/21C07K2317/24C07K2317/565C12N15/8509C12N15/87C12N15/90A01K2217/00
Inventor KUCHERLAPATI, RAJUJAKOBOVITS, AYAKLAPHOLZ, SUEBRENNER, DANIELCAPON, DANIEL
Owner KUCHERLAPATI RAJU
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