KR910009285A - Chimeric Mouse-human Antibodies Specific for HIV Antigens - Google Patents

Abstract

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Description

Chimeric Mouse-human Antibodies Specific for HIV Antigens

As this is a public information case, the full text was not included.

FIG. 9 shows the construction chart for the chimeric mouse-human chimeric 2H chain mammalian expression plasmid, pING3004.

Claims (52)

(a) encoding at least a portion of a variable region of an immunoglobulin chain having specificity for human immunodeficiency virus-1 antigen selected from the group consisting of gp160, gp120, p55, p45, p39, p24, p18, p65 and p51 A polynucleotide molecule consisting of a nucleotide sequence and (b) an additional nucleotide sequence encoding at least a portion of a constant region of a human immunoglobulin chain, the binding state in which both sequences are operable to each other And wherein said polynucleotide molecule encodes a polypeptide capable of binding said antigen. The molecule of claim 1, wherein the antigen is selected from the group consisting of gp160 and gp120. The molecule of claim 1, wherein the antigen is selected from the group consisting of p55, p45, p39, p24 and p18. The molecule of claim 1, wherein said antigen is selected from the group consisting of p65 and p51. The molecule of claim 1, wherein said additional nucleotide sequence is a cDNA sequence. The molecule of claim 1, wherein the molecule is a recombinant DNA molecule. 7. The molecule of claim 6 which is in the form of double stranded DNA. 8. The molecule of claim 7, which is an expression carrier. The molecule of claim 8, wherein said carrier is a plasmid. A prokaryotic host characterized by being transformed with the molecule of claim 1. The host of claim 10, wherein the host is a bacterium. A prokaryotic host characterized in that it is transfected with the molecule of claim 1. 13. The host of claim 12, which is a yeast cell or a mammalian cell. The molecule of claim 1, wherein the immunoglobulin chain is heavy chain. The molecule of claim 1, wherein said immunoglobulin chain is a light chain. Immunoglobulins consisting of at least some human constant regions and at least some variable regions having specificity for human immunodeficiency virus-1 antigen selected from the group consisting of gp160, gp120, p55, p45, p39, p24, p18, p65 and p51 Heavy chain. 17. An immunoglobulin heavy chain according to claim 16, wherein said antigen is selected from the group consisting of gp160 and gp120. 17. An immunoglobulin heavy chain according to claim 16, wherein said antigen is selected from the group consisting of p55, p45, p39, p24, and p18. 17. An immunoglobulin heavy chain according to claim 16, wherein said antigen is selected from the group consisting of p65 and p51. Immunoglobulins consisting of at least some human constant regions and at least some variable regions having specificity for human immunodeficiency virus-1 antigen selected from the group consisting of gp160, gp120, p55, p45, p39, p24, p18, p65 and p51 Light chain. 21. The immunoglobulin light chain of claim 20, wherein the antigen is selected from the group consisting of gp160 and gp120. 21. An immunoglobulin light chain according to claim 20, wherein said antigen is selected from the group consisting of p55, p45, p39, p24 and p18. 21. An immunoglobulin light chain according to claim 20, wherein said antigen is selected from the group consisting of p65 and p51. Consisting of two light chains and two heavy chains, each of said chains being human immunodeficiency virus selected from the group consisting of at least some human constant regions and gp160, gp120, p55, p45, p39, p24, p18, p65 and p51 A chimeric immunoglobulin molecule or cross section or derivative of said immunoglobulin, characterized by consisting of at least some variable regions with specificity for -1 antigen. The chimeric immunoglobulin, fragment or derivative according to claim 24, wherein said antigen is selected from the group consisting of gp160 and gp120. The chimeric immunoglobulin, fragment or derivative according to claim 24, wherein said antigen is selected from the group consisting of p55, p45, p39, p24 and p18. The chimeric immunoglobulin, fragment derivative according to claim 24, wherein said antigen is selected from the group consisting of p65 and p51. The immunoglobulin, fragment or derivative according to claim 24, which is in a detectably labeled form. 29. An immunoglobulin, fragment or derivative according to claim 28 wherein said label is a radionuclide. The immunoglobulin, fragment or derivative of claim 24, wherein the immunoglobulin, fragment or derivative is conjugated to a cytotoxic drug. The immunoglobulin, fragment or derivative of claim 24, wherein said immunoglobulin, fragment or derivative is conjugated to a cytotoxic protein. The immunoglobulin, fragment or derivative of claim 24, wherein the immunoglobulin, fragment or derivative is conjugated to an antiviral agent. The immunoglobulin, fragment or derivative according to claim 24 which is immobilized on a solid phase. A chimeric immunoglobulin molecule, fragment or derivative consisting of at least a portion of a variable region of an immunoglobulin chain derived from an antibody selected from the group consisting of monoclonal antibodies designated 2E12, 2G12, 1C11 and 4D12. (a) cultivating a host capable of expressing a light chain under culture conditions, wherein the heavy chain is at least some human constant region and gp160, gp120, p55, p45, p39, p24, p18, p65 and p51 Having at least some variable regions with specificity for human immunodeficiency virus-1 antigen selected from the group consisting of (b) expressing the heavy chain and (c) recovering the heavy chain from the culture. Method for producing a chimeric type immunoglobulin heavy chain characterized in that. (a) cultivating a host capable of expressing a light chain under culture conditions, wherein the heavy chain is at least some human constant region and gp160, gp120, p55, p45, p39, p24, p18, p65 and p51 Having at least some variable regions with specificity for human immunodeficiency virus-1 antigen selected from the group consisting of (b) expressing the light chain and (c) recovering the light chain from the culture. Method for producing a chimeric type immunoglobulin light chain, characterized in that. (a) culturing a host capable of expressing a light chain under culture conditions, expressing the light chain, recovering the light chain from the culture, and (b) culturing a host capable of expressing a heavy chain. Under culturing separately, expressing the heavy chains, and recovering the heavy chains from the culture, wherein each of the heavy and light chains comprises at least some human constant regions and gp160, gp120, p55, p45, having at least some variable regions with specificity for a human immunodeficiency virus-1 antigen selected from the group consisting of p39, p24, p18, p65 and p51] (c) by combining the recovered heavy and light chains A method for producing a chimeric immunoglobulin, fragment or derivative comprising a heavy chain and a light chain characterized by preparing a chimeric immunoglobulin, fragment or derivative. (a) co-culturing a host capable of expressing a light chain together with a host capable of expressing a heavy chain under culture conditions, (b) expressing the heavy chain and the light chain, wherein each of the heavy chains is And the light chain is at least some human constant region and at least some variable with specificity for human immunodeficiency virus-1 antigen selected from the group consisting of gp160, gp120, p55, p45, p39, p24, p18, p65 and p51. Region) (c) allowing the heavy and light chains to be combined into the chimeric immunoglobulin, fragment or derivative, and (d) recovering the chimeric immunoglobulin, fragment, or derivative from the culture. Method for producing a chimeric type immunoglobulin, fragment or derivative comprising a heavy chain and light chain characterized in that. (a) culturing a host capable of expressing heavy and light chains under culture conditions, wherein each of the heavy and light chains comprises at least some human constant regions and gp160, gp120, p55, p45, p39, having at least some variable regions with specificity for a human immunodeficiency virus-1 antigen selected from the group consisting of p24, p18, p65 and p51] (c) shaping said chimeric immunoglobulin, fragment or derivative ( c) A method for producing a chimeric immunoglobulin, fragment or derivative comprising a heavy chain and a light chain, characterized in that for recovering the chimeric immunoglobulin, fragment or derivative from the culture. 40. The method of any one of claims 35-39, wherein said antigen is selected from the group consisting of gp160 and gp120. 40. The method of any one of claims 35-39, wherein said antigen is selected from the group consisting of p55, p45, p39, p24 and p18. 40. The method of any one of claims 35-39, wherein said antigen is selected from the group consisting of p65 and p51. 40. The method of any one of claims 35-39, wherein said host is a prokaryote. 40. The method of any one of claims 35-39, wherein said host is a eukaryote. (a) contacting a sample with the immunoglobulin, fragment or derivative of claim 24 or 28, and (b) detecting the binding of the immunoglobulin, fragment or derivative to the antigen. -1 Immunoassay to detect antigen. An imaging method for detecting a human immunodeficiency virus-1 antigen in an animal characterized by (a) contacting the labeled immunoglobulin, fragment or derivative of claim 28 and (b) detecting said antigen. (a) adding an immunoglobulin, fragment or derivative according to any one of claims 24 to 32 to the cell, and (b) letting the cell occur, lethal of a cell carrying a human immunodeficiency virus-1 antigen. Way. 48. The method of claim 47, wherein said lethality is caused by antibody-dependent cellular cytotoxicity, proton-dependent cytotoxicity, radiocytotoxicity, cytotoxic drug response, or protein toxin reaction. A method for treating a subject with suspected human immunodeficiency virus-1 infection, comprising administering to the subject an effective dosage of an immunoglobulin, fragment or derivative according to any one of claims 24 to 32. (a) adding a solution to a device comprising an immobilized immunoglobulin, fragment or derivative according to claim 33, and (b) applying a virus, infectious cell, viral antigen or immunocomplex to the immobilized immunoglobulin, fragment or derivative. Human immunodeficiency virus-1, virus-infected cells, human immunodeficiency virus-1 antigen, or viral antigen, characterized in that it removes viruses, infected cells, virus antigens or immune complexes from the fluid by binding. How to get rid of immune complexes. 51. The method of claim 50, wherein said liquid is a bodily fluid. (a) removing an immune complex comprising a virus, a virus infected with a virus, an antigen of the virus or a viral virus from the subject's policy according to the method of claim 50, and (b) returning the body fluid to the subject. A method for treating a subject suspected of human immunodeficiency virus-1 infection. ※ Note: The disclosure is based on the initial application.