Human antibodies derived from immunized xenomice
OwnerRaju Kucherlapati, Aya Jakobovits +3inventors
InventorsRaju Kucherlapati, Aya Jakobovits, Sue Klapholz, Daniel Brenner, Daniel Capon
Life of this patent
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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.
Claims99
A method to produce an immunoglobulin with fully human variable region or an analog thereof, specific for a desired antigen, which method comprises:
- administering said antigen or an immunogenic portion thereof to a nonhuman animal under conditions to stimulate an immune response, whereby said animal produces B cells that secrete immunoglobulin specific for said antigen;
- wherein said nonhuman animal is characterized by being substantially incapable of producing endogenous heavy or light immunoglobulin chain variable regions, but capable of producing human immunoglobulin variable regions;
- and
- recovering said immunoglobulin or analog.
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A antibody containing a fully human variable region or analog thereof which is specifically immunoreactive with an antigen selected from the group consisting of human IL-6, human IL-8, human TNFα, human CD4, human L-selectin, human gp39 and tetanus toxin C (TTC).
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An isolated human antibody or an antigen-binding fragment thereof that specifically binds a leukocyte marker selected from the group consisting of CD2, CD3, CD4, CD5, CD6, CD7, CD8, CD11a, b, c, CD13, CD14, CD18, CD19, CD20, CD22, CD23, CD27, CD28, CD29, CD30, CD40, CD44, CD45 and isoforms, Cdw52 (Campath antigen), CD56, CD58, CD69, CD72, CTLA-4, LFA-1, and TCR,
- wherein said antibody or fragment modulates the activity of said leukocyte marker.
A method of producing an isolated human antibody that specifically binds and modulates the activity of a leukocyte marker selected from the group consisting of CD2, CD3, CD4, CD5, CD6, CD7, CD8, CD11a, b, c, CD13, CD14, CD18, CD19, CD20, CD22, CD23, CD27, CD28, CD29, CD30, CD40, CD44, CD45 and isoforms, Cdw52 (Campath antigen), CD56, CD58, CD69, CD72, CTLA-4, LFA-1, and TCR comprising:
- (a) administering the leukocyte marker or an immunogenic fragment thereof to a mouse capable of expressing human immunoglobulin;
- (b) screening the administered mouse for expression of a human antibody that specifically binds to the leukocyte marker;
- (c) selecting a mouse that produces a human antibody that specifically binds to the leukocyte marker;
- (d) isolating an antibody from the mouse that produces a human antibody that specifically binds to the leukocyte marker;
- and
- (e) determining whether the antibody modulates an activity of the leukocyte marker thereby producing a human antibody that specifically binds to the leukocyte marker and modulates an activity of the leukocyte marker.
A method of producing an isolated human antibody that specifically binds to and modulates the activity of a leukocyte marker selected from the group consisting of CD2, CD3, CD4, CD5, CD6, CD7, CD8, CD11a, b, c, CD13, CD14, CD18, CD19, CD20, CD22, CD23, CD27, CD28, CD29, CD30, CD40, CD44, CD45 and isoforms, Cdw52 (Campath antigen), CD56, CD58, CD69, CD72, CTLA-4, LFA-1, and TCR comprising:
- (a) administering the leukocyte marker or an immunogenic fragment thereof to a mouse capable of expressing human immunoglobulin;
- (b) isolating spleen cells from the mouse that produces a human antibody that specifically binds to the leukocyte marker;
- (c) fusing the spleen cells with a myeloma cell to produce a hybridoma;
- and
- (d) screening the hybridoma for expression of a human antibody that specifically binds to and modulates an activity of the leukocyte marker thereby producing a human monoclonal antibody that specifically binds to and modulates an activity of the leukocyte marker.
A method of increasing an activity of a leukocyte marker selected from the group consisting of CD2, CD3, CD4, CD5, CD6, CD7, CD8, CD11a, b, c, CD13, CD14, CD18, CD19, CD20, CD22, CD23, CD27, CD28, CD29, CD30, CD40, CD44, CD45 and isoforms, Cdw52 (Campath antigen), CD56, CD58, CD69, CD72, CTLA-4, LFA-1, and TCR in a subject comprising administering to the subject an amount of a human antibody that increases an activity of the leukocyte marker.
A method of decreasing an activity of a leukocyte marker selected from the group consisting of CD2, CD3, CD4, CD5, CD6, CD7, CD8, CD11a, b, c, CD13, CD14, CD18, CD19, CD20, CD22, CD23, CD27, CD28, CD29, CD30, CD40, CD44, CD45 and isoforms, Cdw52 (Campath antigen), CD56, CD58, CD69, CD72, CTLA-4, LFA-1, and TCR in a subject comprising administering to the subject an amount of a human antibody that decreases an activity of the leukocyte marker.
Dependencies are inferred from the claim text.