 MYPPPY variants of CTL A4 and uses thereof |
| OF THE INVENTION Definition As used in this application, the following words or phrases have the ... |
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| CTLA4 receptor and uses thereof |
| OF THE INVENTION DEFINITION As used in this application, the following words or phrases have the ... |
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| CTLA4/CD28Ig hybrid fusion proteins and uses thereof |
| OF THE INVENTION DEFINITION As used in this application, the following words or phrases have the ... |
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| Method of regulating cellular processes mediated by B7 and CD28 |
| Accordingly, the present invention identifies the B7 antigen as a ligand recognized by the CD28 ... |
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| Methods of inhibiting T cell proliferation or IL-2 accumulation with CTLA4- specific antibodies |
| This invention is based, at least in part, on the discovery of novel ligands which bind a T cell ... |
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| Method for generating and identifying antibodies directed against a B7 |
| Accordingly, the present invention identifies the B7 antigen as a ligand recognized by the CD28 ... |
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| Polypeptide that interacts with heat shock proteins |
| Described herein are the isolation and characterization of a polypeptide, particularly a ... |
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| 1,2-Biguanides |
| What is claimed is: 1. A substituted biguanide of the formula ##EQU8## wherein R.sub.1 is alkyl of 1... |
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| Biguanide salts |
| OF THE INVENTION The invention relates to biguanide salts. In another aspect, the invention ... |
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Transgenic non-human animals capable of producing heterologous antibodies
| Details |
Inventors: Lonberg, Nils; Kay, Robert M.;
Assignee: GenPharm International, Inc. (Mountain View, CA)
Primary Examiner: Ziska; Suzanne E.
Assistant Examiner:
Attorney, Agent or Firm: Townsend and Townsend and Crew LLP
The invention relates to transgenic non-human animals capable of producing heterologous antibodies, i.e., antibodies encoded by immunoglobulin heavy and light chain genes not normally found in the genome of that species of non-human animal. In one aspect of the invention, transgenes encoding unrearranged heterologous human immunoglobulin heavy and light chains are introduced into a non-human animal thereby forming a transgenic animal capable of producing antibodies encoded by human immunoglobulin genes. Such heterologous human antibodies are produced in B-cells which are thereafter immortalized, e.g., by fusing with an immortalizing cell line such as a myeloma or by manipulating such B-cells by other techniques to perpetuate a cell line capable of producing a monoclonal heterologous antibody. The invention also relates to heavy and light chain immunoglobulin transgenes for making such transgenic non-human animals as well as methods and vectors for disrupting endogenous immunoglobulin loci in the transgenic animal. The invention also includes methods to generate a synthetic immunoglobulin variable region gene segment repertoire used in transgene construction and methods to induce heterologous antibody production using animals containing heterologous rearranged or unrearranged heavy and light chain immunoglobulin transgenes. |
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DETAILED DESCRIPTION The design of a transgenic non-human animal that responds to foreign antigen stimulation with a heterologous antibody repertoire, requires that the heterologous immunoglobulin transgenes contained within the transgenic animal function correctly throughout the pathway of B-cell development.
Accordingly, the transgenes in one aspect of the invention are constructed so as to produce one or all of the following: (1) high level and cell-type specific expression, (2) functional gene rearrangement, (3) activation of and response to allelic exclusion, (4) expression of a sufficient primary repertoire, (5) signal transduction, (6) class switching, (7) somatic hypermutation, and (8) domination of the transgene antibody locus during the immune response.
As will be apparent from the following disclosure, not all of the foregoing criteria need be met.
For example, in those embodiments wherein the endogenous immunoglobulin loci of the transgenic animal are functionally disrupted, the transgene need not activate allelic exclusion.
Further, in those embodiments wherein the transgene comprises a functionally rearranged heavy and/or light chain immunoglobulin gene, the second criteria of functional gene rearrangement is unnecessary, at least for that transgene which is already rearranged.
For background on molecular immunology, see, Fundamental Immunology, 2nd edition (1989), Paul William E.
, ed.
Raven Press, N.
Y.
The Structure and Generation of Antibodies Immunoglobulins, also known as antibodies, are a group of glycoproteins present in the serum and tissue fluids of all mammals.
They are produced in large amounts by plasma cells (also referred to herein as "secondary repertoire B-cells") which develop from precursor B lymphocytes (referred to herein as "primary repertoire B-cells").
Such primary repertoire B-cells carry membrane-bound immunoglobulin which is similar to that produced by the fully differentiated secondary repertoire B-cell.
Contact between primary repertoire B-cells and foreign antigen is required for the induction of antibody formation
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