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AssigneeTherapeutic Human Polyclonals, Inc.
InventorsRoland Buelow, Josef Platzer
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The invention provides a novel approach to increase immunoglobulin expression in non-human transgenic animals. For instance, the invention provides a method to increase humanized immunoglobulin production in animals genetically engineered to express one or several human or humanized immunoglobulin transloci. This can be done by overexpressing the apoptosis inhibitor, i.e. a rabbit bcl-2, whose expression is driven by a B-cell specific promoter specifically in the B-cell of the animal, thereby enhancing the survival of B-cells. This invention further relates to a method for selectively enhancing the survival of exogenous B-cells, that is B-cells expressing any immunoglobulin transgene locus, over the survival of endogenous B-cells that do not express the transgene locus. Selectivity is achieved by expressing the apoptosis-inhibitor only within exogenous B-cells, that is, by coupling exogenous immunoglobulin expression with apoptosis inhibitor expression. This latter method allows for increased expression and production of the transgene encoded product(s) over the endogenously produced immunoglobulin of the transgenic animal. The invention also provides a novel apoptosis-inhibitor, rabbit bcl-2.
1-10. (canceled)
A method for enhancing the expression of an immunoglobulin or immunoglobulin chain in a transgenic animal undergoing short-term lymphopoiesis, comprising introducing into said transgenic animal undergoing short-term lymphopoiesis at least one transgene construct comprising an apoptosis-inhibitor transgene driven by a B-cell specific promoter/enhancer to produce said transgenic animal, whereby apoptosis of the B-cells carrying said transgene construct is inhibited and production of the immunoglobulin or immunoglobulin chain is enhanced.
22-47. (canceled)
Dependencies are inferred from the claim text.