Transgenic mammals and methods of use thereof
AssigneeTrianni, Inc.
InventorMatthias WABL
Life of this patent
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Abstract
The present invention relates to transgenic mammals that express canine-based immunoglobulins, including transgenic rodents that express canine-based immunoglobulins for the development of canine therapeutic antibodies.
Claims18
A method of producing antibodies comprising fully canine heavy and/or light chain variable domains and rodent constant domains, the method comprising:
- (i) providing a transgenic rodent with a genome in which an entire endogenous immunoglobulin variable gene locus has been deleted and replaced with an engineered partly canine immunoglobulin locus comprising canine immunoglobulin variable gene VH, D and JH and/or canine VL and JL coding sequences and rodent immunoglobulin variable gene locus non-coding regulatory sequences, wherein the engineered partly canine immunoglobulin locus of the transgenic rodent is functional and expresses immunoglobulin chains comprised of canine variable domains and rodent constant domains;
- and
- (ii) isolating the antibodies comprising canine carriable regions and rodent constant regions expressed by the transgenic rodent.
A method of producing monoclonal antibodies comprising fully canine variable regions and rodent constant regions, the method comprising:
- (i) providing a transgenic rodent with a genome in which an entire endogenous immunoglobulin variable gene locus has been deleted and replaced with an engineered partly canine immunoglobulin locus comprising canine immunoglobulin variable gene VH, D and JH and/or canine VL and JL coding sequences and rodent immunoglobulin variable gene locus non-coding regulatory sequences, wherein the engineered partly canine immunoglobulin locus of the transgenic mouse is functional and expresses immunoglobulin chains comprised of canine variable domains and rodent constant domains;
- (ii) obtaining B-cells from the transgenic rodent;
- (iii) immortalizing the B-cells;
- and
- (iv) isolating antibodies comprising canine variable domains and rodent constant domains expressed by the immortalized B-cells.
A B lymphocyte from a transgenic rodent with a genome in which an entire endogenous immunoglobulin variable gene locus has been deleted and replaced with an engineered partly canine immunoglobulin locus comprising canine immunoglobulin variable gene VH, D and JH and/or canine VL and JL coding sequences and rodent immunoglobulin variable gene locus non-coding regulatory sequences, wherein the engineered partly canine immunoglobulin locus of the transgenic rodent is functional and expresses immunoglobulin chains comprised of canine variable domains and rodent constant domains.
Dependencies are inferred from the claim text.