Claims for Patent: 5,859,314

Summary for Patent: 5,859,314

Title:	Mice with targeted tyrosine kinase, lyn, disruption
Abstract:	A non-human animal carrying a disruption of a gene encoding a lyn protein tyrosine kinase provides a convenient system for the study of diseases associated with or caused by lyn deficiency, and for the testing of therapeutic agents for the treatment or prevention of diseases which include autoimmune diseases, allergy, asthma and malignant disease.
Inventor(s):	Hibbs; Margaret L. (Parkville, AU), Dunn; Ashley R. (Parkville, AU), Graill; Dianne (Parkville, AU), Hodgson; George (Parkville, AU), Tarlington; David M. (Parkville, AU), Armes; Jane (Heidelberg, AU)
Assignee:	Ludwig Institute for Cancer Research (New York, NY)
Application Number:	08/730,876
Patent Claims:	1. A transgenic mouse carrying a disruption in both alleles of a gene encoding a protein tyrosine kinase, lyn, such that expression of said tyrosine kinase is at a non-existent level, wherein the disruption causes said mouse to display a phenotype characterized by lyn deficiency which results in an autoimmune disease in said mouse, and at least one symptom selected from the group consisting of; depletion of lymphoid tissue with age progression, extramedullary hematopoiesis, expansion of myeloid cells, glomerulonephritis, and defective IgE-mediated anaphylactic response. 2. The transgenic mouse according to claim 1, wherein the disruption results in the inability of the non-human transgenic animal to produce enzymatically active lyn. 3. The transgenic mouse according to claim 1, wherein said gene encoding the protein tyrosine kinase lyn carries a mutation comprising deletion of the lyn promoter and the associated regulatory sequences of said gene that regulate expression of said lyn. 4. The transgenic mouse according to claim 3, wherein said deletion further comprises a deletion in intron 1 between a PstI site and an XbaI site, the PstI site being upstream of the lyn promoter, and the XbaI site being downstream of said lyn promoter. 5. The transgenic mouse according to claim 1, wherein the phenotype is displayed in said mouse by 6-8 weeks, of age. 6. A transgenic mouse carrying a disruption in both alleles of a gene encoding a protein tyrosine kinase, lyn, such that expression of said tyrosine kinase is at a non-existent level, wherein the disruption causes said mouse to display a phenotype characterized by lyn deficiency which results in impaired B cell function and/or pancytopaenia in said mouse. 7. The transgenic mouse of claim 1, wherein said autoimmune disease is selected from the group consisting of glomerulonephritis and pancytopaenia. 8. The transgenic mouse of claim 1, wherein said autoimmune disease manifests itself as lupus erythematosus. 9. A transgenic mouse carrying a disruption in both alleles of a gene encoding a protein tyrosine kinase, lyn, such that expression of the tyrosine kinase is at a non-existent level, wherein the disruption causes said mouse to display a phenotype characterized by lyn deficiency which results in a depletion of lymphoid tissue in said mouse. 10. A transgenic mouse carrying a disruption in both alleles of a gene encoding a protein tyrosine kinase, lyn, such that expression of the tyrosine kinase is at a non-existent level, wherein the disruption causes said mouse to display a phenotype characterized by lyn deficiency which results in a disease characterized by a malignancy of myeloid origin in said mouse. 11. The mouse of claim 10, wherein said malignancy is selected from the group consisting of myeloid leukemia, malignant histocytoma and histocytosis. 12. A transgenic mouse carrying a disruption in both alleles of a gene encoding a protein tyrosine kinase, lyn, such that expression of the tyrosine kinase is at a non-existent level, wherein the disruption causes said mouse to display a phenotype characterized by lyn deficiency, which results in defective IgE anaphylactic response in said mouse. 13. A cell-line derived from the transgenic mouse of claim 1. 14. A method of testing the efficacy of a treatment for an autoimmune disease associated with a non-existent level of protein tyrosine kinase, lyn, comprising subjecting the transgenic mouse of claim 1 to the putative treatment and determining the efficacy of said treatment. 15. The method according to claim 14, wherein said autoimmune disease is selected from the group consisting of allergy, asthma, a disease characterized by a malignancy of myeloid origin and a disease characterized by impaired B cell function. 16. The method according to claim 15, wherein said autoimmune disease is glomerulonephritis or pancytopenia. 17. The method according to claim 15, wherein said disease characterized by a malignancy of myeloid origin produces an overproduction of cells of the myeloid lineage. 18. The method according to claim 15, wherein said treatment comprises administering an analogue of lyn having tyrosine kinase activity to a subject in need thereof. 19. The method according to claim 14, wherein said autoimmune disease is lupus erythematosus. 20. The method according to claim 15, wherein said disease characterized by a malignancy is of myeloid origin and is selected from the group consisting of myeloid leukemia, malignant histocytoma and histocytosis. 21. A method for testing whether an agent is useful for treating a condition associated with non-existent level of lyn protein tyrosine kinase comprising administering said agent to the transgenic mouse of claim 1, and determining a level of lyn protein tyrosine kinase, wherein a change in said non-existent level towards a normal level is indicative of efficacy of said agent. 22. A method for determining whether an agent is useful for restoring B cell function comprising administering said agent to the transgenic mouse of claim 1, and determining any rise B cell function of said non-human transgenic mouse, wherein any rise B cell function is indicative of a restorative effect on B cell function of said agent.

Details for Patent 5,859,314

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132	06/04/1986		2039-02-26
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2039-02-26
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2039-02-26