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Last Updated: April 25, 2024

Claims for Patent: 5,663,482

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Summary for Patent: 5,663,482

Title:	Transgenic mice expressing a mutated human collagen gene
Abstract:	The invention is transgenic mice substantially all of whose cells contain a mutated human collagen gene. Methods for testing therapies for the treatment of osteogenesis imperfecta, osteoporosis, and chondrodysplasia are provided.
Inventor(s):	Prockop; Darwin J. (Philadelphia, PA), Ala-Kokko; Leena (Philadelphia, PA), Khillan; Jaspal S. (Philadelphia, PA), Vandenberg; Philipp (Philadelphia, PA), Kontusaari; Sirpa (Oulu, FI), Helminen; Heikki (Philadelphia, PA), Olsen; Anne (Moraga, CA), Sokolov; Boris (Philadelphia, PA)
Assignee:	Thomas Jefferson University (Philadelphia, PA)
Application Number:	08/210,063
Patent Claims:	1. A transgenic mouse whose somatic and germ cells contain at least one endogenous, normal gene for type I procollagen, and a COL1A1 mini-gene construct, wherein said mini-gene construct comprises a DNA sequence encoding the first 5 exons and the last six exons of the human pro.alpha.1(I) gene operatively linked to a promoter, wherein expression of said COL1A1 mini-gene construct results in the formation of abnormalities in the skeleton of the mouse associated with osteogenesis imperfecta. 2. The transgenic mouse of claim 1, wherein said mini-gene construct further comprises 2.5 kb of the 5' untranslated region of said human pro.alpha.1(I) gene. 3. A transgenic mouse whose somatic and germ cells contain at least one endogenous, normal gene for type I procollagen, and a COL2A1 mini-gene construct, wherein said mini-gene construct comprises a DNA sequence encoding the human pro.alpha.1(II) gene containing a deletion from intron 15 to intron 27 and wherein said DNA sequence is operatively linked to a promoter, wherein expression of the COL2A1 mini-gene construct results in the formation of abnormalities in the skeleton of the mouse associated with chondrodysplasia. 4. A method for testing the efficacy of a compound for the treatment of skeletal abnormalities associated with osteogenesis imperfecta, comprising: administering said compound to a mouse, wherein the somatic and germ cells of said mouse contain at least one endogenous, normal gene for type I procollagen, and a COL1A1 mini-gene construct, wherein said mini-gene construct comprises a DNA sequence encoding the first 5 exons and the last six exons of the human pro.alpha.1(I) gene operatively linked to a promoter, wherein expression of said COL 1A1 mini-gene construct results in the formation of abnormalities in the skeleton of the mouse associated with osteogenesis imperfecta; and monitoring said mouse to determine the effect of said compound on said skeletal abnormalities. 5. The method of claim 4, wherein said mini-gene construct further comprises 2.5 kb of the 5' untranslated region of said human pro.alpha.1(I) gene. 6. A method for testing the efficacy of a compound for the treatment of skeletal abnormalities associated with chondrodysplasia, comprising: administering said compound to a mouse, wherein the somatic and germ cells of said mouse contain at least one endogenous, normal gene for type I procollagen, and a COL2A1 mini-gene construct, wherein said mini-gene construct comprises a DNA sequence encoding the human pro.alpha.1(II) gene containing a deletion from intron 15 to intron 27 and wherein said DNA sequence is operatively linked to a promoter, wherein expression of the COL2A1 mini-gene construct results in the formation of abnormalities in the skeleton of the mouse associated with chondrodysplasia; and monitoring said mouse to determine the effect of said compound on said skeletal abnormalities. 7. The method of claim 6, wherein the chrondrodysplasia is spondyloepiphyseal dysplasia.

Details for Patent 5,663,482

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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	⤷ Try a Trial	2014-09-02
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132		⤷ Try a Trial	2014-09-02
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132		⤷ Try a Trial	2014-09-02
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

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