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Last Updated: May 4, 2024

Claims for Patent: 5,304,489


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Summary for Patent: 5,304,489
Title: DNA sequences to target proteins to the mammary gland for efficient secretion
Abstract:Described is a method of targeting specific genes to the mammary gland which results in the efficient synthesis and secretion of biologically important molecules. Further, there is described as a composition of matter, a transgenic mammal having the ability to reproduce itself and being suitable for the secretion of biologically active agents into its milk. Additionally there is disclosed as a composition of matter, recombinant DNA gene complexes designed to integrate into a mammalian genome and to synthesize and secrete biological active agents into the milk. Furthermore methods of producing and using altered milk are disclosed.
Inventor(s): Rosen; Jeffrey M. (Houston, TX)
Assignee: GenPharm International, Inc. (Mountain View, CA)
Application Number:07/602,066
Patent Claims:1. A recombinant DNA complex to provide preferential mammary gland expression and secretion of a selected polypeptide comprising:

(a) a casein promoter;

(b) a transcribable DNA segment coding for said selected polypeptide, wherein said promoter does not naturally control the transcription of said DNA segment; and

(c) secretory DNA encoding a signal peptide functional in mammary secretory cells operably linked between said promoter and said DNA segment to facilitate secretion of said selected polypeptide,

(d) a casein enhancer sequence capable of conferring enhanced preferential transcription of said recombinant DNA complex in mammary secretory cells when said complex is integrated into the genome of a non-human mammal, and

(e) an intron from a casein gene.

2. The recombinant DNA complex of claim 1 wherein said promoter is from a casein gene selected from the group consisting of .alpha.-casein, .beta.-casein, .gamma.-casein and .kappa.-casein.

3. The recombinant DNA complex of claim 2 wherein said promoter is a .beta.-casein promoter.

4. The recombinant DNA complex of claim 3 wherein said casein enhancer is selected from the group consisting of .alpha.-casein, .beta.-casein, .gamma.-casein and .kappa.-casein enhancers.

5. The recombinant DNA complex of claim 1 further comprising a mouse mammary tumor virus glucocorticoid response element.

6. The recombinant DNA complex of claim 1 wherein said secretory DNA encoding a signal peptide is from a mammary gland specific gene.

7. The recombinant DNA complex of claim 6 wherein said mammary gland specific gene is selected from the group consisting of whey acid protein and casein genes.

8. The recombinant DNA complex of claim 7 wherein said mammary gland specific gene is a casein gene.

9. The recombinant DNA complex of claim 6 wherein said intron is from a casein gene selected from the group consisting of .alpha.-casein, .beta.-casein, and .kappa.-casein genes.

10. The recombinant DNA complex of claim 1 wherein said transcribable DNA segment encodes a normally secreted polypeptide and said secretory DNA encodes the endogenous signal peptide sequence of said secreted polypeptide.

11. The recombinant DNA complex of claim 1 further comprising:

(f) DNA encoding a 5' untranslated sequence from a mammary gland specific gene.

12. The recombinant DNA complex of claim 11 further comprising:

(g) DNA encoding a 3' untranslated sequence.

13. The recombinant DNA complex of claim 1, wherein said intron links said transcribable DNA segment to said promoter.

14. The recombinant DNA complex of claim 1, wherein said intron is located within said transcribable DNA segment.

Details for Patent 5,304,489

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 2011-04-19
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b For Injection 103132 ⤷  Try a Trial 2011-04-19
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b Injection 103132 ⤷  Try a Trial 2011-04-19
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

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