Compositions of hormonally active human and porcine inhibin containing an .alpha. chain and 62 chain

• US 4,798,885 A
• Filed: 12/31/1986
• Issued: 01/17/1989
• Est. Priority Date: 02/07/1986
• Status: Expired due to Term

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Seeburg, Peter H., Mason, Anthony J.
• Primary Examiner(s): SAUNDERS, DAVID A
• Application Number:
  US06/906,729
• Time in Patent Office: 748 Days
• Field of Search: 530/300, 525/455
• US Class Current: 530/350
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 14/575 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin C07K14/665, e.g. corticotropin C07K14/695
• CPC Class Codes: Y10S 930/26 Containing cys-cys disulfide bridge between nonadjacent cysteine residues

Abstract

DNA encoding the prepro inhibin α and β chains has been isolated. This DNA is ligated into expression vectors and used to transform host cells for the preparation of inhibin or activin. Also provided are prohormone domains and other inhibin α or β chain derivatives having therapeutic or diagnostic interest. The compositions provided herein are useful in the manipulation of fertility in animals.

Claims

1. A composition comprising hormonally active human inhibin as a product of recombinant host cell expression, the human inhibin containing an α

chain and a β

chain wherein the α

chain has the amino acid sequence ##STR4## and the β

chain is selected from the β

A chain sequence ##STR5## or the β

B chain sequence ##STR6## and hormonally active, substantially homologous amino acid sequence variants of said human inhibin other than porcine inhibin.

2. The composition of claim 1 wherein the variant is about 90% homologous with the human inhibin amino acid sequences.

3. The composition of claim 1 wherein the variant is a naturally occurring allele.

4. The composition of claim 1 which is completely free of unidentified human proteins.

5. The composition of claim 1 which is a product of recombinant host cell expression in cells of a multicellular organism.

6. The composition of claim 5 wherein the organism is vertebrate.

7. The composition of claim 1 wherein the β

chain is the β

A chain.

8. The composition of claim 7 wherein the β

chain is the β

B chain.

9. The composition of claim 1 further comprising a physiologically acceptable implantable matrix for controlled release of the inhibin into the tissues of an animal.

10. A composition comprising porcine inhibin as a product of recombinant host cell expression, the porcine inhibin containing an α

chain and a β

chain wherein the α

chain has the amino acid sequence ##STR7## and the β

chain is selected from the β

A chain sequence ##STR8## or the β

B chain sequence ##STR9## and hormonally active, substantially homologous amino acid sequence variants of said porcine inhibin other than human inhibin.

11. The composition of claim 10 wherein the variant is about 90% homologous with the porcine inhibin amino acid sequences.

12. The composition of claim 10 wherein the variant is a naturally occurring allele.

13. The composition of claim 10 which is completely free of unidentified porcine proteins.

14. The composition of claim 10 which is a product of recombinant host cell expression in cells of a multicellular organism.

15. The composition of claim 14 wherein the organism is vertebrate.

16. The composition of claim 10 wherein the β

chain is the β

A chain.

17. The composition of claim 16 wherein the β

chain is the β

B chain.

18. The composition of claim 10 further comprising a physiologically acceptable implantable matrix for controlled release of the inhibin into the tissues of an animal.

19. A composition free of human inhibin α

chain comprising a homodimer of a human inhibin β

chain having the amino acid sequence ##STR10##

22. The composition of claim 19 as a product of recombinant host cell expression.

20. A composition free of human inhibin α

chain comprising a homodimer of a human inhibin β

chain having the amino acid sequence ##STR11##

23. The composition of claim 20 as a product of recombinant host cell expression.

21. A composition free of human inhibin α

chain comprising a heterodimer of human inhibin β

chains having the amino acid sequence ##STR12## and ##STR13##

24. The composition of claim 21 as a product of recombinant host cell expression.