Claims for Patent: 5,656,455

Summary for Patent: 5,656,455

Title:	Method and compositions for making ACSF and ACSF antagonists
Abstract:	The complete amino acid and nucleotide sequence for adenylate cyclase stimulating factor is provided, thereby facilitating the synthesis of ACSF in recombinant cell culture. ACSF amino acid sequence variants and ACSF antibodies are provided which are useful in the treatment of humoral hypercalcemia of malignancy or in immunoassays for ACSF. In particular, antibodies capable of binding only the C-terminal domains of ACSF are useful in immunoassays for ACSF which avoid interference by parathyroid hormone. Also provided are novel polypeptides selected from the group of the ACSF basic peptide, the ACSF C-terminal peptide, or the ACSF domain containing both of the basic and C-terminal peptides.
Inventor(s):	Wood; William I. (San Mateo, CA), Martin; Thomas John (Victoria, AU), Suva; Larry John (Victoria, AU)
Assignee:	University of Melbourne (Victoria, AU)
Application Number:	08/330,131
Patent Claims:	1. An isolated nucleic acid which encodes Adenylate Cyclase Stimulating Factor (ACSF) comprising the primary amino acid sequence of FIG. 2. 2. An isolated nucleic acid which encodes a polypeptide comprising about residues 1-83 of the primary amino acid sequence of FIG. 2. 3. The isolated nucleic acid of claim 2, wherein the polypeptide further comprises about residues 84-108 of the primary amino acid sequence of FIG. 2. 4. The isolated nucleic acid of claim 2, wherein the polypeptide further comprises about residues 109-141 of the primary amino acid sequence of FIG. 2. 5. An isolated nucleic acid which encodes a polypeptide comprising about residues 84-108 of the primary amino acid sequence of FIG. 2. 6. The isolated nucleic acid of claim 5, wherein the polypeptide further comprises about residues 109-141 of the primary amino acid sequence of FIG. 2. 7. An isolated nucleic acid which encodes a polypeptide comprising about residues 109-141 of the primary amino acid sequence of FIG. 2. 8. An isolated nucleic acid which encodes an Adenylate Cyclase Stimulating Factor (ACSF) insertion variant polypeptide selected from the group consisting of [V.sub.2 GGS.sub.3 ]ACSF(1-141), [V.sub.2 SS.sub.3 ]ACSF(1-141), [V.sub.2 EKA.sub.3 ]ACSF(1-141), [G.sub.123 PPD.sub.124 ]ACSF(3-141), [S.sub.130 FYT.sub.131 ]ACSF(3-141), [R.sub.139 DYR.sub.140 ]ACSF(3-141), [V.sub.2 AGS.sub.3 ]ACSF(1-141), [T.sub.132 KKKS.sub.133 ]ACSF(1-141), [S.sub.3 EEE.sub.4 ]ACSF(134), [E.sub.4 IH.sub.5 ]ACSF(1-34), [E.sub.4 IH.sub.5 DQ.sub.6 ]ACSF(1-34) and [P.sub.44 DN.sub.45 ]ACSF(1-141). 9. An isolated nucleic acid which encodes an Adenylate Cyclase Stimulating Factor (ACSF) deletion variant polypeptide selected from the group consisting of ACSF(1-83), ACSF(1-34), ACSF(1-84, 109-141), ACSF(1-34, 40-141), ACSF(1-50, 60-141), ACSF(1-75, 84-141), ACSF(1-109), ACSF(3-34), ACSF(4-34), ACSF(5-34), ACSF(6-34) and ACSF(3-124). 10. An isolated nucleic acid which encodes an Adenylate Cyclase Stimulating Factor (ACSF) substitution variant polypeptide selected from the group consisting of PTH(7-34)ACSF(35-141) and PTH(3-34)ACSF(35-141), wherein PTH is parathyroid hormone. 11. An isolated nucleic acid which encodes an Adenylate Cyclase Stimulating Factor (ACSF) substitution variant polypeptide selected from the group consisting of [MY.sub.1 ]ACSF(1-141), [MP.sub.1 ]ACSF(1-141), [MG.sub.1 ]ACSF(1-141), [F.sub.2 ]ACSF(1-141), [Y.sub.2 ]ACSF(1-141), [H.sub.2 ]ACSF(1-141), [D.sub.3 ]ACSF(1-141), [Y.sub.3 ]ACSF(1-141), [H.sub.3 ]ACSF(1-141), [K.sub.20 ]ACSF(1-141), [E.sub.19 ]ACSF(1-141), [V.sub.21 ]ACSF(1-141), [D.sub.20 ]ACSF(1-141), [Y.sub.24 ]ACSF(1-141), [K.sub.25 ]ACSF(1-141), [E.sub.25 ]ACSF(1-141), [M.sub.31 ]ACSF(1-141), [Y.sub.34 ]ACSF(3-141), [I.sub.8, I.sub.18, Y.sub.34 ]ACSF(3-141), [I.sub.8, I.sub.18, Y.sub.34 ]ACSF(3-34), [D.sub.79 ]ACSF(1-141), [P.sub.98 ]ACSF(1-141), [P.sub.105 ]ACSF(1-141), [Y.sub.90 ]ACSF(1-141), [W.sub.89 ]ACSF(1-141), [H.sub.96 ]ACSF(1-141), [F.sub.110 ]ACSF(106-141), [Y.sub.117 ]ACSF(106-141), [D.sub.122 ]ACSF(106-141), [K.sub.125 ]ACSF(106-141), [Y.sub.132 ]ACSF(106-141), [A.sub.133 ]ACSF(106-141) and [D.sub.141 ]ACSF(106-141). 12. A replicable vector comprising a nucleic acid of any one of claims 1-11. 13. The vector of claim 12 wherein the nucleic acid is under the control of an inducible promoter. 14. A cell culture comprising the vector of claim 13. 15. The cell culture of claim 14 wherein the cells are prokaryotes, yeast or obtained from a multicellular organism. 16. The cell culture of claim 15 wherein the cells from a multicellular organism are mammalian. 17. A method for making Adenylate Cyclase Stimulating Factor (ACSF) comprising: (a) isolating nucleic acid encoding a polypeptide comprising the primary amino acid sequence of FIG. 2; (b) inserting the nucleic acid into a replicable vector under the transcriptional control of a promoter; (c) transfecting the vector into a host cell which transcribes the nucleic acid under the control of the promoter; (d) culturing the cell to permit ACSF to accumulate in the cell culture and (e) recovering the ACSF from the cell culture. 18. The method of claim 17 wherein the ACSF is recovered from the culture medium or from the periplasm of the host cell. 19. The method of claim 17 wherein the ACSF is recovered in step (e) by adsorption on a cation exchange resin. 20. The method of claim 17 wherein the nucleic acid encodes a polypeptide comprising about residues 1-83 of the primary amino acid sequence of FIG. 2. 21. The method of claim 20 wherein the polypeptide further comprises about residues 109-141 of the primary amino acid sequence of FIG. 2. 22. The method of claim 20 wherein the polypeptide further comprises about residues 84-108 of the primary amino acid sequence of FIG. 2. 23. The method of claim 17 wherein the nucleic acid encodes a polypeptide comprising about residues 84-108 of the primary amino acid sequence of FIG. 2. 24. The method of claim 23 wherein the polypeptide further comprises about residues 109-141 of the primary amino acid sequence of FIG. 2. 25. The method of claim 17 wherein the nucleic acid encodes a polypeptide comprising about residues 109-141 of the primary amino acid sequence of FIG. 2.

Details for Patent 5,656,455

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2014-08-12