Claims for Patent: 7,262,287

Summary for Patent: 7,262,287

Title:	Hansenula polymorpha yapsin deficient mutant strain and process for the preparation of recombinant proteins using the same
Abstract:	The present invention relates to a nucleic acid molecule comprising the HpYPS1 gene encoding H. polymorpha yapsin1, a polypeptide encoded by the nucleic acid molecule, a H. polymorpha mutant strain having reduced yapsin activity by mutation of the HpYPS gene encoding H. polymorpha yapsin1, a recombinant H. polymorpha strain expressing a foreign protein produced by introducing a gene encoding the foreign protein into the H. polymorpha mutant strain, and a process for preparing a foreign protein comprising culturing the recombinant H. polymorpha strain under conditions to express the foreign protein and isolating the foreign protein from the culture.
Inventor(s):	Kang; Hyun-Ah (Daejeon, KR), Rhee; Sang-Ki (Daejeon, KR), Sohn; Min-Jeong (Daejeon, KR), Kim; Jeong-Yoon (Daejeon, KR)
Assignee:	Korea Research Institute of Bioscience and Biotechnology (Daejeon, KR) Leadbio, Inc. (Daejeon, KR) Bioholdings Co., Ltd. (Daejeon, KR)
Application Number:	10/518,377
Patent Claims:	1. An isolated nucleic acid molecule comprising the sequence set forth in SEQ ID NO:1. 2. An isolated nucleic acid molecule which is the HpYPS1 gene encoding Hansenula polymorpha yapsin1 deposited under Accession No. KCTC 10285BP. 3. An isolated polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2 which is a yapsin1 protease capable of cleaving a protein comprising a basic amino acid residue or paired, dibasic, amino acid residues. 4. A Hansenula polymorpha mutant strain having yapsin1 activity reduced by a mutation or a deletion of the HpYPS1 gene according to claim 1. 5. The Hansenula polymorpha mutant strain according to claim 4 deposited under Accession No. KCTC 10281BP. 6. A recombinant Hansenula polymorpha strain that is capable of expressing a foreign protein which strain is prepared by transforming the Hansenula polymorpha yapsin1 deficient strain according to claim 4 with a gene encoding the foreign protein. 7. A process for preparing and isolating a foreign protein comprising expressing the foreign protein using the Hansenula polymorpha yapsin1 deficient strain according to claim 6 as a host, culturing a cell of the strain under conditions suitable for the exgression of the foreign protein, and isolating the foreign protein from the cultured Hansenula polymorpha yapsin1 deficient strain or the culture medium. 8. The process according to claim 7, in which the foreign protein is a recombinant protein comprising a basic amino acid residue or consecutive dibasic amino acid residues which can be cleaved by the protease having the amino acid sequence set forth in SEQ ID NO:2. 9. The process according to claim 8, in which the protein comprising a basic amino acid residue or paired, dibasic, amino acid residues is selected from the group consisting of human parathyroid hormone, human serum albumin, and an albumin fusion protein. 10. The recombinant Hansenula polymorpha strain according to claim 6, which is hpyps1A-pMOXhPTH deposited under Accession No. KCTC 10282BP. 11. A process for preparing and isolating human parathyroid hormone comprising expressing human parathyroid hormone using the Hansenula polymorpha yapsin1 deficient strain according to claim 10 as a host. 12. The recombinant Hansenula polymorpha strain according to claim 6, which is hpyps1A-pYHSA12 deposited under Accession No. KCTC 10283BP. 13. A process for preparing and isolating human serum albumin comprising expressing human serum albumin using the Hansenula polymorpha yapsin1 deficient strain according to claim 12 as a host. 14. The recombinant Hansenula polymorpha strain according to claim 6, which is hpyps1A-pYHSA13-TIMP2 deposited under Accession No. KCTC 10485BP. 15. A process for preparing and isolating an albumin fusion protein comprising expressing the albumin fusion protein using the Hansenula polymorpha yapsin1 deficient strain according to claim 14 as a host.

Details for Patent 7,262,287

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2022-06-29