KR940703914A - 재조합 골 형태 형성 단백질 헤테로다이머, 그 조성물 및 사용방법(recombinant bone morphogenetic protein heterodimers, compositions and methods of use) - Google Patents
재조합 골 형태 형성 단백질 헤테로다이머, 그 조성물 및 사용방법(recombinant bone morphogenetic protein heterodimers, compositions and methods of use)Info
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- 238000000034 method Methods 0.000 title claims abstract 13
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- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 title 1
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 title 1
- 229940112869 bone morphogenetic protein Drugs 0.000 title 1
- 210000000988 bone and bone Anatomy 0.000 claims abstract 5
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- 210000004027 cell Anatomy 0.000 claims 23
- 108010049931 Bone Morphogenetic Protein 2 Proteins 0.000 claims 7
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 claims 7
- 108020004414 DNA Proteins 0.000 claims 6
- 239000000833 heterodimer Substances 0.000 claims 6
- 238000013518 transcription Methods 0.000 claims 6
- 230000035897 transcription Effects 0.000 claims 6
- 108010049974 Bone Morphogenetic Protein 6 Proteins 0.000 claims 5
- 108010049870 Bone Morphogenetic Protein 7 Proteins 0.000 claims 5
- 102100022525 Bone morphogenetic protein 6 Human genes 0.000 claims 5
- 102100022544 Bone morphogenetic protein 7 Human genes 0.000 claims 5
- 102000053602 DNA Human genes 0.000 claims 5
- 230000001276 controlling effect Effects 0.000 claims 5
- 239000002773 nucleotide Substances 0.000 claims 5
- 125000003729 nucleotide group Chemical group 0.000 claims 5
- 230000001105 regulatory effect Effects 0.000 claims 5
- 108010049976 Bone Morphogenetic Protein 5 Proteins 0.000 claims 4
- 102100022526 Bone morphogenetic protein 5 Human genes 0.000 claims 4
- 102100022545 Bone morphogenetic protein 8B Human genes 0.000 claims 4
- 101000899368 Homo sapiens Bone morphogenetic protein 8B Proteins 0.000 claims 4
- 230000015572 biosynthetic process Effects 0.000 claims 3
- 238000012258 culturing Methods 0.000 claims 3
- 239000001963 growth medium Substances 0.000 claims 2
- 239000000710 homodimer Substances 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 230000000638 stimulation Effects 0.000 claims 2
- 108010049955 Bone Morphogenetic Protein 4 Proteins 0.000 claims 1
- 102100024505 Bone morphogenetic protein 4 Human genes 0.000 claims 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims 1
- 241000238631 Hexapoda Species 0.000 claims 1
- 230000001580 bacterial effect Effects 0.000 claims 1
- 210000000349 chromosome Anatomy 0.000 claims 1
- 239000000539 dimer Substances 0.000 claims 1
- 210000004754 hybrid cell Anatomy 0.000 claims 1
- 239000002085 irritant Substances 0.000 claims 1
- 231100000021 irritant Toxicity 0.000 claims 1
- 210000004962 mammalian cell Anatomy 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 230000004936 stimulating effect Effects 0.000 claims 1
- 210000005253 yeast cell Anatomy 0.000 claims 1
- 206010061363 Skeletal injury Diseases 0.000 abstract 1
- 230000007547 defect Effects 0.000 abstract 1
- 230000035876 healing Effects 0.000 abstract 1
- 230000029663 wound healing Effects 0.000 abstract 1
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Abstract
본 발명은 뼈의 결합 치료, 뼈의 상치 치료 및 일반적인 상처 치료의 분야에서 유용한 재조합 헤테로다이머 BMP 단백질을 제조하는 방법에 관한 것이다. 본 발명은 또한 재조합 헤테로다이며 및 그들을 함유하는 조성물에 관한 것이다.
Description
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
Claims (36)
- 하기 각 서열이 하기 단백질의 동시 발현을 통제할 수 있는 적당한 조절 서열의 조절하에 있는, 첫 번째 선택된 BMP 또는 그 단편을 암호화하는 서열 및 두 번째 선택된 BMP 또는 그 단편을 암호화하는 서열을 가지는 선발된 숙주 세포를 배양하고 배양 배지로부터 하기 헤테로다이며 단백질을 분리함을 특징으로 하는, 골 자극능을 가진 헤테로다이머 단백질의 제조방법.
- 제1항에 있어서, 상기 첫 번째 BMP 또는 그 단편은 상기 숙주 세포내로 트랜스펙션된 첫 번째 벡터상에 존재하고 상기 두 번째 BMP 또는 그 단편은 숙주 세포내로 트랜스펙션된 두 번째 벡터상에 존재하는 방법.
- 제1항에 있어서, 상기 BMP들 또는 그 단편들 양자는 상기 숙주 세포의 염색체 내에 병합되는 방법.
- 제1항에 있어서, BMP들 또는 그 단편들 양자는 단일 벡터상에 존재하는 방법.
- 제2항에 있어서, 상기 BMP 또는 그 단편 각각을 암호화하는 하나이상의 유전자의 복사체가 각 벡터상에 존재하는 방법.
- 제1항에 있어서, 상기 숙주 세포는, 상기 서열이 각 단백질 또는 단편의 발현을 통재할 수 있는 적당한 조절 서열의 조절하에 있는, 선택된 첫 번째 또는 두 번째 BMP 또는 그 단편을 암호화하는 서열로 트랜스펙션된, 각 숙주세포 두 개가 융합되어, 선발된 안정한 숙주 세포를 배양함으로써 제조된 잡종 세포인 방법.
- 제1항에 있어서, 상기 숙주 세포는 포유류 세포인 방법.
- 제1항에 있어서, 상기 숙주 세포는 곤충 세포인 방법.
- 제1항에 있어서, 상기 숙주 세포는 효모 세포인 방법.
- 가용성의 모노머 단백질의 형성에 적당한 조건하에서 단백질 또는 단백질 단편의 발현을 통제할 수 있는 적당한 조절 서열의 조절하에 있는 첫 번째 선택된 BMP 또는 그 단편을 암호화하는 서열을 가지는 선발된 숙주 세포를 배양하고; 두 번째의 가용성 모노머 단백질을 형성하는 상기의 조건하에서 단백질 또는 단백질 단편의 발현을 통제할 수 있는 적당한 조절 서열의 조절하에 있는 두 번째 선택된 BMP 또는 그 단편을 암호화하는 서열을 가지는 선발된 숙주 세포를 배양하고; 및 하나 이상의 다이설파이드 공유 결합에 의해서 결합된 다이머 단백질의 형성을 가능케하는 조건하에서 상기 가용성의 모노머 단백질을 혼합하고; 혼합물로부터 헤테로다이머 단백질을 분리함을 특징으로하는, 세균 세포에서 골자극능을 가지는 헤테로다이머 단백질의 제조방법.
- 제10항에 있어서, 상기 숙주 세포는 이 콜리인 방법.
- 제10항에 있어서, 상기 조건은 가용성화제로 상기 단백질을 처리함을 특징으로 하는 방법.
- BMP-5, BMP-6, BMP-7 및 BMP-8로 구성된 군으로부터 선택된 두 번째 단백질 또는 그 단편과 결합된 BMP-2의 첫 번째 단백질 또는 단편을 특징으로 하는 골자극능을 가지는 재조합 헤테로다이머 단백질.
- 제13항에 있어서, 상기 두 번째 단백질은 BMP-5인 단백질.
- 제13항에 있어서, 상기 두 번째 단백질은 BMP-6인 단백질.
- 제13항에 있어서, 상기 두 번째 단백질은 BMP-7인 단백질.
- 제13항에 있어서, 상기 두 번째 단백질은 BMP-8인 단백질.
- BMP-5, BMP-6, BMP-7 및 BMP-8로 구성된 군으로부터 선택된 두 번째 단백질 또는 그 단편과 결합된 BMP-4의 단백질 또는 단편을 특징으로 하는 골자극능을 가지는 재조합 헤테로다이머 단백질.
- 제18항에 있어서, 상기 두 번째 단백질은 BMP-5인 단백질.
- 제18항에 있어서, 상기 두 번째 단백질은 BMP-6인 단백질.
- 제18항에 있어서, 상기 두 번째 단백질은 BMP-7인 단백질.
- 제18항에 있어서, 상기 두 번째 단백질은 BMP-8인 단백질.
- 선발된 숙주 세포내에서 하기 단백질들을 동시 발현함으로써 제조되는 두 번째 BMP의 단백질 또는 두 번째 BMP의 단편과 결합된 첫 번째 BMP의 단백질 또는 단편을 특징으로 하는 골자극능을 가지는 재조합 헤테로다이머 단백질.
- 제23항에 있어서, 상기 첫 번째 BMP는 BMP-2이고 상기 두 번째 BMP는 BMP-7인 방법.
- 하기 BMP들 또는 그 단편들의 동시 발현 및 헤테로디아머 단백질의 형성을 통제할 수 있는 적당한 발현 조절계의 조절하에 있는 첫 번째 BMP 또는 그 단편을 암호화하는 뉴클레오티드 서열 및 상기의 적당한 발현 조절계하에 있는 두 번째 BMP 또는 그 단편을 암호화하는 뉴클레오티드 서열을 함유하는 세포 계통.
- 제25항에 있어서, 상기 첫 번째 및 두 번째 BMP단백질을 암호화하는 상기 뉴클레오티드 서열은 단일 DNA분자내에 존재하는 세포 계통.
- 제25항에 있어서, 상기 첫 번째 GMP를 암호화하는 상기 뉴클레오티드 서열은 첫 번째 DNA분자상에 존재하고 상기 두 번째 BMP를 암호화하는 상기 뉴클레오티드 서열은 두 번째 DNA분자상에 존재하는 세포 계통.
- 제26항에 있어서, 상기 단일 DNA분자는 첫 번째 GMP 또는 그 단편을 암호화하는 유전자를 가지는 첫 번째 전사 단위 및 두 번째 BMP 또는 그 단편을 암호화하는 유전자를 가지는 두 번째 전사 단위를 함유하는 세포 계통.
- 제26항에 있어서, 상기 단일 DNA분자는 첫 번째 BMP 또는 그 단편을 암호화하는 유전자의 다수 복사체 및 상기 두 번째 BMP 또는 그 단편을 암호화하는 상기 유전자의 다수 복사체를 가지는 단일 전사단위를 함유하는 세포 계통.
- 각 BMP 또는 그 단편의 동시 발현을 통제할 수 있는 하나 이상의 적당한 조절 서열의 조절하에 있는, 첫 번째 선택된 BMP 또는 그 단편을 암호화하는 서열 및 두 번째 선택된 BMP 또는 그 단편을 암호화하는 서열을 함유하는 DNA 분자.
- 제30항에 있어서, 첫 번째 BMP 또는 그 단편을 암호화하는 유전자를 가지는 첫 번째 전사 단위 및 두 번째 BMP 또는 그 단편을 암호화하는 유전자를 가지는 두 번째 전사 단위를 함유하는 분자.
- 제30항에 있어서, 상기 첫 번째 BMP 또는 그 단편을 암호화하는 상기 유전자의 다수의 복사체 및 상기의 두 번째 BMP 또는 그 단편을 암호화하는 상기 유전자의 다수의 복사체를 가지는 단일 전사 단위를 함유하는 분자.
- 제32항에 있어서, 상기 첫 번째 BMP는 BMP-2이고 상기 두 번째 BMP는 BMP-6인 방법.
- 골자극능을 가지는, 이 콜리에서 제조된 제조합 BMP-2호모다이머.
- 이 콜리 숙주 세포를 배양하고, 생성된 배양 배지로부터 하기 단백질을 분리 및 정제함을 특징으로 하는, 골자극능을 가지는 호모다이머 BMP-2 단백질의 제조방법.
- BMP-2의 두 번째 단백질 또는 단편과 결합된 BMP-2의 첫 번째 단백질 또는 단편을 특징으로 하는, 골자극능을 가지는 재조합 헤테로다이머 단백질.※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US78749691A | 1991-11-04 | 1991-11-04 | |
| US787,496 | 1991-11-04 | ||
| US787496 | 1991-11-04 | ||
| US86469292A | 1992-04-07 | 1992-04-07 | |
| US864,692 | 1992-04-07 | ||
| US864692 | 1992-04-07 | ||
| PCT/US1992/009430 WO1993009229A1 (en) | 1991-11-04 | 1992-11-02 | Recombinant bone morphogenetic protein heterodimers, compositions and methods of use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR940703914A true KR940703914A (ko) | 1994-12-12 |
| KR100259827B1 KR100259827B1 (ko) | 2000-06-15 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019940701433A Expired - Lifetime KR100259827B1 (ko) | 1991-11-04 | 1992-11-02 | 재조합 골형태 형성 단백질 헤테로다이머, 그 조성물 및 사용방법 |
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| Country | Link |
|---|---|
| US (5) | US5866364A (ko) |
| EP (1) | EP0612348B1 (ko) |
| JP (2) | JP3504263B2 (ko) |
| KR (1) | KR100259827B1 (ko) |
| AT (1) | ATE238417T1 (ko) |
| AU (1) | AU674500B2 (ko) |
| DE (1) | DE69233022T2 (ko) |
| MX (1) | MX9206315A (ko) |
| WO (1) | WO1993009229A1 (ko) |
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1992
- 1992-11-02 AT AT92924237T patent/ATE238417T1/de not_active IP Right Cessation
- 1992-11-02 KR KR1019940701433A patent/KR100259827B1/ko not_active Expired - Lifetime
- 1992-11-02 AU AU30622/92A patent/AU674500B2/en not_active Expired
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- 1992-11-02 JP JP50867593A patent/JP3504263B2/ja not_active Expired - Fee Related
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- 1992-11-03 MX MX9206315A patent/MX9206315A/es unknown
- 1992-11-27 US US07/989,847 patent/US5866364A/en not_active Expired - Lifetime
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2001
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- 2002-07-22 JP JP2002212805A patent/JP2003125789A/ja active Pending
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Also Published As
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|---|---|
| KR100259827B1 (ko) | 2000-06-15 |
| ATE238417T1 (de) | 2003-05-15 |
| DE69233022T2 (de) | 2004-02-12 |
| US7678885B2 (en) | 2010-03-16 |
| AU674500B2 (en) | 1997-01-02 |
| EP0612348A1 (en) | 1994-08-31 |
| JP2003125789A (ja) | 2003-05-07 |
| US6190880B1 (en) | 2001-02-20 |
| MX9206315A (es) | 1993-05-01 |
| JPH07500968A (ja) | 1995-02-02 |
| AU3062292A (en) | 1993-06-07 |
| EP0612348B1 (en) | 2003-04-23 |
| DE69233022D1 (de) | 2003-05-28 |
| US20030235888A1 (en) | 2003-12-25 |
| US20090105137A1 (en) | 2009-04-23 |
| JP3504263B2 (ja) | 2004-03-08 |
| US5866364A (en) | 1999-02-02 |
| US6593109B1 (en) | 2003-07-15 |
| WO1993009229A1 (en) | 1993-05-13 |
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