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1. 发明授权

US06291205B1 Method of increasing production of disulfide bonded recombinant proteins by saccharomyces cerevisiae 失效
标题翻译：通过酿酒酵母增加二硫键合重组蛋白的产生的方法
公开(公告)号：US06291205B1
公开(公告)日：2001-09-18
申请号：US07901713
申请日：1992-06-12
申请人： Michael F. Tuite , Robert B. Freedman , Loren D. Schultz , Ronald W. Ellis , Henry Z. Markus , Donna L. Montgomery
发明人： Michael F. Tuite , Robert B. Freedman , Loren D. Schultz , Ronald W. Ellis , Henry Z. Markus , Donna L. Montgomery
IPC分类号： C12P2102
CPC分类号： C12N9/90 , C07K14/811 , C07K14/815 , C12N15/81
摘要： Disclosed is a process for increasing the yield of disulfide bonded recombinant proteins produced by yeast, especially recombinant secreted proteins The enzyme protein disulfide isomerase (PDI) catalyzes the formation of disulfide bonds in secretory and cell-surface proteins. We disclose the construction of recombinant strains of the yeast Saccharomyces cerevisiae which overproduce either human PDI or yeast PDI in a regulated fashion. These strains show greatly increased secretion of disulfide bonded proteins of potential therapeutic significance. These strains have the potential to increase the production of various disulfide bonded proteins.
摘要翻译：公开了一种增加由酵母，特别是重组分泌蛋白质产生的二硫键合重组蛋白的产量的方法。酶蛋白二硫键异构酶（PDI）催化分泌和细胞表面蛋白中二硫键的形成。我们公开了以规定的方式过量产生人PDI或酵母PDI的酵母酿酒酵母重组菌株的构建。这些菌株显示出显着增加的二硫键合蛋白的分泌具有潜在的治疗意义。这些菌株有可能增加各种二硫键合蛋白的产生。

2. 发明申请

US20080166371A1 Optimized expression of HPV 31 L1 in yeast 有权
标题翻译：酵母中优化HPV31 L1的表达
公开(公告)号：US20080166371A1
公开(公告)日：2008-07-10
申请号：US11879905
申请日：2007-07-19
申请人： Kathrin U. Jansen , Loren D. Schultz , Michael P. Neeper , Henry Z. Markus
发明人： Kathrin U. Jansen , Loren D. Schultz , Michael P. Neeper , Henry Z. Markus
IPC分类号： A61K39/12 , C07K14/025 , C12P21/00
CPC分类号： C07K14/005 , A61J1/035 , A61J7/04 , A61K31/66 , A61K31/675 , A61K2039/5258 , C12N7/00 , C12N2710/20022 , C12N2710/20023 , C12N2800/22
摘要： Synthetic DNA molecules encoding the HPV31 L1 protein are provided. Specifically, the present invention provides polynucleotides encoding HPV31 L1 protein, wherein said polynucleotides are free from internal transcription termination signals that are recognized by yeast. Also provided are synthetic polynucleotides encoding HPV31 L1 wherein the polynucleotides have been codon-optimized for high level expression in a yeast cell. The synthetic molecules may be used to produce HPV31 virus-like particles (VLPs), and to produce vaccines and pharmaceutical compositions comprising the HPV31 VLPs. The vaccines of the present invention provide effective immunoprophylaxis against papillomavirus infection through neutralizing antibody and cell-mediated immunity.
摘要翻译：提供编码HPV31 L1蛋白的合成DNA分子。具体地，本发明提供编码HPV31 L1蛋白的多核苷酸，其中所述多核苷酸不含被酵母识别的内部转录终止信号。还提供了编码HPV31 L1的合成多核苷酸，其中多核苷酸已被密码子优化用于酵母细胞中的高水平表达。合成分子可用于产生HPV31病毒样颗粒（VLP），以及生产包含HPV31 VLP的疫苗和药物组合物。本发明的疫苗通过中和抗体和细胞介导的免疫来提供对乳头瘤病毒感染的有效免疫预防。

3. 发明授权

US07482428B2 Optimized expression of HPV 31 L1 in yeast 有权
标题翻译：酵母中优化HPV31 L1的表达
公开(公告)号：US07482428B2
公开(公告)日：2009-01-27
申请号：US11879905
申请日：2007-07-19
申请人： Kathrin U. Jansen , Loren D. Schultz , Michael P. Neeper , Henry Z. Markus
发明人： Kathrin U. Jansen , Loren D. Schultz , Michael P. Neeper , Henry Z. Markus
IPC分类号： A61K38/00
CPC分类号： C07K14/005 , A61J1/035 , A61J7/04 , A61K31/66 , A61K31/675 , A61K2039/5258 , C12N7/00 , C12N2710/20022 , C12N2710/20023 , C12N2800/22
摘要： Synthetic DNA molecules encoding the HPV31 L1 protein are provided. Specifically, the present invention provides polynucleotides encoding HPV31 L1 protein, wherein said polynucleotides are free from internal transcription termination signals that are recognized by yeast. Also provided are synthetic polynucleotides encoding HPV31 L1 wherein the polynucleotides have been codon-optimized for high level expression in a yeast cell. The synthetic molecules may be used to produce HPV31 virus-like particles (VLPs), and to produce vaccines and pharmaceutical compositions comprising the HPV31 VLPs. The vaccines of the present invention provide effective immunoprophylaxis against papillomavirus infection through neutralizing antibody and cell-mediated immunity.
摘要翻译：提供编码HPV31 L1蛋白的合成DNA分子。具体地，本发明提供编码HPV31 L1蛋白的多核苷酸，其中所述多核苷酸不含被酵母识别的内部转录终止信号。还提供了编码HPV31 L1的合成多核苷酸，其中多核苷酸已被密码子优化用于酵母细胞中的高水平表达。合成分子可用于产生HPV31病毒样颗粒（VLP），以及生产包含HPV31 VLP的疫苗和药物组合物。本发明的疫苗通过中和抗体和细胞介导的免疫来提供对乳头瘤病毒感染的有效免疫预防。

4. 发明授权

US07276243B2 Optimized expression of HPV31 L1 in yeast 有权
公开(公告)号：US07276243B2
公开(公告)日：2007-10-02
申请号：US10551057
申请日：2004-03-19
申请人： Kathrin U. Jansen , Loren D. Schultz , Michael P. Neeper , Henry Z. Markus
发明人： Kathrin U. Jansen , Loren D. Schultz , Michael P. Neeper , Henry Z. Markus
IPC分类号： A61K39/12
CPC分类号： C07K14/005 , A61J1/035 , A61J7/04 , A61K31/66 , A61K31/675 , A61K2039/5258 , C12N7/00 , C12N2710/20022 , C12N2710/20023 , C12N2800/22
摘要： Synthetic DNA molecules encoding the HPV31 L1 protein are provided. Specifically, the present invention provides polynucleotides encoding HPV31 L1 protein, wherein said polynucleotides are free from internal transcription termination signals that are recognized by yeast. Also provided are synthetic polynucleotides encoding HPV31 L1 wherein the polynucleotides have been codon-optimized for high level expression in a yeast cell. The synthetic molecules may be used to produce HPV31 virus-like particles (VLPs), and to produce vaccines and pharmaceutical compositions comprising the HPV31 VLPs. The vaccines of the present invention provide effective immunoprophylaxis against papillomavirus infection through neutralizing antibody and cell-mediated immunity HPV31 L1 total rebuild nucleotide and amino acid sequence: M S L W R P S 1 ATGTCTTTGT GGAGACCATC E A T V Y L P P V P TGAAGCTACC GTCTACTTGC CACCAGTCCC V S K V V S T 51 AGTCTCTAAG GTCGTCTCTA D E Y V T R T N I Y CCGACGAATA CGTCACCAGA ACCAACATCT Y H A G S A 101 ACTACCACGC TGGTTCTGCT R L L T V G H P Y Y AGATTGTTGA CCGTCGGTCA CCCATACTAC S I P K S D N 151 TCTATCCCAA AGTCTGACAA P K K I V V P K V S CCCAAAGAAG ATCGTCGTCC CAAAGGTCTC G L Q Y R V F 201 TGGTTTGCAA TACAGAGTCT R V R L P D P N K F TCAGAGTCAG ATTGCCAGAC CCAAACAAGT G F P D T S 251 TCGGTTTCCC AGACACCTCT F Y N P E T Q R L V TTCTACAACC CAGAAACCCA AAGATTGGTC W A C V G L E 301 TGGGCTTGTG TCGGTTTGGA V G R G Q P L G V G AGTCGGTAGA GGTCAACCAT TGGGTGTCGG I S G H P L L 351 TATCTCTGGT CACCCATTGT N K F D D T E N S N TGAACAAGTT CGACGACACC GAAAACTCTA R Y A G G P 401 ACAGATACGC TGGTGGTCCA G T D N R E C I S M GGTACCGACA ACAGAGAATG TATCTCTATG D Y K Q T Q L 451 GACTACAAGC AAACCCAATT C L L G C K P P I G GTGTTTGTTG GGTTGTAAGC CACCAATCGG E H W G K G S 501 TGAACACTGG GGTAAGGGTT P C S N N A I T P G CTCCATGTTC TAACAACGCT ATCACCCCAG D C P P L E 551 GTGACTGTCC ACCATTGGAA L K N S V I Q D G D TTGAAGAACT CTGTCATCCA AGACGGTGAC N V D T G F G 601 ATGGTCGACA CCGGTTTCGG A N D F T A L Q D T TGCTATGGAC TTCACCGCTT TGCAAGACAC K S W V P L D 651 CAAGTCTAAC GTCCCATTGG I C N S I C K Y P D ACATCTGTAA CTCTATCTGT AAGTACCCAG Y L K M V A 701 ACTACTTGAA GATGGTCGCT E P Y G D T L F F Y GAACCATACG GCGACACCTT GTTCTTCTAC L R R E Q M F 751 TTGCGTAGAG AACAGATGTT V R H F F N R S G T CGTAAGGCAC TTCTTCAACA GATCCGGCAC V G E S V P T 801 CGTAGGTGAA TCTGTCCCAA D L Y I K G S G S T CCGACCTGTA CATCAAGGGC TCCGGTTCCA A T L A N S 851 CCGCTACCCT GGCTAACTCC T Y F P T P S G S N ACCTACTTCC CAACTCCATC TGGCTCCATG V T S D A Q I 901 GTCACCTCCG ACGCTCAGAT F N K P Y W M Q R A CTTCAACAAG CCATACTGGA TGCAGCGTGC Q G H N N G I 951 ACAGGGTCAC AACAACGGTA C W G N Q L F V T V TCTGTTGGGG TAACCAGCTG TTCGTGACTG V D T T R S 1001 TGGTCGATAC CACGCGTTCT T N N S V C A A I A ACCAACATGT CTGTCTGTGC TGCAATCGCT N S D T T F K 1051 AACTCTGACA CTACCTTCAA S S N F K E Y L R H GTCCTCTAAC TTCAAGGAGT ACCTGAGACA G E E F D L Q 1101 TGGTGAGGAA TTCGATCTGC F I F Q L C K I T L AATTCATCTT CCAGTTGTGC AAGATCACCC S A D I N T 1151 TGTCTGCTGA CATCATGACC Y I H S M N P A I L TACATCCACA GTATGAACCC TGCCATCCTG E D W N F G L 1201 GAGGACTGGA ACTTCGGTCT T T P P S G S L E D GACCACTCCA CCTTCCGGTT CTTTGGAAGA.

5. 发明授权

US4273762A Lyophilization process for live viral compositions 失效
标题翻译：活病毒组合物的冻干过程
公开(公告)号：US4273762A
公开(公告)日：1981-06-16
申请号：US99772
申请日：1979-12-03
申请人： William J. McAleer , Henry Z. Markus
发明人： William J. McAleer , Henry Z. Markus
IPC分类号： C12N7/00 , A61K35/76 , A61K39/00 , A61K39/12 , A61K39/165
CPC分类号： A61K39/165 , A61K39/12 , A61K2039/5254 , C12N2760/18434
摘要： Lyophilization time of live viral compositions is reduced and output per lyophilization unit is increased by lyophilizing a reduced volume of a more concentrated viral composition.
摘要翻译：减少活体病毒组合物的冻干时间，并通过冻干减少体积的更浓缩的病毒组合物来增加每个冻干单元的产量。

6. 发明授权

US4338335A Vaccine stabilizer containing L-glutamic acid and L-arginine 失效
标题翻译：含L-谷氨酸和L-精氨酸的疫苗稳定剂
公开(公告)号：US4338335A
公开(公告)日：1982-07-06
申请号：US173534
申请日：1980-07-30
申请人： William J. McAleer , Henry Z. Markus
发明人： William J. McAleer , Henry Z. Markus
IPC分类号： A61K39/12 , A61K39/165 , A61K39/13 , A61K39/245
CPC分类号： A61K39/165 , A61K39/12 , C12N7/00 , A61K2039/525 , A61K2039/5254 , C12N2760/18434 , C12N2760/18451
摘要： An improved stabilized liquid live viral vaccine contains a live virus, partially hydrolyzed gelatin, a monosaccharide or disaccharide, a cell culture medium, L-glutamic acid, L-arginine and sufficient physiologically acceptable acidic buffer to maintain the pH at from about 6.0 to about 6.5.
摘要翻译：改进的稳定的液体活病毒疫苗含有活病毒，部分水解的明胶，单糖或二糖，细胞培养基，L-谷氨酸，L-精氨酸和足够的生理上可接受的酸性缓冲液，以将pH保持在约6.0至约 6.5。

7. 发明授权

US4301249A High titer production of hepatitis A virus 失效
标题翻译：高滴度生产甲型肝炎病毒
公开(公告)号：US4301249A
公开(公告)日：1981-11-17
申请号：US171621
申请日：1980-07-23
申请人： Henry Z. Markus , William J. McAleer
发明人： Henry Z. Markus , William J. McAleer
IPC分类号： A61K39/29 , C12N7/00
CPC分类号： A61K39/29 , A61K39/12 , C12N2770/32434 , C12N2770/32451
摘要： Hepatitis A virus (HAV) is produced in high titer from tissue cultures grown on a hollow fiber capillary unit.
摘要翻译：从生长在中空纤维毛细管单元上的组织培养物以高效价产生甲型肝炎病毒（HAV）。

8. 发明授权

US5888516A Recombinant papillomavirus vaccines 失效
标题翻译：重组乳头状瘤病毒疫苗
公开(公告)号：US5888516A
公开(公告)日：1999-03-30
申请号：US969523
申请日：1997-10-22
申请人： Kathrin U. Jansen , James C. Cook, III , Hugh A. George , Kathryn J. Hofmann , Joseph G. Joyce , Ernest Dale Lehman , Henry Z. Markus , Mark Rosolowsky , Loren S. Schultz
发明人： Kathrin U. Jansen , James C. Cook, III , Hugh A. George , Kathryn J. Hofmann , Joseph G. Joyce , Ernest Dale Lehman , Henry Z. Markus , Mark Rosolowsky , Loren S. Schultz
IPC分类号： A61K38/00 , A61K39/00 , A61P31/00 , A61P37/04 , C07K14/025 , C12N15/81 , A61K39/12 , C12N7/04
CPC分类号： C07K14/005 , C12N15/81 , A61K38/00 , A61K39/00 , C12N2710/20022 , C12N2710/20023 , C12N2710/20034 , Y10S977/804 , Y10S977/915 , Y10S977/917 , Y10S977/918
摘要： Recombinant expression vectors encoding the L1 and L2 proteins of papillomavirus, methods of making and using the recombinant proteins and purified virus-like particles comprised of the recombinant proteins are provided.
摘要翻译：提供了编码乳头瘤病毒的L1和L2蛋白的重组表达载体，制备和使用由重组蛋白组成的重组蛋白和纯化的病毒样颗粒的方法。

9. 发明授权

US5024836A Stable lyophilized live herpes virus vaccine 失效
标题翻译：稳定的冻干活疱疹病毒疫苗
公开(公告)号：US5024836A
公开(公告)日：1991-06-18
申请号：US423658
申请日：1989-10-19
申请人： William J. McAleer , Robert Z. Maigetter , Henry Z. Markus
发明人： William J. McAleer , Robert Z. Maigetter , Henry Z. Markus
IPC分类号： A61K39/245 , A61K39/295
CPC分类号： A61K39/245 , A61K39/12 , A61K2039/5254 , A61K2039/70 , A61K39/0015 , C12N2710/16734
摘要： The invention comprises a lyophilized live herpes virus vaccine that comprises from about 0.5% to about 8% moisture.
摘要翻译：本发明包括冻干的活疱疹病毒疫苗，其包含约0.5％至约8％的水分。

10. 发明授权

US4337242A Vaccine stabilizer containing L-glutamic acid and L-arginine 失效
公开(公告)号：US4337242A
公开(公告)日：1982-06-29
申请号：US242195
申请日：1981-03-10
申请人： Henry Z. Markus , William J. McAleer
发明人： Henry Z. Markus , William J. McAleer
IPC分类号： A61K39/12 , A61K39/165 , A61K39/13 , A61K39/245
CPC分类号： A61K39/12 , A61K47/183 , A61K47/26 , A61K47/42 , A61K9/0019 , A61K2039/525 , C12N2760/18434
摘要： An improved stabilized liquid live viral vaccine contains a live virus, partially hydrolyzed gelatin, a monosaccharide or disaccharide, a cell culture medium, L-glutamic acid, L-arginine and sufficient physiologically acceptable acidic buffer to maintain the pH at from about 6.0 to about 6.5.

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