CN112442120A - 抗严重急性呼吸系统综合征ii型冠状病毒sars-cov-2的中和抗体 - Google Patents
抗严重急性呼吸系统综合征ii型冠状病毒sars-cov-2的中和抗体 Download PDFInfo
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Abstract
本发明公开了一种抗严重急性呼吸系统综合征II型冠状病毒SARS‑COV‑2的中和抗体,属于生物医药技术领域。本发明从COVID‑19康复患者血液中提取外周免疫细胞,并从中筛选可以和新冠病毒抗原蛋白‑刺突蛋白结合的B细胞,然后对以生产抗体的单个B细胞在单细胞水平上进行分析,获得了B细胞内编码中和抗体可变区重链和轻链的基因序列。这些序列即可用来体外重新构建和表达可中和新冠病毒的中和抗体,有望用于新冠病毒所引起的肺炎等疾病的治疗和预防。
Description
技术领域
本发明涉及一种抗严重急性呼吸系统综合征II型冠状病毒SARS-COV-2的中和抗体,属于生物医药技术领域。
背景技术
抗严重急性呼吸系统综合征II型冠状病毒(SARS-CoV 2)感染引起的肺炎(COVID-19)是严重传染性疾病,并在全球范围内造成了严重影响。寻找针对该病毒的有效治疗方案是一种迫切需求。
中和抗体是指与病毒结合后能消除病毒感染能力的抗体,是当病原微生物侵入机体时由B淋巴细胞而产生的相应的抗体,是由适应性免疫应答细胞分泌的一种可溶性蛋白。病原微生物入侵细胞时需要依赖病原体自身表达的特定分子与细胞上的受体结合,才能感染细胞,并进一步扩增。中和抗体能够与病原微生物表面的抗原结合,从而阻止该病原微生物黏附靶细胞受体,防止侵入细胞。病毒侵入人体之后,B细胞把中和抗体分泌到血液里,抗体与血液里的病毒颗粒结合,阻止病毒感染细胞,破坏病毒颗粒,这样就把病毒“中和”掉了。由此可见,中和抗体在杀灭细胞外的游离病毒时起主要作用。
来自病毒感染治愈患者血液的某些特异性中和抗体具有中和病毒的作用,因而可用于感染性疾病的治疗,使病毒丧失致病力。随着抗体制备技术的进步,治疗性抗体已逐渐在多种疾病的治疗方面发挥了很好的效果。现有的疫苗如麻疹疫苗、脊髓灰质炎疫苗、乙肝疫苗、甲肝疫苗,都是使接种者产生中和抗体以预防病毒感染的。由于中和抗体可在病毒进入细胞之前破坏病毒并可清除体内细胞外的游离病毒,所以,基于病毒感染痊愈患者血液中的中和抗体可用于病毒感染的治疗。
发明内容
为解决上述技术问题,本发明从COVID-19康复患者血液中提取外周免疫细胞,并从中筛选可以和新冠病毒抗原蛋白-刺突蛋白结合的B细胞,然后对以生产抗体的单个B细胞在单细胞水平上进行分析,获得了B细胞内编码中和抗体可变区重链和轻链的基因序列。这些序列即可用来体外重新构建和表达可中和新冠病毒的中和抗体,有望用于新冠病毒所引起的肺炎等疾病的治疗和预防。
本发明的第一个目的是提供一种抗严重急性呼吸系统综合征II型冠状病毒SARS-COV-2的中和抗体,包括:轻链可变区DNA序列,以及重链可变区DNA序列;
所述轻链可变区DNA序列的核苷酸序列为SEQ ID NO.1-5中的一种或多种组合;
所述重链可变区DNA序列的核苷酸序列为SEQ ID NO.6-8中的一种或多种。
进一步地,所述的中和抗体为包含恒定区和可变区的完整抗体、只包含可变区的部分抗体或只包含可变区的嵌合抗体。
本发明的第二个目的是提供一种编码所述的中和抗体的基因。
本发明的第三个目的是提供一种携带所述的基因的表达载体。
本发明的第四个目的是提供一种表达所述的中和抗体的重组细胞。
本发明的第五个目的是提供所述的中和抗体在制备治疗肺炎COVID-19的药物中的应用。
本发明的第六个目的是提供一种治疗肺炎COVID-19的试剂盒,所述试剂盒内含有所述的中和抗体。
本发明的有益效果是:
本发明从COVID-19康复患者血液中提取外周免疫细胞,并从中筛选可以和新冠病毒抗原蛋白-刺突蛋白结合的B细胞,然后对以生产抗体的单个B细胞在单细胞水平上进行分析,获得了B细胞内编码中和抗体可变区重链和轻链的基因序列。这些序列即可用来体外重新构建和表达可中和新冠病毒的中和抗体,有望用于新冠病毒所引起的肺炎等疾病的治疗和预防。
附图说明
图1为利用COVID-19康复患者血液中的单个B细胞筛选中和抗体流程示意图。
具体实施方式
下面结合附图和具体实施例对本发明作进一步说明,以使本领域的技术人员可以更好地理解本发明并能予以实施,但所举实施例不作为对本发明的限定。
实施例1:可和SARS-COV-2结合的单个B细胞的分离提取
抽取多个新冠病毒肺炎康复患者血液约15mL,采用Ficoll梯度法分离提取每个康复患者血液中的外周血单个核细胞(PBMC),并将所得PBMC洗涤两遍后备用。
在每个PBMC样品中先加入Fc block,作用15分钟后依次加入APC-H7标记的抗人CD3抗体,BV421标记的抗人CD19抗体,BB700标记的抗人CD27抗体,Biotin标记的SARS-COV-2刺突蛋白,Biotin标记的SARS-COV-2 Spike RBD。尔后加入Streptavidin-APC并作用30分钟。尔后采用FACS AriaTMIII流式细胞仪上样分析收集抗体标记好的PBMC样品。CD3为T细胞的特异性表面标志物,CD19为B细胞的特异性表面标志物,CD27为记忆性B细胞的特异性表面标志物,Biotin标记的两种抗原可以和APC标记的Streptavidin特异性的结合,所以APC阳性的细胞即是可以和SARS-COV-2特异性结合的细胞。选取CD3-CD19+CD27+APC+的细胞即是我们在寻找的可以和SARS-COV-2特异性结合的记忆性B细胞。将该类B细胞利用流式细胞仪进行单个B细胞分离并直接打入预先载有细胞裂解液的96孔板,立即封膜,并置于干冰上迅速冷冻,然后置于-80℃保存待用。这样即可以分离得到能和SARS-COV-2特异性结合的单个B细胞。
实施例2:单个B细胞中可变区轻链和重链的扩增和测序
因为B细胞为分泌抗体的细胞,所以能和SARS-COV-2结合的B细胞内储存有抗体的序列信息。将96孔板中已经裂解得到的单个B细胞裂解液分成3份。一份用于进行Kappa轻链序列分析,一份进行lamda轻链的序列分析,另一份进行重链序列的分析。
在该部分实验中,先用RT-PCR反转录得到cDNA文库,然后利用巢式PCR技术扩增单个细胞中的DNA序列。因为实验中所使用的的引物为轻链可变区或重链可变区特异性的引物,所以所得序列即为该单个B细胞中的抗体可变区轻链和重链部分的序列。将扩增所得序列进行DNA测序分析即得单个B细胞中所包含的抗体可变区轻链和重链的序列信息。
RT-PCR扩增单B细胞抗体轻重链可变区基因
设计RT-PCR引物(SEQ ID NO.9-25),如表1所示:
表1
以分选出的单个B细胞作为模板,进行单个B细胞RT-PCR。PCR体系配置及加样均在生物安全柜中完成并置于冰上操作,RT-PCR反应体系及反应条件如下:
PCR反应体系:
表2
成分 | 体系 | 终浓度 |
无RNA酶的水 | - | - |
5×RT-PCR缓冲液 | 10.0μl | 1× |
dNTP混合物 | 2.0μl | 每种dNTP 400μM |
A引物 | - | 0.6μM |
B引物 | - | 0.6μM |
混合酶 | 2.0μl | |
RNA酶抑制剂 | - | 5-10个单位 |
模板RNA | - | 1pg–2μg |
总体系 | 50.0μl | - |
PCR反应条件:
巢式PCR扩增单B细胞抗体轻重链可变区基因
设计巢式PCR引物(SEQ ID NO.26-38),如表3所示:
表3
以RT-PCR产物为模板,建立三个PCR反应体系,分别扩增抗体的H链、κ链、λ链的可变区基因,每个反应体系分别使用与其对应的混合引物,巢式PCR反应体系及反应条件如下:
PCR反应体系:
表4
PCR试剂 | 每个样品的体积(μl)(25μl体系) | 最终浓度 |
Taq DNA聚合酶 | 0.25 | 50U ml<sup>-1</sup> |
10×缓冲液 | 2.5 | 1× |
dNTPs(10mM) | 0.5 | 200μM |
正向引物:VH3a和VH3b或PanVκ | 0.5 | 1.2μM |
反向引物:PW-Cgamma或CK494-516 | 0.5 | 1.2μM |
无RNA酶的水 | 17.25-19.25(补齐体系至24μl) | - |
模板 | 1.0 | - |
PCR反应条件:
实施例3:实验结果
本申请从康复患者可以结合新冠病毒刺突蛋白的B细胞中共得到5个轻链可变区序列,3个重链可变区序列。该5个轻链可变区序列和3个重链可变区序列可以自由组合成为抗体即为新冠病毒SARS-COV-2的中和抗体。
以上所述实施例仅是为充分说明本发明而所举的较佳的实施例,本发明的保护范围不限于此。本技术领域的技术人员在本发明基础上所作的等同替代或变换,均在本发明的保护范围之内。本发明的保护范围以权利要求书为准。
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<120> 抗严重急性呼吸系统综合征II型冠状病毒SARS-COV-2的中和抗体
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<210> 1
<211> 501
<212> DNA
<213> (人工序列)
<400> 1
gtcctgctct gtgacactct cctgggagtt acccgattgg agggcgttat ccaccttcca 60
ctgtactttg gcctctctgg gatagaagtt attcagcagg cacacaacag aggcagttcc 120
agatttcaac tgctcatcag atggcgggaa gatgaagaca gatggtgcag ccacagttcg 180
tttgatctcc agcttggtcc cctggccaaa agtgtacaaa ctattatact gttggcagta 240
ataagttgca aaatcatcag gctgcaggct gctgatggtg agagtgaatt ctgtcccaga 300
tccactgccg ctgaaccttg atgggaccac atcttctaaa ctagacgcct tatagatcaa 360
gaccttaggg gctttccctg gtttctgctg ataccaggcc aaccaggtac caatatcttg 420
actggcccgg caagtgatgg tgactctgtc tcctacagat gcagacaggg agaatgggct 480
ggggtcataa cagagcagcg g 501
<210> 2
<211> 503
<212> DNA
<213> (人工序列)
<400> 2
ccctgctgtc ctgctctgtg acactctcct gggagttacc cgattggagg gcgttatcca 60
ccttccactg tactttggcc tctctgggat agaagttatt cagcaggcac acaacagagg 120
cagttccaga tttcaactgc tcatcagatg gcgggaagat gaagacagat ggtgcagcca 180
cagttcgttt gatctccagc ttggtcccct ggccaaaagt gtaaggagtt tgtagagctt 240
gcatgcagta ataaacccca acatcctcag cctccactct gctgattttc agtgtgaaat 300
ctgtgcctga tccactgcca ctgaacctgt cagggacccc ggaggcccga tgagaattca 360
aatagatcag gagctgtgga gactgccctg gcttctgcag gtaccaatcc aaatagttgt 420
atccatcact aagcaggagg ctctgactag acctgcagga gatggaggcc ggctctccag 480
gggtgacggg cagggagaat gga 503
<210> 3
<211> 502
<212> DNA
<213> (人工序列)
<400> 3
ctccattctc cctgcccgtc acccctggag agccggcctc catctcctgc aggtctagtc 60
agaggctcct gcatagtaat ggatacaact atttggattg gtacctgcag aagccagggc 120
agtctccaca gctcctgatc tatttgggtt ctaatcgggc ctccggggtc cctgacaggt 180
tcagtggcag tggatcaggc acagatttta cactgaaaat cagcagagtg gaggctgagg 240
atgttggggt ttattactgc atgcaagctc tgcaaactcc gtggacgttc ggccaaggga 300
ccaaggtgga aatcaaacga actgtggctg caccatctgt cttcatcttc ccgccatctg 360
atgagcagtt gaaatctgga actgcctctg ttgtgtgcct gctgaataac ttctatccca 420
gagaggccaa agtacagtgg aaggtggata acgccctcca atcgggtaac tcccaggaga 480
gtgtcacaga gcaggacagc ag 502
<210> 4
<211> 484
<212> DNA
<213> (人工序列)
<400> 4
cattctccct gtctgcatct gtaggagaca gagtcaccat cacttgccgg gccagtcaga 60
atattaatac ctggttggcc tggtatcagc agaaaccagg gcaagcccct aaggtcctga 120
tccataaggc gtctacctta gaaagtgggg tcccatcaag gatcagcggc agtggatctg 180
ggacagaatt cactctcacc atcagcagcc tgcagcctga tgattttgca acttattact 240
gccaacagta tgattattat cctcacactt ttggccaggg gaccaaagta gatatcaaac 300
gaactgtggc tgcaccatct gtcttcatct tcccgccatc tgatgagcag ttgaaatctg 360
gaactgcctc tgttgtgtgc ctgctgaata acttctatcc cagagaggcc aaagtacagt 420
ggaaggtgga taacgccctc caatcgggta actcccagga gagtgtcaca gagcaggaca 480
gcag 484
<210> 5
<211> 471
<212> DNA
<213> (人工序列)
<220>
<221> misc_feature
<222> (5)..(5)
<223> n is a, c, g, or t
<400> 5
cgatnggagg gcgttatcca ccttttccac ttgtactttt ggccttctcc tgggatagaa 60
gttattcagc aggcacacaa cagaggcaag atccagattt caactgctca tcagatggcg 120
ggaagatgaa gacagatggt gcagccacag ttcgtttgat ctccacctta gtccctccgc 180
cgaaagtgag gggccacctg tcacgctgct gacagtaata aactgcaaaa tcttcaggct 240
ctaggccgcg gatggtgaga gtgaagtctg tcccagaccc actgccactg aacctggcgg 300
ggatgccaga ggccctgacg gacgcatcat agatgaggag cctgggagtc tggccaggtt 360
tgtgttggta ccaggttaag tagaacctaa cactctgact ggtcctacag gagacggtgg 420
ctctgtcccc tgcagacaaa gacagggaga atggagcctg ggttcataat a 471
<210> 6
<211> 466
<212> DNA
<213> (人工序列)
<400> 6
tgaggtgcca cctgttggag tctgggggag gcttggtcca gcctgggggg tccctgagac 60
tctcctgtgc agcctctgga ttcaccttta ataactattg gatgacctgg gtccgccagg 120
ctccagggaa ggggctggaa tgggtggcca gcataaagca agatggaggt gagaaatact 180
ttgtggactc tgtgaagggc cgattcacca tctccagaga caacgccagg aactcactgt 240
atctgcaaat ggacaacctg agagccgacg acacggctct gtattactgt gcgagcctta 300
atgtaattcg atattttgac tggacgacca cgggatactt tgactactgg ggccagggaa 360
ccctggtcac cgtcgcctca gcctccacca agggcccatc ggtcttcccc ctggcgccct 420
gctccaggag cacctccgag agcacagcgg ccctgggctg cctggt 466
<210> 7
<211> 431
<212> DNA
<213> (人工序列)
<400> 7
caggcagccc agggccgctg tgcccccaga ggtgctcttg gaggagggtg ccagggggaa 60
gaccgatggg cccttggtgg aggctgagga gacaatgacc agggttccct ggccccactg 120
ggcagcgtaa ttactgtagg tcccacccca tctcgcacag taatacatgg cggtgtccga 180
ggccttcagg ctgctccact gcaggtaggc ggtgttgatg gacctgtcgg ctgagatggt 240
gacctggcct tgaaaggacg gactgtattt ggtatcagag tcacgaagat agatgattcc 300
caaccactcc aggcccttcc cgggcatctg gcggacccaa ccgatccagt agttgggaaa 360
gttgtttccg aaagccttac aggaaatctt cagagactcc ccgggctttt tcacctctac 420
tccagactcc a 431
<210> 8
<211> 446
<212> DNA
<213> (人工序列)
<400> 8
tgttggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc tcctgtgcag 60
cgtctggatt cagcttcagt agctatggca tgcactgggt ccgccaggct ccaggcaagg 120
ggctggagtg ggtggcagtt atttggtttg atggaagtaa taaatactat gcagactccg 180
tgaagggccg attcaccatc tccagagaca attccaagaa caccctgttt ctgcaaatga 240
gcggcctgag agccgacgac acggctgtct attactgtgc gacagaggtc gtcggccagg 300
gcttctccgg tgacaacggg ggggaccatt ggggccaggg aaccctggtc accgtctcct 360
cagcctccac caagggccca tcggtcttcc ccctggcacc ctcctccaag agcacctctg 420
ggggcacagc ggccctgggc tgcctg 446
<210> 9
<211> 25
<212> DNA
<213> (人工序列)
<400> 9
atgaggstcc cygctcagct gctgg 25
<210> 10
<211> 28
<212> DNA
<213> (人工序列)
<400> 10
ctcttcctcc tgctactctg gctcccag 28
<210> 11
<211> 25
<212> DNA
<213> (人工序列)
<400> 11
atttctctgt tgctctggag ctctg 25
<210> 12
<211> 25
<212> DNA
<213> (人工序列)
<400> 12
agtagtcctt caccaggcag cccag 25
<210> 13
<211> 23
<212> DNA
<213> (人工序列)
<400> 13
ggtcctgggc ccagtctgtg ctg 23
<210> 14
<211> 23
<212> DNA
<213> (人工序列)
<400> 14
ggtcctgggc ccagtctgcc ctg 23
<210> 15
<211> 23
<212> DNA
<213> (人工序列)
<400> 15
gctctgtgac ctcctatgag ctg 23
<210> 16
<211> 23
<212> DNA
<213> (人工序列)
<400> 16
ggtctctctc scagcytgtg ctg 23
<210> 17
<211> 23
<212> DNA
<213> (人工序列)
<400> 17
gttcttgggc caattttatg ctg 23
<210> 18
<211> 23
<212> DNA
<213> (人工序列)
<400> 18
ggtccaattc ycaggctgtg gtg 23
<210> 19
<211> 23
<212> DNA
<213> (人工序列)
<400> 19
gagtggattc tcagactgtg gtg 23
<210> 20
<211> 24
<212> DNA
<213> (人工序列)
<400> 20
caccagtgtg gccttgttgg cttg 24
<210> 21
<211> 24
<212> DNA
<213> (人工序列)
<400> 21
acaggtgccc actcccaggt gcag 24
<210> 22
<211> 23
<212> DNA
<213> (人工序列)
<400> 22
aaggtgtcca gtgtgargtg cag 23
<210> 23
<211> 27
<212> DNA
<213> (人工序列)
<400> 23
cccagatggg tcctgtccca ggtgcag 27
<210> 24
<211> 24
<212> DNA
<213> (人工序列)
<400> 24
caaggagtct gttccgaggt gcag 24
<210> 25
<211> 22
<212> DNA
<213> (人工序列)
<400> 25
tcttgtccac cttggtgttg ct 22
<210> 26
<211> 24
<212> DNA
<213> (人工序列)
<400> 26
atgacccagw ctccabycwc cctg 24
<210> 27
<211> 22
<212> DNA
<213> (人工序列)
<400> 27
gtgctgtcct tgctgtcctg ct 22
<210> 28
<211> 38
<212> DNA
<213> (人工序列)
<400> 28
ctgctaccgg ttcctgggcc cagtctgtgc tgackcag 38
<210> 29
<211> 38
<212> DNA
<213> (人工序列)
<400> 29
ctgctaccgg ttcctgggcc cagtctgccc tgactcag 38
<210> 30
<211> 38
<212> DNA
<213> (人工序列)
<400> 30
ctgctaccgg ttctgtgacc tcctatgagc tgacwcag 38
<210> 31
<211> 37
<212> DNA
<213> (人工序列)
<400> 31
ctgctaccgg ttctctctcs cagcytgtgc tgactca 37
<210> 32
<211> 38
<212> DNA
<213> (人工序列)
<400> 32
ctgctaccgg ttcttgggcc aattttatgc tgactcag 38
<210> 33
<211> 38
<212> DNA
<213> (人工序列)
<400> 33
ctgctaccgg ttccaattcy cagrctgtgg tgacycag 38
<210> 34
<211> 28
<212> DNA
<213> (人工序列)
<400> 34
ctcctcactc gagggyggga acagagtg 28
<210> 35
<211> 18
<212> DNA
<213> (人工序列)
<400> 35
sargtgcagc tcgtggag 18
<210> 36
<211> 18
<212> DNA
<213> (人工序列)
<400> 36
gaggtgcagc tgttggag 18
<210> 37
<211> 20
<212> DNA
<213> (人工序列)
<400> 37
ggaattctca caggagacga 20
<210> 38
<211> 25
<212> DNA
<213> (人工序列)
<400> 38
agtagtcctt gaccaggcag cccag 25
Claims (7)
1.一种抗严重急性呼吸系统综合征II型冠状病毒SARS-COV-2的中和抗体,其特征在于,包括:轻链可变区DNA序列,以及重链可变区DNA序列;
所述轻链可变区DNA序列的核苷酸序列为SEQ ID NO.1-5中的一种或多种组合;
所述重链可变区DNA序列的核苷酸序列为SEQ ID NO.6-8中的一种或多种。
2.根据权利要求1所述的中和抗体,其特征在于,所述的中和抗体为包含恒定区和可变区的完整抗体、只包含可变区的部分抗体或只包含可变区的嵌合抗体。
3.一种编码权利要求1或2所述的中和抗体的基因。
4.一种携带权利要求3所述的基因的表达载体。
5.一种表达权利要求1或2所述的中和抗体的重组细胞。
6.权利要求1或2所述的中和抗体在制备治疗肺炎COVID-19的药物中的应用。
7.一种治疗肺炎COVID-19的试剂盒,其特征在于,所述试剂盒内含有权利要求1或2所述的中和抗体。
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PCT/CN2021/116808 WO2022110962A1 (zh) | 2020-11-25 | 2021-10-12 | 抗严重急性呼吸系统综合征ii型冠状病毒sars-cov-2的中和抗体 |
CN202211606677.0A CN116003584A (zh) | 2020-11-25 | 2021-10-20 | 抗严重急性呼吸系统综合征ii型冠状病毒sars-cov-2的中和抗体 |
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CN202211595499.6A CN117467668B (zh) | 2020-11-25 | 2021-10-20 | 抗严重急性呼吸系统综合征ii型冠状病毒sars-cov-2的中和抗体 |
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CN202211595526.XA CN116254270A (zh) | 2020-11-25 | 2021-10-20 | 抗严重急性呼吸系统综合征ii型冠状病毒sars-cov-2的中和抗体 |
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EP4238988A1 (en) * | 2022-03-01 | 2023-09-06 | Consejo Superior De Investigaciones Científicas | Antibodies against sars-cov-2 and uses thereof |
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2020
- 2020-11-25 CN CN202011339257.1A patent/CN112442120A/zh active Pending
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2021
- 2021-10-12 WO PCT/CN2021/116808 patent/WO2022110962A1/zh active Application Filing
- 2021-10-20 CN CN202211595499.6A patent/CN117467668B/zh active Active
- 2021-10-20 CN CN202111222859.3A patent/CN113801223B/zh active Active
- 2021-10-20 CN CN202211595770.6A patent/CN116396967B/zh active Active
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US11732030B2 (en) | 2020-04-02 | 2023-08-22 | Regeneron Pharmaceuticals, Inc. | Anti-SARS-CoV-2-spike glycoprotein antibodies and antigen-binding fragments |
US11999777B2 (en) | 2020-06-03 | 2024-06-04 | Regeneron Pharmaceuticals, Inc. | Methods for treating or preventing SARS-CoV-2 infections and COVID-19 with anti-SARS-CoV-2 spike glycoprotein antibodies |
US11359007B2 (en) | 2020-09-04 | 2022-06-14 | Newsoara Biopharma Co., Ltd. | Anti-SARS-CoV-2 neutralizing antibodies |
WO2022110962A1 (zh) * | 2020-11-25 | 2022-06-02 | 苏州大学 | 抗严重急性呼吸系统综合征ii型冠状病毒sars-cov-2的中和抗体 |
US11312760B1 (en) | 2021-01-19 | 2022-04-26 | Newsoara Biopharma Co., Ltd. | Expression vector for anti-SARS-CoV-2 neutralizing antibodies |
CN112980885A (zh) * | 2021-03-18 | 2021-06-18 | 恒翼生物医药科技(上海)有限公司 | 抗sars-cov-2中和抗体的表达载体 |
CN112980885B (zh) * | 2021-03-18 | 2022-04-15 | 恒翼生物医药科技(上海)有限公司 | 抗sars-cov-2中和抗体的表达载体 |
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