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On December 8, 2021, China's first anti-COVID-19 drug, Ambavirumab/Romisevirumab (BRII-196/198), was approved[1], bringing China's anti-epidemic into a "premium".
In the new stage of "Miao You Yao", the news of the approval of this monoclonal antibody combination was on the hot search of major media platforms for a while
.
Unexpectedly, the Omicron (B.
1.
1.
529) strain, which appeared in South Africa on November 9, was the second in the approval of ambavirumab/romisevirumab.
Days, it quietly landed in mainland China from Tianjin, which brought enormous pressure to China's anti-epidemic work
.
In mid-November, a study found that there were more than 30 mutations on the spike (S) protein of Omicron, of which 15 mutations were only in the receptor binding region (RBD), which is necessary to infect human cells.
2]
.
Therefore, many researchers believe that Omicron will inevitably seriously affect the effectiveness of vaccines and monoclonal antibody drugs
.
▲ The mutation on the Omicron S protein (image source: https:// is indeed the case, and soon studies have found that some neutralizing antibodies that have been approved show varying degrees of Invalid [3]
.
For a while, many people were worried about the fate of China's first approved anti-new crown antibody combination
.
The good news is that on the evening of December 12, Tengsheng Biopharmaceuticals announced that the laboratory neutralization data showed that the combination therapy of ambavirumab/romisevirumab maintained its resistance to the new coronavirus variant Omicron.
Neutralizing activity [4]
.
Two days later, the famous virologist and Columbia University School of Medicine professor He Dayi's team found that in the neutralization experiment against the Omicron mutant, the neutralizing activities of Sotrovimab and romisevirumab were not among the 19 antibodies.
In addition to being unaffected, the neutralizing activity of other antibodies decreased [5]
.
This news undoubtedly gave the Chinese people a "strengthening shot"
.
So why does the combination of ambavirumab/romisevirumab still maintain its neutralizing activity against omicron when most antibodies fail? We think there are at least two reasons for the combination of ambavirumab/romisevirumab alone
.
Next we will introduce them one by one
.
Super Complementary At the beginning of the research and development, the Tengsheng Biopharmaceutical team, which is quite experienced in the antiviral field, chose the combination therapy of neutralizing antibodies, and also chose a pair of neutralizing antibodies with strong complementarity
.
The purpose of this is to avoid resistance
.
In fact, in June 2020, a team has already found that a non-competitive or partially competitive neutralizing antibody combination can avoid the escape of the new crown mutant [6]
.
This is also the reason why FDA-approved antibody combinations are basically the same
.
▲ The new coronavirus S protein model (image source: NIAID-RML) Since this is the case, why is the neutralization effect of some combinations greatly reduced, while the neutralization effect of ambavirumab/romisevirumab remains very good Okay? To answer this question, we have to start with the complementarity and neutralization mechanisms of antibodies
.
As we all know, the current neutralizing antibodies are all RBDs targeting the S protein of the new coronavirus
.
You know, although the RBD is small, there are many sites for neutralizing antibodies to bind
.
The different binding positions of neutralizing antibody and RBD must have certain influence on the effect of neutralizing antibody
.
As early as 2020, the team of David Veesler of the University of Washington used cryo-electron microscopy to study the binding site of the neutralizing antibody antigen-binding segment (Fab) to the trimer of the new coronavirus S protein, and finally identified 6 on the RBD of the S protein.
different sites (Ia, Ib, IIa, IIb, IIc and IV) [7]
.
▲ 6 different binding sites (the black box represents the binding site of ACE2 and RBD, and the other 6 colors represent the binding site of mAb and RBD respectively).
It is not difficult to find from the above figure that the two bits Ia and Ib The dots all overlap with the receptor-binding motif (RBM) of ACE2 and RBD, but the overlapping regions and ways are different
.
Neutralizing antibodies that bind to the Ia site can only bind to it in the open state of the RBD, and the region overlapping with the RBM is larger than that of class Ib antibodies
.
Neutralizing antibodies that bind to the Ib site can bind to the RBD in the open or closed state, and partially cover the RBM region
.
Therefore, neutralizing antibodies that bind to these two sites prevent the new coronavirus from infecting human cells by competing with ACE [7,8]
.
In other words, the antibodies that bind to the Ia or Ib site compete and are not highly complementary
.
IIa, IIb and IIc are all antibodies that bind to the cryptic site of the RBD and can only bind to it when the RBD is opened, where IIa partially overlaps with the RBM, and IIb and IIc gradually move away from the RBM [7,8]
.
Although the three sites do not compete with ACE2 only in terms of sites, some studies have found that after neutralizing antibodies bind to these three sites, they will block the binding of ACE2 to RBD in other places or spaces [7,8]
.
The IV site is the most special.
It is not only far from the core RBM of RBD, but also studies have shown that antibodies bound to this site will not compete with ACE2 [7,9]
.
Moreover, antibodies can bind to this site whether the RBD is on or off
.
▲ The binding site of some neutralizing antibodies that have been approved for clinical application and RBD [7,8] It is not difficult to see from the above description: the neutralizing antibody that binds the IV site and the neutralizing antibody that binds the two sites Ia and Ib.
Complementarity with antibodies is the strongest
.
Coincidentally, the binding site of ambavirumab is Ia, and the binding site of romisevirumab is IV [5,7,8], so the complementarity of the two is indeed super
.
Let's look at the neutralization mechanism of ambivirumab/romisevirumab
.
Studies have shown that the binding epitope of ambavirumab and RBM is highly consistent with the binding epitope of ACE2 and RBM [10]
.
This highly overlapping feature not only endows Ambavirumab with stronger competitive binding ability, but also makes it more capable of coping with virus escape caused by partial epitope mutation of RBD[11]
.
As for romisevirumab, it binds to the IV site and does not compete with the Ia-binding ambivirumab
.
Not long ago, a research team found that an antibody that binds to the IV site can inhibit the rearrangement of the S protein necessary for the membrane fusion of the virus and the cell, thereby inhibiting the occurrence of viral membrane fusion and preventing the virus from invading cells [12]
.
▲ Schematic diagram of ambavirumab/romisevirumab binding to RBD (photo courtesy of Tengshengbo Pharmaceutical) In general, this super binding site complementarity and different antiviral mechanisms may be Ambavir One of the reasons why the combination therapy of mAb/romisevirumab maintains neutralizing activity against omicron
.
Ultra-high blood concentration So how does the combination therapy of Ambavirumab/Romisevirumab maintain the neutralizing activity of Omicron? After all, the neutralizing activity of ambivirumab that binds to the Ia site has decreased [5]
.
Although in vitro experiments have shown that Omicron has a certain effect on the neutralizing activity of Ambavir, the combined use of Ambavirumab/Romisevirumab has little effect [13]
.
In addition to the complementarity described above, plasma concentrations are also a major contributor to maintaining neutralizing activity
.
Let's first take a look at the blood concentration of patients after the injection of ambavirumab/romisevirumab
.
In order to increase the blood drug concentration as soon as possible to enhance the antiviral effect, combined with the Phase 1 clinical data, and on the premise of ensuring safety, the researchers of Tengsheng Biopharmaceuticals chose a single large-dose administration (1000mg/1000mg) method (NCT04518410)
.
After a single intravenous administration, it only takes about 5 hours for the blood antibody concentration to exceed 300 μg/ml, which is more than 1000 times the IC50 in the blood, and 100 times the IC50 in the lungs (Tengsheng Bo Yao unpublished).
data)
.
That is to say, from the point of view of the blood drug concentration after injection alone, ambavirumab/romisevirumab is sufficient to deal with the Omicron mutant
.
New coronavirus (Image source: NIAID-RML) In addition, it is worth mentioning that the crystallizable segment (Fc) of Ambavirumab/Romisvirumab is modified
.
This modification brings two benefits.
On the one hand, the half-life of ambasvirumab/romisevirumab is 2-3 times that of ordinary antibodies, extending from 21 days to 46-76 days [14,15] On the other hand, it will significantly increase the drug distribution in target organs (lungs) and increase the concentration of antibodies in the lungs [16]
.
Undoubtedly, these two points are also crucial for the maintenance of neutralizing antibody activity
.
It is for the above two reasons that the neutralizing activity of ambavirumab/romisevirumab against omecrop can be maintained
.
Of course, the specific mechanism behind it still needs to be further studied
.
Overall, from the existing research, ambivirumab and romisevirumab bind to two completely different and non-interfering sites of the RBD, which allows them to achieve their true functions.
Complementary
.
In addition, the ultra-high blood drug concentration and higher pulmonary antibody concentration of patients after treatment also contributed a lot to the neutralization activity of Ambavirumab/Romisevirumab against all currently known variants
.
It is understood that the research by Zhang Linqi's team at Tsinghua University on the neutralization of ombavirumab/romisevirumab and Omicron is about to be published.
We look forward to Professor Zhang's more comprehensive answers
.
References: [1].
https:// pdf[3].
Cao YR, Wang J, Jian F, et al.
B.
1.
1.
529 escapes the majority of SARS-CoV-2 neutralizing antibodies of diverse epitopes[J].
BioRxiv, 2021.
[4].
https: //mp.
weixin.
qq.
com/s/48JorUncaQ_isz07rBpVPw[5].
Liu L, Iketani S, Guo Y, et al.
Striking Antibody Evasion Manifested by the Omicron Variant of SARS-CoV-2[J].
nature, 2021 .
[6].
Baum A, Fulton BO, Wloga E, et al.
Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies[J].
Science, 2020, 369(6506): 1014- 1018.
[7].
Piccoli L, Park YJ, Tortorici MA, et al.
Mapping neutralizing and immunodominant sites on the SARS-CoV-2 spike receptor-binding domain by structure-guided high-resolution serology[J].
Cell, 2020 ,183(4): 1024-1042.
e21.
[8].
Corti D, Purcell LA, Snell G, et al.
Tackling COVID-19 with neutralizing monoclonal antibodies[J].
Cell, 2021.
[9].
Pinto D, Park YJ, Beltramello M, et al.
Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody[J].
Nature, 2020, 583(7815): 290-295.
[10].
Ge J, Wang R, Ju B, et al.
Antibody neutralization of SARS-CoV-2 through ACE2 receptor mimicry.
Nat Commun.
2021;12(1):250.
Published 2021 Jan 11.
[11].
Baum A, Fulton BO, Wloga E, et al.
Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies[J].
Science, 2020, 369(6506): 1014-1018.
[12].
Lempp FA, Soriaga LB, Montiel-Ruiz M, et al.
Lectins enhance SARS-CoV-2 infection and influence neutralizing antibodies.
Nature.
2021;598(7880):342-347.
[13].
https://opendata.
ncats.
nih.
gov/ variant/activity[14].
Zhang Y, Hao X, Ma J, et al.
Phase 1 safety and pharmacokinetics studies of BRII-196 and BRII-198, SARS-CoV-2 spike-targeting monoclonal antibodies[J].
medRxiv, 2021.
[15].
Robbie GJ, Criste R, Dall'Acqua WF, et al.
A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults[J].
Antimicrobial agents and chemotherapy, 2013, 57(12 ): 6147-6153.
[16].
Shah DK, Betts AM.
Antibody biodistribution coefficients: inferring tissue concentrations of monoclonal antibodies based on the plasma concentrations in several preclinical species and human.
MAbs.
2013;5(2):297-305 .
doi:10.
4161/mabs.
23684 Author of this articleBioTalkerRobbie GJ, Criste R, Dall'Acqua WF, et al.
A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults[J].
Antimicrobial agents and chemotherapy, 2013, 57( 12): 6147-6153.
[16].
Shah DK, Betts AM.
Antibody biodistribution coefficients: inferring tissue concentrations of monoclonal antibodies based on the plasma concentrations in several preclinical species and human.
MAbs.
2013;5(2):297- 305.
doi:10.
4161/mabs.
23684 Author of this articleBioTalkerRobbie GJ, Criste R, Dall'Acqua WF, et al.
A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults[J].
Antimicrobial agents and chemotherapy, 2013, 57( 12): 6147-6153.
[16].
Shah DK, Betts AM.
Antibody biodistribution coefficients: inferring tissue concentrations of monoclonal antibodies based on the plasma concentrations in several preclinical species and human.
MAbs.
2013;5(2):297- 305.
doi:10.
4161/mabs.
23684 Author of this articleBioTalkerinferring tissue concentrations of monoclonal antibodies based on the plasma concentrations in several preclinical species and human.
MAbs.
2013;5(2):297-305.
doi:10.
4161/mabs.
23684 Author of this articleBioTalkerinferring tissue concentrations of monoclonal antibodies based on the plasma concentrations in several preclinical species and human.
MAbs.
2013;5(2):297-305.
doi:10.
4161/mabs.
23684 Author of this articleBioTalker
In the new stage of "Miao You Yao", the news of the approval of this monoclonal antibody combination was on the hot search of major media platforms for a while
.
Unexpectedly, the Omicron (B.
1.
1.
529) strain, which appeared in South Africa on November 9, was the second in the approval of ambavirumab/romisevirumab.
Days, it quietly landed in mainland China from Tianjin, which brought enormous pressure to China's anti-epidemic work
.
In mid-November, a study found that there were more than 30 mutations on the spike (S) protein of Omicron, of which 15 mutations were only in the receptor binding region (RBD), which is necessary to infect human cells.
2]
.
Therefore, many researchers believe that Omicron will inevitably seriously affect the effectiveness of vaccines and monoclonal antibody drugs
.
▲ The mutation on the Omicron S protein (image source: https:// is indeed the case, and soon studies have found that some neutralizing antibodies that have been approved show varying degrees of Invalid [3]
.
For a while, many people were worried about the fate of China's first approved anti-new crown antibody combination
.
The good news is that on the evening of December 12, Tengsheng Biopharmaceuticals announced that the laboratory neutralization data showed that the combination therapy of ambavirumab/romisevirumab maintained its resistance to the new coronavirus variant Omicron.
Neutralizing activity [4]
.
Two days later, the famous virologist and Columbia University School of Medicine professor He Dayi's team found that in the neutralization experiment against the Omicron mutant, the neutralizing activities of Sotrovimab and romisevirumab were not among the 19 antibodies.
In addition to being unaffected, the neutralizing activity of other antibodies decreased [5]
.
This news undoubtedly gave the Chinese people a "strengthening shot"
.
So why does the combination of ambavirumab/romisevirumab still maintain its neutralizing activity against omicron when most antibodies fail? We think there are at least two reasons for the combination of ambavirumab/romisevirumab alone
.
Next we will introduce them one by one
.
Super Complementary At the beginning of the research and development, the Tengsheng Biopharmaceutical team, which is quite experienced in the antiviral field, chose the combination therapy of neutralizing antibodies, and also chose a pair of neutralizing antibodies with strong complementarity
.
The purpose of this is to avoid resistance
.
In fact, in June 2020, a team has already found that a non-competitive or partially competitive neutralizing antibody combination can avoid the escape of the new crown mutant [6]
.
This is also the reason why FDA-approved antibody combinations are basically the same
.
▲ The new coronavirus S protein model (image source: NIAID-RML) Since this is the case, why is the neutralization effect of some combinations greatly reduced, while the neutralization effect of ambavirumab/romisevirumab remains very good Okay? To answer this question, we have to start with the complementarity and neutralization mechanisms of antibodies
.
As we all know, the current neutralizing antibodies are all RBDs targeting the S protein of the new coronavirus
.
You know, although the RBD is small, there are many sites for neutralizing antibodies to bind
.
The different binding positions of neutralizing antibody and RBD must have certain influence on the effect of neutralizing antibody
.
As early as 2020, the team of David Veesler of the University of Washington used cryo-electron microscopy to study the binding site of the neutralizing antibody antigen-binding segment (Fab) to the trimer of the new coronavirus S protein, and finally identified 6 on the RBD of the S protein.
different sites (Ia, Ib, IIa, IIb, IIc and IV) [7]
.
▲ 6 different binding sites (the black box represents the binding site of ACE2 and RBD, and the other 6 colors represent the binding site of mAb and RBD respectively).
It is not difficult to find from the above figure that the two bits Ia and Ib The dots all overlap with the receptor-binding motif (RBM) of ACE2 and RBD, but the overlapping regions and ways are different
.
Neutralizing antibodies that bind to the Ia site can only bind to it in the open state of the RBD, and the region overlapping with the RBM is larger than that of class Ib antibodies
.
Neutralizing antibodies that bind to the Ib site can bind to the RBD in the open or closed state, and partially cover the RBM region
.
Therefore, neutralizing antibodies that bind to these two sites prevent the new coronavirus from infecting human cells by competing with ACE [7,8]
.
In other words, the antibodies that bind to the Ia or Ib site compete and are not highly complementary
.
IIa, IIb and IIc are all antibodies that bind to the cryptic site of the RBD and can only bind to it when the RBD is opened, where IIa partially overlaps with the RBM, and IIb and IIc gradually move away from the RBM [7,8]
.
Although the three sites do not compete with ACE2 only in terms of sites, some studies have found that after neutralizing antibodies bind to these three sites, they will block the binding of ACE2 to RBD in other places or spaces [7,8]
.
The IV site is the most special.
It is not only far from the core RBM of RBD, but also studies have shown that antibodies bound to this site will not compete with ACE2 [7,9]
.
Moreover, antibodies can bind to this site whether the RBD is on or off
.
▲ The binding site of some neutralizing antibodies that have been approved for clinical application and RBD [7,8] It is not difficult to see from the above description: the neutralizing antibody that binds the IV site and the neutralizing antibody that binds the two sites Ia and Ib.
Complementarity with antibodies is the strongest
.
Coincidentally, the binding site of ambavirumab is Ia, and the binding site of romisevirumab is IV [5,7,8], so the complementarity of the two is indeed super
.
Let's look at the neutralization mechanism of ambivirumab/romisevirumab
.
Studies have shown that the binding epitope of ambavirumab and RBM is highly consistent with the binding epitope of ACE2 and RBM [10]
.
This highly overlapping feature not only endows Ambavirumab with stronger competitive binding ability, but also makes it more capable of coping with virus escape caused by partial epitope mutation of RBD[11]
.
As for romisevirumab, it binds to the IV site and does not compete with the Ia-binding ambivirumab
.
Not long ago, a research team found that an antibody that binds to the IV site can inhibit the rearrangement of the S protein necessary for the membrane fusion of the virus and the cell, thereby inhibiting the occurrence of viral membrane fusion and preventing the virus from invading cells [12]
.
▲ Schematic diagram of ambavirumab/romisevirumab binding to RBD (photo courtesy of Tengshengbo Pharmaceutical) In general, this super binding site complementarity and different antiviral mechanisms may be Ambavir One of the reasons why the combination therapy of mAb/romisevirumab maintains neutralizing activity against omicron
.
Ultra-high blood concentration So how does the combination therapy of Ambavirumab/Romisevirumab maintain the neutralizing activity of Omicron? After all, the neutralizing activity of ambivirumab that binds to the Ia site has decreased [5]
.
Although in vitro experiments have shown that Omicron has a certain effect on the neutralizing activity of Ambavir, the combined use of Ambavirumab/Romisevirumab has little effect [13]
.
In addition to the complementarity described above, plasma concentrations are also a major contributor to maintaining neutralizing activity
.
Let's first take a look at the blood concentration of patients after the injection of ambavirumab/romisevirumab
.
In order to increase the blood drug concentration as soon as possible to enhance the antiviral effect, combined with the Phase 1 clinical data, and on the premise of ensuring safety, the researchers of Tengsheng Biopharmaceuticals chose a single large-dose administration (1000mg/1000mg) method (NCT04518410)
.
After a single intravenous administration, it only takes about 5 hours for the blood antibody concentration to exceed 300 μg/ml, which is more than 1000 times the IC50 in the blood, and 100 times the IC50 in the lungs (Tengsheng Bo Yao unpublished).
data)
.
That is to say, from the point of view of the blood drug concentration after injection alone, ambavirumab/romisevirumab is sufficient to deal with the Omicron mutant
.
New coronavirus (Image source: NIAID-RML) In addition, it is worth mentioning that the crystallizable segment (Fc) of Ambavirumab/Romisvirumab is modified
.
This modification brings two benefits.
On the one hand, the half-life of ambasvirumab/romisevirumab is 2-3 times that of ordinary antibodies, extending from 21 days to 46-76 days [14,15] On the other hand, it will significantly increase the drug distribution in target organs (lungs) and increase the concentration of antibodies in the lungs [16]
.
Undoubtedly, these two points are also crucial for the maintenance of neutralizing antibody activity
.
It is for the above two reasons that the neutralizing activity of ambavirumab/romisevirumab against omecrop can be maintained
.
Of course, the specific mechanism behind it still needs to be further studied
.
Overall, from the existing research, ambivirumab and romisevirumab bind to two completely different and non-interfering sites of the RBD, which allows them to achieve their true functions.
Complementary
.
In addition, the ultra-high blood drug concentration and higher pulmonary antibody concentration of patients after treatment also contributed a lot to the neutralization activity of Ambavirumab/Romisevirumab against all currently known variants
.
It is understood that the research by Zhang Linqi's team at Tsinghua University on the neutralization of ombavirumab/romisevirumab and Omicron is about to be published.
We look forward to Professor Zhang's more comprehensive answers
.
References: [1].
https:// pdf[3].
Cao YR, Wang J, Jian F, et al.
B.
1.
1.
529 escapes the majority of SARS-CoV-2 neutralizing antibodies of diverse epitopes[J].
BioRxiv, 2021.
[4].
https: //mp.
weixin.
qq.
com/s/48JorUncaQ_isz07rBpVPw[5].
Liu L, Iketani S, Guo Y, et al.
Striking Antibody Evasion Manifested by the Omicron Variant of SARS-CoV-2[J].
nature, 2021 .
[6].
Baum A, Fulton BO, Wloga E, et al.
Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies[J].
Science, 2020, 369(6506): 1014- 1018.
[7].
Piccoli L, Park YJ, Tortorici MA, et al.
Mapping neutralizing and immunodominant sites on the SARS-CoV-2 spike receptor-binding domain by structure-guided high-resolution serology[J].
Cell, 2020 ,183(4): 1024-1042.
e21.
[8].
Corti D, Purcell LA, Snell G, et al.
Tackling COVID-19 with neutralizing monoclonal antibodies[J].
Cell, 2021.
[9].
Pinto D, Park YJ, Beltramello M, et al.
Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody[J].
Nature, 2020, 583(7815): 290-295.
[10].
Ge J, Wang R, Ju B, et al.
Antibody neutralization of SARS-CoV-2 through ACE2 receptor mimicry.
Nat Commun.
2021;12(1):250.
Published 2021 Jan 11.
[11].
Baum A, Fulton BO, Wloga E, et al.
Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies[J].
Science, 2020, 369(6506): 1014-1018.
[12].
Lempp FA, Soriaga LB, Montiel-Ruiz M, et al.
Lectins enhance SARS-CoV-2 infection and influence neutralizing antibodies.
Nature.
2021;598(7880):342-347.
[13].
https://opendata.
ncats.
nih.
gov/ variant/activity[14].
Zhang Y, Hao X, Ma J, et al.
Phase 1 safety and pharmacokinetics studies of BRII-196 and BRII-198, SARS-CoV-2 spike-targeting monoclonal antibodies[J].
medRxiv, 2021.
[15].
Robbie GJ, Criste R, Dall'Acqua WF, et al.
A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults[J].
Antimicrobial agents and chemotherapy, 2013, 57(12 ): 6147-6153.
[16].
Shah DK, Betts AM.
Antibody biodistribution coefficients: inferring tissue concentrations of monoclonal antibodies based on the plasma concentrations in several preclinical species and human.
MAbs.
2013;5(2):297-305 .
doi:10.
4161/mabs.
23684 Author of this articleBioTalkerRobbie GJ, Criste R, Dall'Acqua WF, et al.
A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults[J].
Antimicrobial agents and chemotherapy, 2013, 57( 12): 6147-6153.
[16].
Shah DK, Betts AM.
Antibody biodistribution coefficients: inferring tissue concentrations of monoclonal antibodies based on the plasma concentrations in several preclinical species and human.
MAbs.
2013;5(2):297- 305.
doi:10.
4161/mabs.
23684 Author of this articleBioTalkerRobbie GJ, Criste R, Dall'Acqua WF, et al.
A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults[J].
Antimicrobial agents and chemotherapy, 2013, 57( 12): 6147-6153.
[16].
Shah DK, Betts AM.
Antibody biodistribution coefficients: inferring tissue concentrations of monoclonal antibodies based on the plasma concentrations in several preclinical species and human.
MAbs.
2013;5(2):297- 305.
doi:10.
4161/mabs.
23684 Author of this articleBioTalkerinferring tissue concentrations of monoclonal antibodies based on the plasma concentrations in several preclinical species and human.
MAbs.
2013;5(2):297-305.
doi:10.
4161/mabs.
23684 Author of this articleBioTalkerinferring tissue concentrations of monoclonal antibodies based on the plasma concentrations in several preclinical species and human.
MAbs.
2013;5(2):297-305.
doi:10.
4161/mabs.
23684 Author of this articleBioTalker
