RU2800649C2 - Monoclonal antibodies against the receptor-binding domain of sars-cov-2 spike protein and their antigen-binding fragments encoding their nucleic acids, as well as methods of their use - Google Patents

Monoclonal antibodies against the receptor-binding domain of sars-cov-2 spike protein and their antigen-binding fragments encoding their nucleic acids, as well as methods of their use Download PDF

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RU2800649C2
RU2800649C2 RU2021139704A RU2021139704A RU2800649C2 RU 2800649 C2 RU2800649 C2 RU 2800649C2 RU 2021139704 A RU2021139704 A RU 2021139704A RU 2021139704 A RU2021139704 A RU 2021139704A RU 2800649 C2 RU2800649 C2 RU 2800649C2
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Константин Олегович Баранов
Татьяна Николаевна Беловежец
Ольга Юрьевна Волкова
Андрей Александрович Горчаков
Сергей Владимирович Гусельников
Сергей Викторович Кулемзин
Людмила Васильевна Мечетина
Александр Матвеевич Наякшин
Александр Владимирович Таранин
Николай Андреевич Чикаев
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Abstract

FIELD: biotechnology.
SUBSTANCE: invention relates to a monoclonal antibody or antigen-binding fragment selectively binding the RBD fragment of the Spike protein of the SARS-CoV-2 virus, a method of producing it, as well as to a combination containing it. Also a nucleic acid encoding the above antibody, as well as a vector containing it are disclosed. The invention also relates to an antigen receptor that selectively binds an RBD fragment of the SARS-CoV-2 Spike protein containing an antigen-binding region represented by the above antibody or an antigen-binding fragment thereof.
EFFECT: invention is effective for prevention and therapy of infection caused by SARS-CoV-2, as well as for assessing the presence of SARS-CoV-2 infection in mammals.
24 cl, 14 dwg, 3 tbl, 9 ex

Description

Область техники, к которой относится изобретениеThe field of technology to which the invention belongs

Настоящее изобретение относится к моноклональным антителам и их антигенсвязывающим фрагментам, которые связываются с рецептор-связывающим доменом (RBD) Spike-белка вируса SARS-CoV-2.The present invention relates to monoclonal antibodies and antigen-binding fragments thereof that bind to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein.

Уровень техникиState of the art

За два года пандемии, вызванной бетакоронавирусом SARS-CoV-2, была зарегистрирована гибель порядка 5 млн человек. Использование ряда средств профилактики и терапии коронавирусной инфекции, вызванной SARS-CoV-2 (также называемой в данном документе ковид-19), позволяет снизить вероятность заражения, госпитализации и летального исхода. К таким средствам относятся вакцинопрофилактика, использование вирус-специфических малых молекул, препаратов плазмы реконвалесцентов, рекомбинантных Spike-специфичных белков (в том числе антител) и их производных. Несмотря на повсеместное проведение кампаний по иммунизации населения и идентификации нейтрализующих моноклональных антител против Spike-белка вируса SARS-CoV-2, существует значительная потребность в получении новых вариантов таких антител для расширения арсенала диагностических, профилактических и терапевтических средств особенно с учетом появления новых вариантов вируса. Кроме того, существуют группы населения, которым вакцинация либо не показана по медицинским соображениям, либо у которых не может быть выработан протективный иммунный ответ. Таким образом, проведение пассивной иммунизации – введение препаратов моноклональных антител в качестве пред- или пост-экспозиционной профилактики или терапии позволяет защитить таких людей, обеспечить менее длительное и тяжелое течение болезни, в том числе предотвратить развитие пост-ковидных осложнений, и снизить вероятность дальнейшей передачи вируса.During the two years of the pandemic caused by the SARS-CoV-2 betacoronavirus, the death of about 5 million people was recorded. The use of a number of prevention and treatment methods for coronavirus infection caused by SARS-CoV-2 (also referred to as covid-19 in this document) can reduce the likelihood of infection, hospitalization and death. Such means include vaccination, the use of virus-specific small molecules, convalescent plasma preparations, recombinant Spike-specific proteins (including antibodies) and their derivatives. Despite widespread public immunization campaigns and the identification of neutralizing monoclonal antibodies against the spike protein of the SARS-CoV-2 virus, there is a significant need to obtain new variants of such antibodies to expand the arsenal of diagnostic, prophylactic and therapeutic tools, especially given the emergence of new variants of the virus. In addition, there are populations in which vaccination is either not indicated for medical reasons, or in which a protective immune response cannot be developed. Thus, passive immunization - the introduction of monoclonal antibodies as a pre- or post-exposure prophylaxis or therapy allows you to protect such people, ensure a shorter and more severe course of the disease, including preventing the development of post-COVID complications, and reduce the likelihood of further transmission. virus.

Известно, что из трех поверхностных белков SARS-CoV-2 лишь один, Spike, вызывает образование вируснейтрализующих антител. Также было показано, что подавляющее число полученных к настоящему моменту Spike-специфических моноклональных антител, обладающих способностью нейтрализовать вирус, направлены против RBD-домена Spike, ответственного за связывание с основным входным рецептором вируса, белком ACE2.Of the three surface proteins of SARS-CoV-2, only one, Spike, is known to induce the formation of virus-neutralizing antibodies. It has also been shown that the vast majority of Spike-specific monoclonal antibodies obtained to date that have the ability to neutralize the virus are directed against the Spike RBD domain responsible for binding to the main entry receptor of the virus, the ACE2 protein.

Идентификация SARS-CoV-2-специфических нейтрализующих моноклональных антител в основном осуществляется одним из нескольких способов, таких как секвенирование генов иммуноглобулинов из единичных В-клеток людей, перенесших ковид-19, или иммунизированных животных (в. т.ч. гуманизированных) (Brouwer, P. J. M. et al. Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Science 369, 643–650 (2020); Wu, Y. et al. A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2. Science 368, 1274–1278 (2020); Jones, B. E. et al. The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates. Sci. Transl. Med. 13, eabf1906 (2021); Hansen, J. et al. Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science 369, 1010–1014 (2020); Wang, C. et al. A human monoclonal antibody blocking SARS-CoV-2 infection. Nat. Commun. 11, 2251 (2020); Seydoux, E. et al. Analysis of a SARS-CoV-2-infected individual reveals development of potent neutralizing antibodies with limited somatic mutation. Immunity 53, 98–105.e5 (2020); Zost, S. J. et al. Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein. Nat. Med. 26, 1422–1427 (2020); Rogers, T. F. et al. Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Science 369, 956–963 (2020); Shi, R. et al. A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2. Nature 584, 120–124 (2020); Ju, B. et al. Human neutralizing antibodies elicited by SARS-CoV-2 infection. Nature 584, 115–119 (2020); Robbiani, D. F. et al. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature 584, 437–442 (2020); Liu, L. et al. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Nature 584, 450–456 (2020); Chi, X. et al. A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2. Science 369, 650–655 (2020); Wan, J. et al. Human-IgG-neutralizing monoclonal antibodies block the SARS-CoV-2 infection. Cell Rep. 32, 107918 (2020); Kreer, C. et al. Longitudinal isolation of potent near-germline SARS-CoV-2-neutralizing antibodies from COVID-19 patients. Cell 182, 843–854.e12 (2020); Kreye, J. et al. A therapeutic non-self-reactive SARS-CoV-2 antibody protects from lung pathology in a COVID-19 hamster model. Cell 183, 1058–1069.e19 (2020); McCallum, M. et al. N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2. Cell 184, 2332–2347.e16 (2021); Chen, X. et al. Human monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotensin converting enzyme 2 receptor. Cell. Mol. Immunol. 17, 647–649 (2020); Cao, Y. et al. Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients’ B cells. Cell 182, 73–84.e16 (2020); Andreano, E. et al. Extremely potent human monoclonal antibodies from COVID-19 convalescent patients. Cell. 184(7), 1821–1835.e16 (2021)), людей, перенесших инфекцию SARS-CoV (Wec, A. Z. et al. Broad sarbecovirus neutralizing antibodies define a key site of vulnerability on the SARS-CoV-2 spike protein. bioRxiv https://doi.org/10.1101/2020.05.15.096511 (2020); Tian, X. et al. Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody. Emerg. Microbes Infect. 9, 382–385 (2020); Pinto, D. et al. Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature 583, 290–295 (2020)), скрининг библиотек антител, scFv-, Fab- или VH- фрагментов (Li, W. et al. Rapid identification of a human antibody with high prophylactic and therapeutic efficacy in three animal models of SARS-CoV-2 infection. Proc. Natl. Acad. Sci. USA 117, 29832–29838 (2020); Parray, H. A. et al. Identification of an anti-SARS-CoV-2 receptor-binding domain-directed human monoclonal antibody from a naïve semisynthetic library. J. Biol. Chem. 295, 12814–12821 (2020); Wang, B. et al. Bivalent binding of a fully human IgG to the SARS-CoV-2 spike proteins reveals mechanisms of potent neutralization. bioRxiv https://doi.org/10.1101/2020.07.14.203414 (2020); Wu, Y. et al. Identification of Human Single-Domain Antibodies against SARS-CoV-2. Cell Host Microbe 27, 891–898.e5 (2020); Ku, Z. et al. Molecular determinants and mechanism for antibody cocktail preventing SARS-CoV-2 escape. Nat. Commun. 12, 469 (2021); Fagre, A. C. et al. A potent SARS-CoV-2 neutralizing human monoclonal antibody that reduces viral burden and disease severity in Syrian hamsters. Front. Immunol. 11, 614256 (2020); Noy-Porat, T. et al. A panel of human neutralizing mAbs targeting SARS-CoV-2 spike at multiple epitopes. Nat. Commun. 11, 4303 (2020); Yao, H. et al. Rational development of a human antibody cocktail that deploys multiple functions to confer Pan-SARS-CoVs protection. Cell Res. 31, 25–36 (2021); Kim, C. et al. A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein. Nat. Commun. 12, 288 (2021)). Identification of SARS-CoV-2-specific neutralizing monoclonal antibodies is generally done by one of several methods, such as immunoglobulin gene sequencing from single B cells from human covid-19 survivors or immunized (including humanized) animals (Brouwer Wu, P. J. M. et al., Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability Science 369, 643–650 (2020); its receptor ACE2. Science 368, 1274–1278 (2020); Jones, B. E. et al. The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates. Sci. Transl. Med. 13, eabf1906 ( 2021); Hansen, J. et al. Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science 369, 1010–1014 (2020); Wang, C. et al. A human monoclonal antibody blocking SARS -CoV-2 infection Nat Commun 11, 2251 (2020); Seydoux, E. et al. Analysis of a SARS-CoV-2-infected individual reveals development of potent neutralizing antibodies with limited somatic mutation. Immunity 53, 98–105.e5 (2020); Zost, S. J. et al. Rapid isolation and profiling of a diverse panel of human monoclonal targeting antibodies the SARS-CoV-2 spike protein. Nat. Med. 26, 1422–1427 (2020); Rogers, T. F. et al. Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Science 369, 956–963 (2020); Shi, R. et al. A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2. Nature 584, 120–124 (2020); Ju, B. et al. Human neutralizing antibodies elicited by SARS-CoV-2 infection. Nature 584, 115–119 (2020); Robbiani, D. F. et al. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature 584, 437–442 (2020); Liu, L. et al. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Nature 584, 450–456 (2020); Chi, X. et al. A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2. Science 369, 650–655 (2020); Wang, J. et al. Human-IgG-neutralizing monoclonal antibodies block the SARS-CoV-2 infection. Cell Rep. 32, 107918 (2020); Kreer, C. et al. Longitudinal isolation of potent near-germline SARS-CoV-2-neutralizing antibodies from COVID-19 patients. Cell 182, 843–854.e12 (2020); Kreye, J. et al. A therapeutic non-self-reactive SARS-CoV-2 antibody protects from lung pathology in a COVID-19 hamster model. Cell 183, 1058–1069.e19 (2020); McCallum, M. et al. N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2. Cell 184, 2332–2347.e16 (2021); Chen, X. et al. Human monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotensin converting enzyme 2 receptor. cell. Mol. Immunol. 17, 647–649 (2020); Cao, Y. et al. Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients’ B cells. Cell 182, 73–84.e16 (2020); Andreano, E. et al. Extremely potent human monoclonal antibodies from COVID-19 convalescent patients. cell. 184(7), 1821–1835.e16 (2021)), survivors of SARS-CoV infection (Wec, A. Z. et al. Broad sarbecovirus neutralizing antibodies define a key site of vulnerability on the SARS-CoV-2 spike protein. bioRxiv https://doi.org/10.1101/2020.05.15.096511 (2020) Tian, X. et al. Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody Emerg Microbes Infect 9, 382 –385 (2020) Pinto, D. et al Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody Nature 583, 290–295 (2020)), antibody library screening, scFv-, Fab - or VH fragments (Li, W. et al. Rapid identification of a human antibody with high prophylactic and therapeutic efficacy in three animal models of SARS-CoV-2 infection. Proc. Natl. Acad. Sci. USA 117, 29832– 29838 (2020); Parray, H. A. et al. Identification of an anti-SARS-CoV-2 receptor-binding domain-directed human monoclonal antibody from a naïve semisynthetic library. J. Biol. Chem. 295, 12814–12821 (2020) ; Wang, B. et al. Bivalent binding of a fully human IgG to the SARS-CoV-2 spike proteins reveals mechanisms of potent neutralization. bioRxiv https://doi.org/10.1101/2020.07.14.203414 (2020); Wu, Y. et al. Identification of Human Single-Domain Antibodies against SARS-CoV-2. Cell Host Microbe 27, 891–898.e5 (2020); Ku, Z. et al. Molecular determinants and mechanism for antibody cocktail preventing SARS-CoV-2 escape. Nat. commun. 12, 469 (2021); Fagre, A. C. et al. A potent SARS-CoV-2 neutralizing human monoclonal antibody that reduces viral burden and disease severity in Syrian hamsters. front. Immunol. 11, 614256 (2020); Noy-Porat, T. et al. A panel of human neutralizing mAbs targeting SARS-CoV-2 spike at multiple epitopes. Nat. commun. 11, 4303 (2020); Yao, H. et al. Rational development of a human antibody cocktail that deploys multiple functions to confer Pan-SARS-CoVs protection. Cell Res. 31, 25–36 (2021); Kim, C. et al. A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein. Nat. commun. 12, 288 (2021)).

В настоящий момент уже получены сотни различных SARS-CoV-2-специфических, в том числе и вируснейтрализующих, антител, обладающих различными профилями потентности и широты нейтрализации. Однако разработанные моноклональные антитела могут быть неактивными в отношении появившихся новых вариантов SARS-CoV-2. Так, например, моноклональное антитело бамланивимаб не способно нейтрализовать дельта-вариант SARS-CoV-2 (Planas, D. et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature 596, 276–280 (2021)). В отношении бета-варианта бамланивимаб и этесивимаб полностью неактивны, а активность касиривимаба значительно снижена (Wang, P. et al. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature 593, 130–135 (2021)). Таким образом, идентификация и всесторонняя характеризация новых SARS-CoV-2-специфических антител является актуальной задачей и позволяет создавать композиции антител, против новых вирусных вариантов SARS-CoV-2 и потенциально против других, в том числе неописанных, коронавирусов.At the moment, hundreds of different SARS-CoV-2-specific, including virus-neutralizing, antibodies have already been obtained with different potency profiles and neutralization breadths. However, the developed monoclonal antibodies may be inactive against emerging new variants of SARS-CoV-2. For example, the monoclonal antibody bamlanivimab is unable to neutralize the SARS-CoV-2 delta variant (Planas, D. et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature 596, 276–280 (2021)) . In relation to the beta variant, bamlanivimab and etesivimab are completely inactive, and the activity of casirivimab is significantly reduced (Wang, P. et al. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature 593, 130–135 ( 2021)). Thus, the identification and comprehensive characterization of new SARS-CoV-2-specific antibodies is an urgent task and allows you to create antibody compositions against new SARS-CoV-2 viral variants and potentially against other, including undescribed, coronaviruses.

Известно моноклональное антитело мыши IgM изотипа к RBD фрагменту в составе S-белка вируса SARS-CoV-2 (патент RU 2744274). Данное антитело способно детектировать до 1 нг рекомбинантного RBD фрагмента S-белка вируса SARS-CoV-2 в иммуноферментном анализе и обладает вируснейтрализующей активностью in vitro. Недостатками данного мышиного антитела для целей терапии и профилактики коронавирусной инфекции, вызванной SARS-CoV-2, являются его чужеродность для организма человека и короткое время полужизни, вследствие чего введение такого антитела пациентам может быть иммуногенным и сопровождаться нежелательными побочными реакциями. Кроме того, неизвестны уровень и механизм постулированной авторами нейтрализующей активности данного антитела в отношении SARS-CoV-2, детали эпитопной специфичности (а следовательно, и узнавание им вирусных вариантов, отличных от исходного штамма Wuhan-Hu-1, более не представленного среди циркулирующих изолятов) и возможность практического использования в системах, основанных на проточной цитометрии. Также не известен уровень (ауто)реактивности данного антитела по отношению к клеткам человека, поскольку оно было получено в иммунизированных мышах и в процессе созревания В-клетки проходило негативную селекцию против антигенов мыши, а не человека. Наконец, известно, что производство антител IgM изотипа является крайне трудоемким и сопровождается низким выходом, а сохранение всех заявленных свойств данного антитела при его возможной конверсии в IgG1-формат для преодоления данного ограничения является сомнительным, поскольку будет связано как минимум со снижением его авидности.A mouse monoclonal antibody of the IgM isotype to the RBD fragment in the S-protein of the SARS-CoV-2 virus is known (patent RU 2744274). This antibody is capable of detecting up to 1 ng of the recombinant RBD fragment of the S protein of the SARS-CoV-2 virus in an enzyme immunoassay and has virus-neutralizing activity in vitro. The disadvantages of this mouse antibody for the purposes of therapy and prevention of coronavirus infection caused by SARS-CoV-2 are its foreignness to the human body and a short half-life, as a result of which the administration of such an antibody to patients can be immunogenic and be accompanied by undesirable side reactions. In addition, the level and mechanism of the neutralizing activity of this antibody against SARS-CoV-2 postulated by the authors, the details of epitope specificity (and, consequently, its recognition of viral variants other than the original Wuhan-Hu-1 strain, which is no longer present among circulating isolates) are unknown. ) and the possibility of practical use in systems based on flow cytometry. Also, the level of (auto)reactivity of this antibody against human cells is not known, since it was obtained in immunized mice and during the maturation of the B cell was negatively selected against mouse antigens, and not human. Finally, it is known that the production of antibodies of the IgM isotype is extremely laborious and is accompanied by a low yield, and the preservation of all the declared properties of this antibody with its possible conversion to the IgG1 format to overcome this limitation is doubtful, since it will be associated at least with a decrease in its avidity.

Существует множество публикаций, описывающих получение и характеризацию RBD-специфических моноклональных антител человека, в том числе и обладающих вируснейтрализующей активностью. Например, известно моноклональное антитело человека P4A1 (Guo, Y. et al., Nat Commun.12(1), 2623 (2021)). Однако в настоящий момент нет информации о его последовательности, а кроме того нет данных о сохранении им вируснейтрализующей активности в отношении циркулирующих в настоящее время вариантов SARS-CoV-2, а следовательно и о сохранении им терапевтической активности в отношении таких вирусов. Еще одним примером являются упомянутые выше человеческие RBD-специфические нейтрализующие антитела бамланивимаб (LY-CoV555) (Jones, B. et al. The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates. Sci. Transl. Med. 13(593), 1-17 (2021) и этесивимаб (LY-CoV016/JS016/CB6) (Shi, R. et al. A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2. Nature 584, 120–124 (2020)), последовательности которых известны. Однако существенным недостатком данных антител является их неспособность нейтрализовать ряд циркулирующих вирусных вариантов SARS-CoV-2 (https://covdb.stanford.edu/page/susceptibility-data/), что ограничивает их профилактическое и терапевтическое использование.There are many publications describing the production and characterization of RBD-specific human monoclonal antibodies, including those with virus-neutralizing activity. For example, the human monoclonal antibody P4A1 is known (Guo, Y. et al., Nat Commun. 12(1), 2623 (2021)). However, at the moment there is no information about its sequence, and in addition, there is no data on its preservation of virus-neutralizing activity against currently circulating SARS-CoV-2 variants, and therefore on its preservation of therapeutic activity against such viruses. Another example is the above-mentioned human RBD-specific neutralizing antibody bamlanivimab (LY-CoV555) (Jones, B. et al. The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates. Sci. Transl. Med. 13(593), 1-17 (2021) and etesivimab (LY-CoV016/JS016/CB6) (Shi, R. et al. A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2. Nature 584, 120–124 (2020)), the sequences of which are known.However, a significant drawback of these antibodies is their inability to neutralize a number of circulating SARS-CoV-2 viral variants (https://covdb.stanford.edu/page/susceptibility-data/) , which limits their preventive and therapeutic use.

Известна общедоступная база данных CoV-AbDab (http://opig.stats.ox.ac.uk/webapps/covabdab/), содержащая информацию о последовательностях и свойствах сотен RBD-специфических моноклональных антител различного происхождения (в том числе и человеческих), многие из которых обладают вируснейтрализующей активностью в отношении SARS-CoV-2. Недостатками большинства таких антител является их неполная характеризация в плане устойчивости к циркулирующим вариантам SARS-CoV-2, поскольку такие варианты появились позже, чем были получены антитела, а также в плане эпитопной специфичности, широты нейтрализации, наличия или отсутствия ауто- и полиреактивности и т.д.The public database CoV-AbDab is known (http://opig.stats.ox.ac.uk/webapps/covabdab/), containing information on the sequences and properties of hundreds of RBD-specific monoclonal antibodies of various origins (including human), many of which have virus-neutralizing activity against SARS-CoV-2. The disadvantages of most of these antibodies are their incomplete characterization in terms of resistance to circulating SARS-CoV-2 variants, since such variants appeared later than the antibodies were obtained, as well as in terms of epitope specificity, neutralization breadth, the presence or absence of auto- and polyreactivity, etc. .d.

Наиболее близким аналогом настоящего изобретения является разработка, описанная в заявке WO2021211775A1, где раскрыты несколько моноклональных антител человека, способных связываться с RBD фрагментом Spike-белка SARS-CoV-2 и ряда других сарбековирусов, а также обладающих широкой вируснейтрализующей активностью по отношению к различным циркулирующим вариантам SARS-CoV-2 и другим сарбековирусам. Поскольку пандемия, вызванная SARS-CoV-2, продолжается, и согласно молекулярно-эпидемиологическим наблюдениям наблюдается активное формирование все новых и новых вирусных вариантов, устойчивых к уже имеющимся моноклональным антителам и их сочетаниям, в будущем не исключено возникновение вариантов, устойчивых и к антителам, описанным в заявке WO2021211775A1. Таким образом, получение новых детально охарактеризованных RBD-специфических моноклональных антител как нейтрализующих, так и ненейтрализующих, является крайне актуальной задачей, поскольку может обеспечить рациональный дизайн композиций антител, предотвращающих мутационное ускользание вируса, а также более точную диагностику, эффективную терапию и профилактику коронавирусной инфекции.The closest analogue of the present invention is the development described in the application WO2021211775A1, which discloses several human monoclonal antibodies capable of binding to the RBD fragment of the SARS-CoV-2 Spike protein and a number of other sarbecoviruses, as well as having broad virus-neutralizing activity against various circulating variants. SARS-CoV-2 and other sarbecoviruses. Since the pandemic caused by SARS-CoV-2 continues, and according to molecular epidemiological observations, there is an active formation of more and more new viral variants that are resistant to existing monoclonal antibodies and their combinations, the emergence of variants that are resistant to antibodies is also possible in the future. described in application WO2021211775A1. Thus, the preparation of new detailed RBD-specific monoclonal antibodies, both neutralizing and non-neutralizing, is an extremely urgent task, since it can provide a rational design of antibody compositions that prevent mutational escape of the virus, as well as more accurate diagnosis, effective therapy, and prevention of coronavirus infection.

Технической проблемой, решаемой настоящим изобретением, является получение новых моноклональных антител, предпочтительно человеческих моноклональных антител, которые способны к связыванию RBD фрагмента Spike-белка вируса SARS-CoV-2 и с высокой аффинностью распознают различные варианты вируса SARS-CoV-2.The technical problem solved by the present invention is to obtain new monoclonal antibodies, preferably human monoclonal antibodies, which are capable of binding the RBD fragment of the SARS-CoV-2 Spike protein and recognize various variants of the SARS-CoV-2 virus with high affinity.

Раскрытие сущности изобретенияDisclosure of the essence of the invention

Новые варианты вируса SARS-CoV-2 все чаще проявляют устойчивость к нейтрализации одобренными к применению моноклональными антителами. Поэтому расширение репертуара эффективных антител против SARS-CoV-2 продолжает оставаться важнейшей целью в условиях продолжающейся пандемии. New variants of the SARS-CoV-2 virus are increasingly resistant to neutralization by approved monoclonal antibodies. Therefore, expanding the repertoire of effective antibodies against SARS-CoV-2 continues to be a critical goal in the context of the ongoing pandemic.

Таким образом задачей настоящего изобретения является получение новых моноклональных антител, способных к связыванию с RBD-районом Spike-белка SARS-CoV-2, предпочтительно обладающих вируснейтрализующей активностью, а также антиген-связывающих фрагментов таких антител.Thus, the object of the present invention is to provide new monoclonal antibodies capable of binding to the RBD region of the SARS-CoV-2 Spike protein, preferably having virus-neutralizing activity, as well as antigen-binding fragments of such antibodies.

Для ее решения авторами настоящего изобретения была получена панель антител человека, специфичных к RBD Spike-белка SARS-CoV-2 и охарактеризована их активность in vitro и in vivo. To solve it, the authors of the present invention obtained a panel of human antibodies specific to the RBD Spike protein of SARS-CoV-2 and characterized their activity in vitro and in vivo.

Техническим результатом настоящего изобретения является получение новых моноклональных антител, способных к связыванию с RBD Spike-белка SARS-CoV-2. Высокая аффинность заявляемых антител позволит снизить их дозировку при диагностическом, профилактическом и терапевтическом применении.The technical result of the present invention is the production of new monoclonal antibodies capable of binding to the RBD Spike protein of SARS-CoV-2. The high affinity of the claimed antibodies will reduce their dosage for diagnostic, prophylactic and therapeutic use.

Дополнительным техническим результатом для ряда антител является их высокая вируснейтрализующая активность, что обеспечивает возможность их использования в качестве средств профилактики (до- и пост-контактной) и терапии коронавирусной инфекции, вызванной SARS-CoV-2 и близкородственными ему вирусами.An additional technical result for a number of antibodies is their high virus-neutralizing activity, which makes it possible to use them as a means of prevention (pre- and post-exposure) and therapy of coronavirus infection caused by SARS-CoV-2 and its closely related viruses.

Также полученные авторами настоящего изобретения данные говорят о том, что возможен рациональный дизайн широкого репертуара RBD-специфичных коктейлей антител, содержащих неконкурирующие нейтрализующие антитела, которые будут активными как в отношении циркулирующих в настоящее время вариантов вирусов, так и возможных будущих вариантов.Also, the data obtained by the authors of the present invention suggests that it is possible to rationally design a wide repertoire of RBD-specific antibody cocktails containing non-competing neutralizing antibodies that will be active against both currently circulating variants of viruses and possible future variants.

Поэтому дополнительным техническим результатом настоящего изобретения является создание коктейлей антител, содержащих комбинацию антител изобретения, которые обладают широкой вируснейтрализующей активностью по отношению к различным вариантам SARS-CoV-2.Therefore, an additional technical result of the present invention is the creation of antibody cocktails containing a combination of antibodies of the invention, which have a broad virus-neutralizing activity against various variants of SARS-CoV-2.

Антитела и антигенсвязывающие фрагментыAntibodies and antigen-binding fragments

Поставленная задача была решена получением моноклональных антител человека, селективно связывающих RBD фрагмент Spike-белка вируса SARS-CoV-2.The problem was solved by obtaining human monoclonal antibodies that selectively bind the RBD fragment of the Spike protein of the SARS-CoV-2 virus.

Используемый в настоящей заявке термин «антитело» предназначен для обозначения молекулы иммуноглобулина, составленной из четырех полипептидных цепей, при этом две тяжелые (Н) цепи и две легкие (L) цепи связываются друг с другом дисульфидными связями. Каждая тяжелая цепь содержит вариабельную область тяжелой цепи (сокращенно называемую в настоящем документе VH) и константную область тяжелой цепи. Константная область тяжелой цепи состоит из трех доменов: CH1, СН2 и СН3. Каждая легкая цепь содержит вариабельную область легкой цепи (сокращенно называемую в настоящем документе VL) и константную область легкой цепи. Константная область легкой цепи состоит из одного домена: CL. As used herein, the term "antibody" is intended to refer to an immunoglobulin molecule composed of four polypeptide chains, with two heavy (H) chains and two light (L) chains linked to each other by disulfide bonds. Each heavy chain contains a heavy chain variable region (abbreviated herein as VH) and a heavy chain constant region. The heavy chain constant region consists of three domains: CH1, CH2, and CH3. Each light chain contains a light chain variable region (abbreviated herein as VL) and a light chain constant region. The light chain constant region consists of a single domain: CL.

Области VH и VL могут далее подразделяться на гипервариабельные районы, которые называются определяющими комплементарность областями (CDR), перемежаемые областями с более высоким уровнем консервативности, называемыми каркасными областями (FR). Каждая область VH и VL образована тремя CDR и четырьмя FR, расположенными от амино-терминального конца к карбокси-терминальному концу в следующем порядке: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.The VH and VL regions can be further subdivided into hypervariable regions called complementarity determining regions (CDRs) interspersed with regions with a higher level of conservatism called framework regions (FRs). Each VH and VL region is formed by three CDRs and four FRs, arranged from amino-terminal to carboxy-terminal in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.

Четыре каркасных участка формируют конформацию типа бета-складчатого слоя. Участки CDR расположены в близком соседстве друг с другом благодаря каркасным участкам и вносят вклад в образование антигенсвязывающего участка. Участки CDR и каркасные участки антител могут быть определены путем ссылки на нумерационную систему Кабата [Kabat numbering system, Kabat et al., 1987, "Sequences of Proteins of Immunological Interest", US Dept. of Health and Human Services, US Government Printing Office] в сочетании с данными рентгеноструктурного анализа, как указано в заявке WO 91/09967. Участки CDR и каркасные участки антител могут также быть определены по номенклатуре Международной информационной системы по иммуногенетике (International Immunogenetics Information System, www.imgt.org).The four framework regions form a conformation such as a beta sheet. The CDRs are located in close proximity to each other due to the framework regions and contribute to the formation of the antigen-binding site. The CDRs and framework regions of antibodies can be defined by reference to the Kabat numbering system [Kabat numbering system, Kabat et al., 1987, "Sequences of Proteins of Immunological Interest", US Dept. of Health and Human Services, US Government Printing Office] in combination with X-ray diffraction data as described in WO 91/09967. CDRs and framework regions of antibodies can also be defined according to the nomenclature of the International Immunogenetics Information System (International Immunogenetics Information System, www.imgt.org).

Если не указано иное, любая представленная в описании полипептидная цепь имеет аминокислотную последовательность, которая начинается на N-конце и заканчивается на С-конце. Если антигенсвязывающий центр содержит и VH-, и VL-области, то они могут быть расположены на одной и той же полипептидной молекуле или предпочтительно каждая область может располагаться на разных цепях, VH-область может быть частью тяжелой цепи иммуноглобулина или ее фрагмента, а VL-область - частью легкой цепи иммуноглобулина или ее фрагмента.Unless otherwise indicated, any polypeptide chain described herein has an amino acid sequence that begins at the N-terminus and ends at the C-terminus. If the antigen binding site contains both VH and VL regions, they may be located on the same polypeptide molecule, or preferably each region may be located on different chains, the VH region may be part of an immunoglobulin heavy chain or a fragment thereof, and the VL -region - part of the light chain of an immunoglobulin or its fragment.

Как хорошо известно, минорные изменения аминокислотной последовательности, такие как делеция, добавление или замена одной, небольшого количества или даже нескольких аминокислот, могут приводить к получению аллельной формы исходного белка, которая обладает практически идентичными свойствами. Более того, известен способ «перевивки» CDR-петель одного антитела в контекст каркасных последовательностей другого антитела, также с сохранением исходных свойств, что в частности позволяет производить гуманизацию антител, полученных в других млекопитающих. Таким образом, антитело изобретения включает те варианты, аминокислотная последовательность которых вне CDR петель отличается от приведенных в настоящей заявке последовательностей, но которые сохранили ту же антигенсвязывающую активность.As is well known, minor changes in the amino acid sequence, such as deletion, addition or substitution of one, a small number or even a few amino acids, can lead to an allelic form of the original protein, which has almost identical properties. Moreover, a method is known for "grafting" the CDR loops of one antibody into the context of the frame sequences of another antibody, also with the preservation of the original properties, which, in particular, allows the humanization of antibodies obtained in other mammals. Thus, an antibody of the invention includes those variants whose amino acid sequence outside the CDR loops differs from those given in this application, but which retained the same antigen-binding activity.

Антитело настоящего изобретения может быть человеческим антителом, гуманизованным антителом, мышиным антителом, химерным антителом и другими генно-инженерными антителами. The antibody of the present invention may be a human antibody, a humanized antibody, a mouse antibody, a chimeric antibody, and other engineered antibodies.

Также антитело изобретение может представлять собой аффинно-зрелое антитело.Also, an antibody of the invention may be an affinity matured antibody.

Используемый в настоящем документе термин «антиген-связывающий фрагмент» антитела обозначает фрагмент антитела, который сохраняет способность к специфическому связыванию с антигеном. К примерам таких фрагментов, включенных в термин «антиген-связывающий фрагмент» антитела, относятся (i) фрагмент Fab, моновалентный фрагмент, состоящий из доменов VL, VH, CL и CH1; (ii) фрагмент F(ab')2, бивалентный фрагмент, состоящий из двух фрагментов Fab, связанных дисульфидным мостиком в шарнирной области; (iii) фрагмент Fd, состоящий из доменов VH и CH1; (iv) фрагмент Fv, состоящий из доменов VL и VH отдельной области антитела; (v) фрагмент dAb (Ward, E.S. et al. Nature. 241, 544-546, (1989)), состоящий из домена VH; и (vi) отдельная определяющая комплементарность область (CDR). Более того, несмотря на то, что два домена во фрагменте Fv, VL и VH кодируются различными генами, их можно объединить, используя рекомбинантные технологии, посредством синтетического линкера, который позволяет построить из них единую белковую цепочку, в которой области VL и VH связываются с образованием моновалентных молекул (известных как одноцепочечные антитела или scFv; см., например, Bird, R.E. et al. Science. 24, 423-426 (1988); Huston, J.S. et al. Proc. Natl. Acad. Sci. USA 85:5879-5883 (1988)). Такие одноцепочечные антитела также включаются в сферу охвата термина «антиген-связывающий фрагмент» антитела.As used herein, the term "antigen-binding fragment" of an antibody refers to an antibody fragment that retains the ability to specifically bind to an antigen. Examples of such fragments included in the term "antigen-binding fragment" of an antibody include (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL, and CH1 domains; (ii) an F(ab')2 fragment, a bivalent fragment consisting of two Fab fragments linked by a disulfide bridge in the hinge region; (iii) an Fd fragment consisting of VH and CH1 domains; (iv) an Fv fragment consisting of the VL and VH domains of a single antibody region; (v) a dAb fragment (Ward, E. S. et al. Nature. 241, 544-546, (1989)), consisting of a VH domain; and (vi) a distinct complementarity determining region (CDR). Moreover, despite the fact that the two domains in the fragment Fv, VL and VH are encoded by different genes, they can be combined using recombinant technologies through a synthetic linker that allows them to be built into a single protein chain in which the VL and VH regions bind to formation of monovalent molecules (known as single chain antibodies or scFv; see, for example, Bird, R. E. et al. Science. 24, 423-426 (1988); Huston, J. S. et al. Proc. Natl. Acad. Sci. USA 85: 5879-5883 (1988)). Such single chain antibodies are also included within the scope of the term "antigen-binding fragment" of an antibody.

Моноклональные антитела человека являются минимально иммуногенными молекулами, поэтому многие современные методы направлены на их получение. Для этого в частности могут использоваться В лимфоциты, выделенные из периферической крови переболевших или вакцинированных доноров. Human monoclonal antibodies are minimally immunogenic molecules; therefore, many modern methods are aimed at obtaining them. For this, in particular, B lymphocytes isolated from the peripheral blood of recovered or vaccinated donors can be used.

Специфические в отношении RBD Spike-белка SARS-CoV-2 моноклональные антитела настоящего изобретения были получены путем секвенирования и клонирования кДНК генов иммуноглобулинов в отдельных RBD-специфических В-лимфоцитах доноров, перенесших коронавирусную инфекцию ковид-19 в тяжелой форме и сформировавших высокие титры вируснейтрализующих антител в плазме крови.The monoclonal antibodies of the present invention specific for the SARS-CoV-2 RBD Spike protein were obtained by sequencing and cloning cDNA of immunoglobulin genes in individual RBD-specific B-lymphocytes of donors who had a severe form of coronavirus infection with covid-19 and formed high titers of virus-neutralizing antibodies. in blood plasma.

Подходящий способ для выделения антител, эффективных для использования в рамках настоящего изобретения, включает (i) выделение В-лимфоцитов периферической крови доноров, перенесших коронавирусную инфекцию ковид-19 и сформировавших высокие нейтрализующие титры антител в сыворотке крови, (ii) окрашивание В-лимфоцитов флуоресцентно меченными препаратами RBD SARS-CoV-2, (iii) сортировка единичных окрашенных RBD+ В-лимфоцитов, (iv) проведение обратной транскрипции и ПЦР с наборами вырожденных праймеров, комплементарных лидерным и константным последовательностям генов иммуноглобулинов, (v) секвенирование полученных ПЦР продуктов с целью выяснения нуклеотидной и аминокислотной последовательностей экспрессируемых такими В-клетками антител, (vi) клонирование нуклеотидных последовательностей таких антител в экспрессионные векторы для наработки в культуре клеток млекопитающих, (vii) очистка, анализ специфичности и активности рекомбинантных моноклональных антител человека. В последующем также предусмотрено определение аминокислотной последовательности вариабельных доменов таких антител, измерение аффинности и специфичности, нейтрализующих свойств in vitro и in vivo.A suitable method for isolating antibodies effective for use in the present invention comprises (i) isolating peripheral blood B lymphocytes from covid-19 donors who have developed high neutralizing serum antibody titers, (ii) staining B lymphocytes with fluorescent SARS-CoV-2 RBD-labeled preparations, (iii) sorting of single RBD+ stained B-lymphocytes, (iv) performing reverse transcription and PCR with sets of degenerate primers complementary to the leader and constant sequences of immunoglobulin genes, (v) sequencing of the obtained PCR products for the purpose of determining the nucleotide and amino acid sequences of antibodies expressed by such B cells, (vi) cloning the nucleotide sequences of such antibodies into expression vectors for production in mammalian cell culture, (vii) purification, analysis of specificity and activity of recombinant human monoclonal antibodies. The following also provides for the determination of the amino acid sequence of the variable domains of such antibodies, the measurement of affinity and specificity, neutralizing properties in vitro and in vivo.

В результате были получены нуклеотидные последовательности, на основании которых были определены аминокислотные последовательности вариабельных доменов тяжелых и легких цепей антител настоящего изобретения. Участки CDRs были определены по номенклатуре Kabat [Kabat numbering system, Kabat et al., 1987 "Sequences of Proteins of Immunological Interest", US Dept. of Health and Human Services, US Government Printing Office].As a result, nucleotide sequences were obtained, on the basis of which the amino acid sequences of the variable domains of the heavy and light chains of the antibodies of the present invention were determined. The regions of CDRs were determined according to the Kabat nomenclature [Kabat numbering system, Kabat et al., 1987 "Sequences of Proteins of Immunological Interest", US Dept. of Health and Human Services, US Government Printing Office].

Полученное антитело включает вариабельную область тяжелой цепи (VH), которая содержит последовательности гипервариабельных районов: CDRH1, имеющего аминокислотную последовательность, выбранную из SEQ ID NO: 1-23, CDRH2, имеющего аминокислотную последовательность, выбранную из SEQ ID NO: 24-46, и CDRH3, имеющего аминокислотную последовательность, выбранную из SEQ ID NO: 47-69, и вариабельную область легкой цепи (VL), которая содержит последовательности гипервариабельных районов: CDRL1, имеющего аминокислотную последовательность, выбранную из SEQ ID NO: 70-92, CDRL2, имеющего аминокислотную последовательность, выбранную из AAS (SEQ ID NO:93), SNN (SEQ ID NO:94), WAT (SEQ ID NO:95), EVS (SEQ ID NO:96), DAS (SEQ ID NO:97), EVT (SEQ ID NO:98), KAS (SEQ ID NO:99), GAS (SEQ ID NO:100), NNN (SEQ ID NO:101), AAS (SEQ ID NO:102), DAS (SEQ ID NO:103), DVS (SEQ ID NO:104), GAS (SEQ ID NO:105), EVS (SEQ ID NO:106), KAS (SEQ ID NO:107), DAS (SEQ ID NO:108), GTS (SEQ ID NO:109), GAS (SEQ ID NO:110), GAS (SEQ ID NO:111), WAS (SEQ ID NO:112), DAS (SEQ ID NO:113), AAS (SEQ ID NO:114), или AAS (SEQ ID NO:115) и CDRL3, имеющего аминокислотную последовательность, выбранную из SEQ ID NO: 116-138. Также настоящим изобретением предусмотрены антиген-связывающие фрагменты данных моноклональных антител.The resulting antibody comprises a heavy chain variable region (VH) that contains the sequences of hypervariable regions: CDRH1 having an amino acid sequence selected from SEQ ID NOs: 1-23, CDRH2 having an amino acid sequence selected from SEQ ID NOs: 24-46, and CDRH3 having an amino acid sequence selected from SEQ ID NOs: 47-69 and a light chain variable region (VL) that contains sequences of hypervariable regions: CDRL1 having an amino acid sequence selected from SEQ ID NOs: 70-92, CDRL2 having an amino acid sequence selected from AAS (SEQ ID NO:93), SNN (SEQ ID NO:94), WAT (SEQ ID NO:95), EVS (SEQ ID NO:96), DAS (SEQ ID NO:97), EVT (SEQ ID NO:98), KAS (SEQ ID NO:99), GAS (SEQ ID NO:100), NNN (SEQ ID NO:101), AAS (SEQ ID NO:102), DAS (SEQ ID NO:102 :103), DVS (SEQ ID NO:104), GAS (SEQ ID NO:105), EVS (SEQ ID NO:106), KAS (SEQ ID NO:107), DAS (SEQ ID NO:108), GTS (SEQ ID NO:109), GAS (SEQ ID NO:110), GAS (SEQ ID NO:111), WAS (SEQ ID NO:112), DAS (SEQ ID NO:113), AAS (SEQ ID NO: 114), or AAS (SEQ ID NO:115) and CDRL3 having an amino acid sequence selected from SEQ ID NO: 116-138. Also provided by the present invention are antigen-binding fragments of these monoclonal antibodies.

В следующем аспекте изобретения предусмотрено моноклональное антитело или его антигенсвязывающий фрагмент, содержащие вариабельную область тяжелой цепи (VH) с последовательностью аминокислот не менее чем на 90% гомологичную одной из последовательностей SEQ ID NO: 139-161, и вариабельную область легкой цепи (VL) с последовательностью аминокислот не менее чем на 90% гомологичной одной из последовательностей SEQ ID NO: 162-184.In a further aspect of the invention, a monoclonal antibody or antigen-binding fragment thereof is provided, comprising a heavy chain variable region (VH) with an amino acid sequence of at least 90% homologous to one of the sequences of SEQ ID NOs: 139-161, and a light chain variable region (VL) with an amino acid sequence of at least 90% homologous to one of the sequences of SEQ ID NO: 162-184.

В одном из воплощений моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что вариабельный участок тяжелой цепи (VH) содержит:In one embodiment, a monoclonal antibody or antigen-binding fragment thereof that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that the heavy chain variable region (VH) contains:

(i) CDRH1 последовательности GFTFSSYA (SEQ ID NO: 1);(i) CDRH1 sequence GFTFSSYA (SEQ ID NO: 1);

(ii) CDRH2 последовательности ISYDGSNK (SEQ ID NO: 24);(ii) CDRH2 sequence ISYDGSNK (SEQ ID NO: 24);

(iii) CDRH3 последовательности ARARPWRYSYGLYYYYGMDV (SEQ ID NO: 47), и (iii) a CDRH3 sequence of ARARPWRYSYGLYYYYGMDV (SEQ ID NO: 47), and

вариабельный участок легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности QSISSY (SEQ ID NO: 70);(i) CDRL1 sequence QSISSY (SEQ ID NO: 70);

(ii) CDRL2 последовательности AAS (SEQ ID NO: 93);(ii) AAS CDRL2 sequences (SEQ ID NO: 93);

(iii) CDRL3 последовательности QQSYSTPGS (SEQ ID NO: 116) [антитело iB0].(iii) CDRL3 sequence QQSYSTPGS (SEQ ID NO: 116) [antibody iB0].

В другом воплощении моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что вариабельная область тяжелой цепи (VH) содержит:In another embodiment, a monoclonal antibody or antigen-binding fragment thereof that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that the heavy chain variable region (VH) contains:

(i) CDRH1 последовательности SEQ ID NO: 2;(i) CDRH1 sequences of SEQ ID NO: 2;

(ii) CDRH2 последовательности SEQ ID NO: 25;(ii) CDRH2 sequences of SEQ ID NO: 25;

(iii) CDRH3 последовательности SEQ ID NO: 48, и (iii) CDRH3 sequences of SEQ ID NO: 48, and

вариабельная область легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности SEQ ID NO: 71;(i) CDRL1 sequence of SEQ ID NO: 71;

(ii) CDRL2 последовательности SNN (SEQ ID NO:94);(ii) CDRL2 SNN sequences (SEQ ID NO:94);

(iii) CDRL3 последовательности SEQ ID NO: 117 [антитело iB1].(iii) CDRL3 sequence of SEQ ID NO: 117 [antibody iB1].

В следующем воплощении моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что вариабельная область тяжелой цепи (VH) содержит:In a further embodiment, the monoclonal antibody, or antigen-binding fragment thereof, that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that the heavy chain variable region (VH) contains:

(i) CDRH1 последовательности SEQ ID NO: 3;(i) CDRH1 sequences of SEQ ID NO: 3;

(ii) CDRH2 последовательности SEQ ID NO: 26;(ii) CDRH2 sequences of SEQ ID NO: 26;

(iii) CDRH3 последовательности SEQ ID NO: 49, и (iii) CDRH3 sequences of SEQ ID NO: 49, and

вариабельная область легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности SEQ ID NO: 72;(i) CDRL1 sequence of SEQ ID NO: 72;

(ii) CDRL2 последовательности WAT (SEQ ID NO:95);(ii) CDRL2 WAT sequence (SEQ ID NO:95);

(iii) CDRL3 последовательности SEQ ID NO: 118 [антитело iB2].(iii) CDRL3 sequence of SEQ ID NO: 118 [iB2 antibody].

В другом воплощении моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что вариабельная область тяжелой цепи (VH) содержит:In another embodiment, a monoclonal antibody or antigen-binding fragment thereof that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that the heavy chain variable region (VH) contains:

(i) CDRH1 последовательности SEQ ID NO: 4;(i) CDRH1 sequences of SEQ ID NO: 4;

(ii) CDRH2 последовательности SEQ ID NO: 27;(ii) CDRH2 sequences of SEQ ID NO: 27;

(iii) CDRH3 последовательности SEQ ID NO: 50, и (iii) CDRH3 sequences of SEQ ID NO: 50, and

вариабельная область легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности SEQ ID NO: 73;(i) CDRL1 sequence of SEQ ID NO: 73;

(ii) CDRL2 последовательности EVS (SEQ ID NO:96);(ii) CDRL2 EVS sequences (SEQ ID NO:96);

(iii) CDRL3 последовательности SEQ ID NO: 119 [антитело iB3].(iii) CDRL3 sequence of SEQ ID NO: 119 [iB3 antibody].

В еще одном воплощении моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что вариабельная область тяжелой цепи (VH)содержит:In yet another embodiment, a monoclonal antibody or antigen-binding fragment thereof that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that the heavy chain variable region (VH) contains:

(i) CDRH1 последовательности SEQ ID NO: 5;(i) CDRH1 sequences of SEQ ID NO: 5;

(ii) CDRH2 последовательности SEQ ID NO: 28;(ii) CDRH2 sequences of SEQ ID NO: 28;

(iii) CDRH3 последовательности SEQ ID NO: 51, и (iii) CDRH3 sequences of SEQ ID NO: 51, and

вариабельная область легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности SEQ ID NO: 74;(i) CDRL1 sequence of SEQ ID NO: 74;

(ii) CDRL2 последовательности DAS (SEQ ID NO:97);(ii) CDRL2 DAS sequences (SEQ ID NO:97);

(iii) CDRL3 последовательности SEQ ID NO: 120 [антитело iB4].(iii) CDRL3 sequence of SEQ ID NO: 120 [iB4 antibody].

В дополнительном воплощении моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что вариабельная область тяжелой цепи (VH) содержит:In a further embodiment, a monoclonal antibody or antigen-binding fragment thereof that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that the heavy chain variable region (VH) contains:

(i) CDRH1 последовательности SEQ ID NO: 6;(i) CDRH1 sequences of SEQ ID NO: 6;

(ii) CDRH2 последовательности SEQ ID NO: 29;(ii) CDRH2 sequences of SEQ ID NO: 29;

(iii) CDRH3 последовательности SEQ ID NO: 52, и (iii) CDRH3 sequences of SEQ ID NO: 52, and

вариабельная область легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности SEQ ID NO: 75;(i) CDRL1 sequence of SEQ ID NO: 75;

(ii) CDRL2 последовательности EVT (SEQ ID NO:98);(ii) CDRL2 EVT sequence (SEQ ID NO:98);

(iii) CDRL3 последовательности SEQ ID NO: 121 [антитело iB5](iii) CDRL3 sequence of SEQ ID NO: 121 [iB5 antibody]

В следующем воплощении моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что вариабельная область тяжелой цепи (VH) содержит:In a further embodiment, the monoclonal antibody, or antigen-binding fragment thereof, that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that the heavy chain variable region (VH) contains:

(i) CDRH1 последовательности SEQ ID NO: 7;(i) CDRH1 sequences of SEQ ID NO: 7;

(ii) CDRH2 последовательности SEQ ID NO: 30;(ii) CDRH2 sequences of SEQ ID NO: 30;

(iii) CDRH3 последовательности SEQ ID NO: 53, и (iii) CDRH3 sequences of SEQ ID NO: 53, and

вариабельная область легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности SEQ ID NO: 76;(i) CDRL1 sequence of SEQ ID NO: 76;

(ii) CDRL2 последовательности KAS (SEQ ID NO:99);(ii) CDRL2 KAS sequence (SEQ ID NO:99);

(iii) CDRL3 последовательности SEQ ID NO: 122 [антитело iB6].(iii) CDRL3 sequence of SEQ ID NO: 122 [iB6 antibody].

В другом воплощении моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что вариабельная область тяжелой цепи (VH) содержит:In another embodiment, a monoclonal antibody or antigen-binding fragment thereof that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that the heavy chain variable region (VH) contains:

(i) CDRH1 последовательности SEQ ID NO: 8;(i) CDRH1 sequences of SEQ ID NO: 8;

(ii) CDRH2 последовательности SEQ ID NO: 31;(ii) CDRH2 sequences of SEQ ID NO: 31;

(iii) CDRH3 последовательности SEQ ID NO: 54, и (iii) CDRH3 sequences of SEQ ID NO: 54, and

вариабельная область легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности SEQ ID NO: 77;(i) CDRL1 sequence of SEQ ID NO: 77;

(ii) CDRL2 последовательности GAS (SEQ ID NO:100);(ii) CDRL2 GAS sequences (SEQ ID NO:100);

(iii) CDRL3 последовательности SEQ ID NO: 123 [антитело iB9].(iii) CDRL3 sequence of SEQ ID NO: 123 [antibody iB9].

В еще одном воплощении моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что вариабельная область тяжелой цепи (VH) содержит:In yet another embodiment, a monoclonal antibody or antigen-binding fragment thereof that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that the heavy chain variable region (VH) contains:

(i) CDRH1 последовательности SEQ ID NO: 9;(i) CDRH1 sequences of SEQ ID NO: 9;

(ii) CDRH2 последовательности SEQ ID NO: 32;(ii) CDRH2 sequences of SEQ ID NO: 32;

(iii) CDRH3 последовательности SEQ ID NO: 55, и (iii) CDRH3 sequences of SEQ ID NO: 55, and

вариабельная область легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности SEQ ID NO: 78;(i) CDRL1 sequence of SEQ ID NO: 78;

(ii) CDRL2 последовательности NNN (SEQ ID NO:101);(ii) CDRL2 NNN sequence (SEQ ID NO:101);

(iii) CDRL3 последовательности SEQ ID NO: 124 [антитело iB10].(iii) CDRL3 sequence of SEQ ID NO: 124 [antibody iB10].

В альтернативном воплощении моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что вариабельная область тяжелой цепи (VH) содержит:In an alternative embodiment, a monoclonal antibody or antigen-binding fragment thereof that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that the heavy chain variable region (VH) contains:

(i) CDRH1 последовательности SEQ ID NO: 10;(i) CDRH1 sequences of SEQ ID NO: 10;

(ii) CDRH2 последовательности SEQ ID NO: 33;(ii) CDRH2 sequences of SEQ ID NO: 33;

(iii) CDRH3 последовательности SEQ ID NO: 56, и (iii) CDRH3 sequences of SEQ ID NO: 56, and

вариабельная область легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности SEQ ID NO: 79;(i) CDRL1 sequence of SEQ ID NO: 79;

(ii) CDRL2 последовательности AAS (SEQ ID NO:102);(ii) CDRL2 AAS sequences (SEQ ID NO:102);

(iii) CDRL3 последовательности SEQ ID NO: 125 [антитело iB11].(iii) CDRL3 sequence of SEQ ID NO: 125 [antibody iB11].

В другом воплощении моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что вариабельная область тяжелой цепи (VH) содержит:In another embodiment, a monoclonal antibody or antigen-binding fragment thereof that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that the heavy chain variable region (VH) contains:

(i) CDRH1 последовательности SEQ ID NO: 11;(i) CDRH1 sequences of SEQ ID NO: 11;

(ii) CDRH2 последовательности SEQ ID NO: 34;(ii) CDRH2 sequences of SEQ ID NO: 34;

(iii) CDRH3 последовательности SEQ ID NO: 57, и (iii) CDRH3 sequences of SEQ ID NO: 57, and

вариабельная область легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности SEQ ID NO: 80;(i) CDRL1 sequence of SEQ ID NO: 80;

(ii) CDRL2 последовательности DAS (SEQ ID NO:103);(ii) CDRL2 DAS sequences (SEQ ID NO:103);

(iii) CDRL3 последовательности SEQ ID NO: 126 [антитело iB12](iii) CDRL3 sequence of SEQ ID NO: 126 [antibody iB12]

В следующем воплощении моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что вариабельная область тяжелой цепи (VH) содержит:In a further embodiment, the monoclonal antibody, or antigen-binding fragment thereof, that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that the heavy chain variable region (VH) contains:

(i) CDRH1 последовательности SEQ ID NO: 12;(i) CDRH1 sequences of SEQ ID NO: 12;

(ii) CDRH2 последовательности SEQ ID NO: 35;(ii) CDRH2 sequences of SEQ ID NO: 35;

(iii) CDRH3 последовательности SEQ ID NO: 58, и (iii) CDRH3 sequences of SEQ ID NO: 58, and

вариабельная область легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности SEQ ID NO: 81;(i) CDRL1 sequence of SEQ ID NO: 81;

(ii) CDRL2 последовательности DVS (SEQ ID NO:104);(ii) CDRL2 sequence DVS (SEQ ID NO:104);

(iii) CDRL3 последовательности SEQ ID NO: 127 [антитело iB13](iii) CDRL3 sequence of SEQ ID NO: 127 [antibody iB13]

В ином воплощении моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что вариабельная область тяжелой цепи (VH) содержит:In another embodiment, a monoclonal antibody or antigen-binding fragment thereof that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that the heavy chain variable region (VH) contains:

(i) CDRH1 последовательности SEQ ID NO: 13;(i) CDRH1 sequences of SEQ ID NO: 13;

(ii) CDRH2 последовательности SEQ ID NO: 36;(ii) CDRH2 sequences of SEQ ID NO: 36;

(iii) CDRH3 последовательности SEQ ID NO: 59, и (iii) CDRH3 sequences of SEQ ID NO: 59, and

вариабельная область легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности SEQ ID NO: 82;(i) CDRL1 sequence of SEQ ID NO: 82;

(ii) CDRL2 последовательности GAS (SEQ ID NO:105);(ii) CDRL2 GAS sequences (SEQ ID NO:105);

(iii) CDRL3 последовательности SEQ ID NO: 128 [антитело iB14](iii) CDRL3 sequences of SEQ ID NO: 128 [antibody iB14]

В дополнительном воплощении моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что вариабельная область тяжелой цепи (VH) содержит:In a further embodiment, a monoclonal antibody or antigen-binding fragment thereof that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that the heavy chain variable region (VH) contains:

(i) CDRH1 последовательности SEQ ID NO: 14;(i) CDRH1 sequences of SEQ ID NO: 14;

(ii) CDRH2 последовательности SEQ ID NO: 37;(ii) CDRH2 sequences of SEQ ID NO: 37;

(iii) CDRH3 последовательности SEQ ID NO: 60, и (iii) CDRH3 sequences of SEQ ID NO: 60, and

вариабельная область легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности SEQ ID NO: 83;(i) CDRL1 sequence of SEQ ID NO: 83;

(ii) CDRL2 последовательности EVS (SEQ ID NO:106);(ii) CDRL2 EVS sequences (SEQ ID NO:106);

(iii) CDRL3 последовательности SEQ ID NO: 129 [антитело iB15].(iii) CDRL3 sequence of SEQ ID NO: 129 [antibody iB15].

В альтернативном воплощении моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что вариабельная область тяжелой цепи (VH) содержит:In an alternative embodiment, a monoclonal antibody or antigen-binding fragment thereof that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that the heavy chain variable region (VH) contains:

(i) CDRH1 последовательности SEQ ID NO: 15;(i) CDRH1 sequences of SEQ ID NO: 15;

(ii) CDRH2 последовательности SEQ ID NO: 38;(ii) CDRH2 sequences of SEQ ID NO: 38;

(iii) CDRH3 последовательности SEQ ID NO: 61, и (iii) CDRH3 sequences of SEQ ID NO: 61, and

вариабельная область легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности SEQ ID NO: 84;(i) CDRL1 sequence of SEQ ID NO: 84;

(ii) CDRL2 последовательности KAS (SEQ ID NO:107);(ii) CDRL2 KAS sequence (SEQ ID NO:107);

(iii) CDRL3 последовательности SEQ ID NO: 130 [антитело iB16].(iii) CDRL3 sequence of SEQ ID NO: 130 [antibody iB16].

В ином воплощении моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что вариабельная область тяжелой цепи (VH) содержит:In another embodiment, a monoclonal antibody or antigen-binding fragment thereof that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that the heavy chain variable region (VH) contains:

(i) CDRH1 последовательности SEQ ID NO: 16;(i) CDRH1 sequences of SEQ ID NO: 16;

(ii) CDRH2 последовательности SEQ ID NO: 39;(ii) CDRH2 sequences of SEQ ID NO: 39;

(iii) CDRH3 последовательности SEQ ID NO: 62, и (iii) CDRH3 sequences of SEQ ID NO: 62, and

вариабельная область легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности SEQ ID NO: 85;(i) CDRL1 sequence of SEQ ID NO: 85;

(ii) CDRL2 последовательности DAS (SEQ ID NO:108);(ii) CDRL2 DAS sequences (SEQ ID NO:108);

(iii) CDRL3 последовательности SEQ ID NO: 131 [антитело iB17].(iii) CDRL3 sequence of SEQ ID NO: 131 [antibody iB17].

В еще одном воплощении моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что вариабельная область тяжелой цепи (VH) содержит:In yet another embodiment, a monoclonal antibody or antigen-binding fragment thereof that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that the heavy chain variable region (VH) contains:

(i) CDRH1 последовательности SEQ ID NO: 17;(i) CDRH1 sequences of SEQ ID NO: 17;

(ii) CDRH2 последовательности SEQ ID NO: 40;(ii) CDRH2 sequences of SEQ ID NO: 40;

(iii) CDRH3 последовательности SEQ ID NO: 63, и (iii) CDRH3 sequences of SEQ ID NO: 63, and

вариабельная область легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности SEQ ID NO: 86;(i) CDRL1 sequence of SEQ ID NO: 86;

(ii) CDRL2 последовательности GTS (SEQ ID NO:109);(ii) CDRL2 GTS sequence (SEQ ID NO:109);

(iii) CDRL3 последовательности SEQ ID NO: 132 [антитело iB18].(iii) CDRL3 sequence of SEQ ID NO: 132 [antibody iB18].

В другом воплощении моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что вариабельная область тяжелой цепи (VH) содержит:In another embodiment, a monoclonal antibody or antigen-binding fragment thereof that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that the heavy chain variable region (VH) contains:

(i) CDRH1 последовательности SEQ ID NO: 18;(i) CDRH1 sequences of SEQ ID NO: 18;

(ii) CDRH2 последовательности SEQ ID NO: 41;(ii) CDRH2 sequences of SEQ ID NO: 41;

(iii) CDRH3 последовательности SEQ ID NO: 64, и (iii) CDRH3 sequences of SEQ ID NO: 64, and

вариабельная область легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности SEQ ID NO: 87;(i) CDRL1 sequence of SEQ ID NO: 87;

(ii) CDRL2 последовательности GAS (SEQ ID NO:110);(ii) CDRL2 GAS sequences (SEQ ID NO:110);

(iii) CDRL3 последовательности SEQ ID NO: 133 [антитело iB19].(iii) CDRL3 sequence of SEQ ID NO: 133 [antibody iB19].

В дополнительном воплощении моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что вариабельная область тяжелой цепи (VH) содержит:In a further embodiment, a monoclonal antibody or antigen-binding fragment thereof that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that the heavy chain variable region (VH) contains:

(i) CDRH1 последовательности SEQ ID NO: 19;(i) CDRH1 sequences of SEQ ID NO: 19;

(ii) CDRH2 последовательности SEQ ID NO: 42;(ii) CDRH2 sequences of SEQ ID NO: 42;

(iii) CDRH3 последовательности SEQ ID NO: 65, и (iii) CDRH3 sequences of SEQ ID NO: 65, and

вариабельная область легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности SEQ ID NO: 88;(i) CDRL1 sequence of SEQ ID NO: 88;

(ii) CDRL2 последовательности GAS (SEQ ID NO:111);(ii) CDRL2 GAS sequences (SEQ ID NO:111);

(iii) CDRL3 последовательности SEQ ID NO: 134 [антитело iB20].(iii) CDRL3 sequence of SEQ ID NO: 134 [antibody iB20].

В еще одном воплощении моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что вариабельная область тяжелой цепи (VH) содержит:In yet another embodiment, a monoclonal antibody or antigen-binding fragment thereof that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that the heavy chain variable region (VH) contains:

(i) CDRH1 последовательности SEQ ID NO: 20;(i) CDRH1 sequences of SEQ ID NO: 20;

(ii) CDRH2 последовательности SEQ ID NO: 43;(ii) CDRH2 sequences of SEQ ID NO: 43;

(iii) CDRH3 последовательности SEQ ID NO: 66, и (iii) CDRH3 sequences of SEQ ID NO: 66, and

вариабельная область легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности SEQ ID NO: 89;(i) CDRL1 sequence of SEQ ID NO: 89;

(ii) CDRL2 последовательности WAS (SEQ ID NO:112);(ii) CDRL2 WAS sequence (SEQ ID NO:112);

(iii) CDRL3 последовательности SEQ ID NO: 135 [антитело iB21].(iii) CDRL3 sequence of SEQ ID NO: 135 [antibody iB21].

В альтернативном воплощении моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что вариабельная область тяжелой цепи (VH) содержит:In an alternative embodiment, a monoclonal antibody or antigen-binding fragment thereof that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that the heavy chain variable region (VH) contains:

(i) CDRH1 последовательности SEQ ID NO: 21;(i) CDRH1 sequences of SEQ ID NO: 21;

(ii) CDRH2 последовательности SEQ ID NO: 44;(ii) CDRH2 sequences of SEQ ID NO: 44;

(iii) CDRH3 последовательности SEQ ID NO: 67, и (iii) CDRH3 sequences of SEQ ID NO: 67, and

вариабельная область легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности SEQ ID NO: 90;(i) CDRL1 sequence of SEQ ID NO: 90;

(ii) CDRL2 последовательности DAS (SEQ ID NO:113);(ii) CDRL2 DAS sequences (SEQ ID NO:113);

(iii) CDRL3 последовательности SEQ ID NO: 136 [антитело iB24].(iii) CDRL3 sequence of SEQ ID NO: 136 [antibody iB24].

В следующем воплощений моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что содержит:In a further embodiment, a monoclonal antibody or antigen-binding fragment thereof that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that it contains:

(i) CDRH1 последовательности SEQ ID NO: 22;(i) CDRH1 sequences of SEQ ID NO: 22;

(ii) CDRH2 последовательности SEQ ID NO: 45;(ii) CDRH2 sequences of SEQ ID NO: 45;

(iii) CDRH3 последовательности SEQ ID NO: 68, и (iii) CDRH3 sequences of SEQ ID NO: 68, and

вариабельная область легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности SEQ ID NO: 91;(i) CDRL1 sequence of SEQ ID NO: 91;

(ii) CDRL2 последовательности AAS (SEQ ID NO:114);(ii) CDRL2 AAS sequences (SEQ ID NO:114);

(iii) CDRL3 последовательности SEQ ID NO: 137 [антитело iB25].(iii) CDRL3 sequence of SEQ ID NO: 137 [antibody iB25].

В ином воплощении моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающие RBD Spike-белка SARS-CoV-2, характеризуются тем, что вариабельная область тяжелой цепи (VH) содержит:In another embodiment, a monoclonal antibody or antigen-binding fragment thereof that selectively binds the RBD of the SARS-CoV-2 spike protein is characterized in that the heavy chain variable region (VH) contains:

(i) CDRH1 последовательности SEQ ID NO: 23;(i) CDRH1 sequences of SEQ ID NO: 23;

(ii) CDRH2 последовательности SEQ ID NO: 46;(ii) CDRH2 sequences of SEQ ID NO: 46;

(iii) CDRH3 последовательности SEQ ID NO: 69, и (iii) CDRH3 sequences of SEQ ID NO: 69, and

вариабельная область легкой цепи (VL) содержит:the light chain variable region (VL) contains:

(i) CDRL1 последовательности SEQ ID NO: 92;(i) CDRL1 sequence of SEQ ID NO: 92;

(ii) CDRL2 последовательности AAS (SEQ ID NO:115);(ii) CDRL2 AAS sequences (SEQ ID NO:115);

(iii) CDRL3 последовательности SEQ ID NO: 138 [антитело iB26](iii) CDRL3 sequence of SEQ ID NO: 138 [antibody iB26]

В следующем воплощении моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, выбранной из SEQ ID NO: 139-161; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, выбранной из SEQ ID NO: 162-184.In a further embodiment, a monoclonal antibody that selectively binds the SARS-CoV-2 Spike RBD protein comprises a heavy chain variable region (VH) containing an amino acid sequence of at least 90% homology to a sequence selected from SEQ ID NOs: 139-161; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homology to a sequence selected from SEQ ID NOs: 162-184.

В частности моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 139; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 162 [антитело iB0].In particular, a monoclonal antibody that selectively binds the SARS-CoV-2 spike protein RBD comprises a heavy chain variable region (VH) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 139; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 162 [antibody iB0].

В следующем воплощении моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 140; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 163 [антитело iB1].In a further embodiment, a monoclonal antibody that selectively binds the SARS-CoV-2 Spike RBD protein comprises a heavy chain variable region (VH) containing an amino acid sequence of at least 90% homology to SEQ ID NO: 140; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 163 [antibody iB1].

В ином воплощении моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 141; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 164 [антитело iB2].In another embodiment, a monoclonal antibody that selectively binds the SARS-CoV-2 Spike RBD protein comprises a heavy chain variable region (VH) containing an amino acid sequence that is at least 90% homologous to SEQ ID NO: 141; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 164 [antibody iB2].

В другом воплощении моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 142; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 165 [антитело iB3].In another embodiment, a monoclonal antibody that selectively binds the SARS-CoV-2 Spike RBD protein comprises a heavy chain variable region (VH) containing an amino acid sequence that is at least 90% homologous to SEQ ID NO: 142; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 165 [iB3 antibody].

В альтернативном воплощении моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 143; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 166 [антитело iB4].In an alternative embodiment, a monoclonal antibody that selectively binds the SARS-CoV-2 Spike RBD protein comprises a heavy chain variable region (VH) containing an amino acid sequence of at least 90% homology to SEQ ID NO: 143; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 166 [iB4 antibody].

В еще одном воплощении моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 144; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 167 [антитело iB5].In yet another embodiment, a monoclonal antibody that selectively binds the SARS-CoV-2 Spike RBD protein comprises a heavy chain variable region (VH) containing an amino acid sequence of at least 90% homologous to SEQ ID NO: 144; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 167 [iB5 antibody].

В дополнительном воплощении моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 145; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 168 [антитело iB6].In an additional embodiment, a monoclonal antibody that selectively binds the SARS-CoV-2 Spike RBD protein comprises a heavy chain variable region (VH) containing an amino acid sequence that is at least 90% homologous to SEQ ID NO: 145; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 168 [antibody iB6].

В альтернативном моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 146; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 169 [антитело iB9].In an alternative monoclonal antibody that selectively binds the SARS-CoV-2 Spike RBD protein, comprises a heavy chain variable region (VH) containing an amino acid sequence of at least 90% homologous to SEQ ID NO: 146; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 169 [iB9 antibody].

В еще одном моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 147; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 170 [антитело iB10].In yet another monoclonal antibody that selectively binds the SARS-CoV-2 Spike RBD protein, includes a heavy chain variable region (VH) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 147; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 170 [antibody iB10].

В следующем воплощении моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 148; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 171 [антитело iB11].In a further embodiment, a monoclonal antibody that selectively binds the SARS-CoV-2 Spike RBD protein comprises a heavy chain variable region (VH) containing an amino acid sequence that is at least 90% homologous to SEQ ID NO: 148; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 171 [antibody iB11].

В альтернативном моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 149; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 172 [антитело iB12].In an alternative monoclonal antibody that selectively binds the SARS-CoV-2 Spike RBD protein, comprises a heavy chain variable region (VH) containing an amino acid sequence of at least 90% homologous to SEQ ID NO: 149; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 172 [antibody iB12].

В ином воплощении моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую ий последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 150; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 173 [антитело iB13].In another embodiment, a monoclonal antibody that selectively binds the SARS-CoV-2 Spike RBD protein comprises a heavy chain variable region (VH) containing at least 90% amino acid sequence homology to SEQ ID NO: 150; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 173 [antibody iB13].

В дополнительном воплощении моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 151; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 174 [антитело iB14].In an additional embodiment, a monoclonal antibody that selectively binds the SARS-CoV-2 Spike RBD protein comprises a heavy chain variable region (VH) containing an amino acid sequence that is at least 90% homologous to SEQ ID NO: 151; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 174 [antibody iB14].

В другом воплощении моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 152; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 175 [антитело iB15].In another embodiment, a monoclonal antibody that selectively binds the SARS-CoV-2 Spike RBD protein comprises a heavy chain variable region (VH) containing an amino acid sequence that is at least 90% homologous to SEQ ID NO: 152; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 175 [antibody iB15].

В еще одном воплощении моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 153; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 176 [антитело iB16].In yet another embodiment, a monoclonal antibody that selectively binds the SARS-CoV-2 Spike RBD protein comprises a heavy chain variable region (VH) containing an amino acid sequence that is at least 90% homologous to SEQ ID NO: 153; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 176 [antibody iB16].

В следующем воплощении моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 154; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 177 [антитело iB17].In a further embodiment, a monoclonal antibody that selectively binds the SARS-CoV-2 Spike RBD protein comprises a heavy chain variable region (VH) containing an amino acid sequence that is at least 90% homologous to SEQ ID NO: 154; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 177 [antibody iB17].

В дополнительном моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 155; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 178 [антитело iB18].In an additional monoclonal antibody that selectively binds the SARS-CoV-2 Spike RBD protein, includes a heavy chain variable region (VH) containing an amino acid sequence of at least 90% homologous to the sequence, SEQ ID NO: 155; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 178 [antibody iB18].

В еще одном моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 156; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 179 [антитело iB19].In another monoclonal antibody that selectively binds the RBD of the SARS-CoV-2 Spike protein, includes a heavy chain variable region (VH) containing an amino acid sequence of at least 90% homologous to the sequence, SEQ ID NO: 156; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 179 [antibody iB19].

В альтернативном воплощении моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 157; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 180 [антитело iB20].In an alternative embodiment, a monoclonal antibody that selectively binds the SARS-CoV-2 Spike RBD protein comprises a heavy chain variable region (VH) containing an amino acid sequence that is at least 90% homologous to SEQ ID NO: 157; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence, SEQ ID NO: 180 [antibody iB20].

В дополнительном воплощении моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 158; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 181 [антитело iB21].In an additional embodiment, a monoclonal antibody that selectively binds the SARS-CoV-2 Spike RBD protein comprises a heavy chain variable region (VH) containing an amino acid sequence that is at least 90% homologous to SEQ ID NO: 158; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 181 [antibody iB21].

В другом воплощении моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 159; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 182 [антитело iB24].In another embodiment, a monoclonal antibody that selectively binds the SARS-CoV-2 Spike RBD protein comprises a heavy chain variable region (VH) containing an amino acid sequence that is at least 90% homologous to SEQ ID NO: 159; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 182 [antibody iB24].

В следующем воплощении моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 160; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 183 [антитело iB25].In a further embodiment, a monoclonal antibody that selectively binds the SARS-CoV-2 Spike RBD protein comprises a heavy chain variable region (VH) containing an amino acid sequence that is at least 90% homologous to SEQ ID NO: 160; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 183 [antibody iB25].

В дополнительном воплощении моноклональное антитело, селективно связывающее RBD Spike-белка SARS-CoV-2, включает вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 161; и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот не менее чем на 90% гомологичную последовательности, SEQ ID NO: 184 [антитело iB26].In an additional embodiment, a monoclonal antibody that selectively binds the SARS-CoV-2 Spike RBD protein comprises a heavy chain variable region (VH) containing an amino acid sequence of at least 90% homology to SEQ ID NO: 161; and a light chain variable region (VL) containing an amino acid sequence of at least 90% homologous to the sequence of SEQ ID NO: 184 [antibody iB26].

В частности, антитела согласно настоящему изобретению обладают способностью к нейтрализации вируса SARS-CoV-2.In particular, the antibodies of the present invention have the ability to neutralize the SARS-CoV-2 virus.

Новые антитела человека, селективно связываются с RBD Spike-белка SARS-CoV-2, содержат приведенные выше последовательности вариабельных областей и могут содержать консервативные участки обеих цепей, необходимые для функционирования указанных антител. Консервативные участки тяжелых цепей иммуноглобулинов классов IgG, IgM, IgA, IgD или IgE человека и других млекопитающих могут быть использованы в качестве консервативных участков для тяжелых цепей согласно настоящему изобретению. Например, антитело или его антигенсвязывающий фрагмент, согласно изобретению, могут содержать консервативные участки тяжелых цепей, принадлежащие к изотипу IgG1, IgG2, IgG3 или IgG4. Консервативные участки легкой цепи иммуноглобулинов изотипов каппа или лямбда человека и других млекопитающих могут быть использованы в качестве консервативных участков для легких цепей антител согласно настоящему изобретению.New human antibodies selectively bind to the SARS-CoV-2 Spike protein RBD, contain the sequences of the variable regions listed above, and may contain conserved regions of both chains necessary for the functioning of these antibodies. Conserved regions of heavy chains of human and other mammalian IgG, IgM, IgA, IgD or IgE immunoglobulins can be used as conserved regions for heavy chains according to the present invention. For example, an antibody or antigen-binding fragment thereof according to the invention may contain conserved heavy chain regions belonging to the IgG1, IgG2, IgG3, or IgG4 isotype. Conserved light chain regions of human and other mammalian kappa or lambda immunoglobulin isotypes can be used as conserved regions for antibody light chains of the present invention.

В настоящем изобретении фраза «нейтрализующее моноклональное антитело» означает молекулу, которая связывается с SARS-CoV-2, образует стабильный комплекс и препятствует прикреплению и/или проникновению вируса SARS-CoV-2 в клетку. Способность антитела к связыванию с антигеном может быть определена специалистом в данной области с использованием методов, включающих, но не ограничивающихся методом иммуноферментного анализа (ИФА), равновесным диализом, с использованием плазмон-поверхностного резонанса и биослойной интерферометрии (BLI). Методы определения аффинности хорошо известны специалисту в данной области техники, подробно описаны Janeway и соавт. (Immunobiology: The Immune System in Health and Disease (Garland Publishing Company, 1996)).In the present invention, the phrase "neutralizing monoclonal antibody" means a molecule that binds to SARS-CoV-2, forms a stable complex and prevents the SARS-CoV-2 virus from attaching and/or entering a cell. The ability of an antibody to bind to an antigen can be determined by one of skill in the art using methods including but not limited to enzyme immunoassay (ELISA), equilibrium dialysis, surface plasmon resonance, and biolayer interferometry (BLI). Methods for determining affinity are well known to those skilled in the art and are detailed by Janeway et al. (Immunobiology: The Immune System in Health and Disease (Garland Publishing Company, 1996)).

Существующий уровень техники является таким, что позволяет специалисту в данной области синтезировать молекулы ДНК, предлагаемые в изобретении на основе представленной в настоящем описании информации, т.е. аминокислотных последовательностей гипервариабельных участков.The current state of the art is such that it allows a person skilled in the art to synthesize the DNA molecules of the invention based on the information presented in the present description, i.e. amino acid sequences of hypervariable regions.

Нуклеиновые кислотыNucleic acids

Для решения поставленной задачи также были получены нуклеиновые кислоты, кодирующие VH указанных антител, в частности имеющие нуклеотидные последовательности SEQ ID NO: 185-207, и VL указанных антител, в частности имеющие нуклеотидные последовательности SEQ ID NO: 208-230.To solve this problem, nucleic acids encoding the VH of these antibodies, in particular those having the nucleotide sequences of SEQ ID NO: 185-207, and the VL of these antibodies, in particular having the nucleotide sequences of SEQ ID NO: 208-230, were also obtained.

Используемый в настоящем описании термин нуклеиновая кислота относится к фрагменту ДНК или РНК. Предпочтительно нуклеиновой кислотой, кодирующей антитело согласно настоящему изобретению, является фрагмент ДНК, кодирующий вариабельные тяжелую или легкую цепи моноклонального антитела, селективно связывающего RBD Spike-белка SARS-CoV-2, где данное антитело содержит последовательность аминокислот не менее чем на 90% гомологичную SEQ ID NO: 139-161, и последовательность аминокислот не менее чем на 90% гомологичную SEQ ID NO: 162-184.As used herein, the term nucleic acid refers to a piece of DNA or RNA. Preferably, the nucleic acid encoding an antibody of the present invention is a DNA fragment encoding the variable heavy or light chains of a monoclonal antibody that selectively binds the SARS-CoV-2 RBD Spike protein, wherein the antibody contains an amino acid sequence that is at least 90% homologous to SEQ ID NO: 139-161, and an amino acid sequence of at least 90% homology to SEQ ID NO: 162-184.

Специалистам в данной области техники известно, что ввиду вырожденности генетического кода могут быть различия в последовательности ДНК кодирующей одну и ту же аминокислотную последовательность [Льюин Б. Гены. Москва.: Мир, 1987.]. Поэтому последовательности нуклеиновых кислот согласно настоящему изобретению могут отличаться, при условии, что они кодируют участки цепей антитела, содержащего последовательность аминокислот не менее чем на 90% гомологичную SEQ ID NO: 139-161, и последовательность аминокислот не менее чем на 90% гомологичную SEQ ID NO: 162-184.Specialists in the art know that due to the degeneracy of the genetic code, there may be differences in the DNA sequence encoding the same amino acid sequence [Lewin B. Genes. Moscow.: Mir, 1987.]. Therefore, the nucleic acid sequences according to the present invention may differ, provided that they encode portions of the chains of an antibody containing an amino acid sequence of at least 90% homologous to SEQ ID NO: 139-161, and an amino acid sequence of at least 90% homologous to SEQ ID NO: 162-184.

Нуклеиновые кислоты изобретения также включают нуклеиновые кислоты, кодирующие тяжелую и легкую цепи моноклональных антител, селективно связывающих RBD Spike-белка SARS-CoV-2, содержащих последовательности аминокислот SEQ ID NO: 231-253 и последовательности аминокислот SEQ ID NO: 254-276. В частности, этими нуклеиновыми кислотами могут быть ДНК последовательности, которые приведены в перечне последовательностей под номерами SEQ ID NO: 277-299 и SEQ ID NO: 300-322.The nucleic acids of the invention also include nucleic acids encoding the heavy and light chains of monoclonal antibodies selectively binding the SARS-CoV-2 Spike protein RBD, comprising the amino acid sequences of SEQ ID NO: 231-253 and the amino acid sequences of SEQ ID NO: 254-276. In particular, these nucleic acids may be DNA sequences that are listed in the sequences under the numbers SEQ ID NO: 277-299 and SEQ ID NO: 300-322.

Экспрессионный векторExpression vector

В одном воплощении изобретения предусмотрены рекомбинантные экспрессионные векторы, содержащие молекулу нуклеиновой кислоты по изобретению, причем вектор содержит контролирующую экспрессию последовательность, которая способствует экспрессии кодируемого полипептида в прокариотических или эукариотических клетках-хозяевах и функционально связана с данной молекулой нуклеиновой кислоты.In one embodiment of the invention, recombinant expression vectors are provided comprising a nucleic acid molecule of the invention, wherein the vector contains an expression control sequence that promotes expression of the encoded polypeptide in prokaryotic or eukaryotic host cells and is operably linked to the nucleic acid molecule.

Рекомбинантный вектор также может включать последовательности нуклеотидов, которые способствуют, контролируют или регулируют экспрессию и транскрипцию полинуклеотида по изобретению, а также трансляцию полипептида по изобретению, причем эти последовательности выбирают в соответствии с используемыми клетками-хозяевами.The recombinant vector may also include nucleotide sequences that facilitate, control or regulate the expression and transcription of a polynucleotide of the invention, as well as translation of a polypeptide of the invention, these sequences being selected according to the host cells used.

Клетки-хозяева, производящие антителаHost cells that produce antibodies

При использовании в данном документе термин «клетка-хозяин» относится к клетке, в которую была введена экзогенная нуклеиновая кислота, такая как ДНК, например, в составе экспрессионного вектора, и которая способна экспрессировать антитело или антигенсвязывающий фрагмент изобретения. Специалистам в данной области понятно, что такой термин относятся не только к конкретной клетке, в которую была введена экзогенная нуклеиновая кислота, но также к потомству такой клетки. Поскольку определенные изменения могут произойти в последующих поколениях из-за мутаций или воздействий окружающей среды, такое потомство может быть не идентично исходной клетке, но все еще включено в объем термина «клетка-хозяин», используемого в данном документе. В некоторых воплощениях клетки-хозяева включают прокариотические и эукариотические клетки, которые пригодны для экспрессии экзогенной ДНК (например, рекомбинантной последовательности нуклеиновой кислоты). Типичные клетки включают клетки прокариот и эукариот (одноклеточных или многоклеточных), такие как бактериальные клетки, клетки грибов, дрожжевые клетки, клетки растений, клетки насекомых, клетки животных, отличных от человека, и клетки человека. В некоторых воплощениях клетка-хозяин представляет собой клетку HEK293T.As used herein, the term "host cell" refers to a cell into which an exogenous nucleic acid, such as DNA, has been introduced, for example, as part of an expression vector, and which is capable of expressing an antibody or antigen-binding fragment of the invention. Those skilled in the art will appreciate that such a term refers not only to the particular cell into which the exogenous nucleic acid has been introduced, but also to the progeny of such a cell. Because certain changes may occur in subsequent generations due to mutations or environmental influences, such progeny may not be identical to the original cell, but are still included within the scope of the term "host cell" as used herein. In some embodiments, host cells include prokaryotic and eukaryotic cells that are suitable for the expression of exogenous DNA (eg, a recombinant nucleic acid sequence). Representative cells include prokaryotic and eukaryotic (unicellular or multicellular) cells such as bacterial cells, fungal cells, yeast cells, plant cells, insect cells, non-human animal cells, and human cells. In some embodiments, the host cell is a HEK293T cell.

Способы получения антителаMethods for obtaining antibodies

Антитела изобретения могут быть получены рекомбинантным путем, при помощи временной доставки или постоянной интеграции кодирующих их нуклеиновых кислот, например в составе экспрессионного вектора, в клетки-хозяева, такие как клетки млекопитающих, насекомых, дрожжей или растений. После наработки в рекомбинантной системе антитела должны быть очищены до гомогенного состояния при помощи традиционных способов очистки антител, например одной или нескольких стадий хроматографического процесса. Например, антитело или его антигенсвязывающий фрагмент по изобретению может быть получен способом, включающим культивирование или поддержание клетки-хозяина в таких условиях, чтобы указанная клетка-хозяин продуцировала или экспрессировала антитело или его антигенсвязывающий фрагмент по любому изобретению, посредством экспрессии нуклеиновой кислоты, кодирующей тяжелую цепь антитела, и нуклеиновой кислоты, кодирующей легкую цепь антитела, например, в составе вектора, содержащего нуклеиновую кислоту, кодирующую тяжелую цепь антитела, и нуклеиновую кислоту, кодирующую легкую цепь антитела, или векторов, один из которых содержит нуклеиновую кислоту, кодирующую тяжелую цепь антитела, а второй, нуклеиновую кислоту, кодирующую легкую цепь антитела, и, при необходимости, дополнительно включающий выделение антитела или его антигенсвязывающего фрагмента, полученного таким способом.The antibodies of the invention can be produced recombinantly by transient delivery or permanent integration of the nucleic acids encoding them, for example as part of an expression vector, into host cells such as mammalian, insect, yeast or plant cells. Once produced in a recombinant system, the antibodies must be purified to a homogeneous state using conventional antibody purification methods, such as one or more chromatographic process steps. For example, an antibody or antigen-binding fragment of the invention may be produced by a method comprising culturing or maintaining a host cell under conditions such that said host cell produces or expresses an antibody or antigen-binding fragment of any invention by expressing a nucleic acid encoding a heavy chain. an antibody and a nucleic acid encoding an antibody light chain, for example, as part of a vector containing a nucleic acid encoding an antibody heavy chain and a nucleic acid encoding an antibody light chain, or vectors, one of which contains a nucleic acid encoding an antibody heavy chain, and the second, a nucleic acid encoding the light chain of the antibody, and, if necessary, further comprising the isolation of the antibody or its antigen-binding fragment obtained in this way.

Кроме того, известны способы получения антител посредством генетического переноса кодирующих их нуклеиновых кислот in situ или in vivo с использованием, например, внутримышечной инъекции, электропорации, вирусных векторов, наночастиц и липосом, позволяющие обеспечить синтез и продукцию антител и их комбинаций прямо в организме, в результате чего достигается искомый профилактический и/или терапевтический эффект.In addition, methods are known for producing antibodies by genetic transfer of nucleic acids encoding them in situ or in vivo using, for example, intramuscular injection, electroporation, viral vectors, nanoparticles and liposomes, which allow the synthesis and production of antibodies and their combinations directly in the body, in resulting in the desired prophylactic and/or therapeutic effect.

Коктейли и комбинации антителCocktails and combinations of antibodies

Для SARS-CoV-2 описано несколько основных механизмов прямой вируснейтрализующей активности антител. Первый основан на экранировании сайтов связывания S-белка с рецептором Ace2 за счет конкурентного узнавания антителом так называемого рецептор-связывающего мотива (RBM) в пределах RBD. Второй механизм также предотвращает связывание S-белка с Ace2, но за счет узнавания антителом эпитопов, отличных от RBM, при котором молекула антитела стерически мешает взаимодействию Ace2 с RBM. Третьим является дестабилизация антителом пред-фьюжн структуры Spike-белка и индукция его необратимого перехода в пост-фьюжн конформацию. Четвертый, наоборот, основан на стабилизации пред-фьюжн конформации Spike-белка.For SARS-CoV-2, several main mechanisms of direct virus-neutralizing activity of antibodies have been described. The first is based on screening of the S-protein binding sites with the Ace2 receptor due to the competitive recognition of the so-called receptor-binding motif (RBM) within the RBD by the antibody. The second mechanism also prevents the binding of the S protein to Ace2, but at the expense of recognition by the antibody of epitopes other than RBM, in which the antibody molecule sterically interferes with the interaction of Ace2 with RBM. The third is the destabilization of the pre-fusion structure of the Spike protein by the antibody and the induction of its irreversible transition to the post-fusion conformation. The fourth, on the contrary, is based on the stabilization of the pre-fusion conformation of the Spike protein.

Очевидно, что площадь контакта антитела с интерфейсом RBD-Ace2 прямо коррелирует с потенциальной устойчивостью антитела к аминокислотным заменам в Spike-белке. Так как максимальная площадь контакта антитела и антигена ограничена базовыми особенностями структуры вариабельных доменов тяжелой и легкой цепи, она не может быть существенно увеличена для каждого конкретного антитела. Однако, тот же эффект может достигаться за счет одновременного применения различных антител, связывающихся с независимыми или частично перекрывающимися эпитопами на поверхности Spike-белка, поскольку возникновение двух и более мутаций, инактивирующих сразу несколько вируснейтрализующих антител, без негативных последствий для приспособленности вируса крайне маловероятно. Таким образом, оправдано применение коктейлей антител, сформулированных на основе информации об эпитопах связывания со Spike-белком. При этом существует два формальных сценария использования антител в коктейле.Obviously, the contact area of the antibody with the RBD-Ace2 interface directly correlates with the potential resistance of the antibody to amino acid substitutions in the Spike protein. Since the maximum contact area of an antibody and antigen is limited by the basic structural features of the heavy and light chain variable domains, it cannot be significantly increased for each specific antibody. However, the same effect can be achieved through the simultaneous use of various antibodies that bind to independent or partially overlapping epitopes on the surface of the Spike protein, since the occurrence of two or more mutations that inactivate several virus-neutralizing antibodies at once is extremely unlikely without negative consequences for the fitness of the virus. Thus, the use of antibody cocktails formulated on the basis of information about the epitopes of binding to the Spike protein is justified. There are two formal scenarios for using antibodies in a cocktail.

Первый из них рассчитан на одновременное связывание двух или более антител с вирусом (т.е. со Spike-белком) без взаимной конкуренции. Это значительно повышает эффективность вируснейтрализации, однако не является обязательным при использовании высокопотентных антител, каждое из которых по отдельности обладает высоким нейтрализационным потенциалом. Для такого варианта использования антитела не должны конкурировать, что можно установить при помощи специальных способов постановки иммуноферментного анализа, биослойной интерферометрии или структурного анализа комплексов антитело-антиген (криоЭМ, рентгеноструктурный анализ и т.д.).The first of them is designed for the simultaneous binding of two or more antibodies to the virus (i.e., to the Spike protein) without mutual competition. This significantly increases the efficiency of virus neutralization, but is not necessary when using highly potent antibodies, each of which individually has a high neutralization potential. For this use case, antibodies should not compete, which can be established using special methods of enzyme immunoassay, biolayer interferometry or structural analysis of antibody-antigen complexes (cryoEM, X-ray diffraction analysis, etc.).

Второй сценарий использования коктейлей предусматривает комбинирование антител вне зависимости от их сайтов связывания со Spike-белком, но с учетом их чувствительности к мутациям в геноме вируса, приводящим к заменам аминокислотных остатков в Spike-белке. При таком комбинировании антитела подбираются таким образом, чтобы возникающие мутации не инактивировали все антитела в коктейле. Для такого дизайна коктейлей не требуются данные о конкуренции антител, но нужна детальная картина мутационной чувствительности антител, что может быть определено в нейтрализационных тестах с панелью мутантных вариантов Spike-псевдотипированных вирусов или в условиях in vitro/in vivo эволюции системы вирус/антитело. При этом сценарии использования коктейлей разные антитела не взаимодействуют со Spike-белком одновременно, но гарантируют повышенную устойчивость препарата к вновь появляющимся мутациям.The second scenario for the use of cocktails involves the combination of antibodies, regardless of their binding sites with the Spike protein, but taking into account their sensitivity to mutations in the virus genome, leading to amino acid substitutions in the Spike protein. With this combination, the antibodies are selected so that the resulting mutations do not inactivate all the antibodies in the cocktail. This cocktail design does not require data on antibody competition, but requires a detailed picture of the mutational sensitivity of antibodies, which can be determined in neutralization tests with a panel of mutant variants of Spike-pseudotyped viruses or in vitro/in vivo conditions for the evolution of the virus/antibody system. In this scenario of using cocktails, different antibodies do not interact with the Spike protein at the same time, but guarantee an increased resistance of the drug to newly emerging mutations.

Помимо информации о наличии или отсутствии взаимной конкуренции антител за связывание с целевым белком (например, c S-белком SARS-CoV-2), крайне важны данные о механизмах активности, аффинности и фармакодинамики. Например, формирование коктейля из двух антител, связывание одного из которых приводит к стерической реорганизации мишени и исчезновению эпитопа для другого антитела, является заведомо непродуктивным. Кроме того, известны примеры синергичной активности не только вируснейтрализующих антител, но и ненейтрализующих (слабонейтрализующих) антител друг с другом. Наконец, соотношение компонент антительного коктейля не обязательно должно быть эквимолярным, и тем самым оно может в значительной мере определять диапазон терапевтической и/ или профилактической активности.In addition to information about the presence or absence of mutual competition of antibodies for binding to a target protein (for example, with the S protein of SARS-CoV-2), data on the mechanisms of activity, affinity, and pharmacodynamics are extremely important. For example, the formation of a cocktail of two antibodies, the binding of one of which leads to steric reorganization of the target and the disappearance of the epitope for the other antibody, is obviously unproductive. In addition, examples of synergistic activity of not only virus-neutralizing antibodies, but also non-neutralizing (weakly neutralizing) antibodies with each other are known. Finally, the ratio of the components of the antibody cocktail does not have to be equimolar, and thus it can largely determine the range of therapeutic and/or prophylactic activity.

Таким образом, полученная в данной работе информация о взаимной конкуренции антител друг с другом за связывание с RBD, а также данные о чувствительности антител к аминокислотным заменам в RBD, позволяют осуществлять рациональный дизайн коктейлей антител друг с другом и известными коммерческими нейтрализующими антителами. Например, антитела iB6 можно комбинировать не только друг с другом iB20 (как показано в соответствующих примерах), но и с REGN10987 и формулировать тем самым трехкомпонентный коктейль, целиком состоящий из неконкурирующих нейтрализующих антител против района взаимодействия ACE2 и RBD. Также возможны другие подобные комбинации, обеспечивающие большую устойчивость к возникающим заменам в структуре Spike-белка SARS-CoV-2, такие как iB14 + COVA2-15 или iB14 + COV2-2504 и т.д.Thus, the information obtained in this work on the mutual competition of antibodies with each other for binding to RBD, as well as data on the sensitivity of antibodies to amino acid substitutions in RBD, allow for the rational design of antibody cocktails with each other and known commercial neutralizing antibodies. For example, iB6 antibodies can be combined not only with each other iB20 (as shown in the respective examples), but also with REGN10987 and thereby formulate a three-component cocktail consisting entirely of non-competing neutralizing antibodies against the ACE2 interaction region and RBD. Other similar combinations are also possible, providing greater resistance to emerging substitutions in the structure of the SARS-CoV-2 Spike protein, such as iB14 + COVA2-15 or iB14 + COV2-2504, etc.

Применение антител в лечении и диагностикеThe use of antibodies in the treatment and diagnosis

Возможность использования моноклональных антител для целей диагностики является их ценным свойством. В частности распространены тест-системы, основанные на принципах иммуноферментного и иммунохроматографического (lateral flow) анализа, позволяющие специфично и селективно детектировать и измерять уровень интересующего аналита в сложных смесях и биологических жидкостях организма. Важными областями применения RBD-специфических моноклональных антител являются диагностика наличия коронавирусной инфекции у человека и других млекопитающих, оценка ее динамики, выяснение принадлежности обнаруженного изолята SARS-CoV-2 к той или иной кладе и, следовательно, прогноз его устойчивости к препаратам моноклональных антител, а также оценка уровня нейтрализующих антител в сыворотке крови и других биологических жидкостях млекопитающих.The possibility of using monoclonal antibodies for diagnostic purposes is their valuable property. In particular, there are widespread test systems based on the principles of enzyme immunoassay and immunochromatographic (lateral flow) analysis, which make it possible to specifically and selectively detect and measure the level of an analyte of interest in complex mixtures and body fluids. Important areas of application of RBD-specific monoclonal antibodies are diagnosing the presence of coronavirus infection in humans and other mammals, assessing its dynamics, determining whether a detected SARS-CoV-2 isolate belongs to a particular clade and, therefore, predicting its resistance to monoclonal antibody preparations, and also assessment of the level of neutralizing antibodies in the blood serum and other biological fluids of mammals.

Для целей терапии RBD-специфические моноклональные антитела и их комбинации могут быть использованы при введении человеку или другому млекопитающему в короткий срок после появления первых симптомов заболевания, вызванного SARS-CoV-2. Пути введения антител могут включать внутривенную и внутримышечную инъекцию, доставку аэрозолем в дыхательные пути или подкожное введение. Антитело или его антигенсвязывающий фрагмент изобретения могут быть введены системно, назально или путем прямой доставки кодирующих его нуклеиновых кислот в организм млекопитающих. Помимо терапевтического применения антитела могут быть введены заранее в качестве меры профилактики. В таком случае целесообразно использование антител для лиц, имеющих высокий риск заражения вирусом SARS-CoV-2, тяжелого течения заболевания и не подлежащих вакцинации по медицинским или иным причинам. При профилактическом использовании необходимо учитывать период полужизни антител в кровотоке, который в среднем для антител изотипа IgG1 составляет 21 день, но может быть значительно увеличен за счет модификации последовательности аминокислотных остатков в Fc-части.For therapeutic purposes, RBD-specific monoclonal antibodies and combinations thereof can be used when administered to a human or other mammal shortly after the onset of the first symptoms of disease caused by SARS-CoV-2. Routes of administration of antibodies may include intravenous and intramuscular injection, aerosol delivery to the respiratory tract, or subcutaneous administration. An antibody or antigen-binding fragment thereof of the invention may be administered systemically, nasally, or by direct delivery of nucleic acids encoding it into a mammalian body. In addition to therapeutic use, antibodies can be administered in advance as a prophylactic measure. In this case, it is advisable to use antibodies for people who are at high risk of infection with the SARS-CoV-2 virus, have a severe course of the disease and are not subject to vaccination for medical or other reasons. In prophylactic use, it is necessary to take into account the half-life of antibodies in the bloodstream, which on average for antibodies of the IgG1 isotype is 21 days, but can be significantly increased by modifying the sequence of amino acid residues in the Fc-part.

Кроме того, необходимо учитывать то, что человек – не единственный вид млекопитающих, для которого показана возможность инфицирования SARS-CoV-2 и близкими ему вирусами. В частности, случаи заражения SARS-CoV-2 были показаны для многих представителей семейства кошачьих (кошка, лев, тигр, снежный барс, пума), куньих (норка, хорек), приматов (горилла, макаки), псовых (собака, енотовидная собака) рукокрылых, грызунов (хомячки), оленевых (белохвостый олень) и панголинов. Несмотря на то, что эффективный перенос вируса и его вариантов внутри этих видов животных и тем более обратного заражения от них человека происходит редко (например, известны случаи заражения людей от выращиваемых в зверохозяйствах норок), возможность формирования новых зоонозных очагов SARS-CoV-2 является эпидемиологической угрозой и требует развития надежного молекулярного инструментария, позволяющего детектировать, типировать, а при необходимости и нейтрализовать SARS-CoV-2, включая его варианты, также и в других видах млекопитающих.In addition, it must be taken into account that humans are not the only species of mammals for which the possibility of infection with SARS-CoV-2 and related viruses has been shown. In particular, cases of infection with SARS-CoV-2 have been shown for many members of the feline family (cat, lion, tiger, snow leopard, puma), mustelids (mink, ferret), primates (gorilla, macaque), canines (dog, raccoon dog ) bats, rodents (hamsters), deer (white-tailed deer) and pangolins. Despite the fact that the effective transmission of the virus and its variants within these animal species, and even more so the reverse infection of humans from them, is rare (for example, cases of human infection from minks grown in fur farms are known), the possibility of the formation of new zoonotic foci of SARS-CoV-2 is epidemiological threat and requires the development of reliable molecular tools to detect, type, and, if necessary, neutralize SARS-CoV-2, including its variants, also in other mammalian species.

Химерные антигенные рецепторыChimeric antigen receptors

В некоторых воплощениях настоящее изобретение относится к химерному антигенному рецептору, содержащему антигенсвязывающий сайт антитела настоящего изобретения. Используемый в данном документе термин «химерный антигенный рецептор» или «CAR» относится к рекомбинантному трансмембранному белку, экспрессируемому в клетке млекопитающего, который включает, по меньшей мере, внеклеточный домен, трансмембранный домен и внутриклеточный домен сигнализации. Необязательно, белок CAR включает «спейсер», который ковалентно связывает внеклеточный домен с трансмембранным доменом. Спейсер часто представляет собой полипептид. CAR обычно экспрессируется в лимфоцитах млекопитающих. В некоторых воплощениях CAR экспрессируется в клетке млекопитающих, такой как Т-клетка, NK-клетка, макрофаг или инфильтрирующий опухоль лимфоцит (TIL). CAR, экспрессируемый на Т-клетках, упоминается в данном документе как “CAR T-клетка” или “CAR-T.” В некоторых воплощениях CAR-T представляет собой хелперную Т-клетку, цитотоксическую Т-клетку, Т-клетку естественного киллера, Т-клетку памяти, регуляторную Т-клетку или гамма-дельта-Т-клетку. CAR-Т часто является аутологичной CAR-Т, хотя аллогенные CAR-Т включены в объем изобретения. Внеклеточный домен CAR включает антигенсвязывающую область, такую как антитело или его антигенсвязывающий фрагмент (например, scFv), который специфически связывается в физиологических условиях с антигеном, таким как S-белок вируса SARS-CoV-2. При специфическом связывании биохимическая цепь событий (т.е. сигнальная трансдукция) приводит к модуляции иммунологической активности CAR-T. Так, например, специфическое связывание антигенсвязывающей области CAR с его антигеном может приводить к изменениям иммунологической активности активности CAR Т-клеток, что отражается на изменениях цитотоксичности, пролиферации или продукции цитокинов. Передача сигнала при активации CAR достигается в некоторых воплощениях CD3-дзета цепью («CD3z»), которая участвует в трансдукции сигнала в нативных Т-клетках млекопитающего. CAR-T могут дополнительно содержать один или несколько костимулирующих доменов, заимствованных от таких белков как CD28, 41BB, OX40 или ICOS для дальнейшей модуляции иммуномодулирующего ответа Т-клетки. CD3z включает консервативный мотив, известный как мотив активации на основе тирозина на основе иммунорецептора (ITAM), который участвует в трансдукции сигнала Т-клеточного рецептора.In some embodiments, the present invention relates to a chimeric antigen receptor containing the antigen-binding site of an antibody of the present invention. As used herein, the term "chimeric antigen receptor" or "CAR" refers to a recombinant transmembrane protein expressed in a mammalian cell that includes at least an extracellular domain, a transmembrane domain, and an intracellular signaling domain. Optionally, the CAR protein includes a "spacer" that covalently links the extracellular domain to the transmembrane domain. The spacer is often a polypeptide. CAR is usually expressed in mammalian lymphocytes. In some embodiments, the CAR is expressed in a mammalian cell, such as a T cell, NK cell, macrophage, or tumor infiltrating lymphocyte (TIL). CAR expressed on T cells is referred to herein as “CAR T cell” or “CAR-T.” In some embodiments, a CAR-T is a helper T cell, a cytotoxic T cell, a natural killer T cell, a memory T cell, a regulatory T cell, or a gamma delta T cell. CAR-T is often autologous CAR-T, although allogeneic CAR-Ts are included within the scope of the invention. The extracellular domain of a CAR includes an antigen-binding region, such as an antibody or an antigen-binding fragment thereof (eg, scFv), that specifically binds under physiological conditions to an antigen, such as the S protein of the SARS-CoV-2 virus. Upon specific binding, a biochemical chain of events (ie, signal transduction) results in modulation of the immunological activity of CAR-T. For example, specific binding of the antigen-binding region of a CAR to its antigen can lead to changes in the immunological activity of the activity of CAR T cells, which is reflected in changes in cytotoxicity, proliferation, or cytokine production. CAR activation signaling is achieved in some embodiments by a CD3 zeta chain ("CD3z") that is involved in signal transduction in native mammalian T cells. CAR-Ts may additionally contain one or more co-stimulatory domains derived from proteins such as CD28, 41BB, OX40, or ICOS to further modulate the immunomodulatory response of the T cell. CD3z includes a conserved motif known as the immunoreceptor-based tyrosine activation motif (ITAM), which is involved in T-cell receptor signal transduction.

Краткое описание чертежей и таблиц, иллюстрирующих изобретениеBrief description of the drawings and tables illustrating the invention

На Фиг. 1 показаны результаты иммуноферментного анализа сывороток четырех доноров-реконвалесцентов (С33, С34, С35, С36) и контрольной сыворотки здорового донора (К-) против RBD SARS-CoV-2 (изолят Wuhan-Hu-1), иммобилизованного в лунках планшета.On FIG. 1 shows the results of ELISA analysis of sera of four convalescent donors (C33, C34, C35, C36) and control serum of a healthy donor (K-) against SARS-CoV-2 RBD (Wuhan-Hu-1 isolate) immobilized in the wells of the plate.

На Фиг. 2 показана стратегия гейтирования и репрезентативные результаты FACS-окрашивания В-лимфоцитов донора-реконвалесцента С34.On FIG. 2 shows the gating strategy and representative FACS staining of B lymphocytes from a C34 convalescent donor.

На Фиг. 3 показаны результаты разделения очищенных рекомбинантных RBD-специфических антител в SDS-полиакриламидном геле. М – маркер молекулярного веса, LC – легкая цепь антитела, HC – тяжелая цепь антитела.On FIG. 3 shows the results of the separation of purified recombinant RBD-specific antibodies in SDS-polyacrylamide gel. M, molecular weight marker; LC, antibody light chain; HC, antibody heavy chain.

На Фиг. 4 показаны результаты BLI-анализа аффинности моноклональных антител к RBD SARS-CoV-2 (26,7 нМ). Представлены только данные для антител, обнаруживших заметное связывание с RBD. Данные для остальных антител аналогичны glVRC01 (негативный контроль, отсутствие связывания).On FIG. 4 shows the results of a BLI affinity assay for SARS-CoV-2 RBD monoclonal antibodies (26.7 nM). Only data are shown for antibodies that showed appreciable binding to RBD. Data for other antibodies are similar to glVRC01 (negative control, no binding).

На Фиг. 5 показаны результаты BLI-анализа аффинности наиболее потентных моноклональных антител к RBD SARS-CoV-2.On FIG. 5 shows the results of a BLI affinity analysis of the most potent monoclonal antibodies to SARS-CoV-2 RBD.

На Фиг. 6 показаны результаты цитометрического анализа окрашивания клеток линии HEK293T с поверхностной экспрессией Spike-белка коронавирусов HCoV-229E, HCoV-NL63 и SARS-CoV-2 моноклональными антителами против RBD SARS-CoV-2.On FIG. 6 shows the results of cytometric analysis of staining of HEK293T cells with surface expression of the Spike protein of coronaviruses HCoV-229E, HCoV-NL63 and SARS-CoV-2 with monoclonal antibodies against SARS-CoV-2 RBD.

На Фиг. 7 показаны результаты нейтрализационных тестов моноклональных антител iB-серии, а также известных референсных SARS-CoV-2-нейтрализующих антител (REGN10933, REGN10987, COVA2-15, COV2-2504) в псевдовирусной (А) и аутентичной (Б) вирусной системе.On FIG. 7 shows the results of neutralization tests of iB-series monoclonal antibodies, as well as known reference SARS-CoV-2 neutralizing antibodies (REGN10933, REGN10987, COVA2-15, COV2-2504) in pseudoviral (A) and authentic (B) virus systems.

На Фиг. 8 показаны данные анализа попарной конкуренции моноклональных антител за связывание с RBD SARS-CoV-2, полученные при помощи биослойной интерферометрии.On FIG. 8 shows data from the analysis of pairwise competition of monoclonal antibodies for binding to SARS-CoV-2 RBD obtained using biolayer interferometry.

На Фиг. 9 представлены результаты BLI-анализа конкуренции вируснейтрализующих RBD-спрецифических моноклональных антител COVA2-15, iB12, iB15, REGN10933, iB4, iB6 с REGN10987, COVA2-15, iB12 и iB20 за связывание с RBD SARS-CoV-2.On FIG. 9 shows the results of a BLI analysis of the competition of virus-neutralizing RBD-specific monoclonal antibodies COVA2-15, iB12, iB15, REGN10933, iB4, iB6 with REGN10987, COVA2-15, iB12 and iB20 for binding to SARS-CoV-2 RBD.

На Фиг. 10 показаны данные BLI-анализа, свидетельствующие об отсутствии взаимной конкуренции вируснейтрализующих моноклональных антител iB20, REGN10987 и iB6 за связывание с RBD SARS-CoV-2 (A), и Венн-диаграмма перекрывания эпитопов представленных моноклональных антител.On FIG. 10 shows BLI analysis data showing no mutual competition between virus-neutralizing monoclonal antibodies iB20, REGN10987, and iB6 for binding to the SARS-CoV-2 RBD (A), and a Venn diagram of epitope overlap of the presented monoclonal antibodies.

На Фиг. 11 приведены данные анализа активности моноклональных антител iB12, iB14 и смеси iB6+iB20 терапевтическом и профилактическом введении на модели заражения SARS-CoV-2 сирийских хомячков. А – динамика изменения веса подопытных животных, Б - вирусная нагрузка (количество копий вирусной РНК на 1 мг ткани, данные для гена RdRp SARS-CoV-2) в легких хомяков на 5 день после заражения, В – степень легочной патологии.On FIG. 11 shows the analysis of the activity of monoclonal antibodies iB12, iB14 and a mixture of iB6 + iB20 therapeutic and prophylactic administration in the SARS-CoV-2 infection model of Syrian hamsters. A - the dynamics of changes in the weight of experimental animals, B - viral load (the number of copies of viral RNA per 1 mg of tissue, data for the SARS-CoV-2 RdRp gene) in the lungs of hamsters on the 5th day after infection, C - the degree of pulmonary pathology.

На Фиг. 12 приведены данные гистопатологического анализа срезов легких хомяков на 5 день после инфицирования SARS-CoV-2 (окрашивание гематоксилин-эозином, представлены репрезентативные изображения для каждой группы).On FIG. 12 shows histopathological analysis of hamster lung sections 5 days after infection with SARS-CoV-2 (hematoxylin-eosin staining, representative images for each group are shown).

На Фиг. 13 представлена диаграмма изменения нейтрализующих свойств моноклональных RBD-специфических антител против вариантов Spike-белка (одноаминокислотные замены (А) и комбинации замен (Б)) на системе нейтрализации Spike-псевдотипированных лентивирусных частиц. * - замены, отсутствующие среди циркулирующих изолятов SARS-CoV-2.On FIG. 13 shows a diagram of the change in the neutralizing properties of monoclonal RBD-specific antibodies against Spike protein variants (single amino acid substitutions (A) and combinations of substitutions (B)) on the system for neutralizing Spike pseudotyped lentiviral particles. * - substitutions absent among circulating SARS-CoV-2 isolates.

На Фиг. 14 показано сохранение (зеленый круг) или потеря (красный квадрат) нейтрализующей активности в отношении SKEN-псевдотипированных лентивирусных частиц различными моноклональными антителами и их комбинациями. Представлено изменение значений IC50 относительно предкового варианта Spike (изолят Wuhan-Hu-1), серым выделен диапазон 5-кратного изменения IC50, не являющийся существенным в плане потентности исследуемых антител.On FIG. 14 shows the retention (green circle) or loss (red square) of neutralizing activity against S KEN pseudotyped lentiviral particles by various monoclonal antibodies and combinations thereof. The change in IC 50 values relative to the ancestral Spike variant (Wuhan-Hu-1 isolate) is shown, the range of a 5-fold change in IC 50 is highlighted in gray, which is not significant in terms of the potency of the antibodies under study.

В Табл. 1 представлены характеристики полученных моноклональных антител (серия iB) и известных антител, специфичных к RBD SARS-CoV-2. Блокирование ACE2-RBD 1 было протестировано путем добавления смеси антитело /RBD к клеткам линии ACE2-HEK293T. Способность моноклонального антитела предотвращать связывание RBD с ACE2 была измерена при помощи проточной цитометрии. Протективный эффект был рассчитан по формуле (1 - (MFIантитело - MFIфон)/(MFIтолько RBD – MFIфон)) × 100%. Способность моноклональных антител связываться со Spike-белком на клеточной поверхности была исследована с использованием клеток линии HEK293T с поверхностной экспрессией Spike-белка SARS-CoV-2. Аутореактивность3 исследована при помощи окрашивания клеток линии HEP-2, параметры вируснейтрализации - в системе Spike-псевдотипированных лентивирусных частиц4 и аутентичного вируса SARS-CoV-25. Константы афинности6 были измерены при помощи биослойной интерферометрии или получены из литературных источников. MFI – средняя интенсивность флуоресценции, NT – не исследовано, ND – не детектировано, NA – не известно.In Table. 1 shows the characteristics of the obtained monoclonal antibodies (iB series) and known antibodies specific for RBD SARS-CoV-2. Blocking of ACE2-RBD 1 was tested by adding an antibody/RBD mixture to the ACE2-HEK293T cell line. The ability of a monoclonal antibody to prevent binding of RBD to ACE2 was measured by flow cytometry. The protective effect was calculated by the formula (1 - (MFI antibody - MFI background )/(MFI only RBD - MFI background )) × 100%. The ability of monoclonal antibodies to bind to the Spike protein on the cell surface was investigated using HEK293T cells with surface expression of the SARS-CoV-2 Spike protein. The autoreactivity of 3 was studied by staining the HEP-2 cell line, the parameters of virus neutralization - in the system of Spike-pseudotyped lentiviral particles 4 and the authentic SARS-CoV-25 virus. Affinity constants 6 were measured using biolayer interferometry or obtained from literature sources. MFI—mean fluorescence intensity, NT—not studied, ND—not detected, NA—not known.

В Табл. 2 представлены результаты иммуноферментного анализа способности полученных моноклональных антител связываться с RBD SARS-CoV-2 дикого типа (изолят Wuhan-Hu-1), а также с RBD вариантов delta и beta. (+) – связывание, (-) – отсутствие связывания, (+/-) – слабое связывание.In Table. Figure 2 shows the results of an enzyme immunoassay of the ability of the obtained monoclonal antibodies to bind to the SARS-CoV-2 wild-type RBD (Wuhan-Hu-1 isolate), as well as to the delta and beta RBD variants. (+) - binding, (-) - no binding, (+/-) - weak binding.

В Табл. 3 представлены результаты Вестерн-блот гибридизации очищенного RBD SARS-CoV-2 и неочищенного рекомбинантного S-белка SARS-CoV-2 с полученными моноклональными антителами в присутствии и в отсутствие восстановителя. (+) – связывание, (-) – отсутствие связывания, (-/+) – слабое связывание.In Table. 3 shows the results of Western blot hybridization of purified SARS-CoV-2 RBD and crude recombinant SARS-CoV-2 S-protein with generated monoclonal antibodies in the presence and absence of a reducing agent. (+) - binding, (-) - no binding, (-/+) - weak binding.

Осуществление изобретенияImplementation of the invention

Последующие примеры приведены исключительно для целей объяснения и не предназначены для ограничения каким-либо образом объема настоящего изобретения.The following examples are provided solely for purposes of explanation and are not intended to limit the scope of the present invention in any way.

Пример 1. Выделение В-лимфоцитов человека, специфических к RBD Spike-белка вируса SARS-CoV-2.Example 1 Isolation of human B lymphocytes specific for the RBD Spike protein of the SARS-CoV-2 virus.

Образцы инактивированной прогреванием в течение 30 минут при +56°С плазмы доноров, перенесших коронавирусную инфекцию ковид-19, были проанализированы при помощи набора SARS-СоV-2-IgG-ИФА (ООО «Хема-Медика»). Затем, у доноров, образцы плазмы которых обнаруживали титры RBD-специфических антител 1:5000 и выше (Фиг. 1), был произведен забор периферической венозной крови и выделение живых CD19+ IgG+ B-лимфоцитов (окрашивание DAPI, конъюгатами anti-human CD19-PE (ООО «Сорбент»), anti-human IgG-FITC (ООО «Сорбент»), 5 мкл/106 мононуклеарных клеток крови). B-лимфоциты были дополнительно окрашены биотинилированным рекомбинантным RBD SARS-CoV-2 (2 мкг/мл) с последующей детекцией при помощи конъюгата APC-стрептавидин (Thermo Fisher Scientific). Поверхностный фенотип целевой популяции В-лимфоцитов для сортировки единичных клеток в индивидуальные ПЦР-пробирки таким образом был RBDhighCD19+IgG+DAPI (Фиг. 2). Окрашенные аналогичным образом В-лимфоциты здоровых доноров были использованы в качестве негативного контроля.Samples of plasma inactivated by heating for 30 minutes at +56°C from donors who had experienced coronavirus infection covid-19 were analyzed using the SARS-CoV-2-IgG-ELISA kit (OOO Chema-Medica). Then, from donors whose plasma samples showed RBD-specific antibody titers of 1:5000 and higher (Fig. 1), peripheral venous blood was taken and live CD19 + IgG + B-lymphocytes were isolated (stained with DAPI, anti-human CD19 conjugates -PE (LLC "Sorbent"), anti-human IgG-FITC (LLC "Sorbent"), 5 μl/10 6 mononuclear blood cells). B-lymphocytes were further stained with biotinylated recombinant SARS-CoV-2 RBD (2 µg/mL) followed by detection with APC-streptavidin conjugate (Thermo Fisher Scientific). The surface phenotype of the target population of B lymphocytes for single cell sorting into individual PCR tubes was thus RBD high CD19 + IgG + DAPI (FIG. 2). Similarly stained B-lymphocytes from healthy donors were used as a negative control.

Пример 2. Получение моноклональных антитела человека против RBD Spike-белка вируса SARS-CoV-2.Example 2. Production of human monoclonal antibodies against the RBD Spike protein of the SARS-CoV-2 virus.

Процедуры синтеза кДНК с единичных В-лимфоцитов и ПЦР с обратной транскрипцией проводили, как описано в работе Guselnikov и соавт (Guselnikov, S. V. et al. A simple way to increase recovery of the expressed VH and VL genes in single-sorted human B cells. BioTechniques 67, 184–187 (2019)), за исключением того, что для амплификации последовательностей, кодирующих γ- и λ-цепи антител, был использован протокол для μ-цепей. В частности для амплификации последовательностей генов VHγ, Vκ и Vλ были использован набор вырожденных праймеров из работы Tiller и соавт. (Tiller, T. et al. Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning. J. Immunol. Methods 329, 112–124 (2008)). Парные образцы ПЦР-ампликонов (VHγ + Vκ или Vλ) секвенировали по Сэнгеру и клонировали в векторы для эукариотической экспрессии, кодирующие константные районы γ1, κ или λ-цепей иммуноглобулинов человека (Tiller, T. et al. Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning. J. Immunol. Methods 329, 112–124 (2008)).Procedures for cDNA synthesis from single B-lymphocytes and reverse transcription PCR were performed as described by Guselnikov et al. (Guselnikov, S. V. et al. A simple way to increase recovery of the expressed VH and VL genes in single-sorted human B cells. BioTechniques 67, 184-187 (2019)), except that the μ-chain protocol was used to amplify the antibody γ- and λ-chain coding sequences. In particular, a set of degenerate primers from Tiller et al. was used to amplify the VHγ, Vκ, and Vλ gene sequences. (Tiller, T. et al. Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning. J. Immunol. Methods 329, 112–124 (2008)). Paired samples of PCR amplicons (VHγ + Vκ or Vλ) were sequenced according to Sanger and cloned into vectors for eukaryotic expression encoding constant regions of γ1, κ, or λ-chains of human immunoglobulins (Tiller, T. et al. Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning J. Immunol Methods 329, 112–124 (2008)).

Таким образом были получены пары последовательностей VH- и VL-генов для 33 B-лимфоцитов, из которых 28 были представлены уникальными комбинациями последовательностей. Смесь плазмидных ДНК экспрессионных конструкций, кодирующих корректные пары легких и тяжелых цепей антител, была доставлена в клетки линии HEK293T, используя метод кальций-фосфатной трансфекции (Chenuet, S. et al. Calcium phosphate transfection generates mammalian recombinant cell lines with higher specific productivity than polyfection. Biotechnol. Bioeng. 101, 937–945 (2008)). Как правило, за 12 часов до проведения трансфекции 107 клеток рассаживали в культуральные флаконы площадью 150 см2 в среде IMDM (Gibco, Thermo Fisher Scientific) с добавлением 10% FBS (Gibco, Thermo Fisher Scientific) и смеси пенициллина/стрептомицина (Gibco, Thermo Fisher Scientific). Плазмидные ДНК смешивали в молярном соотношении 1:1, к полученной смеси добавляли 2 М CaCl2 до финальной концентрации 25 мМ и доводили суммарный объем смеси стерильной водой до 3 мл. Затем смесь медленно добавляли к 3 мл раствора 2× HBS (50 мМ HEPES, 1,5 мМ Na2HPO4, 280 мМ NaCl, 10 мМ KCl, 12 мМ сахароза, pH = 7.11) при постоянном интенсивном перемешивании. Полученный раствор добавляли по каплям к клеткам. Спустя 8 часов, культуральную среду заменяли на бессывороточную среду EX-CELL® 293 Serum-Free Medium (Sigma). Трансфицированные клетки росли в течение 6 дней в CO2-инкубаторе при 37°C, 5% CO2. Супернатантны, очищенные от клеточного дебриса при помощи центрифугирования (4000× g, 10 мин), фильтровали через 0.22 мкм PES-фильтр (TPP). Антитела очищали на колонке с Protein A агарозой (McLab, USA, #PPA-503) в соответствии с инструкциями производителя. Вкратце, после загрузки колонку промывали дважды PBS. Антитела элюировали раствором 0.1 M глицина, pH 2,7, 150 мМ NaCl в нейтрализующий буфер состава 1 M Tris, pH 8,0, в соотношении 1:10. Чистоту и выход препаратов антител контролировали посредством разделения в 15% SDS-полиакриламидном геле (Фиг. 3). Затем проводили диализ в течение ночи в PBS и концентрировали с использованием колонок Ultra-15 Ultracel-100K (Amicon) до финальной концентрации 2 мг/мл.Thus, sequence pairs of VH and VL genes were obtained for 33 B-lymphocytes, of which 28 were represented by unique combinations of sequences. A mixture of plasmid DNA expression constructs encoding the correct pairs of antibody light and heavy chains was delivered to HEK293T cells using the calcium phosphate transfection method (Chenuet, S. et al. Calcium phosphate transfection generates mammalian recombinant cell lines with higher specific productivity than polyfection Biotechnol Bioeng 101, 937–945 (2008)). Typically, 12 hours prior to transfection, 10 7 cells were seeded into 150 cm2 culture flasks in IMDM (Gibco, Thermo Fisher Scientific) supplemented with 10% FBS (Gibco, Thermo Fisher Scientific) and a penicillin/streptomycin mixture (Gibco, Thermo Fisher Scientific. Plasmid DNA was mixed in a 1:1 molar ratio, 2 M CaCl 2 was added to the resulting mixture to a final concentration of 25 mM, and the total volume of the mixture was adjusted to 3 ml with sterile water. The mixture was then slowly added to 3 ml of a 2x HBS solution (50 mM HEPES, 1.5 mM Na 2 HPO 4 , 280 mM NaCl, 10 mM KCl, 12 mM sucrose, pH = 7.11) with constant vigorous stirring. The resulting solution was added dropwise to the cells. After 8 hours, the culture medium was changed to serum-free EX-CELL® 293 Serum-Free Medium (Sigma). The transfected cells were grown for 6 days in a CO 2 incubator at 37°C, 5% CO 2 . The supernatants, cleared of cell debris by centrifugation (4000×g, 10 min), were filtered through a 0.22 µm PES filter (TPP). Antibodies were purified on a Protein A agarose column (McLab, USA, #PPA-503) according to the manufacturer's instructions. Briefly, after loading the column was washed twice with PBS. Antibodies were eluted with a solution of 0.1 M glycine, pH 2.7, 150 mM NaCl in a neutralizing buffer of 1 M Tris, pH 8.0, in a ratio of 1:10. The purity and yield of antibody preparations were controlled by separation on a 15% SDS-polyacrylamide gel (FIG. 3). It was then dialyzed overnight in PBS and concentrated using Ultra-15 Ultracel-100K columns (Amicon) to a final concentration of 2 mg/mL.

Для измерения кинетики взаимодействия антител с RBD была использована биослойная интерферометрия (прибор Octet (ForteBio), биосенсоры NTA). С этой целью была вначале проведена иммобилизация рекомбинантного белка RBD-His6 (30 мкг/мл) на поверхности биосенсора. Нерелевантный белок Fn3, также несущий His6-эпитоп и обладающий схожим молекулярным весом, был иммобилизован на контрольном сенсоре (30 мкг/мл), после чего производили необратимую иммобилизацию данных белков на сенсорах при помощи EDC/NHS, в соответствии с инструкциями производителя. Значения KD были получены с использованием концентрации RBD-His6, равной 26,7 нМ. Для обработки данных были использованы параметры полного локального фиттинга, бивалентная модель, R2 > 0,9, Χ2 < 3 (Фиг. 4). Затем для девяти наиболее аффинных моноклональных антител (iB3, iB6, iB9, iB12, iB13, iB14, iB15, iB19 и iB20) была проведена более точная характеризация связывания в диапазоне 6 концентраций RBD-His6 (6,25 нМ, 12,5 нМ, 25 нМ, 50 нМ, 100 нМ, 200 нМ). С этой целью были использованы AHC-биосенсоры и проведена иммобилизация антител. В качестве нерелевантного антитела было использовано моноклональное антитело человека glVRC01 (Georgiev I. S. et al. Antibodies VRC01 and 10E8 neutralize HIV-1 with high breadth and potency even with Ig-framework regions substantially reverted to germline. J Immunol. 192(3), 1100-1106 (2014)). Для обработки данных были использованы параметры полного глобального фиттинга, бивалентная модель, R2 > 0,9, Χ2 < 3 и последовательный переход между режимами: Baseline 30 с, Loading 300 с, Baseline2 60 с, Association 600 с, Dissociation 1500 с, Regeneration 3 × 5 с (Фиг. 5). Значения KD, Kon и Koff для 23 моноклональных антител приведены в Табл. 1.Biolayer interferometry (Octet device (ForteBio), NTA biosensors) was used to measure the kinetics of the interaction of antibodies with RBD. For this purpose, the immobilization of the recombinant protein RBD-His6 (30 μg/mL) on the surface of the biosensor was first carried out. The irrelevant Fn3 protein, also carrying the His6 epitope and having a similar molecular weight, was immobilized on the control sensor (30 μg/ml), after which these proteins were irreversibly immobilized on the sensors using EDC/NHS, according to the manufacturer's instructions. KD values were obtained using a RBD-His6 concentration of 26.7 nM. For data processing, full local fitting parameters were used, bivalent model, R 2 > 0.9, Χ 2 < 3 (Fig. 4). The nine highest affinity monoclonal antibodies (iB3, iB6, iB9, iB12, iB13, iB14, iB15, iB19 and iB20) were then further characterized for binding over a range of 6 concentrations of RBD-His6 (6.25 nM, 12.5 nM, 25 nM, 50 nM, 100 nM, 200 nM). For this purpose, AHC biosensors were used and antibodies were immobilized. The human monoclonal antibody glVRC01 (Georgiev IS et al. Antibodies VRC01 and 10E8 neutralize HIV-1 with high breadth and potency even with Ig-framework regions substantially reverted to germline. J Immunol. 192(3), 1100- 1106 (2014)). For data processing, the parameters of the full global fitting, bivalent model, R 2 > 0.9, Χ 2 < 3, and sequential transition between modes: Baseline 30 s, Loading 300 s, Baseline2 60 s, Association 600 s, Dissociation 1500 s, Regeneration 3×5 s (Fig. 5). The values of K D , K on and K off for 23 monoclonal antibodies are shown in Table. 1.

Способность всех 23 моноклональных антител узнавать RBD в контексте Spike-белка SARS-CoV-2, а не только рекомбинантный RBD, была подтверждена с использованием проточной цитометрии клеток HEK293T, экспрессирующих Spike-белок SARS-CoV-2 на своей поверхности (Фиг. 6, Табл. 1). Более того, ни одно из полученных моноклональных антител не было способно узнавать Spike-белки двух родственных альфакоронавирусов, HCoV-229E и HCoV-NL63 (Фиг. 6), в полном соответствии со значительной степенью эволюционной дивергенции их последовательностей RBD и использованной стратегией отбора В-лимфоцитов именно против RBD Spike-белка SARS-CoV-2.The ability of all 23 monoclonal antibodies to recognize RBD in the context of the SARS-CoV-2 Spike protein, and not just recombinant RBD, was confirmed using flow cytometry of HEK293T cells expressing the SARS-CoV-2 Spike protein on their surface (Fig. 6, Table 1). Moreover, none of the obtained monoclonal antibodies was able to recognize the spike proteins of the two related alphacoronaviruses, HCoV-229E and HCoV-NL63 (Fig. 6), in full accordance with the significant degree of evolutionary divergence of their RBD sequences and the B-selection strategy used. lymphocytes specifically against the RBD Spike protein of SARS-CoV-2.

На основании полученных данных с учетом генетического кода были определены аминокислотные последовательности вариабельных доменов тяжелых (SEQ ID NO: 139-161) и легких (SEQ ID NO: 162-184) цепей 23 моноклональных антител, специфичных к RBD Spike-белка SARS-CoV-2. Участки CDRs VH (SEQ ID NO: 1-69) и VL (SEQ ID NO: 70-138) были определены по номенклатуре Kabat [Kabat numbering system, Kabat et al., 1987 "Sequences of Proteins of Immunological Interest", US Dept. of Health and Human Services, US Government Printing Office].Based on the obtained data, taking into account the genetic code, the amino acid sequences of the variable domains of the heavy (SEQ ID NO: 139-161) and light (SEQ ID NO: 162-184) chains of 23 monoclonal antibodies specific to the RBD Spike protein of SARS-CoV- 2. The VH (SEQ ID NO: 1-69) and VL (SEQ ID NO: 70-138) CDRs were determined using the Kabat nomenclature [Kabat numbering system, Kabat et al., 1987 "Sequences of Proteins of Immunological Interest", US Dept. . of Health and Human Services, US Government Printing Office].

Таким образом, были получены аминокислотные последовательности SEQ ID NO: 139-161 и SEQ ID NO: 162-184, а также кодирующие их нуклеотидные последовательности SEQ ID NO: 185-207 и SEQ ID NO: 208-230.Thus, the amino acid sequences SEQ ID NO: 139-161 and SEQ ID NO: 162-184, as well as the nucleotide sequences encoding them SEQ ID NO: 185-207 and SEQ ID NO: 208-230 were obtained.

Проведенный биоинформатический анализ последовательностей этих антител против известных последовательностей антител к SARS-CoV-2 не выявил антител, на 100% совпадающих по последовательностям легкой и тяжелой цепи с антителами изобретения.The bioinformatic analysis of the sequences of these antibodies against the known sequences of antibodies to SARS-CoV-2 did not reveal antibodies that 100% match the light and heavy chain sequences with the antibodies of the invention.

Пример 3. Определение вируснейтрализующей активности моноклональных антител человека in vitro.Example 3 Determination of the virus-neutralizing activity of human monoclonal antibodies in vitro.

Для оценки уровня вируснейтрализующей активности моноклональных антител использовали два подхода: суррогатный тест с использованием псевдотипированных лентивирусных частиц и микронейтрализационный тест с использованием аутентичного вируса SARS-CoV-2.To assess the level of virus-neutralizing activity of monoclonal antibodies, two approaches were used: a surrogate test using pseudotyped lentiviral particles and a microneutralization test using an authentic SARS-CoV-2 virus.

Для получения лентивирусных частиц, псевдотипированных Spike-белком SARS-CoV-2 проводили кальций-фосфатную трансфекцию клеток линии HEK293T смесью плазмид psPAX2, pLV-EGFP и pCAGGS-SpikeΔ19 в молярном соотношении 4:6:3. Плазмида pCAGGS-SpikeΔ19 кодировала укороченный с С-конца на 19 аминокислотных остатков Spike-белок, соответствующий исходному штамму Wuhan-Hu-1 SARS-CoV-2 или мутантным вариантам Spike SARS-CoV-2 (SΔ19). Через восемь часов после трансфекции среду заменяли на Opti-Mem (Gibco, Thermo Fisher Scientific) с добавлением 2,5% FBS (Gibco, Thermo Fisher Scientific). Супернатанты собирали два дня спустя, центрифугировали при 4000 об/мин в течение 5 минут, после чего лентивирусные частицы концентрировали путем центрифугирования при 20000× g, 4°C в течение 90 минут. Для проведения нейтрализационного теста в качестве мишеней использовали клетки линии ACE2-HEK293T со стабильной поверхностной экспрессией белка ACE2, рассаженные с плотностью 30000 клеток/лунку в 96-луночном штативе в день проведения теста. Антитела серийно двукратно разводили в среде Opti-MEM с добавлением 2,5% FBS в диапазоне от 0,5 нг/мл до 1 мкг/мл и ко-инкубировали с 20000 лентивирусных частиц, псевдотипированных Spike-белком SARS-CoV-2 в течение 30 мин при 37°C в объеме 100 мкл. Полученную смесь антител и лентивирусных частиц добавляли к клеткам ACE2-HEK293T и возвращали в CO2-инкубатор. Спустя 72 часа после трансдукции измеряли процент трансдуцированных (GFP+) клеток, используя проточный цитометр. Значение концентрации полумаксимального ингибирования IC50 определяли, используя нелинейную регрессию, как концентрацию, обеспечивавшую нейтрализацию 50% псевдотипированных лентивирусных частиц (Фиг. 7а).To obtain lentiviral particles pseudotyped with the SARS-CoV-2 Spike protein, calcium phosphate transfection of HEK293T cells was performed with a mixture of psPAX2, pLV-EGFP, and pCAGGS-SpikeΔ19 plasmids in a molar ratio of 4:6:3. Plasmid pCAGGS-SpikeΔ19 encoded a C-terminally truncated 19 amino acid Spike protein corresponding to the original Wuhan-Hu-1 SARS-CoV-2 strain or mutant SARS-CoV-2 Spike variants (SΔ19). Eight hours after transfection, the medium was changed to Opti-Mem (Gibco, Thermo Fisher Scientific) supplemented with 2.5% FBS (Gibco, Thermo Fisher Scientific). The supernatants were collected two days later, centrifuged at 4000 rpm for 5 minutes, after which the lentiviral particles were concentrated by centrifugation at 20,000×g, 4°C for 90 minutes. For the neutralization test, ACE2-HEK293T cells with stable surface expression of the ACE2 protein, seeded at a density of 30,000 cells/well in a 96-well rack on the day of the test, were used as targets. Antibodies were serially diluted twice in Opti-MEM medium supplemented with 2.5% FBS in the range from 0.5 ng/ml to 1 µg/ml and co-incubated with 20,000 lentiviral particles pseudotyped with the SARS-CoV-2 Spike protein for 30 min at 37°C in a volume of 100 µl. The resulting mixture of antibodies and lentiviral particles was added to ACE2-HEK293T cells and returned to the CO 2 incubator. 72 hours after transduction, the percentage of transduced (GFP + ) cells was measured using a flow cytometer. The IC 50 half-maximal inhibition concentration was determined using non-linear regression as the concentration that neutralized 50% of the pseudotyped lentiviral particles (FIG. 7a).

Микронейтрализационный тест с использованием аутентичного вируса SARS-CoV-2 проводили, как описано в работе Nurtop и соавторов (Nurtop, E. et al. Combination of ELISA screening and seroneutralisation tests to expedite Zika virus seroprevalence studies. Virol. J. 15, 192 (2018)) в 96-луночных планшетах (Costar), используя в качестве мишеней клетки линии VeroE6, культивируемые в среде DMEM с добавлением 5% FBS. Вирусный супернатант (100 TCID50) смешивали с равным объемом серийных разведений моноклональных антител и инкубировали при 37°C в течение 1 часа. Затем полученные смеси вирус/антитело (100 мкл) переносили в лунки планшета с монослоем клеток линии VeroE6. Спустя 5-7 дней лунки c клетками анализировали визуально при помощи инвертированного микроскопа и выясняли IC100 (наименьшая концентрация антитела, обеспечивавшая полную защиту от заражения 100 TCID50 вируса SARS-CoV-2 (Фиг. 7б). Значения вируснейтрализующей активности моноклональных антител в обоих тестах in vitro приведены в Табл. 1. Таким образом, установлено, что моноклональные антитела iВ12, iВ15, iB14, iB3 являются ультрапотентными нейтрализаторами SARS-CoV-2 (IC100<16 нг/мл), вируснейтрализующая активность iB9, iB20, iB6, iB13, iB19, iB18, iB24, iB11, iB4 значительно ниже и находится в диапазоне 125 нг/мл – 25 мкг/мл, а остальные моноклональные RBD-специфические антитела не обладают выраженной вируснейтрализующей активностью (Табл. 1).A microneutralization test using authentic SARS-CoV-2 virus was performed as described by Nurtop et al. 2018)) in 96-well plates (Costar) using VeroE6 cells cultured in DMEM supplemented with 5% FBS as targets. Viral supernatant (100 TCID 50 ) was mixed with an equal volume of serial dilutions of monoclonal antibodies and incubated at 37°C for 1 hour. Then the resulting virus/antibody mixtures (100 µl) were transferred into the wells of the plate with a monolayer of VeroE6 cells. After 5-7 days, the wells with cells were analyzed visually using an inverted microscope and the IC 100 was determined (the lowest concentration of the antibody that provided complete protection against infection with 100 TCID 50 of the SARS-CoV-2 virus (Fig. 7b). The values of the virus-neutralizing activity of monoclonal antibodies in both in vitro tests are shown in Table 1. Thus, it was found that monoclonal antibodies iB12, iB15, iB14, iB3 are ultrapotent neutralizers of SARS-CoV-2 (IC 100 <16 ng/ml), virus-neutralizing activity of iB9, iB20, iB6, iB13, iB19, iB18, iB24, iB11, iB4 are significantly lower and are in the range of 125 ng/ml - 25 µg/ml, and the remaining monoclonal RBD-specific antibodies do not have a pronounced virus-neutralizing activity (Table 1).

Пример 4. Определение конкурентных взаимоотношений между моноклональными антителами за связывание с эпитопами RBD.Example 4 Determination of competitive relationships between monoclonal antibodies for binding to RBD epitopes.

Мы обратились к анализу на основе биослойной интерферометрии для выяснения попарной конкуренции 22 RBD-специфических моноклональных антител за связывание с RBD. С этой целью рекомбинантный RBD-His6 (14 мкг/мл) был иммобилизован на NTA-биосенсор, после чего к нему было добавлено насыщающее количество первого антитела (Ab1, 75 мкг/мл (500 нМ). Сформированный таким образом комплекс RBD-Ab1 затем инкубировали со вторым антителом, Ab2. В целом была использована следующая 6-шаговая схема: Baseline 60 с, Loading 200 с, Baseline2 30 с, Saturation Ab1 600 с, Competing Ab2 600 с, Regeneration в глицин-HCl, pH 1,7, 5 × 3 с.We turned to an analysis based on biolayer interferometry to elucidate the pairwise competition of 22 RBD-specific monoclonal antibodies for binding to RBD. For this purpose, recombinant RBD-His6 (14 μg/ml) was immobilized on an NTA biosensor, after which a saturating amount of the first antibody (Ab1, 75 μg/ml (500 nM) was added to it. The RBD-Ab1 complex thus formed was then incubated with a second antibody, Ab2.In general, the following 6-step scheme was used: Baseline 60 s, Loading 200 s, Baseline2 30 s, Saturation Ab1 600 s, Competing Ab2 600 s, Regeneration in glycine-HCl, pH 1.7, 5 × 3 s.

Большинство нейтрализующих моноклональных антител формировали два крупных кластера (Фиг. 8). В первый кластер входили высокопотентные антитела iB3, iB12, iB14 и iB15, а также умереннопотентное iB13 и слабопотентное iB11. Кластер II состоял из умеренно- и слабопотентных антител iB9, iB17, iB18, iB19, iB20, iB24 и iB25. Нейтрализующее моноклональное антитело iB6 не принадлежало ни одному из этих кластеров. Ненейтрализующие антитела также формировали свой отдельный кластер.Most neutralizing monoclonal antibodies formed two large clusters (Fig. 8). The first cluster included highly potent antibodies iB3, iB12, iB14 and iB15, as well as moderately potent iB13 and low potent iB11. Cluster II consisted of moderate and low potency antibodies iB9, iB17, iB18, iB19, iB20, iB24, and iB25. The neutralizing monoclonal antibody iB6 did not belong to any of these clusters. Non-neutralizing antibodies also formed their own separate cluster.

Данный анализ был расширен с целью выяснения возможности комбинирования выделенных нами 9 лидирующих нейтрализующих антител с рядом известных нейтрализующих антител, в частности REGN10933, REGN10987, COVA2-15 и COV2-2504 (Brouwer, P. J. M. et al. Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Science 369, 643–650 (2020); Hansen, J. et al. Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science 369, 1010-1014 (2020). Zost, S. J. et al. Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein. Nat. Med. 26, 1422–1427 (2020)). Было обнаружено, что моноклональные нейтрализующие антитела iB20, iB6, и REGN10987 не конкурируют друг с другом и могут одновременно связываться с RBD, т.е. их эпитопы не перекрываются. Эпитопы остальных моноклональных антител в разной степени перекрываются друг с другом (Фиг. 9, Фиг. 10). В частности, моноклональные нейтрализующие антитела iB3, iB12, iB13, iB14, iB15, REGN10933 и COV2-2504 конкурируют друг с другом за связывание с RBD, однако различаются между собой в плане конкуренции с СOVA2-15 и REGN10987. Последние два антитела конкурируют с iB3 и iB12, но не с iB13 и iB14. В то же время, REGN10933, iB15 и COV2-2504 не обнаруживают конкуренции с REGN10987, но конкурируют с COVA2-15. Антитела iB3, iB12, iB13, iB14, iB15, REGN10933, СOV2-2504 и COVA2-15, связанные с RBD, предотвращают связывание iB9, iB19 и iB20. Однако при обратной постановке эксперимента блокирование оказывается неполным. Таким образом, проведенный конкурентный анализ свидетельствует о том, что 13 нейтрализующих моноклональных антител образуют 8 эпитопных групп: iB13/iB14, REGN10933/COV2-2504/iB15, iB3/iB12, iB9, COVA2-15, iB19/iB20, iB6 и REGN10987 (Фиг. 10), что открывает значительный простор для создания различных композиций неконкурирующих друг с другом вируснейтрализующих антител. Например, такие композиции могут быть образованы сочетаниями iB14 + COVA2-15, iB14 + REGN10987, iB20 + iB6, iB15 + REGN10987, COV2-2504 + REGN10987, iB20 + REGN10987 или iB6 + iB20 + REGN10987.This analysis was expanded to determine the possibility of combining the 9 leading neutralizing antibodies we isolated with a number of known neutralizing antibodies, in particular REGN10933, REGN10987, COVA2-15 and COV2-2504 (Brouwer, P. J. M. et al. Potent neutralizing antibodies from COVID-19 define patients multiple targets of vulnerability Science 369, 643-650 (2020) Hansen, J. et al Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail Science 369, 1010-1014 (2020) Zost , S. J. et al., Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein, Nat Med. 26, 1422–1427 (2020)). It was found that the monoclonal neutralizing antibodies iB20, iB6, and REGN10987 do not compete with each other and can simultaneously bind to RBD, ie. their epitopes do not overlap. The epitopes of the remaining monoclonal antibodies overlap to varying degrees (Fig. 9, Fig. 10). In particular, monoclonal neutralizing antibodies iB3, iB12, iB13, iB14, iB15, REGN10933 and COV2-2504 compete with each other for binding to RBD, but differ in terms of competition with COVA2-15 and REGN10987. The last two antibodies compete with iB3 and iB12 but not with iB13 and iB14. At the same time, REGN10933, iB15 and COV2-2504 do not compete with REGN10987, but compete with COVA2-15. Antibodies iB3, iB12, iB13, iB14, iB15, REGN10933, COV2-2504 and COVA2-15 associated with RBD prevent the binding of iB9, iB19 and iB20. However, in the reverse formulation of the experiment, the blocking turns out to be incomplete. Thus, the conducted competitive analysis indicates that 13 neutralizing monoclonal antibodies form 8 epitope groups: iB13/iB14, REGN10933/COV2-2504/iB15, iB3/iB12, iB9, COVA2-15, iB19/iB20, iB6 and REGN10987 ( Fig. 10), which opens up considerable scope for creating various compositions of virus-neutralizing antibodies that do not compete with each other. For example, such compositions can be formed by combinations of iB14+COVA2-15, iB14+REGN10987, iB20+iB6, iB15+REGN10987, COV2-2504+REGN10987, iB20+REGN10987 or iB6 + iB20 + REGN10987.

Пример 5. Вируснейтрализующая активность моноклональных антител и их комбинаций in vivo.Example 5. Virus-neutralizing activity of monoclonal antibodies and their combinations in vivo.

Для оценки вируснейтрализующей активности моноклональных антител и их комбинаций in vivo была использована модель инфекции SARS-CoV-2 на сирийских хомячках. Вначале была исследована активность iB12 и смеси iB6/iB20 (1:1) в качестве профилактики и/или терапии инфекции SARS-CoV-2 и вызванной этим вирусом легочной патологии (Фиг. 11, верхняя панель). Дополнительно был проведен независимый эксперимент с антителами iB14, поскольку оно было более устойчиво к некоторым из замен в последовательности Spike-белка у циркулировавших в 2020-2021 годах вариантов SARS-CoV-2 (Фиг. 11, нижняя панель). В профилактической схеме было сформировано семь групп животных (n = 6), которым внутрибрюшинно вводили моноклональные антитела: 10 мг/кг iB12 (группа 1), 1 мг/кг iB12 (группа 2), 10 мг/кг 1:1 смесь iB6 и iВ20 (группа 3), 1 мг/кг смесь iB6 и iВ20 (группа 4), 10 мг/кг суммарный иммуноглобулин IgG человека (группа 5, негативный контроль) за 24 часа до инфекции (–1 dpi). Животные, не получившие ни антител, ни вирус (группа 6), были использованы в качестве дополнительного негативного контроля. На следующий день (0 dpi) животных интаназально зараражали SARS-CoV-2 (50 мкл/нозд.) в суммарной дозе 1,3 × 103 БОЕ. В терапевтической схеме животные получали iB12 (10 мг/кг, внутрибрюшинно) 6 часов после заражения (группа 7). Животных взвешивали ежедневно. В каждой группе троих животных усыпляли на 5 день после заражения (5 dpi), легкие выделяли для оценки вирусной нагрузки и патолого-морфологического исследования. Также производили забор крови для измерения уровня иммуноглобулинов человека IgG в сыворотке животных. В эксперименте по оценке протективных свойств моноклонального антитела iB14 была проверена дополнительная временная точка, 24 ч после инфекции (6-7 животных на группу).To assess the virus-neutralizing activity of monoclonal antibodies and their combinations in vivo, a model of SARS-CoV-2 infection in Syrian hamsters was used. Initially, the activity of iB12 and a mixture of iB6/iB20 (1:1) was investigated as a prophylaxis and/or therapy for SARS-CoV-2 infection and pulmonary disease caused by this virus (Fig. 11, upper panel). Additionally, an independent experiment was performed with iB14 antibodies, since it was more resistant to some of the changes in the Spike protein sequence in SARS-CoV-2 variants circulating in 2020-2021 (Fig. 11, lower panel). In the prophylactic scheme, seven groups of animals (n = 6) were formed, which were intraperitoneally injected with monoclonal antibodies: 10 mg/kg iB12 (group 1), 1 mg/kg iB12 (group 2), 10 mg/kg 1:1 mixture of iB6 and iB20 (group 3), 1 mg/kg mixture of iB6 and iB20 (group 4), 10 mg/kg total human IgG (group 5, negative control) 24 hours before infection (–1 dpi). Animals that received neither antibodies nor virus (Group 6) were used as an additional negative control. The next day (0 dpi), animals were intranasally infected with SARS-CoV-2 (50 μl/nost.) at a total dose of 1.3 × 10 3 PFU. In the therapeutic regimen, animals received iB12 (10 mg/kg, ip) 6 hours after challenge (group 7). Animals were weighed daily. In each group, three animals were euthanized on the 5th day after infection (5 dpi), lungs were isolated for viral load assessment and pathological examination. Blood samples were also taken to measure the level of human IgG immunoglobulins in animal serum. In an experiment to evaluate the protective properties of the monoclonal antibody iB14, an additional time point was tested, 24 hours after infection (6-7 animals per group).

Как профилактическое, так и терапевтическое введение антител обладало выраженным эффектом. В то время как контрольные животные прогрессивно теряли в весе (снижение на 15% к 5 дню после заражения), все животные из экспериментальных групп прибавляли в весе, начиная с 3 дня после заражения (Фиг. 11А). Кроме того, измерение уровней вирусной нагрузки в гомогенатах легких хомяков (ртПЦР) свидетельствовало о том, что животные, получившие моноклональные антитела профилактически имели уровни вирусной РНК, сниженные по сравнению с контролем, на 2–6 порядков. Терапевтическое применение моноклональных антител iB12 и iB14 в дозировке 1 мг на животное также обладало протективным эффектом, выражавшимся в снижении вирусной нагрузки в легких (Фиг. 11Б). В легких контрольных животных были обнаружены признаки интерстициальной пневмонии, включая множественные перибронхиальные и периваскулярные очаги лейкоцитарной инфильтрации в сочетании с отеком, множественными некротическими изменениями в интерстиции и выраженной консолидацией легочной ткани (более 50%). Профилактическое введение iB12 (1 мг) обладало наибольшим протективным эффектом в отношении легких: у животных из этой группы уровень легочной патологии был минимальным. Снижение дозы моноклонального антитела iB12 (0,1 мг), использование смеси iB6 + iB20 (0,1 и 1 мг), а также терапевтическое введение iB12 предотвращало развитие пневмонии, хотя иногда и наблюдалось утолщение альвеолярных перегородок с незначительной гиперплазией альвеолярных эпителиоцитов второго типа или десквамацией эпителия бронхиол, а также периваскулярные отеки (Фиг. 11В, Фиг. 12). Терапевтическое введение сниженной дозы моноклонального антитела iB14 или его отложенное введение через 24 часа после заражения не отражалось на уровне вирусной РНК в легких хомяков, однако потеря веса у таких животных была значительно меньше, чем в контроле (Фиг. 11А,Б). Измерение уровня вирусной РНК в гомогенатах легких хомяков проводили с использованием количественной обратной ПЦР в реальном времени. Для этой цели половину левой доли легкого взвешивали, помещали в раствор LIRA (Биолабмикс) и замораживали. Образцы тщательно гомогенизировали и использовали для выделения РНК в соответствии с инструкциями производителя. Используя набор RevertAid cDNA synthesis kit (Thermo Scientific) и случайные гексамерные олигонуклеотиды, была получена кДНК с 1 мг суммарной РНК. Для проведения обратной ПЦР в реальном времени были использованы два набора праймеров, специфически узнающих последовательности генов RdRp и E SARS-CoV-2 (Corman, V. M. et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. 25, 2000045 (2020)), а также нормировочные праймеры, соответствующие транскриптам гена Rpl18 хомяка (Zivcec, M., Safronetz, D., Haddock, E., Feldmann, H. & Ebihara, H. Validation of assays to monitor immune responses in the Syrian golden hamster (Mesocricetus auratus). J. Immunol. Methods 368, 24–35 (2011)).Both prophylactic and therapeutic administration of antibodies had a pronounced effect. While the control animals progressively lost weight (15% decrease by day 5 post challenge), all animals from the experimental groups gained weight from day 3 post challenge (FIG. 11A). In addition, the measurement of viral load levels in hamster lung homogenates (rtPCR) indicated that animals that received monoclonal antibodies prophylactically had viral RNA levels reduced by 2–6 orders of magnitude compared to control. The therapeutic use of monoclonal antibodies iB12 and iB14 at a dosage of 1 mg per animal also had a protective effect, expressed in a decrease in viral load in the lungs (Fig. 11B). In the lungs of control animals, signs of interstitial pneumonia were found, including multiple peribronchial and perivascular foci of leukocyte infiltration in combination with edema, multiple necrotic changes in the interstitium, and pronounced consolidation of the lung tissue (more than 50%). Prophylactic administration of iB12 (1 mg) had the greatest protective effect on the lungs: in animals from this group, the level of pulmonary pathology was minimal. Reducing the dose of the monoclonal antibody iB12 (0.1 mg), using a mixture of iB6 + iB20 (0.1 and 1 mg), and therapeutic administration of iB12 prevented the development of pneumonia, although thickening of the alveolar septa with slight hyperplasia of alveolar epithelial cells of the second type was sometimes observed. desquamation of the epithelium of the bronchioles, as well as perivascular edema (Fig. 11B, Fig. 12). Therapeutic administration of a reduced dose of iB14 monoclonal antibody or its delayed administration 24 hours after infection did not affect the level of viral RNA in the lungs of hamsters, however, weight loss in such animals was significantly less than in controls (Fig. 11A,B). Measurement of viral RNA levels in hamster lung homogenates was performed using quantitative real-time reverse PCR. For this purpose, half of the left lobe of the lung was weighed, placed in a LIRA solution (Biolabmix) and frozen. The samples were carefully homogenized and used for RNA isolation according to the manufacturer's instructions. Using the RevertAid cDNA synthesis kit (Thermo Scientific) and random hexameric oligonucleotides, cDNA was generated from 1 mg of total RNA. For real-time reverse PCR, two sets of primers were used that specifically recognize the SARS-CoV-2 RdRp and E gene sequences (Corman, V. M. et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. 25, 2000045 (2020)), as well as normalization primers corresponding to hamster Rpl18 gene transcripts (Zivcec, M., Safronetz, D., Haddock, E., Feldmann, H. & Ebihara, H. Validation of assays to monitor immune responses in the Syrian golden hamster (Mesocricetus auratus. J. Immunol. Methods 368, 24–35 (2011)).

Пример 6. Изучение чувствительности нейтрализующих моноклональных антител к разнообразным заменам в Spike-белка SARS-CoV-2, в том числе присутствующим в циркулирующих вирусных вариантах.Example 6. Study of the sensitivity of neutralizing monoclonal antibodies to various substitutions in the SARS-CoV-2 Spike protein, including those present in circulating viral variants.

С целью выяснения возможной чувствительности нейтрализующих моноклональных антител к заменам в RBD Spike-белка SARS-CoV-2 с использованием направленного мутагенеза была получена панель экспрессионных конструкций, кодирующих 9 одноаминокислотных вариантов Spike-белка (K417N, N439K, K444Q, N460T, A475V, Е484K, F486K, F490L и N501Y) SARS-CoV-2. Такие конструкции были использованы для получения псевдотипированных лентивирусных частиц и проведения суррогатного теста на вируснейтрализацию с моноклональными нейтрализующими антителами iB3, iB6, iB9, iB12, iB14, iB15 и iB20), а также четырьмя референсными нейтрализующими антителами REGN10987, REGN10933, COVA2-15 и COV2-2504. Замена N501Y присутствует в нескольких циркулирующих вариантах вируса SARS-CoV-2, а именно в 501Y.V1 (клада B.1.1.7), 501Y.V2 (клада B.1.351) и 501Y.V3 (клада P.1). В последних двух случаях, N501Y встречается в сочетании с заменами K417N и E484K. В свою очередь замена E484K встречается в кладе B.1.525 и обусловливает устойчивость таких вирусов к некоторым известным нейтрализующим моноклональным антителам (Jones, B.E. et al. The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates. Sci. Transl. Med. 13, eabf1906 (2021); Hansen, J. et al. Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science 369, 1010–1014 (2020); Barnes, C.O. et al. Structures of human antibodies bound to SARS-CoV-2 spike reveal common epitopes and recurrent features of antibodies. Cell 182, 828–842.e16 (2020); Weisblum, Y. et al. Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. elife 9, e61312 (2020); Starr, T.N. et al. Prospective mapping of viral mutations that escape antibodies used to treat COVID-19. Science 371, 850–854 (2021); Baum, A. et al. Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science 369, 1014–1018 (2020); Greaney, A.J. et al. Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition. Cell Host Microbe 29, 44–57.e9 (2021)).In order to elucidate the possible sensitivity of neutralizing monoclonal antibodies to substitutions in the RBD of the SARS-CoV-2 spike protein using site-directed mutagenesis, a panel of expression constructs encoding 9 single-amino acid variants of the Spike protein (K417N, N439K, K444Q, N460T, A475V, E484K, F486K, F490L and N501Y) SARS-CoV-2. Such constructs were used to obtain pseudotyped lentiviral particles and perform a surrogate virus neutralization test with monoclonal neutralizing antibodies iB3, iB6, iB9, iB12, iB14, iB15 and iB20), as well as four reference neutralizing antibodies REGN10987, REGN10933, COVA2-15 and COV2- 2504. The N501Y substitution is present in several circulating variants of the SARS-CoV-2 virus, namely 501Y.V1 (clade B.1.1.7), 501Y.V2 (clade B.1.351), and 501Y.V3 (clade P.1). In the last two cases, N501Y is found in combination with the K417N and E484K replacements. In turn, the E484K substitution occurs in the B.1.525 clade and determines the resistance of such viruses to some known neutralizing monoclonal antibodies (Jones, B.E. et al. The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates. Sci Transl. Med. 13, eabf1906 (2021); Hansen, J. et al. Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science 369, 1010–1014 (2020); Barnes, C. O. et al. Structures of human antibodies bound to SARS-CoV-2 spike reveal common epitopes and recurrent features of antibodies. Cell 182, 828–842.e16 (2020); Weisblum, Y. et al. Escape from neutralizing antibodies by SARS-CoV -2 spike protein variants elife 9, e61312 (2020), Starr, T. N. et al, Prospective mapping of viral mutations that escape antibodies used to treat COVID-19, Science 371, 850–854 (2021), Baum, A. et al Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science 369, 1014–1018 (2020); Greeney, A.J. et al. Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition. Cell Host Microbe 29, 44–57.e9 (2021)).

Полученные нами данные свидетельствуют о том, что из исследованных вирусных вариантов три - Е484K, F486K и F490L обладают наибольшим негативным эффектом на нейтрализующую активность протестированных моноклональных антител (Фиг. 13А). В частности, вариант E484K не нейтрализовался 7 из 11 антител. Три антитела, - iB14, iB20 и REGN10987 сохраняли активность в отношении этого варианта, в то время как нейтрализующая активность REGN10933 была снижена в ~11 раз. F490L полностью блокировал активность iB12 и iB15, снижал активность iB3 и COV2-2504 примерно в 20 раз, и незначительно снижал активность iB9, iB20 и COVA2-15. Антитело iB20 теряло нейтрализующую активность по отношению к вариантам N460T и A475V. В соответствии с опубликованными данными замена K417N приводила к снижению нейтрализующей активности REGN10933, а варианты N439K и K444Q негативно влияли на активность REGN10987 (Starr, T.N. et al. Prospective mapping of viral mutations that escape antibodies used to treat COVID-19. Science 371, 850–854 (2021); Baum, A. et al. Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science 369, 1014–1018 (2020)). Важно отметить, что ни одна из последних трех замен не влияла на нейтрализующую активность полученных нами моноклональных нейтрализующих антител. Из исследованных моноклональных антител лишь одно, COVA2-15, проявляло умеренную чувствительность к варианту N501Y в соответствии с опубликованными данными (Shen, X. et al. SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral Spike vaccines. Cell Host Microbe. 29, 529-539.e3 (2021)).Our data indicate that three of the studied viral variants - E484K, F486K and F490L have the greatest negative effect on the neutralizing activity of the tested monoclonal antibodies (Fig. 13A). In particular, the E484K variant was not neutralized by 7 out of 11 antibodies. Three antibodies, iB14, iB20, and REGN10987, retained activity against this variant, while the neutralizing activity of REGN10933 was reduced by ~11-fold. F490L completely blocked the activity of iB12 and iB15, reduced the activity of iB3 and COV2-2504 by about 20-fold, and slightly reduced the activity of iB9, iB20 and COVA2-15. The iB20 antibody lost its neutralizing activity against the N460T and A475V variants. According to published data, the K417N substitution led to a decrease in the neutralizing activity of REGN10933, while the N439K and K444Q variants negatively affected the activity of REGN10987 (Starr, T.N. et al. Prospective mapping of viral mutations that escape antibodies used to treat COVID-19. Science 371, 850 –854 (2021) Baum, A. et al Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Science 369, 1014–1018 (2020)). It is important to note that none of the last three substitutions affected the neutralizing activity of the monoclonal neutralizing antibodies we obtained. Of the studied monoclonal antibodies, only one, COVA2-15, showed moderate sensitivity to the N501Y variant in accordance with published data (Shen, X. et al. SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral Spike vaccines Cell Host Microbe 29, 529-539.e3 (2021)).

Затем мы проверили, сохраняют ли моноклональные антитела iB14 и iB20 нейтрализующую активность против вариантов Spike-белка с тремя заменами - K417, E484 и N501 (KEN) – в пределах RBD, поскольку данная комбинация замен встречается в двух кладах циркулирующих вариантов SARS-CoV-2, 501Y.V2 и 501Y.V3. В полном соответствии с данными, что индивидуальные замены приводят к устойчивости таких вариантов Spike к iB14 и iB20, а также к REGN10987, наблюдалось сохранение полной нейтрализующей активности этих трех антител по отношению к KEN-варианту Spike. Антитела iB6 и COVA2-15 при этом полностью теряли такую активность (Фиг. 13Б). Соответственно, композиции антитела iB6 с iB20 или REGN10987, а также антитела COVA2-15 с iB14 также полностью нейтрализовали данный вариант (Фиг. 14).We then tested whether monoclonal antibodies iB14 and iB20 retained neutralizing activity against three substitution variants of the Spike protein - K417, E484 and N501 (KEN) - within the RBD, since this combination of substitutions occurs in two clades of circulating SARS-CoV-2 variants. , 501Y.V2 and 501Y.V3. In full agreement with the findings that individual substitutions result in resistance of such Spike variants to iB14 and iB20, as well as to REGN10987, the full neutralizing activity of these three antibodies against the KEN variant of Spike was observed. Antibodies iB6 and COVA2-15 completely lost this activity (Fig. 13B). Accordingly, formulations of iB6 antibody with iB20 or REGN10987 as well as COVA2-15 antibody with iB14 also completely neutralized this variant (FIG. 14).

Наконец, отдельно была исследована способность моноклональных нейтрализующих антител iB6, iB14 и iB20 нейтрализовать лентивирусные частицы, псевдотипированные вариантами Spike-белка с заменами в RBD, присутствующими в кладах SARS-CoV-2 delta (B.1.617.2 (L452R + T478K)), kappa (B.1.617.1 (L452R + E484Q)) и lambda (C.37 (L452Q + F490S)), которые появились в циркуляции в 2020-2021 годах. Антитела iB14 и iB20 сохраняют активность на полном уровне в отношении этих трех вариантов вируса (Фиг. 13Б), в отличие от iB6, которое оказалось чувствительно к заменам по остатку L452. Таким образом, полученные данные свидетельствуют о возможности применения моноклональных антител iB14 и iB20 в качестве профилактики заражения и терапии пациентов, зараженных данными вариантами SARS-CoV-2.Finally, the ability of monoclonal neutralizing antibodies iB6, iB14, and iB20 to neutralize lentiviral particles pseudotyped with RBD substitutional Spike protein variants present in the SARS-CoV-2 delta clades (B.1.617.2 (L452R + T478K)), was separately investigated. kappa (B.1.617.1 (L452R + E484Q)) and lambda (C.37 (L452Q + F490S)), which appeared in circulation in 2020-2021. Antibodies iB14 and iB20 retain full activity against these three variants of the virus (Fig. 13B), in contrast to iB6, which was sensitive to substitutions at the L452 residue. Thus, the data obtained indicate the possibility of using monoclonal antibodies iB14 and iB20 as a prophylaxis of infection and therapy for patients infected with these variants of SARS-CoV-2.

Пример 7. Оценка способности RBD-специфических моноклональных антител узнавать RBD SARS-CoV-2, а также RBD циркулирующих вариантов вируса, delta и beta, в формате иммуноферментного анализа.Example 7 Evaluation of the ability of RBD-specific monoclonal antibodies to recognize the RBD of SARS-CoV-2, as well as the RBD of the circulating variants of the virus, delta and beta, in the format of an enzyme immunoassay.

С целью верификации возможности использования полученных RBD-специфических рекомбинантных моноклональных антител в диагностических целях был проведен иммуноферментный анализ их связывания с RBD Spike-белка SARS-CoV-2, соответствующих трем его вариантам (исходный изолят Wuhan-Hu-1, delta (замены L452R + T478K) и beta (замены K417N+E484K+N501Y, KEN). Антиген (RBD-His6) был разбавлен в 0,1 M NaHCO3 до концентрации 3 мкг/мл и перенесен в объеме 100 мкл в лунки 96-луночного планшета повышенной сорбции, Greiner Bio-One, Германия. После инкубирования в течение ночи при 4°C раствор, содержащий антиген, удаляли, промывали 5 раз отмывочным буфером, содержащим 0,1 M NaHCO3 и 0,1% Triton X-100, и проводили блокировку свободных центров связывания с использованием 150  мкл 2% (w/v) обезжиренного сухого молока (Santa Cruz, США) в 0,1 M NaHCO3 в течение 1 часа при комнатной температуре. Затем лунки 5 раз промывали отмывочным буфером и добавляли двукратные разведения антител в диапазоне от 1 мкг/мл до 7,5 нг/мл в отмывочном буфере (100 мкл на лунку). По завершении инкубирования при комнатной температуре в течение 1 часа лунки промывали 5 раз отмывочным буфером. Затем в каждую лунку добавляли по 100 мкл конъюгата мышиных моноклональных антител против IgG человека с пероксидазой (Вектор, Кольцово) (разведение 1:12000) в отмывочном буфере. Через 1час инкубирования планшета при комнатной температуре лунки промывали пять раз отмывочным буфером и добавляли 100 мкл субстратного раствора для пероксидазы: 0,5 M Na-цитратный буфер, pH 5,2, содержащий 5 мг/мл орто-фенилендиамина и 0,01% H2O2. После развития цветной реакции в течение 5-10 минут окрашивание останавливали внесением 0,5 М серной кислоты (100 мкл на лунку). Измерения оптической плотности сформированного в результате реакции продукта проводили при длине волны 490 нм (OD490) с использованием планшетного спектрофотометра Multiskan. Специфичность по отношению к RBD SARS-CoV-2 исходного изолята Wuhan-Hu-1 была подтверждена для всех приведенных в Таблице 2 антител. Вместе с тем необходимо отметить, что в соответствии с данными экспериментов по изучению чувствительности нейтрализующих моноклональных антител к разнообразным заменам в Spike-белке SARS-CoV-2, в том числе и присутствующим в циркулирующих вирусных вариантах (Пример 6), в формате иммуноферментного анализа обнаруживалась неспособность некоторых из моноклональных антител детектировать варианты RBD, соответствующие последовательностям Spike в кладах delta и beta. Другими словами, использование нечувствительных к указанным заменам антител (например, iB0, iB14, iB20) позволяет детектировать SARS-CoV-2 исходного типа, delta и beta, а использование комбинаций антител, напротив, теряющих сродство к RBD delta и/или beta, позволяет дифференцировать/типировать такие образцы и отличать от исходного, немутированного варианта, при проведении иммуноферментного анализа.In order to verify the possibility of using the obtained RBD-specific recombinant monoclonal antibodies for diagnostic purposes, an enzyme-linked immunosorbent assay of their binding to the RBD of the SARS-CoV-2 Spike protein corresponding to its three variants (original isolate Wuhan-Hu-1, delta (substitutions L452R + T478K) and beta (substitutions K417N+E484K+N501Y, KEN) The antigen (RBD-His6) was diluted in 0.1 M NaHCO 3 to a concentration of 3 µg/ml and transferred in a volume of 100 µl to the wells of a 96-well high absorption plate , Greiner Bio-One, Germany After an overnight incubation at 4°C, the solution containing the antigen was removed, washed 5 times with wash buffer containing 0.1 M NaHCO 3 and 0.1% Triton X-100, and blocked free binding sites using 150 µl of 2% (w/v) skimmed milk powder (Santa Cruz, USA) in 0.1 M NaHCO 3 for 1 hour at room temperature Then the wells were washed 5 times with wash buffer and 2-fold antibody dilutions were added in the range from 1 µg/ml to 7.5 ng/ml in wash buffer (100 µl per well). After incubation at room temperature for 1 hour, the wells were washed 5 times with wash buffer. Then, 100 µl of mouse monoclonal antibodies against human IgG peroxidase conjugate (Vector, Koltsovo) (1:12000 dilution) in wash buffer was added to each well. After a 1 hour incubation of the plate at room temperature, the wells were washed five times with wash buffer and 100 µl of peroxidase substrate solution was added: 0.5 M Na-citrate buffer, pH 5.2, containing 5 mg/ml o-phenylenediamine and 0.01% H 2 O 2 . After the development of a color reaction within 5-10 minutes, the staining was stopped by adding 0.5 M sulfuric acid (100 μl per well). Optical density measurements of the product formed as a result of the reaction were carried out at a wavelength of 490 nm (OD 490 ) using a Multiskan plate spectrophotometer. The RBD specificity of SARS-CoV-2 of the original Wuhan-Hu-1 isolate was confirmed for all antibodies listed in Table 2. At the same time, it should be noted that, in accordance with the data of experiments on the study of the sensitivity of neutralizing monoclonal antibodies to various substitutions in the SARS-CoV-2 Spike protein, including those present in circulating viral variants (Example 6), the inability of some of the monoclonal antibodies to detect RBD variants corresponding to Spike sequences in the delta and beta clades. In other words, the use of antibodies insensitive to these substitutions (for example, iB0, iB14, iB20) allows the detection of SARS-CoV-2 of the original type, delta and beta, and the use of combinations of antibodies, on the contrary, losing affinity for RBD delta and/or beta, allows differentiate/type such samples and distinguish from the original, non-mutated variant, when conducting enzyme immunoassay.

Название
антитела
Name
antibodies
RBD (Wuhan-Hu-1)RBD (Wuhan-Hu-1) RBD
(delta)
RBD
(delta)
RBD (beta)RBD (beta)
iB0iB0 ++ ++ ++ iB3iB3 ++ ++ -- iB4iB4 ++ ++ -- iB6iB6 ++ +/-+/- -- iB9iB9 ++ +/-+/- -- iB10iB10 +/-+/- -- -- iB11iB11 ++ ++ -- iB12iB12 ++ ++ -- iB13iB13 ++ -- ++ iB14iB14 ++ ++ ++ iB15iB15 ++ ++ -- iB17iB17 ++ ++ -- iB18iB18 ++ ++ -- iB19iB19 ++ ++ -- iB20iB20 ++ ++ ++ iB24iB24 ++ ++ -- iB26iB26 ++ ++ --

Таблица 2table 2

Пример 8. Оценка способности RBD-специфических моноклональных антител узнавать RBD и S-белок SARS-CoV-2 в условиях иммуноблоттинга.Example 8 Evaluation of the ability of RBD-specific monoclonal antibodies to recognize RBD and SARS-CoV-2 S protein under immunoblot conditions.

Важным свойством любого моноклонального антитела является его способность узнавать целевой антиген в условиях иммуноблоттинга, при которых данный антиген может быть полностью или частично денатурирован/ренатурирован. Как правило, антитела, узнающие линейные эпитопы, обладают способностью эффективно детектировать целевые антигены в условиях иммуноблотинга независимо от условий денатурации, а именно присутствия или отсутствия в системе восстановителей дисульфидных связей, таких как бета-меркаптоэтанол, дитиотреитол и т.д. Полученные в данной заявке антитела были протестированы на способность узнавать RBD и S-белок SARS-CoV-2 в иммуноблоттинге при добавлении или без добавления бета-меркаптоэтанола. Данные, полученные в результате этих экспериментов, суммированы в Табл. 3, и свидетельствуют о том, что в отсутствие восстановителя большинство протестированных RBD-специфических моноклональных антител способно распознавать RBD и S-белок SARS-CoV-2, т.е. такие агенты обладают потенциалом для использования в качестве инструмента детекции. В то же время необходимо отметить, что в денатурирующих условиях ни одно из антител не узнает RBD или S-белок, что косвенно указывает на то, что сайты связывания полученных антител представлены сложными конформационными эпитопами.An important property of any monoclonal antibody is its ability to recognize the target antigen under immunoblot conditions, under which the antigen can be completely or partially denatured/renatured. As a rule, antibodies recognizing linear epitopes are able to effectively detect target antigens under immunoblotting conditions, regardless of denaturation conditions, namely, the presence or absence of disulfide bond reducing agents, such as beta-mercaptoethanol, dithiothreitol, etc., in the system. The antibodies obtained in this application were tested for the ability to recognize the RBD and S protein of SARS-CoV-2 in immunoblotting with or without the addition of beta-mercaptoethanol. The data obtained from these experiments are summarized in Table. 3 and indicate that in the absence of a reducing agent, most of the tested RBD-specific monoclonal antibodies are able to recognize RBD and SARS-CoV-2 S protein, i.e. such agents have the potential to be used as a detection tool. At the same time, it should be noted that under denaturing conditions, none of the antibodies recognize RBD or S protein, which indirectly indicates that the binding sites of the obtained antibodies are represented by complex conformational epitopes.

Антитело iBAntibody iB 00 11 22 33 44 55 66 99 1010 11eleven 1212 1313 без b-МЭwithout b-ME ++ -/+-/+ -/+-/+ ++ -/+-/+ -/+-/+ ++ ++ -/+-/+ ++ ++ ++ с b-МЭwith b-ME -- -- -- -- -- -- -- -- -- -- -- -- Антитело iBAntibody iB 1414 1515 1616 1717 1818 1919 2020 2121 2424 2525 2626 без b-МЭwithout b-ME ++ ++ -/+-/+ -/+-/+ -/+-/+ -/+-/+ ++ ++ -/+-/+ -- -/+-/+ с b-МЭwith b-ME -- -- -- -- -- -- -- -- -- -- --

Таблица 3Table 3

Пример 9. Оценка уровня аутореактивности RBD-специфических моноклональных антител.Example 9. Assessment of the level of autoreactivity of RBD-specific monoclonal antibodies.

Чтобы узнать, обладают ли полученные моноклональные RBD-специфические антитела аутореактивностью, т.е. способностью связываться с антигенами человека, как это было показано для некоторых SARS-CoV-2-специфических антител (Kreer, C. et al. Longitudinal isolation of potent near-germline SARS-CoV-2-neutralizing antibodies from COVID-19 patients. Cell 182, 843–854.e12 (2020); Kreye, J. et al. A therapeutic non-self-reactive SARS-CoV-2 antibody protects from lung pathology in a COVID-19 hamster model. Cell 183, 1058–1069.e19 (2020)), был использован протокол иммуноокрашивания клеток линии HEp-2 с последующей детекцией при помощи проточной цитометрии. Для этого клетки данной линии открепляли от поверхности культурального пластика используя раствор Версена, трижды промывали PBS и фиксировали в 2% параформальдегиде на льду в течение 10 минут. Затем для пермеабилизации клеток к ним добавляли сапонин до финальной концентрации 0,05%. В качестве позитивных контролей использовали первичные антитела против актина (ab3280, Abcam) и BIP (ab21685, Abcam). Для всех последующих шагов иммуноокрашивания использовали FACS-буфер с сапонином. Суспензии клеток инкубировали с антителами (5 мкг/мл) в течение получаса, трижды отмывали, после чего к клеткам добавляли APC-конъюгированные антитела donkey-anti-human IgG (1:600) (Jackson ImmunoResearch), goat-anti-rabbit-Alexa488 (1:600, Thermo Fisher Scientific), или goat-anti-mouse-Alexa488 (1:600, Thermo Fisher Scientific). Клетки без добавления первичных антител (но с добавлением конъюгатов) использовали для определения уровня фоновой флуоресценции. Уровень аутореактивности рассчитывали по формуле: MFI(антитело)–MFI(фон)/MFI(фон) (Табл. 1). To find out if the obtained monoclonal RBD-specific antibodies are self-reactive, i.e. the ability to bind to human antigens, as has been shown for some SARS-CoV-2-specific antibodies (Kreer, C. et al. Longitudinal isolation of potent near-germline SARS-CoV-2-neutralizing antibodies from COVID-19 patients. Cell 182, 843–854.e12 (2020) Kreye, J. et al A therapeutic non-self-reactive SARS-CoV-2 antibody protects from lung pathology in a COVID-19 hamster model Cell 183, 1058–1069. e19 (2020)), a protocol was used for immunostaining of HEp-2 cells followed by detection using flow cytometry. To do this, the cells of this line were detached from the surface of the culture plastic using Versen's solution, washed three times with PBS, and fixed in 2% paraformaldehyde on ice for 10 minutes. Then, to permeabilize the cells, saponin was added to them to a final concentration of 0.05%. Primary antibodies against actin (ab3280, Abcam) and BIP (ab21685, Abcam) were used as positive controls. Saponin FACS buffer was used for all subsequent immunostaining steps. Cell suspensions were incubated with antibodies (5 μg/ml) for half an hour, washed three times, after which APC-conjugated donkey-anti-human IgG antibodies (1:600) (Jackson ImmunoResearch), goat-anti-rabbit-Alexa488 were added to the cells. (1:600, Thermo Fisher Scientific), or goat-anti-mouse-Alexa488 (1:600, Thermo Fisher Scientific). Cells without the addition of primary antibodies (but with the addition of conjugates) were used to determine the level of background fluorescence. The level of autoreactivity was calculated by the formula: MFI(antibody)–MFI(background)/MFI(background) (Table 1).

--->--->

Sequence Listing Information:Sequence Listing Information:

DTD Version: V1_3 DTD Version: V1_3

File Name: R211040 sequence listing.xml File Name: R211040 sequence listing.xml

Software Name: WIPO Sequence Software Name: WIPO Sequence

Software Version: 1.1.0 Software Version: 1.1.0

Production Date: 2021-12-28 Production Date: 2021-12-28

General Information:General Information:

Current application / Applicant file reference: R21100410 Current application / Applicant file reference: R21100410

Applicant name: Общество с ограниченной ответственностью "Имген+" Applicant name: Limited Liability Company "Imgen+"

Applicant name / Language: ru Applicant name / Language: en

Applicant name / Name Latin: Obshchestvo s ogranichennoj otvetstvennostju Applicant name / Name Latin: Obshchestvo s ogranichennoj otvetstvennostju

"Imgen+" "Imgen+"

Invention title: Моноклональные антитела против рецептор-связывающего Invention title: Anti-receptor-binding monoclonal antibody

домена SPIKE-белка вируса SARS-COV-2 и их антигенсвязывающие фрагменты, SPIKE protein domain of the SARS-COV-2 virus and their antigen-binding fragments,

кодирующие их нуклеиновые кислоты, а также способы применения (Ru) nucleic acids encoding them, as well as methods of application (Ru)

Sequence Total Quantity: 322 Sequence Total Quantity: 322

Sequences: sequences:

Sequence Number (ID): 1 Sequence Number (ID): 1

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Residues: Residents:

GFTFSSYA 8 GFTFSSYA 8

Sequence Number (ID): 2 Sequence Number (ID): 2

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH1 > NOTE, CDRH1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

GFSFNTYS 8 GFSFNTYS 8

Sequence Number (ID): 3 Sequence Number (ID): 3

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH1 > NOTE, CDRH1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

GGSLSGYY 8 GGSLSGYY 8

Sequence Number (ID): 4 Sequence Number (ID): 4

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH1 > NOTE, CDRH1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

GYTFTGYY 8 GYTFTGYY 8

Sequence Number (ID): 5 Sequence Number (ID): 5

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH1 > NOTE, CDRH1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

GYTFTGYY 8 GYTFTGYY 8

Sequence Number (ID): 6 Sequence Number (ID): 6

Length: 10 Length: 10

Molecule Type: AA Molecule Type: AA

Residues: Residents:

GGSISSGDYY 10 GGSISSGDYY 10

Sequence Number (ID): 7 Sequence Number (ID): 7

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH1 > NOTE, CDRH1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

GGTFITYA 8 GGTFITYA 8

Sequence Number (ID): 8 Sequence Number (ID): 8

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH1 > NOTE, CDRH1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

GGTFSNYA 8 GGTFSNYA 8

Sequence Number (ID): 9 Sequence Number (ID): 9

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Residues: Residents:

GFTFSDYY 8 GFTFSDYY 8

Sequence Number (ID): 10 Sequence Number (ID): 10

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH1 > NOTE, CDRH1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

GYTFTSYY 8 GYTFTSYY 8

Sequence Number (ID): 11 Sequence Number (ID): 11

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH1 > NOTE, CDRH1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

GYLFTGYY 8 GYLFTGYY 8

Sequence Number (ID): 12 Sequence Number (ID): 12

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH1 > NOTE, CDRH1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

GFTFSSYA 8 GFTFSSYA 8

Sequence Number (ID): 13 Sequence Number (ID): 13

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH1 > NOTE, CDRH1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

GFTFPSSA 8 GFTFPSSA 8

Sequence Number (ID): 14 Sequence Number (ID): 14

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH1 > NOTE, CDRH1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

GYTFTNYD 8 GYTFTNYD 8

Sequence Number (ID): 15 Sequence Number (ID): 15

Length: 10 Length: 10

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..10 - SOURCE, 1..10

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH1 > NOTE, CDRH1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

GGSISSSSYY 10 GGSISSSSYY 10

Sequence Number (ID): 16 Sequence Number (ID): 16

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH1 > NOTE, CDRH1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

GYTFTSYY 8 GYTFTSYY 8

Sequence Number (ID): 17 Sequence Number (ID): 17

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Residues: Residents:

GFTVSSNY 8 GFTVSSNY 8

Sequence Number (ID): 18 Sequence Number (ID): 18

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH1 > NOTE, CDRH1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EFTVSSNY 8 EFTVSSNY 8

Sequence Number (ID): 19 Sequence Number (ID): 19

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Residues: Residents:

GFTVSRNY 8 GFTVSRNY 8

Sequence Number (ID): 20 Sequence Number (ID): 20

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH1 > NOTE, CDRH1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

GFTFSSYA 8 GFTFSSYA 8

Sequence Number (ID): 21 Sequence Number (ID): 21

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Residues: Residents:

GFTVSSNY 8 GFTVSSNY 8

Sequence Number (ID): 22 Sequence Number (ID): 22

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH1 > NOTE, CDRH1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

GLTVSSNY 8 GLTVSSNY 8

Sequence Number (ID): 23 Sequence Number (ID): 23

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH1 > NOTE, CDRH1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

GFTFSSYG 8 GFTFSSYG 8

Sequence Number (ID): 24 Sequence Number (ID): 24

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ISYDGSNK 8 ISYDGSNK 8

Sequence Number (ID): 25 Sequence Number (ID): 25

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ISSSGSIL 8 ISSGSIL 8

Sequence Number (ID): 26 Sequence Number (ID): 26

Length: 10 Length: 10

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..10 - SOURCE, 1..10

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ITQSGGT 7 ITQSGGT 7

Sequence Number (ID): 27 Sequence Number (ID): 27

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

INPNSGAT 8 INPNSGAT 8

Sequence Number (ID): 28 Sequence Number (ID): 28

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

INPNSGGT 8 INPNSGGT 8

Sequence Number (ID): 29 Sequence Number (ID): 29

Length: 10 Length: 10

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..10 - SOURCE, 1..10

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

IFYSGST 7 IFYSGST 7

Sequence Number (ID): 30 Sequence Number (ID): 30

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

IIPILGIT 8 IIPILGIT 8

Sequence Number (ID): 31 Sequence Number (ID): 31

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

IIPILGIA 8 IIPILGIA 8

Sequence Number (ID): 32 Sequence Number (ID): 32

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ISSSGSTI 8 ISSGSTI 8

Sequence Number (ID): 33 Sequence Number (ID): 33

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

INPSGGST 8 INPSGGST 8

Sequence Number (ID): 34 Sequence Number (ID): 34

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

INPNSGGT 8 INPNSGGT 8

Sequence Number (ID): 35 Sequence Number (ID): 35

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

VSGSGGST 8 VSGSGGST 8

Sequence Number (ID): 36 Sequence Number (ID): 36

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

IVVGSGNT 8 IVVGSGNT 8

Sequence Number (ID): 37 Sequence Number (ID): 37

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

MNPNSGNT 8 MNPNSGNT 8

Sequence Number (ID): 38 Sequence Number (ID): 38

Length: 10 Length: 10

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..10 - SOURCE, 1..10

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

IYYSGST 7 IYYSGST 7

Sequence Number (ID): 39 Sequence Number (ID): 39

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

INPSGGST 8 INPSGGST 8

Sequence Number (ID): 40 Sequence Number (ID): 40

Length: 10 Length: 10

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..10 - SOURCE, 1..10

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

IYSGGST 7 IYSGGST 7

Sequence Number (ID): 41 Sequence Number (ID): 41

Length: 10 Length: 10

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..10 - SOURCE, 1..10

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

IYSGGST 7 IYSGGST 7

Sequence Number (ID): 42 Sequence Number (ID): 42

Length: 10 Length: 10

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..10 - SOURCE, 1..10

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

IYSGGST 7 IYSGGST 7

Sequence Number (ID): 43 Sequence Number (ID): 43

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ISGSGGST 8 ISGSGGST 8

Sequence Number (ID): 44 Sequence Number (ID): 44

Length: 10 Length: 10

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..10 - SOURCE, 1..10

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

IYSGGST 7 IYSGGST 7

Sequence Number (ID): 45 Sequence Number (ID): 45

Length: 10 Length: 10

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..10 - SOURCE, 1..10

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

IYSGGST 7 IYSGGST 7

Sequence Number (ID): 46 Sequence Number (ID): 46

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH2 > NOTE, CDRH2

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ISYDGSNK 8 ISYDGSNK 8

Sequence Number (ID): 47 Sequence Number (ID): 47

Length: 20 Length: 20

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..20 - SOURCE, 1..20

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ARARPWRYSY GLYYYYGMDV 20 ARARPWRYSY GLYYYYGMDV 20

Sequence Number (ID): 48 Sequence Number (ID): 48

Length: 20 Length: 20

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..20 - SOURCE, 1..20

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ARVGTRVGAS NFDYYYGMDV 20 ARVGTRVGAS NFDYYYGMDV 20

Sequence Number (ID): 49 Sequence Number (ID): 49

Length: 17 Length: 17

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..17 - SOURCE, 1..17

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ARGGYDDNRG YYAYFDY 17 ARGGYDDNRG YYAYFDY 17

Sequence Number (ID): 50 Sequence Number (ID): 50

Length: 28 Length: 28

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..28 - SOURCE, 1..28

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ARVAQVVSNP LPYDVLTGLT YYYYGMDV 28 ARVAQVVSNP LPYDVLTGLT YYYYGMDV 28

Sequence Number (ID): 51 Sequence Number (ID): 51

Length: 14 Length: 14

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..14 - SOURCE, 1..14

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ARDYYYDSSV NPDY 14 ARDYYYDSSV NPDY 14

Sequence Number (ID): 52 Sequence Number (ID): 52

Length: 15 Length: 15

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..15 - SOURCE, 1..15

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ARRCRFVDTS MAFDY 15 ARRCRFVDTS MAFDY 15

Sequence Number (ID): 53 Sequence Number (ID): 53

Length: 14 Length: 14

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..14 - SOURCE, 1..14

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ARGGRGANPG WFDY 14 ARGGRGANPG WFDY 14

Sequence Number (ID): 54 Sequence Number (ID): 54

Length: 16 Length: 16

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..16 - SOURCE, 1..16

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ARTAYEYDSS GYFLDY 16 ARTAYEYDSS GYFLDY 16

Sequence Number (ID): 55 Sequence Number (ID): 55

Length: 13 Length: 13

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..13 - SOURCE, 1..13

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ARHPMVRGVI GDY 13 ARHPMVRGVI GDY 13

Sequence Number (ID): 56 Sequence Number (ID): 56

Length: 18 Length: 18

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..18 - SOURCE, 1..18

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: residences:

ARGHSGYDRL PQPPYFDY 18 ARGHSGYDRL PQPPYFDY 18

Sequence Number (ID): 57 Sequence Number (ID): 57

Length: 14 Length: 14

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..14 - SOURCE, 1..14

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ARSGYYTSAV NFDY 14 ARSGYYTSAV NFDY 14

Sequence Number (ID): 58 Sequence Number (ID): 58

Length: 25 Length: 25

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..25 - SOURCE, 1..25

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

AKTVLAGRDD SSGYFTVYYY FGMDV 25 AKTVLAGRDD SSGYFTVYYY FGMDV 25

Sequence Number (ID): 59 Sequence Number (ID): 59

Length: 16 Length: 16

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..16 - SOURCE, 1..16

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

AAPYCSGGSC YDGFDI 16 AAPYCSGGSC YDGFDI 16

Sequence Number (ID): 60 Sequence Number (ID): 60

Length: 24 Length: 24

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..24 - SOURCE, 1..24

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ARAYQNRPIA VTDMGYYYYY GMDV 24 ARAYQNRPIA VTDMGYYYYY GMDV 24

Sequence Number (ID): 61 Sequence Number (ID): 61

Length: 16 Length: 16

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..16 - SOURCE, 1..16

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ARGGSIYDYG DYEFDS 16 ARGGSIYDYG DYEFDS 16

Sequence Number (ID): 62 Sequence Number (ID): 62

Length: 14 Length: 14

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..14 - SOURCE, 1..14

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

AILGLHLGEL LFDP 14 AILGLHLGEL LFDP 14

Sequence Number (ID): 63 Sequence Number (ID): 63

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ARDFGEQWFD Y 11 ARDFGEQWFD Y 11

Sequence Number (ID): 64 Sequence Number (ID): 64

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ARDFGDYYFD Y 11 ARDFGDYYFD Y 11

Sequence Number (ID): 65 Sequence Number (ID): 65

Length: 12 Length: 12

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..12 - SOURCE, 1..12

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ARDLLEVGGS DY 12 ARDLLEVGGS DY 12

Sequence Number (ID): 66 Sequence Number (ID): 66

Length: 21 Length: 21

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..21 - SOURCE, 1..21

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

AKPLLGYDFW SGYYRGGWFD P 21 AKPLLGYDFW SGYYRGGWFD P 21

Sequence Number (ID): 67 Sequence Number (ID): 67

Length: 13 Length: 13

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..13 - SOURCE, 1..13

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ARDPYSYGRG GGY 13 ARDPYSYGRG GGY 13

Sequence Number (ID): 68 Sequence Number (ID): 68

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

ARDGVYYGMD V 11 ARDGVYYGMD V 11

Sequence Number (ID): 69 Sequence Number (ID): 69

Length: 17 Length: 17

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..17 - SOURCE, 1..17

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRH3 > NOTE, CDRH3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

AKDYDFWSGY YPQPFDY 17 AKDYDFWSGY YPQPFDY 17

Sequence Number (ID): 70 Sequence Number (ID): 70

Length: 9 Length: 9

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..9 - SOURCE, 1..9

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSISSY 6 QSISSY 6

Sequence Number (ID): 71 Sequence Number (ID): 71

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

SSNIGRNT 8 SSNIGRNT 8

Sequence Number (ID): 72 Sequence Number (ID): 72

Length: 12 Length: 12

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..12 - SOURCE, 1..12

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSVLYSFRNK IC 12 QSVLYSFRNK IC 12

Sequence Number (ID): 73 Sequence Number (ID): 73

Length: 12 Length: 12

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..12 - SOURCE, 1..12

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

SSDVGSYNL 9 SSDVGSYNL 9

Sequence Number (ID): 74 Sequence Number (ID): 74

Length: 9 Length: 9

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..9 - SOURCE, 1..9

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QDISNY 6 QDISNY 6

Sequence Number (ID): 75 Sequence Number (ID): 75

Length: 12 Length: 12

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..12 - SOURCE, 1..12

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

SSDVGSYDL 9 SSDVGSYDL 9

Sequence Number (ID): 76 Sequence Number (ID): 76

Length: 9 Length: 9

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..9 - SOURCE, 1..9

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSISSW 6 QSISSW 6

Sequence Number (ID): 77 Sequence Number (ID): 77

Length: 10 Length: 10

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..10 - SOURCE, 1..10

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSVSSSY 7 QSVSSSY 7

Sequence Number (ID): 78 Sequence Number (ID): 78

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

SSNIGSNT 8 SSNIGSNT 8

Sequence Number (ID): 79 Sequence Number (ID): 79

Length: 9 Length: 9

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..9 - SOURCE, 1..9

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSISKY 6 QSISKY 6

Sequence Number (ID): 80 Sequence Number (ID): 80

Length: 9 Length: 9

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..9 - SOURCE, 1..9

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QDISNY 6 QDISNY 6

Sequence Number (ID): 81 Sequence Number (ID): 81

Length: 12 Length: 12

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..12 - SOURCE, 1..12

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

SSDIGGYNY 9 SSDIGGYNY 9

Sequence Number (ID): 82 Sequence Number (ID): 82

Length: 10 Length: 10

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..10 - SOURCE, 1..10

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSVSSSY 7 QSVSSSY 7

Sequence Number (ID): 83 Sequence Number (ID): 83

Length: 12 Length: 12

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..12 - SOURCE, 1..12

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

SSDVGSYNL 9 SSDVGSYNL 9

Sequence Number (ID): 84 Sequence Number (ID): 84

Length: 9 Length: 9

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..9 - SOURCE, 1..9

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSISSW 6 QSISSW 6

Sequence Number (ID): 85 Sequence Number (ID): 85

Length: 9 Length: 9

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..9 - SOURCE, 1..9

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QDISNY 6 QDISNY 6

Sequence Number (ID): 86 Sequence Number (ID): 86

Length: 10 Length: 10

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..10 - SOURCE, 1..10

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSVSSSY 7 QSVSSSY 7

Sequence Number (ID): 87 Sequence Number (ID): 87

Length: 10 Length: 10

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..10 - SOURCE, 1..10

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSVSSSY 7 QSVSSSY 7

Sequence Number (ID): 88 Sequence Number (ID): 88

Length: 10 Length: 10

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..10 - SOURCE, 1..10

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSISSSY 7 QSISSSY 7

Sequence Number (ID): 89 Sequence Number (ID): 89

Length: 15 Length: 15

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..15 - SOURCE, 1..15

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSVLYSSNNK NY 12 QSVLYSSNNK NY 12

Sequence Number (ID): 90 Sequence Number (ID): 90

Length: 9 Length: 9

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..9 - SOURCE, 1..9

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QDISNY 6 QDISNY 6

Sequence Number (ID): 91 Sequence Number (ID): 91

Length: 9 Length: 9

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..9 - SOURCE, 1..9

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QGISSY 6 QGISSY 6

Sequence Number (ID): 92 Sequence Number (ID): 92

Length: 9 Length: 9

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..9 - SOURCE, 1..9

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL1 > NOTE, CDRL1

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QGIRND 6 QGIRND 6

Sequence Number (ID): 93 Sequence Number (ID): 93

Residues: Residents:

000 000

Sequence Number (ID): 94 Sequence Number (ID): 94

Residues: Residents:

000 000

Sequence Number (ID): 95 Sequence Number (ID): 95

Residues: Residents:

000 000

Sequence Number (ID): 96 Sequence Number (ID): 96

Residues: Residents:

000 000

Sequence Number (ID): 97 Sequence Number (ID): 97

Residues: Residents:

000 000

Sequence Number (ID): 98 Sequence Number (ID): 98

Residues: residences:

000 000

Sequence Number (ID): 99 Sequence Number (ID): 99

Residues: residences:

000 000

Sequence Number (ID): 100 Sequence Number (ID): 100

Residues: Residents:

000 000

Sequence Number (ID): 101 Sequence Number (ID): 101

Residues: Residents:

000 000

Sequence Number (ID): 102 Sequence Number (ID): 102

Residues: Residents:

000 000

Sequence Number (ID): 103 Sequence Number (ID): 103

Residues: residences:

000 000

Sequence Number (ID): 104 Sequence Number (ID): 104

Residues: Residents:

000 000

Sequence Number (ID): 105 Sequence Number (ID): 105

Residues: Residents:

000 000

Sequence Number (ID): 106 Sequence Number (ID): 106

Residues: Residents:

000 000

Sequence Number (ID): 107 Sequence Number (ID): 107

Residues: Residents:

000 000

Sequence Number (ID): 108 Sequence Number (ID): 108

Residues: Residents:

000 000

Sequence Number (ID): 109 Sequence Number (ID): 109

Residues: Residents:

000 000

Sequence Number (ID): 110 Sequence Number (ID): 110

Residues: Residents:

000 000

Sequence Number (ID): 111 Sequence Number (ID): 111

Residues: Residents:

000 000

Sequence Number (ID): 112 Sequence Number (ID): 112

Residues: Residents:

000 000

Sequence Number (ID): 113 Sequence Number (ID): 113

Residues: Residents:

000 000

Sequence Number (ID): 114 Sequence Number (ID): 114

Residues: Residents:

000 000

Sequence Number (ID): 115 Sequence Number (ID): 115

Residues: Residents:

000 000

Sequence Number (ID): 116 Sequence Number (ID): 116

Length: 12 Length: 12

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..12 - SOURCE, 1..12

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QQSYSTPGS 9 QQSYSTPGS 9

Sequence Number (ID): 117 Sequence Number (ID): 117

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

AAWDDSLNGL V 11 AAWDDSLNGL V 11

Sequence Number (ID): 118 Sequence Number (ID): 118

Length: 12 Length: 12

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..12 - SOURCE, 1..12

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QQFYSTPWT 9 QQFYSTPWT 9

Sequence Number (ID): 119 Sequence Number (ID): 119

Length: 10 Length: 10

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..10 - SOURCE, 1..10

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

CSYADSRTLV 10 CSYADSRTLV 10

Sequence Number (ID): 120 Sequence Number (ID): 120

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QQYDNLPPRV T 11 QQYDNLPPRV T 11

Sequence Number (ID): 121 Sequence Number (ID): 121

Length: 12 Length: 12

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..12 - SOURCE, 1..12

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

CSFAGSSPL 9 CSFAGSSPL 9

Sequence Number (ID): 122 Sequence Number (ID): 122

Length: 12 Length: 12

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..12 - SOURCE, 1..12

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QQYNSYSPM 9 QQYNSYSPM 9

Sequence Number (ID): 123 Sequence Number (ID): 123

Length: 12 Length: 12

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..12 - SOURCE, 1..12

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: residences:

HQYGSSPRT 9 HQYGSSPRT 9

Sequence Number (ID): 124 Sequence Number (ID): 124

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: residences:

AAWDDSLNGY V 11 AAWDDSLNGY V 11

Sequence Number (ID): 125 Sequence Number (ID): 125

Length: 12 Length: 12

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..12 - SOURCE, 1..12

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QQSYSTPPT 9 QQSYSTPPPT 9

Sequence Number (ID): 126 Sequence Number (ID): 126

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QQYDNLPPRL T 11 QQYDNLPPRL T 11

Sequence Number (ID): 127 Sequence Number (ID): 127

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

SSYTRSSTQV V 11 SSYTRSSTQV V 11

Sequence Number (ID): 128 Sequence Number (ID): 128

Length: 12 Length: 12

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..12 - SOURCE, 1..12

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QQYGTSPWT 9 QQYGTSPWT 9

Sequence Number (ID): 129 Sequence Number (ID): 129

Length: 12 Length: 12

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..12 - SOURCE, 1..12

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

CSYARISTPG FV 12 CSYARISTPG FV 12

Sequence Number (ID): 130 Sequence Number (ID): 130

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QQYNSYST 8 QQYNSYST 8

Sequence Number (ID): 131 Sequence Number (ID): 131

Length: 13 Length: 13

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..13 - SOURCE, 1..13

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QQYDNLLGVT 10 QQYDNLLGVT 10

Sequence Number (ID): 132 Sequence Number (ID): 132

Length: 12 Length: 12

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..12 - SOURCE, 1..12

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QQYGSSPRT 9 QQYGSSPRT 9

Sequence Number (ID): 133 Sequence Number (ID): 133

Length: 12 Length: 12

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..12 - SOURCE, 1..12

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QQYGSSPRT 9 QQYGSSPRT 9

Sequence Number (ID): 134 Sequence Number (ID): 134

Length: 10 Length: 10

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..10 - SOURCE, 1..10

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QQYGSSPPIT 10 QQYGSPPIT 10

Sequence Number (ID): 135 Sequence Number (ID): 135

Length: 10 Length: 10

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..10 - SOURCE, 1..10

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QQYYSTLLLT 10 QQYYSTLLLT 10

Sequence Number (ID): 136 Sequence Number (ID): 136

Length: 12 Length: 12

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..12 - SOURCE, 1..12

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QQYDNLPIT 9 QQYDNLPIT 9

Sequence Number (ID): 137 Sequence Number (ID): 137

Length: 11 Length: 11

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..11 - SOURCE, 1..11

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QHLNSYPSMY T 11 QHLNSYPSMY T 11

Sequence Number (ID): 138 Sequence Number (ID): 138

Length: 12 Length: 12

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..12 - SOURCE, 1..12

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, CDRL3 > NOTE, CDRL3

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

LQDYNYPRT 9 LQDYNYPRT 9

Sequence Number (ID): 139 Sequence Number (ID): 139

Length: 127 Length: 127

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..127 - SOURCE, 1..127

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EVQLVESGGG VVQPGRSLRL SCAASGFTFS SYAMHWVRQA PGKGLEWVAV ISYDGSNKYY 60 EVQLVESGGG VVQPGRSLRL SCAASGFTFS SYAMHWVRQA PGKGLEWVAV ISYDGSNKYY 60

ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCARAR PWRYSYGLYY YYGMDVWGQG 120 ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCARAR PWRYSYGLYY YYGMDVWGQG 120

TTVTVSS 127 TTVTVSS 127

Sequence Number (ID): 140 Sequence Number (ID): 140

Length: 127 Length: 127

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..127 - SOURCE, 1..127

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EVQLVESGGG LVQSGGSLRL SCAASGFSFN TYSMNWVRQA PGKGLEWVSY ISSSGSILHY 60 EVQLVESGGG LVQSGGSLRL SCAASGFSFN TYSMNWVRQA PGKGLEWVSY ISSSGSILHY 60

ADSVKGRLTI SRDNAKNSLY LQMNSLRAED TAVYYCARVG TRVGASNFDY YYGMDVWGQG 120 ADSVKGRLTI SRDNAKNSLY LQMNSLRAED TAVYYCARVG TRVGASNFDY YYGMDVWGQG 120

TTVTVSS 127 TTVTVSS 127

Sequence Number (ID): 141 Sequence Number (ID): 141

Length: 123 Length: 123

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..123 - SOURCE, 1..123

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QVQLRQWGSG LLKPSETLSL TCAVYGGSLS GYYWSYFRQP PGKGLEWIGE ITQSGGTNYN 60 QVQLRQWGSG LLKPSETLSL TCAVYGGSLS GYYWSYFRQP PGKGLEWIGE ITQSGGTNYN 60

PSLKSRITIS VDTSKNQFSL DLSSVTAADT AVYYCARGGY DDNRGYYAYF DYWGQGTLVT 120 PSLKSRITIS VDTSKNQFSL DLSSVTAADT AVYYCARGGY DDNRGYYAYF DYWGQGTLVT 120

VSS 123 VSS 123

Sequence Number (ID): 142 Sequence Number (ID): 142

Length: 135 Length: 135

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..135 - SOURCE, 1..135

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QVQLVQSGAE VKKPGASVKV SCKASGYTFT GYYIHWVRQA PGQGLEWMGW INPNSGATNY 60 QVQLVQSGAE VKKPGASVKV SCKASGYTFT GYYIHWVRQA PGQGLEWMGW INPNSGATNY 60

AQKFQGRVTV TRDTSISTAY MELSRLRSDD TAVYYCARVA QVVSNPLPYD VLTGLTYYYY 120 AQKFQGRVTV TRDTSISTAY MELSRLRSDD TAVYYCARVA QVVSNPLPYD VLTGLTYYYY 120

GMDVWGQGTT VTVSS 135 GMDVWGQGTT VTVSS 135

Sequence Number (ID): 143 Sequence Number (ID): 143

Length: 121 Length: 121

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..121 - SOURCE, 1..121

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QVQLVQSGAE VKKPGASVKV SCKASGYTFT GYYMHWVRQA PGQGLEWMGW INPNSGGTNY 60 QVQLVQSGAE VKKPGASVKV SCKASGYTFT GYYMHWVRQA PGQGLEWMGW INPNSGGTNY 60

AQKFQGRVTM TRDTSITTAY MELSRLRSDD TAVYYCARDY YYDSSVNPDY WGQGTLVTVS 120 AQKFQGRVTM TRDTSITTAY MELSRLRSDD TAVYYCARDY YYDSSVNPDY WGQGTLVTVS 120

S 121 S 121

Sequence Number (ID): 144 Sequence Number (ID): 144

Length: 123 Length: 123

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..123 - SOURCE, 1..123

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QVQLQESGPG LVKPSQTLSL TCTVSGGSIS SGDYYWSWIR QHPGKGLEWI GYIFYSGSTY 60 QVQLQESGPG LVKPSQTLSL TCTVSGGSIS SGDYYWSWIR QHPGKGLEWI GYIFYSGSTY 60

YNPSLKSRVT ISVDTSKNQF SLKLSSVTAA DTAVYYCARR CRFVDTSMAF DYWGQGTLVT 120 YNPSLKSRVT ISVDTSKNQF SLKLSSVTAA DTAVYYCARR CRFVDTSMAF DYWGQGTLVT 120

VSS 123 VSS 123

Sequence Number (ID): 145 Sequence Number (ID): 145

Length: 121 Length: 121

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..121 - SOURCE, 1..121

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QVQLVQSGAE VKKPGSSVKV SCKASGGTFI TYAFSWVRQA PGQGLEWMGR IIPILGITNY 60 QVQLVQSGAE VKKPGSSVKV SCKASGGTFI TYAFSWVRQA PGQGLEWMGR IIPILGITNY 60

AQKFQGRVTI TADKSTSTAY MELSSLRSED TAVYYCARGG RGANPGWFDY WGQGTLVTVS 120 AQKFQGRVTI TADKSTSTAY MELSSLRSED TAVYYCARGG RGANPGWFDY WGQGTLVTVS 120

S 121 S 121

Sequence Number (ID): 146 Sequence Number (ID): 146

Length: 123 Length: 123

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..123 - SOURCE, 1..123

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QVQLVQSGAE VKKPGSSVKV SCKASGGTFS NYAISWVRQA PGQGLEWMGR IIPILGIANY 60 QVQLVQSGAE VKKPGSSVKV SCKASGGTFS NYAISWVRQA PGQGLEWMGR IIPILGIANY 60

AQKFQGRLTI TADKSTSTAY MELSSLRSED TAVYYCARTA YEYDSSGYFL DYWGQGTLVT 120 AQKFQGRLTI TADKSTSTAY MELSSLRSED TAVYYCARTA YEYDSSGYFL DYWGQGTLVT 120

VSS 123 VSS 123

Sequence Number (ID): 147 Sequence Number (ID): 147

Length: 120 Length: 120

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..120 - SOURCE, 1..120

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EVQLLESGGG LVKPGGSLRL SCAASGFTFS DYYMSWIRQA PGKGLEWVSY ISSSGSTIYY 60 EVQLLESGGG LVKPGGSLRL SCAASGFTFS DYYMSWIRQA PGKGLEWVSY ISSSGSTIYY 60

ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARHP MVRGVIGDYW GQGTLVTVSS 120 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARHP MVRGVIGDYW GQGTLVTVSS 120

Sequence Number (ID): 148 Sequence Number (ID): 148

Length: 125 Length: 125

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..125 - SOURCE, 1..125

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QVQLVQSGAE VKKPGASVKV SCKASGYTFT SYYMHWVRQA PGQGLEWMGI INPSGGSTSY 60 QVQLVQSGAE VKKPGASVKV SCKASGYTFT SYYMHWVRQA PGQGLEWMGI INPSGGSTSY 60

VQKFQGRVTM TRDTSTSTVY MELSSLRFED TAVYYCARGH SGYDRLPQPP YFDYWGQGTL 120 VQKFQGRVTM TRDTSTSTVY MELSSLRFED TAVYYCARGH SGYDRLPQPP YFDYWGQGTL 120

VTVSS 125 VTVSS 125

Sequence Number (ID): 149 Sequence Number (ID): 149

Length: 121 Length: 121

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..121 - SOURCE, 1..121

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QVQLVQSGAE VKKPGASVKV SCKASGYLFT GYYMHWVRQA PGQGLEWMGW INPNSGGTNY 60 QVQLVQSGAE VKKPGASVKV SCKASGYLFT GYYMHWVRQA PGQGLEWMGW INPNSGGTNY 60

AQKFQDRVTM TRDTSITTAY MELSRLRSDD TAVYYCARSG YYTSAVNFDY WGQGTLVTVS 120 AQKFQDRVTM TRDTSITTAY MELSRLRSDD TAVYYCARSG YYTSAVNFDY WGQGTLVTVS 120

S 121 S 121

Sequence Number (ID): 150 Sequence Number (ID): 150

Length: 132 Length: 132

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..132 - SOURCE, 1..132

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EVQLLESGGG LVQPGGSLRL SCAASGFTFS SYAMSWVRQA PGKGLEWVSA VSGSGGSTYY 60 EVQLLESGGG LVQPGGSLRL SCAASGFTFS SYAMSWVRQA PGKGLEWVSA VSGSGGSTYY 60

ADSVKGRFTI SRDNSKNMLY LQMNSLRAED TAVYYCAKTV LAGRDDSSGY FTVYYYFGMD 120 ADSVKGRFTI SRDNSKNMLY LQMNSLRAED TAVYYCAKTV LAGRDDSSGY FTVYYYFGMD 120

VWGQGTTVTV SS 132 VWGQGTTVTV SS 132

Sequence Number (ID): 151 Sequence Number (ID): 151

Length: 123 Length: 123

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..123 - SOURCE, 1..123

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QVQLVQSGPE VKKPGTSVKV SCKASGFTFP SSAVQWVRQA RGQRLEWIGW IVVGSGNTNY 60 QVQLVQSGPE VKKPGTSVKV SCKASGFTFP SSAVQWVRQA RGQRLEWIGW IVVGSGNTNY 60

AQKFQERVTI TRDMSTSTAY MELSSLRSED TAVYYCAAPY CSGGSCYDGF DIWGQGTMVT 120 AQKFQERVTI TRDMSTSTAY MELSSLRSED TAVYYCAAPY CSGGSCYDGF DIWGQGTMVT 120

VSS 123 VSS 123

Sequence Number (ID): 152 Sequence Number (ID): 152

Length: 131 Length: 131

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..131 - SOURCE, 1..131

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QVQLVQSGAE VKKPGASVKV SCKASGYTFT NYDINWVRQA TGQGLEWMGW MNPNSGNTGF 60 QVQLVQSGAE VKKPGASVKV SCKASGYTFT NYDINWVRQA TGQGLEWMGW MNPNSGNTGF 60

AQKFQGRVTM TRNTSIRTVY MELSSLRSED TAVYYCARAY QNRPIAVTDM GYYYYYGMDV 120 AQKFQGRVTM TRNTSIRTVY MELSSLRSED TAVYYCARAY QNRPIAVTDM GYYYYYGMDV 120

WGQGTTVTVS S 131 WGQGTTVTVS S 131

Sequence Number (ID): 153 Sequence Number (ID): 153

Length: 124 Length: 124

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..124 - SOURCE, 1..124

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QLQLQESGPG LVKPSETLSL TCTVSGGSIS SSSYYWGWIR QPPGKGLEWI GSIYYSGSTY 60 QLQLQESGPG LVKPSETLSL TCTVSGGSIS SSSYYWGWIR QPPGKGLEWI GSIYYSGSTY 60

YNPSLKSRVT ISVDTSKNQF SLKLSSVTAA DTALYYCARG GSIYDYGDYE FDSWGQGTLV 120 YNPSLKSRVT ISVDTSKNQF SLKLSSVTAA DTALYYCARG GSIYDYGDYE FDSWGQGTLV 120

TVSS 124 TVSS 124

Sequence Number (ID): 154 Sequence Number (ID): 154

Length: 121 Length: 121

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..121 - SOURCE, 1..121

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QVQLVQSGAE VKKPGASVKV SCKASGYTFT SYYMHWVRQA PGQGLEWMGI INPSGGSTSY 60 QVQLVQSGAE VKKPGASVKV SCKASGYTFT SYYMHWVRQA PGQGLEWMGI INPSGGSTSY 60

AQKFQGRVTM TRDTSTSTVY MELSSLRSED TAVYYCAILG LHLGELLFDP WGQGTLVTVS 120 AQKFQGRVTM TRDTSTSTVY MELSSLRSED TAVYYCAILG LHLGELLFDP WGQGTLVTVS 120

S 121 S 121

Sequence Number (ID): 155 Sequence Number (ID): 155

Length: 117 Length: 117

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..117 - SOURCE, 1..117

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EVQLVESGGG LIQPGGSLRL SCAASGFTVS SNYMSWVRQA PGKGLEWVSV IYSGGSTFYA 60 EVQLVESGGG LIQPGGSLRL SCAASGFTVS SNYMSWVRQA PGKGLEWVSV IYSGGSTFYA 60

DSVKGRFTIS RDNSKNTLYL QMNSLRAEDT AVYYCARDFG EQWFDYWGQG TLVTVSS 117 DSVKGRFTIS RDNSKNTLYL QMNSLRAEDT AVYYCARDFG EQWFDYWGQG TLVTVSS 117

Sequence Number (ID): 156 Sequence Number (ID): 156

Length: 117 Length: 117

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..117 - SOURCE, 1..117

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EVQLVESGGG LVQPGGSLRL SCAASEFTVS SNYMSWVRQA PGKGLEWVSV IYSGGSTYYA 60 EVQLVESGGG LVQPGGSLRL SCAASEFTVS SNYMSWVRQA PGKGLEWVSV IYSGGSTYYA 60

DSVKGRFTIS RDNSKNTLYL QMNSLRAEDT AVYYCARDFG DYYFDYWGQG TLVTVSS 117 DSVKGRFTIS RDNSKNTLYL QMNSLRAEDT AVYYCARDFG DYYFDYWGQG TLVTVSS 117

Sequence Number (ID): 157 Sequence Number (ID): 157

Length: 118 Length: 118

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..118 - SOURCE, 1..118

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EVQLVETGGG LIQPGGSLRL SCAASGFTVS RNYMSWVRQA PGKGLEWVSL IYSGGSTFYA 60 EVQLVETGGG LIQPGGSLRL SCAASGFTVS RNYMSWVRQA PGKGLEWVSL IYSGGSTFYA 60

DSVKGRFTIS RDDSKNTLYL QMNSLRAEDT AVYYCARDLL EVGGSDYWGQ GTLVTVSS 118 DSVKGRFTIS RDDSKNTLYL QMNSLRAEDT AVYYCARDLL EVGGSDYWGQ GTLVTVSS 118

Sequence Number (ID): 158 Sequence Number (ID): 158

Length: 128 Length: 128

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..128 - SOURCE, 1..128

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EVQLLESGGG LVQPGGSLRL SCAASGFTFS SYAMSWVRQA PGKGLEWVSA ISGSGGSTYY 60 EVQLLESGGG LVQPGGSLRL SCAASGFTFS SYAMSWVRQA PGKGLEWVSA ISGSGGSTYY 60

ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCAKPL LGYDFWSGYY RGGWFDPWGQ 120 ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCAKPL LGYDFWSGYY RGGWFDPWGQ 120

GTLVTVSS 128 GTLVTVSS 128

Sequence Number (ID): 159 Sequence Number (ID): 159

Length: 119 Length: 119

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..119 - SOURCE, 1..119

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EVQLVESGGG LIQPGGSLRL SCAASGFTVS SNYMSWVRQA PGKGLEWVSV IYSGGSTYYA 60 EVQLVESGGG LIQPGGSLRL SCAASGFTVS SNYMSWVRQA PGKGLEWVSV IYSGGSTYYA 60

DSVKGRFIIS RDNSKNTLYL QMNSLRAEDT AVYYCARDPY SYGRGGGYWG QGTLVTVSS 119 DSVKGRFIIS RDNSKNTLYL QMNSLRAEDT AVYYCARDPY SYGRGGGYWG QGTLVTVSS 119

Sequence Number (ID): 160 Sequence Number (ID): 160

Length: 117 Length: 117

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..117 - SOURCE, 1..117

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EVQLVETGGG LIQPGGSLRL SCAASGLTVS SNYMNWVRQA PGKGLEWVSV IYSGGSTYYA 60 EVQLVETGGG LIQPGGSLRL SCAASGLTVS SNYMNWVRQA PGKGLEWVSV IYSGGSTYYA 60

DSVKGRFTIS RDNSKNTLYL QMNSLRAEDT AVYYCARDGV YYGMDVWGQG TTVTVSS 117 DSVKGRFTIS RDNSKNTLYL QMNSLRAEDT AVYYCARDGV YYGMDVWGQG TTVTVSS 117

Sequence Number (ID): 161 Sequence Number (ID): 161

Length: 124 Length: 124

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..124 - SOURCE, 1..124

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VH > NOTE, VH

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EVQLVESGGG VVQPGRSLRL SCAASGFTFS SYGMHWVRQA PGKGLEWVAV ISYDGSNKYY 60 EVQLVESGGG VVQPGRSLRL SCAASGFTFS SYGMHWVRQA PGKGLEWVAV ISYDGSNKYY 60

ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCAKDY DFWSGYYPQP FDYWGQGTLV 120 ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCAKDY DFWSGYYPQP FDYWGQGTLV 120

TVSS 124 TVSS 124

Sequence Number (ID): 162 Sequence Number (ID): 162

Length: 107 Length: 107

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..107 - SOURCE, 1..107

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIQMTQSPSS LSASVGDRVT ITCRASQSIS SYLNWYQQKP GKAPKLLIYA ASSLQSGVPS 60 DIQMTQSPSS LSASVGDRVT ITCRASQSIS SYLNWYQQKP GKAPKLLIYA ASSLQSGVPS 60

RFSGSGSGTD FTLTISSLQP EDFATYYCQQ SYSTPGSFGQ GTKLEIK 107 RFSGSGSGTD FTLTISSLQP EDFATYYCQQ SYSTPGSFGQ GTKLEIK 107

Sequence Number (ID): 163 Sequence Number (ID): 163

Length: 110 Length: 110

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..110 - SOURCE, 1..110

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSVLTQPPSA SGTPGQRVTI SCSGSSSNIG RNTVNWYQQL PGTAPKLVIY SNNQRPSGVP 60 QSVLTQPPSA SGTPGQRVTI SCSGSSSNIG RNTVNWYQQL PGTAPKLVIY SNNQRPSGVP 60

DRFSGSKSGT SASLAISGLQ SEDEADYYCA AWDDSLNGLV FGGGTKLTVL 110 DRFSGSKSGT SASLAISGLQ SEDEADYYCA AWDDSLNGLV FGGGTKLTVL 110

Sequence Number (ID): 164 Sequence Number (ID): 164

Length: 113 Length: 113

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..113 - SOURCE, 1..113

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIVMTQSPDS LAVSLGERAT INCKSSQSVL YSFRNKICLA WYQQKPGQPP KLLIYWATTR 60 DIVMTQSPDS LAVSLGERAT INCKSSQSVL YSFRNKICLA WYQQKPGQPP KLLIYWATTR 60

ESGVPDRFSG SGSGTDFTLT ISSLQAEDVA VYYCQQFYST PWTFGQGTKV EIK 113 ESGVPDRFSG SGSGTDFTLT ISSLQAEDVA VYYCQQFYST PWTFGQGTKV EIK 113

Sequence Number (ID): 165 Sequence Number (ID): 165

Length: 110 Length: 110

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..110 - SOURCE, 1..110

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSALTQSASV SGSPGQPITI SCTGTSSDVG SYNLVSWYQQ HPGKAPKLMI YEVSKRPSGV 60 QSALTQSASV SGSPGQPITI SCTGTSSDVG SYNLVSWYQQ HPGKAPKLMI YEVSKRPSGV 60

SNRFSGSKSG NTASLTISGL QAEDEADYYC CSYADSRTLV FGGGTKLTVL 110 SNRFSGSKSG NTASLTISGL QAEDEADYYC CSYADSRTLV FGGGTKLTVL 110

Sequence Number (ID): 166 Sequence Number (ID): 166

Length: 109 Length: 109

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..109 - SOURCE, 1..109

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIQMTQSPSS LSASVGDRVT ITCQASQDIS NYLNWYQQKP GKAPKLLIYD ASNLETGVPS 60 DIQMTQSPSS LSASVGDRVT ITCQASQDIS NYLNWYQQKP GKAPKLLIYD ASNLETGVPS 60

RFSGSGSGTD FTFTISSLQP EDIATYYCQQ YDNLPPRVTF GQGTKVEIK 109 RFSGSGSGTD FTFTISSLQP EDIATYYCQQ YDNLPPRVTF GQGTKVEIK 109

Sequence Number (ID): 167 Sequence Number (ID): 167

Length: 109 Length: 109

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..109 - SOURCE, 1..109

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSALTQPASV SGSPGQSITI SCTGTSSDVG SYDLVSWYQQ HPGKAPKLMI YEVTKRPSGV 60 QSALTQPASV SGSPGQSITI SCTGTSSDVG SYDLVSWYQQ HPGKAPKLMI YEVTKRPSGV 60

SNRFSGSKSG NTASLTISGL QAEDEADYYC CSFAGSSPLF GGGTKLTVL 109 SNRFSGSKSG NTASLTISGL QAEDEADYYC CSFAGSSPLF GGGTKLTVL 109

Sequence Number (ID): 168 Sequence Number (ID): 168

Length: 107 Length: 107

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..107 - SOURCE, 1..107

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIQMTQSPST LSASVGDRVT ITCRASQSIS SWLAWYQQKP GKAPKVLIYK ASSLESGVPS 60 DIQMTQSPST LSASVGDRVT ITCRASQSIS SWLAWYQQKP GKAPKVLIYK ASSLESGVPS 60

RFSGSGSGTE FTLTISSLQP DDFATYYCQQ YNSYSPMFGQ GTKVEIK 107 RFSGSGSGTE FTLTISSLQP DDFATYYCQQ YNSYSPMFGQ GTKVEIK 107

Sequence Number (ID): 169 Sequence Number (ID): 169

Length: 108 Length: 108

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..108 - SOURCE, 1..108

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: residences:

EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQK PGQAPRLLIY GASSRATGIP 60 EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQK PGQAPRLLIY GASSRATGIP 60

DRFSGSGSGT DFTLTISRLE PEDFAVYYCH QYGSSPRTFG QGTKVEIK 108 DRFSGSGSGT DFTLTISRLE PEDFAVYYCH QYGSSPRTFG QGTKVEIK 108

Sequence Number (ID): 170 Sequence Number (ID): 170

Length: 110 Length: 110

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..110 - SOURCE, 1..110

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSVLTQPPSA SGTPGQRVTI SCSGSSSNIG SNTVNWYQQL PGTAPKLLIY NNNQRPSGVP 60 QSVLTQPPSA SGTPGQRVTI SCSGSSSNIG SNTVNWYQQL PGTAPKLLIY NNNQRPSGVP 60

DRFSGSKSGT SASLAISGLQ SEDEADYYCA AWDDSLNGYV FGTGTKVTVL 110 DRFSGSKSGT SASLAISGLQ SEDEADYYCA AWDDSLNGYV FGTGTKVTVL 110

Sequence Number (ID): 171 Sequence Number (ID): 171

Length: 107 Length: 107

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..107 - SOURCE, 1..107

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIQMTQSPSS LSTSVGDRVT ITCRASQSIS KYLNWYQQKP GKAPKLLIYA ASSLQSGVPS 60 DIQMTQSPSS LSTSVGDRVT ITCRASQSIS KYLNWYQQKP GKAPKLLIYA ASSLQSGVPS 60

RFSGSGSGTD FTLTISSLQP EDFATYYCQQ SYSTPPTFGQ GTKVEIK 107 RFSGSGSGTD FTLTISSLQP EDFATYYCQQ SYSTPPTFGQ GTKVEIK 107

Sequence Number (ID): 172 Sequence Number (ID): 172

Length: 109 Length: 109

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..109 - SOURCE, 1..109

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIQMTQSPSS LSASVGDRVT ITCQASQDIS NYLNWYQQKP GKAPKLLIYD ASNLETGVPS 60 DIQMTQSPSS LSASVGDRVT ITCQASQDIS NYLNWYQQKP GKAPKLLIYD ASNLETGVPS 60

RFSGSGSGTD FTFTISSLQP EDIATYYCQQ YDNLPPRLTF GGGTKVEIK 109 RFSGSGSGTD FTFTISSLQP EDIATYYCQQ YDNLPPRLTF GGGTKVEIK 109

Sequence Number (ID): 173 Sequence Number (ID): 173

Length: 111 Length: 111

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..111 - SOURCE, 1..111

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSALTQPASV SGSPGQSITI SCTGTSSDIG GYNYVSWYQQ HPGKAPKLMI YDVSNRPSGV 60 QSALTQPASV SGSPGQSITI SCTGTSSDIG GYNYVSWYQQ HPGKAPKLMI YDVSNRPSGV 60

SNRFSGSKSG NTASLTISGL QAEDEAEYYC SSYTRSSTQV VFGGGTKLTV L 111 SNRFSGSKSG NTASLTISGL QAEDEAEYYC SSYTRSSTQV VFGGGTKLTV L 111

Sequence Number (ID): 174 Sequence Number (ID): 174

Length: 108 Length: 108

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..108 - SOURCE, 1..108

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQK PGQAPRLLIY GASSRATGIP 60 EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQK PGQAPRLLIY GASSRATGIP 60

DRFSGSGSGT DFTLTISRLE PEDFAVYHCQ QYGTSPWTFG QGTKVEIK 108 DRFSGSGSGT DFTLTISRLE PEDFAVYHCQ QYGTSPWTFG QGTKVEIK 108

Sequence Number (ID): 175 Sequence Number (ID): 175

Length: 112 Length: 112

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..112 - SOURCE, 1..112

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSALTQPASV SGSPGQSITI SCTGTSSDVG SYNLVSWYQQ HPGKAPKLMI YEVSKRPSGV 60 QSALTQPASV SGSPGQSITI SCTGTSSDVG SYNLVSWYQQ HPGKAPKLMI YEVSKRPSGV 60

SNRFSGSKSG NTASLTISGL QAEDEADYYC CSYARISTPG FVFGTGTKVT VL 112 SNRFSGSKSG NTASLTISGL QAEDEADYYC CSYARISTPG FVFGTGTKVT VL 112

Sequence Number (ID): 176 Sequence Number (ID): 176

Length: 106 Length: 106

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..106 - SOURCE, 1..106

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIQMTQSPST LSASVGDRVT ITCRASQSIS SWLAWYQQKP GKAPKLLIYK ASNLESGVPS 60 DIQMTQSPST LSASVGDRVT ITCRASQSIS SWLAWYQQKP GKAPKLLIYK ASNLESGVPS 60

RFSGSGSGTE FTLTISSLQP DDFATYYCQQ YNSYSTFGQG TKVEIK 106 RFSGSGSGTE FTLTISSLQP DDFATYYCQQ YNSYSTFGQG TKVEIK 106

Sequence Number (ID): 177 Sequence Number (ID): 177

Length: 108 Length: 108

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..108 - SOURCE, 1..108

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIQMTQSPSS LSASLGDRVT ITCQASQDIS NYLNWYQQKP GKAPKLLIYD ASNLQTGVPS 60 DIQMTQSPSS LSASLGDRVT ITCQASQDIS NYLNWYQQKP GKAPKLLIYD ASNLQTGVPS 60

RFSGGGSGTD FTFTISSLQP EDIATYYCQQ YDNLLGVTFG PGTKVDIK 108 RFSGGGSGTD FTFTISSLQP EDIATYYCQQ YDNLLGVTFG PGTKVDIK 108

Sequence Number (ID): 178 Sequence Number (ID): 178

Length: 108 Length: 108

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..108 - SOURCE, 1..108

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQS PGQAPRLLIY GTSSRATGIP 60 EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQS PGQAPRLLIY GTSSRATGIP 60

DRFSGSGSGT DFTLTISRLE PEDFAVYYCQ QYGSSPRTFG QGTKVEIK 108 DRFSGSGSGT DFTLTISRLE PEDFAVYYCQ QYGSSPRTFG QGTKVEIK 108

Sequence Number (ID): 179 Sequence Number (ID): 179

Length: 108 Length: 108

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..108 - SOURCE, 1..108

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQK PGQAPRLLIY GASSRATGIP 60 EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQK PGQAPRLLIY GASSRATGIP 60

DRFSGSGSGT DFTLTISRLE PEDFAVYYCQ QYGSSPRTFG QGTKVEIK 108 DRFSGSGSGT DFTLTISRLE PEDFAVYYCQ QYGSSPRTFG QGTKVEIK 108

Sequence Number (ID): 180 Sequence Number (ID): 180

Length: 109 Length: 109

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..109 - SOURCE, 1..109

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EIVLTQSPGT LSLSPGERAT LSCRASQSIS SSYLAWYQQK PGQAPRLLFY GASSRATGIP 60 EIVLTQSPGT LSLSPGERAT LSCRASQSIS SSYLAWYQQK PGQAPRLLFY GASSRATGIP 60

DRFSGSGSGT DFTLTISKLE PEDFAVYYCQ QYGSSPPITF GQGTRLEIK 109 DRFSGSGSGT DFTLTISKLE PEDFAVYYCQ QYGSSPPITF GQGTRLEIK 109

Sequence Number (ID): 181 Sequence Number (ID): 181

Length: 114 Length: 114

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..114 - SOURCE, 1..114

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIVMTQSPDS LAVSLGERAT INCKSSQSVL YSSNNKNYLA WYQQKPGQPP KLLIYWASTR 60 DIVMTQSPDS LAVSLGERAT INCKSSQSVL YSSNNKNYLA WYQQKPGQPP KLLIYWASTR 60

ESGVPDRFSG SGSGTDFTLT ISSLQAEDVA VYYCQQYYST LLLTFGGGTK VEIK 114 ESGVPDRFSG SGSGTDFTLT ISSLQAEDVA VYYCQQYYST LLLTFGGGTK VEIK 114

Sequence Number (ID): 182 Sequence Number (ID): 182

Length: 107 Length: 107

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..107 - SOURCE, 1..107

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIQMTQSPSS LSASVGDRVT ITCQASQDIS NYLNWYQQKP GKAPKLLIYD ASNLETGVPS 60 DIQMTQSPSS LSASVGDRVT ITCQASQDIS NYLNWYQQKP GKAPKLLIYD ASNLETGVPS 60

RFSGSGSGTD FTFTISSLQP EDIATYYCQQ YDNLPITFGQ GTRLEIK 107 RFSGSGSGTD FTFTISSLQP EDIATYYCQQ YDNLPITFGQ GTRLEIK 107

Sequence Number (ID): 183 Sequence Number (ID): 183

Length: 109 Length: 109

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..109 - SOURCE, 1..109

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIQLTQSPSF LSASVGDRVT ITCRASQGIS SYLAWYQQKP GKAPKLLIFA ASTLQSGVPS 60 DIQLTQSPSF LSASVGDRVT ITCRASQGIS SYLAWYQQKP GKAPKLLIFA ASTLQSGVPS 60

RFSASGSGTE FTLTISSLQP EDFATYYCQH LNSYPSMYTF GQGTKLEIK 109 RFSASGSGTE FTLTISSLQP EDFATYYCQH LNSYPSMYTF GQGTKLEIK 109

Sequence Number (ID): 184 Sequence Number (ID): 184

Length: 107 Length: 107

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..107 - SOURCE, 1..107

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, VL > NOTE, VL

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIQMTQSPSS LSASVGDRVT ITCRASQGIR NDLGWYQQKP GKAPKLLIYA ASSLQSGVPS 60 DIQMTQSPSS LSASVGDRVT ITCRASQGIR NDLGWYQQKP GKAPKLLIYA ASSLQSGVPS 60

RFSGSGSGTD FTLTISSLQP EDFATYYCLQ DYNYPRTFGQ GTKVEIK 107 RFSGSGSGTD FTLTISSLQP EDFATYYCLQ DYNYPRTFGQ GTKVEIK 107

Sequence Number (ID): 185 Sequence Number (ID): 185

Length: 381 Length: 381

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..381 - source, 1..381

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gaggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60 gaggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60

tcctgtgcag cctctggatt caccttcagt agctatgcta tgcactgggt ccgccaggct 120 tcctgtgcag cctctggatt caccttcagt agctatgcta tgcactgggt ccgccaggct 120

ccaggcaagg ggctggagtg ggtggcagtt atatcgtatg atggaagtaa taaatactac 180 ccaggcaagg ggctggagtg ggtggcagtt atatcgtatg atggaagtaa taaatactac 180

gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240 gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240

ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gagagcccgt 300 ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gagagcccgt 300

ccgtggagat acagctatgg cctctactac tactacggta tggacgtctg gggccaaggg 360 ccgtggagat acagctatgg cctctactac tactacggta tggacgtctg gggccaaggg 360

accacggtca ccgtctcctc a 381 accacggtca ccgtctcctc a 381

Sequence Number (ID): 186 Sequence Number (ID): 186

Length: 381 Length: 381

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..381 - source, 1..381

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gaggtgcagc tggtggagtc tgggggaggc ttggtacagt cgggggggtc cctgagactc 60 gaggtgcagc tggtggagtc tgggggaggc ttggtacagt cgggggggtc cctgagactc 60

tcctgtgcag cctctggatt cagcttcaat acctatagca tgaactgggt ccgccaggct 120 tcctgtgcag cctctggatt cagcttcaat acctatagca tgaactgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtttcatac attagcagta gtggtagtat cttgcactac 180 ccagggaagg ggctggagtg ggtttcatac attagcagta gtggtagtat cttgcactac 180

gcagactctg tgaagggccg actcaccatt tccagagaca acgccaagaa ctcactgtat 240 gcagactctg tgaagggccg actcaccatt tccagagaca acgccaagaa ctcactgtat 240

ctgcaaatga acagcctgag agccgaggac acggctgtgt attactgtgc gagagtgggg 300 ctgcaaatga acagcctgag agccgaggac acggctgtgt attactgtgc gagagtgggg 300

acccgagtgg gagcttcaaa cttcgactac tactacggta tggacgtctg gggccaaggg 360 acccgagtgg gagcttcaaa cttcgactac tactacggta tggacgtctg gggccaaggg 360

accacggtca ccgtctcctc a 381 accacggtca ccgtctcctc a 381

Sequence Number (ID): 187 Sequence Number (ID): 187

Length: 369 Length: 369

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..369 - source, 1..369

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

caggtgcagc tacgccagtg gggctcagga ctgttgaagc cttcggagac cctgtccctc 60 caggtgcagc tacgccagtg gggctcagga ctgttgaagc cttcggagac cctgtccctc 60

acctgcgctg tgtatggtgg gtctctaagt ggttactact ggagctactt ccgccagccc 120 acctgcgctg tgtatggtgg gtctctaagt ggttactact ggagctactt ccgccagccc 120

ccagggaagg ggctggagtg gattggggaa atcactcaaa gtggcggcac caactacaac 180 ccagggaagg ggctggagtg gattggggaa atcactcaaa gtggcggcac caactacaac 180

ccgtccctca agagtcggat cacaatatca gtggacacgt ccaagaatca gttctctttg 240 ccgtccctca agagtcggat cacaatatca gtggacacgt ccaagaatca gttctctttg 240

gacctgagct ctgtgaccgc cgcggacacg gctgtgtatt actgtgcgag aggcggatac 300 gacctgagct ctgtgaccgc cgcggacacg gctgtgtatt actgtgcgag aggcggatac 300

gatgataata gaggttatta cgcgtatttt gactactggg gccagggaac cctggtcacc 360 gatgataata gaggttatta cgcgtatttt gactactggg gccagggaac cctggtcacc 360

gtctcctca 369 gtctcctca 369

Sequence Number (ID): 188 Sequence Number (ID): 188

Length: 405 Length: 405

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..405 - source, 1..405

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60 caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60

tcctgcaagg cttctggata caccttcacc ggctactata tacactgggt gcgacaggcc 120 tcctgcaagg cttctggata caccttcacc ggctactata tacactgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgc cacaaactat 180 cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgc cacaaactat 180

gcacagaagt ttcagggcag ggtcaccgtg accagggaca cgtccatcag cacagcctac 240 gcacagaagt ttcagggcag ggtcaccgtg accagggaca cgtccatcag cacagcctac 240

atggagctga gcaggctgag atctgacgac acggccgtgt attactgtgc gagagttgcc 300 atggagctga gcaggctgag atctgacgac acggccgtgt attactgtgc gagagttgcc 300

caagtcgtgt ccaacccact gccttacgat gttttgactg gtttaaccta ttactactac 360 caagtcgtgt ccaacccact gccttacgat gttttgactg gtttaaccta ttactactac 360

ggtatggacg tctggggcca agggaccacg gtcaccgtct cctca 405 ggtatggacg tctggggcca agggaccacg gtcaccgtct cctca 405

Sequence Number (ID): 189 Sequence Number (ID): 189

Length: 363 Length: 363

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..363 - source, 1..363

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60 caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60

tcctgcaagg cttctggata caccttcacc ggctactata tgcactgggt gcgacaggcc 120 tcctgcaagg cttctggata caccttcacc ggctactata tgcactgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgg cacaaactat 180 cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgg cacaaactat 180

gcacagaagt ttcagggcag ggtcaccatg accagggaca cgtccatcac cacagcctac 240 gcacagaagt ttcaggggcag ggtcaccatg accagggaca cgtccatcac cacagcctac 240

atggagctga gcaggctgag atctgacgac acggccgtgt attactgtgc gagagactac 300 atggagctga gcaggctgag atctgacgac acggccgtgt attactgtgc gagagactac 300

tactatgata gtagtgtgaa ccctgactac tggggccagg gaaccctggt caccgtctcc 360 tactatgata gtagtgtgaa ccctgactac tggggccagg gaaccctggt caccgtctcc 360

tca 363 tca 363

Sequence Number (ID): 190 Sequence Number (ID): 190

Length: 369 Length: 369

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..369 - source, 1..369

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

caggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60 caggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc 60

acctgcactg tctctggtgg ctccatcagc agtggtgatt actactggag ctggatccgc 120 acctgcactg tctctggtgg ctccatcagc agtggtgatt actactggag ctggatccgc 120

cagcacccag ggaagggcct ggagtggatt gggtacatct tttacagtgg gagcacctac 180 cagcacccag ggaagggcct ggagtggatt gggtacatct tttacagtgg gagcacctac 180

tacaacccgt ccctcaagag tcgggttacc atatcagtag acacgtctaa gaaccagttc 240 tacaacccgt ccctcaagag tcgggttacc atatcagtag acacgtctaa gaaccagttc 240

tccctgaagc tgagctctgt gactgccgcg gacacggccg tgtattactg tgcgaggagg 300 tccctgaagc tgagctctgt gactgccgcg gacacggccg tgtattactg tgcgaggagg 300

tgccgttttg tagatacatc tatggcattt gactactggg gccagggaac cctggtcacc 360 tgccgttttg tagatacatc tatggcattt gactactggg gccagggaac cctggtcacc 360

gtctcctca 369 gtctcctca 369

Sequence Number (ID): 191 Sequence Number (ID): 191

Length: 363 Length: 363

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..363 - source, 1..363

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60

tcctgcaagg cttctggagg caccttcatc acctatgctt tcagctgggt acgacaggcc 120 tcctgcaagg cttctggagg caccttcatc acctatgctt tcagctgggt acgacaggcc 120

cctggacaag ggcttgagtg gatgggaagg atcatcccta tccttggtat aacaaactac 180 ccttggacaag ggcttgagtg gatgggaagg atcatcccta tccttggtat aacaaactac 180

gcacagaagt tccagggcag agtcacgatt accgcggaca aatccacgag cacagcctac 240 240

atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc gagaggggga 300 atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc gagaggggga 300

cgcggtgcta accccggttg gtttgactac tggggccagg gaaccctggt caccgtctcc 360 cgcggtgcta accccggttg gtttgactac tggggccagg gaaccctggt caccgtctcc 360

tca 363 tca 363

Sequence Number (ID): 192 Sequence Number (ID): 192

Length: 369 Length: 369

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..369 - source, 1..369

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60

tcctgcaagg cttctggagg caccttcagc aactatgcta tcagctgggt gcgacaggcc 120 tcctgcaagg cttctggagg caccttcagc aactatgcta tcagctgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggaagg atcatcccta tccttggtat agcaaactac 180 ccttggacaag ggcttgagtg gatgggaagg atcatcccta tccttggtat agcaaactac 180

gcacagaagt tccagggcag actcacgatt accgcggaca aatccacgag cacagcctac 240 gcacagaagt tccaggggcag actcacgatt accgcggaca aatccacgag cacagcctac 240

atggagctga gcagcctaag atctgaggac acggccgtgt attactgtgc gaggacggcg 300 atggagctga gcagcctaag atctgaggac acggccgtgt attactgtgc gaggacggcg 300

tatgaatatg atagtagtgg ttatttcctt gactactggg gccagggaac cctggtcacc 360 tatgaatatg atagtagtgg ttatttcctt gactactggg gccagggaac cctggtcacc 360

gtctcctca 369 gtctcctca 369

Sequence Number (ID): 193 Sequence Number (ID): 193

Length: 360 Length: 360

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..360 - source, 1..360

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gaggtgcagc tgttggagtc tgggggaggc ttggtcaagc ctggagggtc cctgagactc 60 gaggtgcagc tgttggagtc tgggggaggc ttggtcaagc ctggagggtc cctgagactc 60

tcctgtgcag cctctggatt caccttcagt gactactaca tgagctggat ccgccaggct 120 tcctgtgcag cctctggatt caccttcagt gactactaca tgagctggat ccgccaggct 120

ccagggaagg ggctggagtg ggtttcatac attagtagta gtggtagtac catatactac 180 ccagggaagg ggctggagtg ggtttcatac attagtagta gtggtagtac catatactac 180

gcagactctg tgaagggccg attcaccatc tccagggaca acgccaagaa ctcactgtat 240 gcagactctg tgaagggccg attcaccatc tccagggaca acgccaagaa ctcactgtat 240

ctgcaaatga acagcctgag agccgaggac acggccgtgt attactgtgc gaggcatcct 300 ctgcaaatga acagcctgag agccgaggac acggccgtgt attactgtgc gaggcatcct 300

atggttcggg gagttatcgg agactactgg ggccagggaa ccctggtcac cgtctcctca 360 atggttcggg gagttatcgg agactactgg ggccagggaa ccctggtcac cgtctcctca 360

Sequence Number (ID): 194 Sequence Number (ID): 194

Length: 375 Length: 375

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..375 - source, 1..375

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtt 60 caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtt 60

tcctgcaagg catctggata caccttcacc agctactata tgcactgggt gcgacaggcc 120 tcctgcaagg catctggata caccttcacc agctactata tgcactgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggaata atcaacccta gtggaggtag cacaagctac 180 cctggacaag ggcttgagtg gatgggaata atcaacccta gtggaggtag cacaagctac 180

gtacagaagt tccagggcag agtcaccatg accagggaca cgtccacgag cacagtctac 240 gtacagaagt tccagggcag agtcaccatg accagggaca cgtccacgag cacagtctac 240

atggagctga gcagcctgag atttgaggac acggccgtgt attactgtgc gagaggtcat 300 atggagctga gcagcctgag atttgaggac acggccgtgt attactgtgc gagaggtcat 300

agtggctacg atcggttacc tcaaccccct tactttgact actggggcca gggaaccctg 360 agtggctacg atcggttacc tcaaccccct tactttgact actggggcca gggaaccctg 360

gtcaccgtct cctca 375 gtcaccgtct cctca 375

Sequence Number (ID): 195 Sequence Number (ID): 195

Length: 363 Length: 363

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..363 - source, 1..363

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60 caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60

tcctgcaagg cttctggata cctcttcacc ggctactata tgcactgggt gcgacaggcc 120 tcctgcaagg cttctggata cctcttcacc ggctactata tgcactgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgg cacaaactat 180 cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgg cacaaactat 180

gcacagaagt ttcaggacag ggtcaccatg accagggaca cgtccatcac cacagcctac 240 gcacagaagt ttcaggacag ggtcaccatg accagggaca cgtccatcac cacagcctac 240

atggagctga gcaggctgag atctgacgac acggccgtgt attactgtgc caggagtggt 300 atggagctga gcaggctgag atctgacgac acggccgtgt attactgtgc caggagtggt 300

tattatacga gtgctgtaaa ctttgactac tggggccagg gaaccctggt caccgtctcc 360 tattatacga gtgctgtaaa ctttgactac tggggccagg gaaccctggt caccgtctcc 360

tca 363 tca 363

Sequence Number (ID): 196 Sequence Number (ID): 196

Length: 396 Length: 396

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..396 - source, 1..396

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggatt cacctttagc agctatgcca tgagttgggt ccgccaggct 120 tcctgtgcag cctctggatt cacctttagc agctatgcca tgagttggggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagct gttagtggta gtggtggtag cacatactac 180 ccagggaagg ggctggagtg ggtctcagct gttagtggta gtggtggtag cacatactac 180

gcagactccg tgaagggccg gttcaccatc tccagagaca attccaagaa catgctgtat 240 gcagactccg tgaagggccg gttcaccatc tccagagaca attccaagaa catgctgtat 240

ctgcaaatga acagcctgag agccgaggac acggccgtat attactgtgc gaaaaccgtt 300 ctgcaaatga acagcctgag agccgaggac acggccgtat attactgtgc gaaaaccgtt 300

ttggctggtc gcgacgatag cagtggctac ttcacggttt actactactt cggtatggac 360 ttggctggtc gcgacgatag cagtggctac ttcacggttt actactactt cggtatggac 360

gtctggggcc aggggaccac ggtcaccgtc tcctca 396 gtctggggcc aggggaccac ggtcaccgtc tcctca 396

Sequence Number (ID): 197 Sequence Number (ID): 197

Length: 369 Length: 369

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..369 - source, 1..369

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

caggtgcagc tggtgcagtc tgggcctgag gtgaagaagc ctgggacctc agtgaaggtc 60 caggtgcagc tggtgcagtc tgggcctgag gtgaagaagc ctgggacctc agtgaaggtc 60

tcctgcaagg cttctggatt cacctttcct agctctgctg tgcagtgggt gcgacaggct 120 tcctgcaagg cttctggatt cacctttcct agctctgctg tgcagtgggt gcgacaggct 120

cgtggacaac gccttgagtg gataggatgg atcgtcgttg gcagtggtaa cacaaactac 180 cgtggacaac gccttgagtg gataggatgg atcgtcgttg gcagtggtaa cacaaactac 180

gcacagaagt tccaggaaag agtcaccatt accagggaca tgtccacaag cacagcctac 240 gcacagaagt tcggaaag agtcaccatt accagggaca tgtccacaag cacagcctac 240

atggagctga gcagcctgag atccgaggac acggccgtgt attactgtgc ggctccctat 300 atggagctga gcagcctgag atccgaggac acggccgtgt attactgtgc ggctccctat 300

tgtagtggtg gtagctgtta tgatggtttt gatatctggg gccaagggac aatggtcacc 360 tgtagtggtg gtagctgtta tgatggtttt gatatctggg gccaagggac aatggtcacc 360

gtctcttca 369 gtctcttca 369

Sequence Number (ID): 198 Sequence Number (ID): 198

Length: 393 Length: 393

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..393 -source, 1..393

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60 caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60

tcctgcaagg cttctggata caccttcacc aattatgata tcaactgggt gcgacaggcc 120 tcctgcaagg cttctggata caccttcacc aattatgata tcaactgggt gcgacaggcc 120

actggacaag ggcttgagtg gatgggatgg atgaacccta acagtggtaa cacaggcttt 180 actggacaag ggcttgagtg gatgggatgg atgaacccta acagtggtaa cacaggcttt 180

gcacagaagt tccagggcag agtcaccatg accaggaaca cctccataag aacagtctac 240 gcacagaagt tccagggcag agtcaccatg accaggaaca cctccataag aacagtctac 240

atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc gagagcctat 300 atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc gagagcctat 300

caaaatagac cgatagcagt aactgatatg ggttactact actactacgg tatggacgtc 360 caaaatagac cgatagcagt aactgatatg ggttactact actactacgg tatggacgtc 360

tggggccaag ggaccacggt caccgtctcc tca 393 tggggccaag ggaccacggt caccgtctcc tca 393

Sequence Number (ID): 199 Sequence Number (ID): 199

Length: 372 Length: 372

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..372 - source, 1..372

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: residences:

cagctgcagc tgcaggagtc gggcccagga ctggtgaagc cttcggagac cctgtccctc 60 cagctgcagc tgcaggagtc gggcccagga ctggtgaagc cttcggagac cctgtccctc 60

acctgcactg tctctggtgg ctccatcagc agtagtagtt actactgggg ctggatccgc 120 acctgcactg tctctggtgg ctccatcagc agtagtagtt actactgggg ctggatccgc 120

cagcccccag ggaaggggct ggagtggatt gggagtatct attatagtgg gagcacctac 180 cagcccccag ggaaggggct ggagtggatt gggagtatct attatagtgg gagcacctac 180

tacaacccgt ccctcaagag tcgagtcacc atatcagtag acacgtccaa gaaccagttc 240 tacaacccgt ccctcaagag tcgagtcacc atatcagtag acacgtccaa gaaccagttc 240

tccctgaagc tgagctctgt gaccgccgcg gacacggcct tgtattactg tgcgagaggg 300 tccctgaagc tgagctctgt gaccgccgcg gacacggcct tgtattactg tgcgagaggg 300

gggtcgatct atgactacgg tgactacgaa tttgactcct ggggccaggg aaccctggtc 360 gggtcgatct atgactacgg tgactacgaa tttgactcct ggggccaggg aaccctggtc 360

accgtctcct ca 372 accgtctcct ca 372

Sequence Number (ID): 200 Sequence Number (ID): 200

Length: 363 Length: 363

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..363 - source, 1..363

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtt 60 caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtt 60

tcctgcaagg catctggata caccttcacc agctactata tgcactgggt gcgacaggcc 120 tcctgcaagg catctggata caccttcacc agctactata tgcactgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggaata atcaacccta gtggtggtag cacaagctac 180 cctggacaag ggcttgagtg gatgggaata atcaacccta gtggtggtag cacaagctac 180

gcacagaagt tccagggcag agtcaccatg accagggaca cgtccacgag cacagtctac 240 240

atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc gatattaggg 300 atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc gatattaggg 300

ttacatttgg gggagttatt attcgacccc tggggccagg gaaccctggt caccgtctcc 360 ttacatttgg gggagttatt attcgacccc tggggccagg gaaccctggt caccgtctcc 360

tca 363 tca 363

Sequence Number (ID): 201 Sequence Number (ID): 201

Length: 351 Length: 351

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..351 - source, 1..351

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gaggtgcagc tggtggagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60 gaggtgcagc tggtggagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctcggggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120 tcctgtgcag cctcggggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac attctacgca 180 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac attctacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240 gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatttcgga 300 caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatttcgga 300

gaacagtggt ttgactactg gggccaggga accctggtca ccgtctcctc a 351 gaacagtggt ttgactactg gggccaggga accctggtca ccgtctcctc a 351

Sequence Number (ID): 202 Sequence Number (ID): 202

Length: 351 Length: 351

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..351 - source, 1..351

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60 gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgaatt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120 tcctgtgcag cctctgaatt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggcagatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240 gactccgtga agggcagatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag agatttcggg 300 caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag agatttcggg 300

gactactact ttgactactg gggccaggga accctggtca ccgtctcctc a 351 gactactact ttgactactg gggccaggga accctggtca ccgtctcctc a 351

Sequence Number (ID): 203 Sequence Number (ID): 203

Length: 354 Length: 354

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..354 - source, 1..354

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gaggtgcagc tggtggagac tggaggaggc ttgatccagc ctggggggtc cctgagactc 60 gaggtgcagc tggtggagac tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggctt caccgtcagt aggaactaca tgagctgggt ccgccaggct 120 tcctgtgcag cctctggctt caccgtcagt aggaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcactt atttatagtg gtggtagcac attctacgca 180 ccagggaagg ggctggagtg ggtctcactt atttatagtg gtggtagcac attctacgca 180

gactccgtga agggccgatt caccatctcc agagacgatt ccaagaacac gttgtatctt 240 gactccgtga agggccgatt caccatctcc agagacgatt ccaagaacac gttgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctcctc 300 caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctcctc 300

gaggtgggag gcagcgacta ctggggccag ggaaccctgg tcaccgtctc ctca 354 gaggtgggag gcagcgacta ctggggccag ggaaccctgg tcaccgtctc ctca 354

Sequence Number (ID): 204 Sequence Number (ID): 204

Length: 384 Length: 384

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..384 - source, 1..384

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggatt cacctttagc agctatgcca tgagctgggt ccgccaggct 120 tcctgtgcag cctctggatt cacctttagc agctatgcca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagct attagtggta gtggtggtag cacatactac 180 ccagggaagg ggctggagtg ggtctcagct attagtggta gtggtggtag cacatactac 180

gcagactccg tgaagggccg gttcaccatc tccagagaca attccaagaa cacgctgtat 240 gcagactccg tgaagggccg gttcaccatc tccagagaca attccaagaa cacgctgtat 240

ctgcaaatga acagcctgag agccgaggac acggccgtat attactgtgc gaaaccactc 300 ctgcaaatga acagcctgag agccgaggac acggccgtat attactgtgc gaaaccactc 300

ttggggtacg atttttggag tggttattat cggggtggct ggttcgaccc ctggggccag 360 ttggggtacg atttttggag tggttattat cggggtggct ggttcgaccc ctggggccag 360

ggaaccctgg tcaccgtctc ctca 384 ggaaccctgg tcaccgtctc ctca 384

Sequence Number (ID): 205 Sequence Number (ID): 205

Length: 357 Length: 357

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..357 - source, 1..357

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gaggtgcagc tggtggagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60 gaggtgcagc tggtggagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120 tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt catcatctcc agagacaatt ccaagaacac gctgtatctt 240 gactccgtga agggccgatt catcatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatccatac 300 caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatccatac 300

agctatggtc gaggtggcgg ctactggggc cagggaaccc tggtcaccgt ctcctca 357 agctatggtc gaggtggcgg ctactggggc cagggaaccc tggtcaccgt ctcctca 357

Sequence Number (ID): 206 Sequence Number (ID): 206

Length: 351 Length: 351

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..351 - source, 1..351

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gaggtgcagc tggtggagac tggaggaggc ttgatccagc ctggggggtc cctgagactc 60 gaggtgcagc tggtggagac tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggct caccgtcagt agcaactaca tgaactgggt ccgccaggct 120 tcctgtgcag cctctgggct caccgtcagt agcaactaca tgaactgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240 gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatggggtc 300 caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatggggtc 300

tactacggta tggacgtctg gggccaaggg accacggtca ccgtctcctc a 351 tactacggta tggacgtctg gggccaaggg accacggtca ccgtctcctc a 351

Sequence Number (ID): 207 Sequence Number (ID): 207

Length: 372 Length: 372

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..372 - source, 1..372

> mol_type, other DNA > mol_type, other DNA

> note, VH > note, VH

> organism, synthetic construct > organisms, synthetic constructs

Residues: residences:

gaggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60 gaggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60

tcctgtgcag cctctggatt caccttcagt agctatggca tgcactgggt ccgccaggct 120 tcctgtgcag cctctggatt caccttcagt agctatggca tgcactgggt ccgccaggct 120

ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactac 180 ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactac 180

gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240 gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240

ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gaaggattac 300 ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gaaggattac 300

gatttttgga gtggttatta cccccagccc tttgactact ggggccaggg aaccctggtc 360 gatttttgga gtggttatta cccccagccc tttgactact ggggccaggg aaccctggtc 360

accgtctcct ca 372 accgtctcct ca 372

Sequence Number (ID): 208 Sequence Number (ID): 208

Length: 321 Length: 321

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..321 - source, 1..321

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120 atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180 gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240 aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240

gaagattttg caacttacta ctgtcaacag agttacagta cccctggcag ttttggccag 300 gaagattttg caacttacta ctgtcaacag agttacagta cccctggcag ttttggccag 300

gggaccaagc tggagatcaa a 321 gggaccaagc tggagatcaa a 321

Sequence Number (ID): 209 Sequence Number (ID): 209

Length: 330 Length: 330

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..330 - source, 1..330

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

cagtctgtgc tgactcagcc accctcagcg tctgggaccc ccgggcagag ggtcaccatc 60 cagtctgtgc tgactcagcc accctcagcg tctgggaccc ccggggcagag ggtcaccatc 60

tcttgttctg gaagtagctc caacatcgga agaaatactg taaactggta ccagcagctc 120 120

ccaggaacgg cccccaaact cgtcatctat agtaataatc agcggccctc aggggtccct 180 cgggaacgg cccccaaact cgtcatctat agtaataatc agcggccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240 gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttactgtgca gcatgggatg acagcctgaa tggtctggta 300 tctgaggatg aggctgatta ttactgtgca gcatgggatg acagcctgaa tggtctggta 300

ttcggcggag ggaccaagct gaccgtccta 330 ttcggcggag ggaccaagct gaccgtccta 330

Sequence Number (ID): 210 Sequence Number (ID): 210

Length: 339 Length: 339

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..339 -source, 1..339

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gacatcgtga tgacccagtc tccagactcc ctggctgtgt ctctgggcga gagggccacc 60 gacatcgtga tgacccagtc tccagactcc ctggctgtgt ctctgggcga gagggccacc 60

atcaactgca agtccagcca gagtgtttta tacagcttca ggaataagat ctgcttagct 120 atcaactgca agtccagcca gagtgtttta tacagcttca ggaataagat ctgcttagct 120

tggtaccagc agaaaccagg acagcctcct aaactgctca tttactgggc aactacccgg 180 tggtaccagc agaaaccagg acagcctcct aaactgctca tttactgggc aactacccgg 180

gaatccgggg tccctgaccg attcagtggc agcgggtctg ggacagattt cactctcacc 240 gaatccgggg tccctgaccg attcagtggc agcgggtctg ggacagattt cactctcacc 240

atcagcagcc tgcaggctga agatgtggct gtttattact gtcagcaatt ttatagtact 300 atcagcagcc tgcaggctga agatgtggct gtttattact gtcagcaatt ttatagtact 300

ccgtggacgt tcggccaagg gaccaaggtg gaaatcaaa 339 ccgtggacgt tcggccaagg gaccaaggtg gaaatcaaa 339

Sequence Number (ID): 211 Sequence Number (ID): 211

Length: 330 Length: 330

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..330 - source, 1..330

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

cagtctgccc tgactcagtc tgcctccgtg tctgggtctc ctggacagcc gatcaccatc 60 cagtctgccc tgactcagtc tgcctccgtg tctgggtctc ctggacagcc gatcaccatc 60

tcctgcactg gaaccagcag tgatgttggg agttataacc ttgtctcctg gtaccaacag 120 tcctgcactg gaaccagcag tgatgttggg agttataacc ttgtctcctg gtaccaacag 120

cacccaggca aagcccccaa actcatgatt tatgaggtca gtaagcggcc ctcaggggtt 180 cacccaggca aagcccccaa actcatgatt tatgaggtca gtaagcggcc ctcaggggtt 180

tctaatcgct tctctggctc caagtctggc aacacggcct ccctgacaat ctctgggctc 240 tctaatcgct tctctggctc caagtctggc aacacggcct ccctgacaat ctctgggctc 240

caggctgagg acgaggctga ttattactgc tgctcatatg cagatagtag gactttggtg 300 caggctgagg acgaggctga ttattactgc tgctcatatg cagatagtag gactttggtg 300

ttcggcggag ggaccaagct gaccgtccta 330 ttcggcggag ggaccaagct gaccgtccta 330

Sequence Number (ID): 212 Sequence Number (ID): 212

Length: 327 Length: 327

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..327 - source, 1..327

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc aggcgagtca ggacattagc aactatttaa attggtatca gcagaaacca 120 atcacttgcc aggcgagtca ggacattagc aactatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctacgat gcatccaatt tggaaacagg ggtcccatca 180 gggaaagccc ctaagctcct gatctacgat gcatccaatt tggaaacagg ggtcccatca 180

aggttcagtg gaagtggatc tgggacagat tttactttca ccatcagcag cctgcagcct 240 aggttcagtg gaagtggatc tgggacagat tttactttca ccatcagcag cctgcagcct 240

gaagatattg caacatatta ctgtcaacag tatgataatc tccctccgag ggtgacgttc 300 gaagatattg caacatatta ctgtcaacag tatgataatc tccctccgag ggtgacgttc 300

ggccaaggga ccaaggtgga aatcaaa 327 ggccaaggga ccaaggtgga aatcaaa 327

Sequence Number (ID): 213 Sequence Number (ID): 213

Length: 327 Length: 327

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..327 - source, 1..327

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

cagtctgccc tgactcagcc tgcctccgtg tctgggtctc ctggacagtc gatcaccatc 60 cagtctgccc tgactcagcc tgcctccgtg tctgggtctc ctggacagtc gatcaccatc 60

tcctgcactg gaaccagcag tgatgttggg agttatgacc ttgtctcctg gtaccaacag 120 tcctgcactg gaaccagcag tgatgttggg agttatgacc ttgtctcctg gtaccaacag 120

cacccaggca aagcccccaa actcatgatt tatgaggtca ctaagcggcc ctcaggggtt 180 cacccaggca aagcccccaa actcatgatt tatgaggtca ctaagcggcc ctcaggggtt 180

tctaatcgct tctctggctc caagtctggc aacacggcct ccctgacaat ctctgggctc 240 tctaatcgct tctctggctc caagtctggc aacacggcct ccctgacaat ctctgggctc 240

caggctgagg acgaggctga ttattactgc tgctcatttg caggtagtag ccccttgttc 300 caggctgagg acgaggctga ttattactgc tgctcatttg caggtagtag ccccttgttc 300

ggcggaggga ccaagctgac cgtccta 327 ggcgggaggga ccaagctgac cgtccta 327

Sequence Number (ID): 214 Sequence Number (ID): 214

Length: 321 Length: 321

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..321 - source, 1..321

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gacatccaga tgacccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60 gacatccaga tgacccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gagtattagt agctggttgg cctggtatca gcagaaacca 120 atcacttgcc gggccagtca gagtattagt agctggttgg cctggtatca gcagaaacca 120

gggaaagccc ctaaggtcct gatctataag gcgtctagtt tagaaagtgg ggtcccatca 180 gggaaagccc ctaaggtcct gatctataag gcgtctagtt tagaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240 aggttcagcg gcagtggatc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240

gatgattttg caacttatta ctgccaacag tataatagtt attctccaat gttcggccaa 300 gatgattttg caacttatta ctgccaacag tataatagtt attctccaat gttcggccaa 300

gggaccaagg tggaaatcaa a 321 gggaccaagg tggaaatcaa a 321

Sequence Number (ID): 215 Sequence Number (ID): 215

Length: 324 Length: 324

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..324 - source, 1..324

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60 gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60

ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120 ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120

cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180 cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180

gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240 gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240

cctgaagatt ttgcagtgta ttactgtcac cagtatggta gctcacctcg aacgttcggc 300 cctgaagatt ttgcagtgta ttactgtcac cagtatggta gctcacctcg aacgttcggc 300

caagggacca aggtggagat caaa 324 caagggacca aggtggagat caaa 324

Sequence Number (ID): 216 Sequence Number (ID): 216

Length: 330 Length: 330

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..330 - source, 1..330

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

cagtctgtgc tgactcagcc accctcagcg tctgggaccc ccgggcagag ggtcaccatc 60 cagtctgtgc tgactcagcc accctcagcg tctgggaccc ccggggcagag ggtcaccatc 60

tcttgttctg gaagcagctc caacatcgga agtaatactg taaactggta ccagcagctc 120 120

ccaggaacgg cccccaaact cctcatctat aataataatc aacggccctc aggggtccct 180 cgggaacgg cccccaaact cctcatctat aataataatc aacggccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240 gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttactgtgca gcatgggatg acagcctgaa tggttatgtc 300 tctgaggatg aggctgatta ttactgtgca gcatgggatg acagcctgaa tggttatgtc 300

ttcggaactg ggaccaaggt caccgtccta 330 ttcggaactg ggaccaaggt caccgtccta 330

Sequence Number (ID): 217 Sequence Number (ID): 217

Length: 321 Length: 321

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..321 - source, 1..321

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gacatccaga tgacccagtc tccatcctcc ctgtctacat ctgtaggaga cagagtcacc 60 gacatccaga tgacccagtc tccatcctcc ctgtctacat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gagcattagc aagtatttaa attggtatca gcagaaacca 120 atcacttgcc gggcaagtca gagcattagc aagtatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180 gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240 aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240

gaagattttg caacttacta ctgtcaacag agttatagta cccctccgac gttcggccaa 300 gaagattttg caacttacta ctgtcaacag agttatagta cccctccgac gttcggccaa 300

gggaccaagg tggaaatcaa a 321 gggaccaagg tggaaatcaa a 321

Sequence Number (ID): 218 Sequence Number (ID): 218

Length: 327 Length: 327

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..327 - source, 1..327

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc aggcgagtca ggacattagc aactatttaa attggtatca gcagaaacca 120 atcacttgcc aggcgagtca ggacattagc aactatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctacgat gcatccaatt tggaaacagg ggtcccatca 180 gggaaagccc ctaagctcct gatctacgat gcatccaatt tggaaacagg ggtcccatca 180

aggttcagtg gaagtggatc tgggacagat tttactttca ccatcagcag cctgcagcct 240 aggttcagtg gaagtggatc tgggacagat tttactttca ccatcagcag cctgcagcct 240

gaagatattg ctacatatta ctgtcaacag tatgataatc tccctccgcg gctcactttc 300 gaagatattg ctacatatta ctgtcaacag tatgataatc tccctccgcg gctcactttc 300

ggcggaggga ccaaggtgga aatcaaa 327 ggcgggaggga ccaaggtgga aatcaaa 327

Sequence Number (ID): 219 Sequence Number (ID): 219

Length: 333 Length: 333

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..333 - source, 1..333

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

cagtctgccc tgactcagcc tgcctccgtg tctgggtctc ctggacagtc gatcaccatc 60 cagtctgccc tgactcagcc tgcctccgtg tctgggtctc ctggacagtc gatcaccatc 60

tcctgcactg gaaccagcag tgacattggt ggttataact atgtctcctg gtaccaacaa 120 tcctgcactg gaaccagcag tgacattggt ggttataact atgtctcctg gtaccaacaa 120

cacccaggca aagcccccaa actcatgatt tatgatgtca gtaatcggcc ctcaggggtt 180 cacccaggca aagcccccaa actcatgatt tatgatgtca gtaatcggcc ctcaggggtt 180

tctaatcgct tctctggctc caagtctggc aacacggcct ccctgaccat ctctgggctc 240 tctaatcgct tctctggctc caagtctggc aacacggcct ccctgaccat ctctgggctc 240

caggctgagg acgaggctga atattactgc agctcatata caagaagcag cactcaggtg 300 caggctgagg acgaggctga atattactgc agctcatata caagaagcag cactcaggtg 300

gtattcggcg gagggaccaa gctgaccgtc cta 333 gtattcggcg gagggaccaa gctgaccgtc cta 333

Sequence Number (ID): 220 Sequence Number (ID): 220

Length: 324 Length: 324

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..324 - source, 1..324

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60 gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60

ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120 ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120

cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180 cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180

gacaggttca gtggcagtgg gtctgggaca gacttcactc tcactatcag cagactggag 240 gacaggttca gtggcagtgg gtctgggaca gacttcactc tcactatcag cagactggag 240

cctgaagatt ttgcagtgta tcactgtcag cagtatggta cctcaccgtg gacgttcggc 300 cctgaagatt ttgcagtgta tcactgtcag cagtatggta cctcaccgtg gacgttcggc 300

caagggacca aggtggaaat caaa 324 caagggacca aggtggaaat caaa 324

Sequence Number (ID): 221 Sequence Number (ID): 221

Length: 336 Length: 336

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..336 - source, 1..336

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

cagtctgccc tgactcagcc tgcctccgtg tctgggtctc ctggacagtc gatcaccatc 60 cagtctgccc tgactcagcc tgcctccgtg tctgggtctc ctggacagtc gatcaccatc 60

tcctgcactg gaaccagcag tgatgttggg agttataacc ttgtctcctg gtaccaacag 120 tcctgcactg gaaccagcag tgatgttggg agttataacc ttgtctcctg gtaccaacag 120

cacccaggca aagcccccaa actcatgatt tatgaagtca gtaagcggcc ctcaggggtt 180 cacccaggca aagcccccaa actcatgatt tatgaagtca gtaagcggcc ctcaggggtt 180

tctaatcgct tctctggctc caagtctggc aacacggcct ccctgacaat ctctgggctc 240 tctaatcgct tctctggctc caagtctggc aacacggcct ccctgacaat ctctgggctc 240

caggctgagg acgaggctga ttattactgc tgctcatatg cacgtattag cacccccgga 300 caggctgagg acgaggctga ttattactgc tgctcatatg cacgtattag cacccccggga 300

tttgtcttcg gaactgggac caaggtcacc gtccta 336 tttgtcttcg gaactgggac caaggtcacc gtccta 336

Sequence Number (ID): 222 Sequence Number (ID): 222

Length: 318 Length: 318

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..318 - source, 1..318

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gacatccaga tgacccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60 gacatccaga tgacccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gagtattagt agctggttgg cctggtatca gcagaaacca 120 atcacttgcc gggccagtca gagtattagt agctggttgg cctggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctataag gcatctaatt tagaaagtgg ggtcccatca 180 gggaaagccc ctaagctcct gatctataag gcatctaatt tagaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240 aggttcagcg gcagtggatc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240

gatgattttg caacttatta ctgccaacag tataatagtt attcgacgtt cggccaaggg 300 gatgattttg caacttatta ctgccaacag tataatagtt attcgacgtt cggccaaggg 300

accaaggtgg agatcaaa 318 accaaggtgg agatcaaa 318

Sequence Number (ID): 223 Sequence Number (ID): 223

Length: 324 Length: 324

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..324 - source, 1..324

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: residences:

gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctctaggaga cagagtcacc 60 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctctaggaga cagagtcacc 60

atcacttgcc aggcgagtca ggacattagc aactatttaa attggtatca gcagaaacca 120 atcacttgcc aggcgagtca ggacattagc aactatttaa attggtatca gcagaaacca 120

gggaaggccc ctaagctcct gatctacgat gcatccaatt tgcaaacagg ggtcccatca 180 gggaaggccc ctaagctcct gatctacgat gcatccaatt tgcaaacagg ggtcccatca 180

aggttcagtg gaggtggatc tgggacagat tttactttca ccatcagcag cctgcagcct 240 aggttcagtg gaggtggatc tgggacagat tttactttca ccatcagcag cctgcagcct 240

gaagatattg caacatatta ctgtcaacag tatgataatc tcctgggagt cactttcggc 300 gaagatattg caacatatta ctgtcaacag tatgataatc tcctgggagt cactttcggc 300

cctgggacca aagtggatat caaa 324 cctgggacca aagtggatat caaa 324

Sequence Number (ID): 224 Sequence Number (ID): 224

Length: 324 Length: 324

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..324 - source, 1..324

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60 gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60

ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagagt 120 ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagagt 120

cctggccagg ctcccaggct cctcatctat ggtacatcca gcagggccac tggcatccca 180 cctggccagg ctcccaggct cctcatctat ggtacatcca gcagggccac tggcatccca 180

gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240 gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240

cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcacctag aacgttcggc 300 cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcacctag aacgttcggc 300

caagggacca aggtggagat caaa 324 caagggacca aggtggagat caaa 324

Sequence Number (ID): 225 Sequence Number (ID): 225

Length: 324 Length: 324

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..324 - source, 1..324

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60 gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60

ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120 ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120

cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180 cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180

gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240 gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240

cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcacctcg aacgttcggc 300 cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcacctcg aacgttcggc 300

caagggacca aggtggagat caaa 324 caagggacca aggtggagat caaa 324

Sequence Number (ID): 226 Sequence Number (ID): 226

Length: 327 Length: 327

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..327 - source, 1..327

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60 gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60

ctctcctgca gggccagcca gagtattagc agcagctact tagcctggta ccagcagaaa 120 ctctcctgca gggccagcca gagtattagc agcagctact tagcctggta ccagcagaaa 120

cctggccagg ctcccaggct cctcttctat ggtgcatcca gcagggccac tggcatccca 180 cctggccagg ctcccaggct cctcttctat ggtgcatcca gcagggccac tggcatccca 180

gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag caaactggag 240 gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag caaactggag 240

cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcacctcc gatcaccttc 300 cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcacctcc gatcaccttc 300

ggccaaggga cacgactgga gattaaa 327 ggccaaggga cacgactggga gattaaa 327

Sequence Number (ID): 227 Sequence Number (ID): 227

Length: 342 Length: 342

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..342 - source, 1..342

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gacatcgtga tgacccagtc tccagactcc ctggctgtgt ctctgggcga gagggccacc 60 gacatcgtga tgacccagtc tccagactcc ctggctgtgt ctctgggcga gagggccacc 60

atcaactgca agtccagcca gagtgtttta tacagctcca acaataagaa ctacttagct 120 atcaactgca agtccagcca gagtgtttta tacagctcca acaataagaa ctacttagct 120

tggtaccagc agaaaccagg acagcctcct aagctgctca tttactgggc atctacccgg 180 tggtaccagc agaaaccagg acagcctcct aagctgctca tttactgggc atctacccgg 180

gaatccgggg tccctgaccg attcagtggc agcgggtctg ggacagattt cactctcacc 240 gaatccgggg tccctgaccg attcagtggc agcgggtctg ggacagattt cactctcacc 240

atcagcagcc tgcaggctga agatgtggca gtttattact gtcagcaata ttatagtact 300 atcagcagcc tgcaggctga agatgtggca gtttattact gtcagcaata ttatagtact 300

ctcttgctca ctttcggcgg agggaccaag gtggagatca aa 342 ctcttgctca ctttcggcgg agggaccaag gtggagatca aa 342

Sequence Number (ID): 228 Sequence Number (ID): 228

Length: 321 Length: 321

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..321 - source, 1..321

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc aggcgagtca ggacattagc aactatttaa attggtatca gcagaaacca 120 atcacttgcc aggcgagtca ggacattagc aactatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctacgat gcatccaatt tggaaacagg ggtcccatca 180 gggaaagccc ctaagctcct gatctacgat gcatccaatt tggaaacagg ggtcccatca 180

aggttcagtg gaagtggatc tgggacagat tttactttca ccatcagcag cctgcagcct 240 aggttcagtg gaagtggatc tgggacagat tttactttca ccatcagcag cctgcagcct 240

gaagatattg caacatatta ctgtcaacag tatgataatc tcccgatcac cttcggccaa 300 gaagatattg caacatatta ctgtcaacag tatgataatc tcccgatcac cttcggccaa 300

gggacacgac tggagattaa a 321 gggacacgac tggagattaa a 321

Sequence Number (ID): 229 Sequence Number (ID): 229

Length: 327 Length: 327

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..327 - source, 1..327

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gacatccagt tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60 gacatccagt tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120 atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120

gggaaagccc ctaagctcct gatctttgct gcatccactt tgcagagtgg ggtcccatca 180 gggaaagccc ctaagctcct gatctttgct gcatccactt tgcagagtgg ggtcccatca 180

aggttcagcg ccagtggatc tgggacagaa ttcactctca caatcagcag cctgcagcct 240 aggttcagcg ccagtggatc tgggacagaa ttcactctca caatcagcag cctgcagcct 240

gaagattttg caacttatta ctgtcaacac cttaatagtt acccttctat gtacactttt 300 gaagattttg caacttatta ctgtcaacac cttaatagtt acccttctat gtacactttt 300

ggccagggga ccaagctgga gatcaaa 327 ggccagggga ccaagctgga gatcaaa 327

Sequence Number (ID): 230 Sequence Number (ID): 230

Length: 321 Length: 321

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..321 - source, 1..321

> mol_type, other DNA > mol_type, other DNA

> note, VL > note, VL

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gggcattaga aatgatttag gctggtatca gcagaaacca 120 atcacttgcc gggcaagtca gggcattaga aatgatttag gctggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tacaaagtgg ggtcccatca 180 gggaaagccc ctaagctcct gatctatgct gcatccagtt tacaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tggcacagat ttcactctca ccatcagcag cctgcagcct 240 aggttcagcg gcagtggatc tggcacagat ttcactctca ccatcagcag cctgcagcct 240

gaagattttg caacttatta ctgtctacaa gattacaatt accctcggac gttcggccaa 300 gaagattttg caacttatta ctgtctacaa gattacaatt accctcggac gttcggccaa 300

gggaccaagg tggaaatcaa a 321 gggaccaagg tggaaatcaa a 321

Sequence Number (ID): 231 Sequence Number (ID): 231

Length: 457 Length: 457

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..457 - SOURCE, 1..457

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EVQLVESGGG VVQPGRSLRL SCAASGFTFS SYAMHWVRQA PGKGLEWVAV ISYDGSNKYY 60 EVQLVESGGG VVQPGRSLRL SCAASGFTFS SYAMHWVRQA PGKGLEWVAV ISYDGSNKYY 60

ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCARAR PWRYSYGLYY YYGMDVWGQG 120 ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCARAR PWRYSYGLYY YYGMDVWGQG 120

TTVTVSSAST KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF PEPVTVSWNS GALTSGVHTF 180 TTVTVSSAST KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF PEPVTVSWNS GALTSGVHTF 180

PAVLQSSGLY SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKRVEPKSC DKTHTCPPCP 240 PAVLQSSGLY SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKRVEPKSC DKTHTCPPCP 240

APELLGGPSV FLFPPKPKDT LMISRTPEVT CVVVDVSHED PEVKFNWYVD GVEVHNAKTK 300 APELLGGPSV FLFPPKPKDT LMISRTPEVT CVVVDVSHED PEVKFNWYVD GVEVHNAKTK 300

PREEQYNSTY RVVSVLTVLH QDWLNGKEYK CKVSNKALPA PIEKTISKAK GQPREPQVYT 360 PREEQYNSTY RVVSVLTVLH QDWLNGKEYK CKVSNKALPA PIEKTISKAK GQPREPQVYT 360

LPPSREEMTK NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPVLDS DGSFFLYSKL 420 LPPSREEMTK NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPVLDS DGSFFLYSKL 420

TVDKSRWQQG NVFSCSVMHE ALHNHYTQKS LSLSPGK 457 TVDKSRWQQG NVFSCSVMHE ALHNHYTQKS LSLSPGK 457

Sequence Number (ID): 232 Sequence Number (ID): 232

Length: 457 Length: 457

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..457 - SOURCE, 1..457

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EVQLVESGGG LVQSGGSLRL SCAASGFSFN TYSMNWVRQA PGKGLEWVSY ISSSGSILHY 60 EVQLVESGGG LVQSGGSLRL SCAASGFSFN TYSMNWVRQA PGKGLEWVSY ISSSGSILHY 60

ADSVKGRLTI SRDNAKNSLY LQMNSLRAED TAVYYCARVG TRVGASNFDY YYGMDVWGQG 120 ADSVKGRLTI SRDNAKNSLY LQMNSLRAED TAVYYCARVG TRVGASNFDY YYGMDVWGQG 120

TTVTVSSAST KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF PEPVTVSWNS GALTSGVHTF 180 TTVTVSSAST KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF PEPVTVSWNS GALTSGVHTF 180

PAVLQSSGLY SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKRVEPKSC DKTHTCPPCP 240 PAVLQSSGLY SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKRVEPKSC DKTHTCPPCP 240

APELLGGPSV FLFPPKPKDT LMISRTPEVT CVVVDVSHED PEVKFNWYVD GVEVHNAKTK 300 APELLGGPSV FLFPPKPKDT LMISRTPEVT CVVVDVSHED PEVKFNWYVD GVEVHNAKTK 300

PREEQYNSTY RVVSVLTVLH QDWLNGKEYK CKVSNKALPA PIEKTISKAK GQPREPQVYT 360 PREEQYNSTY RVVSVLTVLH QDWLNGKEYK CKVSNKALPA PIEKTISKAK GQPREPQVYT 360

LPPSREEMTK NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPVLDS DGSFFLYSKL 420 LPPSREEMTK NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPVLDS DGSFFLYSKL 420

TVDKSRWQQG NVFSCSVMHE ALHNHYTQKS LSLSPGK 457 TVDKSRWQQG NVFSCSVMHE ALHNHYTQKS LSLSPGK 457

Sequence Number (ID): 233 Sequence Number (ID): 233

Length: 453 Length: 453

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..453 - SOURCE, 1..453

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: residences:

QVQLRQWGSG LLKPSETLSL TCAVYGGSLS GYYWSYFRQP PGKGLEWIGE ITQSGGTNYN 60 QVQLRQWGSG LLKPSETLSL TCAVYGGSLS GYYWSYFRQP PGKGLEWIGE ITQSGGTNYN 60

PSLKSRITIS VDTSKNQFSL DLSSVTAADT AVYYCARGGY DDNRGYYAYF DYWGQGTLVT 120 PSLKSRITIS VDTSKNQFSL DLSSVTAADT AVYYCARGGY DDNRGYYAYF DYWGQGTLVT 120

VSSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV TVSWNSGALT SGVHTFPAVL 180 VSSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV TVSWNSGALT SGVHTFPAVL 180

QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKR VEPKSCDKTH TCPPCPAPEL 240 QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKR VEPKSCDKTH TCPPCPAPEL 240

LGGPSVFLFP PKPKDTLMIS RTPEVTCVVV DVSHEDPEVK FNWYVDGVEV HNAKTKPREE 300 LGGPSVFLFP PKPKDTLMIS RTPEVTCVVV DVSHEDPEVK FNWYVDGVEV HNAKTKPREE 300

QYNSTYRVVS VLTVLHQDWL NGKEYKCKVS NKALPAPIEK TISKAKGQPR EPQVYTLPPS 360 QYNSTYRVVS VLTVLHQDWL NGKEYKCKVS NKALPAPIEK TISKAKGQPR EPQVYTLPPS 360

REEMTKNQVS LTCLVKGFYP SDIAVEWESN GQPENNYKTT PPVLDSDGSF FLYSKLTVDK 420 REEMTKNQVS LTCLVKGFYP SDIAVEWESN GQPENNYKTT PPVLDSDGSF FLYSKLTVDK 420

SRWQQGNVFS CSVMHEALHN HYTQKSLSLS PGK 453 SRWQQGNVFS CSVMHEALHN HYTQKSLSLS PGK 453

Sequence Number (ID): 234 Sequence Number (ID): 234

Length: 465 Length: 465

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..465 - SOURCE, 1..465

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QVQLVQSGAE VKKPGASVKV SCKASGYTFT GYYIHWVRQA PGQGLEWMGW INPNSGATNY 60 QVQLVQSGAE VKKPGASVKV SCKASGYTFT GYYIHWVRQA PGQGLEWMGW INPNSGATNY 60

AQKFQGRVTV TRDTSISTAY MELSRLRSDD TAVYYCARVA QVVSNPLPYD VLTGLTYYYY 120 AQKFQGRVTV TRDTSISTAY MELSRLRSDD TAVYYCARVA QVVSNPLPYD VLTGLTYYYY 120

GMDVWGQGTT VTVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE PVTVSWNSGA 180 GMDVWGQGTT VTVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE PVTVSWNSGA 180

LTSGVHTFPA VLQSSGLYSL SSVVTVPSSS LGTQTYICNV NHKPSNTKVD KRVEPKSCDK 240 LTSGVHTFPA VLQSSGLYSL SSVVTVPSSS LGTQTYICNV NHKPSNTKVD KRVEPKSCDK 240

THTCPPCPAP ELLGGPSVFL FPPKPKDTLM ISRTPEVTCV VVDVSHEDPE VKFNWYVDGV 300 THTCPPCPAP ELLGGPSVFL FPPKPKDTLM ISRTPEVTCV VVDVSHEDPE VKFNWYVDGV 300

EVHNAKTKPR EEQYNSTYRV VSVLTVLHQD WLNGKEYKCK VSNKALPAPI EKTISKAKGQ 360 EVHNAKTKPR EEQYNSTYRV VSVLTVLHQD WLNGKEYKCK VSNKALPAPI EKTISKAKGQ 360

PREPQVYTLP PSREEMTKNQ VSLTCLVKGF YPSDIAVEWE SNGQPENNYK TTPPVLDSDG 420 PREPQVYTLP PSREEMTKNQ VSLTCLVKGF YPSDIAVEWE SNGQPENNYK TTPPVLDSDG 420

SFFLYSKLTV DKSRWQQGNV FSCSVMHEAL HNHYTQKSLS LSPGK 465 SFFLYSKLTV DKSRWQQGNV FSCSVMHEAL HNHYTQKSLS LSPGK 465

Sequence Number (ID): 235 Sequence Number (ID): 235

Length: 451 Length: 451

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..451 - SOURCE, 1..451

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QVQLVQSGAE VKKPGASVKV SCKASGYTFT GYYMHWVRQA PGQGLEWMGW INPNSGGTNY 60 QVQLVQSGAE VKKPGASVKV SCKASGYTFT GYYMHWVRQA PGQGLEWMGW INPNSGGTNY 60

AQKFQGRVTM TRDTSITTAY MELSRLRSDD TAVYYCARDY YYDSSVNPDY WGQGTLVTVS 120 AQKFQGRVTM TRDTSITTAY MELSRLRSDD TAVYYCARDY YYDSSVNPDY WGQGTLVTVS 120

SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV SWNSGALTSG VHTFPAVLQS 180 SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV SWNSGALTSG VHTFPAVLQS 180

SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKRVE PKSCDKTHTC PPCPAPELLG 240 SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKRVE PKSCDKTHTC PPCPAPELLG 240

GPSVFLFPPK PKDTLMISRT PEVTCVVVDV SHEDPEVKFN WYVDGVEVHN AKTKPREEQY 300 GPSVFLFPPK PKDTLMISRT PEVTCVVVDV SHEDPEVKFN WYVDGVEVHN AKTKPREEQY 300

NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALPAPIEKTI SKAKGQPREP QVYTLPPSRE 360 NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALPAPIEKTI SKAKGQPREP QVYTLPPSRE 360

EMTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTTPP VLDSDGSFFL YSKLTVDKSR 420 EMTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTTPP VLDSDGSFFL YSKLTVDKSR 420

WQQGNVFSCS VMHEALHNHY TQKSLSLSPG K 451 WQQGNVFSCS VMHEALHNHY TQKSLSLSPGK 451

Sequence Number (ID): 236 Sequence Number (ID): 236

Length: 453 Length: 453

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..453 - SOURCE, 1..453

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QVQLQESGPG LVKPSQTLSL TCTVSGGSIS SGDYYWSWIR QHPGKGLEWI GYIFYSGSTY 60 QVQLQESGPG LVKPSQTLSL TCTVSGGSIS SGDYYWSWIR QHPGKGLEWI GYIFYSGSTY 60

YNPSLKSRVT ISVDTSKNQF SLKLSSVTAA DTAVYYCARR CRFVDTSMAF DYWGQGTLVT 120 YNPSLKSRVT ISVDTSKNQF SLKLSSVTAA DTAVYYCARR CRFVDTSMAF DYWGQGTLVT 120

VSSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV TVSWNSGALT SGVHTFPAVL 180 VSSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV TVSWNSGALT SGVHTFPAVL 180

QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKR VEPKSCDKTH TCPPCPAPEL 240 QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKR VEPKSCDKTH TCPPCPAPEL 240

LGGPSVFLFP PKPKDTLMIS RTPEVTCVVV DVSHEDPEVK FNWYVDGVEV HNAKTKPREE 300 LGGPSVFLFP PKPKDTLMIS RTPEVTCVVV DVSHEDPEVK FNWYVDGVEV HNAKTKPREE 300

QYNSTYRVVS VLTVLHQDWL NGKEYKCKVS NKALPAPIEK TISKAKGQPR EPQVYTLPPS 360 QYNSTYRVVS VLTVLHQDWL NGKEYKCKVS NKALPAPIEK TISKAKGQPR EPQVYTLPPS 360

REEMTKNQVS LTCLVKGFYP SDIAVEWESN GQPENNYKTT PPVLDSDGSF FLYSKLTVDK 420 REEMTKNQVS LTCLVKGFYP SDIAVEWESN GQPENNYKTT PPVLDSDGSF FLYSKLTVDK 420

SRWQQGNVFS CSVMHEALHN HYTQKSLSLS PGK 453 SRWQQGNVFS CSVMHEALHN HYTQKSLSLS PGK 453

Sequence Number (ID): 237 Sequence Number (ID): 237

Length: 451 Length: 451

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..451 - SOURCE, 1..451

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QVQLVQSGAE VKKPGSSVKV SCKASGGTFI TYAFSWVRQA PGQGLEWMGR IIPILGITNY 60 QVQLVQSGAE VKKPGSSVKV SCKASGGTFI TYAFSWVRQA PGQGLEWMGR IIPILGITNY 60

AQKFQGRVTI TADKSTSTAY MELSSLRSED TAVYYCARGG RGANPGWFDY WGQGTLVTVS 120 AQKFQGRVTI TADKSTSTAY MELSSLRSED TAVYYCARGG RGANPGWFDY WGQGTLVTVS 120

SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV SWNSGALTSG VHTFPAVLQS 180 SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV SWNSGALTSG VHTFPAVLQS 180

SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKRVE PKSCDKTHTC PPCPAPELLG 240 SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKRVE PKSCDKTHTC PPCPAPELLG 240

GPSVFLFPPK PKDTLMISRT PEVTCVVVDV SHEDPEVKFN WYVDGVEVHN AKTKPREEQY 300 GPSVFLFPPK PKDTLMISRT PEVTCVVVDV SHEDPEVKFN WYVDGVEVHN AKTKPREEQY 300

NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALPAPIEKTI SKAKGQPREP QVYTLPPSRE 360 NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALPAPIEKTI SKAKGQPREP QVYTLPPSRE 360

EMTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTTPP VLDSDGSFFL YSKLTVDKSR 420 EMTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTTPP VLDSDGSFFL YSKLTVDKSR 420

WQQGNVFSCS VMHEALHNHY TQKSLSLSPG K 451 WQQGNVFSCS VMHEALHNHY TQKSLSLSPGK 451

Sequence Number (ID): 238 Sequence Number (ID): 238

Length: 453 Length: 453

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..453 - SOURCE, 1..453

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QVQLVQSGAE VKKPGSSVKV SCKASGGTFS NYAISWVRQA PGQGLEWMGR IIPILGIANY 60 QVQLVQSGAE VKKPGSSVKV SCKASGGTFS NYAISWVRQA PGQGLEWMGR IIPILGIANY 60

AQKFQGRLTI TADKSTSTAY MELSSLRSED TAVYYCARTA YEYDSSGYFL DYWGQGTLVT 120 AQKFQGRLTI TADKSTSTAY MELSSLRSED TAVYYCARTA YEYDSSGYFL DYWGQGTLVT 120

VSSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV TVSWNSGALT SGVHTFPAVL 180 VSSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV TVSWNSGALT SGVHTFPAVL 180

QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKR VEPKSCDKTH TCPPCPAPEL 240 QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKR VEPKSCDKTH TCPPCPAPEL 240

LGGPSVFLFP PKPKDTLMIS RTPEVTCVVV DVSHEDPEVK FNWYVDGVEV HNAKTKPREE 300 LGGPSVFLFP PKPKDTLMIS RTPEVTCVVV DVSHEDPEVK FNWYVDGVEV HNAKTKPREE 300

QYNSTYRVVS VLTVLHQDWL NGKEYKCKVS NKALPAPIEK TISKAKGQPR EPQVYTLPPS 360 QYNSTYRVVS VLTVLHQDWL NGKEYKCKVS NKALPAPIEK TISKAKGQPR EPQVYTLPPS 360

REEMTKNQVS LTCLVKGFYP SDIAVEWESN GQPENNYKTT PPVLDSDGSF FLYSKLTVDK 420 REEMTKNQVS LTCLVKGFYP SDIAVEWESN GQPENNYKTT PPVLDSDGSF FLYSKLTVDK 420

SRWQQGNVFS CSVMHEALHN HYTQKSLSLS PGK 453 SRWQQGNVFS CSVMHEALHN HYTQKSLSLS PGK 453

Sequence Number (ID): 239 Sequence Number (ID): 239

Length: 450 Length: 450

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..450 - SOURCE, 1..450

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EVQLLESGGG LVKPGGSLRL SCAASGFTFS DYYMSWIRQA PGKGLEWVSY ISSSGSTIYY 60 EVQLLESGGG LVKPGGSLRL SCAASGFTFS DYYMSWIRQA PGKGLEWVSY ISSSGSTIYY 60

ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARHP MVRGVIGDYW GQGTLVTVSS 120 ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TAVYYCARHP MVRGVIGDYW GQGTLVTVSS 120

ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 180 ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 180

GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKRVEP KSCDKTHTCP PCPAPELLGG 240 GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKRVEP KSCDKTHTCP PCPAPELLGG 240

PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN 300 PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN 300

STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSREE 360 STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSREE 360

MTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW 420 MTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW 420

QQGNVFSCSV MHEALHNHYT QKSLSLSPGK 450 QQGNVFSCSV MHEALHNHYT QKSLSLSPGK 450

Sequence Number (ID): 240 Sequence Number (ID): 240

Length: 455 Length: 455

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..455 - SOURCE, 1..455

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: residences:

QVQLVQSGAE VKKPGASVKV SCKASGYTFT SYYMHWVRQA PGQGLEWMGI INPSGGSTSY 60 QVQLVQSGAE VKKPGASVKV SCKASGYTFT SYYMHWVRQA PGQGLEWMGI INPSGGSTSY 60

VQKFQGRVTM TRDTSTSTVY MELSSLRFED TAVYYCARGH SGYDRLPQPP YFDYWGQGTL 120 VQKFQGRVTM TRDTSTSTVY MELSSLRFED TAVYYCARGH SGYDRLPQPP YFDYWGQGTL 120

VTVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE PVTVSWNSGA LTSGVHTFPA 180 VTVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE PVTVSWNSGA LTSGVHTFPA 180

VLQSSGLYSL SSVVTVPSSS LGTQTYICNV NHKPSNTKVD KRVEPKSCDK THTCPPCPAP 240 VLQSSGLYSL SSVVTVPSSS LGTQTYICNV NHKPSNTKVD KRVEPKSCDK THTCPPCPAP 240

ELLGGPSVFL FPPKPKDTLM ISRTPEVTCV VVDVSHEDPE VKFNWYVDGV EVHNAKTKPR 300 ELLGGPSVFL FPPKPKDTLM ISRTPEVTCV VVDVSHEDPE VKFNWYVDGV EVHNAKTKPR 300

EEQYNSTYRV VSVLTVLHQD WLNGKEYKCK VSNKALPAPI EKTISKAKGQ PREPQVYTLP 360 EEQYNSTYRV VSVLTVLHQD WLNGKEYKCK VSNKALPAPI EKTISKAKGQ PREPQVYTLP 360

PSREEMTKNQ VSLTCLVKGF YPSDIAVEWE SNGQPENNYK TTPPVLDSDG SFFLYSKLTV 420 PSREEMTKNQ VSLTCLVKGF YPSDIAVEWE SNGQPENNYK TTPPVLDSDG SFFLYSKLTV 420

DKSRWQQGNV FSCSVMHEAL HNHYTQKSLS LSPGK 455 DKSRWQQGNV FSCSVMHEAL HNHYTQKSLS LSPGK 455

Sequence Number (ID): 241 Sequence Number (ID): 241

Length: 451 Length: 451

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..451 - SOURCE, 1..451

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QVQLVQSGAE VKKPGASVKV SCKASGYLFT GYYMHWVRQA PGQGLEWMGW INPNSGGTNY 60 QVQLVQSGAE VKKPGASVKV SCKASGYLFT GYYMHWVRQA PGQGLEWMGW INPNSGGTNY 60

AQKFQDRVTM TRDTSITTAY MELSRLRSDD TAVYYCARSG YYTSAVNFDY WGQGTLVTVS 120 AQKFQDRVTM TRDTSITTAY MELSRLRSDD TAVYYCARSG YYTSAVNFDY WGQGTLVTVS 120

SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV SWNSGALTSG VHTFPAVLQS 180 SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV SWNSGALTSG VHTFPAVLQS 180

SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKRVE PKSCDKTHTC PPCPAPELLG 240 SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKRVE PKSCDKTHTC PPCPAPELLG 240

GPSVFLFPPK PKDTLMISRT PEVTCVVVDV SHEDPEVKFN WYVDGVEVHN AKTKPREEQY 300 GPSVFLFPPK PKDTLMISRT PEVTCVVVDV SHEDPEVKFN WYVDGVEVHN AKTKPREEQY 300

NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALPAPIEKTI SKAKGQPREP QVYTLPPSRE 360 NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALPAPIEKTI SKAKGQPREP QVYTLPPSRE 360

EMTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTTPP VLDSDGSFFL YSKLTVDKSR 420 EMTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTTPP VLDSDGSFFL YSKLTVDKSR 420

WQQGNVFSCS VMHEALHNHY TQKSLSLSPG K 451 WQQGNVFSCS VMHEALHNHY TQKSLSLSPGK 451

Sequence Number (ID): 242 Sequence Number (ID): 242

Length: 462 Length: 462

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..462 - SOURCE, 1..462

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EVQLLESGGG LVQPGGSLRL SCAASGFTFS SYAMSWVRQA PGKGLEWVSA VSGSGGSTYY 60 EVQLLESGGG LVQPGGSLRL SCAASGFTFS SYAMSWVRQA PGKGLEWVSA VSGSGGSTYY 60

ADSVKGRFTI SRDNSKNMLY LQMNSLRAED TAVYYCAKTV LAGRDDSSGY FTVYYYFGMD 120 ADSVKGRFTI SRDNSKNMLY LQMNSLRAED TAVYYCAKTV LAGRDDSSGY FTVYYYFGMD 120

VWGQGTTVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT VSWNSGALTS 180 VWGQGTTVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT VSWNSGALTS 180

GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK PSNTKVDKRV EPKSCDKTHT 240 GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK PSNTKVDKRV EPKSCDKTHT 240

CPPCPAPELL GGPSVFLFPP KPKDTLMISR TPEVTCVVVD VSHEDPEVKF NWYVDGVEVH 300 CPPCPAPELL GGPSVFLFPP KPKDTLMISR TPEVTCVVVD VSHEDPEVKF NWYVDGVEVH 300

NAKTKPREEQ YNSTYRVVSV LTVLHQDWLN GKEYKCKVSN KALPAPIEKT ISKAKGQPRE 360 NAKTKPREEQ YNSTYRVVSV LTVLHQDWLN GKEYKCKVSN KALPAPIEKT ISKAKGQPRE 360

PQVYTLPPSR EEMTKNQVSL TCLVKGFYPS DIAVEWESNG QPENNYKTTP PVLDSDGSFF 420 PQVYTLPPSR EEMTKNQVSL TCLVKGFYPS DIAVEWESNG QPENNYKTTP PVLDSDGSFF 420

LYSKLTVDKS RWQQGNVFSC SVMHEALHNH YTQKSLSLSP GK 462 LYSKLTVDKS RWQQGNVFSC SVMHEALHNH YTQKSLSLSP GK 462

Sequence Number (ID): 243 Sequence Number (ID): 243

Length: 453 Length: 453

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..453 - SOURCE, 1..453

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QVQLVQSGPE VKKPGTSVKV SCKASGFTFP SSAVQWVRQA RGQRLEWIGW IVVGSGNTNY 60 QVQLVQSGPE VKKPGTSVKV SCKASGFTFP SSAVQWVRQA RGQRLEWIGW IVVGSGNTNY 60

AQKFQERVTI TRDMSTSTAY MELSSLRSED TAVYYCAAPY CSGGSCYDGF DIWGQGTMVT 120 AQKFQERVTI TRDMSTSTAY MELSSLRSED TAVYYCAAPY CSGGSCYDGF DIWGQGTMVT 120

VSSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV TVSWNSGALT SGVHTFPAVL 180 VSSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV TVSWNSGALT SGVHTFPAVL 180

QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKR VEPKSCDKTH TCPPCPAPEL 240 QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKR VEPKSCDKTH TCPPCPAPEL 240

LGGPSVFLFP PKPKDTLMIS RTPEVTCVVV DVSHEDPEVK FNWYVDGVEV HNAKTKPREE 300 LGGPSVFLFP PKPKDTLMIS RTPEVTCVVV DVSHEDPEVK FNWYVDGVEV HNAKTKPREE 300

QYNSTYRVVS VLTVLHQDWL NGKEYKCKVS NKALPAPIEK TISKAKGQPR EPQVYTLPPS 360 QYNSTYRVVS VLTVLHQDWL NGKEYKCKVS NKALPAPIEK TISKAKGQPR EPQVYTLPPS 360

REEMTKNQVS LTCLVKGFYP SDIAVEWESN GQPENNYKTT PPVLDSDGSF FLYSKLTVDK 420 REEMTKNQVS LTCLVKGFYP SDIAVEWESN GQPENNYKTT PPVLDSDGSF FLYSKLTVDK 420

SRWQQGNVFS CSVMHEALHN HYTQKSLSLS PGK 453 SRWQQGNVFS CSVMHEALHN HYTQKSLSLS PGK 453

Sequence Number (ID): 244 Sequence Number (ID): 244

Length: 461 Length: 461

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..461 - SOURCE, 1..461

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QVQLVQSGAE VKKPGASVKV SCKASGYTFT NYDINWVRQA TGQGLEWMGW MNPNSGNTGF 60 QVQLVQSGAE VKKPGASVKV SCKASGYTFT NYDINWVRQA TGQGLEWMGW MNPNSGNTGF 60

AQKFQGRVTM TRNTSIRTVY MELSSLRSED TAVYYCARAY QNRPIAVTDM GYYYYYGMDV 120 AQKFQGRVTM TRNTSIRTVY MELSSLRSED TAVYYCARAY QNRPIAVTDM GYYYYYGMDV 120

WGQGTTVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV SWNSGALTSG 180 WGQGTTVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV SWNSGALTSG 180

VHTFPAVLQS SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKRVE PKSCDKTHTC 240 VHTFPAVLQS SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKRVE PKSCDKTHTC 240

PPCPAPELLG GPSVFLFPPK PKDTLMISRT PEVTCVVVDV SHEDPEVKFN WYVDGVEVHN 300 PPCPAPELLG GPSVFLFPPK PKDTLMISRT PEVTCVVVDV SHEDPEVKFN WYVDGVEVHN 300

AKTKPREEQY NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALPAPIEKTI SKAKGQPREP 360 AKTKPREEQY NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALPAPIEKTI SKAKGQPREP 360

QVYTLPPSRE EMTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTTPP VLDSDGSFFL 420 QVYTLPPSRE EMTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTTPP VLDSDGSFFL 420

YSKLTVDKSR WQQGNVFSCS VMHEALHNHY TQKSLSLSPG K 461 YSKLTVDKSR WQQGNVFSCS VMHEALHNHY TQKSLSLSPGK 461

Sequence Number (ID): 245 Sequence Number (ID): 245

Length: 454 Length: 454

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..454 - SOURCE, 1..454

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QLQLQESGPG LVKPSETLSL TCTVSGGSIS SSSYYWGWIR QPPGKGLEWI GSIYYSGSTY 60 QLQLQESGPG LVKPSETLSL TCTVSGGSIS SSSYYWGWIR QPPGKGLEWI GSIYYSGSTY 60

YNPSLKSRVT ISVDTSKNQF SLKLSSVTAA DTALYYCARG GSIYDYGDYE FDSWGQGTLV 120 YNPSLKSRVT ISVDTSKNQF SLKLSSVTAA DTALYYCARG GSIYDYGDYE FDSWGQGTLV 120

TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP VTVSWNSGAL TSGVHTFPAV 180 TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP VTVSWNSGAL TSGVHTFPAV 180

LQSSGLYSLS SVVTVPSSSL GTQTYICNVN HKPSNTKVDK RVEPKSCDKT HTCPPCPAPE 240 LQSSGLYSLS SVVTVPSSSL GTQTYICNVN HKPSNTKVDK RVEPKSCDKT HTCPPCPAPE 240

LLGGPSVFLF PPKPKDTLMI SRTPEVTCVV VDVSHEDPEV KFNWYVDGVE VHNAKTKPRE 300 LLGGPSVFLF PPKPKDTLMI SRTPEVTCVV VDVSHEDPEV KFNWYVDGVE VHNAKTKPRE 300

EQYNSTYRVV SVLTVLHQDW LNGKEYKCKV SNKALPAPIE KTISKAKGQP REPQVYTLPP 360 EQYNSTYRVV SVLTVLHQDW LNGKEYKCKV SNKALPAPIE KTISKAKGQP REPQVYTLPP 360

SREEMTKNQV SLTCLVKGFY PSDIAVEWES NGQPENNYKT TPPVLDSDGS FFLYSKLTVD 420 SREEMTKNQV SLTCLVKGFY PSDIAVEWES NGQPENNYKT TPPVLDSDGS FFLYSKLTVD 420

KSRWQQGNVF SCSVMHEALH NHYTQKSLSL SPGK 454 KSRWQQGNVF SCSVMHEALH NHYTQKSLSL SPGK 454

Sequence Number (ID): 246 Sequence Number (ID): 246

Length: 451 Length: 451

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..451 - SOURCE, 1..451

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QVQLVQSGAE VKKPGASVKV SCKASGYTFT SYYMHWVRQA PGQGLEWMGI INPSGGSTSY 60 QVQLVQSGAE VKKPGASVKV SCKASGYTFT SYYMHWVRQA PGQGLEWMGI INPSGGSTSY 60

AQKFQGRVTM TRDTSTSTVY MELSSLRSED TAVYYCAILG LHLGELLFDP WGQGTLVTVS 120 AQKFQGRVTM TRDTSTSTVY MELSSLRSED TAVYYCAILG LHLGELLFDP WGQGTLVTVS 120

SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV SWNSGALTSG VHTFPAVLQS 180 SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV SWNSGALTSG VHTFPAVLQS 180

SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKRVE PKSCDKTHTC PPCPAPELLG 240 SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKRVE PKSCDKTHTC PPCPAPELLG 240

GPSVFLFPPK PKDTLMISRT PEVTCVVVDV SHEDPEVKFN WYVDGVEVHN AKTKPREEQY 300 GPSVFLFPPK PKDTLMISRT PEVTCVVVDV SHEDPEVKFN WYVDGVEVHN AKTKPREEQY 300

NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALPAPIEKTI SKAKGQPREP QVYTLPPSRE 360 NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALPAPIEKTI SKAKGQPREP QVYTLPPSRE 360

EMTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTTPP VLDSDGSFFL YSKLTVDKSR 420 EMTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTTPP VLDSDGSFFL YSKLTVDKSR 420

WQQGNVFSCS VMHEALHNHY TQKSLSLSPG K 451 WQQGNVFSCS VMHEALHNHY TQKSLSLSPGK 451

Sequence Number (ID): 247 Sequence Number (ID): 247

Length: 447 Length: 447

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..447 - SOURCE, 1..447

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EVQLVESGGG LIQPGGSLRL SCAASGFTVS SNYMSWVRQA PGKGLEWVSV IYSGGSTFYA 60 EVQLVESGGG LIQPGGSLRL SCAASGFTVS SNYMSWVRQA PGKGLEWVSV IYSGGSTFYA 60

DSVKGRFTIS RDNSKNTLYL QMNSLRAEDT AVYYCARDFG EQWFDYWGQG TLVTVSSAST 120 DSVKGRFTIS RDNSKNTLYL QMNSLRAEDT AVYYCARDFG EQWFDYWGQG TLVTVSSAST 120

KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF PEPVTVSWNS GALTSGVHTF PAVLQSSGLY 180 KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF PEPVTVSWNS GALTSGVHTF PAVLQSSGLY 180

SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKRVEPKSC DKTHTCPPCP APELLGGPSV 240 SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKRVEPKSC DKTHTCPPCP APELLGGPSV 240

FLFPPKPKDT LMISRTPEVT CVVVDVSHED PEVKFNWYVD GVEVHNAKTK PREEQYNSTY 300 FLFPPKPKDT LMISRTPEVT CVVVDVSHED PEVKFNWYVD GVEVHNAKTK PREQYNSTY 300

RVVSVLTVLH QDWLNGKEYK CKVSNKALPA PIEKTISKAK GQPREPQVYT LPPSREEMTK 360 RVVSVLTVLH QDWLNGKEYK CKVSNKALPA PIEKTISKAK GQPREPQVYT LPPSREEMTK 360

NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPVLDS DGSFFLYSKL TVDKSRWQQG 420 NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPVLDS DGSFFLYSKL TVDKSRWQQG 420

NVFSCSVMHE ALHNHYTQKS LSLSPGK 447 NVFSCSVMHE ALHNHYTQKS LSLSPGK 447

Sequence Number (ID): 248 Sequence Number (ID): 248

Length: 447 Length: 447

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..447 - SOURCE, 1..447

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: residences:

EVQLVESGGG LVQPGGSLRL SCAASEFTVS SNYMSWVRQA PGKGLEWVSV IYSGGSTYYA 60 EVQLVESGGG LVQPGGSLRL SCAASEFTVS SNYMSWVRQA PGKGLEWVSV IYSGGSTYYA 60

DSVKGRFTIS RDNSKNTLYL QMNSLRAEDT AVYYCARDFG DYYFDYWGQG TLVTVSSAST 120 DSVKGRFTIS RDNSKNTLYL QMNSLRAEDT AVYYCARDFG DYYFDYWGQG TLVTVSSAST 120

KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF PEPVTVSWNS GALTSGVHTF PAVLQSSGLY 180 KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF PEPVTVSWNS GALTSGVHTF PAVLQSSGLY 180

SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKRVEPKSC DKTHTCPPCP APELLGGPSV 240 SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKRVEPKSC DKTHTCPPCP APELLGGPSV 240

FLFPPKPKDT LMISRTPEVT CVVVDVSHED PEVKFNWYVD GVEVHNAKTK PREEQYNSTY 300 FLFPPKPKDT LMISRTPEVT CVVVDVSHED PEVKFNWYVD GVEVHNAKTK PREQYNSTY 300

RVVSVLTVLH QDWLNGKEYK CKVSNKALPA PIEKTISKAK GQPREPQVYT LPPSREEMTK 360 RVVSVLTVLH QDWLNGKEYK CKVSNKALPA PIEKTISKAK GQPREPQVYT LPPSREEMTK 360

NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPVLDS DGSFFLYSKL TVDKSRWQQG 420 NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPVLDS DGSFFLYSKL TVDKSRWQQG 420

NVFSCSVMHE ALHNHYTQKS LSLSPGK 447 NVFSCSVMHE ALHNHYTQKS LSLSPGK 447

Sequence Number (ID): 249 Sequence Number (ID): 249

Length: 448 Length: 448

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..448 - SOURCE, 1..448

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EVQLVETGGG LIQPGGSLRL SCAASGFTVS RNYMSWVRQA PGKGLEWVSL IYSGGSTFYA 60 EVQLVETGGG LIQPGGSLRL SCAASGFTVS RNYMSWVRQA PGKGLEWVSL IYSGGSTFYA 60

DSVKGRFTIS RDDSKNTLYL QMNSLRAEDT AVYYCARDLL EVGGSDYWGQ GTLVTVSSAS 120 DSVKGRFTIS RDDSKNTLYL QMNSLRAEDT AVYYCARDLL EVGGSDYWGQ GTLVTVSSAS 120

TKGPSVFPLA PSSKSTSGGT AALGCLVKDY FPEPVTVSWN SGALTSGVHT FPAVLQSSGL 180 TKGPSVFPLA PSSKSTSGGT AALGCLVKDY FPEPVTVSWN SGALTSGVHT FPAVLQSSGL 180

YSLSSVVTVP SSSLGTQTYI CNVNHKPSNT KVDKRVEPKS CDKTHTCPPC PAPELLGGPS 240 YSLSSVVTVP SSSLGTQTYI CNVNHKPSNT KVDKRVEPKS CDKTHTCPPC PAPELLGGPS 240

VFLFPPKPKD TLMISRTPEV TCVVVDVSHE DPEVKFNWYV DGVEVHNAKT KPREEQYNST 300 VFLFPPKPKD TLMISRTPEV TCVVVDVSHE DPEVKFNWYV DGVEVHNAKT KPREEQYNST 300

YRVVSVLTVL HQDWLNGKEY KCKVSNKALP APIEKTISKA KGQPREPQVY TLPPSREEMT 360 YRVVSVLTVL HQDWLNGKEY KCKVSNKALP APIEKTISKA KGQPREPQVY TLPPSREEMT 360

KNQVSLTCLV KGFYPSDIAV EWESNGQPEN NYKTTPPVLD SDGSFFLYSK LTVDKSRWQQ 420 KNQVSLTCLV KGFYPSDIAV EWESNGQPEN NYKTTPPVLD SDGSFFLYSK LTVDKSRWQQ 420

GNVFSCSVMH EALHNHYTQK SLSLSPGK 448 GNVFSCSVMH EALHNHYTQK SLSLSPGK 448

Sequence Number (ID): 250 Sequence Number (ID): 250

Length: 458 Length: 458

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..458 - SOURCE, 1..458

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EVQLLESGGG LVQPGGSLRL SCAASGFTFS SYAMSWVRQA PGKGLEWVSA ISGSGGSTYY 60 EVQLLESGGG LVQPGGSLRL SCAASGFTFS SYAMSWVRQA PGKGLEWVSA ISGSGGSTYY 60

ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCAKPL LGYDFWSGYY RGGWFDPWGQ 120 ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCAKPL LGYDFWSGYY RGGWFDPWGQ 120

GTLVTVSSAS TKGPSVFPLA PSSKSTSGGT AALGCLVKDY FPEPVTVSWN SGALTSGVHT 180 GTLVTVSSAS TKGPSVFPLA PSSKSTSGGT AALGCLVKDY FPEPVTVSWN SGALTSGVHT 180

FPAVLQSSGL YSLSSVVTVP SSSLGTQTYI CNVNHKPSNT KVDKRVEPKS CDKTHTCPPC 240 FPAVLQSSGL YSLSSVVTVP SSSLGTQTYI CNVNHKPSNT KVDKRVEPKS CDKTHTCPPC 240

PAPELLGGPS VFLFPPKPKD TLMISRTPEV TCVVVDVSHE DPEVKFNWYV DGVEVHNAKT 300 PAPELLGGPS VFLFPPKPKD TLMISRTPEV TCVVVDVSHE DPEVKFNWYV DGVEVHNAKT 300

KPREEQYNST YRVVSVLTVL HQDWLNGKEY KCKVSNKALP APIEKTISKA KGQPREPQVY 360 KPREEQYNST YRVVSVLTVL HQDWLNGKEY KCKVSNKALP APIEKTISKA KGQPREPQVY 360

TLPPSREEMT KNQVSLTCLV KGFYPSDIAV EWESNGQPEN NYKTTPPVLD SDGSFFLYSK 420 TLPPSREEMT KNQVSLTCLV KGFYPSDIAV EWESNGQPEN NYKTTPPVLD SDGSFFLYSK 420

LTVDKSRWQQ GNVFSCSVMH EALHNHYTQK SLSLSPGK 458 LTVDKSRWQQ GNVFSCSVMH EALHNHYTQK SLSLSPGK 458

Sequence Number (ID): 251 Sequence Number (ID): 251

Length: 449 Length: 449

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..449 - SOURCE, 1..449

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EVQLVESGGG LIQPGGSLRL SCAASGFTVS SNYMSWVRQA PGKGLEWVSV IYSGGSTYYA 60 EVQLVESGGG LIQPGGSLRL SCAASGFTVS SNYMSWVRQA PGKGLEWVSV IYSGGSTYYA 60

DSVKGRFIIS RDNSKNTLYL QMNSLRAEDT AVYYCARDPY SYGRGGGYWG QGTLVTVSSA 120 DSVKGRFIIS RDNSKNTLYL QMNSLRAEDT AVYYCARDPY SYGRGGGYWG QGTLVTVSSA 120

STKGPSVFPL APSSKSTSGG TAALGCLVKD YFPEPVTVSW NSGALTSGVH TFPAVLQSSG 180 STKGPSVFPL APSSKSTSGG TAALGCLVKD YFPEPVTVSW NSGALTSGVH TFPAVLQSSG 180

LYSLSSVVTV PSSSLGTQTY ICNVNHKPSN TKVDKRVEPK SCDKTHTCPP CPAPELLGGP 240 LYSLSSVVTV PSSSLGTQTY ICNVNHKPSN TKVDKRVEPK SCDKTHTCPP CPAPELLGGP 240

SVFLFPPKPK DTLMISRTPE VTCVVVDVSH EDPEVKFNWY VDGVEVHNAK TKPREEQYNS 300 SVFLFPPKPK DTLMISRTPE VTCVVVDVSH EDPEVKFNWY VDGVEVHNAK TKPREEQYNS 300

TYRVVSVLTV LHQDWLNGKE YKCKVSNKAL PAPIEKTISK AKGQPREPQV YTLPPSREEM 360 TYRVVSVLTV LHQDWLNGKE YKCKVSNKAL PAPIEKTISK AKGQPREPQV YTLPPSREEM 360

TKNQVSLTCL VKGFYPSDIA VEWESNGQPE NNYKTTPPVL DSDGSFFLYS KLTVDKSRWQ 420 TKNQVSLTCL VKGFYPSDIA VEWESNGQPE NNYKTTPPVL DSDGSFFLYS KLTVDKSRWQ 420

QGNVFSCSVM HEALHNHYTQ KSLSLSPGK 449 QGNVFSCSVM HEALHNHYTQ KSLSLSPGK 449

Sequence Number (ID): 252 Sequence Number (ID): 252

Length: 447 Length: 447

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..447 - SOURCE, 1..447

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EVQLVETGGG LIQPGGSLRL SCAASGLTVS SNYMNWVRQA PGKGLEWVSV IYSGGSTYYA 60 EVQLVETGGG LIQPGGSLRL SCAASGLTVS SNYMNWVRQA PGKGLEWVSV IYSGGSTYYA 60

DSVKGRFTIS RDNSKNTLYL QMNSLRAEDT AVYYCARDGV YYGMDVWGQG TTVTVSSAST 120 DSVKGRFTIS RDNSKNTLYL QMNSLRAEDT AVYYCARDGV YYGMDVWGQG TTVTVSSAST 120

KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF PEPVTVSWNS GALTSGVHTF PAVLQSSGLY 180 KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF PEPVTVSWNS GALTSGVHTF PAVLQSSGLY 180

SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKRVEPKSC DKTHTCPPCP APELLGGPSV 240 SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKRVEPKSC DKTHTCPPCP APELLGGPSV 240

FLFPPKPKDT LMISRTPEVT CVVVDVSHED PEVKFNWYVD GVEVHNAKTK PREEQYNSTY 300 FLFPPKPKDT LMISRTPEVT CVVVDVSHED PEVKFNWYVD GVEVHNAKTK PREQYNSTY 300

RVVSVLTVLH QDWLNGKEYK CKVSNKALPA PIEKTISKAK GQPREPQVYT LPPSREEMTK 360 RVVSVLTVLH QDWLNGKEYK CKVSNKALPA PIEKTISKAK GQPREPQVYT LPPSREEMTK 360

NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPVLDS DGSFFLYSKL TVDKSRWQQG 420 NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPVLDS DGSFFLYSKL TVDKSRWQQG 420

NVFSCSVMHE ALHNHYTQKS LSLSPGK 447 NVFSCSVMHE ALHNHYTQKS LSLSPGK 447

Sequence Number (ID): 253 Sequence Number (ID): 253

Length: 454 Length: 454

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..454 - SOURCE, 1..454

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, heavy chain > NOTE, heavy chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EVQLVESGGG VVQPGRSLRL SCAASGFTFS SYGMHWVRQA PGKGLEWVAV ISYDGSNKYY 60 EVQLVESGGG VVQPGRSLRL SCAASGFTFS SYGMHWVRQA PGKGLEWVAV ISYDGSNKYY 60

ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCAKDY DFWSGYYPQP FDYWGQGTLV 120 ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCAKDY DFWSGYYPQP FDYWGQGTLV 120

TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP VTVSWNSGAL TSGVHTFPAV 180 TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP VTVSWNSGAL TSGVHTFPAV 180

LQSSGLYSLS SVVTVPSSSL GTQTYICNVN HKPSNTKVDK RVEPKSCDKT HTCPPCPAPE 240 LQSSGLYSLS SVVTVPSSSL GTQTYICNVN HKPSNTKVDK RVEPKSCDKT HTCPPCPAPE 240

LLGGPSVFLF PPKPKDTLMI SRTPEVTCVV VDVSHEDPEV KFNWYVDGVE VHNAKTKPRE 300 LLGGPSVFLF PPKPKDTLMI SRTPEVTCVV VDVSHEDPEV KFNWYVDGVE VHNAKTKPRE 300

EQYNSTYRVV SVLTVLHQDW LNGKEYKCKV SNKALPAPIE KTISKAKGQP REPQVYTLPP 360 EQYNSTYRVV SVLTVLHQDW LNGKEYKCKV SNKALPAPIE KTISKAKGQP REPQVYTLPP 360

SREEMTKNQV SLTCLVKGFY PSDIAVEWES NGQPENNYKT TPPVLDSDGS FFLYSKLTVD 420 SREEMTKNQV SLTCLVKGFY PSDIAVEWES NGQPENNYKT TPPVLDSDGS FFLYSKLTVD 420

KSRWQQGNVF SCSVMHEALH NHYTQKSLSL SPGK 454 KSRWQQGNVF SCSVMHEALH NHYTQKSLSL SPGK 454

Sequence Number (ID): 254 Sequence Number (ID): 254

Length: 214 Length: 214

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..214 - SOURCE, 1..214

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIQMTQSPSS LSASVGDRVT ITCRASQSIS SYLNWYQQKP GKAPKLLIYA ASSLQSGVPS 60 DIQMTQSPSS LSASVGDRVT ITCRASQSIS SYLNWYQQKP GKAPKLLIYA ASSLQSGVPS 60

RFSGSGSGTD FTLTISSLQP EDFATYYCQQ SYSTPGSFGQ GTKLEIKRTV AAPSVFIFPP 120 RFSGSGSGTD FTLTISSLQP EDFATYYCQQ SYSTPGSFGQ GTKLEIKRTV APSVFIFPP 120

SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT 180 SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT 180

LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC 214 LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC 214

Sequence Number (ID): 255 Sequence Number (ID): 255

Length: 216 Length: 216

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..216 - SOURCE, 1..216

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSVLTQPPSA SGTPGQRVTI SCSGSSSNIG RNTVNWYQQL PGTAPKLVIY SNNQRPSGVP 60 QSVLTQPPSA SGTPGQRVTI SCSGSSSNIG RNTVNWYQQL PGTAPKLVIY SNNQRPSGVP 60

DRFSGSKSGT SASLAISGLQ SEDEADYYCA AWDDSLNGLV FGGGTKLTVL GQPKAAPSVT 120 DRFSGSKSGT SASLAISGLQ SEDEADYYCA AWDDSLNGLV FGGGTKLTVL GQPKAAPSVT 120

LFPPSSEELQ ANKATLVCLI SDFYPGAVTV AWKADSSPVK AGVETTTPSK QSNNKYAASS 180 LFPPSSEELQ ANKATLVCLI SDFYPGAVTV AWKADSSPVK AGVETTTPSK QSNNKYAASS 180

YLSLTPEQWK SHRSYSCQVT HEGSTVEKTV APTECS 216 YLSLTPEQWK SHRSYSCQVT HEGSTVEKTV APTECS 216

Sequence Number (ID): 256 Sequence Number (ID): 256

Length: 220 Length: 220

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..220 - SOURCE, 1..220

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIVMTQSPDS LAVSLGERAT INCKSSQSVL YSFRNKICLA WYQQKPGQPP KLLIYWATTR 60 DIVMTQSPDS LAVSLGERAT INCKSSQSVL YSFRNKICLA WYQQKPGQPP KLLIYWATTR 60

ESGVPDRFSG SGSGTDFTLT ISSLQAEDVA VYYCQQFYST PWTFGQGTKV EIKRTVAAPS 120 ESGVPDRFSG SGSGTDFTLT ISSLQAEDVA VYYCQQFYST PWTFGQGTKV EIKRTVAAPS 120

VFIFPPSDEQ LKSGTASVVC LLNNFYPREA KVQWKVDNAL QSGNSQESVT EQDSKDSTYS 180 VFIFPPSDEQ LKSGTASVVC LLNNFYPREA KVQWKVDNAL QSGNSQESVT EQDSKDSTYS 180

LSSTLTLSKA DYEKHKVYAC EVTHQGLSSP VTKSFNRGEC 220 LSSTLTLSKA DYEKHKVYAC EVTHQGLSSP VTKSFNRGEC 220

Sequence Number (ID): 257 Sequence Number (ID): 257

Length: 216 Length: 216

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..216 - SOURCE, 1..216

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSALTQSASV SGSPGQPITI SCTGTSSDVG SYNLVSWYQQ HPGKAPKLMI YEVSKRPSGV 60 QSALTQSASV SGSPGQPITI SCTGTSSDVG SYNLVSWYQQ HPGKAPKLMI YEVSKRPSGV 60

SNRFSGSKSG NTASLTISGL QAEDEADYYC CSYADSRTLV FGGGTKLTVL GQPKAAPSVT 120 SNRFSGSKSG NTASLTISGL QAEDEADYYC CSYADSRTLV FGGGTKLTVL GQPKAAPSVT 120

LFPPSSEELQ ANKATLVCLI SDFYPGAVTV AWKADSSPVK AGVETTTPSK QSNNKYAASS 180 LFPPSSEELQ ANKATLVCLI SDFYPGAVTV AWKADSSPVK AGVETTTPSK QSNNKYAASS 180

YLSLTPEQWK SHRSYSCQVT HEGSTVEKTV APTECS 216 YLSLTPEQWK SHRSYSCQVT HEGSTVEKTV APTECS 216

Sequence Number (ID): 258 Sequence Number (ID): 258

Length: 216 Length: 216

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..216 - SOURCE, 1..216

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIQMTQSPSS LSASVGDRVT ITCQASQDIS NYLNWYQQKP GKAPKLLIYD ASNLETGVPS 60 DIQMTQSPSS LSASVGDRVT ITCQASQDIS NYLNWYQQKP GKAPKLLIYD ASNLETGVPS 60

RFSGSGSGTD FTFTISSLQP EDIATYYCQQ YDNLPPRVTF GQGTKVEIKR TVAAPSVFIF 120 RFSGSGSGTD FTFTISSLQP EDIATYYCQQ YDNLPPRVTF GQGTKVEIKR TVAAPSVFIF 120

PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN SQESVTEQDS KDSTYSLSST 180 PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN SQESVTEQDS KDSTYSLSST 180

LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC 216 LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC 216

Sequence Number (ID): 259 Sequence Number (ID): 259

Length: 215 Length: 215

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..215 - SOURCE, 1..215

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSALTQPASV SGSPGQSITI SCTGTSSDVG SYDLVSWYQQ HPGKAPKLMI YEVTKRPSGV 60 QSALTQPASV SGSPGQSITI SCTGTSSDVG SYDLVSWYQQ HPGKAPKLMI YEVTKRPSGV 60

SNRFSGSKSG NTASLTISGL QAEDEADYYC CSFAGSSPLF GGGTKLTVLG QPKAAPSVTL 120 SNRFSGSKSG NTASLTISGL QAEDEADYYC CSFAGSSPLF GGGTKLTVLG QPKAAPSVTL 120

FPPSSEELQA NKATLVCLIS DFYPGAVTVA WKADSSPVKA GVETTTPSKQ SNNKYAASSY 180 FPPSSEELQA NKATLVCLIS DFYPGAVTVA WKADSSPVKA GVETTTPSKQ SNNKYAASSY 180

LSLTPEQWKS HRSYSCQVTH EGSTVEKTVA PTECS 215 LSLTPEQWKS HRSYSCQVTH EGSTVEKTVA PTECS 215

Sequence Number (ID): 260 Sequence Number (ID): 260

Length: 214 Length: 214

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..214 - SOURCE, 1..214

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIQMTQSPST LSASVGDRVT ITCRASQSIS SWLAWYQQKP GKAPKVLIYK ASSLESGVPS 60 DIQMTQSPST LSASVGDRVT ITCRASQSIS SWLAWYQQKP GKAPKVLIYK ASSLESGVPS 60

RFSGSGSGTE FTLTISSLQP DDFATYYCQQ YNSYSPMFGQ GTKVEIKRTV AAPSVFIFPP 120 RFSGSGSGTE FTLTISSLQP DDFATYYCQQ YNSYSPMFGQ GTKVEIKRTV APSVFIFPP 120

SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT 180 SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT 180

LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC 214 LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC 214

Sequence Number (ID): 261 Sequence Number (ID): 261

Length: 215 Length: 215

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..215 - SOURCE, 1..215

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQK PGQAPRLLIY GASSRATGIP 60 EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQK PGQAPRLLIY GASSRATGIP 60

DRFSGSGSGT DFTLTISRLE PEDFAVYYCH QYGSSPRTFG QGTKVEIKRT VAAPSVFIFP 120 DRFSGSGSGT DFTLTISRLE PEDFAVYYCH QYGSSPRTFG QGTKVEIKRT VAAPSVFIFP 120

PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS QESVTEQDSK DSTYSLSSTL 180 PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS QESVTEQDSK DSTYSLSSTL 180

TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGEC 215 TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGEC 215

Sequence Number (ID): 262 Sequence Number (ID): 262

Length: 216 Length: 216

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..216 - SOURCE, 1..216

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSVLTQPPSA SGTPGQRVTI SCSGSSSNIG SNTVNWYQQL PGTAPKLLIY NNNQRPSGVP 60 QSVLTQPPSA SGTPGQRVTI SCSGSSSNIG SNTVNWYQQL PGTAPKLLIY NNNQRPSGVP 60

DRFSGSKSGT SASLAISGLQ SEDEADYYCA AWDDSLNGYV FGTGTKVTVL GQPKANPTVT 120 DRFSGSKSGT SASLAISGLQ SEDEADYYCA AWDDSLNGYV FGTGTKVTVL GQPKANPTVT 120

LFPPSSEELQ ANKATLVCLI SDFYPGAVTV AWKADSSPVK AGVETTTPSK QSNNKYAASS 180 LFPPSSEELQ ANKATLVCLI SDFYPGAVTV AWKADSSPVK AGVETTTPSK QSNNKYAASS 180

YLSLTPEQWK SHRSYSCQVT HEGSTVEKTV APTECS 216 YLSLTPEQWK SHRSYSCQVT HEGSTVEKTV APTECS 216

Sequence Number (ID): 263 Sequence Number (ID): 263

Length: 214 Length: 214

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..214 - SOURCE, 1..214

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIQMTQSPSS LSTSVGDRVT ITCRASQSIS KYLNWYQQKP GKAPKLLIYA ASSLQSGVPS 60 DIQMTQSPSS LSTSVGDRVT ITCRASQSIS KYLNWYQQKP GKAPKLLIYA ASSLQSGVPS 60

RFSGSGSGTD FTLTISSLQP EDFATYYCQQ SYSTPPTFGQ GTKVEIKRTV AAPSVFIFPP 120 RFSGSGSGTD FTLTISSLQP EDFATYYCQQ SYSTPPTFGQ GTKVEIKRTV APSVFIFPP 120

SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT 180 SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT 180

LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC 214 LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC 214

Sequence Number (ID): 264 Sequence Number (ID): 264

Length: 216 Length: 216

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..216 - SOURCE, 1..216

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIQMTQSPSS LSASVGDRVT ITCQASQDIS NYLNWYQQKP GKAPKLLIYD ASNLETGVPS 60 DIQMTQSPSS LSASVGDRVT ITCQASQDIS NYLNWYQQKP GKAPKLLIYD ASNLETGVPS 60

RFSGSGSGTD FTFTISSLQP EDIATYYCQQ YDNLPPRLTF GGGTKVEIKR TVAAPSVFIF 120 RFSGSGSGTD FTFTISSLQP EDIATYYCQQ YDNLPPRLTF GGGTKVEIKR TVAAPSVFIF 120

PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN SQESVTEQDS KDSTYSLSST 180 PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN SQESVTEQDS KDSTYSLSST 180

LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC 216 LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC 216

Sequence Number (ID): 265 Sequence Number (ID): 265

Length: 217 Length: 217

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..217 - SOURCE, 1..217

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSALTQPASV SGSPGQSITI SCTGTSSDIG GYNYVSWYQQ HPGKAPKLMI YDVSNRPSGV 60 QSALTQPASV SGSPGQSITI SCTGTSSDIG GYNYVSWYQQ HPGKAPKLMI YDVSNRPSGV 60

SNRFSGSKSG NTASLTISGL QAEDEAEYYC SSYTRSSTQV VFGGGTKLTV LGQPKAAPSV 120 SNRFSGSKSG NTASLTISGL QAEDEAEYYC SSYTRSSTQV VFGGGTKLTV LGQPKAAPSV 120

TLFPPSSEEL QANKATLVCL ISDFYPGAVT VAWKADSSPV KAGVETTTPS KQSNNKYAAS 180 TLFPPSSEEL QANKATLVCL ISDFYPGAVT VAWKADSSPV KAGVETTTPS KQSNNKYAAS 180

SYLSLTPEQW KSHRSYSCQV THEGSTVEKT VAPTECS 217 SYLSLTPEQW KSHRSYSCQV THEGSTVEKT VAPTECS 217

Sequence Number (ID): 266 Sequence Number (ID): 266

Length: 215 Length: 215

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..215 - SOURCE, 1..215

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQK PGQAPRLLIY GASSRATGIP 60 EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQK PGQAPRLLIY GASSRATGIP 60

DRFSGSGSGT DFTLTISRLE PEDFAVYHCQ QYGTSPWTFG QGTKVEIKRT VAAPSVFIFP 120 DRFSGSGSGT DFTLTISRLE PEDFAVYHCQ QYGTSPWTFG QGTKVEIKRT VAAPSVFIFP 120

PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS QESVTEQDSK DSTYSLSSTL 180 PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS QESVTEQDSK DSTYSLSSTL 180

TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGEC 215 TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGEC 215

Sequence Number (ID): 267 Sequence Number (ID): 267

Length: 218 Length: 218

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..218 - SOURCE, 1..218

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

QSALTQPASV SGSPGQSITI SCTGTSSDVG SYNLVSWYQQ HPGKAPKLMI YEVSKRPSGV 60 QSALTQPASV SGSPGQSITI SCTGTSSDVG SYNLVSWYQQ HPGKAPKLMI YEVSKRPSGV 60

SNRFSGSKSG NTASLTISGL QAEDEADYYC CSYARISTPG FVFGTGTKVT VLGQPKANPT 120 SNRFSGSKSG NTASLTISGL QAEDEADYYC CSYARISTPG FVFGTGTKVT VLGQPKANPT 120

VTLFPPSSEE LQANKATLVC LISDFYPGAV TVAWKADSSP VKAGVETTTP SKQSNNKYAA 180 VTLFPPSSEE LQANKATLVC LISDFYPGAV TVAWKADSSP VKAGVETTTP SKQSNNKYAA 180

SSYLSLTPEQ WKSHRSYSCQ VTHEGSTVEK TVAPTECS 218 SSYLSLTPEQ WKSHRSYSCQ VTHEGSTVEK TVAPTECS 218

Sequence Number (ID): 268 Sequence Number (ID): 268

Length: 213 Length: 213

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..213 - SOURCE, 1..213

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIQMTQSPST LSASVGDRVT ITCRASQSIS SWLAWYQQKP GKAPKLLIYK ASNLESGVPS 60 DIQMTQSPST LSASVGDRVT ITCRASQSIS SWLAWYQQKP GKAPKLLIYK ASNLESGVPS 60

RFSGSGSGTE FTLTISSLQP DDFATYYCQQ YNSYSTFGQG TKVEIKRTVA APSVFIFPPS 120 RFSGSGSGTE FTLTISSLQP DDFATYYCQQ YNSYSTFGQG TKVEIKRTVA APSVFIFPPS 120

DEQLKSGTAS VVCLLNNFYP REAKVQWKVD NALQSGNSQE SVTEQDSKDS TYSLSSTLTL 180 DEQLKSGTAS VVCLLNNFYP REAKVQWKVD NALQSGNSQE SVTEQDSKDS TYSLSSTLTL 180

SKADYEKHKV YACEVTHQGL SSPVTKSFNR GEC 213 SKADYEKHKV YACEVTHQGL SSPVTKSFNR GEC 213

Sequence Number (ID): 269 Sequence Number (ID): 269

Length: 215 Length: 215

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..215 - SOURCE, 1..215

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIQMTQSPSS LSASLGDRVT ITCQASQDIS NYLNWYQQKP GKAPKLLIYD ASNLQTGVPS 60 DIQMTQSPSS LSASLGDRVT ITCQASQDIS NYLNWYQQKP GKAPKLLIYD ASNLQTGVPS 60

RFSGGGSGTD FTFTISSLQP EDIATYYCQQ YDNLLGVTFG PGTKVDIKRT VAAPSVFIFP 120 RFSGGGSGTD FTFTISSLQP EDIATYYCQQ YDNLLGVTFG PGTKVDIKRT VAAPSVFIFP 120

PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS QESVTEQDSK DSTYSLSSTL 180 PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS QESVTEQDSK DSTYSLSSTL 180

TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGEC 215 TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGEC 215

Sequence Number (ID): 270 Sequence Number (ID): 270

Length: 215 Length: 215

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..215 - SOURCE, 1..215

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQS PGQAPRLLIY GTSSRATGIP 60 EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQS PGQAPRLLIY GTSSRATGIP 60

DRFSGSGSGT DFTLTISRLE PEDFAVYYCQ QYGSSPRTFG QGTKVEIKRT VAAPSVFIFP 120 DRFSGSGSGT DFTLTISRLE PEDFAVYYCQ QYGSSPRTFG QGTKVEIKRT VAAPSVFIFP 120

PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS QESVTEQDSK DSTYSLSSTL 180 PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS QESVTEQDSK DSTYSLSSTL 180

TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGEC 215 TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGEC 215

Sequence Number (ID): 271 Sequence Number (ID): 271

Length: 215 Length: 215

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..215 - SOURCE, 1..215

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQK PGQAPRLLIY GASSRATGIP 60 EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQK PGQAPRLLIY GASSRATGIP 60

DRFSGSGSGT DFTLTISRLE PEDFAVYYCQ QYGSSPRTFG QGTKVEIKRT VAAPSVFIFP 120 DRFSGSGSGT DFTLTISRLE PEDFAVYYCQ QYGSSPRTFG QGTKVEIKRT VAAPSVFIFP 120

PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS QESVTEQDSK DSTYSLSSTL 180 PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS QESVTEQDSK DSTYSLSSTL 180

TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGEC 215 TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGEC 215

Sequence Number (ID): 272 Sequence Number (ID): 272

Length: 216 Length: 216

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..216 - SOURCE, 1..216

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

EIVLTQSPGT LSLSPGERAT LSCRASQSIS SSYLAWYQQK PGQAPRLLFY GASSRATGIP 60 EIVLTQSPGT LSLSPGERAT LSCRASQSIS SSYLAWYQQK PGQAPRLLFY GASSRATGIP 60

DRFSGSGSGT DFTLTISKLE PEDFAVYYCQ QYGSSPPITF GQGTRLEIKR TVAAPSVFIF 120 DRFSGSGSGT DFTLTISKLE PEDFAVYYCQ QYGSSPPITF GQGTRLEIKR TVAAPSVFIF 120

PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN SQESVTEQDS KDSTYSLSST 180 PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN SQESVTEQDS KDSTYSLSST 180

LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC 216 LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC 216

Sequence Number (ID): 273 Sequence Number (ID): 273

Length: 221 Length: 221

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..221 - SOURCE, 1..221

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIVMTQSPDS LAVSLGERAT INCKSSQSVL YSSNNKNYLA WYQQKPGQPP KLLIYWASTR 60 DIVMTQSPDS LAVSLGERAT INCKSSQSVL YSSNNKNYLA WYQQKPGQPP KLLIYWASTR 60

ESGVPDRFSG SGSGTDFTLT ISSLQAEDVA VYYCQQYYST LLLTFGGGTK VEIKRTVAAP 120 ESGVPDRFSG SGSGTDFTLT ISSLQAEDVA VYYCQQYYST LLLTFGGGTK VEIKRTVAAP 120

SVFIFPPSDE QLKSGTASVV CLLNNFYPRE AKVQWKVDNA LQSGNSQESV TEQDSKDSTY 180 SVFIFPPSDE QLKSGTASVV CLLNNFYPRE AKVQWKVDNA LQSGNSQESV TEQDSKDSTY 180

SLSSTLTLSK ADYEKHKVYA CEVTHQGLSS PVTKSFNRGE C 221 SLSSTLTLSK ADYEKHKVYA CEVTHQGLSS PVTKSFNRGE C 221

Sequence Number (ID): 274 Sequence Number (ID): 274

Length: 214 Length: 214

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..214 - SOURCE, 1..214

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIQMTQSPSS LSASVGDRVT ITCQASQDIS NYLNWYQQKP GKAPKLLIYD ASNLETGVPS 60 DIQMTQSPSS LSASVGDRVT ITCQASQDIS NYLNWYQQKP GKAPKLLIYD ASNLETGVPS 60

RFSGSGSGTD FTFTISSLQP EDIATYYCQQ YDNLPITFGQ GTRLEIKRTV AAPSVFIFPP 120 RFSGSGSGTD FTFTISSLQP EDIATYYCQQ YDNLPITFGQ GTRLEIKRTV AAPSSVFIFPP 120

SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT 180 SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT 180

LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC 214 LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC 214

Sequence Number (ID): 275 Sequence Number (ID): 275

Length: 216 Length: 216

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..216 - SOURCE, 1..216

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIQLTQSPSF LSASVGDRVT ITCRASQGIS SYLAWYQQKP GKAPKLLIFA ASTLQSGVPS 60 DIQLTQSPSF LSASVGDRVT ITCRASQGIS SYLAWYQQKP GKAPKLLIFA ASTLQSGVPS 60

RFSASGSGTE FTLTISSLQP EDFATYYCQH LNSYPSMYTF GQGTKLEIKR TVAAPSVFIF 120 RFSASGSGTE FTLTISSLQP EDFATYYCQH LNSYPSMYTF GQGTKLEIKR TVAAPSVFIF 120

PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN SQESVTEQDS KDSTYSLSST 180 PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN SQESVTEQDS KDSTYSLSST 180

LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC 216 LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC 216

Sequence Number (ID): 276 Sequence Number (ID): 276

Length: 214 Length: 214

Molecule Type: AA Molecule Type: AA

Features Location/Qualifiers: Features Location/Qualifiers:

- SOURCE, 1..214 - SOURCE, 1..214

> MOL_TYPE, protein > MOL_TYPE, protein

> NOTE, light chain > NOTE, light chain

> ORGANISM, synthetic construct > ORGANISM, synthetic construct

Residues: Residents:

DIQMTQSPSS LSASVGDRVT ITCRASQGIR NDLGWYQQKP GKAPKLLIYA ASSLQSGVPS 60 DIQMTQSPSS LSASVGDRVT ITCRASQGIR NDLGWYQQKP GKAPKLLIYA ASSLQSGVPS 60

RFSGSGSGTD FTLTISSLQP EDFATYYCLQ DYNYPRTFGQ GTKVEIKRTV AAPSVFIFPP 120 RFSGSGSGTD FTLTISSLQP EDFATYYCLQ DYNYPRTFGQ GTKVEIKRTV APSVFIFPP 120

SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT 180 SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT 180

LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC 214 LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC 214

Sequence Number (ID): 277 Sequence Number (ID): 277

Length: 1428 Length: 1428

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1428 - source, 1..1428

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgag 60

gtgcagctgg tggagtctgg gggaggcgtg gtccagcctg ggaggtccct gagactctcc 120 gtgcagctgg tggagtctgg gggaggcgtg gtccagcctg ggaggtccct gagactctcc 120

tgtgcagcct ctggattcac cttcagtagc tatgctatgc actgggtccg ccaggctcca 180 tgtgcagcct ctggattcac cttcagtagc tatgctatgc actgggtccg ccaggctcca 180

ggcaaggggc tggagtgggt ggcagttata tcgtatgatg gaagtaataa atactacgca 240 ggcaaggggc tggagtgggt ggcagttata tcgtatgatg gaagtaataa atactacgca 240

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctg 300 gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctg 300

caaatgaaca gcctgagagc tgaggacacg gctgtgtatt actgtgcgag agcccgtccg 360 caaatgaaca gcctgagagc tgaggacacg gctgtgtatt actgtgcgag agcccgtccg 360

tggagataca gctatggcct ctactactac tacggtatgg acgtctgggg ccaagggacc 420 tggagataca gctatggcct ctactactac tacggtatgg acgtctgggg ccaagggacc 420

acggtcaccg tctcctcagc gtcgaccaag ggcccatcgg tcttccccct ggcaccctcc 480 acggtcaccg tctcctcagc gtcgaccaag ggcccatcgg tcttccccct ggcaccctcc 480

tccaagagca cctctggggg cacagcggcc ctgggctgcc tggtcaagga ctacttcccc 540 tccaagagca cctctggggg cacagcggcc ctgggctgcc tggtcaagga ctacttcccc 540

gaacctgtga cggtctcgtg gaactcaggc gccctgacca gcggcgtgca caccttcccg 600 gaacctgtga cggtctcgtg gaactcaggc gccctgacca gcggcgtgca caccttcccg 600

gctgtcctac agtcctcagg actctactcc ctcagcagcg tggtgaccgt gccctccagc 660 gctgtcctac agtcctcagg actctactcc ctcagcagcg tggtgaccgt gccctccagc 660

agcttgggca cccagaccta catctgcaac gtgaatcaca agcccagcaa caccaaggtg 720 agcttgggca cccagaccta catctgcaac gtgaatcaca agcccagcaa caccaaggtg 720

gacaagagag ttgagcccaa atcttgtgac aaaactcaca catgcccacc gtgcccagca 780 gacaagagag ttgagcccaa atcttgtgac aaaactcaca catgcccacc gtgcccagca 780

cctgaactcc tggggggacc gtcagtcttc ctcttccccc caaaacccaa ggacaccctc 840 cctgaactcc tggggggacc gtcagtcttc ctcttccccc caaaacccaa ggacaccctc 840

atgatctccc ggacccctga ggtcacatgc gtggtggtgg acgtgagcca cgaagaccct 900 atgatctccc ggacccctga ggtcacatgc gtggtggtgg acgtgagcca cgaagaccct 900

gaggtcaagt tcaactggta cgtggacggc gtggaggtgc ataatgccaa gacaaagccg 960 gaggtcaagt tcaactggta cgtggacggc gtggaggtgc ataatgccaa gacaaagccg 960

cgggaggagc agtacaacag cacgtaccgt gtggtcagcg tcctcaccgt cctgcaccag 1020 cgggaggagc agtacaacag cacgtaccgt gtggtcagcg tcctcaccgt cctgcaccag 1020

gactggctga atggcaagga gtacaagtgc aaggtctcca acaaagccct cccagccccc 1080 gactggctga atggcaagga gtacaagtgc aaggtctcca acaaagccct cccagccccc 1080

atcgagaaaa ccatctccaa agccaaaggg cagccccgag aaccacaggt gtacaccctg 1140 atcgagaaaa ccatctccaa agccaaaggg cagccccgag aaccacaggt gtacaccctg 1140

cccccatccc gggaggagat gaccaagaac caggtcagcc tgacctgcct ggtcaaaggc 1200 cccccatccc gggaggagat gaccaagaac caggtcagcc tgacctgcct ggtcaaaggc 1200

ttctatccca gcgacatcgc cgtggagtgg gagagcaatg ggcagccgga gaacaactac 1260 ttctatccca gcgacatcgc cgtggagtgg gagagcaatg ggcagccggga gaacaactac 1260

aagaccacgc ctcccgtgct ggactccgac ggctccttct tcctctatag caagctcacc 1320 aagaccacgc ctcccgtgct ggactccgac ggctccttct tcctctatag caagctcacc 1320

gtggacaaga gcaggtggca gcaggggaac gtcttctcat gctccgtgat gcatgaggct 1380 gtggacaaga gcaggtggca gcaggggaac gtcttctcat gctccgtgat gcatgaggct 1380

ctgcacaacc actacacgca gaagagcctc tccctgtccc cgggtaaa 1428 ctgcacaacc actacacgca gaagagcctc tccctgtccc cgggtaaa 1428

Sequence Number (ID): 278 Sequence Number (ID): 278

Length: 1428 Length: 1428

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1428 - source, 1..1428

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgag 60

gtgcagctgg tggagtctgg gggaggcttg gtacagtcgg gggggtccct gagactctcc 120 gtgcagctgg tggagtctgg gggaggcttg gtacagtcgg gggggtccct gagactctcc 120

tgtgcagcct ctggattcag cttcaatacc tatagcatga actgggtccg ccaggctcca 180 tgtgcagcct ctggattcag cttcaatacc tatagcatga actgggtccg ccaggctcca 180

gggaaggggc tggagtgggt ttcatacatt agcagtagtg gtagtatctt gcactacgca 240 gggaaggggc tggagtgggt ttcatacatt agcagtagtg gtagtatctt gcactacgca 240

gactctgtga agggccgact caccatttcc agagacaacg ccaagaactc actgtatctg 300 gactctgtga agggccgact caccattttcc agagacaacg ccaagaactc actgtatctg 300

caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag agtggggacc 360 caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag agtggggacc 360

cgagtgggag cttcaaactt cgactactac tacggtatgg acgtctgggg ccaagggacc 420 cgagtgggag cttcaaactt cgactactac tacggtatgg acgtctgggg ccaagggacc 420

acggtcaccg tctcctcagc gtcgaccaag ggcccatcgg tcttccccct ggcaccctcc 480 acggtcaccg tctcctcagc gtcgaccaag ggcccatcgg tcttccccct ggcaccctcc 480

tccaagagca cctctggggg cacagcggcc ctgggctgcc tggtcaagga ctacttcccc 540 tccaagagca cctctggggg cacagcggcc ctgggctgcc tggtcaagga ctacttcccc 540

gaacctgtga cggtctcgtg gaactcaggc gccctgacca gcggcgtgca caccttcccg 600 gaacctgtga cggtctcgtg gaactcaggc gccctgacca gcggcgtgca caccttcccg 600

gctgtcctac agtcctcagg actctactcc ctcagcagcg tggtgaccgt gccctccagc 660 gctgtcctac agtcctcagg actctactcc ctcagcagcg tggtgaccgt gccctccagc 660

agcttgggca cccagaccta catctgcaac gtgaatcaca agcccagcaa caccaaggtg 720 agcttgggca cccagaccta catctgcaac gtgaatcaca agcccagcaa caccaaggtg 720

gacaagagag ttgagcccaa atcttgtgac aaaactcaca catgcccacc gtgcccagca 780 gacaagagag ttgagcccaa atcttgtgac aaaactcaca catgcccacc gtgcccagca 780

cctgaactcc tggggggacc gtcagtcttc ctcttccccc caaaacccaa ggacaccctc 840 cctgaactcc tggggggacc gtcagtcttc ctcttccccc caaaacccaa ggacaccctc 840

atgatctccc ggacccctga ggtcacatgc gtggtggtgg acgtgagcca cgaagaccct 900 atgatctccc ggacccctga ggtcacatgc gtggtggtgg acgtgagcca cgaagaccct 900

gaggtcaagt tcaactggta cgtggacggc gtggaggtgc ataatgccaa gacaaagccg 960 gaggtcaagt tcaactggta cgtggacggc gtggaggtgc ataatgccaa gacaaagccg 960

cgggaggagc agtacaacag cacgtaccgt gtggtcagcg tcctcaccgt cctgcaccag 1020 cgggaggagc agtacaacag cacgtaccgt gtggtcagcg tcctcaccgt cctgcaccag 1020

gactggctga atggcaagga gtacaagtgc aaggtctcca acaaagccct cccagccccc 1080 gactggctga atggcaagga gtacaagtgc aaggtctcca acaaagccct cccagccccc 1080

atcgagaaaa ccatctccaa agccaaaggg cagccccgag aaccacaggt gtacaccctg 1140 atcgagaaaa ccatctccaa agccaaaggg cagccccgag aaccacaggt gtacaccctg 1140

cccccatccc gggaggagat gaccaagaac caggtcagcc tgacctgcct ggtcaaaggc 1200 cccccatccc gggaggagat gaccaagaac caggtcagcc tgacctgcct ggtcaaaggc 1200

ttctatccca gcgacatcgc cgtggagtgg gagagcaatg ggcagccgga gaacaactac 1260 ttctatccca gcgacatcgc cgtggagtgg gagagcaatg ggcagccggga gaacaactac 1260

aagaccacgc ctcccgtgct ggactccgac ggctccttct tcctctatag caagctcacc 1320 aagaccacgc ctcccgtgct ggactccgac ggctccttct tcctctatag caagctcacc 1320

gtggacaaga gcaggtggca gcaggggaac gtcttctcat gctccgtgat gcatgaggct 1380 gtggacaaga gcaggtggca gcaggggaac gtcttctcat gctccgtgat gcatgaggct 1380

ctgcacaacc actacacgca gaagagcctc tccctgtccc cgggtaaa 1428 ctgcacaacc actacacgca gaagagcctc tccctgtccc cgggtaaa 1428

Sequence Number (ID): 279 Sequence Number (ID): 279

Length: 1416 Length: 1416

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1416 - source, 1..1416

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60

gtgcagctac gccagtgggg ctcaggactg ttgaagcctt cggagaccct gtccctcacc 120 gtgcagctac gccagtgggg ctcaggactg ttgaagcctt cggagaccct gtccctcacc 120

tgcgctgtgt atggtgggtc tctaagtggt tactactgga gctacttccg ccagccccca 180 tgcgctgtgt atggtgggtc tctaagtggt tactactgga gctacttccg ccagccccca 180

gggaaggggc tggagtggat tggggaaatc actcaaagtg gcggcaccaa ctacaacccg 240 gggaaggggc tggagtggat tggggaaatc actcaaagtg gcggcaccaa ctacaacccg 240

tccctcaaga gtcggatcac aatatcagtg gacacgtcca agaatcagtt ctctttggac 300 tccctcaaga gtcggatcac aatatcagtg gacacgtcca agaatcagtt ctctttggac 300

ctgagctctg tgaccgccgc ggacacggct gtgtattact gtgcgagagg cggatacgat 360 ctgagctctg tgaccgccgc ggacacggct gtgtattact gtgcgagagg cggatacgat 360

gataatagag gttattacgc gtattttgac tactggggcc agggaaccct ggtcaccgtc 420 gataatagag gttattacgc gtattttgac tactggggcc agggaaccct ggtcaccgtc 420

tcctcagcgt cgaccaaggg cccatcggtc ttccccctgg caccctcctc caagagcacc 480 tcctcagcgt cgaccaaggg cccatcggtc ttccccctgg caccctcctc caagagcacc 480

tctgggggca cagcggccct gggctgcctg gtcaaggact acttccccga acctgtgacg 540 tctgggggca cagcggccct gggctgcctg gtcaaggact acttccccga acctgtgacg 540

gtctcgtgga actcaggcgc cctgaccagc ggcgtgcaca ccttcccggc tgtcctacag 600 gtctcgtgga actcaggcgc cctgaccagc ggcgtgcaca ccttcccggc tgtcctacag 600

tcctcaggac tctactccct cagcagcgtg gtgaccgtgc cctccagcag cttgggcacc 660 tcctcaggac tctactccct cagcagcgtg gtgaccgtgc cctccagcag cttgggcacc 660

cagacctaca tctgcaacgt gaatcacaag cccagcaaca ccaaggtgga caagagagtt 720 cagacctaca tctgcaacgt gaatcacaag cccagcaaca ccaaggtgga caagagagtt 720

gagcccaaat cttgtgacaa aactcacaca tgcccaccgt gcccagcacc tgaactcctg 780 gagcccaaat cttgtgacaa aactcacaca tgcccaccgt gcccagcacc tgaactcctg 780

gggggaccgt cagtcttcct cttcccccca aaacccaagg acaccctcat gatctcccgg 840 gggggaccgt cagtcttcct cttcccccca aaacccaagg acaccctcat gatctcccgg 840

acccctgagg tcacatgcgt ggtggtggac gtgagccacg aagaccctga ggtcaagttc 900 acccctgagg tcacatgcgt ggtggtggac gtgagccacg aagaccctga ggtcaagttc 900

aactggtacg tggacggcgt ggaggtgcat aatgccaaga caaagccgcg ggaggagcag 960 aactggtacg tggacggcgt ggaggtgcat aatgccaaga caaagccgcg ggaggagcag 960

tacaacagca cgtaccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaat 1020 tacaacagca cgtaccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaat 1020

ggcaaggagt acaagtgcaa ggtctccaac aaagccctcc cagcccccat cgagaaaacc 1080 ggcaaggagt acaagtgcaa ggtctccaac aaagccctcc cagcccccat cgagaaaacc 1080

atctccaaag ccaaagggca gccccgagaa ccacaggtgt acaccctgcc cccatcccgg 1140 atctccaaag ccaaagggca gccccgagaa ccacaggtgt acaccctgcc cccatcccgg 1140

gaggagatga ccaagaacca ggtcagcctg acctgcctgg tcaaaggctt ctatcccagc 1200 gaggagatga ccaagaacca ggtcagcctg acctgcctgg tcaaaggctt ctatcccagc 1200

gacatcgccg tggagtggga gagcaatggg cagccggaga acaactacaa gaccacgcct 1260 gacatcgccg tggagtggga gagcaatggg cagccggaga acaactacaa gaccacgcct 1260

cccgtgctgg actccgacgg ctccttcttc ctctatagca agctcaccgt ggacaagagc 1320 cccgtgctgg actccgacgg ctccttcttc ctctatagca agctcaccgt ggacaagagc 1320

aggtggcagc aggggaacgt cttctcatgc tccgtgatgc atgaggctct gcacaaccac 1380 aggtggcagc aggggaacgt cttctcatgc tccgtgatgc atgaggctct gcacaaccac 1380

tacacgcaga agagcctctc cctgtccccg ggtaaa 1416 tacacgcaga agagcctctc cctgtccccg ggtaaa 1416

Sequence Number (ID): 280 Sequence Number (ID): 280

Length: 1452 Length: 1452

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1452 - source, 1..1452

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60

gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg gggcctcagt gaaggtctcc 120 gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg gggcctcagt gaaggtctcc 120

tgcaaggctt ctggatacac cttcaccggc tactatatac actgggtgcg acaggcccct 180 tgcaaggctt ctggatacac cttcaccggc tactatatac actgggtgcg acaggcccct 180

ggacaagggc ttgagtggat gggatggatc aaccctaaca gtggtgccac aaactatgca 240 ggacaagggc ttgagtggat gggatggatc aaccctaaca gtggtgccac aaactatgca 240

cagaagtttc agggcagggt caccgtgacc agggacacgt ccatcagcac agcctacatg 300 cagaagtttc agggcagggt caccgtgacc agggacacgt ccatcagcac agcctacatg 300

gagctgagca ggctgagatc tgacgacacg gccgtgtatt actgtgcgag agttgcccaa 360 360

gtcgtgtcca acccactgcc ttacgatgtt ttgactggtt taacctatta ctactacggt 420 gtcgtgtcca acccactgcc ttacgatgtt ttgactggtt taacctatta ctactacggt 420

atggacgtct ggggccaagg gaccacggtc accgtctcct cagcgtcgac caagggccca 480 atggacgtct ggggccaagg gaccacggtc accgtctcct cagcgtcgac caagggccca 480

tcggtcttcc ccctggcacc ctcctccaag agcacctctg ggggcacagc ggccctgggc 540 tcggtcttcc ccctggcacc ctcctccaag agcacctctg ggggcacagc ggccctgggc 540

tgcctggtca aggactactt ccccgaacct gtgacggtct cgtggaactc aggcgccctg 600 tgcctggtca aggactactt ccccgaacct gtgacggtct cgtggaactc aggcgccctg 600

accagcggcg tgcacacctt cccggctgtc ctacagtcct caggactcta ctccctcagc 660 accagcggcg tgcacacctt cccggctgtc ctacagtcct caggactcta ctccctcagc 660

agcgtggtga ccgtgccctc cagcagcttg ggcacccaga cctacatctg caacgtgaat 720 agcgtggtga ccgtgccctc cagcagcttg ggcacccaga cctacatctg caacgtgaat 720

cacaagccca gcaacaccaa ggtggacaag agagttgagc ccaaatcttg tgacaaaact 780 cacaagccca gcaacaccaa ggtggacaag agagttgagc ccaaatcttg tgacaaaact 780

cacacatgcc caccgtgccc agcacctgaa ctcctggggg gaccgtcagt cttcctcttc 840 cacacatgcc caccgtgccc agcacctgaa ctcctggggg gaccgtcagt cttcctcttc 840

cccccaaaac ccaaggacac cctcatgatc tcccggaccc ctgaggtcac atgcgtggtg 900 cccccaaaac ccaaggacac cctcatgatc tcccggaccc ctgaggtcac atgcgtggtg 900

gtggacgtga gccacgaaga ccctgaggtc aagttcaact ggtacgtgga cggcgtggag 960 gtggacgtga gccacgaaga ccctgaggtc aagttcaact ggtacgtgga cggcgtggag 960

gtgcataatg ccaagacaaa gccgcgggag gagcagtaca acagcacgta ccgtgtggtc 1020 gtgcataatg ccaagacaaa gccgcgggag gagcagtaca acagcacgta ccgtgtggtc 1020

agcgtcctca ccgtcctgca ccaggactgg ctgaatggca aggagtacaa gtgcaaggtc 1080 agcgtcctca ccgtcctgca ccaggactgg ctgaatggca aggagtacaa gtgcaaggtc 1080

tccaacaaag ccctcccagc ccccatcgag aaaaccatct ccaaagccaa agggcagccc 1140 tccaacaaag ccctcccagc ccccatcgag aaaaccatct ccaaagccaa agggcagccc 1140

cgagaaccac aggtgtacac cctgccccca tcccgggagg agatgaccaa gaaccaggtc 1200 cgagaaccac aggtgtacac cctgccccca tcccgggagg agatgaccaa gaaccaggtc 1200

agcctgacct gcctggtcaa aggcttctat cccagcgaca tcgccgtgga gtgggagagc 1260 agcctgacct gcctggtcaa aggcttctat cccagcgaca tcgccgtgga gtgggagagc 1260

aatgggcagc cggagaacaa ctacaagacc acgcctcccg tgctggactc cgacggctcc 1320 aatgggcagc cggagaacaa ctacaagacc acgcctcccg tgctggactc cgacggctcc 1320

ttcttcctct atagcaagct caccgtggac aagagcaggt ggcagcaggg gaacgtcttc 1380 ttcttcctct atagcaagct caccgtggac aagagcaggt ggcagcaggg gaacgtcttc 1380

tcatgctccg tgatgcatga ggctctgcac aaccactaca cgcagaagag cctctccctg 1440 tcatgctccg tgatgcatga ggctctgcac aaccactaca cgcagaagag cctctccctg 1440

tccccgggta aa 1452 tccccgggta aa 1452

Sequence Number (ID): 281 Sequence Number (ID): 281

Length: 1410 Length: 1410

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1410 - source, 1..1410

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60

gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg gggcctcagt gaaggtctcc 120 gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg gggcctcagt gaaggtctcc 120

tgcaaggctt ctggatacac cttcaccggc tactatatgc actgggtgcg acaggcccct 180 tgcaaggctt ctggatacac cttcaccggc tactatatgc actgggtgcg acaggcccct 180

ggacaagggc ttgagtggat gggatggatc aaccctaaca gtggtggcac aaactatgca 240 ggacaagggc ttgagtggat gggatggatc aaccctaaca gtggtggcac aaactatgca 240

cagaagtttc agggcagggt caccatgacc agggacacgt ccatcaccac agcctacatg 300 cagaagtttc agggcagggt caccatgacc agggacacgt ccatcaccac agcctacatg 300

gagctgagca ggctgagatc tgacgacacg gccgtgtatt actgtgcgag agactactac 360 gagctgagca ggctgagatc tgacgacacg gccgtgtatt actgtgcgag agactactac 360

tatgatagta gtgtgaaccc tgactactgg ggccagggaa ccctggtcac cgtctcctca 420 tatgatagta gtgtgaaccc tgactactgg ggccagggaa ccctggtcac cgtctcctca 420

gcgtcgacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 480 gcgtcgacca agggcccatc ggtcttcccc ctggcaccct cctccaagag caccctctggg 480

ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaacctgt gacggtctcg 540 ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaacctgt gacggtctcg 540

tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 600 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 600

ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 660 ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 660

tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagag agttgagccc 720 tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagag agttgagccc 720

aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 780 aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 780

ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 840 ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 840

gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 900 gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 900

tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 960 tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcggggagga gcagtacaac 960

agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 1020 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 1020

gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1080 gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1080

aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggaggag 1140 aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggaggag 1140

atgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1200 atgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1200

gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1260 gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1260

ctggactccg acggctcctt cttcctctat agcaagctca ccgtggacaa gagcaggtgg 1320 ctggactccg acggctcctt cttcctctat agcaagctca ccgtggacaa gagcaggtgg 1320

cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1380 cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1380

cagaagagcc tctccctgtc cccgggtaaa 1410 cagaagagcc tctccctgtc ccggggtaaa 1410

Sequence Number (ID): 282 Sequence Number (ID): 282

Length: 1416 Length: 1416

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1416 - source, 1..1416

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60

gtgcagctgc aggagtcggg cccaggactg gtgaagcctt cacagaccct gtccctcacc 120 gtgcagctgc aggagtcggg cccaggactg gtgaagcctt cacagaccct gtccctcacc 120

tgcactgtct ctggtggctc catcagcagt ggtgattact actggagctg gatccgccag 180 tgcactgtct ctggtggctc catcagcagt ggtgattact actggagctg gatccgccag 180

cacccaggga agggcctgga gtggattggg tacatctttt acagtgggag cacctactac 240 cacccaggga agggcctgga gtggattggg tacatctttt acagtgggag cacctactac 240

aacccgtccc tcaagagtcg ggttaccata tcagtagaca cgtctaagaa ccagttctcc 300 aacccgtccc tcaagagtcg ggttaccata tcagtagaca cgtctaagaa ccagttctcc 300

ctgaagctga gctctgtgac tgccgcggac acggccgtgt attactgtgc gaggaggtgc 360 ctgaagctga gctctgtgac tgccgcggac acggccgtgt attactgtgc gaggaggtgc 360

cgttttgtag atacatctat ggcatttgac tactggggcc agggaaccct ggtcaccgtc 420 cgttttgtag atacatctat ggcatttgac tactggggcc agggaaccct ggtcaccgtc 420

tcctcagcgt cgaccaaggg cccatcggtc ttccccctgg caccctcctc caagagcacc 480 tcctcagcgt cgaccaaggg cccatcggtc ttccccctgg caccctcctc caagagcacc 480

tctgggggca cagcggccct gggctgcctg gtcaaggact acttccccga acctgtgacg 540 tctgggggca cagcggccct gggctgcctg gtcaaggact acttccccga acctgtgacg 540

gtctcgtgga actcaggcgc cctgaccagc ggcgtgcaca ccttcccggc tgtcctacag 600 gtctcgtgga actcaggcgc cctgaccagc ggcgtgcaca ccttcccggc tgtcctacag 600

tcctcaggac tctactccct cagcagcgtg gtgaccgtgc cctccagcag cttgggcacc 660 tcctcaggac tctactccct cagcagcgtg gtgaccgtgc cctccagcag cttgggcacc 660

cagacctaca tctgcaacgt gaatcacaag cccagcaaca ccaaggtgga caagagagtt 720 cagacctaca tctgcaacgt gaatcacaag cccagcaaca ccaaggtgga caagagagtt 720

gagcccaaat cttgtgacaa aactcacaca tgcccaccgt gcccagcacc tgaactcctg 780 gagcccaaat cttgtgacaa aactcacaca tgcccaccgt gcccagcacc tgaactcctg 780

gggggaccgt cagtcttcct cttcccccca aaacccaagg acaccctcat gatctcccgg 840 gggggaccgt cagtcttcct cttcccccca aaacccaagg acaccctcat gatctcccgg 840

acccctgagg tcacatgcgt ggtggtggac gtgagccacg aagaccctga ggtcaagttc 900 acccctgagg tcacatgcgt ggtggtggac gtgagccacg aagaccctga ggtcaagttc 900

aactggtacg tggacggcgt ggaggtgcat aatgccaaga caaagccgcg ggaggagcag 960 aactggtacg tggacggcgt ggaggtgcat aatgccaaga caaagccgcg ggaggagcag 960

tacaacagca cgtaccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaat 1020 tacaacagca cgtaccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaat 1020

ggcaaggagt acaagtgcaa ggtctccaac aaagccctcc cagcccccat cgagaaaacc 1080 ggcaaggagt acaagtgcaa ggtctccaac aaagccctcc cagcccccat cgagaaaacc 1080

atctccaaag ccaaagggca gccccgagaa ccacaggtgt acaccctgcc cccatcccgg 1140 atctccaaag ccaaagggca gccccgagaa ccacaggtgt acaccctgcc cccatcccgg 1140

gaggagatga ccaagaacca ggtcagcctg acctgcctgg tcaaaggctt ctatcccagc 1200 gaggagatga ccaagaacca ggtcagcctg acctgcctgg tcaaaggctt ctatcccagc 1200

gacatcgccg tggagtggga gagcaatggg cagccggaga acaactacaa gaccacgcct 1260 gacatcgccg tggagtggga gagcaatggg cagccggaga acaactacaa gaccacgcct 1260

cccgtgctgg actccgacgg ctccttcttc ctctatagca agctcaccgt ggacaagagc 1320 cccgtgctgg actccgacgg ctccttcttc ctctatagca agctcaccgt ggacaagagc 1320

aggtggcagc aggggaacgt cttctcatgc tccgtgatgc atgaggctct gcacaaccac 1380 aggtggcagc aggggaacgt cttctcatgc tccgtgatgc atgaggctct gcacaaccac 1380

tacacgcaga agagcctctc cctgtccccg ggtaaa 1416 tacacgcaga agagcctctc cctgtccccg ggtaaa 1416

Sequence Number (ID): 283 Sequence Number (ID): 283

Length: 1410 Length: 1410

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1410 - source, 1..1410

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60

gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg ggtcctcggt gaaggtctcc 120 gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg ggtcctcggt gaaggtctcc 120

tgcaaggctt ctggaggcac cttcatcacc tatgctttca gctgggtacg acaggcccct 180 tgcaaggctt ctggaggcac cttcatcacc tatgctttca gctgggtacg acaggcccct 180

ggacaagggc ttgagtggat gggaaggatc atccctatcc ttggtataac aaactacgca 240 ggacaagggc ttgagtggat gggaaggatc atccctatcc ttggtataac aaactacgca 240

cagaagttcc agggcagagt cacgattacc gcggacaaat ccacgagcac agcctacatg 300 cagaagttcc agggcagagt cacgattacc gcggacaaat ccacgagcac agcctacatg 300

gagctgagca gcctgagatc tgaggacacg gccgtgtatt actgtgcgag agggggacgc 360 gagctgagca gcctgagatc tgaggacacg gccgtgtatt actgtgcgag agggggacgc 360

ggtgctaacc ccggttggtt tgactactgg ggccagggaa ccctggtcac cgtctcctca 420 ggtgctaacc ccggttggtt tgactactgg ggccagggaa ccctggtcac cgtctcctca 420

gcgtcgacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 480 gcgtcgacca agggcccatc ggtcttcccc ctggcaccct cctccaagag caccctctggg 480

ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaacctgt gacggtctcg 540 ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaacctgt gacggtctcg 540

tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 600 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 600

ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 660 ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 660

tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagag agttgagccc 720 tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagag agttgagccc 720

aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 780 aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 780

ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 840 ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 840

gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 900 gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 900

tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 960 tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcggggagga gcagtacaac 960

agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 1020 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 1020

gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1080 gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1080

aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggaggag 1140 aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggaggag 1140

atgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1200 atgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1200

gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1260 gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1260

ctggactccg acggctcctt cttcctctat agcaagctca ccgtggacaa gagcaggtgg 1320 ctggactccg acggctcctt cttcctctat agcaagctca ccgtggacaa gagcaggtgg 1320

cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1380 cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1380

cagaagagcc tctccctgtc cccgggtaaa 1410 cagaagagcc tctccctgtc ccggggtaaa 1410

Sequence Number (ID): 284 Sequence Number (ID): 284

Length: 1416 Length: 1416

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1416 - source, 1..1416

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60

gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg ggtcctcggt gaaggtctcc 120 gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg ggtcctcggt gaaggtctcc 120

tgcaaggctt ctggaggcac cttcagcaac tatgctatca gctgggtgcg acaggcccct 180 tgcaaggctt ctggaggcac cttcagcaac tatgctatca gctgggtgcg acaggcccct 180

ggacaagggc ttgagtggat gggaaggatc atccctatcc ttggtatagc aaactacgca 240 ggacaagggc ttgagtggat gggaaggatc atccctatcc ttggtatagc aaactacgca 240

cagaagttcc agggcagact cacgattacc gcggacaaat ccacgagcac agcctacatg 300 cagaagttcc agggcagact cacgattacc gcggacaaat ccacgagcac agcctacatg 300

gagctgagca gcctaagatc tgaggacacg gccgtgtatt actgtgcgag gacggcgtat 360 gagctgagca gcctaagatc tgaggacacg gccgtgtatt actgtgcgag gacggcgtat 360

gaatatgata gtagtggtta tttccttgac tactggggcc agggaaccct ggtcaccgtc 420 gaatatgata gtagtggtta tttccttgac tactggggcc agggaaccct ggtcaccgtc 420

tcctcagcgt cgaccaaggg cccatcggtc ttccccctgg caccctcctc caagagcacc 480 tcctcagcgt cgaccaaggg cccatcggtc ttccccctgg caccctcctc caagagcacc 480

tctgggggca cagcggccct gggctgcctg gtcaaggact acttccccga acctgtgacg 540 tctgggggca cagcggccct gggctgcctg gtcaaggact acttccccga acctgtgacg 540

gtctcgtgga actcaggcgc cctgaccagc ggcgtgcaca ccttcccggc tgtcctacag 600 gtctcgtgga actcaggcgc cctgaccagc ggcgtgcaca ccttcccggc tgtcctacag 600

tcctcaggac tctactccct cagcagcgtg gtgaccgtgc cctccagcag cttgggcacc 660 tcctcaggac tctactccct cagcagcgtg gtgaccgtgc cctccagcag cttgggcacc 660

cagacctaca tctgcaacgt gaatcacaag cccagcaaca ccaaggtgga caagagagtt 720 cagacctaca tctgcaacgt gaatcacaag cccagcaaca ccaaggtgga caagagagtt 720

gagcccaaat cttgtgacaa aactcacaca tgcccaccgt gcccagcacc tgaactcctg 780 gagcccaaat cttgtgacaa aactcacaca tgcccaccgt gcccagcacc tgaactcctg 780

gggggaccgt cagtcttcct cttcccccca aaacccaagg acaccctcat gatctcccgg 840 gggggaccgt cagtcttcct cttcccccca aaacccaagg acaccctcat gatctcccgg 840

acccctgagg tcacatgcgt ggtggtggac gtgagccacg aagaccctga ggtcaagttc 900 acccctgagg tcacatgcgt ggtggtggac gtgagccacg aagaccctga ggtcaagttc 900

aactggtacg tggacggcgt ggaggtgcat aatgccaaga caaagccgcg ggaggagcag 960 aactggtacg tggacggcgt ggaggtgcat aatgccaaga caaagccgcg ggaggagcag 960

tacaacagca cgtaccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaat 1020 tacaacagca cgtaccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaat 1020

ggcaaggagt acaagtgcaa ggtctccaac aaagccctcc cagcccccat cgagaaaacc 1080 ggcaaggagt acaagtgcaa ggtctccaac aaagccctcc cagcccccat cgagaaaacc 1080

atctccaaag ccaaagggca gccccgagaa ccacaggtgt acaccctgcc cccatcccgg 1140 atctccaaag ccaaagggca gccccgagaa ccacaggtgt acaccctgcc cccatcccgg 1140

gaggagatga ccaagaacca ggtcagcctg acctgcctgg tcaaaggctt ctatcccagc 1200 gaggagatga ccaagaacca ggtcagcctg acctgcctgg tcaaaggctt ctatcccagc 1200

gacatcgccg tggagtggga gagcaatggg cagccggaga acaactacaa gaccacgcct 1260 gacatcgccg tggagtggga gagcaatggg cagccggaga acaactacaa gaccacgcct 1260

cccgtgctgg actccgacgg ctccttcttc ctctatagca agctcaccgt ggacaagagc 1320 cccgtgctgg actccgacgg ctccttcttc ctctatagca agctcaccgt ggacaagagc 1320

aggtggcagc aggggaacgt cttctcatgc tccgtgatgc atgaggctct gcacaaccac 1380 aggtggcagc aggggaacgt cttctcatgc tccgtgatgc atgaggctct gcacaaccac 1380

tacacgcaga agagcctctc cctgtccccg ggtaaa 1416 tacacgcaga agagcctctc cctgtccccg ggtaaa 1416

Sequence Number (ID): 285 Sequence Number (ID): 285

Length: 1407 Length: 1407

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1407 - source, 1..1407

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgag 60

gtgcagctgt tggagtctgg gggaggcttg gtcaagcctg gagggtccct gagactctcc 120 gtgcagctgt tggagtctgg gggaggcttg gtcaagcctg gagggtccct gagactctcc 120

tgtgcagcct ctggattcac cttcagtgac tactacatga gctggatccg ccaggctcca 180 tgtgcagcct ctggattcac cttcagtgac tactacatga gctggatccg ccaggctcca 180

gggaaggggc tggagtgggt ttcatacatt agtagtagtg gtagtaccat atactacgca 240 gggaaggggc tggagtgggt ttcatacatt agtagtagtg gtagtaccat atactacgca 240

gactctgtga agggccgatt caccatctcc agggacaacg ccaagaactc actgtatctg 300 gactctgtga agggccgatt caccatctcc agggacaacg ccaagaactc actgtatctg 300

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag gcatcctatg 360 360

gttcggggag ttatcggaga ctactggggc cagggaaccc tggtcaccgt ctcctcagcg 420 gttcggggag ttatcggaga ctactggggc cagggaaccc tggtcaccgt ctcctcagcg 420

tcgaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 480 tcgaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 480

acagcggccc tgggctgcct ggtcaaggac tacttccccg aacctgtgac ggtctcgtgg 540 acagcggccc tgggctgcct ggtcaaggac tacttccccg aacctgtgac ggtctcgtgg 540

aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 600 aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 600

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 660 ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 660

atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagagagt tgagcccaaa 720 atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagagagt tgagcccaaa 720

tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 780 tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 780

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 840 tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 840

gtcacatgcg tggtggtgga cgtgagccac gaagaccctg aggtcaagtt caactggtac 900 gtcacatgcg tggtggtgga cgtgagccac gaagaccctg aggtcaagtt caactggtac 900

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 960 gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 960

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 1020 acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 1020

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1080 tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1080

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggaggagatg 1140 gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggaggagatg 1140

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1200 accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1200

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1260 1260 gtggagtggg agagcaatgg gcagccggag

gactccgacg gctccttctt cctctatagc aagctcaccg tggacaagag caggtggcag 1320 gactccgacg gctccttctt cctctatagc aagctcaccg tggacaagag caggtggcag 1320

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1380 cagggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1380

aagagcctct ccctgtcccc gggtaaa 1407 aagagcctct ccctgtcccc gggtaaa 1407

Sequence Number (ID): 286 Sequence Number (ID): 286

Length: 1422 Length: 1422

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1422 - source, 1..1422

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60

gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg gggcctcagt gaaggtttcc 120 gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg gggcctcagt gaaggtttcc 120

tgcaaggcat ctggatacac cttcaccagc tactatatgc actgggtgcg acaggcccct 180 tgcaaggcat ctggatacac cttcaccagc tactatatgc actgggtgcg acaggcccct 180

ggacaagggc ttgagtggat gggaataatc aaccctagtg gaggtagcac aagctacgta 240 ggacaagggc ttgagtggat gggaataatc aaccctagtg gaggtagcac aagctacgta 240

cagaagttcc agggcagagt caccatgacc agggacacgt ccacgagcac agtctacatg 300 cagaagttcc agggcagagt caccatgacc agggacacgt ccacgagcac agtctacatg 300

gagctgagca gcctgagatt tgaggacacg gccgtgtatt actgtgcgag aggtcatagt 360 gagctgagca gcctgagatt tgaggacacg gccgtgtatt actgtgcgag aggtcatagt 360

ggctacgatc ggttacctca acccccttac tttgactact ggggccaggg aaccctggtc 420 ggctacgatc ggttacctca acccccttac tttgactact ggggccaggg aaccctggtc 420

accgtctcct cagcgtcgac caagggccca tcggtcttcc ccctggcacc ctcctccaag 480 accgtctcct cagcgtcgac caagggccca tcggtcttcc ccctggcacc ctcctccaag 480

agcacctctg ggggcacagc ggccctgggc tgcctggtca aggactactt ccccgaacct 540 agcacctctg ggggcacagc ggccctgggc tgcctggtca aggactactt ccccgaacct 540

gtgacggtct cgtggaactc aggcgccctg accagcggcg tgcacacctt cccggctgtc 600 gtgacggtct cgtggaactc aggcgccctg accagcggcg tgcacacctt cccggctgtc 600

ctacagtcct caggactcta ctccctcagc agcgtggtga ccgtgccctc cagcagcttg 660 ctacagtcct caggactcta ctccctcagc agcgtggtga ccgtgccctc cagcagcttg 660

ggcacccaga cctacatctg caacgtgaat cacaagccca gcaacaccaa ggtggacaag 720 ggcaccaga cctacatctg caacgtgaat cacaagccca gcaacaccaa ggtggacaag 720

agagttgagc ccaaatcttg tgacaaaact cacacatgcc caccgtgccc agcacctgaa 780 agagttgagc ccaaatcttg tgacaaaact cacacatgcc caccgtgccc agcacctgaa 780

ctcctggggg gaccgtcagt cttcctcttc cccccaaaac ccaaggacac cctcatgatc 840 ctcctggggg gaccgtcagt cttcctcttc cccccaaaac ccaaggacac cctcatgatc 840

tcccggaccc ctgaggtcac atgcgtggtg gtggacgtga gccacgaaga ccctgaggtc 900 tcccggaccc ctgaggtcac atgcgtggtg gtggacgtga gccacgaaga ccctgaggtc 900

aagttcaact ggtacgtgga cggcgtggag gtgcataatg ccaagacaaa gccgcgggag 960 aagttcaact ggtacgtgga cggcgtggag gtgcataatg ccaagacaaa gccgcgggag 960

gagcagtaca acagcacgta ccgtgtggtc agcgtcctca ccgtcctgca ccaggactgg 1020 gagcagtaca acagcacgta ccgtgtggtc agcgtcctca ccgtcctgca ccaggactgg 1020

ctgaatggca aggagtacaa gtgcaaggtc tccaacaaag ccctcccagc ccccatcgag 1080 ctgaatggca aggagtacaa gtgcaaggtc tccaacaaag ccctcccagc ccccatcgag 1080

aaaaccatct ccaaagccaa agggcagccc cgagaaccac aggtgtacac cctgccccca 1140 aaaaccatct ccaaagccaa aggcagccc cgagaaccac aggtgtacac cctgccccca 1140

tcccgggagg agatgaccaa gaaccaggtc agcctgacct gcctggtcaa aggcttctat 1200 tcccgggagg agatgaccaa gaaccaggtc agcctgacct gcctggtcaa aggcttctat 1200

cccagcgaca tcgccgtgga gtgggagagc aatgggcagc cggagaacaa ctacaagacc 1260 cccagcgaca tcgccgtgga gtggggagagc aatgggcagc cggagaacaa ctacaagacc 1260

acgcctcccg tgctggactc cgacggctcc ttcttcctct atagcaagct caccgtggac 1320 acgcctcccg tgctggactc cgacggctcc ttcttcctct atagcaagct caccgtggac 1320

aagagcaggt ggcagcaggg gaacgtcttc tcatgctccg tgatgcatga ggctctgcac 1380 aagagcaggt ggcagcaggg gaacgtcttc tcatgctccg tgatgcatga ggctctgcac 1380

aaccactaca cgcagaagag cctctccctg tccccgggta aa 1422 aaccactaca cgcagaagag cctctccctg tccccgggta aa 1422

Sequence Number (ID): 287 Sequence Number (ID): 287

Length: 1410 Length: 1410

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1410 - source, 1..1410

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60

gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg gggcctcagt gaaggtctcc 120 gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg gggcctcagt gaaggtctcc 120

tgcaaggctt ctggatacct cttcaccggc tactatatgc actgggtgcg acaggcccct 180 tgcaaggctt ctggatacct cttcaccggc tactatatgc actgggtgcg acaggcccct 180

ggacaagggc ttgagtggat gggatggatc aaccctaaca gtggtggcac aaactatgca 240 ggacaagggc ttgagtggat gggatggatc aaccctaaca gtggtggcac aaactatgca 240

cagaagtttc aggacagggt caccatgacc agggacacgt ccatcaccac agcctacatg 300 cagaagtttc aggacagggt caccatgacc agggacacgt ccatcaccac agcctacatg 300

gagctgagca ggctgagatc tgacgacacg gccgtgtatt actgtgccag gagtggttat 360 gagctgagca ggctgagatc tgacgacacg gccgtgtatt actgtgccag gagtggttat 360

tatacgagtg ctgtaaactt tgactactgg ggccagggaa ccctggtcac cgtctcctca 420 tatacgagtg ctgtaaactt tgactactgg ggccagggaa ccctggtcac cgtctcctca 420

gcgtcgacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 480 gcgtcgacca agggcccatc ggtcttcccc ctggcaccct cctccaagag caccctctggg 480

ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaacctgt gacggtctcg 540 ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaacctgt gacggtctcg 540

tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 600 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 600

ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 660 ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 660

tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagag agttgagccc 720 tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagag agttgagccc 720

aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 780 aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 780

ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 840 ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 840

gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 900 gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 900

tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 960 tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcggggagga gcagtacaac 960

agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 1020 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 1020

gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1080 gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1080

aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggaggag 1140 aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggaggag 1140

atgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1200 atgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1200

gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1260 gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1260

ctggactccg acggctcctt cttcctctat agcaagctca ccgtggacaa gagcaggtgg 1320 ctggactccg acggctcctt cttcctctat agcaagctca ccgtggacaa gagcaggtgg 1320

cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1380 cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1380

cagaagagcc tctccctgtc cccgggtaaa 1410 cagaagagcc tctccctgtc ccggggtaaa 1410

Sequence Number (ID): 288 Sequence Number (ID): 288

Length: 1443 Length: 1443

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1443 - source, 1..1443

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgag 60

gtgcagctgt tggagtctgg gggaggcttg gtacagcctg gggggtccct gagactctcc 120 gtgcagctgt tggagtctgg gggaggcttg gtacagcctg gggggtccct gagactctcc 120

tgtgcagcct ctggattcac ctttagcagc tatgccatga gttgggtccg ccaggctcca 180 tgtgcagcct ctggattcac ctttagcagc tatgccatga gttgggtccg ccaggctcca 180

gggaaggggc tggagtgggt ctcagctgtt agtggtagtg gtggtagcac atactacgca 240 gggaaggggc tggagtgggt ctcagctgtt agtggtagtg gtggtagcac atactacgca 240

gactccgtga agggccggtt caccatctcc agagacaatt ccaagaacat gctgtatctg 300 gactccgtga agggccggtt caccatctcc agagacaatt ccaagaacat gctgtatctg 300

caaatgaaca gcctgagagc cgaggacacg gccgtatatt actgtgcgaa aaccgttttg 360 caaatgaaca gcctgagagc cgaggacacg gccgtatatt actgtgcgaa aaccgttttg 360

gctggtcgcg acgatagcag tggctacttc acggtttact actacttcgg tatggacgtc 420 gctggtcgcg acgatagcag tggctacttc acggtttact actacttcgg tatggacgtc 420

tggggccagg ggaccacggt caccgtctcc tcagcgtcga ccaagggccc atcggtcttc 480 tggggccagg ggaccacggt caccgtctcc tcagcgtcga ccaagggccc atcggtcttc 480

cccctggcac cctcctccaa gagcacctct gggggcacag cggccctggg ctgcctggtc 540 cccctggcac cctcctccaa gagcacctct gggggcacag cggccctggg ctgcctggtc 540

aaggactact tccccgaacc tgtgacggtc tcgtggaact caggcgccct gaccagcggc 600 aaggactact tccccgaacc tgtgacggtc tcgtggaact caggcgccct gaccagcggc 600

gtgcacacct tcccggctgt cctacagtcc tcaggactct actccctcag cagcgtggtg 660 gtgcacacct tcccggctgt cctacagtcc tcaggactct actccctcag cagcgtggtg 660

accgtgccct ccagcagctt gggcacccag acctacatct gcaacgtgaa tcacaagccc 720 accgtgccct ccagcagctt gggcacccag acctacatct gcaacgtgaa tcacaagccc 720

agcaacacca aggtggacaa gagagttgag cccaaatctt gtgacaaaac tcacacatgc 780 agcaacacca aggtggacaa gagagttgag cccaaatctt gtgacaaaac tcacacatgc 780

ccaccgtgcc cagcacctga actcctgggg ggaccgtcag tcttcctctt ccccccaaaa 840 ccaccgtgcc cagcacctga actcctgggg ggaccgtcag tcttcctctt ccccccaaaa 840

cccaaggaca ccctcatgat ctcccggacc cctgaggtca catgcgtggt ggtggacgtg 900 cccaaggaca ccctcatgat ctcccggacc cctgaggtca catgcgtggt ggtggacgtg 900

agccacgaag accctgaggt caagttcaac tggtacgtgg acggcgtgga ggtgcataat 960 agccacgaag accctgaggt caagttcaac tggtacgtgg acggcgtgga ggtgcataat 960

gccaagacaa agccgcggga ggagcagtac aacagcacgt accgtgtggt cagcgtcctc 1020 gccaagacaa agccgcggga ggagcagtac aacagcacgt accgtgtggt cagcgtcctc 1020

accgtcctgc accaggactg gctgaatggc aaggagtaca agtgcaaggt ctccaacaaa 1080 accgtcctgc accaggactg gctgaatggc aaggagtaca agtgcaaggt ctccaacaaa 1080

gccctcccag cccccatcga gaaaaccatc tccaaagcca aagggcagcc ccgagaacca 1140 gccctcccag cccccatcga gaaaaccatc tccaaagcca aagggcagcc ccgagaacca 1140

caggtgtaca ccctgccccc atcccgggag gagatgacca agaaccaggt cagcctgacc 1200 caggtgtaca ccctgccccc atcccgggag gagatgacca agaaccaggt cagcctgacc 1200

tgcctggtca aaggcttcta tcccagcgac atcgccgtgg agtgggagag caatgggcag 1260 tgcctggtca aaggcttcta tcccagcgac atcgccgtgg agtgggagag caatgggcag 1260

ccggagaaca actacaagac cacgcctccc gtgctggact ccgacggctc cttcttcctc 1320 ccggagaaca actacaagac cacgcctccc gtgctggact ccgacggctc cttcttcctc 1320

tatagcaagc tcaccgtgga caagagcagg tggcagcagg ggaacgtctt ctcatgctcc 1380 tatagcaagc tcaccgtgga caagagcagg tggcagcagg ggaacgtctt ctcatgctcc 1380

gtgatgcatg aggctctgca caaccactac acgcagaaga gcctctccct gtccccgggt 1440 gtgatgcatg aggctctgca caaccactac acgcagaaga gcctctccct gtccccgggt 1440

aaa 1443 aaa 1443

Sequence Number (ID): 289 Sequence Number (ID): 289

Length: 1416 Length: 1416

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1416 - source, 1..1416

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60

gtgcagctgg tgcagtctgg gcctgaggtg aagaagcctg ggacctcagt gaaggtctcc 120 gtgcagctgg tgcagtctgg gcctgaggtg aagaagcctg ggacctcagt gaaggtctcc 120

tgcaaggctt ctggattcac ctttcctagc tctgctgtgc agtgggtgcg acaggctcgt 180 tgcaaggctt ctggattcac ctttcctagc tctgctgtgc agtgggtgcg acaggctcgt 180

ggacaacgcc ttgagtggat aggatggatc gtcgttggca gtggtaacac aaactacgca 240 ggacaacgcc ttgagtggat aggatggatc gtcgttggca gtggtaacac aaactacgca 240

cagaagttcc aggaaagagt caccattacc agggacatgt ccacaagcac agcctacatg 300 cagaagttcc aggaaagagt caccattacc agggacatgt ccacaagcac agcctacatg 300

gagctgagca gcctgagatc cgaggacacg gccgtgtatt actgtgcggc tccctattgt 360 gagctgagca gcctgagatc cgaggacacg gccgtgtatt actgtgcggc tccctattgt 360

agtggtggta gctgttatga tggttttgat atctggggcc aagggacaat ggtcaccgtc 420 agtggtggta gctgttatga tggttttgat atctggggcc aagggacaat ggtcaccgtc 420

tcttcagcgt cgaccaaggg cccatcggtc ttccccctgg caccctcctc caagagcacc 480 tcttcagcgt cgaccaaggg cccatcggtc ttccccctgg caccctcctc caagagcacc 480

tctgggggca cagcggccct gggctgcctg gtcaaggact acttccccga acctgtgacg 540 tctgggggca cagcggccct gggctgcctg gtcaaggact acttccccga acctgtgacg 540

gtctcgtgga actcaggcgc cctgaccagc ggcgtgcaca ccttcccggc tgtcctacag 600 gtctcgtgga actcaggcgc cctgaccagc ggcgtgcaca ccttcccggc tgtcctacag 600

tcctcaggac tctactccct cagcagcgtg gtgaccgtgc cctccagcag cttgggcacc 660 tcctcaggac tctactccct cagcagcgtg gtgaccgtgc cctccagcag cttgggcacc 660

cagacctaca tctgcaacgt gaatcacaag cccagcaaca ccaaggtgga caagagagtt 720 cagacctaca tctgcaacgt gaatcacaag cccagcaaca ccaaggtgga caagagagtt 720

gagcccaaat cttgtgacaa aactcacaca tgcccaccgt gcccagcacc tgaactcctg 780 gagcccaaat cttgtgacaa aactcacaca tgcccaccgt gcccagcacc tgaactcctg 780

gggggaccgt cagtcttcct cttcccccca aaacccaagg acaccctcat gatctcccgg 840 gggggaccgt cagtcttcct cttcccccca aaacccaagg acaccctcat gatctcccgg 840

acccctgagg tcacatgcgt ggtggtggac gtgagccacg aagaccctga ggtcaagttc 900 acccctgagg tcacatgcgt ggtggtggac gtgagccacg aagaccctga ggtcaagttc 900

aactggtacg tggacggcgt ggaggtgcat aatgccaaga caaagccgcg ggaggagcag 960 aactggtacg tggacggcgt ggaggtgcat aatgccaaga caaagccgcg ggaggagcag 960

tacaacagca cgtaccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaat 1020 tacaacagca cgtaccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaat 1020

ggcaaggagt acaagtgcaa ggtctccaac aaagccctcc cagcccccat cgagaaaacc 1080 ggcaaggagt acaagtgcaa ggtctccaac aaagccctcc cagcccccat cgagaaaacc 1080

atctccaaag ccaaagggca gccccgagaa ccacaggtgt acaccctgcc cccatcccgg 1140 atctccaaag ccaaagggca gccccgagaa ccacaggtgt acaccctgcc cccatcccgg 1140

gaggagatga ccaagaacca ggtcagcctg acctgcctgg tcaaaggctt ctatcccagc 1200 gaggagatga ccaagaacca ggtcagcctg acctgcctgg tcaaaggctt ctatcccagc 1200

gacatcgccg tggagtggga gagcaatggg cagccggaga acaactacaa gaccacgcct 1260 gacatcgccg tggagtggga gagcaatggg cagccggaga acaactacaa gaccacgcct 1260

cccgtgctgg actccgacgg ctccttcttc ctctatagca agctcaccgt ggacaagagc 1320 cccgtgctgg actccgacgg ctccttcttc ctctatagca agctcaccgt ggacaagagc 1320

aggtggcagc aggggaacgt cttctcatgc tccgtgatgc atgaggctct gcacaaccac 1380 aggtggcagc aggggaacgt cttctcatgc tccgtgatgc atgaggctct gcacaaccac 1380

tacacgcaga agagcctctc cctgtccccg ggtaaa 1416 tacacgcaga agagcctctc cctgtccccg ggtaaa 1416

Sequence Number (ID): 290 Sequence Number (ID): 290

Length: 1440 Length: 1440

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1440 - source, 1..1440

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60

gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg gggcctcagt gaaggtctcc 120 gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg gggcctcagt gaaggtctcc 120

tgcaaggctt ctggatacac cttcaccaat tatgatatca actgggtgcg acaggccact 180 tgcaaggctt ctggatacac cttcaccaat tatgatatca actgggtgcg acaggccact 180

ggacaagggc ttgagtggat gggatggatg aaccctaaca gtggtaacac aggctttgca 240 ggacaagggc ttgagtggat gggatggatg aaccctaaca gtggtaacac aggctttgca 240

cagaagttcc agggcagagt caccatgacc aggaacacct ccataagaac agtctacatg 300 cagaagttcc agggcagagt caccatgacc aggaacacct ccataagaac agtctacatg 300

gagctgagca gcctgagatc tgaggacacg gccgtgtatt actgtgcgag agcctatcaa 360 gagctgagca gcctgagatc tgaggacacg gccgtgtatt actgtgcgag agcctatcaa 360

aatagaccga tagcagtaac tgatatgggt tactactact actacggtat ggacgtctgg 420 aatagaccga tagcagtaac tgatatgggt tactactact actacggtat ggacgtctgg 420

ggccaaggga ccacggtcac cgtctcctca gcgtcgacca agggcccatc ggtcttcccc 480 ggccaaggga ccacggtcac cgtctcctca gcgtcgacca agggcccatc ggtcttcccc 480

ctggcaccct cctccaagag cacctctggg ggcacagcgg ccctgggctg cctggtcaag 540 ctggcaccct ccctccaaag caccctctgggg ggcacagcgg ccctggggctg ccctggtcaag 540

gactacttcc ccgaacctgt gacggtctcg tggaactcag gcgccctgac cagcggcgtg 600 gactacttcc ccgaacctgt gacggtctcg tggaactcag gcgccctgac cagcggcgtg 600

cacaccttcc cggctgtcct acagtcctca ggactctact ccctcagcag cgtggtgacc 660 cacaccttcc cggctgtcct acagtcctca ggactctact ccctcagcag cgtggtgacc 660

gtgccctcca gcagcttggg cacccagacc tacatctgca acgtgaatca caagcccagc 720 gtgccctcca gcagcttggg cacccagacc tacatctgca acgtgaatca caagcccagc 720

aacaccaagg tggacaagag agttgagccc aaatcttgtg acaaaactca cacatgccca 780 aacaccaagg tggacaagag agttgagccc aaatcttgtg acaaaactca cacatgccca 780

ccgtgcccag cacctgaact cctgggggga ccgtcagtct tcctcttccc cccaaaaccc 840 ccgtgcccag cacctgaact cctgggggga ccgtcagtct tcctcttccc cccaaaaccc 840

aaggacaccc tcatgatctc ccggacccct gaggtcacat gcgtggtggt ggacgtgagc 900 aaggacaccc tcatgatctc ccggacccct gaggtcacat gcgtggtggt ggacgtgagc 900

cacgaagacc ctgaggtcaa gttcaactgg tacgtggacg gcgtggaggt gcataatgcc 960 cacgaagacc ctgaggtcaa gttcaactgg tacgtggacg gcgtggaggt gcataatgcc 960

aagacaaagc cgcgggagga gcagtacaac agcacgtacc gtgtggtcag cgtcctcacc 1020 aagacaaagc cgcgggga gcagtacaac agcacgtacc gtgtggtcag cgtcctcacc 1020

gtcctgcacc aggactggct gaatggcaag gagtacaagt gcaaggtctc caacaaagcc 1080 gtcctgcacc aggactggct gaatggcaag gagtacaagt gcaaggtctc caacaaagcc 1080

ctcccagccc ccatcgagaa aaccatctcc aaagccaaag ggcagccccg agaaccacag 1140 ctcccagccc ccatcgagaa aaccatctcc aaagccaaag ggcagccccg agaaccacag 1140

gtgtacaccc tgcccccatc ccgggaggag atgaccaaga accaggtcag cctgacctgc 1200 gtgtacaccc tgcccccatc ccgggaggag atgaccaaga accaggtcag cctgacctgc 1200

ctggtcaaag gcttctatcc cagcgacatc gccgtggagt gggagagcaa tgggcagccg 1260 ctggtcaaag gcttctatcc cagcgacatc gccgtggagt gggagagcaa tgggcagccg 1260

gagaacaact acaagaccac gcctcccgtg ctggactccg acggctcctt cttcctctat 1320 gagaacaact acaagaccac gcctcccgtg ctggactccg acggctcctt cttcctctat 1320

agcaagctca ccgtggacaa gagcaggtgg cagcagggga acgtcttctc atgctccgtg 1380 agcaagctca ccgtggacaa gagcaggtgg cagcagggga acgtcttctc atgctccgtg 1380

atgcatgagg ctctgcacaa ccactacacg cagaagagcc tctccctgtc cccgggtaaa 1440 atgcatgagg ctctgcacaa ccactacacg cagaagagcc tctccctgtc ccggggtaaa 1440

Sequence Number (ID): 291 Sequence Number (ID): 291

Length: 1419 Length: 1419

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1419 - source, 1..1419

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60

ctgcagctgc aggagtcggg cccaggactg gtgaagcctt cggagaccct gtccctcacc 120 ctgcagctgc aggagtcggg cccaggactg gtgaagcctt cggagaccct gtccctcacc 120

tgcactgtct ctggtggctc catcagcagt agtagttact actggggctg gatccgccag 180 tgcactgtct ctggtggctc catcagcagt agtagttact actggggctg gatccgccag 180

cccccaggga aggggctgga gtggattggg agtatctatt atagtgggag cacctactac 240 cccccaggga aggggctgga gtggattggg agtatctatt atagtgggag cacctactac 240

aacccgtccc tcaagagtcg agtcaccata tcagtagaca cgtccaagaa ccagttctcc 300 aacccgtccc tcaagagtcg agtcaccata tcagtagaca cgtccaagaa ccagttctcc 300

ctgaagctga gctctgtgac cgccgcggac acggccttgt attactgtgc gagagggggg 360 ctgaagctga gctctgtgac cgccgcggac acggccttgt attactgtgc gagagggggg 360

tcgatctatg actacggtga ctacgaattt gactcctggg gccagggaac cctggtcacc 420 tcgatctatg actacggtga ctacgaattt gactcctggg gccagggaac cctggtcacc 420

gtctcctcag cgtcgaccaa gggcccatcg gtcttccccc tggcaccctc ctccaagagc 480 gtctcctcag cgtcgaccaa gggcccatcg gtcttccccc tggcaccctc ctccaagagc 480

acctctgggg gcacagcggc cctgggctgc ctggtcaagg actacttccc cgaacctgtg 540 acctctgggg gcacagcggc cctgggctgc ctggtcaagg actacttccc cgaacctgtg 540

acggtctcgt ggaactcagg cgccctgacc agcggcgtgc acaccttccc ggctgtccta 600 acggtctcgt ggaactcagg cgccctgacc agcggcgtgc acaccttccc ggctgtccta 600

cagtcctcag gactctactc cctcagcagc gtggtgaccg tgccctccag cagcttgggc 660 cagtcctcag gactctactc cctcagcagc gtggtgaccg tgccctccag cagcttgggc 660

acccagacct acatctgcaa cgtgaatcac aagcccagca acaccaaggt ggacaagaga 720 acccagacct acatctgcaa cgtgaatcac aagcccagca acaccaaggt ggacaagaga 720

gttgagccca aatcttgtga caaaactcac acatgcccac cgtgcccagc acctgaactc 780 gttgagccca aatcttgtga caaaactcac acatgcccac cgtgcccagc acctgaactc 780

ctggggggac cgtcagtctt cctcttcccc ccaaaaccca aggacaccct catgatctcc 840 ctggggggac cgtcagtctt cctcttcccc ccaaaaccca aggacaccct catgatctcc 840

cggacccctg aggtcacatg cgtggtggtg gacgtgagcc acgaagaccc tgaggtcaag 900 cggacccctg aggtcacatg cgtggtggtg gacgtgagcc acgaagaccc tgaggtcaag 900

ttcaactggt acgtggacgg cgtggaggtg cataatgcca agacaaagcc gcgggaggag 960 ttcaactggt acgtggacgg cgtggaggtg cataatgcca agacaaagcc gcgggaggag 960

cagtacaaca gcacgtaccg tgtggtcagc gtcctcaccg tcctgcacca ggactggctg 1020 cagtacaaca gcacgtaccg tgtggtcagc gtcctcaccg tcctgcacca ggactggctg 1020

aatggcaagg agtacaagtg caaggtctcc aacaaagccc tcccagcccc catcgagaaa 1080 aatggcaagg agtacaagtg caaggtctcc aacaaagccc tcccagcccc catcgagaaa 1080

accatctcca aagccaaagg gcagccccga gaaccacagg tgtacaccct gcccccatcc 1140 accatctcca aagccaaagg gcagccccga gaaccacagg tgtacaccct gcccccatcc 1140

cgggaggaga tgaccaagaa ccaggtcagc ctgacctgcc tggtcaaagg cttctatccc 1200 cgggaggaga tgaccaagaa ccaggtcagc ctgacctgcc tggtcaaagg cttctatccc 1200

agcgacatcg ccgtggagtg ggagagcaat gggcagccgg agaacaacta caagaccacg 1260 agcgacatcg ccgtggagtg ggagagcaat gggcagccgg agaacaacta caagaccacg 1260

cctcccgtgc tggactccga cggctccttc ttcctctata gcaagctcac cgtggacaag 1320 cctcccgtgc tggactccga cggctccttc ttcctctata gcaagctcac cgtggacaag 1320

agcaggtggc agcaggggaa cgtcttctca tgctccgtga tgcatgaggc tctgcacaac 1380 agcaggtggc agcaggggaa cgtcttctca tgctccgtga tgcatgaggc tctgcacaac 1380

cactacacgc agaagagcct ctccctgtcc ccgggtaaa 1419 cactacacgc agaagagcct ctccctgtcc ccgggtaaa 1419

Sequence Number (ID): 292 Sequence Number (ID): 292

Length: 1410 Length: 1410

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1410 - source, 1..1410

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcccag 60

gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg gggcctcagt gaaggtttcc 120 gtgcagctgg tgcagtctgg ggctgaggtg aagaagcctg gggcctcagt gaaggtttcc 120

tgcaaggcat ctggatacac cttcaccagc tactatatgc actgggtgcg acaggcccct 180 tgcaaggcat ctggatacac cttcaccagc tactatatgc actgggtgcg acaggcccct 180

ggacaagggc ttgagtggat gggaataatc aaccctagtg gtggtagcac aagctacgca 240 ggacaagggc ttgagtggat gggaataatc aaccctagtg gtggtagcac aagctacgca 240

cagaagttcc agggcagagt caccatgacc agggacacgt ccacgagcac agtctacatg 300 cagaagttcc agggcagagt caccatgacc agggacacgt ccacgagcac agtctacatg 300

gagctgagca gcctgagatc tgaggacacg gccgtgtatt actgtgcgat attagggtta 360 gagctgagca gcctgagatc tgaggacacg gccgtgtatt actgtgcgat attagggtta 360

catttggggg agttattatt cgacccctgg ggccagggaa ccctggtcac cgtctcctca 420 catttggggg agttattatt cgaccctgg ggccagggaa ccctggtcac cgtctcctca 420

gcgtcgacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 480 gcgtcgacca agggcccatc ggtcttcccc ctggcaccct cctccaagag caccctctggg 480

ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaacctgt gacggtctcg 540 ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaacctgt gacggtctcg 540

tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 600 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 600

ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 660 ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 660

tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagag agttgagccc 720 tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagag agttgagccc 720

aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 780 aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 780

ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 840 ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 840

gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 900 gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 900

tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 960 tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcggggagga gcagtacaac 960

agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 1020 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 1020

gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1080 gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1080

aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggaggag 1140 aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggaggag 1140

atgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1200 atgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1200

gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1260 gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1260

ctggactccg acggctcctt cttcctctat agcaagctca ccgtggacaa gagcaggtgg 1320 ctggactccg acggctcctt cttcctctat agcaagctca ccgtggacaa gagcaggtgg 1320

cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1380 cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1380

cagaagagcc tctccctgtc cccgggtaaa 1410 cagaagagcc tctccctgtc ccggggtaaa 1410

Sequence Number (ID): 293 Sequence Number (ID): 293

Length: 1398 Length: 1398

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1398 - source, 1..1398

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgag 60

gtgcagctgg tggagtctgg aggaggcttg atccagcctg gggggtccct gagactctcc 120 gtgcagctgg tggagtctgg aggaggcttg atccagcctg gggggtccct gagactctcc 120

tgtgcagcct cggggttcac cgtcagtagc aactacatga gctgggtccg ccaggctcca 180 tgtgcagcct cggggttcac cgtcagtagc aactacatga gctgggtccg ccaggctcca 180

gggaaggggc tggagtgggt ctcagttatt tatagcggtg gtagcacatt ctacgcagac 240 gggaaggggc tggagtgggt ctcagttatt tatagcggtg gtagcacatt ctacgcagac 240

tccgtgaagg gccgattcac catctccaga gacaattcca agaacacgct gtatcttcaa 300 tccgtgaagg gccgattcac catctccaga gacaattcca agaacacgct gtatcttcaa 300

atgaacagcc tgagagccga ggacacggcc gtgtattact gtgcgagaga tttcggagaa 360 gtgtattact gtgcgagaga tttcggagaa 360

cagtggtttg actactgggg ccagggaacc ctggtcaccg tctcctcagc gtcgaccaag 420 cagtggtttg actactgggg ccagggaacc ctggtcaccg tctcctcagc gtcgaccaag 420

ggcccatcgg tcttccccct ggcaccctcc tccaagagca cctctggggg cacagcggcc 480 ggcccatcgg tcttccccct ggcaccctcc tccaagagca cctctggggg cacagcggcc 480

ctgggctgcc tggtcaagga ctacttcccc gaacctgtga cggtctcgtg gaactcaggc 540 ctgggctgcc tggtcaagga ctacttcccc gaacctgtga cggtctcgtg gaactcaggc 540

gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 600 gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 600

ctcagcagcg tggtgaccgt gccctccagc agcttgggca cccagaccta catctgcaac 660 ctcagcagcg tggtgaccgt gccctccagc agcttgggca cccagaccta catctgcaac 660

gtgaatcaca agcccagcaa caccaaggtg gacaagagag ttgagcccaa atcttgtgac 720 gtgaatcaca agcccagcaa caccaaggtg gacaagagag ttgagcccaa atcttgtgac 720

aaaactcaca catgcccacc gtgcccagca cctgaactcc tggggggacc gtcagtcttc 780 aaaactcaca catgcccacc gtgcccagca cctgaactcc tggggggacc gtcagtcttc 780

ctcttccccc caaaacccaa ggacaccctc atgatctccc ggacccctga ggtcacatgc 840 ctcttcccc caaaacccaa ggacaccctc atgatctccc ggacccctga ggtcacatgc 840

gtggtggtgg acgtgagcca cgaagaccct gaggtcaagt tcaactggta cgtggacggc 900 gtggtggtgg acgtgagcca cgaagaccct gaggtcaagt tcaactggta cgtggacggc 900

gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agtacaacag cacgtaccgt 960 gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agtacaacag cacgtaccgt 960

gtggtcagcg tcctcaccgt cctgcaccag gactggctga atggcaagga gtacaagtgc 1020 gtggtcagcg tcctcaccgt cctgcaccag gactggctga atggcaagga gtacaagtgc 1020

aaggtctcca acaaagccct cccagccccc atcgagaaaa ccatctccaa agccaaaggg 1080 aaggtctcca acaaagccct cccagccccc atcgagaaaa ccatctccaa agccaaaggg 1080

cagccccgag aaccacaggt gtacaccctg cccccatccc gggaggagat gaccaagaac 1140 cagccccgag aaccacaggt gtacaccctg cccccatccc gggaggagat gaccaagaac 1140

caggtcagcc tgacctgcct ggtcaaaggc ttctatccca gcgacatcgc cgtggagtgg 1200 caggtcagcc tgacctgcct ggtcaaaggc ttctatccca gcgacatcgc cgtggagtgg 1200

gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 1260 gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 1260

ggctccttct tcctctatag caagctcacc gtggacaaga gcaggtggca gcaggggaac 1320 ggctccttct tcctctatag caagctcacc gtggacaaga gcaggtggca gcaggggaac 1320

gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacgca gaagagcctc 1380 gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacgca gaagagcctc 1380

tccctgtccc cgggtaaa 1398 tccctgtccc cgggtaaa 1398

Sequence Number (ID): 294 Sequence Number (ID): 294

Length: 1398 Length: 1398

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1398 - source, 1..1398

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgag 60

gtgcagctgg tggagtctgg gggaggcttg gtccagcctg gggggtccct gagactctcc 120 gtgcagctgg tggagtctgg gggaggcttg gtccagcctg gggggtccct gagactctcc 120

tgtgcagcct ctgaattcac cgtcagtagc aactacatga gctgggtccg ccaggctcca 180 tgtgcagcct ctgaattcac cgtcagtagc aactacatga gctgggtccg ccaggctcca 180

gggaaggggc tggagtgggt ctcagttatt tatagcggtg gtagcacata ctacgcagac 240 gggaaggggc tggagtgggt ctcagttatt tatagcggtg gtagcacata ctacgcagac 240

tccgtgaagg gcagattcac catctccaga gacaattcca agaacacgct gtatcttcaa 300 tccgtgaagg gcagattcac catctccaga gacaattcca agaacacgct gtatcttcaa 300

atgaacagcc tgagagccga ggacacggct gtgtattact gtgcgagaga tttcggggac 360 gtgtattact gtgcgagaga tttcggggac 360

tactactttg actactgggg ccagggaacc ctggtcaccg tctcctcagc gtcgaccaag 420 tactactttg actactgggg ccagggaacc ctggtcaccg tctcctcagc gtcgaccaag 420

ggcccatcgg tcttccccct ggcaccctcc tccaagagca cctctggggg cacagcggcc 480 ggcccatcgg tcttccccct ggcaccctcc tccaagagca cctctggggg cacagcggcc 480

ctgggctgcc tggtcaagga ctacttcccc gaacctgtga cggtctcgtg gaactcaggc 540 ctgggctgcc tggtcaagga ctacttcccc gaacctgtga cggtctcgtg gaactcaggc 540

gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 600 gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 600

ctcagcagcg tggtgaccgt gccctccagc agcttgggca cccagaccta catctgcaac 660 ctcagcagcg tggtgaccgt gccctccagc agcttgggca cccagaccta catctgcaac 660

gtgaatcaca agcccagcaa caccaaggtg gacaagagag ttgagcccaa atcttgtgac 720 gtgaatcaca agcccagcaa caccaaggtg gacaagagag ttgagcccaa atcttgtgac 720

aaaactcaca catgcccacc gtgcccagca cctgaactcc tggggggacc gtcagtcttc 780 aaaactcaca catgcccacc gtgcccagca cctgaactcc tggggggacc gtcagtcttc 780

ctcttccccc caaaacccaa ggacaccctc atgatctccc ggacccctga ggtcacatgc 840 ctcttcccc caaaacccaa ggacaccctc atgatctccc ggacccctga ggtcacatgc 840

gtggtggtgg acgtgagcca cgaagaccct gaggtcaagt tcaactggta cgtggacggc 900 gtggtggtgg acgtgagcca cgaagaccct gaggtcaagt tcaactggta cgtggacggc 900

gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agtacaacag cacgtaccgt 960 gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agtacaacag cacgtaccgt 960

gtggtcagcg tcctcaccgt cctgcaccag gactggctga atggcaagga gtacaagtgc 1020 gtggtcagcg tcctcaccgt cctgcaccag gactggctga atggcaagga gtacaagtgc 1020

aaggtctcca acaaagccct cccagccccc atcgagaaaa ccatctccaa agccaaaggg 1080 aaggtctcca acaaagccct cccagccccc atcgagaaaa ccatctccaa agccaaaggg 1080

cagccccgag aaccacaggt gtacaccctg cccccatccc gggaggagat gaccaagaac 1140 cagccccgag aaccacaggt gtacaccctg cccccatccc gggaggagat gaccaagaac 1140

caggtcagcc tgacctgcct ggtcaaaggc ttctatccca gcgacatcgc cgtggagtgg 1200 caggtcagcc tgacctgcct ggtcaaaggc ttctatccca gcgacatcgc cgtggagtgg 1200

gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 1260 gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 1260

ggctccttct tcctctatag caagctcacc gtggacaaga gcaggtggca gcaggggaac 1320 ggctccttct tcctctatag caagctcacc gtggacaaga gcaggtggca gcaggggaac 1320

gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacgca gaagagcctc 1380 gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacgca gaagagcctc 1380

tccctgtccc cgggtaaa 1398 tccctgtccc cgggtaaa 1398

Sequence Number (ID): 295 Sequence Number (ID): 295

Length: 1401 Length: 1401

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1401 - source, 1..1401

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgag 60

gtgcagctgg tggagactgg aggaggcttg atccagcctg gggggtccct gagactctcc 120 gtgcagctgg tggagactgg aggaggcttg atccagcctg gggggtccct gagactctcc 120

tgtgcagcct ctggcttcac cgtcagtagg aactacatga gctgggtccg ccaggctcca 180 tgtgcagcct ctggcttcac cgtcagtagg aactacatga gctgggtccg ccaggctcca 180

gggaaggggc tggagtgggt ctcacttatt tatagtggtg gtagcacatt ctacgcagac 240 gggaaggggc tggagtgggt ctcacttatt tatagtggtg gtagcacatt ctacgcagac 240

tccgtgaagg gccgattcac catctccaga gacgattcca agaacacgtt gtatcttcaa 300 tccgtgaagg gccgattcac catctccaga gacgattcca agaacacgtt gtatcttcaa 300

atgaacagcc tgagagccga ggacacggcc gtgtattact gtgcgagaga tctcctcgag 360 atgaacagcc tgagagccga ggacacggcc gtgtattact gtgcgagaga tctcctcgag 360

gtgggaggca gcgactactg gggccaggga accctggtca ccgtctcctc agcgtcgacc 420 gtgggaggca gcgactactg gggccaggga accctggtca ccgtctcctc agcgtcgacc 420

aagggcccat cggtcttccc cctggcaccc tcctccaaga gcacctctgg gggcacagcg 480 aagggcccat cggtcttccc cctggcaccc tcctccaaga gcacctctgg gggcacagcg 480

gccctgggct gcctggtcaa ggactacttc cccgaacctg tgacggtctc gtggaactca 540 gccctgggct gcctggtcaa ggactacttc cccgaacctg tgacggtctc gtggaactca 540

ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac 600 ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac 600

tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacccagac ctacatctgc 660 tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcaccagac ctacatctgc 660

aacgtgaatc acaagcccag caacaccaag gtggacaaga gagttgagcc caaatcttgt 720 aacgtgaatc acaagcccag caacaccaag gtggacaaga gagttgagcc caaatcttgt 720

gacaaaactc acacatgccc accgtgccca gcacctgaac tcctgggggg accgtcagtc 780 gacaaaactc acacatgccc accgtgccca gcacctgaac tcctgggggg accgtcagtc 780

ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca 840 ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca 840

tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac 900 tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac 900

ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtac 960 ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtac 960

cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaatggcaa ggagtacaag 1020 cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaatggcaa ggagtacaag 1020

tgcaaggtct ccaacaaagc cctcccagcc cccatcgaga aaaccatctc caaagccaaa 1080 tgcaaggtct ccaacaaagc cctcccagcc cccatcgaga aaaccatctc caaagccaaa 1080

gggcagcccc gagaaccaca ggtgtacacc ctgcccccat cccgggagga gatgaccaag 1140 gggcagcccc gagaaccaca ggtgtacacc ctgcccccat cccgggagga gatgaccaag 1140

aaccaggtca gcctgacctg cctggtcaaa ggcttctatc ccagcgacat cgccgtggag 1200 aaccaggtca gcctgacctg cctggtcaaa ggcttctatc ccagcgacat cgccgtggag 1200

tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 1260 tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 1260

gacggctcct tcttcctcta tagcaagctc accgtggaca agagcaggtg gcagcagggg 1320 gacggctcct tcttcctcta tagcaagctc accgtggaca agagcaggtg gcagcagggg 1320

aacgtcttct catgctccgt gatgcatgag gctctgcaca accactacac gcagaagagc 1380 aacgtcttct catgctccgt gatgcatgag gctctgcaca accactacac gcagaagagc 1380

ctctccctgt ccccgggtaa a 1401 ctctccctgt ccccggggtaa a 1401

Sequence Number (ID): 296 Sequence Number (ID): 296

Length: 1431 Length: 1431

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1431 - source, 1..1431

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgag 60

gtgcagctgt tggagtctgg gggaggcttg gtacagcctg gggggtccct gagactctcc 120 gtgcagctgt tggagtctgg gggaggcttg gtacagcctg gggggtccct gagactctcc 120

tgtgcagcct ctggattcac ctttagcagc tatgccatga gctgggtccg ccaggctcca 180 tgtgcagcct ctggattcac ctttagcagc tatgccatga gctgggtccg ccaggctcca 180

gggaaggggc tggagtgggt ctcagctatt agtggtagtg gtggtagcac atactacgca 240 gggaaggggc tggagtgggt ctcagctatt agtggtagtg gtggtagcac atactacgca 240

gactccgtga agggccggtt caccatctcc agagacaatt ccaagaacac gctgtatctg 300 gactccgtga agggccggtt caccatctcc agagacaatt ccaagaacac gctgtatctg 300

caaatgaaca gcctgagagc cgaggacacg gccgtatatt actgtgcgaa accactcttg 360 caaatgaaca gcctgagagc cgaggacacg gccgtatatt actgtgcgaa accactcttg 360

gggtacgatt tttggagtgg ttattatcgg ggtggctggt tcgacccctg gggccaggga 420 gggtacgatt tttggagtgg ttattatcgg ggtggctggt tcgacccctg gggccaggga 420

accctggtca ccgtctcctc agcgtcgacc aagggcccat cggtcttccc cctggcaccc 480 accctggtca ccgtctcctc agcgtcgacc aagggcccat cggtcttccc cctggcaccc 480

tcctccaaga gcacctctgg gggcacagcg gccctgggct gcctggtcaa ggactacttc 540 tcctccaaga gcacctctgg gggcacagcg gccctgggct gcctggtcaa ggactacttc 540

cccgaacctg tgacggtctc gtggaactca ggcgccctga ccagcggcgt gcacaccttc 600 cccgaacctg tgacggtctc gtggaactca ggcgccctga ccagcggcgt gcacaccttc 600

ccggctgtcc tacagtcctc aggactctac tccctcagca gcgtggtgac cgtgccctcc 660 ccggctgtcc tacagtcctc aggactctac tccctcagca gcgtggtgac cgtgccctcc 660

agcagcttgg gcacccagac ctacatctgc aacgtgaatc acaagcccag caacaccaag 720 agcagcttgg gcaccagac ctacatctgc aacgtgaatc acaagcccag caacaccaag 720

gtggacaaga gagttgagcc caaatcttgt gacaaaactc acacatgccc accgtgccca 780 gtggacaaga gagttgagcc caaatcttgt gacaaaactc acacatgccc accgtgccca 780

gcacctgaac tcctgggggg accgtcagtc ttcctcttcc ccccaaaacc caaggacacc 840 gcacctgaac tcctgggggg accgtcagtc ttcctcttcc ccccaaaacc caaggacacc 840

ctcatgatct cccggacccc tgaggtcaca tgcgtggtgg tggacgtgag ccacgaagac 900 ctcatgatct cccggacccc tgaggtcaca tgcgtggtgg tggacgtgag cccgaagac 900

cctgaggtca agttcaactg gtacgtggac ggcgtggagg tgcataatgc caagacaaag 960 cctgaggtca agttcaactg gtacgtggac ggcgtggagg tgcataatgc caagacaaag 960

ccgcgggagg agcagtacaa cagcacgtac cgtgtggtca gcgtcctcac cgtcctgcac 1020 ccgcgggagg agcagtacaa cagcacgtac cgtgtggtca gcgtcctcac cgtcctgcac 1020

caggactggc tgaatggcaa ggagtacaag tgcaaggtct ccaacaaagc cctcccagcc 1080 caggactggc tgaatggcaa ggagtacaag tgcaaggtct ccaacaaagc cctcccagcc 1080

cccatcgaga aaaccatctc caaagccaaa gggcagcccc gagaaccaca ggtgtacacc 1140 cccatcgaga aaaccatctc caaagccaaa gggcagcccc gagaaccaca ggtgtacacc 1140

ctgcccccat cccgggagga gatgaccaag aaccaggtca gcctgacctg cctggtcaaa 1200 ctgcccccat cccggggagga gatgaccaag aaccaggtca gcctgacctg cctggtcaaa 1200

ggcttctatc ccagcgacat cgccgtggag tgggagagca atgggcagcc ggagaacaac 1260 ggcttctatc ccagcgacat cgccgtggag tgggagca atgggcagcc ggagaacaac 1260

tacaagacca cgcctcccgt gctggactcc gacggctcct tcttcctcta tagcaagctc 1320 tacaagacca cgcctcccgt gctggactcc gacggctcct tcttcctcta tagcaagctc 1320

accgtggaca agagcaggtg gcagcagggg aacgtcttct catgctccgt gatgcatgag 1380 accgtggaca agagcaggtg gcagcagggg aacgtcttct catgctccgt gatgcatgag 1380

gctctgcaca accactacac gcagaagagc ctctccctgt ccccgggtaa a 1431 gctctgcaca accactacac gcagaagagc ctctccctgt ccccgggtaa a 1431

Sequence Number (ID): 297 Sequence Number (ID): 297

Length: 1404 Length: 1404

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1404 - source, 1..1404

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgag 60

gtgcagctgg tggagtctgg aggaggcttg atccagcctg gggggtccct gagactctcc 120 gtgcagctgg tggagtctgg aggaggcttg atccagcctg gggggtccct gagactctcc 120

tgtgcagcct ctgggttcac cgtcagtagc aactacatga gctgggtccg ccaggctcca 180 tgtgcagcct ctgggttcac cgtcagtagc aactacatga gctgggtccg ccaggctcca 180

gggaaggggc tggagtgggt ctcagttatt tatagcggtg gtagcacata ctacgcagac 240 gggaaggggc tggagtgggt ctcagttatt tatagcggtg gtagcacata ctacgcagac 240

tccgtgaagg gccgattcat catctccaga gacaattcca agaacacgct gtatcttcaa 300 tccgtgaagg gccgattcat catctccaga gacaattcca agaacacgct gtatcttcaa 300

atgaacagcc tgagagccga ggacacggcc gtgtattact gtgcgagaga tccatacagc 360 atgaacagcc tgagagccga ggacacggcc gtgtattact gtgcgagaga tccatacagc 360

tatggtcgag gtggcggcta ctggggccag ggaaccctgg tcaccgtctc ctcagcgtcg 420 tatggtcgag gtggcggcta ctggggccag ggaaccctgg tcaccgtctc ctcagcgtcg 420

accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480 accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480

gcggccctgg gctgcctggt caaggactac ttccccgaac ctgtgacggt ctcgtggaac 540 gcggccctgg gctgcctggt caaggactac ttccccgaac ctgtgacggt ctcgtggaac 540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600 tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660 tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agagagttga gcccaaatct 720 tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agagagttga gcccaaatct 720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780 tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840 gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840

acatgcgtgg tggtggacgt gagccacgaa gaccctgagg tcaagttcaa ctggtacgtg 900 acatgcgtgg tggtggacgt gagccacgaa gaccctgagg tcaagttcaa ctggtacgtg 900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960 gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020 taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080 aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga ggagatgacc 1140 aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga ggagatgacc 1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200 aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260 1260

tccgacggct ccttcttcct ctatagcaag ctcaccgtgg acaagagcag gtggcagcag 1320 tccgacggct ccttcttcct ctatagcaag ctcaccgtgg acaagagcag gtggcagcag 1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380 gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380

agcctctccc tgtccccggg taaa 1404 agcctctccc tgtcccgggg taaa 1404

Sequence Number (ID): 298 Sequence Number (ID): 298

Length: 1398 Length: 1398

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1398 - source, 1..1398

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgag 60

gtgcagctgg tggagactgg aggaggcttg atccagcctg gggggtccct gagactctcc 120 gtgcagctgg tggagactgg aggaggcttg atccagcctg gggggtccct gagactctcc 120

tgtgcagcct ctgggctcac cgtcagtagc aactacatga actgggtccg ccaggctcca 180 tgtgcagcct ctgggctcac cgtcagtagc aactacatga actgggtccg ccaggctcca 180

gggaaggggc tggagtgggt ctcagttatt tatagcggtg gtagcacata ctacgcagac 240 gggaaggggc tggagtgggt ctcagttatt tatagcggtg gtagcacata ctacgcagac 240

tccgtgaagg gccgattcac catctccaga gacaattcca agaacacgct gtatcttcaa 300 tccgtgaagg gccgattcac catctccaga gacaattcca agaacacgct gtatcttcaa 300

atgaacagcc tgagagccga ggacacggcc gtgtattact gtgcgagaga tggggtctac 360 atgaacagcc tgagagccga ggacacggcc gtgtattact gtgcgagaga tggggtctac 360

tacggtatgg acgtctgggg ccaagggacc acggtcaccg tctcctcagc gtcgaccaag 420 tacggtatgg acgtctgggg ccaagggacc acggtcaccg tctcctcagc gtcgaccaag 420

ggcccatcgg tcttccccct ggcaccctcc tccaagagca cctctggggg cacagcggcc 480 ggcccatcgg tcttccccct ggcaccctcc tccaagagca cctctggggg cacagcggcc 480

ctgggctgcc tggtcaagga ctacttcccc gaacctgtga cggtctcgtg gaactcaggc 540 ctgggctgcc tggtcaagga ctacttcccc gaacctgtga cggtctcgtg gaactcaggc 540

gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 600 gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 600

ctcagcagcg tggtgaccgt gccctccagc agcttgggca cccagaccta catctgcaac 660 ctcagcagcg tggtgaccgt gccctccagc agcttgggca cccagaccta catctgcaac 660

gtgaatcaca agcccagcaa caccaaggtg gacaagagag ttgagcccaa atcttgtgac 720 gtgaatcaca agcccagcaa caccaaggtg gacaagagag ttgagcccaa atcttgtgac 720

aaaactcaca catgcccacc gtgcccagca cctgaactcc tggggggacc gtcagtcttc 780 aaaactcaca catgcccacc gtgcccagca cctgaactcc tggggggacc gtcagtcttc 780

ctcttccccc caaaacccaa ggacaccctc atgatctccc ggacccctga ggtcacatgc 840 ctcttcccc caaaacccaa ggacaccctc atgatctccc ggacccctga ggtcacatgc 840

gtggtggtgg acgtgagcca cgaagaccct gaggtcaagt tcaactggta cgtggacggc 900 gtggtggtgg acgtgagcca cgaagaccct gaggtcaagt tcaactggta cgtggacggc 900

gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agtacaacag cacgtaccgt 960 gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agtacaacag cacgtaccgt 960

gtggtcagcg tcctcaccgt cctgcaccag gactggctga atggcaagga gtacaagtgc 1020 gtggtcagcg tcctcaccgt cctgcaccag gactggctga atggcaagga gtacaagtgc 1020

aaggtctcca acaaagccct cccagccccc atcgagaaaa ccatctccaa agccaaaggg 1080 aaggtctcca acaaagccct cccagccccc atcgagaaaa ccatctccaa agccaaaggg 1080

cagccccgag aaccacaggt gtacaccctg cccccatccc gggaggagat gaccaagaac 1140 cagccccgag aaccacaggt gtacaccctg cccccatccc gggaggagat gaccaagaac 1140

caggtcagcc tgacctgcct ggtcaaaggc ttctatccca gcgacatcgc cgtggagtgg 1200 caggtcagcc tgacctgcct ggtcaaaggc ttctatccca gcgacatcgc cgtggagtgg 1200

gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 1260 gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 1260

ggctccttct tcctctatag caagctcacc gtggacaaga gcaggtggca gcaggggaac 1320 ggctccttct tcctctatag caagctcacc gtggacaaga gcaggtggca gcaggggaac 1320

gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacgca gaagagcctc 1380 gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacgca gaagagcctc 1380

tccctgtccc cgggtaaa 1398 tccctgtccc cgggtaaa 1398

Sequence Number (ID): 299 Sequence Number (ID): 299

Length: 1419 Length: 1419

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..1419 - source, 1..1419

> mol_type, other DNA > mol_type, other DNA

> note, heavy chain > note, heavy chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: residences:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgag 60

gtgcagctgg tggagtctgg gggaggcgtg gtccagcctg ggaggtccct gagactctcc 120 gtgcagctgg tggagtctgg gggaggcgtg gtccagcctg ggaggtccct gagactctcc 120

tgtgcagcct ctggattcac cttcagtagc tatggcatgc actgggtccg ccaggctcca 180 tgtgcagcct ctggattcac cttcagtagc tatggcatgc actgggtccg ccaggctcca 180

ggcaaggggc tggagtgggt ggcagttata tcatatgatg gaagtaataa atactacgca 240 ggcaaggggc tggagtgggt ggcagttata tcatatgatg gaagtaataa atactacgca 240

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctg 300 gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctg 300

caaatgaaca gcctgagagc tgaggacacg gctgtgtatt actgtgcgaa ggattacgat 360 caaatgaaca gctgagagc tgaggacacg gctgtgtatt actgtgcgaa ggattacgat 360

ttttggagtg gttattaccc ccagcccttt gactactggg gccagggaac cctggtcacc 420 ttttggagtg gttattaccc ccagcccttt gactactggg gccagggaac cctggtcacc 420

gtctcctcag cgtcgaccaa gggcccatcg gtcttccccc tggcaccctc ctccaagagc 480 gtctcctcag cgtcgaccaa gggcccatcg gtcttccccc tggcaccctc ctccaagagc 480

acctctgggg gcacagcggc cctgggctgc ctggtcaagg actacttccc cgaacctgtg 540 acctctgggg gcacagcggc cctgggctgc ctggtcaagg actacttccc cgaacctgtg 540

acggtctcgt ggaactcagg cgccctgacc agcggcgtgc acaccttccc ggctgtccta 600 acggtctcgt ggaactcagg cgccctgacc agcggcgtgc acaccttccc ggctgtccta 600

cagtcctcag gactctactc cctcagcagc gtggtgaccg tgccctccag cagcttgggc 660 cagtcctcag gactctactc cctcagcagc gtggtgaccg tgccctccag cagcttgggc 660

acccagacct acatctgcaa cgtgaatcac aagcccagca acaccaaggt ggacaagaga 720 acccagacct acatctgcaa cgtgaatcac aagcccagca acaccaaggt ggacaagaga 720

gttgagccca aatcttgtga caaaactcac acatgcccac cgtgcccagc acctgaactc 780 gttgagccca aatcttgtga caaaactcac acatgcccac cgtgcccagc acctgaactc 780

ctggggggac cgtcagtctt cctcttcccc ccaaaaccca aggacaccct catgatctcc 840 ctggggggac cgtcagtctt cctcttcccc ccaaaaccca aggacaccct catgatctcc 840

cggacccctg aggtcacatg cgtggtggtg gacgtgagcc acgaagaccc tgaggtcaag 900 cggacccctg aggtcacatg cgtggtggtg gacgtgagcc acgaagaccc tgaggtcaag 900

ttcaactggt acgtggacgg cgtggaggtg cataatgcca agacaaagcc gcgggaggag 960 ttcaactggt acgtggacgg cgtggaggtg cataatgcca agacaaagcc gcgggaggag 960

cagtacaaca gcacgtaccg tgtggtcagc gtcctcaccg tcctgcacca ggactggctg 1020 cagtacaaca gcacgtaccg tgtggtcagc gtcctcaccg tcctgcacca ggactggctg 1020

aatggcaagg agtacaagtg caaggtctcc aacaaagccc tcccagcccc catcgagaaa 1080 aatggcaagg agtacaagtg caaggtctcc aacaaagccc tcccagcccc catcgagaaa 1080

accatctcca aagccaaagg gcagccccga gaaccacagg tgtacaccct gcccccatcc 1140 accatctcca aagccaaagg gcagccccga gaaccacagg tgtacaccct gcccccatcc 1140

cgggaggaga tgaccaagaa ccaggtcagc ctgacctgcc tggtcaaagg cttctatccc 1200 cgggaggaga tgaccaagaa ccaggtcagc ctgacctgcc tggtcaaagg cttctatccc 1200

agcgacatcg ccgtggagtg ggagagcaat gggcagccgg agaacaacta caagaccacg 1260 agcgacatcg ccgtggagtg ggagagcaat gggcagccgg agaacaacta caagaccacg 1260

cctcccgtgc tggactccga cggctccttc ttcctctata gcaagctcac cgtggacaag 1320 cctcccgtgc tggactccga cggctccttc ttcctctata gcaagctcac cgtggacaag 1320

agcaggtggc agcaggggaa cgtcttctca tgctccgtga tgcatgaggc tctgcacaac 1380 agcaggtggc agcaggggaa cgtcttctca tgctccgtga tgcatgaggc tctgcacaac 1380

cactacacgc agaagagcct ctccctgtcc ccgggtaaa 1419 cactacacgc agaagagcct ctccctgtcc ccgggtaaa 1419

Sequence Number (ID): 300 Sequence Number (ID): 300

Length: 699 Length: 699

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..699 -source, 1..699

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgac 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgac 60

atccagatga cccagtctcc atcctccctg tctgcatctg taggagacag agtcaccatc 120 atccagatga cccagtctcc atcctccctg tctgcatctg taggagacag agtcaccatc 120

acttgccggg caagtcagag cattagcagc tatttaaatt ggtatcagca gaaaccaggg 180 acttgccggg caagtcagag cattagcagc tatttaaatt ggtatcagca gaaaccaggg 180

aaagccccta agctcctgat ctatgctgca tccagtttgc aaagtggggt cccatcaagg 240 aaagccccta agctcctgat ctatgctgca tccagtttgc aaagtggggt cccatcaagg 240

ttcagtggca gtggatctgg gacagatttc actctcacca tcagcagtct gcaacctgaa 300 ttcagtggca gtggatctgg gacagatttc actctcacca tcagcagtct gcaacctgaa 300

gattttgcaa cttactactg tcaacagagt tacagtaccc ctggcagttt tggccagggg 360 gattttgcaa cttactactg tcaacagagt tacagtaccc ctggcagttt tggccagggg 360

accaagctgg agatcaaacg tacggtggct gcaccatctg tcttcatctt cccgccatct 420 accaagctgg agatcaaacg tacggtggct gcaccatctg tcttcatctt cccgccatct 420

gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 480 gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 480

agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 540 agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 540

agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 600 agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 600

agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg 660 agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg 660

agctcgcccg tcacaaagag cttcaacagg ggagagtgt 699 agctcgcccg tcacaaagag cttcaacagg ggagagtgt 699

Sequence Number (ID): 301 Sequence Number (ID): 301

Length: 705 Length: 705

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..705 - source, 1..705

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggttc ctgggcccag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggttc ctgggcccag 60

tctgtgctga ctcagccacc ctcagcgtct gggacccccg ggcagagggt caccatctct 120 tctgtgctga ctcagccacc ctcagcgtct gggacccccg ggcagagggt caccatctct 120

tgttctggaa gtagctccaa catcggaaga aatactgtaa actggtacca gcagctccca 180 tgttctggaa gtagctccaa catcggaaga aatactgtaa actggtacca gcagctccca 180

ggaacggccc ccaaactcgt catctatagt aataatcagc ggccctcagg ggtccctgac 240 ggaacggccc ccaaactcgt catctatagt aataatcagc ggccctcagg ggtccctgac 240

cgattctctg gctccaagtc tggcacctca gcctccctgg ccatcagtgg gctccagtct 300 cgattctctg gctccaagtc tggcacctca gcctccctgg ccatcagtgg gctccagtct 300

gaggatgagg ctgattatta ctgtgcagca tgggatgaca gcctgaatgg tctggtattc 360 gaggatgagg ctgattatta ctgtgcagca tgggatgaca gcctgaatgg tctggtattc 360

ggcggaggga ccaagctgac cgtcctaggt cagcccaagg ctgccccctc ggtcactctg 420 ggcgggaggga ccaagctgac cgtcctaggt cagcccaagg ctgccccctc ggtcactctg 420

ttcccaccct cgagtgagga gcttcaagcc aacaaggcca cactggtgtg tctcataagt 480 ttcccaccct cgagtgagga gcttcaagcc aacaaggcca cactggtgtg tctcataagt 480

gacttctacc cgggagccgt gacagtggcc tggaaggcag atagcagccc cgtcaaggcg 540 gacttctacc cgggagccgt gacagtggcc tggaaggcag atagcagccc cgtcaaggcg 540

ggagtggaga ccaccacacc ctccaaacaa agcaacaaca agtacgcggc cagcagctac 600 ggagtggaga ccaccacacc ctccaaacaa agcaacaaca agtacgcggc cagcagctac 600

ctgagcctga cgcctgagca gtggaagtcc cacagaagct acagctgcca ggtcacgcat 660 ctgagcctga cgcctgagca gtggaagtcc cacagaagct acagctgcca ggtcacgcat 660

gaagggagca ccgtggagaa gacagtcgcc ccaactgagt gttct 705 gaagggagca ccgtggagaa gacagtcgcc ccaactgagt gttct 705

Sequence Number (ID): 302 Sequence Number (ID): 302

Length: 717 Length: 717

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..717 - source, 1..717

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcggac 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcggac 60

atcgtgatga cccagtctcc agactccctg gctgtgtctc tgggcgagag ggccaccatc 120 atcgtgatga cccagtctcc agactccctg gctgtgtctc tgggcgagag ggccaccatc 120

aactgcaagt ccagccagag tgttttatac agcttcagga ataagatctg cttagcttgg 180 180

taccagcaga aaccaggaca gcctcctaaa ctgctcattt actgggcaac tacccgggaa 240 taccagcaga aaccaggaca gcctcctaaa ctgctcattt actgggcaac tacccgggaa 240

tccggggtcc ctgaccgatt cagtggcagc gggtctggga cagatttcac tctcaccatc 300 tccggggtcc ctgaccgatt cagtggcagc gggtctggga cagatttcac tctcaccatc 300

agcagcctgc aggctgaaga tgtggctgtt tattactgtc agcaatttta tagtactccg 360 agcagcctgc aggctgaaga tgtggctgtt tattactgtc agcaatttta tagtactccg 360

tggacgttcg gccaagggac caaggtggaa atcaaacgta cggtggctgc accatctgtc 420 tggacgttcg gccaagggac caaggtggaa atcaaacgta cggtggctgc accatctgtc 420

ttcatcttcc cgccatctga tgagcagttg aaatctggaa ctgcctctgt tgtgtgcctg 480 ttcatcttcc cgccatctga tgagcagttg aaatctggaa ctgcctctgt tgtgtgcctg 480

ctgaataact tctatcccag agaggccaaa gtacagtgga aggtggataa cgccctccaa 540 ctgaataact tctatcccag agaggccaaa gtacagtgga aggtggataa cgccctccaa 540

tcgggtaact cccaggagag tgtcacagag caggacagca aggacagcac ctacagcctc 600 tcgggtaact cccaggagag tgtcacagag caggacagca aggacagcac ctacagcctc 600

agcagcaccc tgacgctgag caaagcagac tacgagaaac acaaagtcta cgcctgcgaa 660 agcagcaccc tgacgctgag caaagcagac tacgagaaac acaaagtcta cgcctgcgaa 660

gtcacccatc agggcctgag ctcgcccgtc acaaagagct tcaacagggg agagtgt 717 gtcacccatc agggcctgag ctcgcccgtc acaaagagct tcaacagggg agagtgt 717

Sequence Number (ID): 303 Sequence Number (ID): 303

Length: 705 Length: 705

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..705 - source, 1..705

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggttc ctgggcccag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggttc ctgggcccag 60

tctgccctga ctcagtctgc ctccgtgtct gggtctcctg gacagccgat caccatctcc 120 tctgccctga ctcagtctgc ctccgtgtct gggtctcctg gacagccgat caccatctcc 120

tgcactggaa ccagcagtga tgttgggagt tataaccttg tctcctggta ccaacagcac 180 tgcactggaa ccagcagtga tgttgggagt tataaccttg tctcctggta ccaacagcac 180

ccaggcaaag cccccaaact catgatttat gaggtcagta agcggccctc aggggtttct 240 ccaggcaaag cccccaaact catgattat gaggtcagta agcggccctc aggggtttct 240

aatcgcttct ctggctccaa gtctggcaac acggcctccc tgacaatctc tgggctccag 300 aatcgcttct ctggctccaa gtctggcaac acggcctccc tgacaatctc tgggctccag 300

gctgaggacg aggctgatta ttactgctgc tcatatgcag atagtaggac tttggtgttc 360 gctgaggacg aggctgatta ttactgctgc tcatatgcag atagtaggac tttggtgttc 360

ggcggaggga ccaagctgac cgtcctaggt cagcccaagg ctgccccctc ggtcactctg 420 ggcgggaggga ccaagctgac cgtcctaggt cagcccaagg ctgccccctc ggtcactctg 420

ttcccgccct cgagtgagga gcttcaagcc aacaaggcca cactggtgtg tctcataagt 480 ttcccgccct cgagtgagga gcttcaagcc aacaaggcca cactggtgtg tctcataagt 480

gacttctacc cgggagccgt gacagtggcc tggaaggcag atagcagccc cgtcaaggcg 540 gacttctacc cgggagccgt gacagtggcc tggaaggcag atagcagccc cgtcaaggcg 540

ggagtggaga ccaccacacc ctccaaacaa agcaacaaca agtacgcggc cagcagctac 600 ggagtggaga ccaccacacc ctccaaacaa agcaacaaca agtacgcggc cagcagctac 600

ctgagcctga cgcctgagca gtggaagtcc cacagaagct acagctgcca ggtcacgcat 660 ctgagcctga cgcctgagca gtggaagtcc cacagaagct acagctgcca ggtcacgcat 660

gaagggagca ccgtggagaa gacagtcgcc ccaactgagt gttct 705 gaagggagca ccgtggagaa gacagtcgcc ccaactgagt gttct 705

Sequence Number (ID): 304 Sequence Number (ID): 304

Length: 705 Length: 705

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..705 - source, 1..705

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgac 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgac 60

atccagatga cccagtctcc atcctccctg tctgcatctg taggagacag agtcaccatc 120 atccagatga cccagtctcc atcctccctg tctgcatctg taggagacag agtcaccatc 120

acttgccagg cgagtcagga cattagcaac tatttaaatt ggtatcagca gaaaccaggg 180 acttgccagg cgagtcagga cattagcaac tatttaaatt ggtatcagca gaaaccaggg 180

aaagccccta agctcctgat ctacgatgca tccaatttgg aaacaggggt cccatcaagg 240 aaagccccta agctcctgat ctacgatgca tccaatttgg aaacaggggt cccatcaagg 240

ttcagtggaa gtggatctgg gacagatttt actttcacca tcagcagcct gcagcctgaa 300 ttcagtggaa gtggatctgg gacagatttt actttcacca tcagcagcct gcagcctgaa 300

gatattgcaa catattactg tcaacagtat gataatctcc ctccgagggt gacgttcggc 360 gatattgcaa catattactg tcaacagtat gataatctcc ctccgagggt gacgttcggc 360

caagggacca aggtggaaat caaacgtacg gtggctgcac catctgtctt catcttcccg 420 caagggacca aggtggaaat caaacgtacg gtggctgcac catctgtctt catcttcccg 420

ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 480 ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 480

tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 540 tatccgag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 540

caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 600 caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 600

acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 660 acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 660

ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgt 705 ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgt 705

Sequence Number (ID): 305 Sequence Number (ID): 305

Length: 702 Length: 702

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..702 - source, 1..702

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggttc ctgggcccag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggttc ctgggcccag 60

tctgccctga ctcagcctgc ctccgtgtct gggtctcctg gacagtcgat caccatctcc 120 tctgccctga ctcagcctgc ctccgtgtct gggtctcctg gacagtcgat caccatctcc 120

tgcactggaa ccagcagtga tgttgggagt tatgaccttg tctcctggta ccaacagcac 180 tgcactggaa ccagcagtga tgttgggagt tatgaccttg tctcctggta ccaacagcac 180

ccaggcaaag cccccaaact catgatttat gaggtcacta agcggccctc aggggtttct 240 ccaggcaaag cccccaaact catgattat gaggtcacta agcggccctc aggggtttct 240

aatcgcttct ctggctccaa gtctggcaac acggcctccc tgacaatctc tgggctccag 300 aatcgcttct ctggctccaa gtctggcaac acggcctccc tgacaatctc tgggctccag 300

gctgaggacg aggctgatta ttactgctgc tcatttgcag gtagtagccc cttgttcggc 360 gctgaggacg aggctgatta ttactgctgc tcatttgcag gtagtagccc cttgttcggc 360

ggagggacca agctgaccgt cctaggtcag cccaaggctg ccccctcggt cactctgttc 420 ggagggacca agctgaccgt cctaggtcag cccaaggctg ccccctcggt cactctgttc 420

ccaccctcga gtgaggagct tcaagccaac aaggccacac tggtgtgtct cataagtgac 480 ccaccctcga gtgaggagct tcaagccaac aaggccacac tggtgtgtct cataagtgac 480

ttctacccgg gagccgtgac agtggcctgg aaggcagata gcagccccgt caaggcggga 540 ttctacccgg gagccgtgac agtggcctgg aaggcagata gcagccccgt caaggcggga 540

gtggagacca ccacaccctc caaacaaagc aacaacaagt acgcggccag cagctacctg 600 gtggagacca ccacaccctc caaacaaagc aacaacaagt acgcggccag cagctacctg 600

agcctgacgc ctgagcagtg gaagtcccac agaagctaca gctgccaggt cacgcatgaa 660 agcctgacgc ctgagcagtg gaagtcccac agaagctaca gctgccaggt cacgcatgaa 660

gggagcaccg tggagaagac agtcgcccca actgagtgtt ct 702 gggagcaccg tggagaagac agtcgcccca actgagtgtt ct 702

Sequence Number (ID): 306 Sequence Number (ID): 306

Length: 699 Length: 699

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..699 -source, 1..699

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgac 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgac 60

atccagatga cccagtctcc ttccaccctg tctgcatctg taggagacag agtcaccatc 120 atccagatga cccagtctcc ttccaccctg tctgcatctg taggagacag agtcaccatc 120

acttgccggg ccagtcagag tattagtagc tggttggcct ggtatcagca gaaaccaggg 180 acttgccggg ccagtcagag tattagtagc tggttggcct ggtatcagca gaaaccaggg 180

aaagccccta aggtcctgat ctataaggcg tctagtttag aaagtggggt cccatcaagg 240 aaagccccta aggtcctgat ctataaggcg tctagtttag aaagtggggt cccatcaagg 240

ttcagcggca gtggatctgg gacagaattc actctcacca tcagcagcct gcagcctgat 300 ttcagcggca gtggatctgg gacagaattc actctcacca tcagcagcct gcagcctgat 300

gattttgcaa cttattactg ccaacagtat aatagttatt ctccaatgtt cggccaaggg 360 gattttgcaa cttattactg ccaacagtat aatagtttatt ctccaatgtt cggccaaggg 360

accaaggtgg aaatcaaacg tacggtggct gcaccatctg tcttcatctt cccgccatct 420 accaaggtgg aaatcaaacg tacggtggct gcaccatctg tcttcatctt cccgccatct 420

gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 480 gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 480

agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 540 agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 540

agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 600 agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 600

agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg 660 agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg 660

agctcgcccg tcacaaagag cttcaacagg ggagagtgt 699 agctcgcccg tcacaaagag cttcaacagg ggagagtgt 699

Sequence Number (ID): 307 Sequence Number (ID): 307

Length: 702 Length: 702

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..702 - source, 1..702

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcagaa 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcagaa 60

attgtgttga cgcagtctcc aggcaccctg tctttgtctc caggggaaag agccaccctc 120 attgtgttga cgcagtctcc aggcaccctg tctttgtctc caggggaaag agccaccctc 120

tcctgcaggg ccagtcagag tgttagcagc agctacttag cctggtacca gcagaaacct 180 tcctgcaggg ccagtcagag tgttagcagc agctacttag cctggtacca gcagaaacct 180

ggccaggctc ccaggctcct catctatggt gcatccagca gggccactgg catcccagac 240 ggccaggctc ccaggctcct catctatggt gcatccagca gggccactgg catcccagac 240

aggttcagtg gcagtgggtc tgggacagac ttcactctca ccatcagcag actggagcct 300 aggttcagtg gcagtgggtc tgggacagac ttcactctca ccatcagcag actggagcct 300

gaagattttg cagtgtatta ctgtcaccag tatggtagct cacctcgaac gttcggccaa 360 gaagattttg cagtgtatta ctgtcaccag tatggtagct cacctcgaac gttcggccaa 360

gggaccaagg tggagatcaa acgtacggtg gctgcaccat ctgtcttcat cttcccgcca 420 gggaccaagg tggagatcaa acgtacggtg gctgcaccat ctgtcttcat cttcccgcca 420

tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480

cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540

gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600

ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 660 ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 660

ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gt 702 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gt 702

Sequence Number (ID): 308 Sequence Number (ID): 308

Length: 705 Length: 705

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..705 - source, 1..705

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggttc ctgggcccag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggttc ctgggcccag 60

tctgtgctga ctcagccacc ctcagcgtct gggacccccg ggcagagggt caccatctct 120 tctgtgctga ctcagccacc ctcagcgtct gggacccccg ggcagagggt caccatctct 120

tgttctggaa gcagctccaa catcggaagt aatactgtaa actggtacca gcagctccca 180 tgttctggaa gcagctccaa catcggaagt aatactgtaa actggtacca gcagctccca 180

ggaacggccc ccaaactcct catctataat aataatcaac ggccctcagg ggtccctgac 240 ggaacggccc ccaaactcct catctataat aataatcaac ggccctcagg ggtccctgac 240

cgattctctg gctccaagtc tggcacctca gcctccctgg ccatcagtgg gctccagtct 300 cgattctctg gctccaagtc tggcacctca gcctccctgg ccatcagtgg gctccagtct 300

gaggatgagg ctgattatta ctgtgcagca tgggatgaca gcctgaatgg ttatgtcttc 360 360

ggaactggga ccaaggtcac cgtcctaggt cagcccaagg ccaaccccac tgtcactctg 420 ggaactggga ccaaggtcac cgtcctaggt cagcccaagg ccaaccccac tgtcactctg 420

ttcccaccct cgagtgagga gcttcaagcc aacaaggcca cactggtgtg tctcataagt 480 ttcccaccct cgagtgagga gcttcaagcc aacaaggcca cactggtgtg tctcataagt 480

gacttctacc cgggagccgt gacagtggcc tggaaggcag atagcagccc cgtcaaggcg 540 gacttctacc cgggagccgt gacagtggcc tggaaggcag atagcagccc cgtcaaggcg 540

ggagtggaga ccaccacacc ctccaaacaa agcaacaaca agtacgcggc cagcagctac 600 ggagtggaga ccaccacacc ctccaaacaa agcaacaaca agtacgcggc cagcagctac 600

ctgagcctga cgcctgagca gtggaagtcc cacagaagct acagctgcca ggtcacgcat 660 ctgagcctga cgcctgagca gtggaagtcc cacagaagct acagctgcca ggtcacgcat 660

gaagggagca ccgtggagaa gacagtcgcc ccaactgagt gttct 705 gaagggagca ccgtggagaa gacagtcgcc ccaactgagt gttct 705

Sequence Number (ID): 309 Sequence Number (ID): 309

Length: 699 Length: 699

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..699 -source, 1..699

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgac 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgac 60

atccagatga cccagtctcc atcctccctg tctacatctg taggagacag agtcaccatc 120 atccagatga cccagtctcc atcctccctg tctacatctg taggagacag agtcaccatc 120

acttgccggg caagtcagag cattagcaag tatttaaatt ggtatcagca gaaaccaggg 180 acttgccggg caagtcagag cattagcaag tatttaaatt ggtatcagca gaaaccaggg 180

aaagccccta agctcctgat ctatgctgca tccagtttgc aaagtggggt cccatcaagg 240 aaagccccta agctcctgat ctatgctgca tccagtttgc aaagtggggt cccatcaagg 240

ttcagtggca gtggatctgg gacagatttc actctcacca tcagcagtct gcaacctgaa 300 ttcagtggca gtggatctgg gacagatttc actctcacca tcagcagtct gcaacctgaa 300

gattttgcaa cttactactg tcaacagagt tatagtaccc ctccgacgtt cggccaaggg 360 gattttgcaa cttactactg tcaacagagt tatagtaccc ctccgacgtt cggccaaggg 360

accaaggtgg aaatcaaacg tacggtggct gcaccatctg tcttcatctt cccgccatct 420 accaaggtgg aaatcaaacg tacggtggct gcaccatctg tcttcatctt cccgccatct 420

gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 480 gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 480

agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 540 agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 540

agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 600 agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 600

agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg 660 agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg 660

agctcgcccg tcacaaagag cttcaacagg ggagagtgt 699 agctcgcccg tcacaaagag cttcaacagg ggagagtgt 699

Sequence Number (ID): 310 Sequence Number (ID): 310

Length: 705 Length: 705

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..705 - source, 1..705

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgac 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgac 60

atccagatga cccagtctcc atcctccctg tctgcatctg taggagacag agtcaccatc 120 atccagatga cccagtctcc atcctccctg tctgcatctg taggagacag agtcaccatc 120

acttgccagg cgagtcagga cattagcaac tatttaaatt ggtatcagca gaaaccaggg 180 acttgccagg cgagtcagga cattagcaac tatttaaatt ggtatcagca gaaaccaggg 180

aaagccccta agctcctgat ctacgatgca tccaatttgg aaacaggggt cccatcaagg 240 aaagccccta agctcctgat ctacgatgca tccaatttgg aaacaggggt cccatcaagg 240

ttcagtggaa gtggatctgg gacagatttt actttcacca tcagcagcct gcagcctgaa 300 ttcagtggaa gtggatctgg gacagatttt actttcacca tcagcagcct gcagcctgaa 300

gatattgcta catattactg tcaacagtat gataatctcc ctccgcggct cactttcggc 360 gatattgcta catattactg tcaacagtat gataatctcc ctccgcggct cactttcggc 360

ggagggacca aggtggaaat caaacgtacg gtggctgcac catctgtctt catcttcccg 420 ggagggacca aggtggaaat caaacgtacg gtggctgcac catctgtctt catcttcccg 420

ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 480 ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 480

tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 540 tatccgag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 540

caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 600 caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 600

acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 660 acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 660

ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgt 705 ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgt 705

Sequence Number (ID): 311 Sequence Number (ID): 311

Length: 708 Length: 708

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..708 - source, 1..708

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggttc ctgggcccag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggttc ctgggcccag 60

tctgccctga ctcagcctgc ctccgtgtct gggtctcctg gacagtcgat caccatctcc 120 tctgccctga ctcagcctgc ctccgtgtct gggtctcctg gacagtcgat caccatctcc 120

tgcactggaa ccagcagtga cattggtggt tataactatg tctcctggta ccaacaacac 180 tgcactggaa ccagcagtga cattggtggt tataactatg tctcctggta ccaacaacac 180

ccaggcaaag cccccaaact catgatttat gatgtcagta atcggccctc aggggtttct 240 ccaggcaaag cccccaaact catgattat gatgtcagta atcggccctc aggggtttct 240

aatcgcttct ctggctccaa gtctggcaac acggcctccc tgaccatctc tgggctccag 300 aatcgcttct ctggctccaa gtctggcaac acggcctccc tgaccatctc tgggctccag 300

gctgaggacg aggctgaata ttactgcagc tcatatacaa gaagcagcac tcaggtggta 360 gctgaggacg aggctgaata ttactgcagc tcatatacaa gaagcagcac tcaggtggta 360

ttcggcggag ggaccaagct gaccgtccta ggtcagccca aggctgcccc ctcggtcact 420 ttcggcggag ggaccaagct gaccgtccta ggtcagccca aggctgcccc ctcggtcact 420

ctgttcccac cctcgagtga ggagcttcaa gccaacaagg ccacactggt gtgtctcata 480 ctgttcccac cctcgagtga ggagcttcaa gccaacaagg ccacactggt gtgtctcata 480

agtgacttct acccgggagc cgtgacagtg gcctggaagg cagatagcag ccccgtcaag 540 agtgacttct acccgggagc cgtgacagtg gcctggaagg cagatagcag ccccgtcaag 540

gcgggagtgg agaccaccac accctccaaa caaagcaaca acaagtacgc ggccagcagc 600 gcgggagtgg agaccaccac accctccaaa caaagcaaca acaagtacgc ggccagcagc 600

tacctgagcc tgacgcctga gcagtggaag tcccacagaa gctacagctg ccaggtcacg 660 tacctgagcc tgacgcctga gcagtggaag tcccacagaa gctacagctg ccaggtcacg 660

catgaaggga gcaccgtgga gaagacagtc gccccaactg agtgttct 708 catgaaggga gcaccgtgga gaagacagtc gccccaactg agtgttct 708

Sequence Number (ID): 312 Sequence Number (ID): 312

Length: 702 Length: 702

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..702 - source, 1..702

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcagaa 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcagaa 60

attgtgttga cgcagtctcc aggcaccctg tctttgtctc caggggaaag agccaccctc 120 attgtgttga cgcagtctcc aggcaccctg tctttgtctc caggggaaag agccaccctc 120

tcctgcaggg ccagtcagag tgttagcagc agctacttag cctggtacca gcagaaacct 180 tcctgcaggg ccagtcagag tgttagcagc agctacttag cctggtacca gcagaaacct 180

ggccaggctc ccaggctcct catctatggt gcatccagca gggccactgg catcccagac 240 ggccaggctc ccaggctcct catctatggt gcatccagca gggccactgg catcccagac 240

aggttcagtg gcagtgggtc tgggacagac ttcactctca ctatcagcag actggagcct 300 aggttcagtg gcagtgggtc tgggacagac ttcactctca ctatcagcag actggagcct 300

gaagattttg cagtgtatca ctgtcagcag tatggtacct caccgtggac gttcggccaa 360 gaagattttg cagtgtatca ctgtcagcag tatggtacct caccgtggac gttcggccaa 360

gggaccaagg tggaaatcaa acgtacggtg gctgcaccat ctgtcttcat cttcccgcca 420 gggaccaagg tggaaatcaa acgtacggtg gctgcaccat ctgtcttcat cttcccgcca 420

tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480

cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540

gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600

ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 660 ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 660

ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gt 702 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gt 702

Sequence Number (ID): 313 Sequence Number (ID): 313

Length: 711 Length: 711

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..711 - source, 1..711

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggttc ctgggcccag 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggttc ctgggcccag 60

tctgccctga ctcagcctgc ctccgtgtct gggtctcctg gacagtcgat caccatctcc 120 tctgccctga ctcagcctgc ctccgtgtct gggtctcctg gacagtcgat caccatctcc 120

tgcactggaa ccagcagtga tgttgggagt tataaccttg tctcctggta ccaacagcac 180 tgcactggaa ccagcagtga tgttgggagt tataaccttg tctcctggta ccaacagcac 180

ccaggcaaag cccccaaact catgatttat gaagtcagta agcggccctc aggggtttct 240 ccaggcaaag cccccaaact catgattat gaagtcagta agcggccctc aggggtttct 240

aatcgcttct ctggctccaa gtctggcaac acggcctccc tgacaatctc tgggctccag 300 aatcgcttct ctggctccaa gtctggcaac acggcctccc tgacaatctc tgggctccag 300

gctgaggacg aggctgatta ttactgctgc tcatatgcac gtattagcac ccccggattt 360 gctgaggacg aggctgatta ttactgctgc tcatatgcac gtattagcac ccccggattt 360

gtcttcggaa ctgggaccaa ggtcaccgtc ctaggtcagc ccaaggccaa ccccactgtc 420 gtcttcggaa ctgggaccaa ggtcaccgtc ctaggtcagc ccaaggccaa ccccactgtc 420

actctgttcc cgccctcgag tgaggagctt caagccaaca aggccacact ggtgtgtctc 480 actctgttcc cgccctcgag tgaggagctt caagccaaca aggccacact ggtgtgtctc 480

ataagtgact tctacccggg agccgtgaca gtggcctgga aggcagatag cagccccgtc 540 ataagtgact tctacccggg agccgtgaca gtggcctgga aggcagatag cagccccgtc 540

aaggcgggag tggagaccac cacaccctcc aaacaaagca acaacaagta cgcggccagc 600 aaggcgggag tggagaccac cacaccctcc aaacaaagca acaacaagta cgcggccagc 600

agctacctga gcctgacgcc tgagcagtgg aagtcccaca gaagctacag ctgccaggtc 660 agctacctga gcctgacgcc tgagcagtgg aagtcccaca gaagctacag ctgccaggtc 660

acgcatgaag ggagcaccgt ggagaagaca gtcgccccaa ctgagtgttc t 711 acgcatgaag ggagcaccgt ggagaagaca gtcgccccaa ctgagtgttc t 711

Sequence Number (ID): 314 Sequence Number (ID): 314

Length: 696 Length: 696

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..696 - source, 1..696

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgac 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgac 60

atccagatga cccagtctcc ttccaccctg tctgcatctg taggagacag agtcaccatc 120 atccagatga cccagtctcc ttccaccctg tctgcatctg taggagacag agtcaccatc 120

acttgccggg ccagtcagag tattagtagc tggttggcct ggtatcagca gaaaccaggg 180 acttgccggg ccagtcagag tattagtagc tggttggcct ggtatcagca gaaaccaggg 180

aaagccccta agctcctgat ctataaggca tctaatttag aaagtggggt cccatcaagg 240 aaagccccta agctcctgat ctataaggca tctaatttag aaagtggggt cccatcaagg 240

ttcagcggca gtggatctgg gacagaattc actctcacca tcagcagcct gcagcctgat 300 ttcagcggca gtggatctgg gacagaattc actctcacca tcagcagcct gcagcctgat 300

gattttgcaa cttattactg ccaacagtat aatagttatt cgacgttcgg ccaagggacc 360 gattttgcaa cttattactg ccaacagtat aatagttatt cgacgttcgg ccaagggacc 360

aaggtggaga tcaaacgtac ggtggctgca ccatctgtct tcatcttccc gccatctgat 420 aaggtggaga tcaaacgtac ggtggctgca ccatctgtct tcatcttccc gccatctgat 420

gagcagttga aatctggaac tgcctctgtt gtgtgcctgc tgaataactt ctatcccaga 480 gagcagttga aatctggaac tgcctctgtt gtgtgcctgc tgaataactt ctatcccaga 480

gaggccaaag tacagtggaa ggtggataac gccctccaat cgggtaactc ccaggagagt 540 gaggccaaag tacagtggaa ggtggataac gccctccaat cgggtaactc ccaggagagt 540

gtcacagagc aggacagcaa ggacagcacc tacagcctca gcagcaccct gacgctgagc 600 gtcacagagc aggacagcaa ggacagcacc tacagcctca gcagcaccct gacgctgagc 600

aaagcagact acgagaaaca caaagtctac gcctgcgaag tcacccatca gggcctgagc 660 aaagcagact acgagaaaca caaagtctac gcctgcgaag tcacccatca gggcctgagc 660

tcgcccgtca caaagagctt caacagggga gagtgt 696 tcgcccgtca caaagagctt caacagggga gagtgt 696

Sequence Number (ID): 315 Sequence Number (ID): 315

Length: 702 Length: 702

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..702 - source, 1..702

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgac 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgac 60

atccagatga cccagtctcc atcctccctg tctgcatctc taggagacag agtcaccatc 120 atccagatga cccagtctcc atcctccctg tctgcatctc taggagacag agtcaccatc 120

acttgccagg cgagtcagga cattagcaac tatttaaatt ggtatcagca gaaaccaggg 180 acttgccagg cgagtcagga cattagcaac tatttaaatt ggtatcagca gaaaccaggg 180

aaggccccta agctcctgat ctacgatgca tccaatttgc aaacaggggt cccatcaagg 240 aaggccccta agctcctgat ctacgatgca tccaatttgc aaacaggggt cccatcaagg 240

ttcagtggag gtggatctgg gacagatttt actttcacca tcagcagcct gcagcctgaa 300 ttcagtggag gtggatctgg gacagatttt actttcacca tcagcagcct gcagcctgaa 300

gatattgcaa catattactg tcaacagtat gataatctcc tgggagtcac tttcggccct 360 gatattgcaa catattactg tcaacagtat gataatctcc tgggagtcac tttcggccct 360

gggaccaaag tggatatcaa acgtacggtg gctgcaccat ctgtcttcat cttcccgcca 420 gggaccaaag tggatatcaa acgtacggtg gctgcaccat ctgtcttcat cttcccgcca 420

tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480

cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540

gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600

ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 660 ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 660

ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gt 702 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gt 702

Sequence Number (ID): 316 Sequence Number (ID): 316

Length: 702 Length: 702

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..702 - source, 1..702

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcagaa 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcagaa 60

attgtgttga cgcagtctcc aggcaccctg tctttgtctc caggggaaag agccaccctc 120 attgtgttga cgcagtctcc aggcaccctg tctttgtctc caggggaaag agccaccctc 120

tcctgcaggg ccagtcagag tgttagcagc agctacttag cctggtacca gcagagtcct 180 tcctgcaggg ccagtcagag tgttagcagc agctacttag cctggtacca gcagagtcct 180

ggccaggctc ccaggctcct catctatggt acatccagca gggccactgg catcccagac 240 ggccaggctc ccaggctcct catctatggt acatccagca gggccactgg catcccagac 240

aggttcagtg gcagtgggtc tgggacagac ttcactctca ccatcagcag actggagcct 300 aggttcagtg gcagtgggtc tgggacagac ttcactctca ccatcagcag actggagcct 300

gaagattttg cagtgtatta ctgtcagcag tatggtagct cacctagaac gttcggccaa 360 gaagattttg cagtgtatta ctgtcagcag tatggtagct cacctagaac gttcggccaa 360

gggaccaagg tggagatcaa acgtacggtg gctgcaccat ctgtcttcat cttcccgcca 420 gggaccaagg tggagatcaa acgtacggtg gctgcaccat ctgtcttcat cttcccgcca 420

tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480

cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540

gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600

ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 660 ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 660

ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gt 702 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gt 702

Sequence Number (ID): 317 Sequence Number (ID): 317

Length: 702 Length: 702

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..702 - source, 1..702

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcagaa 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcagaa 60

attgtgttga cgcagtctcc aggcaccctg tctttgtctc caggggaaag agccaccctc 120 attgtgttga cgcagtctcc aggcaccctg tctttgtctc caggggaaag agccaccctc 120

tcctgcaggg ccagtcagag tgttagcagc agctacttag cctggtacca gcagaaacct 180 tcctgcaggg ccagtcagag tgttagcagc agctacttag cctggtacca gcagaaacct 180

ggccaggctc ccaggctcct catctatggt gcatccagca gggccactgg catcccagac 240 ggccaggctc ccaggctcct catctatggt gcatccagca gggccactgg catcccagac 240

aggttcagtg gcagtgggtc tgggacagac ttcactctca ccatcagcag actggagcct 300 aggttcagtg gcagtgggtc tgggacagac ttcactctca ccatcagcag actggagcct 300

gaagattttg cagtgtatta ctgtcagcag tatggtagct cacctcgaac gttcggccaa 360 gaagattttg cagtgtatta ctgtcagcag tatggtagct cacctcgaac gttcggccaa 360

gggaccaagg tggagatcaa acgtacggtg gctgcaccat ctgtcttcat cttcccgcca 420 gggaccaagg tggagatcaa acgtacggtg gctgcaccat ctgtcttcat cttcccgcca 420

tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480

cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540

gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600

ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 660 ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 660

ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gt 702 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gt 702

Sequence Number (ID): 318 Sequence Number (ID): 318

Length: 705 Length: 705

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..705 - source, 1..705

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcagaa 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcagaa 60

attgtgttga cgcagtctcc aggcaccctg tctttgtctc caggggaaag agccaccctc 120 attgtgttga cgcagtctcc aggcaccctg tctttgtctc caggggaaag agccaccctc 120

tcctgcaggg ccagccagag tattagcagc agctacttag cctggtacca gcagaaacct 180 tcctgcaggg ccagccagag tattagcagc agctacttag cctggtacca gcagaaacct 180

ggccaggctc ccaggctcct cttctatggt gcatccagca gggccactgg catcccagac 240 ggccaggctc ccaggctcct cttctatggt gcatccagca gggccactgg catccgac 240

aggttcagtg gcagtgggtc tgggacagac ttcactctca ccatcagcaa actggagcct 300 aggttcagtg gcagtgggtc tgggacagac ttcactctca ccatcagcaa actggagcct 300

gaagattttg cagtgtatta ctgtcagcag tatggtagct cacctccgat caccttcggc 360 gaagattttg cagtgtatta ctgtcagcag tatggtagct cacctccgat caccttcggc 360

caagggacac gactggagat taaacgtacg gtggctgcac catctgtctt catcttcccg 420 caagggacac gactggagat taaacgtacg gtggctgcac catctgtctt catcttcccg 420

ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 480 ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 480

tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 540 tatccgag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 540

caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 600 caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 600

acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 660 acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 660

ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgt 705 ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgt 705

Sequence Number (ID): 319 Sequence Number (ID): 319

Length: 720 Length: 720

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..720 - source, 1..720

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcggac 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcggac 60

atcgtgatga cccagtctcc agactccctg gctgtgtctc tgggcgagag ggccaccatc 120 atcgtgatga cccagtctcc agactccctg gctgtgtctc tgggcgagag ggccaccatc 120

aactgcaagt ccagccagag tgttttatac agctccaaca ataagaacta cttagcttgg 180 180

taccagcaga aaccaggaca gcctcctaag ctgctcattt actgggcatc tacccgggaa 240 taccagcaga aaccaggaca gcctcctaag ctgctcattt actgggcatc tacccgggaa 240

tccggggtcc ctgaccgatt cagtggcagc gggtctggga cagatttcac tctcaccatc 300 tccggggtcc ctgaccgatt cagtggcagc gggtctggga cagatttcac tctcaccatc 300

agcagcctgc aggctgaaga tgtggcagtt tattactgtc agcaatatta tagtactctc 360 agcagcctgc aggctgaaga tgtggcagtt tattactgtc agcaatatta tagtactctc 360

ttgctcactt tcggcggagg gaccaaggtg gagatcaaac gtacggtggc tgcaccatct 420 ttgctcactt tcggcgggagg gaccaaggtg gagatcaaac gtacggtggc tgcaccatct 420

gtcttcatct tcccgccatc tgatgagcag ttgaaatctg gaactgcctc tgttgtgtgc 480 gtcttcatct tcccgccatc tgatgagcag ttgaaatctg gaactgcctc tgttgtgtgc 480

ctgctgaata acttctatcc cagagaggcc aaagtacagt ggaaggtgga taacgccctc 540 ctgctgaata acttctatcc cagagaggcc aaagtacagt ggaaggtgga taacgccctc 540

caatcgggta actcccagga gagtgtcaca gagcaggaca gcaaggacag cacctacagc 600 caatcgggta actcccagga gagtgtcaca gagcaggaca gcaaggacag cacctacagc 600

ctcagcagca ccctgacgct gagcaaagca gactacgaga aacacaaagt ctacgcctgc 660 ctcagcagca ccctgacgct gagcaaagca gactacgaga aacacaaagt ctacgcctgc 660

gaagtcaccc atcagggcct gagctcgccc gtcacaaaga gcttcaacag gggagagtgt 720 gaagtcaccc atcagggcct gagctcgccc gtcacaaaga gcttcaacag gggagagtgt 720

Sequence Number (ID): 320 Sequence Number (ID): 320

Length: 699 Length: 699

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..699 -source, 1..699

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgac 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgac 60

atccagatga cccagtctcc atcctccctg tctgcatctg taggagacag agtcaccatc 120 atccagatga cccagtctcc atcctccctg tctgcatctg taggagacag agtcaccatc 120

acttgccagg cgagtcagga cattagcaac tatttaaatt ggtatcagca gaaaccaggg 180 acttgccagg cgagtcagga cattagcaac tatttaaatt ggtatcagca gaaaccaggg 180

aaagccccta agctcctgat ctacgatgca tccaatttgg aaacaggggt cccatcaagg 240 aaagccccta agctcctgat ctacgatgca tccaatttgg aaacaggggt cccatcaagg 240

ttcagtggaa gtggatctgg gacagatttt actttcacca tcagcagcct gcagcctgaa 300 ttcagtggaa gtggatctgg gacagatttt actttcacca tcagcagcct gcagcctgaa 300

gatattgcaa catattactg tcaacagtat gataatctcc cgatcacctt cggccaaggg 360 gatattgcaa catattactg tcaacagtat gataatctcc cgatcacctt cggccaaggg 360

acacgactgg agattaaacg tacggtggct gcaccatctg tcttcatctt cccgccatct 420 acacgactgg agattaaacg tacggtggct gcaccatctg tcttcatctt cccgccatct 420

gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 480 gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 480

agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 540 agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 540

agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 600 agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 600

agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg 660 agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg 660

agctcgcccg tcacaaagag cttcaacagg ggagagtgt 699 agctcgcccg tcacaaagag cttcaacagg ggagagtgt 699

Sequence Number (ID): 321 Sequence Number (ID): 321

Length: 705 Length: 705

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..705 - source, 1..705

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcagac 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattcagac 60

atccagttga cccagtctcc atccttcctg tctgcatctg taggagacag agtcaccatc 120 atccagttga cccagtctcc atccttcctg tctgcatctg taggagacag agtcaccatc 120

acttgccggg ccagtcaggg cattagcagt tatttagcct ggtatcagca aaaaccaggg 180 acttgccggg ccagtcaggg cattagcagt tatttagcct ggtatcagca aaaaccaggg 180

aaagccccta agctcctgat ctttgctgca tccactttgc agagtggggt cccatcaagg 240 aaagccccta agctcctgat ctttgctgca tccactttgc agagtggggt cccatcaagg 240

ttcagcgcca gtggatctgg gacagaattc actctcacaa tcagcagcct gcagcctgaa 300 ttcagcgcca gtggatctgg gacagaattc actctcacaa tcagcagcct gcagcctgaa 300

gattttgcaa cttattactg tcaacacctt aatagttacc cttctatgta cacttttggc 360 gattttgcaa cttattactg tcaacacctt aatagttacc cttctatgta cacttttggc 360

caggggacca agctggagat caaacgtacg gtggctgcac catctgtctt catcttcccg 420 caggggacca agctggagat caaacgtacg gtggctgcac catctgtctt catcttcccg 420

ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 480 ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 480

tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 540 tatccgag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 540

caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 600 caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 600

acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 660 acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 660

ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgt 705 ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgt 705

Sequence Number (ID): 322 Sequence Number (ID): 322

Length: 699 Length: 699

Molecule Type: DNA Molecule Type: DNA

Features Location/Qualifiers: Features Location/Qualifiers:

- source, 1..699 -source, 1..699

> mol_type, other DNA > mol_type, other DNA

> note, light chain > note, light chain

> organism, synthetic construct > organisms, synthetic constructs

Residues: Residents:

atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgac 60 atgggatggt catgtatcat cctttttcta gtagcaactg caaccggtgt acattctgac 60

atccagatga cccagtctcc atcctccctg tctgcatctg taggagacag agtcaccatc 120 atccagatga cccagtctcc atcctccctg tctgcatctg taggagacag agtcaccatc 120

acttgccggg caagtcaggg cattagaaat gatttaggct ggtatcagca gaaaccaggg 180 acttgccggg caagtcaggg cattagaaat gatttaggct ggtatcagca gaaaccaggg 180

aaagccccta agctcctgat ctatgctgca tccagtttac aaagtggggt cccatcaagg 240 aaagccccta agctcctgat ctatgctgca tccagtttac aaagtggggt cccatcaagg 240

ttcagcggca gtggatctgg cacagatttc actctcacca tcagcagcct gcagcctgaa 300 ttcagcggca gtggatctgg cacagatttc actctcacca tcagcagcct gcagcctgaa 300

gattttgcaa cttattactg tctacaagat tacaattacc ctcggacgtt cggccaaggg 360 gattttgcaa cttattactg tctacaagat tacaattacc ctcggacgtt cggccaaggg 360

accaaggtgg aaatcaaacg tacggtggct gcaccatctg tcttcatctt cccgccatct 420 accaaggtgg aaatcaaacg tacggtggct gcaccatctg tcttcatctt cccgccatct 420

gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 480 gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 480

agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 540 agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 540

agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 600 agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 600

agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg 660 agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg 660

agctcgcccg tcacaaagag cttcaacagg ggagagtgt 699 agctcgcccg tcacaaagag cttcaacagg ggagagtgt 699

<---<---

Claims (425)

1. Моноклональное антитело или его антигенсвязывающий фрагмент, селективно связывающее RBD фрагмент Spike-белка вируса SARS-CoV-2, где антитело или антигенсвязывающий фрагмент выбраны из:1. A monoclonal antibody or antigen-binding fragment selectively binding the RBD fragment of the SARS-CoV-2 Spike protein, where the antibody or antigen-binding fragment is selected from: (a) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(a) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 1;(i) CDRH1 sequence SEQ ID NO: 1; (ii) CDRH2 последовательности SEQ ID NO: 24;(ii) CDRH2 sequences of SEQ ID NO: 24; (iii) CDRH3 последовательности SEQ ID NO: 47, и (iii) CDRH3 sequences of SEQ ID NO: 47, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 70;(i) CDRL1 sequence of SEQ ID NO: 70; (ii) CDRL2 последовательности AAS (SEQ ID NO:93);(ii) CDRL2 AAS sequences (SEQ ID NO:93); (iii) CDRL3 последовательности SEQ ID NO: 116;(iii) CDRL3 sequences of SEQ ID NO: 116; (b) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(b) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 2;(i) CDRH1 sequences of SEQ ID NO: 2; (ii) CDRH2 последовательности SEQ ID NO: 25;(ii) CDRH2 sequences of SEQ ID NO: 25; (iii) CDRH3 последовательности SEQ ID NO: 48, и (iii) CDRH3 sequences of SEQ ID NO: 48, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 71;(i) CDRL1 sequence of SEQ ID NO: 71; (ii) CDRL2 последовательности SNN (SEQ ID NO:94);(ii) CDRL2 SNN sequences (SEQ ID NO:94); (iii) CDRL3 последовательности SEQ ID NO: 117;(iii) CDRL3 sequences of SEQ ID NO: 117; (с) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(c) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 3;(i) CDRH1 sequences of SEQ ID NO: 3; (ii) CDRH2 последовательности SEQ ID NO: 26;(ii) CDRH2 sequences of SEQ ID NO: 26; (iii) CDRH3 последовательности SEQ ID NO: 49, и (iii) CDRH3 sequences of SEQ ID NO: 49, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 72;(i) CDRL1 sequence of SEQ ID NO: 72; (ii) CDRL2 последовательности WAT (SEQ ID NO:95);(ii) CDRL2 WAT sequence (SEQ ID NO:95); (iii) CDRL3 последовательности SEQ ID NO: 118;(iii) CDRL3 sequences of SEQ ID NO: 118; (d) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(d) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 4;(i) CDRH1 sequences of SEQ ID NO: 4; (ii) CDRH2 последовательности SEQ ID NO: 27;(ii) CDRH2 sequences of SEQ ID NO: 27; (iii) CDRH3 последовательности SEQ ID NO: 50, и (iii) CDRH3 sequences of SEQ ID NO: 50, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 73;(i) CDRL1 sequence of SEQ ID NO: 73; (ii) CDRL2 последовательности EVS (SEQ ID NO:96);(ii) CDRL2 EVS sequences (SEQ ID NO:96); (iii) CDRL3 последовательности SEQ ID NO: 119;(iii) CDRL3 sequences of SEQ ID NO: 119; (e) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(e) an antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 5;(i) CDRH1 sequences of SEQ ID NO: 5; (ii) CDRH2 последовательности SEQ ID NO: 28;(ii) CDRH2 sequences of SEQ ID NO: 28; (iii) CDRH3 последовательности SEQ ID NO: 51, и (iii) CDRH3 sequences of SEQ ID NO: 51, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 74;(i) CDRL1 sequence of SEQ ID NO: 74; (ii) CDRL2 последовательности DAS (SEQ ID NO:97);(ii) CDRL2 DAS sequences (SEQ ID NO:97); (iii) CDRL3 последовательности SEQ ID NO: 120;(iii) CDRL3 sequences of SEQ ID NO: 120; (f) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(f) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 6;(i) CDRH1 sequences of SEQ ID NO: 6; (ii) CDRH2 последовательности SEQ ID NO: 29;(ii) CDRH2 sequences of SEQ ID NO: 29; (iii) CDRH3 последовательности SEQ ID NO: 52, и (iii) CDRH3 sequences of SEQ ID NO: 52, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 75;(i) CDRL1 sequence of SEQ ID NO: 75; (ii) CDRL2 последовательности EVT (SEQ ID NO:98);(ii) CDRL2 EVT sequence (SEQ ID NO:98); (iii) CDRL3 последовательности SEQ ID NO: 121;(iii) CDRL3 sequences of SEQ ID NO: 121; (g) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(g) an antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 7;(i) CDRH1 sequences of SEQ ID NO: 7; (ii) CDRH2 последовательности SEQ ID NO: 30;(ii) CDRH2 sequences of SEQ ID NO: 30; (iii) CDRH3 последовательности SEQ ID NO: 53, и (iii) CDRH3 sequences of SEQ ID NO: 53, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 76;(i) CDRL1 sequence of SEQ ID NO: 76; (ii) CDRL2 последовательности KAS (SEQ ID NO:99);(ii) CDRL2 KAS sequence (SEQ ID NO:99); (iii) CDRL3 последовательности SEQ ID NO: 122;(iii) CDRL3 sequences of SEQ ID NO: 122; (h) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(h) an antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 8;(i) CDRH1 sequences of SEQ ID NO: 8; (ii) CDRH2 последовательности SEQ ID NO: 31;(ii) CDRH2 sequences of SEQ ID NO: 31; (iii) CDRH3 последовательности SEQ ID NO: 54, и (iii) CDRH3 sequences of SEQ ID NO: 54, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 77;(i) CDRL1 sequence of SEQ ID NO: 77; (ii) CDRL2 последовательности GAS (SEQ ID NO:100);(ii) CDRL2 GAS sequences (SEQ ID NO:100); (iii) CDRL3 последовательности SEQ ID NO: 123;(iii) CDRL3 sequences of SEQ ID NO: 123; (i) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(i) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 9;(i) CDRH1 sequences of SEQ ID NO: 9; (ii) CDRH2 последовательности SEQ ID NO: 32;(ii) CDRH2 sequences of SEQ ID NO: 32; (iii) CDRH3 последовательности SEQ ID NO: 55, и (iii) CDRH3 sequences of SEQ ID NO: 55, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 78;(i) CDRL1 sequence of SEQ ID NO: 78; (ii) CDRL2 последовательности NNN (SEQ ID NO:101);(ii) CDRL2 NNN sequence (SEQ ID NO:101); (iii) CDRL3 последовательности SEQ ID NO: 124;(iii) CDRL3 sequences of SEQ ID NO: 124; (j) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(j) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 10;(i) CDRH1 sequences of SEQ ID NO: 10; (ii) CDRH2 последовательности SEQ ID NO: 33;(ii) CDRH2 sequences of SEQ ID NO: 33; (iii) CDRH3 последовательности SEQ ID NO: 56, и (iii) CDRH3 sequences of SEQ ID NO: 56, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 79;(i) CDRL1 sequence of SEQ ID NO: 79; (ii) CDRL2 последовательности AAS (SEQ ID NO:102);(ii) CDRL2 AAS sequences (SEQ ID NO:102); (iii) CDRL3 последовательности SEQ ID NO: 125;(iii) CDRL3 sequences of SEQ ID NO: 125; (k) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(k) an antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 11;(i) CDRH1 sequences of SEQ ID NO: 11; (ii) CDRH2 последовательности SEQ ID NO: 34;(ii) CDRH2 sequences of SEQ ID NO: 34; (iii) CDRH3 последовательности SEQ ID NO: 57, и (iii) CDRH3 sequences of SEQ ID NO: 57, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 80;(i) CDRL1 sequence of SEQ ID NO: 80; (ii) CDRL2 последовательности DAS (SEQ ID NO:103);(ii) CDRL2 DAS sequences (SEQ ID NO:103); (iii) CDRL3 последовательности SEQ ID NO: 126;(iii) CDRL3 sequences of SEQ ID NO: 126; (l) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(l) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 12;(i) CDRH1 sequences of SEQ ID NO: 12; (ii) CDRH2 последовательности SEQ ID NO: 35;(ii) CDRH2 sequences of SEQ ID NO: 35; (iii) CDRH3 последовательности SEQ ID NO: 58, и (iii) CDRH3 sequences of SEQ ID NO: 58, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 81;(i) CDRL1 sequence of SEQ ID NO: 81; (ii) CDRL2 последовательности DVS (SEQ ID NO:104);(ii) CDRL2 sequence DVS (SEQ ID NO:104); (iii) CDRL3 последовательности SEQ ID NO: 127;(iii) CDRL3 sequences of SEQ ID NO: 127; (m) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(m) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 13;(i) CDRH1 sequences of SEQ ID NO: 13; (ii) CDRH2 последовательности SEQ ID NO: 36;(ii) CDRH2 sequences of SEQ ID NO: 36; (iii) CDRH3 последовательности SEQ ID NO: 59, и (iii) CDRH3 sequences of SEQ ID NO: 59, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 82;(i) CDRL1 sequence of SEQ ID NO: 82; (ii) CDRL2 последовательности GAS (SEQ ID NO:105);(ii) CDRL2 GAS sequences (SEQ ID NO:105); (iii) CDRL3 последовательности SEQ ID NO: 128;(iii) CDRL3 sequences of SEQ ID NO: 128; (n) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(n) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 14;(i) CDRH1 sequences of SEQ ID NO: 14; (ii) CDRH2 последовательности SEQ ID NO: 37;(ii) CDRH2 sequences of SEQ ID NO: 37; (iii) CDRH3 последовательности SEQ ID NO: 60, и (iii) CDRH3 sequences of SEQ ID NO: 60, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 83;(i) CDRL1 sequence of SEQ ID NO: 83; (ii) CDRL2 последовательности EVS (SEQ ID NO:106);(ii) CDRL2 EVS sequences (SEQ ID NO:106); (iii) CDRL3 последовательности SEQ ID NO: 129;(iii) CDRL3 sequences of SEQ ID NO: 129; (o) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(o) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 15;(i) CDRH1 sequences of SEQ ID NO: 15; (ii) CDRH2 последовательности SEQ ID NO: 38;(ii) CDRH2 sequences of SEQ ID NO: 38; (iii) CDRH3 последовательности SEQ ID NO: 61, и (iii) CDRH3 sequences of SEQ ID NO: 61, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 84;(i) CDRL1 sequence of SEQ ID NO: 84; (ii) CDRL2 последовательности KAS (SEQ ID NO:107);(ii) CDRL2 KAS sequence (SEQ ID NO:107); (iii) CDRL3 последовательности SEQ ID NO: 130;(iii) CDRL3 sequences of SEQ ID NO: 130; (p) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(p) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 16;(i) CDRH1 sequences of SEQ ID NO: 16; (ii) CDRH2 последовательности SEQ ID NO: 39;(ii) CDRH2 sequences of SEQ ID NO: 39; (iii) CDRH3 последовательности SEQ ID NO: 62, и (iii) CDRH3 sequences of SEQ ID NO: 62, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 85;(i) CDRL1 sequence of SEQ ID NO: 85; (ii) CDRL2 последовательности DAS (SEQ ID NO:108);(ii) CDRL2 DAS sequences (SEQ ID NO:108); (iii) CDRL3 последовательности SEQ ID NO: 131;(iii) CDRL3 sequences of SEQ ID NO: 131; (q) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(q) an antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 17;(i) CDRH1 sequences of SEQ ID NO: 17; (ii) CDRH2 последовательности SEQ ID NO: 40;(ii) CDRH2 sequences of SEQ ID NO: 40; (iii) CDRH3 последовательности SEQ ID NO: 63, и (iii) CDRH3 sequences of SEQ ID NO: 63, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 86;(i) CDRL1 sequence of SEQ ID NO: 86; (ii) CDRL2 последовательности GTS (SEQ ID NO:109);(ii) CDRL2 GTS sequence (SEQ ID NO:109); (iii) CDRL3 последовательности SEQ ID NO: 132;(iii) CDRL3 sequences of SEQ ID NO: 132; (r) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(r) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 18;(i) CDRH1 sequences of SEQ ID NO: 18; (ii) CDRH2 последовательности SEQ ID NO: 41;(ii) CDRH2 sequences of SEQ ID NO: 41; (iii) CDRH3 последовательности SEQ ID NO: 64, и (iii) CDRH3 sequences of SEQ ID NO: 64, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 87;(i) CDRL1 sequence of SEQ ID NO: 87; (ii) CDRL2 последовательности GAS (SEQ ID NO:110);(ii) CDRL2 GAS sequences (SEQ ID NO:110); (iii) CDRL3 последовательности SEQ ID NO: 133;(iii) CDRL3 sequences of SEQ ID NO: 133; (s) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(s) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 19;(i) CDRH1 sequences of SEQ ID NO: 19; (ii) CDRH2 последовательности SEQ ID NO: 42;(ii) CDRH2 sequences of SEQ ID NO: 42; (iii) CDRH3 последовательности SEQ ID NO: 65, и (iii) CDRH3 sequences of SEQ ID NO: 65, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 88;(i) CDRL1 sequence of SEQ ID NO: 88; (ii) CDRL2 последовательности GAS (SEQ ID NO:111);(ii) CDRL2 GAS sequences (SEQ ID NO:111); (iii) CDRL3 последовательности SEQ ID NO: 134;(iii) CDRL3 sequences of SEQ ID NO: 134; (t) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(t) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 20;(i) CDRH1 sequences of SEQ ID NO: 20; (ii) CDRH2 последовательности SEQ ID NO: 43;(ii) CDRH2 sequences of SEQ ID NO: 43; (iii) CDRH3 последовательности SEQ ID NO: 66, и (iii) CDRH3 sequences of SEQ ID NO: 66, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 89;(i) CDRL1 sequence of SEQ ID NO: 89; (ii) CDRL2 последовательности WAS (SEQ ID NO:112);(ii) CDRL2 WAS sequence (SEQ ID NO:112); (iii) CDRL3 последовательности SEQ ID NO: 135;(iii) CDRL3 sequences of SEQ ID NO: 135; (u) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(u) an antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 21;(i) CDRH1 sequences of SEQ ID NO: 21; (ii) CDRH2 последовательности SEQ ID NO: 44;(ii) CDRH2 sequences of SEQ ID NO: 44; (iii) CDRH3 последовательности SEQ ID NO: 67, и (iii) CDRH3 sequences of SEQ ID NO: 67, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 90;(i) CDRL1 sequence of SEQ ID NO: 90; (ii) CDRL2 последовательности DAS (SEQ ID NO:113);(ii) CDRL2 DAS sequences (SEQ ID NO:113); (iii) CDRL3 последовательности SEQ ID NO: 136;(iii) CDRL3 sequences of SEQ ID NO: 136; (v) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(v) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 22;(i) CDRH1 sequences of SEQ ID NO: 22; (ii) CDRH2 последовательности SEQ ID NO: 45;(ii) CDRH2 sequences of SEQ ID NO: 45; (iii) CDRH3 последовательности SEQ ID NO: 68, и (iii) CDRH3 sequences of SEQ ID NO: 68, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 91;(i) CDRL1 sequence of SEQ ID NO: 91; (ii) CDRL2 последовательности AAS (SEQ ID NO:114);(ii) CDRL2 AAS sequences (SEQ ID NO:114); (iii) CDRL3 последовательности SEQ ID NO: 137;(iii) CDRL3 sequences of SEQ ID NO: 137; (w) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(w) an antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 23;(i) CDRH1 sequences of SEQ ID NO: 23; (ii) CDRH2 последовательности SEQ ID NO: 46;(ii) CDRH2 sequences of SEQ ID NO: 46; (iii) CDRH3 последовательности SEQ ID NO: 69, и (iii) CDRH3 sequences of SEQ ID NO: 69, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 92;(i) CDRL1 sequence of SEQ ID NO: 92; (ii) CDRL2 последовательности AAS (SEQ ID NO:115);(ii) CDRL2 AAS sequences (SEQ ID NO:115); (iii) CDRL3 последовательности SEQ ID NO: 138.(iii) CDRL3 sequences of SEQ ID NO: 138. 2. Антитело или его антигенсвязывающий фрагмент по п.1, содержащее вариабельную область тяжелой цепи (VH), содержащую последовательность аминокислот, не менее чем на 90% гомологичную одной из SEQ ID NO: 139-161, и вариабельную область легкой цепи (VL), содержащую последовательность аминокислот, не менее чем на 90% гомологичную одной из SEQ ID NO: 162-184.2. An antibody or antigen-binding fragment thereof according to claim 1, containing a heavy chain variable region (VH) containing an amino acid sequence at least 90% homologous to one of SEQ ID NOs: 139-161, and a light chain variable region (VL) containing an amino acid sequence at least 90% homologous to one of SEQ ID NO: 162-184. 3. Антитело или его антигенсвязывающий фрагмент по любому из пп.1-2, которое является антителом человека.3. An antibody or antigen-binding fragment thereof according to any one of claims 1 to 2, which is a human antibody. 4. Антитело или его антигенсвязывающий фрагмент по любому из пп.1-2, где антитело представляет собой химерное антитело, мышиное антитело и/или антитело, прошедшее созревание аффинности.4. An antibody or antigen-binding fragment thereof according to any one of claims 1 to 2, wherein the antibody is a chimeric antibody, a mouse antibody, and/or an affinity matured antibody. 5. Антитело или его антигенсвязывающий фрагмент по любому из пп.1-4, где антитело или антигенсвязывающий фрагмент обладают вируснейтрализующей активностью.5. An antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, wherein the antibody or antigen-binding fragment has virus-neutralizing activity. 6. Антитело или его антигенсвязывающий фрагмент по любому из пп.1-5, где антитело или его антигенсвязывающий фрагмент содержат консервативные участки тяжелых цепей, относящиеся к классу IgG, IgM, IgA, IgD или IgE.6. An antibody or antigen-binding fragment thereof according to any one of claims 1 to 5, wherein the antibody or antigen-binding fragment thereof comprises heavy chain conserved regions of the IgG, IgM, IgA, IgD, or IgE class. 7. Антитело или его антигенсвязывающий фрагмент по любому из пп.1-6, где антитело или его антигенсвязывающий фрагмент содержат консервативные участки тяжелых цепей, принадлежащие к изотипу IgG1, IgG2, IgG3 или IgG4.7. An antibody or antigen-binding fragment thereof according to any one of claims 1 to 6, wherein the antibody or antigen-binding fragment thereof comprises conserved heavy chain regions belonging to the IgG1, IgG2, IgG3 or IgG4 isotype. 8. Антитело или его антигенсвязывающий фрагмент по любому из пп.1-5, где антигенсвязывающий фрагмент представляет собой Fv, scFv, Fab, F(ab′)2 или Fab′.8. An antibody or antigen-binding fragment thereof according to any one of claims 1 to 5, wherein the antigen-binding fragment is Fv, scFv, Fab, F(ab') 2 or Fab'. 9. Нуклеиновая кислота, кодирующая антитело по любому из пп. 1-9.9. Nucleic acid encoding an antibody according to any one of paragraphs. 1-9. 10. Нуклеиновая кислота по п.9, которая представляет собой ДНК.10. Nucleic acid according to claim 9, which is DNA. 11. Нуклеиновая кислота по любому из пп.9-10, содержащая нуклеотидную последовательность, выбранную из SEQ ID NO: 185-207, и нуклеотидную последовательность, выбранную из SEQ ID NO: 208-230.11. A nucleic acid according to any one of claims 9-10, comprising a nucleotide sequence selected from SEQ ID NOs: 185-207 and a nucleotide sequence selected from SEQ ID NOs: 208-230. 12. Нуклеиновая кислота по любому из пп.9-10 содержащая нуклеотидную последовательность, выбранную из SEQ ID NO: 277-299, и нуклеотидную последовательность, выбранную из SEQ ID NO: 300-322.12. A nucleic acid according to any one of claims 9-10, comprising a nucleotide sequence selected from SEQ ID NOs: 277-299 and a nucleotide sequence selected from SEQ ID NOs: 300-322. 13. Экспрессионный вектор, содержащий нуклеиновую кислоту по любому из пп.9-12.13. An expression vector containing a nucleic acid according to any one of claims 9-12. 14. Клетка-хозяин для экспрессии антитела или его антигенсвязывающего фрагмента по любому из пп.1-8, содержащая нуклеиновую кислоту по любому из пп.9-12, или экспрессионный вектор по п.13. 14. A host cell for expressing an antibody or an antigen-binding fragment thereof according to any one of claims 1 to 8, containing a nucleic acid according to any one of claims 9 to 12, or an expression vector according to claim 13. 15. Способ получения антитела или его антигенсвязывающего фрагмента по любому из пп.1-8, включающий культивирование или поддержание клетки-хозяина по п. 14 в таких условиях, чтобы указанная клетка-хозяин продуцировала или экспрессировала антитело или его антигенсвязывающий фрагмент по любому из пп.1-8, посредством экспрессии нуклеиновой кислоты по любому из пп. 9-12, например, в составе вектора по п.13, и, при необходимости, дополнительно включающий выделение антитела или его антигенсвязывающего фрагмента по любому из пп.1-8, полученного таким способом. 15. A method for producing an antibody or antigen-binding fragment thereof according to any one of claims 1 to 8, including culturing or maintaining a host cell according to claim 14 under such conditions that said host cell produces or expresses an antibody or antigen-binding fragment according to any one of claims .1-8, by expressing the nucleic acid according to any one of paragraphs. 9-12, for example, as part of a vector according to claim 13, and, if necessary, further comprising the isolation of an antibody or antigen-binding fragment according to any of claims 1-8 obtained in this way. 16. Комбинация антител для профилактики и терапии инфекции, вызванной SARS-CoV-2, у субъекта, содержащая по меньшей мере два антитела, где антитела направлены на эпитопы на поверхности Spike-белка, где по меньшей мере одно из этих антител представляет собой антитело по любому из пп.1-8, где данное антитело обладает нейтрализующей активностью и выбрано из:16. An antibody combination for the prevention and treatment of infection caused by SARS-CoV-2 in a subject, containing at least two antibodies, where the antibodies are directed to epitopes on the surface of the Spike protein, where at least one of these antibodies is an antibody according to any of claims 1 to 8, wherein the antibody has neutralizing activity and is selected from: (d) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(d) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 4;(i) CDRH1 sequences of SEQ ID NO: 4; (ii) CDRH2 последовательности SEQ ID NO: 27;(ii) CDRH2 sequences of SEQ ID NO: 27; (iii) CDRH3 последовательности SEQ ID NO: 50, и (iii) CDRH3 sequences of SEQ ID NO: 50, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 73;(i) CDRL1 sequence of SEQ ID NO: 73; (ii) CDRL2 последовательности EVS (SEQ ID NO:96);(ii) CDRL2 EVS sequences (SEQ ID NO:96); (iii) CDRL3 последовательности SEQ ID NO: 119; (iii) CDRL3 sequences of SEQ ID NO: 119; (e) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(e) an antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 5;(i) CDRH1 sequences of SEQ ID NO: 5; (ii) CDRH2 последовательности SEQ ID NO: 28;(ii) CDRH2 sequences of SEQ ID NO: 28; (iii) CDRH3 последовательности SEQ ID NO: 51, и (iii) CDRH3 sequences of SEQ ID NO: 51, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 74;(i) CDRL1 sequence of SEQ ID NO: 74; (ii) CDRL2 последовательности DAS (SEQ ID NO:97);(ii) CDRL2 DAS sequences (SEQ ID NO:97); (iii) CDRL3 последовательности SEQ ID NO: 120; (iii) CDRL3 sequences of SEQ ID NO: 120; (g) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(g) an antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 7;(i) CDRH1 sequences of SEQ ID NO: 7; (ii) CDRH2 последовательности SEQ ID NO: 30;(ii) CDRH2 sequences of SEQ ID NO: 30; (iii) CDRH3 последовательности SEQ ID NO: 53, и (iii) CDRH3 sequences of SEQ ID NO: 53, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 76;(i) CDRL1 sequence of SEQ ID NO: 76; (ii) CDRL2 последовательности KAS (SEQ ID NO:99);(ii) CDRL2 KAS sequence (SEQ ID NO:99); (iii) CDRL3 последовательности SEQ ID NO: 122; (iii) CDRL3 sequences of SEQ ID NO: 122; (h) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(h) an antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 8;(i) CDRH1 sequences of SEQ ID NO: 8; (ii) CDRH2 последовательности SEQ ID NO: 31;(ii) CDRH2 sequences of SEQ ID NO: 31; (iii) CDRH3 последовательности SEQ ID NO: 54, и (iii) CDRH3 sequences of SEQ ID NO: 54, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 77;(i) CDRL1 sequence of SEQ ID NO: 77; (ii) CDRL2 последовательности GAS (SEQ ID NO:100);(ii) CDRL2 GAS sequences (SEQ ID NO:100); (iii) CDRL3 последовательности SEQ ID NO: 123; (iii) CDRL3 sequences of SEQ ID NO: 123; (j) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(j) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 10;(i) CDRH1 sequences of SEQ ID NO: 10; (ii) CDRH2 последовательности SEQ ID NO: 33;(ii) CDRH2 sequences of SEQ ID NO: 33; (iii) CDRH3 последовательности SEQ ID NO: 56, и (iii) CDRH3 sequences of SEQ ID NO: 56, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 79;(i) CDRL1 sequence of SEQ ID NO: 79; (ii) CDRL2 последовательности AAS (SEQ ID NO:102);(ii) CDRL2 AAS sequences (SEQ ID NO:102); (iii) CDRL3 последовательности SEQ ID NO: 125;(iii) CDRL3 sequences of SEQ ID NO: 125; (k) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(k) an antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: i) CDRH1 последовательности SEQ ID NO: 11;i) CDRH1 sequences of SEQ ID NO: 11; (ii) CDRH2 последовательности SEQ ID NO: 34;(ii) CDRH2 sequences of SEQ ID NO: 34; (iii) CDRH3 последовательности SEQ ID NO: 57, и (iii) CDRH3 sequences of SEQ ID NO: 57, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 80;(i) CDRL1 sequence of SEQ ID NO: 80; (ii) CDRL2 последовательности DAS (SEQ ID NO:103);(ii) CDRL2 DAS sequences (SEQ ID NO:103); (iii) CDRL3 последовательности SEQ ID NO: 126; (iii) CDRL3 sequences of SEQ ID NO: 126; (l) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(l) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 12;(i) CDRH1 sequences of SEQ ID NO: 12; (ii) CDRH2 последовательности SEQ ID NO: 35;(ii) CDRH2 sequences of SEQ ID NO: 35; (iii) CDRH3 последовательности SEQ ID NO: 58, и (iii) CDRH3 sequences of SEQ ID NO: 58, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 81;(i) CDRL1 sequence of SEQ ID NO: 81; (ii) CDRL2 последовательности DVS (SEQ ID NO:104);(ii) CDRL2 sequence DVS (SEQ ID NO:104); (iii) CDRL3 последовательности SEQ ID NO: 127; (iii) CDRL3 sequences of SEQ ID NO: 127; (m) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(m) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: i) CDRH1 последовательности SEQ ID NO: 13;i) CDRH1 sequences of SEQ ID NO: 13; (ii) CDRH2 последовательности SEQ ID NO: 36;(ii) CDRH2 sequences of SEQ ID NO: 36; (iii) CDRH3 последовательности SEQ ID NO: 59, и (iii) CDRH3 sequences of SEQ ID NO: 59, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 82;(i) CDRL1 sequence of SEQ ID NO: 82; (ii) CDRL2 последовательности GAS (SEQ ID NO:105);(ii) CDRL2 GAS sequences (SEQ ID NO:105); (iii) CDRL3 последовательности SEQ ID NO: 128; (iii) CDRL3 sequences of SEQ ID NO: 128; (n) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(n) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 14;(i) CDRH1 sequences of SEQ ID NO: 14; (ii) CDRH2 последовательности SEQ ID NO: 37;(ii) CDRH2 sequences of SEQ ID NO: 37; (iii) CDRH3 последовательности SEQ ID NO: 60, и (iii) CDRH3 sequences of SEQ ID NO: 60, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 83;(i) CDRL1 sequence of SEQ ID NO: 83; (ii) CDRL2 последовательности EVS (SEQ ID NO:106);(ii) CDRL2 EVS sequences (SEQ ID NO:106); (iii) CDRL3 последовательности SEQ ID NO: 129; (iii) CDRL3 sequences of SEQ ID NO: 129; (r) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(r) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 18;(i) CDRH1 sequences of SEQ ID NO: 18; (ii) CDRH2 последовательности SEQ ID NO: 41;(ii) CDRH2 sequences of SEQ ID NO: 41; (iii) CDRH3 последовательности SEQ ID NO: 64, и (iii) CDRH3 sequences of SEQ ID NO: 64, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 87;(i) CDRL1 sequence of SEQ ID NO: 87; (ii) CDRL2 последовательности GAS (SEQ ID NO:110);(ii) CDRL2 GAS sequences (SEQ ID NO:110); (iii) CDRL3 последовательности SEQ ID NO: 133; (iii) CDRL3 sequences of SEQ ID NO: 133; (s) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(s) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 19;(i) CDRH1 sequences of SEQ ID NO: 19; (ii) CDRH2 последовательности SEQ ID NO: 42;(ii) CDRH2 sequences of SEQ ID NO: 42; (iii) CDRH3 последовательности SEQ ID NO: 65, и (iii) CDRH3 sequences of SEQ ID NO: 65, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 88;(i) CDRL1 sequence of SEQ ID NO: 88; (ii) CDRL2 последовательности GAS (SEQ ID NO:111);(ii) CDRL2 GAS sequences (SEQ ID NO:111); (iii) CDRL3 последовательности SEQ ID NO: 134; или(iii) CDRL3 sequences of SEQ ID NO: 134; or (u) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(u) an antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 21;(i) CDRH1 sequences of SEQ ID NO: 21; (ii) CDRH2 последовательности SEQ ID NO: 44;(ii) CDRH2 sequences of SEQ ID NO: 44; (iii) CDRH3 последовательности SEQ ID NO: 67, и (iii) CDRH3 sequences of SEQ ID NO: 67, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 90;(i) CDRL1 sequence of SEQ ID NO: 90; (ii) CDRL2 последовательности DAS (SEQ ID NO:113);(ii) CDRL2 DAS sequences (SEQ ID NO:113); (iii) CDRL3 последовательности SEQ ID NO: 136.(iii) CDRL3 sequences of SEQ ID NO: 136. 17. Комбинация антител по п.16, где субъектом является человек или другое млекопитающее.17. An antibody combination according to claim 16, wherein the subject is a human or other mammal. 18. Комбинация антител по любому из пп.16-17, которая нейтрализует различные варианты вируса.18. The combination of antibodies according to any one of claims 16-17, which neutralizes different variants of the virus. 19. Применение антитела или его антигенсвязывающего фрагмента по любому из пп.1-8, для лечения инфекции, вызванной вирусом SARS-CoV-2 у человека и других млекопитающих, где антитело выбрано из: 19. The use of an antibody or antigen-binding fragment thereof according to any one of claims 1 to 8 for the treatment of infection caused by the SARS-CoV-2 virus in humans and other mammals, where the antibody is selected from: (d) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(d) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 4;(i) CDRH1 sequences of SEQ ID NO: 4; (ii) CDRH2 последовательности SEQ ID NO: 27;(ii) CDRH2 sequences of SEQ ID NO: 27; (iii) CDRH3 последовательности SEQ ID NO: 50, и (iii) CDRH3 sequences of SEQ ID NO: 50, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 73;(i) CDRL1 sequence of SEQ ID NO: 73; (ii) CDRL2 последовательности EVS (SEQ ID NO:96);(ii) CDRL2 EVS sequences (SEQ ID NO:96); (iii) CDRL3 последовательности SEQ ID NO: 119; (iii) CDRL3 sequences of SEQ ID NO: 119; (e) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(e) an antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 5;(i) CDRH1 sequences of SEQ ID NO: 5; (ii) CDRH2 последовательности SEQ ID NO: 28;(ii) CDRH2 sequences of SEQ ID NO: 28; (iii) CDRH3 последовательности SEQ ID NO: 51, и (iii) CDRH3 sequences of SEQ ID NO: 51, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 74;(i) CDRL1 sequence of SEQ ID NO: 74; (ii) CDRL2 последовательности DAS (SEQ ID NO:97);(ii) CDRL2 DAS sequences (SEQ ID NO:97); (iii) CDRL3 последовательности SEQ ID NO: 120; (iii) CDRL3 sequences of SEQ ID NO: 120; (g) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(g) an antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 7;(i) CDRH1 sequences of SEQ ID NO: 7; (ii) CDRH2 последовательности SEQ ID NO: 30;(ii) CDRH2 sequences of SEQ ID NO: 30; (iii) CDRH3 последовательности SEQ ID NO: 53, и (iii) CDRH3 sequences of SEQ ID NO: 53, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 76;(i) CDRL1 sequence of SEQ ID NO: 76; (ii) CDRL2 последовательности KAS (SEQ ID NO:99);(ii) CDRL2 KAS sequence (SEQ ID NO:99); (iii) CDRL3 последовательности SEQ ID NO: 122; (iii) CDRL3 sequences of SEQ ID NO: 122; (h) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(h) an antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 8;(i) CDRH1 sequences of SEQ ID NO: 8; (ii) CDRH2 последовательности SEQ ID NO: 31;(ii) CDRH2 sequences of SEQ ID NO: 31; (iii) CDRH3 последовательности SEQ ID NO: 54, и (iii) CDRH3 sequences of SEQ ID NO: 54, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 77;(i) CDRL1 sequence of SEQ ID NO: 77; (ii) CDRL2 последовательности GAS (SEQ ID NO:100);(ii) CDRL2 GAS sequences (SEQ ID NO:100); (iii) CDRL3 последовательности SEQ ID NO: 123; (iii) CDRL3 sequences of SEQ ID NO: 123; (j) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(j) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 10;(i) CDRH1 sequences of SEQ ID NO: 10; (ii) CDRH2 последовательности SEQ ID NO: 33;(ii) CDRH2 sequences of SEQ ID NO: 33; (iii) CDRH3 последовательности SEQ ID NO: 56, и (iii) CDRH3 sequences of SEQ ID NO: 56, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 79;(i) CDRL1 sequence of SEQ ID NO: 79; (ii) CDRL2 последовательности AAS (SEQ ID NO:102);(ii) CDRL2 AAS sequences (SEQ ID NO:102); (iii) CDRL3 последовательности SEQ ID NO: 125;(iii) CDRL3 sequences of SEQ ID NO: 125; (k) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(k) an antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: i) CDRH1 последовательности SEQ ID NO: 11;i) CDRH1 sequences of SEQ ID NO: 11; (ii) CDRH2 последовательности SEQ ID NO: 34;(ii) CDRH2 sequences of SEQ ID NO: 34; (iii) CDRH3 последовательности SEQ ID NO: 57, и (iii) CDRH3 sequences of SEQ ID NO: 57, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 80;(i) CDRL1 sequence of SEQ ID NO: 80; (ii) CDRL2 последовательности DAS (SEQ ID NO:103);(ii) CDRL2 DAS sequences (SEQ ID NO:103); (iii) CDRL3 последовательности SEQ ID NO: 126; (iii) CDRL3 sequences of SEQ ID NO: 126; (l) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(l) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 12;(i) CDRH1 sequences of SEQ ID NO: 12; (ii) CDRH2 последовательности SEQ ID NO: 35;(ii) CDRH2 sequences of SEQ ID NO: 35; (iii) CDRH3 последовательности SEQ ID NO: 58, и (iii) CDRH3 sequences of SEQ ID NO: 58, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 81;(i) CDRL1 sequence of SEQ ID NO: 81; (ii) CDRL2 последовательности DVS (SEQ ID NO:104);(ii) CDRL2 sequence DVS (SEQ ID NO:104); (iii) CDRL3 последовательности SEQ ID NO: 127; (iii) CDRL3 sequences of SEQ ID NO: 127; (m) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(m) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: i) CDRH1 последовательности SEQ ID NO: 13;i) CDRH1 sequences of SEQ ID NO: 13; (ii) CDRH2 последовательности SEQ ID NO: 36;(ii) CDRH2 sequences of SEQ ID NO: 36; (iii) CDRH3 последовательности SEQ ID NO: 59, и (iii) CDRH3 sequences of SEQ ID NO: 59, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 82;(i) CDRL1 sequence of SEQ ID NO: 82; (ii) CDRL2 последовательности GAS (SEQ ID NO:105);(ii) CDRL2 GAS sequences (SEQ ID NO:105); (iii) CDRL3 последовательности SEQ ID NO: 128; (iii) CDRL3 sequences of SEQ ID NO: 128; (n) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(n) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 14;(i) CDRH1 sequences of SEQ ID NO: 14; (ii) CDRH2 последовательности SEQ ID NO: 37;(ii) CDRH2 sequences of SEQ ID NO: 37; (iii) CDRH3 последовательности SEQ ID NO: 60, и (iii) CDRH3 sequences of SEQ ID NO: 60, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 83;(i) CDRL1 sequence of SEQ ID NO: 83; (ii) CDRL2 последовательности EVS (SEQ ID NO:106);(ii) CDRL2 EVS sequences (SEQ ID NO:106); (iii) CDRL3 последовательности SEQ ID NO: 129; (iii) CDRL3 sequences of SEQ ID NO: 129; (r) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(r) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 18;(i) CDRH1 sequences of SEQ ID NO: 18; (ii) CDRH2 последовательности SEQ ID NO: 41;(ii) CDRH2 sequences of SEQ ID NO: 41; (iii) CDRH3 последовательности SEQ ID NO: 64, и (iii) CDRH3 sequences of SEQ ID NO: 64, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 87;(i) CDRL1 sequence of SEQ ID NO: 87; (ii) CDRL2 последовательности GAS (SEQ ID NO:110);(ii) CDRL2 GAS sequences (SEQ ID NO:110); (iii) CDRL3 последовательности SEQ ID NO: 133; (iii) CDRL3 sequences of SEQ ID NO: 133; (s) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(s) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 19;(i) CDRH1 sequences of SEQ ID NO: 19; (ii) CDRH2 последовательности SEQ ID NO: 42;(ii) CDRH2 sequences of SEQ ID NO: 42; (iii) CDRH3 последовательности SEQ ID NO: 65, и (iii) CDRH3 sequences of SEQ ID NO: 65, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 88;(i) CDRL1 sequence of SEQ ID NO: 88; (ii) CDRL2 последовательности GAS (SEQ ID NO:111);(ii) CDRL2 GAS sequences (SEQ ID NO:111); (iii) CDRL3 последовательности SEQ ID NO: 134; или(iii) CDRL3 sequences of SEQ ID NO: 134; or (u) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(u) an antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 21;(i) CDRH1 sequences of SEQ ID NO: 21; (ii) CDRH2 последовательности SEQ ID NO: 44;(ii) CDRH2 sequences of SEQ ID NO: 44; (iii) CDRH3 последовательности SEQ ID NO: 67, и (iii) CDRH3 sequences of SEQ ID NO: 67, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 90;(i) CDRL1 sequence of SEQ ID NO: 90; (ii) CDRL2 последовательности DAS (SEQ ID NO:113);(ii) CDRL2 DAS sequences (SEQ ID NO:113); (iii) CDRL3 последовательности SEQ ID NO: 136.(iii) CDRL3 sequences of SEQ ID NO: 136. 20. Применение по п.19, где антитело или его антигенсвязывающий фрагмент применяют для лечения человека.20. Use according to claim 19, wherein the antibody, or antigen-binding fragment thereof, is used to treat a human. 21. Применение по любому из пп.19-20, где антитело или его антигенсвязывающий фрагмент вводится системно, назально или путем прямой доставки кодирующих его нуклеиновых кислот в организм млекопитающих.21. Use according to any one of claims 19-20, wherein the antibody or antigen-binding fragment thereof is administered systemically, nasally, or by direct delivery of nucleic acids encoding it into a mammalian body. 22. Применение антитела или его антигенсвязывающего фрагмента по любому из пп.1-8, где антитело выбрано из:22. Use of an antibody or antigen-binding fragment thereof according to any one of claims 1 to 8, wherein the antibody is selected from: (a) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(a) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности GFTFSSYA (SEQ ID NO: 1);(i) CDRH1 sequence GFTFSSYA (SEQ ID NO: 1); (ii) CDRH2 последовательности ISYDGSNK (SEQ ID NO: 24);(ii) CDRH2 sequence ISYDGSNK (SEQ ID NO: 24); (iii) CDRH3 последовательности ARARPWRYSYGLYYYYGMDV (SEQ ID NO: 47), и (iii) a CDRH3 sequence of ARARPWRYSYGLYYYYGMDV (SEQ ID NO: 47), and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности QSISSY (SEQ ID NO: 70);(i) CDRL1 sequence QSISSY (SEQ ID NO: 70); (ii) CDRL2 последовательности AAS (SEQ ID NO: 93);(ii) AAS CDRL2 sequences (SEQ ID NO: 93); (iii) CDRL3 последовательности QQSYSTPGS (SEQ ID NO: 116); или(iii) CDRL3 sequence QQSYSTPGS (SEQ ID NO: 116); or (m) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(m) an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 13;(i) CDRH1 sequences of SEQ ID NO: 13; (ii) CDRH2 последовательности SEQ ID NO: 36;(ii) CDRH2 sequences of SEQ ID NO: 36; (iii) CDRH3 последовательности SEQ ID NO: 59, и (iii) CDRH3 sequences of SEQ ID NO: 59, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 82;(i) CDRL1 sequence of SEQ ID NO: 82; (ii) CDRL2 последовательности GAS (SEQ ID NO:105);(ii) CDRL2 GAS sequences (SEQ ID NO:105); (iii) CDRL3 последовательности SEQ ID NO: 128; или(iii) CDRL3 sequences of SEQ ID NO: 128; or (s) антитела или его антигенсвязывающего фрагмента, содержащего вариабельную область тяжелой цепи (VH), содержащую:(s) an antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region (VH) comprising: (i) CDRH1 последовательности SEQ ID NO: 19;(i) CDRH1 sequences of SEQ ID NO: 19; (ii) CDRH2 последовательности SEQ ID NO: 42;(ii) CDRH2 sequences of SEQ ID NO: 42; (iii) CDRH3 последовательности SEQ ID NO: 65, и (iii) CDRH3 sequences of SEQ ID NO: 65, and вариабельную область легкой цепи (VL), содержащую:a light chain variable region (VL) containing: (i) CDRL1 последовательности SEQ ID NO: 88;(i) CDRL1 sequence of SEQ ID NO: 88; (ii) CDRL2 последовательности GAS (SEQ ID NO:111);(ii) CDRL2 GAS sequences (SEQ ID NO:111); (iii) CDRL3 последовательности SEQ ID NO: 134, (iii) CDRL3 sequences of SEQ ID NO: 134, для оценки наличия инфекции SARS-CoV-2 у млекопитающих.to assess the presence of SARS-CoV-2 infection in mammals. 23. Применение по п.22, где млекопитающее является человеком.23. Use according to claim 22, wherein the mammal is a human. 24. Химерный антигенный рецептор, который селективно связывает RBD фрагмент Spike-белка вируса SARS-CoV-2, где химерный антигенный рецептор содержит антигенсвязывающую область, представленную антителом или его антигенсвязывающим фрагментом по любому из пп. 1-8. 24. A chimeric antigen receptor that selectively binds the RBD fragment of the SARS-CoV-2 Spike protein, wherein the chimeric antigen receptor contains an antigen-binding region represented by an antibody or antigen-binding fragment thereof according to any one of paragraphs. 1-8.
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