US20210292393A1 - Anti-Coronavirus Antibodies and Methods of Use - Google Patents
Anti-Coronavirus Antibodies and Methods of Use Download PDFInfo
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- US20210292393A1 US20210292393A1 US17/116,588 US202017116588A US2021292393A1 US 20210292393 A1 US20210292393 A1 US 20210292393A1 US 202017116588 A US202017116588 A US 202017116588A US 2021292393 A1 US2021292393 A1 US 2021292393A1
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- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
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- G01N2800/26—Infectious diseases, e.g. generalised sepsis
Definitions
- This disclosure generally relates to the fields of medicine, immunology, and infectious disease. More specifically, the disclosure relates to anti-coronavirus antibodies (e.g., anti-SARS-CoV-2 antibodies) and antibody-like molecules and, in particular, to human antibodies, antibody fragments, and nucleic-acid-vectored versions thereof, and methods for treating coronavirus infections, methods for prophylaxis against coronavirus infections, and immunoassays for the detection of coronaviruses.
- anti-coronavirus antibodies e.g., anti-SARS-CoV-2 antibodies
- antibody-like molecules e.g., anti-SARS-CoV-2 antibodies
- human antibodies, antibody fragments, and nucleic-acid-vectored versions thereof e.g., to human antibodies, antibody fragments, and nucleic-acid-vectored versions thereof.
- SARS-CoV Severe Acute Respiratory Syndrome coronavirus
- West Nile West Nile
- Ebola Middle Eastern Respiratory Syndrome Coronavirus
- Zika Zika
- pandemic influenza The risk of a pandemic is multiplied by growing populations and urbanization, climate change, global travel, and civil conflict.
- 2019 novel coronavirus (SARS-CoV-2) outbreak has led the World Health Organization (WHO) to declare a global health emergency.
- Pandemic outbreaks present a serious risk to global security and trade.
- the 1918 H1N1 pandemic influenza virus (Spanish flu) claimed an estimated 50 million lives in a matter of months.
- the World Bank estimates that a pandemic to that scale would cost about 5% global gross domestic product (GDP), or about $3 trillion USD.
- GDP global gross domestic product
- the more recent 2009 H1N1 pandemic is estimated to have infected 11-21% of the world's population (80% under the age of 65) and claimed between 151,700 to 575,400 lives.
- the WHO estimates three to five million cases of severe influenza, resulting in 250,000 to 500,000 global deaths.
- the propensity for rapid genetic change, antigenic diversity, and the breadth of potential hosts gives influenza type A significant pandemic potential.
- the rapid mutation of surface antigens allows the virus to evade the immune response, requiring an annual prediction of circulating strains to include in seasonal vaccines.
- a universal flu vaccine that could provide long-term and cross-strain protection has so far been elusive, and while there are candidates in preclinical and clinical trials, it will likely be several years before one becomes available. Less predictable than seasonal drifts, genetic reassortments (antigenic shift) of hemagglutinin or neuraminidase in zoonotic hosts can generate novel strains of influenza virus that can transfer to humans and cause a fast-spreading pandemic across an immunologically na ⁇ ve population.
- the California 2009 H1N1 strain was discovered to have originated in swine, and both the Spanish flu and Hong Kong 1957 pandemic strains are thought to have originated from an avian source.
- Coronaviruses are a large family of viruses that infect mammals and birds, with four endemic strains that circulate commonly in humans, including human coronavirus 229E, OC43, NL63 and HKU1. These endemic strains generally cause mild flu-like symptoms, but can also cause more serious pneumonia in vulnerable populations. However, when new coronaviruses jump from zoonotic hosts (bats, birds, camels, etc.) to humans, they can result in a much more severe respiratory disease that can spread quickly through the population.
- SARS severe Acute Respiratory Syndrome
- SARS-CoV SARS-associated coronavirus
- MERS Middle Eastern Respiratory Syndrome
- SARS-CoV-2 a new coronavirus
- COVID-19 a severe respiratory disease referred to as COVID-19
- SARS-Cov-2 is now the most serious coronavirus outbreak in history.
- MERS-CoV and SARS-CoV SARS-CoV-2 has spread rapidly on a global scale, with confirmed cases in more than 90 countries to date. In response to this outbreak, there is an urgent need for antibody-based therapeutics, prophylactics, and diagnostics to treat, prevent, and detect the disease.
- vaccines are the cheapest and most effective protective countermeasures, their use is limited against viruses with high antigenic drift, antigenic shift, and against newly emerging viral strains from zoonotic hosts to which humans have little or no herd immunity. After vaccination, it takes several days post-immunization for the immune system to generate protective immunity—this is often impractical in pandemic situations where human efforts must be rapidly deployed in outbreak areas and immediate action is needed to prevent or treat infections. Passive immunization with antiviral monoclonal antibodies (mAbs) has emerged as a viable strategy to protect at-risk populations from seasonal epidemics and fast-moving pandemics.
- mAbs antiviral monoclonal antibodies
- the hybridoma method has historically been the main driver of antibody discovery, but it is very inefficient for finding rare mAbs.
- In silico display technologies overcome some of hybridoma's inefficiencies, but mAb panels discovered this way bypass nature's rigorous selection process and as a consequence often suffer from low diversity and poor developability.
- the recent burst in rare mAb discovery i.e. against HIV, RSV, HMPV, Lassa, and HCMV
- This high-throughput interrogation of natural immune-reservoirs can identify rare cross-reactive and potent mAbs, which can reduce dosing frequency and, with it, the unit cost of treatment.
- Molecular engineering can additionally improve both potency and cross-reactivity, and extend mAb half-life.
- Recent advances in nucleic acid-based mAb delivery have shown promise to decrease both costs and dosing frequencies.
- Clinical studies have demonstrated that administration of mRNA-encoded antibodies against Chikungunya virus could generate neutralizing titers without toxicity in human patients. These can furthermore be produced at commercial scale with high purity, and formulated to facilitate storage and shipping, which are all important factors in deploying mAbs rapidly and globally.
- Pandemic Prevention Platform P3 program of the US Defense Advanced Research Projects Agency (DARPA)
- DRPA US Defense Advanced Research Projects Agency
- P3 in a simulated pandemic scenario, we used microfluidic high-throughput single B cell screening to discover mAbs against pandemic 2009 H1N1 influenza directly from a human donor.
- We designed machine learning tools to automate high-confidence selection of mAbs during screening, rapidly sequenced hundreds of H1-reactive mAbs, and downselected candidates for preclinical testing using a bioinformatic pipeline and data visualization software.
- the present disclosure relates to methods, compositions of matter, and articles of manufacture that may be used in the diagnosis, monitoring, and treatment or prevention of SARS-Co-V and SARS-CoV-2-linked diseases such as COVID-19.
- S spike
- SARS-CoV-2 a large library of fully human antibodies against the spike (S) protein of coronaviruses, e.g., SARS-CoV-2.
- VH and VL The sequences of the heavy chain and light chain variable regions (VH and VL) of these antibodies were originally identified from a convalescent patient following infection with a coronavirus, converted to full-length human IgG1 isotype (e.g., IgG1m3 allotype), and the recombinant versions of these antibodies were subsequently produced and characterized as described herein. Therefore, these antibodies are recombinant in nature.
- the antibodies provided herein each binds to the spike protein of SARS-CoV-2 virus, and some of the antibodies cross-react with the spike protein of one or more other coronaviruses.
- the library is stored as a collection of electronic DNA sequences of the heavy and light chain variable regions of each member of the library. In another embodiment the library is stored as DNA molecules that encode the heavy and light chain variable regions of each member in the library. In another embodiment, the library is stored as antibody protein molecules for rapid testing. In another embodiment, the library is stored as nucleic acid-encoded versions of the antibody proteins, in mRNA or DNA formats and expression vectors suitable for direct administration to humans as nucleic acids instead of proteins.
- anti-coronavirus antibodies e.g., anti-SARS-CoV-2 antibodies
- anti-SARS-CoV-2 antibodies e.g., anti-SARS-CoV-2 antibodies
- antibodies 258 to 577 and 589 to 1587 are disclosed herein and are set forth in SEQ ID NOs: 1-5316.
- Nucleic acids encoding the heavy chain variable regions (VH) of these antibodies are set forth in odd numbered sequences in SEQ ID NOs: 1-660, 1321-2750, and 4181-4748 detailed herein.
- Nucleic acids encoding the light chain variable regions (VL) of these antibodies are set forth in even numbered sequences in SEQ ID NOs: 1-660, 1321-2750, and 4181-4748 detailed herein.
- Amino acid sequences of the heavy chain variable regions (VH) of these antibodies are set forth in odd numbered sequences in SEQ ID NOs: 661-1320, 2751-4180, and 4749-5316 detailed herein. Amino acid sequences of the light chain variable regions of these antibodies are set forth in even numbered sequences of SEQ ID NOs: 661-1320, 2751-4180, and 4749-5316 detailed herein. As one of skill in the art will appreciate, the four sequences pertaining to any particular antibody will be separated by sequences pertaining to other antibodies.
- the SEQ ID NOs assigned to the first antibody are SEQ ID NOs: 1, 2, 661 and 662 while the SEQ ID NOs assigned to the second antibody (designated 259) are SEQ ID NOs: 3, 4, 663 and 664 and so on all the way to the one thousand three hundred and twenty ninth antibody (designated 1587), which is assigned SEQ ID NOs: 4747, 4748, 5315, and 5316.
- the anti-coronavirus antibody e.g., anti-SARS-CoV-2 antibody
- antigen-binding fragment thereof comprises (a) a heavy chain variable region comprising residues 31-35 for CDR-H1, residues 50-65 for CDR-H2, and residues 95-102 for CDR-H3; and (b) a light chain variable region comprising residues 24-34 for CDR-L1, residues 50-56 for CDR-L2, and residues 89-97 for CDR-L3; wherein the CDR numbering is according to Kabat.
- the anti-coronavirus antibody e.g., anti-SARS-CoV-2 antibody
- antigen-binding fragment thereof comprises: (a) a heavy chain variable region comprising residues 26-32 for CDR-H1, residues 50-58 for CDR-H2, and residues 95-102 for CDR-H3; and (b) a light chain variable region comprising residues 24-34 for CDR-L1, residues 50-56 of SEQ ID NO: 62 for CDR-L2, and residues 89-97 of SEQ ID NO: 62 for CDR-L3; wherein the CDR numbering is according to Chothia.
- the anti-coronavirus antibody e.g., anti-SARS-CoV-2 antibody
- antigen-binding fragment thereof comprises: (a) a heavy chain variable region comprising residues 30-35 for CDR-H1, residues 47-58 for CDR-H2, and residues 93-101 for CDR-H3; and (b) a light chain variable region comprising residues 30-36 for CDR-L1, residues 46-55 for CDR-L2, and for CDR-L3; wherein the CDR numbering is according to MacCallum.
- the anti-coronavirus antibody e.g., anti-SARS-CoV-2 antibody
- antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to one of the heavy chain variable region sequences explicitly disclosed in SEQ ID NOs: 660-1320 and 2751-4180 and a light chain variable region having an amino acid sequence that is at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to one of the light chain variable region sequences explicitly disclosed in SEQ ID NOs: 660-1320 and 2751-4180.
- members of the antibody library are specific to SARS-CoV-2.
- the antibodies are known to cross-react against SARS-CoV and SARS-CoV-2 spike proteins.
- the antibodies are specific to SARS-CoV spike protein.
- the anti-coronavirus antibody e.g., anti-SARS-CoV-2 antibody
- antigen-binding fragment thereof is a neutralizing antibody.
- the antibody or antigen-binding fragment thereof is a depleting antibody.
- the antibody or antigen-binding fragment thereof comprises at least one amino acid substitution.
- the at least one amino acid substitution is a conservative substitution.
- the at least one amino acid substitution is a substitution of an amino acid for a non-genetically encoded amino acid or a synthetic amino acid.
- the antibody or antigen-binding fragment thereof is conjugated to an immunomodulator, a cytokine, a cytotoxic agent, a chemotherapeutic agent, a diagnostic agent, an antiviral agent, an antimicrobial agent, or a drug.
- the antibody or antigen-binding fragment thereof is formulated as a pharmaceutical composition.
- the pharmaceutical composition may comprise one or more pharmaceutically acceptable carriers, diluents, or excipients.
- the antibody or antigen-binding fragment thereof may be conjugated to an immunomodulator, a cytokine, a cytotoxic agent, a chemotherapeutic agent, a diagnostic agent, an antiviral agent, an antimicrobial agent, or a drug prior to formulation.
- inventions disclosed herein also encompass isolated nucleic acids encoding part or all of the anti-coronavirus antibodies (e.g., anti-SARS-CoV-2 antibodies) and antigen-binding fragments thereof disclosed herein.
- the foregoing nucleic acids may be incorporated into a vector.
- the foregoing nucleic acids may be incorporated into a host cell or a vector then into a host cell.
- the inventions disclosed herein also encompass methods of identifying a SARS-CoV-2-infected cell comprising contacting a cell with an anti-coronavirus antibody (e.g., anti-SARS-CoV-2 antibody) or antigen-binding fragment thereof conjugated to a detectable agent and detecting specific binding of the antibody or antigen-binding fragment thereof to the cell.
- an anti-coronavirus antibody e.g., anti-SARS-CoV-2 antibody
- antigen-binding fragment thereof conjugated to a detectable agent
- inventions disclosed herein also encompass methods of using an anti-coronavirus antibody (e.g., anti-SARS-CoV-2 antibody) or antigen-binding fragment thereof as a test reagent for the development and production of a vaccine (e.g., an inactivated virus) against a SARS-CoV-2 disease (such as COVID-19).
- an anti-coronavirus antibody e.g., anti-SARS-CoV-2 antibody
- a vaccine e.g., an inactivated virus
- COVID-19 a virus-associated virus
- the inventions disclosed herein also encompass methods of diagnosing a SARS-CoV-2 infection in a patient comprising contacting a sample obtained from a patient with a SARS-CoV-2 antibody or antigen-binding fragment thereof conjugated to a detectable agent and detecting specific binding of the antibody or antigen-binding fragment thereof to a SARS-CoV-2 antigen present in the sample.
- the inventions disclosed herein also encompass methods of treating a SARS-Co-V-linked disease (SARS) or SARS-Co-V-2-linked disease (such as COVID-19) comprising administering to a patient a therapeutically effective amount of a SARS-CoV-2 antibody or antigen-binding fragment thereof.
- SARS SARS-Co-V-linked disease
- SARS-Co-V-2-linked disease such as COVID-19
- the antibody or antigen-binding fragment thereof may be conjugated (for example, to an anti-viral agent) or formulated as a pharmaceutical composition.
- inventions disclosed herein also encompass articles of manufacture useful for diagnosing or treating a SARS-Co-V-2-linked disease comprising a receptacle comprising a SARS-CoV-2 antibody or antigen-binding fragment thereof, or antibody conjugate, or pharmaceutical composition as well as instructional materials for using the same to treat or diagnose the SARS-Co-V-2-linked disease.
- the inventions disclosed herein also encompass processes for producing a SARS-CoV-2 antibody comprising cultivating a host cell under conditions such that the antibody is expressed and recovering the expressed antibody.
- FIG. 2A shows the binding kinetics curve of Fab 555 to SARS-CoV-2 spike protein.
- FIG. 2B shows representative negative stain electron microscopy images of Fab 555 in complex with the trimeric SARS-CoV-2 spike protein.
- FIG. 2C shows a three-dimensional reconstruction of the complex of Fab 555 and SARS-CoV-2 spike protein within the class-averaged image density; with the peptide regions corresponding to the epitope information derived from HDXMS experiments labeled dark grey.
- FIG. 3A shows the binding kinetics curve of Fab 447 to SARS-CoV-2 spike protein.
- FIG. 3B shows representative negative stain electron microscopy images of Fab 447 in complex with the trimeric SARS-CoV-2 spike protein.
- FIG. 3C shows a three-dimensional reconstruction of the complex of Fab 447 and SARS-CoV-2 spike protein within the class-averaged image density.
- FIG. 4A shows the binding kinetics curve of Fab 483 to SARS-CoV-2 spike protein.
- FIG. 4B shows representative negative stain electron microscopy images of Fab 483 in complex with the trimeric SARS-CoV-2 spike protein.
- FIG. 4C shows a three-dimensional reconstruction of the complex of Fab 483 and SARS-CoV-2 spike protein within the class-averaged image density.
- FIG. 5A shows the binding kinetics curve of Fab 419 to SARS-CoV-2 spike protein.
- FIG. 5B shows representative negative stain electron microscopy images of Fab 419 in complex with the trimeric SARS-CoV-2 spike protein.
- FIG. 5C shows a three-dimensional reconstruction of the complex of Fab 419 and SARS-CoV-2 spike protein within the class-averaged image density.
- FIG. 6A shows the binding kinetics curve of Fab 388 to SARS-CoV-2 spike protein.
- FIG. 6B shows representative negative stain electron microscopy images of Fab 388 in complex with the trimeric SARS-CoV-2 spike protein.
- FIG. 6C shows a three-dimensional reconstruction of the complex of Fab 388 and SARS-CoV-2 spike protein within the class-averaged image density.
- FIG. 7 shows the relative binding site of Fabs 555, 447, 483, 419, 388 on SARS-CoV-2 spike protein.
- FIG. 8A shows the binding kinetics curve of Fab 494 to SARS-CoV-2 spike protein.
- FIG. 8B shows representative negative stain electron microscopy images of Fab 494 in complex with the trimeric SARS-CoV-2 spike protein.
- FIG. 8C shows a three-dimensional reconstruction of the complex of Fab 494 and SARS-CoV-2 spike protein within the class-averaged image density.
- FIG. 9A is a ribbon diagram of Fab 555/481/488: RBD domain complex structured as determined by X-ray crystallography.
- FIG. 9B shows the crystal structure of the RBD-Fab555 complex superimposed with the ACE2 receptor from a structure of the RBD-ACE2 complex (PDB ID: 6M0J).
- FIG. 9C is a zoomed-in view of key atomic interactions at the interface of the Fab 555 light chain and the RBD of SARS-CoV-2 spike protein.
- FIG. 9D is a zoomed-in view of key atomic interactions at the interface of the Fab 555 heavy chain and the RBD of SARS-CoV-2 spike protein.
- FIG. 9A is a ribbon diagram of Fab 555/481/488: RBD domain complex structured as determined by X-ray crystallography.
- FIG. 9B shows the crystal structure of the RBD-Fab555 complex superimposed with the ACE2 receptor from a structure of the RBD-ACE2 complex (PDB ID: 6
- FIG. 9E shows the cryo-EM structure of the Fab 555-spike protein complex low-pass filtered to 8 ⁇ resolution and shown at low threshold in order to visualize all three Fabs.
- FIG. 9F is a high-resolution cryo-EM map of the Fab555-spike protein complex.
- FIGS. 10A-10H show the effect of mAb 555 (aka LY-CoV555) on the viral loads in rhesus macaques challenged with SARS-CoV-2. 24 hours prior to viral challenge, Rhesus macaques were administered varying amounts of LY-CoV555 as a single IV dose.
- Viral loads in the BAL FIGS. 10A and 10B
- throat swabs FIGS. 10C and 10D
- nasal swabs FIGS. 10E and 10F
- lung tissue FIGS. 10G and 10H
- FIGS. 10A-10F Values represent the mean and standard error of the mean for 3 or 4 animals.
- the inventions disclosed herein encompass an antibody or antigen-binding fragment thereof that specifically binds to a SARS-CoV-2 antigen, SARS-CoV-2 viral particle, or SARS-CoV-2-infected cell, wherein the antibody or antigen-binding fragment thereof comprises:
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Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20210355196A1 (en) * | 2020-05-17 | 2021-11-18 | Astrazeneca Uk Limited | Sars-cov-2 antibodies and methods of selecting and using the same |
US20220018838A1 (en) * | 2020-07-20 | 2022-01-20 | Bio-Rad Laboratories, Inc. | Immunoassay for sars-cov-2 neutralizing antibodies and materials therefor |
US11440952B2 (en) | 2020-10-16 | 2022-09-13 | Invisishield Technologies Ltd. | Compositions for preventing or treating viral and other microbial infections |
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Families Citing this family (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6323840B1 (en) | 1999-09-17 | 2001-11-27 | Cts Corporation | Surface-mount pointing device |
AU2004260884B2 (en) * | 2003-07-22 | 2009-11-19 | Crucell Holland B.V. | Binding molecules against SARS-coronavirus and uses thereof |
AU2005303758B2 (en) | 2004-11-11 | 2011-04-28 | Crucell Holland B.V. | Compositions against SARS-coronavirus and uses thereof |
CN111592595B (zh) * | 2020-04-27 | 2021-02-19 | 南京医科大学 | 抗新型冠状病毒SARS-Cov-2的中和性抗体及其应用 |
CN112300375B (zh) * | 2020-11-06 | 2022-10-25 | 江苏三木化工股份有限公司 | 一种水性光固化环氧丙烯酸树脂的制备方法 |
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