Broadly neutralizing antibodies against RSV and MPV paramyxoviruses

Abstract

The present disclosure provides antibodies and antigen-binding fragments capable of binding to RSV and / or MPV fusion glycoproteins and neutralizing RSV and / or MPV infection. Polynucleotides encoding the antibodies, vectors containing such polynucleotides, host cells capable of expressing the antibodies, related compositions, and methods of using the compositions disclosed herein, for example, to treat or prevent RSV and / or MPV infection, are also provided.

Description

[Technical Field]

[0001] Reference to Electronic Sequence Listing The contents of the electronic sequence listing (430WO_SeqListing.xml, size: 1030 kilobytes, and created on July 26, 2023) are incorporated herein by reference in their entirety. [Background technology]

[0002] Respiratory syncytial virus (RSV) and metapneumovirus (MPV) are common cold viruses belonging to the Paramyxoviridae family that share target populations and represent major health problems in newborns and immunocompromised patients.

[0003] RSV is a leading cause of acute respiratory tract illness in infants and adults worldwide. 0.5% to 3.2% of children with RSV infection require hospitalization (Thompson et al., JAMA: The Journal of the American Medical Association 289:179-186 (2003)), and 5% to 10% of children have prolonged, severe infection, a factor thought to predispose to wheezing and asthma-like symptoms later in childhood. Because immunity to RSV does not appear to last long, reinfection is frequent (Ogra, Paediatric Respiratory Reviews 5 Suppl A:S119-126 (2003)).

[0004] Human MPV, first isolated in 2001, is now recognized as the second leading cause of acute respiratory tract illness in infants and adults. It is estimated that more than 50% of infants are infected by age 2 years and nearly all children by age 5 years. MPV accounts for approximately 5-15% of respiratory illnesses in hospitalized infants (Alto, The Journal of the American Board of Family Practice / American Board of Family Practice 17:466-469 (2004); Williams et al., N Engl J Med 350:443-450 (2004)). MPV infection is a significant disease burden in at-risk low birth weight infants, those with chronic lung disease, congestive heart disease, and immunodeficiency (Martino et al., Biology of Blood and Marrow Transplantation: Journal of the American Society for Blood and Marrow Transplantation 11:781-796 (2005)).

[0005] Co-infection with MPV and RSV may be common given their prevalence and overlapping winter epidemics. Although it is unclear whether synergistic pathology between these two viruses can occur, exacerbations resulting in particularly severe respiratory tract disease have been observed in some children coinfected with MPV and RSV (Greensill, Emerging Infectious Diseases 9:372 (2003)).

[0006] RSV, which belongs to the genus Pneumovirus in the subfamily Pneumoviriniae, and MPV, which belongs to the genus Metapneumovirus in the subfamily Pneumoviriniae, share some similarities in their genetic structure, but MPV lacks the nonstructural genes NS1 and NS2 found in RSV. The RSV and MPV envelopes contain three virus-encoded transmembrane surface glycoproteins: the major attachment glycoprotein G, the fusion glycoprotein F, and a low-molecular-weight hydrophobic SH protein. It is important to note that while the RSV and MPV envelopes contain functionally similar proteins, the F proteins of RSV and MPV share only 33% amino acid sequence identity.

[0007] The F glycoproteins of RSV and MPV direct viral entry by fusion between the virion envelope and the host cell plasma membrane. Late in infection, F proteins expressed on the cell surface can mediate fusion with neighboring cells to form syncytia (Collins et al., PNAS 81:7683-7687 (1984)). In both cases, the N-terminus of the F subunit, created by proteolytic cleavage and containing a hydrophobic stretch of amino acids called the fusion peptide, inserts directly into the target membrane to initiate fusion. After target cell binding and subsequent activation, the metastable pre-fusion F protein undergoes a series of structural rearrangements that result in the insertion of the fusion peptide into the target cell membrane, followed by the formation of a stable helical bundle that forms when the viral and cellular membranes confront each other. These structural changes result in the formation of a stable post-fusion F protein.

[0008] Only one vaccine against RSV has been approved in the United States, and it is available only for elderly patients, and no vaccine is available for MPV. Even if more vaccines are developed as more RSV cases become known, they may not be readily available for all age groups.

[0009] Evidence that serum antibodies play a role in protection against RSV virus has emerged from epidemiological and animal studies. In infants, the titer of maternally transmitted antibodies correlates with resistance to severe disease (Glezen et al., The Journal of Pediatrics 98:708-715 (1981)), and in adults, the incidence and severity of lower respiratory tract lesions are reduced in the presence of high levels of serum RSV-neutralizing antibodies (Mcintosh et al., The Journal of Infectious Diseases 138:24-32 (1978)). The monoclonal antibody palivizumab (Synagis) has been registered for the prevention of RSV infection in low birth weight infants. However, palivizumab is not consistently effective in preventing RSV infection and is not therapeutically effective. Furthermore, prolonged pulmonary replication of RSV in the presence of palivizumab resulted in the emergence of resistant virus strains in animals (Zhao and Sullender, Journal of Virology 79:3962-3968 (2005)). Another monoclonal antibody, nirsevimab (Astra Zeneca / Sanofi), was recently approved in Europe and is still undergoing approval for RSV infection in infants and very young children, and creslovimab (Merck) is in clinical trials. Longer-term studies of this antibody are not available. Currently, no monoclonal antibodies exist for the treatment or prevention of MPV infection.

[0010] The lack of a good working animal model for the most severe forms of RSV infection is related to the fact that RSV and MPV are host-restricted pneumovirus pathogens. The development of new drugs for the treatment of RSV and MPV infection has been hindered by the lack of an animal model that can reproduce all the symptoms and severity of human disease. Indeed, RSV and MPV are not natural mouse pathogens and induce only limited, minimally symptomatic, rapidly terminated primary infections in response to large, nonphysiological inocula of virus. Pneumonia virus of mice (PVM) is a natural rodent pneumovirus pathogen that belongs to the same family, subfamily, and genus (Pneumovirus) as human and bovine RSV.

[0011] Although the PVM F protein shares only 40% amino acid identity with the human RSV F protein, it has the same genetic organization, except for the M2-L duplication, which is present in RSV but not in PVM. Infection with the natural mouse pathogen PVM reproduces many of the signs and symptoms of the most severe forms of RSV, such as those that occur in human infants. PVM infection is characterized by rapid viral replication accompanied by a massive inflammatory response that leads to respiratory failure and death (Rosemberg and Domachowske, Immunology Letters 118:6-12 (2008)). Therefore, PVM infection in mice is considered to be the most relevant animal model of severe RSV and MPV infection in humans. The lack of preventative treatments and widely available vaccines against MPV infection, as well as the therapeutic ineffectiveness of palivizumab and the lack of long-term data on nirsevimab and cleslovimab, highlight the need for new preventative and therapeutic agents against these prominent human pathogens. [Brief explanation of the drawings]

[0012] [Figure 1] 1 shows the results of a neutralization assay against RSV infection in HEp-2 cells, as described in Example 1. [Figure 2]1 shows the results of a neutralization assay against MPV infection in HEp-2 cells (reported as IC50 in μg / ml), as described in Example 3. Antibody MPH12 was also tested along with antibodies MPE33, MPE8, MPF5, and RSD5. [Figure 3A] Figures 3A-3R (see also Figure 3V) show antibody binding to RSV-F, MPV-F D280 ("MPV-F" in the figures), and MPV-F N280 proteins (also referred to as "MPV-F D280N") as measured by surface plasmon resonance (SPR), as described in Example 6. The sample IDs at the top of each graph in Figures 3A-3R correlate with the MPK antibody name (e.g., Sample 9 is MPK9, Sample 44 is MPK44, etc.). Figures 3S-3U show data for antibodies MPH12, MPE8, or RSD5, as indicated by the sample IDs at the top of each figure. [Figure 3B] Figures 3A-3R (see also Figure 3V) show antibody binding to RSV-F, MPV-F D280 ("MPV-F" in the figures), and MPV-F N280 proteins (also referred to as "MPV-F D280N") as measured by surface plasmon resonance (SPR), as described in Example 6. The sample IDs at the top of each graph in Figures 3A-3R correlate with the MPK antibody name (e.g., Sample 9 is MPK9, Sample 44 is MPK44, etc.). Figures 3S-3U show data for antibodies MPH12, MPE8, or RSD5, as indicated by the sample IDs at the top of each figure. [Figure 3C]Figures 3A-3R (see also Figure 3V) show antibody binding to RSV-F, MPV-F D280 ("MPV-F" in the figures), and MPV-F N280 proteins (also referred to as "MPV-F D280N") as measured by surface plasmon resonance (SPR), as described in Example 6. The sample IDs at the top of each graph in Figures 3A-3R correlate with the MPK antibody name (e.g., Sample 9 is MPK9, Sample 44 is MPK44, etc.). Figures 3S-3U show data for antibodies MPH12, MPE8, or RSD5, as indicated by the sample IDs at the top of each figure. [Figure 3D] Figures 3A-3R (see also Figure 3V) show antibody binding to RSV-F, MPV-F D280 ("MPV-F" in the figures), and MPV-F N280 proteins (also referred to as "MPV-F D280N") as measured by surface plasmon resonance (SPR), as described in Example 6. The sample IDs at the top of each graph in Figures 3A-3R correlate with the MPK antibody name (e.g., Sample 9 is MPK9, Sample 44 is MPK44, etc.). Figures 3S-3U show data for antibodies MPH12, MPE8, or RSD5, as indicated by the sample IDs at the top of each figure. [Figure 3E] Figures 3A-3R (see also Figure 3V) show antibody binding to RSV-F, MPV-F D280 ("MPV-F" in the figures), and MPV-F N280 proteins (also referred to as "MPV-F D280N") as measured by surface plasmon resonance (SPR), as described in Example 6. The sample IDs at the top of each graph in Figures 3A-3R correlate with the MPK antibody name (e.g., Sample 9 is MPK9, Sample 44 is MPK44, etc.). Figures 3S-3U show data for antibodies MPH12, MPE8, or RSD5, as indicated by the sample IDs at the top of each figure. [Figure 3F]Figures 3A-3R (see also Figure 3V) show antibody binding to RSV-F, MPV-F D280 ("MPV-F" in the figures), and MPV-F N280 proteins (also referred to as "MPV-F D280N") as measured by surface plasmon resonance (SPR), as described in Example 6. The sample IDs at the top of each graph in Figures 3A-3R correlate with the MPK antibody name (e.g., Sample 9 is MPK9, Sample 44 is MPK44, etc.). Figures 3S-3U show data for antibodies MPH12, MPE8, or RSD5, as indicated by the sample IDs at the top of each figure. [Figure 3G] Figures 3A-3R (see also Figure 3V) show antibody binding to RSV-F, MPV-F D280 ("MPV-F" in the figures), and MPV-F N280 proteins (also referred to as "MPV-F D280N") as measured by surface plasmon resonance (SPR), as described in Example 6. The sample IDs at the top of each graph in Figures 3A-3R correlate with the MPK antibody name (e.g., Sample 9 is MPK9, Sample 44 is MPK44, etc.). Figures 3S-3U show data for antibodies MPH12, MPE8, or RSD5, as indicated by the sample IDs at the top of each figure. [Figure 3H] Figures 3A-3R (see also Figure 3V) show antibody binding to RSV-F, MPV-F D280 ("MPV-F" in the figures), and MPV-F N280 proteins (also referred to as "MPV-F D280N") as measured by surface plasmon resonance (SPR), as described in Example 6. The sample IDs at the top of each graph in Figures 3A-3R correlate with the MPK antibody name (e.g., Sample 9 is MPK9, Sample 44 is MPK44, etc.). Figures 3S-3U show data for antibodies MPH12, MPE8, or RSD5, as indicated by the sample IDs at the top of each figure. [Figure 3I]Figures 3A-3R (see also Figure 3V) show antibody binding to RSV-F, MPV-F D280 ("MPV-F" in the figures), and MPV-F N280 proteins (also referred to as "MPV-F D280N") as measured by surface plasmon resonance (SPR), as described in Example 6. The sample IDs at the top of each graph in Figures 3A-3R correlate with the MPK antibody name (e.g., Sample 9 is MPK9, Sample 44 is MPK44, etc.). Figures 3S-3U show data for antibodies MPH12, MPE8, or RSD5, as indicated by the sample IDs at the top of each figure. [Figure 3J] Figures 3A-3R (see also Figure 3V) show antibody binding to RSV-F, MPV-F D280 ("MPV-F" in the figures), and MPV-F N280 proteins (also referred to as "MPV-F D280N") as measured by surface plasmon resonance (SPR), as described in Example 6. The sample IDs at the top of each graph in Figures 3A-3R correlate with the MPK antibody name (e.g., Sample 9 is MPK9, Sample 44 is MPK44, etc.). Figures 3S-3U show data for antibodies MPH12, MPE8, or RSD5, as indicated by the sample IDs at the top of each figure. [Figure 3K] Figures 3A-3R (see also Figure 3V) show antibody binding to RSV-F, MPV-F D280 ("MPV-F" in the figures), and MPV-F N280 proteins (also referred to as "MPV-F D280N") as measured by surface plasmon resonance (SPR), as described in Example 6. The sample IDs at the top of each graph in Figures 3A-3R correlate with the MPK antibody name (e.g., Sample 9 is MPK9, Sample 44 is MPK44, etc.). Figures 3S-3U show data for antibodies MPH12, MPE8, or RSD5, as indicated by the sample IDs at the top of each figure. [Figure 3L]Figures 3A-3R (see also Figure 3V) show antibody binding to RSV-F, MPV-F D280 ("MPV-F" in the figures), and MPV-F N280 proteins (also referred to as "MPV-F D280N") as measured by surface plasmon resonance (SPR), as described in Example 6. The sample IDs at the top of each graph in Figures 3A-3R correlate with the MPK antibody name (e.g., Sample 9 is MPK9, Sample 44 is MPK44, etc.). Figures 3S-3U show data for antibodies MPH12, MPE8, or RSD5, as indicated by the sample IDs at the top of each figure. [Figure 3M] Figures 3A-3R (see also Figure 3V) show antibody binding to RSV-F, MPV-F D280 ("MPV-F" in the figures), and MPV-F N280 proteins (also referred to as "MPV-F D280N") as measured by surface plasmon resonance (SPR), as described in Example 6. The sample IDs at the top of each graph in Figures 3A-3R correlate with the MPK antibody name (e.g., Sample 9 is MPK9, Sample 44 is MPK44, etc.). Figures 3S-3U show data for antibodies MPH12, MPE8, or RSD5, as indicated by the sample IDs at the top of each figure. [Figure 3N] Figures 3A-3R (see also Figure 3V) show antibody binding to RSV-F, MPV-F D280 ("MPV-F" in the figures), and MPV-F N280 proteins (also referred to as "MPV-F D280N") as measured by surface plasmon resonance (SPR), as described in Example 6. The sample IDs at the top of each graph in Figures 3A-3R correlate with the MPK antibody name (e.g., Sample 9 is MPK9, Sample 44 is MPK44, etc.). Figures 3S-3U show data for antibodies MPH12, MPE8, or RSD5, as indicated by the sample IDs at the top of each figure. [Figure 3O]Figures 3A-3R (see also Figure 3V) show antibody binding to RSV-F, MPV-F D280 ("MPV-F" in the figures), and MPV-F N280 proteins (also referred to as "MPV-F D280N") as measured by surface plasmon resonance (SPR), as described in Example 6. The sample IDs at the top of each graph in Figures 3A-3R correlate with the MPK antibody name (e.g., Sample 9 is MPK9, Sample 44 is MPK44, etc.). Figures 3S-3U show data for antibodies MPH12, MPE8, or RSD5, as indicated by the sample IDs at the top of each figure. [Figure 3P] Figures 3A-3R (see also Figure 3V) show antibody binding to RSV-F, MPV-F D280 ("MPV-F" in the figures), and MPV-F N280 proteins (also referred to as "MPV-F D280N") as measured by surface plasmon resonance (SPR), as described in Example 6. The sample IDs at the top of each graph in Figures 3A-3R correlate with the MPK antibody name (e.g., Sample 9 is MPK9, Sample 44 is MPK44, etc.). Figures 3S-3U show data for antibodies MPH12, MPE8, or RSD5, as indicated by the sample IDs at the top of each figure. [Figure 3Q] Figures 3A-3R (see also Figure 3V) show antibody binding to RSV-F, MPV-F D280 ("MPV-F" in the figures), and MPV-F N280 proteins (also referred to as "MPV-F D280N") as measured by surface plasmon resonance (SPR), as described in Example 6. The sample IDs at the top of each graph in Figures 3A-3R correlate with the MPK antibody name (e.g., Sample 9 is MPK9, Sample 44 is MPK44, etc.). Figures 3S-3U show data for antibodies MPH12, MPE8, or RSD5, as indicated by the sample IDs at the top of each figure. [Figure 3R]Figures 3A-3R (see also Figure 3V) show antibody binding to RSV-F, MPV-F D280 ("MPV-F" in the figures), and MPV-F N280 proteins (also referred to as "MPV-F D280N") as measured by surface plasmon resonance (SPR), as described in Example 6. The sample IDs at the top of each graph in Figures 3A-3R correlate with the MPK antibody name (e.g., Sample 9 is MPK9, Sample 44 is MPK44, etc.). Figures 3S-3U show data for antibodies MPH12, MPE8, or RSD5, as indicated by the sample IDs at the top of each figure. [Figure 3S] Figures 3A-3R (see also Figure 3V) show antibody binding to RSV-F, MPV-F D280 ("MPV-F" in the figures), and MPV-F N280 proteins (also referred to as "MPV-F D280N") as measured by surface plasmon resonance (SPR), as described in Example 6. The sample IDs at the top of each graph in Figures 3A-3R correlate with the MPK antibody name (e.g., Sample 9 is MPK9, Sample 44 is MPK44, etc.). Figures 3S-3U show data for antibodies MPH12, MPE8, or RSD5, as indicated by the sample IDs at the top of each figure. [Figure 3T] Figures 3A-3R (see also Figure 3V) show antibody binding to RSV-F, MPV-F D280 ("MPV-F" in the figures), and MPV-F N280 proteins (also referred to as "MPV-F D280N") as measured by surface plasmon resonance (SPR), as described in Example 6. The sample IDs at the top of each graph in Figures 3A-3R correlate with the MPK antibody name (e.g., Sample 9 is MPK9, Sample 44 is MPK44, etc.). Figures 3S-3U show data for antibodies MPH12, MPE8, or RSD5, as indicated by the sample IDs at the top of each figure. [Figure 3U]Figures 3A-3R (see also Figure 3V) show antibody binding to RSV-F, MPV-F D280 ("MPV-F" in the figures), and MPV-F N280 proteins (also referred to as "MPV-F D280N") as measured by surface plasmon resonance (SPR), as described in Example 6. The sample IDs at the top of each graph in Figures 3A-3R correlate with the MPK antibody name (e.g., Sample 9 is MPK9, Sample 44 is MPK44, etc.). Figures 3S-3U show data for antibodies MPH12, MPE8, or RSD5, as indicated by the sample IDs at the top of each figure. [Figure 4A] Individual SPR data plots are shown for each antibody pair tested in a competitive binding assay, as described in Example 6. [Figure 4B] Individual SPR data plots are shown for each antibody pair tested in a competitive binding assay, as described in Example 6. [Figure 4C] Individual SPR data plots are shown for each antibody pair tested in a competitive binding assay, as described in Example 6. [Figure 4D] Individual SPR data plots are shown for each antibody pair tested in a competitive binding assay, as described in Example 6. [Figure 4E] Individual SPR data plots are shown for each antibody pair tested in a competitive binding assay, as described in Example 6. [Figure 4F] Individual SPR data plots are shown for each antibody pair tested in a competitive binding assay, as described in Example 6. [Figure 4G] Individual SPR data plots are shown for each antibody pair tested in a competitive binding assay, as described in Example 6. [Figure 4H] Individual SPR data plots are shown for each antibody pair tested in a competitive binding assay, as described in Example 6. [Figure 4I] Individual SPR data plots are shown for each antibody pair tested in a competitive binding assay, as described in Example 6. [Figure 5A] As described in Example 6, the results of a post-fusion RSV F protein binding assay using MPE8 are shown. [Figure 5B] As described in Example 6, the results of a post-fusion RSV F protein binding assay using MPH12 are shown. [Figure 6A] Figure 6 shows neutralization of RSV A and B strains, and MPV A and B strains by MPE8 and MPH12 antibodies (reported as ng / ml), as described in Example 7. Figure 6A shows neutralization of RSV strains. Figure 6B shows neutralization of MPV A and B strains. [Figure 6B] Figure 6 shows neutralization of RSV A and B strains, and MPV A and B strains by MPE8 and MPH12 antibodies (reported as ng / ml), as described in Example 7. Figure 6A shows neutralization of RSV strains. Figure 6B shows neutralization of MPV A and B strains. [Figure 7] Figure 1 shows the binding of MPH12-v1, MPH12-v2, MPH12-v3, and MPH12-v4 to DS-Cav1 (reported in ng / ml) as measured by ELISA as described in Example 8. MPH12 was tested as a reference. [Figure 8A] 8A and 8B show the neutralization of RSV A / A2 / 61 (FIG. 8A) and MPV A1 / 6621 (FIG. 8B) by antibodies MPH12v1, MPH12v2, MPH12v3, and MPH12v4, as measured by ELISA (reported in ng / ml), as described in Example 8. MPH12 without mutations ("MPH12-rIgG1") was tested as a reference. [Figure 8B] 8A and 8B show the neutralization of RSV A / A2 / 61 (FIG. 8A) and MPV A1 / 6621 (FIG. 8B) by antibodies MPH12v1, MPH12v2, MPH12v3, and MPH12v4, as measured by ELISA (reported in ng / ml), as described in Example 8. MPH12 without mutations ("MPH12-rIgG1") was tested as a reference. [Figure 9A]Figure 1 shows two rotation views of the MPH12 H-CDR3 model generated using homology modeling as described in Example 9. The five homology models are shown in various shades of green, and the crystal structure of MPH12 is shown in gray. [Figure 9B] Figure 1 shows two rotation views of the MPH12 H-CDR3 model generated using homology modeling as described in Example 9. The five homology models are shown in various shades of green, and the crystal structure of MPH12 is shown in gray. [Figure 10A] Four rotation views of the Fab structure of MPH12 are shown, as described in Example 9. In Figure 10C, a groove corresponding to the space occupied by H-CDR3 is shown between L-CDR1 and L-CDR3. H-CDR3 is shown occupying the groove. [Figure 10B] Four rotation views of the Fab structure of MPH12 are shown, as described in Example 9. In Figure 10C, a groove corresponding to the space occupied by H-CDR3 is shown between L-CDR1 and L-CDR3. H-CDR3 is shown occupying the groove. [Figure 10C] Four rotation views of the Fab structure of MPH12 are shown, as described in Example 9. In Figure 10C, a groove corresponding to the space occupied by H-CDR3 is shown between L-CDR1 and L-CDR3. H-CDR3 is shown occupying the groove. [Figure 10D] Four rotation views of the Fab structure of MPH12 are shown, as described in Example 9. In Figure 10C, a groove corresponding to the space occupied by H-CDR3 is shown between L-CDR1 and L-CDR3. H-CDR3 is shown occupying the groove. [Figure 11A] As described in Example 9, two rotational diagrams of the MPH12 H-CDR3 conformation are shown at temperatures of 100 K (FIG. 11A) and 293 K (room temperature - FIG. 11B). [Figure 11B] As described in Example 9, two rotational diagrams of the MPH12 H-CDR3 conformation are shown at temperatures of 100 K (FIG. 11A) and 293 K (room temperature - FIG. 11B). [Figure 12A] 12A and 12B show the binding of MPH12 to purified RSV-F (FIG. 12A) and purified MPV-F D280 (labeled "MPV-F" in the figure) (FIG. 12B) as measured by SPR, as described in Example 9. [Figure 12B] 12A and 12B show the binding of MPH12 to purified RSV-F (FIG. 12A) and purified MPV-F D280 (labeled "MPV-F" in the figure) (FIG. 12B) as measured by SPR, as described in Example 9. [Figure 13] 1 shows the Fab structure of MPH12 obtained using the 2.5A room temperature X-ray structure with the broadest CDR definitions (all CDR definitions combined), as described in Example 10. [Figure 14] Figure 1 shows production titers of six mutant antibodies (MPH12-v16, MPH12-v17, MPH12-v28, MPH12-v29, MPH12-v34, and MPH12-v35, shown in Tables 2 and 20, with reference to Table 1 and the Sequence Listing) selected for further characterization as described in Example 11. MPH12* (parent MPH12-wt) was included as a comparison. [Figure 15A] 15A shows the binding of MPH12 and MPH12 mutant antibodies (MPH12-v16, MPH12-v17, MPH12-v28, MPH12-v29, MPH12-v34, and MPH12-v35) to RSV-F (FIG. 15A), MPV-F D280 (labeled "MPV-F" in the figure) (FIG. 15B), and MPV-F N280 (FIG. 15C), as measured using biolayer interferometry (BLI), as described in Example 11. [Figure 15B] 15A shows the binding of MPH12 and MPH12 mutant antibodies (MPH12-v16, MPH12-v17, MPH12-v28, MPH12-v29, MPH12-v34, and MPH12-v35) to RSV-F (FIG. 15A), MPV-F D280 (labeled "MPV-F" in the figure) (FIG. 15B), and MPV-F N280 (FIG. 15C), as measured using biolayer interferometry (BLI), as described in Example 11. [Figure 15C] 15A shows the binding of MPH12 and MPH12 mutant antibodies (MPH12-v16, MPH12-v17, MPH12-v28, MPH12-v29, MPH12-v34, and MPH12-v35) to RSV-F (FIG. 15A), MPV-F D280 (labeled "MPV-F" in the figure) (FIG. 15B), and MPV-F N280 (FIG. 15C), as measured using biolayer interferometry (BLI), as described in Example 11. [Figure 16A] 16A and 16B show the neutralization of RSV (FIG. 16A) and MPV (FIG. 16B) by six MPH12 mutant antibodies, as measured using a GFP-based in vitro neutralization assay, as described in Example 11. [Figure 16B] 16A and 16B show the neutralization of RSV (FIG. 16A) and MPV (FIG. 16B) by six MPH12 mutant antibodies, as measured using a GFP-based in vitro neutralization assay, as described in Example 11. [Figure 17] Figure 1 shows the thermal stability of six MPH12 mutant antibodies, measured using the ProteinShift assay as described in Example 11. The MPH12 parent antibody and rituximab were included as comparisons. [Figure 18] Figure 1 shows the lack of polyreactivity of six MPH12 mutant antibodies when tested in the Eurimmune 293 slide assay, as described in Example 11. The MPH12 parent antibody ("WT") was included as a comparison. [Figure 19A]Activation of FcγRIIIa (F158 allele) and FcγRIIa (H131 allele) is shown, as described in Example 11. MPH12-v16 and MPH12-v34 were tested alongside comparative antibodies, MPE8-v3(p11), MPE8-v3(p12), palivizumab, and MEDI8897-YTE. Activation of Jurkat-FcγRIIIa (F158 allele) using Expi293 target cells transfected with RSV-F (FIG. 19A), Jurkat-FcγRIIIa (F158 allele) using Expi293 target cells transfected with MPV-F D280 (FIG. 19B), and Jurkat-FcγRIIa (H131 allele) by Expi293 target cells transfected with RSV-F (FIG. 19C) was tested. [Figure 19B] Activation of FcγRIIIa (F158 allele) and FcγRIIa (H131 allele) is shown, as described in Example 11. MPH12-v16 and MPH12-v34 were tested alongside comparative antibodies, MPE8-v3(p11), MPE8-v3(p12), palivizumab, and MEDI8897-YTE. Activation of Jurkat-FcγRIIIa (F158 allele) using Expi293 target cells transfected with RSV-F (FIG. 19A), Jurkat-FcγRIIIa (F158 allele) using Expi293 target cells transfected with MPV-F D280 (FIG. 19B), and Jurkat-FcγRIIa (H131 allele) by Expi293 target cells transfected with RSV-F (FIG. 19C) was tested. [Figure 19C]Activation of FcγRIIIa (F158 allele) and FcγRIIa (H131 allele) is shown, as described in Example 11. MPH12-v16 and MPH12-v34 were tested alongside comparative antibodies, MPE8-v3(p11), MPE8-v3(p12), palivizumab, and MEDI8897-YTE. Activation of Jurkat-FcγRIIIa (F158 allele) using Expi293 target cells transfected with RSV-F (FIG. 19A), Jurkat-FcγRIIIa (F158 allele) using Expi293 target cells transfected with MPV-F D280 (FIG. 19B), and Jurkat-FcγRIIa (H131 allele) by Expi293 target cells transfected with RSV-F (FIG. 19C) was tested. [Figure 20-1] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-2] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-3] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-4] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-5]1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-6] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-7] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-8] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-9] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-10] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-11]1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-12] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-13] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-14] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-15] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-16] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-17]1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-18] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-19] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-20] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-21] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-22] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-23]1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-24] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-25] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-26] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-27] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-28] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-29]1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-30] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-31] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-32] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-33] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-34] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-35]1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-36] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-37] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-38] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-39] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-40] 1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 20-41]1 shows the results of competition / binning assays for MPK73, MPK65, MPK44, MPK36, MPK15, and MPH12 with comparative antibodies MPE8, D25, and RSD5 (shown in Tables 2, 3, and 4, with reference to Table 1 and the Sequence Listing), as described in Example 12. [Figure 21] As described in Example 13, the results of an RSV ADCC assay for MPK44 and MPK65-v2 (shown in Table 2, with reference to Table 1 and the Sequence Listing) are shown. [Figure 22] 1 shows the results of an MPV ADCC assay for MPK15 (shown in Table 2 with reference to Table 1 and the Sequence Listing), as described in Example 13. [Figure 23A] 1 shows the results of a RSV ADCC assay for various monoclonal antibodies (mAbs), as described in Example 13. [Figure 23B] 1 shows the results of an MPV ADCC assay for various mAbs, as described in Example 13. [Figure 24] 1 shows the results of an RSV-based ADCP assay for MPK44 and MPK65-v2, as described in Example 14. [Figure 25] 1 shows the results of an MPV-based ADCP assay for MPK15 and comparative antibodies MPE33 and MPF5, as described in Example 14. [Figure 26A] As described in Example 14, the results of i) an RSV-based ADCP assay (Figures 26A and 26B), and ii) an MPV-based ADCP assay (Figures 26C and 26D) for various antibodies are shown. [Figure 26B] As described in Example 14, the results of i) an RSV-based ADCP assay (Figures 26A and 26B), and ii) an MPV-based ADCP assay (Figures 26C and 26D) for various antibodies are shown. [Figure 26C]As described in Example 14, the results of i) an RSV-based ADCP assay (Figures 26A and 26B), and ii) an MPV-based ADCP assay (Figures 26C and 26D) for various antibodies are shown. [Figure 26D] As described in Example 14, the results of i) an RSV-based ADCP assay (Figures 26A and 26B), and ii) an MPV-based ADCP assay (Figures 26C and 26D) for various antibodies are shown. [Figure 27] 1 shows the results of an RSV escape mutant assay for various mAbs, as described in Example 15. [Figure 28] 1 shows the results of an MPV escape mutant assay for various mAbs, as described in Example 16. [Figure 29] 1 shows the results of MPK190 and MPK77 and the comparator antibody nirsevimab on weight loss in RSV-infected mice, as described in Example 17. [Figure 30] 1 shows the results of MPK190 and MPK77 and the comparator antibody nirsevimab on survival in RSV-infected mice, as described in Example 17. [Figure 31] 1 shows the results of MPK51 and MPK190 and the comparator antibody nirsevimab on weight loss and survival in RSV-infected mice, as described in Example 17. [Figure 32] 1 shows the effects of low doses of MPK190 and the comparator antibody nirsevimab on weight loss and survival in RSV-infected mice, as described in Example 17. [Figure 33] 1 shows a heat map of mutant antibody binding to RSV A and RSV B strains as assessed by fluorescence-activated cell sorting (FACS), as described in Example 18. [Figure 34] 1 shows a heat map of mutant antibody binding to MPV strains assessed by FACS as described in Example 19. [Figure 35]2 shows the results of MPK190 incubated with RSV A-GFP added to HEp-2 and LLC-MK2 cells after 8 cycles of reinfection, as described in Example 21. [Figure 36] 1 shows the results of MPK104 incubated with RSV A-GFP added to HEp-2 and LLC-MK2 cells after 8 cycles of reinfection, as described in Example 21. [Figure 37] 2 shows the results of MPK51 incubated with RSV A-GFP added to HEp-2 and LLC-MK2 cells after 8 cycles of reinfection, as described in Example 21. [Figure 38] 1 shows the results of MPK77 incubated with RSV A-GFP added to HEp-2 and LLC-MK2 cells after 8 cycles of reinfection, as described in Example 21. [Figure 39] 2 shows the results of palivizumab incubated with RSV A-GFP added to HEp-2 and LLC-MK2 cells after 8 cycles of reinfection, as described in Example 21. [Figure 40] 1 shows the results of MPK190 incubated with MPV A2-GFP added to HEp-2 and LLC-MK2 cells after 8 cycles of reinfection, as described in Example 21. [Figure 41] 1 shows the results of MPK104 incubated with MPV A2-GFP added to HEp-2 and LLC-MK2 cells after 8 cycles of reinfection, as described in Example 21. [Figure 42] 1 shows the results of MPK51 incubated with MPV A2-GFP added to HEp-2 and LLC-MK2 cells after 8 cycles of reinfection, as described in Example 21. [Figure 43] 1 shows the results of MPK77 incubated with MPV A2-GFP added to HEp-2 and LLC-MK2 cells after 8 cycles of reinfection, as described in Example 21. [Figure 44]1 shows the results of MPE8 incubated with MPV A2-GFP added to HEp-2 and LLC-MK2 cells after 8 cycles of reinfection, as described in Example 21. [Figure 45] 1 shows a graph of mAb concentration versus days for MPK190, MPK51, MPK104, and MPK77 in an in vivo PK study as described in Example 22. [Figure 46] 1 shows an IC50 graph of neutralization of mouse-adapted RSV clones by MPK190, MPK104, MPK51, MPK77, and MEDI8897 in RSV-infected mice, as described in Example 17. [Figure 47] 1 shows the results of MPK104 and MPK51 and the comparator antibody nirsevimab on weight loss in RSV-infected mice, as described in Example 17. [Figure 48] 1 shows the results of MPK104 and MPK51 and the comparator antibody nirsevimab on survival in RSV-infected mice, as described in Example 17. [Figure 49] Figure 1 shows the lack of polyreactivity of selected MPK mutant antibodies when tested in the Euroimmun 1522-2010 slide assay, as described in Example 23. MPK wild-type antibody ("WT") was included as a comparison. [Figure 50A] Binding of MPK104 mutant antibodies (MPK104-v1.1, MPK104-v1.2, MPK104-v1.3, MPK104-v4.1, MPK104-v4.2, and MPK104-v4.3) to RSV-F (Figure 50A), MPV-F (Figure 50B), and MPV-F D280N (Figure 50C) measured using BLI as described in Example 23. [Figure 50B]Binding of MPK104 mutant antibodies (MPK104-v1.1, MPK104-v1.2, MPK104-v1.3, MPK104-v4.1, MPK104-v4.2, and MPK104-v4.3) to RSV-F (Figure 50A), MPV-F (Figure 50B), and MPV-F D280N (Figure 50C) measured using BLI as described in Example 23. [Figure 50C] Binding of MPK104 mutant antibodies (MPK104-v1.1, MPK104-v1.2, MPK104-v1.3, MPK104-v4.1, MPK104-v4.2, and MPK104-v4.3) to RSV-F (Figure 50A), MPV-F (Figure 50B), and MPV-F D280N (Figure 50C) measured using BLI as described in Example 23. [Figure 51A] Binding of MPK190 mutant antibodies (MPK190-v1.1, MPK190-v1.3, MPK190-v3.1, MPK190-v3.3, MPK190-v4.1, and MPK190-v4.3) to RSV-F (Figure 51A), MPV-F (Figure 51B), and MPV-F D280N (Figure 51C) was measured using BLI as described in Example 23. [Figure 51B] Binding of MPK190 mutant antibodies (MPK190-v1.1, MPK190-v1.3, MPK190-v3.1, MPK190-v3.3, MPK190-v4.1, and MPK190-v4.3) to RSV-F (Figure 51A), MPV-F (Figure 51B), and MPV-F D280N (Figure 51C) was measured using BLI as described in Example 23. [Figure 51C] Binding of MPK190 mutant antibodies (MPK190-v1.1, MPK190-v1.3, MPK190-v3.1, MPK190-v3.3, MPK190-v4.1, and MPK190-v4.3) to RSV-F (Figure 51A), MPV-F (Figure 51B), and MPV-F D280N (Figure 51C) was measured using BLI as described in Example 23. [Figure 52A]52A, 52B, and 52C show the binding of MPK51 mutant antibodies (MPK51-v1.1, MPK51-v3.1, and MPK51-v4.1) to RSV-F (Figure 52A), MPV-F (Figure 52B), and MPV-F D280N (Figure 52C) measured using BLI, as described in Example 23. [Figure 52B] 52A, 52B, and 52C show the binding of MPK51 mutant antibodies (MPK51-v1.1, MPK51-v3.1, and MPK51-v4.1) to RSV-F (Figure 52A), MPV-F (Figure 52B), and MPV-F D280N (Figure 52C) measured using BLI, as described in Example 23. [Figure 52C] 52A, 52B, and 52C show the binding of MPK51 mutant antibodies (MPK51-v1.1, MPK51-v3.1, and MPK51-v4.1) to RSV-F (Figure 52A), MPV-F (Figure 52B), and MPV-F D280N (Figure 52C) measured using BLI, as described in Example 23. [Figure 53A] 53A, 53B, and 53C show the binding of MPK77 mutant antibodies (MPK77-v3.1 and MPK-v1.1) to RSV-F (Figure 53A), MPV-F (Figure 53B), and MPV-F D280N (Figure 53C) measured using BLI as described in Example 23. [Figure 53B] 53A, 53B, and 53C show the binding of MPK77 mutant antibodies (MPK77-v3.1 and MPK-v1.1) to RSV-F (Figure 53A), MPV-F (Figure 53B), and MPV-F D280N (Figure 53C) measured using BLI as described in Example 23. [Figure 53C] 53A, 53B, and 53C show the binding of MPK77 mutant antibodies (MPK77-v3.1 and MPK-v1.1) to RSV-F (Figure 53A), MPV-F (Figure 53B), and MPV-F D280N (Figure 53C) measured using BLI as described in Example 23. [Figure 54A] 54A), MPV-F (FIG. 54B), and MPV-F D280N (FIG. 54C) after forced deamidation. [Figure 54B] 54A), MPV-F (FIG. 54B), and MPV-F D280N (FIG. 54C) after forced deamidation. [Figure 54C] 54A), MPV-F (FIG. 54B), and MPV-F D280N (FIG. 54C) after forced deamidation. [Figure 55] 1 shows binding of MPK190 mutants to MPV-F D280N after forced deamidation of MPK-190, as measured using BLI, as described in Example 24. [Figure 56] 1 shows the lack of polyreactivity of selected MPK mutant antibodies when tested in the Euroimmun 1522-2010 slide assay, as described in Example 26. [Figure 57A] As described in Example 28, the results of binding (FACS) of MPK antibody mutants to RSV F TM WT (Figure 57A), MPV F D280N (Figure 57B), MPV F (Figure 57C), and mock binding (Figure 57D) are shown. [Figure 57B] As described in Example 28, the results of binding (FACS) of MPK antibody mutants to RSV F TM WT (Figure 57A), MPV F D280N (Figure 57B), MPV F (Figure 57C), and mock binding (Figure 57D) are shown. [Figure 57C] As described in Example 28, the results of binding (FACS) of MPK antibody mutants to RSV F TM WT (Figure 57A), MPV F D280N (Figure 57B), MPV F (Figure 57C), and mock binding (Figure 57D) are shown. [Figure 57D] As described in Example 28, the results of binding (FACS) of MPK antibody mutants to RSV F TM WT (Figure 57A), MPV F D280N (Figure 57B), MPV F (Figure 57C), and mock binding (Figure 57D) are shown. [Figure 58A]As described in Example 28, the results of PK studies on MPK190-v1.1 tested for binding to RSV F (FIG. 58A), MPV F (FIG. 58B), and D280N F (FIG. 58C) on transfected cells are shown. [Figure 58B] As described in Example 28, the results of PK studies on MPK190-v1.1 tested for binding to RSV F (FIG. 58A), MPV F (FIG. 58B), and D280N F (FIG. 58C) on transfected cells are shown. [Figure 58C] As described in Example 28, the results of PK studies on MPK190-v1.1 tested for binding to RSV F (FIG. 58A), MPV F (FIG. 58B), and D280N F (FIG. 58C) on transfected cells are shown. [Figure 59A] As described in Example 29, MPK190-v1.3 (an MPK190 variant with an NG motif) is shown to activate FcγRIIa (ADCP) and FcRγIIIa (ADCC) and induce NK cell killing (ADCC) compared to nirsevimab in RSV A-infected Hep2 cells (Figure 59A) and MPV A1-infected Hep2 cells (Figure 57B) (NK-mediated cell killing not shown in Figure 59B). [Figure 59B] As described in Example 29, MPK190-v1.3 (an MPK190 variant with an NG motif) is shown to activate FcγRIIa (ADCP) and FcRγIIIa (ADCC) and induce NK cell killing (ADCC) compared to nirsevimab in RSV A-infected Hep2 cells (Figure 59A) and MPV A1-infected Hep2 cells (Figure 57B) (NK-mediated cell killing not shown in Figure 59B). [Figure 60A] 60A and 60B show the results of MPK190-v1.3, MEDI18897, MPE8-v3, and the comparator antibody palivizumab at 2 mg / kg (FIG. 60A) and 0.5 mg / kg (FIG. 60B) on weight loss in RSV-infected mice, as described in Example 30. [Figure 60B]60A and 60B show the results of MPK190-v1.3, MEDI18897, MPE8-v3, and the comparator antibody palivizumab at 2 mg / kg (FIG. 60A) and 0.5 mg / kg (FIG. 60B) on weight loss in RSV-infected mice, as described in Example 30. [Figure 61A] 61A and 61B show the results of MPK190-v1.3, MEDI18897, MPE8-v3, and the comparator antibody palivizumab at 2 mg / kg (FIG. 61A) and 0.5 mg / kg (FIG. 61B) on survival in RSV-infected mice, as described in Example 30. [Figure 61B] 61A and 61B show the results of MPK190-v1.3, MEDI18897, MPE8-v3, and the comparator antibody palivizumab at 2 mg / kg (FIG. 61A) and 0.5 mg / kg (FIG. 61B) on survival in RSV-infected mice, as described in Example 30. [Figure 62A] 1 shows the results of a neutralization screen of MPV / RSV antibodies, including MPK190-v1.3 (designated MPK 190 in the figures), against MPV A and MPV B strains, as described in Examples 31 and 32. [Figure 62B] 1 shows the results of a neutralization screen of MPV / RSV antibodies, including MPK190-v1.3 (designated MPK 190 in the figures), against MPV A and MPV B strains, as described in Examples 31 and 32. [Figure 63] 1 shows a heat map of RSV-only antibodies and their binding to a panel of F proteins of currently circulating RSV B strains, as described in Example 31. [Figure 64A (IC50)] 1 shows the results of neutralization screening of MPV / RSV antibodies, including MPK190-v1.3, and RSV-only antibodies, including MPK102 and MPK176, against various RSV A and RSV B lab-adapted and pandemic strains, as described in Examples 31 and 32. [Figure 64B (IC90)]1 shows the results of neutralization screening of MPV / RSV antibodies, including MPK190-v1.3, and RSV-only antibodies, including MPK102 and MPK176, against various RSV A and RSV B lab-adapted and pandemic strains, as described in Examples 31 and 32. [Figure 65] 1 shows the results of neutralization studies of MPK190-v1.3 and various comparator antibodies against representatives of all four MPV subtypes, as described in Example 32. [Figure 66] 1 shows the results of MPK190-v1.3 neutralization of a representative MPV B1 strain virus (NL / 1 / 99), as described in Example 32. [Figure 67] 1 shows the results of an ADCC test using Hep-2 cells infected with RSV strain A2 (MOI 2.5, NK 10:1) and MPK190, as described in Example 32. [Figure 68A] Figure 68A shows the emission of FcγRIIIa (F158 allele) using Expi293 target cells transfected with RSV-FA (Figure 68A), RSV-FB (Figure 68B), MPV-FA (Figure 68D), or MPV-FB (Figure 68E), and antibody-dependent killing of RSV-A2-transfected Hep-2 cells (Figure 68C), as described in Examples 31 and 32. The legend for Figures 68A-C is shown in Figure 68C, and the legend for Figures 68D-E is shown in Figure 68E. [Figure 69B]Figure 68A shows the emission of FcγRIIIa (F158 allele) using Expi293 target cells transfected with RSV-FA (Figure 68A), RSV-FB (Figure 68B), MPV-FA (Figure 68D), or MPV-FB (Figure 68E), and antibody-dependent killing of RSV-A2-transfected Hep-2 cells (Figure 68C), as described in Examples 31 and 32. The legend for Figures 68A-C is shown in Figure 68C, and the legend for Figures 68D-E is shown in Figure 68E. [Figure 68C] Figure 68A shows the emission of FcγRIIIa (F158 allele) using Expi293 target cells transfected with RSV-FA (Figure 68A), RSV-FB (Figure 68B), MPV-FA (Figure 68D), or MPV-FB (Figure 68E), and antibody-dependent killing of RSV-A2-transfected Hep-2 cells (Figure 68C), as described in Examples 31 and 32. The legend for Figures 68A-C is shown in Figure 68C, and the legend for Figures 68D-E is shown in Figure 68E. [Figure 68D] Figure 68A shows the emission of FcγRIIIa (F158 allele) using Expi293 target cells transfected with RSV-FA (Figure 68A), RSV-FB (Figure 68B), MPV-FA (Figure 68D), or MPV-FB (Figure 68E), and antibody-dependent killing of RSV-A2-transfected Hep-2 cells (Figure 68C), as described in Examples 31 and 32. The legend for Figures 68A-C is shown in Figure 68C, and the legend for Figures 68D-E is shown in Figure 68E. [Figure 68E]Figure 68A shows the emission of FcγRIIIa (F158 allele) using Expi293 target cells transfected with RSV-FA (Figure 68A), RSV-FB (Figure 68B), MPV-FA (Figure 68D), or MPV-FB (Figure 68E), and antibody-dependent killing of RSV-A2-transfected Hep-2 cells (Figure 68C), as described in Examples 31 and 32. The legend for Figures 68A-C is shown in Figure 68C, and the legend for Figures 68D-E is shown in Figure 68E. [Figure 69A] 69A and 69B show the effect of various doses of MPK190-v1.3 and control antibodies on viral titers in cotton rats challenged with RSV A (FIG. 69A) or RSV B (FIG. 69B), as described in Example 30. [Figure 69B] 69A and 69B show the effect of various doses of MPK190-v1.3 and control antibodies on viral titers in cotton rats challenged with RSV A (FIG. 69A) or RSV B (FIG. 69B), as described in Example 30. [Figure 70A] As described in Example 32, synergy between MPK190 and selected RSV-only antibodies is shown for neutralization of RSV A (Figures 70A-70C) or RSV F (Figures 70D-70F). [Figure 70B] As described in Example 32, synergy between MPK190 and selected RSV-only antibodies is shown for neutralization of RSV A (Figures 70A-70C) or RSV F (Figures 70D-70F). [Figure 70C] As described in Example 32, synergy between MPK190 and selected RSV-only antibodies is shown for neutralization of RSV A (Figures 70A-70C) or RSV F (Figures 70D-70F). [Figure 70D] As described in Example 32, synergy between MPK190 and selected RSV-only antibodies is shown for neutralization of RSV A (Figures 70A-70C) or RSV F (Figures 70D-70F). [Figure 70E] As described in Example 32, synergy between MPK190 and selected RSV-only antibodies is shown for neutralization of RSV A (Figures 70A-70C) or RSV F (Figures 70D-70F). [Figure 70F] As described in Example 32, synergy between MPK190 and selected RSV-only antibodies is shown for neutralization of RSV A (Figures 70A-70C) or RSV F (Figures 70D-70F). [Figure 71A] As described in Example 30, the effects of MPK176, MPK201, and MPK65-v2, and comparison antibodies, at 2 mg / kg (Figures 71A and 71C) and 0.5 mg / kg (Figures 71B and 71D) on weight change and survival in RSV-infected mice are shown. [Figure 71B] As described in Example 30, the effects of MPK176, MPK201, and MPK65-v2, and comparison antibodies, at 2 mg / kg (Figures 71A and 71C) and 0.5 mg / kg (Figures 71B and 71D) on weight change and survival in RSV-infected mice are shown. [Figure 72] 1 shows neutralization of various MPV subtypes by MPK190-v1.3, as described in Example 32. [Figure 73A] 1 shows the effect of various doses of MPK190-v1.3 and comparator antibodies on viral titers in cotton rats challenged with MPV, as described in Example 30. [Figure 73B] 1 shows the effect of various doses of MPK190-v1.3 and comparator antibodies on viral titers in cotton rats challenged with MPV, as described in Example 30. [Figure 74] As described in Example 32, the predicted RSV F binding of MPK190-v1.3 to RSVF is shown compared to the binding of the comparative antibodies MPE8 and MPH12. [Figure 75A]1 shows the emission of FcγRIIIa (V158 allele) using RSV-FB transfected Expi293 target cells for various combinations of MPK190-v1.2 and RSV-only antibodies, as described in Example 33. [Figure 75B] 1 shows the emission of FcγRIIIa (V158 allele) using RSV-FB transfected Expi293 target cells for various combinations of MPK190-v1.2 and RSV-only antibodies, as described in Example 33. [Figure 75C] 1 shows the emission of FcγRIIIa (V158 allele) using RSV-FB transfected Expi293 target cells for various combinations of MPK190-v1.2 and RSV-only antibodies, as described in Example 33. [Figure 75D] 1 shows the emission of FcγRIIIa (V158 allele) using RSV-FB transfected Expi293 target cells for various combinations of MPK190-v1.2 and RSV-only antibodies, as described in Example 33. [Figure 75E] 1 shows the emission of FcγRIIIa (V158 allele) using RSV-FB transfected Expi293 target cells for various combinations of MPK190-v1.2 and RSV-only antibodies, as described in Example 33. [Figure 76] 75A-75E show AUC results for the data in FIG. 75A-E, as described in Example 33. [Figure 77] 7A-7E show graphs summarizing RSV A2 neutralization data for individual antibodies and for the combination of RSV-only antibodies and MPK190-v1.3, as described in Example 33. [Figure 78] 1 shows a summary of RSV A2 neutralization data for combinations of RSV-only antibodies and MPK190-v1.3, as described in Example 33. [Figure 79A]As described in Examples 31 and 32, neutralization data (Figure 79A) and a summary graph (Figure 79B) are shown for RSV-only antibodies and Fab fragments of MPK190-v1.3 against RSV A (top graph) and MPV (bottom graph). [Figure 79B] As described in Examples 31 and 32, neutralization data (Figure 79A) and a summary graph (Figure 79B) are shown for RSV-only antibodies and Fab fragments of MPK190-v1.3 against RSV A (top graph) and MPV (bottom graph). [Figure 80] 1 shows a summary of the effector functions of MPK190-v1.3 and RSV-only antibodies, as described in Examples 31 and 32. DETAILED DESCRIPTION OF THE INVENTION

[0013] Provided herein are antibodies and antigen-binding fragments that can bind to RSV and / or MPV and, in some embodiments, potently neutralize infection therewith. Also provided are polynucleotides, vectors, host cells, and related compositions encoding the antibodies and antigen-binding fragments, as well as methods of using the antibodies, nucleic acids, vectors, host cells, and related compositions to treat (e.g., reduce, delay, eliminate, or prevent) a RSV and / or MPV infection in a subject and / or in the manufacture of a medicament for treating a RSV and / or MPV infection in a subject.

[0014] In some embodiments, the antibodies or antigen-binding fragments thereof of the present disclosure may be capable of treating infections with MPV harboring the D280N mutation, as well as other variants of MPV, the D280N mutation found in the B2 viral subtype, which has proven difficult to treat with other potential therapeutic agents.

[0015] In some embodiments, the antibodies or antigen-binding fragments thereof of the present disclosure may bind to and / or neutralize multiple RSV and / or MPV strains (sometimes referred to as RSV and / or MPV types or subtypes) to treat and / or prevent infection by those strains.

[0016] In other embodiments, the antibodies or antigen-binding fragments thereof of the present disclosure may promote survival and reduce weight loss in RSV-infected patients at least as effectively as nirsevimab, an anti-RSV antibody that has had favorable clinical trial results.

[0017] In some embodiments, the antibodies or antigen-binding fragments thereof of the present disclosure may provide unique broad-spectrum treatment and protection to patients without the need for complex diagnostics to determine whether the infection is with RSV or MPV, or which MPV, because the antibodies or antigen-binding fragments may be able to effectively bind the F proteins of both RSV and MPV, even when the D280N mutation is present in MPV.

[0018] Before setting forth the present disclosure in more detail, it may be helpful to an understanding of the disclosure to provide definitions of certain terms used herein. Additional definitions are set out throughout the disclosure.

[0019] As used herein, any concentration range, percentage range, ratio range, or integer range should be understood to include any integer value within the recited range, and, where appropriate, fractions thereof (such as tenths and hundredths of integers), unless otherwise indicated. Additionally, any numerical range recited herein with respect to any physical characteristic (e.g., polymer subunits, size, or thickness) should be understood to include any integer within the recited range, unless otherwise indicated. As used herein, the term "about" means ±20% of the recited range, value, or structure, unless otherwise indicated. As used herein, the terms "a" and "an" should be understood to refer to "one or more" of the recited components. The use of alternatives (e.g., "or") should be understood to mean either one, both, or any combination thereof of the alternatives. As used herein, the terms "include," "have," and "comprise" are used interchangeably, and these terms and variations thereof are intended to be non-limiting.

[0020] "Optional" or "optionally" means that the subsequently described element, component, event, or circumstance may or may not occur, and that the description includes instances when the element, component, event, or circumstance occurs or does not occur.

[0021] Additionally, it should be understood that individual constructs or groups of constructs derived from various combinations of the structures and subunits described herein are disclosed by this application to the same extent as if each construct or group of constructs were individually described, and thus selection of a particular structure or particular subunit is within the scope of this disclosure.

[0022] The term "consisting essentially of" is not equivalent to "comprising" and refers to specified materials or steps within a claim or that do not materially affect the basic characteristics of the claimed subject matter. For example, a protein domain, region, or module (e.g., a binding domain) or protein "consists essentially of" a particular amino acid sequence if the amino acid sequence of the domain, region, module, or protein includes extensions, deletions, mutations, or combinations thereof (e.g., amino- or carboxy-terminal or inter-domain amino acids) that, in combination, contribute to at most 20% (e.g., at most 15%, 10%, 8%, 6%, 5%, 4%, 3%, 2%, or 1%) of the length of the domain, region, module, or protein and do not substantially affect (i.e., do not reduce) the activity of the domain, region, module, or protein (e.g., the target binding affinity of a binding protein) by more than 50%, such as by 40%, 30%, 25%, 20%, 15%, 10%, 5%, or 1% or less).

[0023] As used herein, "amino acid" refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as amino acids that are later modified, such as hydroxyproline, γ-carboxyglutamate, and O-phosphoserine. Amino acid analogs refer to compounds that have the same basic chemical structure as a naturally occurring amino acid, i.e., an α-carbon bonded to a hydrogen, a carboxyl group, an amino group, and an R group (e.g., homoserine, norleucine, methionine sulfoxide, methionine methylsulfonium). Such analogs have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid. Amino acid mimetics refer to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but that function in a manner similar to a naturally occurring amino acid.

[0024] As used herein, "mutation" refers to a change in the sequence of a nucleic acid molecule or polypeptide molecule compared to a reference or wild-type nucleic acid molecule or polypeptide molecule, respectively. Mutations can result in several different types of changes in the sequence, including nucleotide or amino acid substitutions, insertions, or deletions.

[0025] A "conservative substitution" refers to an amino acid substitution that does not significantly affect or alter the binding characteristics of a particular protein. Generally, a conservative substitution is one in which the substituted amino acid residue is replaced with an amino acid residue having a similar side chain. Conservative substitutions include those found in one of the following groups: Group 1: alanine (Ala or A), glycine (Gly or G), serine (Ser or S), threonine (Thr or T), Group 2: aspartic acid (Asp or D), glutamic acid (Glu or Z), Group 3: asparagine (Asn or N), glutamine (Gln or Q), Group 4: arginine (Arg or R), lysine (Lys or K), histidine (His or H), Group 5: isoleucine (Ile or I), leucine (Leu or L), methionine (Met or M), valine (Val or V), and Group 6: phenylalanine (Phe or F), tyrosine (Tyr or Y), tryptophan (Trp or W). Additionally or alternatively, amino acids can be grouped into conservative substitution groups by similar function, chemical structure, or composition (e.g., acidic, basic, aliphatic, aromatic, or sulfur-containing). For example, aliphatic groups may include, for substitution purposes, Gly, Ala, Val, Leu, and Ile. Other conservative substitution groups include: sulfur-containing: Met and cysteine (Cys or C); acidic: Asp, Glu, Asn, and Gln; small aliphatic nonpolar or slightly polar residues: Ala, Ser, Thr, Pro, and Gly; polar negatively charged residues and their amides: Asp, Asn, Glu, and Gln; polar positively charged residues: His, Arg, and Lys; large aliphatic nonpolar residues: Met, Leu, Ile, Val, and Cys; and large aromatic residues: Phe, Tyr, and Trp. Further information can be found in Creighton (1984) Proteins, WH Freeman and Company.

[0026] As used herein, "protein" or "polypeptide" refers to a polymer of amino acid residues. Proteins include naturally occurring amino acid polymers, amino acid polymers in which one or more amino acid residues are artificial chemical mimetics of corresponding naturally occurring amino acids, and non-naturally occurring amino acid polymers. Variants of the proteins, peptides, and polypeptides of the present disclosure are also contemplated. In certain embodiments, variant proteins, peptides, and polypeptides comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 99.9% identical to the amino acid sequence of a defined or reference amino acid sequence described herein.

[0027] A "nucleic acid molecule" or "polynucleotide" or "polynucleic acid" refers to a polymeric compound containing covalently linked nucleotides, which may be composed of natural subunits (e.g., purine or pyrimidine bases) or non-natural subunits (e.g., morpholine rings). Purine bases include adenine, guanine, hypoxanthine, and xanthine, while pyrimidine bases include uracil, thymine, and cytosine. Nucleic acid molecules include polyribonucleic acid (RNA), including mRNA, microRNA, siRNA, viral genomic RNA, and synthetic RNA, and polydeoxyribonucleic acid (DNA), including cDNA, genomic DNA, and synthetic DNA, either of which may be single-stranded or double-stranded. If single-stranded, the nucleic acid molecule may be the coding strand or the non-coding (antisense) strand. A nucleic acid molecule encoding an amino acid sequence includes all nucleotide sequences that encode the same amino acid sequence. Some versions of a nucleotide sequence may also contain introns, to the extent that the introns are removed via co-transcriptional or post-transcriptional mechanisms. In other words, different nucleotide sequences may encode the same amino acid sequence as a result of redundancy or degeneracy in the genetic code, or by splicing.

[0028] Variants of the nucleic acid molecules of the present disclosure are also contemplated. Variant nucleic acid molecules are at least 70%, 75%, 80%, 85%, 90%, preferably 95%, 96%, 97%, 98%, 99%, or 99.9% identical to a nucleic acid molecule of a defined or reference polynucleotide described herein, where percent sequence identity is defined as set forth below. Nucleic acid molecule variants retain the ability to encode their binding domains having the functionality described herein, such as binding to a target molecule.

[0029] "Percent sequence identity" refers to the relationship between two or more sequences, as determined by comparing the sequences. Preferred methods for determining sequence identity are designed to give the best match between the compared sequences. For example, sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced into one or both of the first and second amino acid or nucleic acid sequences for optimal alignment). Furthermore, non-homologous sequences may be ignored for comparison purposes. Percent sequence identity referred to herein is calculated over the length of the reference sequence, unless otherwise indicated. Methods for determining sequence identity and similarity can be found in publicly available computer programs. Sequence alignment and percent identity calculations may be performed using a BLAST program (e.g., BLAST 2.0, BLASTP, BLASTN, or BLASTX). The mathematical algorithm used in the BLAST program can be found in Altschul et al., Nucleic Acids Res. 25:3389-3402, 1997. Within the context of this disclosure, when sequence analysis software is used for analysis, it is understood that the results of the analysis will be based on the "default values" of the referenced program. "Default values" refers to any set of values or parameters that are initially loaded with the software when first initialized. Other examples include Clustal W, MAFFT, Clustal Omega, AlignMe, Praline, GAP, BESTFIT, Needle (EMBOSS), Stretcher (EMBOSS), GGEARCH2SEQ, Water (EMBOSS), Matcher (EMBOSS), LALIGN, and SSEARCH2SEQ. A global alignment algorithm, such as the Needleman and Wunsch algorithm, can be used to align two sequences over their entire length, maximizing the number of matches and minimizing the number of gaps. Default values can be used.

[0030] To generate a similarity score for two amino acid sequences, a scoring matrix can be used that assigns positive scores to some non-identical amino acids (e.g., conservative amino acid substitutions, amino acids with similar physiochemical properties, and / or amino acids that show frequent substitutions in orthologs, homologs, or paralogs). Non-limiting examples of scoring matrices include PAM30, PAM70, PAM250, BLOSUM45, BLOSUM50, BLOUM62, BLOSUM80, and BLOSUM90.

[0031] The term "isolated" means that the material is removed from its original environment (e.g., the natural environment if it is naturally occurring). For example, a naturally occurring nucleic acid or polypeptide present in a living animal is not isolated, but the same nucleic acid or polypeptide separated from some or all of the coexisting materials in the natural system is isolated. Such a nucleic acid may be part of a vector and / or such a nucleic acid or polypeptide may be part of a composition (e.g., a cell lysate), but such a nucleic acid is still isolated in that such a vector or composition is not part of the nucleic acid's or polypeptide's natural environment.

[0032] The term "gene" refers to a segment of DNA or RNA involved in producing a polypeptide chain, but in certain contexts it also includes the regions before and after the coding region (e.g., the 5' untranslated region (UTR) and the 3' UTR), as well as intervening sequences (introns) between individual coding segments (exons).

[0033] A "functional variant" refers to a polypeptide or polynucleotide that is structurally similar or substantially structurally similar to a parent or reference compound of the present disclosure, but that differs slightly in composition (e.g., one base, atom, or functional group is different, added, or removed) such that the polypeptide or encoded polypeptide performs one or more functions of the parent polypeptide with at least 50% efficiency, preferably at least 55%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.9%, or 100% activity level. In other words, a functional variant of a polypeptide or encoded polypeptide of the present disclosure will perform better in a selected assay, e.g., an assay for measuring binding affinity (e.g., association constant (Ka) or dissociation constant (K)), compared to the parent or reference polypeptide. D Functional variants can be said to have "similar binding," "similar affinity," or "similar activity" if they exhibit no more than a 50% reduction in performance in a Biacore® or tetramer staining assay, which measures binding affinity.

[0034] As used herein, a "functional portion" or "functional fragment" refers to a polypeptide or polynucleotide that comprises only a domain, portion, or fragment of a parent or reference compound, where the polypeptide or encoded polypeptide retains at least 50% of the activity associated with the domain, portion, or fragment of the parent or reference compound, preferably at least 55%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.9%, or 100% of the level of activity of the parent polypeptide, or provides a biological benefit (e.g., effector function). A "functional portion" or "functional fragment" of a polypeptide or encoded polypeptide of the present disclosure is said to have "similar binding" or "similar activity" if the functional portion or fragment exhibits no more than a 50% decrease in performance in a selected assay compared to the parent or reference polypeptide (preferably no more than 20% or no more than 10% or no more than a log difference in affinity compared to the parent or reference).

[0035] As used herein, the terms "genetically engineered," "recombinant," or "non-naturally occurring" refer to an organism, microorganism, cell, nucleic acid molecule, or vector that contains one or more genetic modifications or that has been modified by the introduction of an exogenous or heterologous nucleic acid molecule, where such modifications or alterations are introduced by genetic engineering (i.e., human intervention). Genetic modifications include, for example, modifications that introduce expressible nucleic acid molecules that encode functional RNA, proteins, fusion proteins, or enzymes, or the addition, deletion, substitution, or other functional disruption of other nucleic acid molecules, or the genetic material of a cell. Further modifications include, for example, non-coding regulatory regions, where the modifications alter the expression of a polynucleotide, gene, or operon.

[0036] As used herein, "heterologous" or "non-endogenous" or "exogenous" refers to any gene, protein, compound, nucleic acid molecule, or activity that is not native to a host cell or subject, or any gene, protein, compound, nucleic acid molecule, or activity that is native to a host cell or subject that has been modified. Heterologous, non-endogenous, or exogenous includes genes, proteins, compounds, or nucleic acid molecules that have been mutated or otherwise modified such that the structure, activity, or both differ between the native and modified gene, protein, compound, or nucleic acid molecule. In certain embodiments, a heterologous, non-endogenous, or exogenous gene, protein, or nucleic acid molecule (e.g., receptor, ligand, etc.) may not be endogenous to the host cell or subject, but instead, a nucleic acid encoding such a gene, protein, or nucleic acid molecule may have been added to the host cell by conjugation, transformation, transfection, electroporation, etc., and the added nucleic acid molecule may be integrated into the host cell genome or may exist as extrachromosomal genetic material (e.g., as a plasmid or other self-replicating vector). The term "homologous" or "homolog" refers to a gene, protein, compound, nucleic acid molecule, or activity found in or derived from a host cell, species, or strain. For example, a heterologous or exogenous polynucleotide or gene encoding a polypeptide may be homologous to a native polynucleotide or gene and may encode a homologous polypeptide or activity, but the polynucleotide or polypeptide may have an altered structure, sequence, expression level, or any combination thereof. The non-endogenous polynucleotide or gene, and the encoded polypeptide or activity, can be from the same species, different species, or a combination thereof.

[0037] In certain embodiments, a nucleic acid molecule or portion thereof native to a host cell is considered heterologous to the host cell if it has been modified or mutated, or a nucleic acid molecule native to the host cell can be considered heterologous if it has been modified with heterologous expression control sequences or with endogenous expression control sequences that are not normally associated with nucleic acid molecules native to the host cell. In addition, the term "heterologous" can refer to biological activity that is different, altered, or not endogenous to the host cell. As described herein, two or more heterologous nucleic acid molecules can be introduced into a host cell as separate nucleic acid molecules, as multiple individually regulated genes, as a polycistronic nucleic acid molecule, as a single nucleic acid molecule encoding a fusion protein, or any combination thereof.

[0038] As used herein, the terms "endogenous" or "native" refer to a polynucleotide, gene, protein, compound, molecule, or activity that is normally present in a host cell or subject.

[0039] As used herein, the term "expression" refers to the process by which a polypeptide is produced based on a coding sequence of a nucleic acid molecule, such as a gene. This process may include transcription, post-transcriptional control, post-transcriptional modification, translation, post-translational control, post-translational modification, or any combination thereof. An expressed nucleic acid molecule is typically operably linked to an expression control sequence (e.g., a promoter).

[0040] The term "operably linked" refers to the association of two or more nucleic acid molecules on a single nucleic acid fragment such that the function of one is affected by the other. For example, a promoter is operably linked to a coding sequence if it is capable of affecting the expression of that coding sequence (i.e., the coding sequence is under the transcriptional control of the promoter). "Unlinked" means that the associated genetic elements are not closely related to each other so that the function of one does not affect the other.

[0041] As described herein, two or more heterologous nucleic acid molecules can be introduced into a host cell as separate nucleic acid molecules, as multiple individually regulated genes, as a polycistronic nucleic acid molecule, as a single nucleic acid molecule encoding a protein (e.g., the heavy chain of an antibody), or any combination thereof. When two or more heterologous nucleic acid molecules are introduced into a host cell, it is understood that the two or more heterologous nucleic acid molecules can be introduced as a single nucleic acid molecule (e.g., on a single vector), introduced on separate vectors, integrated into a host chromosome at a single site or multiple sites, or any combination thereof. The number of heterologous nucleic acid molecules or protein activities referred to refers to the number of encoding nucleic acid molecules or protein activities, not the number of separate nucleic acid molecules introduced into the host cell.

[0042] The term "construct" refers to any polynucleotide containing a recombinant nucleic acid molecule (or, when the context clearly indicates, a fusion protein of the present disclosure). The (polynucleotide) construct may be present in a vector (e.g., a bacterial vector, a viral vector) or may be integrated into a genome. A "vector" is a nucleic acid molecule that transports another nucleic acid molecule. A vector may be, for example, a plasmid, cosmid, virus, or RNA vector. Alternatively, a vector may be a linear or circular DNA or RNA molecule, which may comprise a chromosomal, non-chromosomal, semisynthetic, or synthetic nucleic acid molecule. Vectors of the present disclosure also include transposon systems (e.g., Sleeping Beauty; see, e.g., Geurts et al., Mol. Ther. 8:108, 2003; Mates et al., Nat. Genet. 41:753, 2009). Exemplary vectors are those that replicate autonomously (episomal vectors), deliver polynucleotides to a cellular genome (e.g., viral vectors), or express nucleic acid molecules to which they are linked (expression vectors).

[0043] As used herein, "expression vector" or "vector" refers to a DNA construct comprising a nucleic acid molecule operably linked to suitable control sequences that effect expression of the nucleic acid molecule in a suitable host. Such control sequences include a promoter to drive transcription, an optional operator sequence to control such transcription, a sequence encoding a suitable mRNA ribosomal binding site, and sequences that control the termination of transcription and translation. A vector can be a plasmid, a phage particle, a virus, or simply a potential genomic insert. Once transformed into a suitable host, the vector can replicate and function independently of the host genome, or in some cases, can integrate into the genome itself or deliver a polynucleotide contained in the vector into the genome without vector sequences. Herein, "plasmid," "expression plasmid," "virus," and "vector" are often used interchangeably.

[0044] The term "introduced" in the context of inserting a nucleic acid molecule into a cell means "transfection," "transformation," or "transduction," and includes reference to the incorporation of a nucleic acid molecule into a eukaryotic or prokaryotic cell, where the nucleic acid molecule may be integrated into the cell's genome (e.g., chromosome, plasmid, plastid, or mitochondrial DNA), converted into an autonomous replicon, or transiently expressed (e.g., transfected mRNA).

[0045] In certain embodiments, the polynucleotide of the present disclosure may be operably linked to certain elements of a vector. For example, a polynucleotide sequence may be operably linked if it is required to effect expression and processing of the linked coding sequence. Expression control sequences may include appropriate transcription initiation, termination, promoter, and enhancer sequences, efficient RNA processing signals such as splicing and polyadenylation signals, sequences that stabilize cytoplasmic mRNA, sequences that enhance translation efficiency (i.e., Kozak consensus sequences), sequences that enhance protein stability, and possibly sequences that enhance protein secretion. Expression control sequences may be operably linked if they are adjacent to the gene of interest and are expression control sequences that act in trans or at a distance to control the gene of interest.

[0046] In certain embodiments, the vector comprises a plasmid vector or a viral vector (e.g., a lentiviral vector or a gamma-retroviral vector). Viral vectors include retroviruses, adenoviruses, parvoviruses (e.g., adeno-associated viruses), coronaviruses, negative-strand RNA viruses such as orthomyxoviruses (e.g., influenza viruses), rhabdoviruses (e.g., rabies and vesicular stomatitis viruses), and paramyxoviruses (e.g., measles and Sendai viruses), positive-strand RNA viruses such as picornaviruses and alphaviruses, and double-stranded DNA viruses, including adenoviruses, herpesviruses (e.g., herpes simplex virus types 1 and 2, Epstein-Barr virus, cytomegalovirus), and poxviruses (e.g., vaccinia, fowlpox, and canarypox). Other viruses include, for example, Norwalk virus, togaviruses, flaviviruses, reoviruses, papovaviruses, hepadnaviruses, and hepatitis viruses. Examples of retroviruses include avian leukosis sarcoma, mammalian type C viruses, type B viruses, type D viruses, the HTLV-BLV group, lentiviruses, and spumaviruses (Coffin, JM, Retroviridae: The viruses and their replication, Fundamental Virology, Third Edition, BN Fields et al., Eds., Lippincott-Raven Publishers, Philadelphia, 1996).

[0047] A "retrovirus" is a virus with an RNA genome that is reverse transcribed into DNA using reverse transcriptase, which then integrates into the host cell genome. "Gammaretrovirus" refers to a genus of the Retroviridae family. Examples of gammaretroviruses include murine stem cell virus, murine leukemia virus, feline leukemia virus, feline sarcoma virus, and avian reticuloendotheliosis virus.

[0048] "Lentiviral vector" includes HIV-based lentiviral vectors for gene delivery, which can be integrating or non-integrating, have a relatively large packaging capacity, and are capable of transducing a variety of different cell types. Lentiviral vectors are typically generated after transient transfection of three or more plasmids (packaging, envelope, and transfer) into producer cells. Like HIV, lentiviral vectors enter target cells through interaction of viral surface glycoproteins with receptors on the cell surface. Upon entry, viral RNA undergoes reverse transcription mediated by the viral reverse transcriptase complex. The product of reverse transcription is double-stranded linear viral DNA, which is the substrate for viral integration into the DNA of infected cells.

[0049] In certain embodiments, the viral vector may be a gammaretrovirus, such as a Moloney murine leukemia virus (MLV)-derived vector. In other embodiments, the viral vector may be a more complex retrovirus-derived vector, such as a lentivirus-derived vector. HIV-1-derived vectors fall into this category. Other examples include lentiviral vectors derived from HIV-2, FIV, equine infectious anemia virus, SIV, and Maedi-Visna virus (ovine lentivirus). Methods for using retroviral and lentiviral viral vectors and packaging cells to transduce mammalian host cells with viral particles containing a transgene are known in the art and have been previously described, for example, in U.S. Patent No. 8,119,772; Walchli et al., PLoS One 6:327930, 2011; Zhao et al., J. Immunol. 174:4415, 2005; Engels et al., Hum. Gene Ther. 14:1155, 2003; Frecha et al., Mol. Ther. 18:1748, 2010; and Verhoeyen et al., Methods Mol. Biol. 506:97, 2009. Retroviral and lentiviral vector constructs and expression systems are also commercially available. Other viral vectors can also be used for polynucleotide delivery, including, for example: DNA viral vectors (including, for example, adenovirus-based vectors and adeno-associated virus (AAV)-based vectors), herpes simplex virus (HSV)-derived vectors (including amplicon vectors, replication-deficient HSV, and attenuated HSV) (Krisky et al., Gene Ther. 5:1517, 1998).

[0050] Other vectors that can be used with the compositions and methods of the present disclosure include those derived from baculovirus and alphavirus (Jolly, D J. 1999. Emerging Viral Vectors. pp 209-40 in Friedmann T. ed. The Development of Human Gene Therapy. New York: Cold Spring Harbor Lab), or plasmid vectors (such as sleeping beauty or other transposon vectors).

[0051] When the viral vector genome contains multiple polynucleotides that are expressed as separate transcripts in a host cell, the viral vector may also contain additional sequences between the two (or more) transcripts that enable bicistronic or multicistronic expression. Examples of such sequences used in viral vectors include an internal ribosome entry site (IRES), a furin cleavage site, a viral 2A peptide, or any combination thereof.

[0052] Plasmid vectors, including plasmid vectors encoding DNA-based antibodies or antigen-binding fragments, for direct administration to a subject are further described herein.

[0053] As used herein, the term "host" refers to a cell or microorganism that is targeted for genetic modification with a heterologous nucleic acid molecule to produce a polypeptide of interest (e.g., an antibody of the present disclosure).

[0054] A host cell can include any individual cell or cell culture that can receive vector or nucleic acid uptake or express protein. The term also encompasses progeny of the host cell, whether genetically or phenotypically identical or different. Suitable host cells can depend on the vector, but can include mammalian cells, animal cells, human cells, simian cells, insect cells, yeast cells, and bacterial cells. These cells can be induced to incorporate vectors or other materials by the use of viral vectors, transformation by calcium phosphate precipitation, DEAE-dextran, electroporation, microinjection, or other methods. See, e.g., Sambrook et al., Molecular Cloning: A Laboratory Manual, 2d ed. (Cold Spring Harbor Laboratory, 1989).

[0055] In the context of RSV or MPV infection, "host" refers to a cell or subject infected with RSV or MPV.

[0056] "Antigen" or "Ag," as used herein, refers to an immunogenic molecule that elicits an immune response. This immune response may include the production of antibodies, activation of specific immunocompetent cells, complement activation, antibody-dependent cellular cytotoxicity, or any combination thereof. An antigen (immunogenic molecule) may be, for example, a peptide, glycopeptide, polypeptide, glycopolypeptide, polynucleotide, polysaccharide, lipid, etc. It is readily apparent that antigens can be synthesized, recombinantly produced, or derived from a biological sample. Exemplary biological samples that may contain one or more antigens include tissue samples, fecal samples, cells, biological fluids, or combinations thereof. Antigens may be produced by cells modified or genetically engineered to express the antigen. Antigens may also be present in RSV and / or MPV fusion glycoprotein antigens, such as those present in virions, or expressed or displayed on the surface of cells infected with RSV and / or MPV.

[0057] The term "epitope" or "antigenic epitope" includes any molecule, structure, amino acid sequence, or protein determinant that is recognized and specifically bound by a cognate binding molecule such as an immunoglobulin, or other binding molecule, domain, or protein. Epitopic determinants generally comprise chemically active surface groupings of molecules such as amino acids or sugar side chains and can have specific three-dimensional structural characteristics, as well as specific charge characteristics. When the antigen is or comprises a peptide or protein, the epitope can be composed of contiguous amino acids (e.g., a linear epitope), or amino acids from different parts or regions of the protein that are brought into proximity by protein folding (e.g., a discontinuous or conformational epitope), or noncontiguous amino acids that are brought into proximity without regard to protein folding.

[0058] Antibodies, antigen-binding fragments, and compositions In one aspect, the present disclosure provides isolated antibodies or antigen-binding fragments that bind to a fusion glycoprotein derived from RSV and / or MPV and / or neutralize RSV and / or MPV in a human subject. Reference to an antibody or antigen-binding fragment of the present disclosure that "binds" to RSV or MPV refers to binding to the fusion glycoprotein of such viruses. Furthermore, any antibody or antigen-binding fragment of the present disclosure that "binds" to RSV or MPV (or any further specified antigen, epitope, or binding site thereof) is "capable of binding" or "able to bind" to such RSV or MPV.

[0059] In certain embodiments, the antibodies or antigen-binding fragments of the present disclosure associate with or associate with the fusion glycoprotein of RSV or MPV, or the fusion glycoprotein of both RSV and MPV, but do not significantly associate with or associate with any other molecules or components in the sample.

[0060] In certain embodiments, the antibodies or antigen-binding fragments of the present disclosure specifically bind to the RSV fusion glycoprotein (also referred to herein as "RSV-F") and / or the MPV fusion glycoprotein (also referred to herein as "MPV-F"). In certain embodiments, the antibodies or antigen-binding fragments bind to RSV-F in a pre-fusion conformation, and in some embodiments, also in a post-fusion conformation. Unless otherwise specified herein, binding to RSV-F refers to binding to the pre-fusion conformation. In some embodiments, the MPV-F is a wild-type protein or a protein in which D280 is wild-type but contains other mutations (also referred to herein as "MPV-F D280"). However, in other embodiments, the MPV-F contains the D280N mutation (also referred to herein as "MPV-F N280" or "D280N"). In some embodiments, MPV-F is otherwise a wild-type protein having a mutation at D280 other than N (for purposes of this disclosure, it may be considered MPV-F D280 if it behaves like MPV-F without a mutation at D280, or MPV-F D280N if it behaves like MPV-F with the D280N mutation).

[0061] In some embodiments, the RSV / MPV cross-binding and / or neutralizing antibodies or antigen-binding fragments of the present disclosure specifically bind to i) both RSV-F and MPV-F D280, ii) both RSV-F and MPV-F N280, or iii) and / or iii) RSV-F, MPV-F D280, or MPV-F N280. In some embodiments, the RSV-binding and / or neutralizing antibodies or antigen-binding fragments of the present disclosure specifically bind to RSV-F. In some embodiments, the MPV-binding and / or neutralizing antibodies or antigen-binding fragments of the present disclosure specifically bind to i) MPV-F N280, ii) MPV-F D280, or iii) both MPV-F N280 and MPV-F D280.

[0062] As used herein, "specifically binds" refers to the affinity or K of an antibody or antigen-binding fragment for an antigen. a (i.e., the equilibrium binding constant of a particular binding interaction, which has units of 1 / M) and 5 M -1 (This means that for this association reaction, the on-rate [K on ] versus off-rate [K off ]) while not significantly associating or combining with any other molecule or component in the sample. Alternatively, affinity may be expressed in units of M (e.g., 10 -5 M~10 -13 M) of a particular binding interaction, d Antibodies can be classified as "high affinity" or "low affinity" antibodies. A "high affinity" antibody has a specific affinity of at least 10 9 M -1 , at least 10 10 M -1 , at least 10 11 M -1 , at least 10 12 M -1 , or at least 10 13 M -1 K a A "low affinity" antibody refers to an antibody having a K a But, 10 8 M -1 Up to 10 7 M -1 Up to 10 6 M -1 Up to 10 5 M -1 Alternatively, affinity is measured in units of M (e.g., 10 -5 M~10 -13 M) of a particular binding interaction, d )

[0063] A variety of assays are known for identifying antibodies of the present disclosure that bind to a particular target and for determining the affinity of a binding domain or binding protein, such as Western blot, ELISA (e.g., direct, indirect, or sandwich), analytical ultracentrifugation, spectroscopy, and surface plasmon resonance (Biacore®) analysis (see, e.g., Scatchard et al., Ann. NY Acad. Sci. 51:660, 1949; Wilson, Science 295:2103, 2002; Wolff et al., Cancer Res. 53:2560, 1993; and U.S. Pat. Nos. 5,283,173, 5,468,614, or equivalents). Assays for assessing affinity, apparent affinity, or relative affinity are also known.

[0064] In certain instances, binding can be determined by recombinantly expressing RSV-F and / or MPV-F antigens in host cells (e.g., by transfection), immunostaining the host cells (e.g., fixed or fixed and permeabilized) with antibodies, and analyzing binding by flow cytometry (e.g., using a ZE5 Cell Analyzer (BioRad®) and FlowJo software (TreeStar)). In some embodiments, positive binding can be defined by differential staining of RSV-F and / or MPV-F-expressing cells with antibodies versus control (e.g., mock-stained) cells.

[0065] In some embodiments, the antibodies or antigen-binding fragments of the present disclosure bind to RSV-F and / or MPV-F as measured using biolayer interferometry or by surface plasmon resonance.

[0066] In some embodiments, an antibody or antigen-binding fragment of the present disclosure can be assessed for competitive binding to another antibody or antigen-binding fragment using surface plasmon resonance.

[0067] Certain characteristics of the antibodies or antigen-binding fragments of the present disclosure can be described using IC50 or EC50 values. In certain embodiments, IC50 is the concentration of a composition (e.g., an antibody) that results in half-maximal inhibition of a designated biological or biochemical function, activity, or response. In certain embodiments, EC50 is the concentration of a composition that provides a half-maximal response in an assay. In some embodiments, IC50 and EC50 are used interchangeably to describe the ability of an antibody or antigen-binding fragment of the present disclosure to neutralize infection by, for example, RSV and / or MPV.

[0068] In certain embodiments, the antibodies or antigen-binding fragments of the present disclosure neutralize infection by RSV and / or MPV. As used herein, a "neutralizing antibody" is an antibody that "neutralizes," i.e., prevents, inhibits, reduces, interferes with, or interferes with, the ability of a pathogen to initiate and / or perpetuate infection in a host. The terms "neutralizing antibody" and "neutralizing antibody" or "neutralizing antibodies" are used interchangeably herein. In any of the embodiments of the present disclosure, the antibody or antigen-binding fragment prevents and / or neutralizes RSV and / or MPV infection in an in vitro model of infection, in an in vivo animal model of infection, and / or in humans. A "neutralizing antibody" is also "capable of" or "able to perform" any of the activities ascribed to a neutralizing antibody in this paragraph, and a "neutralizing" antibody or antigen-binding fragment thereof is also "capable of" or "able to neutralize."

[0069] In certain embodiments, the antibody or antigen-binding fragment is a RSV-binding and / or neutralizing antibody or antigen-binding fragment shown in Table 2 with reference to Table 1 and the sequence definitions in the sequence listing.

[0070] In certain embodiments, the antibody or antigen-binding fragment is an MPV-binding and / or neutralizing antibody or antigen-binding fragment shown in Table 2 with reference to Table 1 and the sequence definitions in the sequence listing.

[0071] In certain embodiments, the antibody or antigen-binding fragment is a RSV / MPV cross-binding and / or neutralizing antibody or antigen-binding fragment shown in Table 2 with reference to Table 1, Table 20, and the sequence definitions in the sequence listing.

[0072] A similar naming convention is used for the antibodies herein, following the principles that apply to antibody and variant names.

[0073] As used herein, "MPH12" not further specified as a variant (e.g., MPH12-v2) refers to an antibody having the CRD associated with the MPH12 VH and MPH-12 VL shown in Tables 1 and 2 and the Sequence Listing, or the MPH12 VH and MPH-12 VL shown in Tables 1 and 2 and the Sequence Listing, and an rIgG1 constant region. "MPH-v[#]" refers to the variants of MPH12 shown in Tables 2 and 20 with reference to Table 1 and the Sequence Listing, collectively referred to as MPH12 "variants." The first or only number in a variant refers to the VH variant, and a variant with two numbers, "xy," refers to the VH.VL variant. Typically, VH.1 refers to the parent VH, and VL.1 refers to the parent VL, unless otherwise indicated by the sequences herein.

[0074] MPK[#], as used herein, refers to antibodies whose names begin with "MPK" in Table 1 and Table 2 with reference to the Sequence Listing. Collectively, these antibodies may be referred to as "MPK antibodies."

[0075] Other MP[letter][#] combinations, as used herein, each refer to antibodies whose names begin with "MP[letter][#]" in Table 1 and Table 2 with reference to the Sequence Listing, in a manner similar to the MPK antibodies. Collectively, antibodies having the same MP[letter][#] combination may be referred to as that particular "MP[letter][#] antibody."

[0076] "MP[Letter][#]-v[#].[#]" refers to variants of MP[Letter][#] shown in Tables 2 and 20 with reference to Table 1 and the Sequence Listing, collectively referred to as MP[Letter][#] "variants." The first number in the variant refers to the VH variant, and the second number refers to the VL variant. For example, MPK190-v1.3 refers to an MPK190 antibody with VH.1 and VL.3 variants of the parent MPK190. MPK176-v1.3 refers to an antibody with VH.1 and VL.3 variants of the parent MPK176. MPK 176-v4.3 refers to an antibody with VH.4 and VL.3 variants of the parent MPK176. MPK201-v1.2 refers to an antibody with VH.1 and VL.2 variants of the parent MPK201. MPK201-v4.1 refers to an antibody with VH.4 and VL.2 variants of the parent MPK201.

[0077] Certain antibodies are designated as variants of a parent antibody without reference to specific VH and VL variants. These antibodies are designated MP[letter][#]-v[#] (where v[#] is a single number) and may be considered the parent antibody or referred to without the "v[#]" designation. MPK65-v2 is an example of such an antibody. The VH and VL variants of such antibodies are designated similarly to other MP[letter][#] antibodies. For example, MPK65-v2-v1.2 refers to an antibody with VH.1 and VL.2 variants of the parent MPK65-v2. MPK65-v2-v3.1 refers to an antibody with VH.3 and VL.1 variants of the parent MPK65-v2. MPK65-v2 is sometimes referred to simply as "MPK65."

[0078] Certain comparative antibodies, or antibodies that may be used in various combinations with MPH, MPK, MPM, MPO, MPP, MPR, or other MP[Letter][#] antibodies (including HMB[#]), and RSD5, are described in Tables 3 and 4 with reference to Table 1 and the Sequence Listing. MPE33 and MPE8 are described in Corti et al. Nature. 2013 Sep 19;501(7467):439-43. doi:10.1038 / nature12442. Epub 2013 Aug 18. MPF5 and RSD5 are described in Jones et al. PLoS Patho. 15(7):e1007944(2019); doi:10.1371 / journal.ppat.1007944. Antibodies with the same VH and VL as these reference antibodies but with diversity in the Fc region can also be used in place of them, as they are expected to have similar binding properties.

[0079] In certain embodiments, the antibody or antigen-binding fragment thereof is human, humanized, or chimeric.

[0080] In certain embodiments, the antibody or antigen-binding fragment comprises one or more of a VH and / or a VL, and / or two or more of a CDRH1, a CDRH2, a CDRH3, a CDRL1, a CRL2, and / or a CDRL3 set forth in SEQ ID NOs: 1-530, 811-862, and 891-903, and has a nucleotide sequence of 1.0E-12 or less, 1.0E-11 or less, 4.5E-11 or less, 1.0E-10 or less, The antibody binds to RSV-F in a prefusion conformation with a KD (M unit) of 1.0E-9 or less, 1.0E-8 or less, or 1.0E-7 or less, or in the range of 1.0E-12 to 1.0E-7, 1.0E-12 to 1.0E-8, 1.0E-12 to 1.0E-9, 1.0E-12 to 1.0E-10, or 1.0E-12 to 1.0E-11, optionally as assessed by surface plasmon resonance (SPR). In some embodiments, binding is any of the foregoing values or ranges that are 1.0E-9 or less, which is high affinity binding according to the present disclosure.

[0081] In certain embodiments, the antibody or antigen-binding fragment comprises one or more of a VH and / or a VL, and / or two or more of a CDRH1, CDRH2, CDRH3, CDRL1, CRL2, and / or CDRL3 set forth in SEQ ID NOs:531-556, and binds to RSV-F in a prefusion conformation with a KD (M units) of 1.0E-10 or less, 7.5E-10 or less, 1.0E-9 or less, or 1.5E-9 or less, or in the range of 1.0E-10 to 1.5E-9, 1.0E-10 to 1.0E-9, 1.0E-10 to 7.5E-10, or 7.5E-10 to 1.5E-9, optionally as assessed by surface plasmon resonance (SPR). In some embodiments, binding is any of the foregoing values or ranges of 1.0E-9 or less, which is high affinity binding according to the present disclosure.

[0082] In certain embodiments, the antibody or antigen-binding fragment comprises one or more of a VH and / or a VL, and / or two or more of a CDRH1, a CDRH2, a CDRH3, a CDRL1, a CRL2, and / or a CDRL3 set forth in SEQ ID NOs: 1-530, 811-862, and 891-903, and has a nucleotide sequence of 1.0E-12M or less, 1.0E-11 or less, 4.5E-11 or less, or less, 1.0E-10 or less, 1.0E-9 or less, 8.0E-9 or less, 1.0E-8 or less, or 1.0E-7 or less, or in the ranges of 1.0E-12 to 1.0E-7, 1.0E-12 to 8.0E-9, 1.0E-12 to 1.0E-10, 1.0E-12 to 4.5E-11, 1.0E-12 to 1.0E-11, or 4.5E-11 to 8.0E-9, optionally wherein the binding is assessed by surface plasmon resonance (SPR). In some embodiments, the binding is any of the aforementioned values or ranges that are 1.0E-9 or less, which is high affinity binding according to the present disclosure.

[0083] In certain embodiments, the antibody or antigen-binding fragment comprises one or more of a VH and / or a VL, and / or two or more of a CDRH1, a CDRH2, a CDRH3, a CDRL1, a CRL2, and / or a CDRL3 set forth in SEQ ID NOs: 531-556, and binds to MPV-F D280 with a KD (in M units) of 1.0E-12 or less, 1.0E-11 or less, 4.5E-11 or less, or 1.0E-10 or less, or in the range of 1.0E-12 to 1.0E-11, 1.0E-12 to 4.5E-11, or 1.0E-12 to 1.0E-10, optionally wherein the binding is assessed by surface plasmon resonance (SPR).

[0084] In certain embodiments, the antibody or antigen-binding fragment comprises one or more of a VH and / or a VL, and / or two or more of a CDRH1, a CDRH2, a CDRH3, a CDRL1, a CRL2, and / or a CDRL3 set forth in SEQ ID NOs: 1-530, 811-862, and 891-903, and has a nucleotide sequence of 1.0E-12 or less, 1.0E-11 or less, 5.8E-11 or less, 1.0E-1 and binds to MPV-F N280 with a KD (in M) of 0 or less, 1.0E-9 or less, 8.0E-9 or less, 1.0E-8 or less, or 1.0E-7 or less, or in the ranges of 1.0E-12 to 1.0E-7, 1.0E-12 to 1.0E-11, 1.0E-12 to 1.0E-10, 1.0E-12 to 1.0E-9, 1.0E-12 to 1.0E-8, 1.0E-12 to 1.0E-7, or 1.0E-12 to 5.8E-11, optionally wherein the binding is assessed by surface plasmon resonance (SPR). In some embodiments, the binding is any of the aforementioned values or ranges that are 1.0E-9 or less, which is designated as high affinity binding according to the present disclosure.

[0085] In certain embodiments, the antibody or antigen-binding fragment comprises one or more of a VH and / or a VL and / or two or more of a CDRH1, CDRH2, CDRH3, CDRL1, CRL2, and / or CDRL3 set forth in SEQ ID NOs:531-556, and binds to MPV-F N280 with a KD (in M units) of 1.0E-10 or less, 1.0E-9 or less, 2.5E-9 or less, or 1.0E-8 or less, or in the range of 1.0E-10 to 1.0E-8, 1.0E-10 to 1.0E-9, or 1.0E-10 to 2.5E-9, optionally as assessed by surface plasmon resonance (SPR). In some embodiments, binding is any of the foregoing values or ranges that are 1.0E-9 or less, which is high affinity binding according to the present disclosure.

[0086] In certain embodiments, the antibody or antigen-binding fragment comprises one or more of a VH and / or a VL, and / or two or more of a CDRH1, CDRH2, CDRH3, CDRL1, CRL2, and / or CDRL3 set forth in SEQ ID NOs: 1-530, 811-862, and 891-903, and neutralizes RSV as measured in vitro with an IC50 of 30 ng / ml or less, 15 ng / ml or less, 10 ng / ml or less, 2.0 ng / ml or less, 1.0 ng / ml or less, or 0.2 ng / ml or less, or in the range of 0.2 ng / ml to 30 ng / ml, 0.2 ng / ml to 15 ng / ml, 0.2 ng / ml to 2.0 ng / ml, 1.0 ng / ml to 30 ng / ml, or 2.0 ng / ml to 15 ng / ml.

[0087] In certain embodiments, the antibody or antigen-binding fragment comprises one or more of a VH and / or a VL, and / or two or more of a CDRH1, CDRH2, CDRH3, CDRL1, CRL2, and / or CDRL3 set forth in SEQ ID NOs: 1-530, 811-862, and 891-903, and has a saturation of 30 ng / ml or less, 15 ng / ml or less, 10 ng / ml or less, 7.0 ng / ml or less, 6.0 ng / ml or less, 5 ng / ml or less, or neutralizes MPV, as measured in vitro, with an IC50 of 1.5 ng / ml or less, or in the range of 1.0 ng / ml to 30 ng / ml, 1.0 ng / ml to 15 ng / ml, 1.0 ng / ml to 10 ng / ml, 1.0 ng / ml to 7.0 ng / ml, 1.0 ng / ml to 5.0 ng / ml, 5.0 ng / ml to 30 ng / ml, 5.0 ng / ml to 15 ng / ml, 7.0 ng / ml to 30 ng / ml, or 7.0 ng / ml to 15 ng / ml.

[0088] In certain embodiments, the antibody or antigen-binding fragment comprises one or more of a VH and / or a VL, and / or two or more of a CDRH1, a CDRH2, a CDRH3, a CDRL1, a CRL2, and / or a CDRL3 set forth in SEQ ID NOs: 531-556, and neutralizes RSV as measured in vitro with an IC50 of 30 ng / ml or less, 15 ng / ml or less, 10 ng / ml or less, 8.0 ng / ml or less, 5.0 ng / ml or less, or 3.5 ng / ml or less, or in the range of 3.0 ng / ml to 30 ng / ml, 3.0 ng / ml to 15 ng / ml, 3.0 ng / ml to 10 ng / ml, 3.0 ng / ml to 8 ng / ml, 3.0 ng / ml to 5.0 ng / ml, 5.0 ng / ml to 30 ng / ml, or 5.0 ng / ml to 15 ng / ml.

[0089] In certain embodiments, the antibody or antigen-binding fragment comprises one or more of a VH and / or a VL and / or two or more of a CDRH1, a CDRH2, a CDRH3, a CDRL1, a CRL2, and / or a CDRL3 set forth in SEQ ID NOs: 531-556, and neutralizes MPV, as measured in vitro, with an IC50 of 30 ng / ml or less, 15 ng / ml or less, 10 ng / ml or less, 5.0 ng / ml or less, or 3.8 ng / ml or less, or in the range of 3.5 ng / ml to 30 ng / ml, 3.5 ng / ml to 15 ng / ml, 3.5 ng / ml to 10 ng / ml, 3.5 ng / ml to 5.0 ng / ml, 5.0 ng / ml to 30 ng / ml, or 5.0 ng / ml to 15 ng / ml.

[0090] In certain embodiments, the in vitro measurement comprises an ELISA.

[0091] In certain embodiments, the antibody or antigen-binding fragment binds to or neutralizes two or more of RSV-F, MPV-F D280, and MPV-F N280 with the above KD or IC50 for each protein.

[0092] In certain embodiments, the antibody or antigen-binding fragment binds to or neutralizes DS-Cav1, or two or more of DS-Cav1, RSV-F, MPV-F D280, and MPV-F N280 with the above KD or IC50 for each protein.

[0093] In certain embodiments, the RSV-F comprises DS-Cav1, a stable trimer of the pre-fusion conformation of the RSV-F protein comprising the amino acid mutations S155C, S190F, V207L, and S290C, and optionally, the RSV comprises strain B18537 (NCBI: txid11251).

[0094] In certain embodiments, the antibody or antigen-binding fragment activates human FcγRIIIa (or is "capable of" or "able to" activate human FcγRIIIa). In a further embodiment, activation is determined after incubation (e.g., for 23 hours) of the antibody or antigen-binding fragment with target cells (e.g., Expi293 cells) transiently transfected with RSV-F and / or MPV-F using host cells (optionally Jurkat cells) comprising (i) human FcγRIIIa (optionally the F158 allele) and (ii) an NFAT expression control sequence operably linked to a sequence encoding a reporter, such as a luciferase reporter. In yet a further embodiment, activation is determined after incubation (optionally for about 23 hours) of the antibody or antigen-binding fragment with target cells transiently transfected with RSV-F and / or MPV-F.

[0095] In certain embodiments, the antibody or antigen-binding fragment neutralizes infection by RSV and / or MPV. In certain embodiments, the RSV and / or MPV is antiviral-resistant (e.g., ribavirin-resistant). In certain embodiments, the MPV does not contain a D280N mutation in its fusion glycoprotein. In certain embodiments, the MPV contains a D280N mutation in its fusion glycoprotein.

[0096] In certain embodiments, the antibody or antigen-binding fragment treats and / or prevents (or is "capable of treating and / or preventing" or "able to treat and / or prevent") (i) RSV infection and / or (ii) MPV infection in a subject.

[0097] In certain embodiments, the antibody or antigen-binding fragment extends the survival of (or is "capable of extending the survival of") a subject with a RSV infection and / or an MPV infection.

[0098] In certain embodiments, the antibody or antigen-binding fragment reduces (or is "capable of reducing" or "able to reduce") the viral load in nasal tissue, nasal homogenate, bronchoalveolar fluid (BALF), and / or lung homogenate of a subject with RSV infection and / or MPV infection.

[0099] In certain embodiments, the antibody or antigen-binding fragment reduces (or is "capable of reducing" or "can reduce") infection-associated pulmonary pathology in a subject with RSV and / or MPV infection.

[0100] In any of the above embodiments, the antibody or antigen-binding fragment may treat and / or attenuate (or "may be capable of treating and / or attenuating" or "may be capable of treating and / or attenuating") infection by an MPV virus expressing MPV-F D280, such as MPV-F wt, and / or by an MPV virus expressing MPV-F N280. Such antibodies may be administered therapeutically to a human subject without having to determine whether the MPV virus infecting the subject contains the MPV-F N280 mutation.

[0101] Similarly, if the antibody or antigen-binding fragment may treat and / or attenuate (or "may be capable of treating and / or attenuating" or "may be capable of treating and / or attenuating") infection with both RSV and MPV, optionally both MPV with or without the D280N mutation, the antibody or antigen-binding fragment may be administered therapeutically to a human subject without having to determine whether the virus infecting the subject has a RSV infection or an MPV infection, or optionally whether the virus contains the MPV-F N280 mutation.

[0102] In some embodiments, the antibodies or antigen-binding fragments thereof of the present disclosure may bind to, neutralize, neutralize infection by, prevent infection by, treat infection by, reduce viral load of, reduce infection-associated lung pathology of, or any combination thereof, multiple RSV and / or MPV strains (sometimes referred to as RSV and / or MPV types or subtypes).

[0103] For example, a RSV-binding antibody or antigen-binding fragment thereof may bind to, neutralize, neutralize infection by, prevent infection by, treat infection by, reduce viral load, reduce infection-associated lung lesions, or any combination thereof, both RSV A strain and RSV B strain. A RSV-binding antibody may bind to, neutralize, neutralize infection by, prevent infection by, treat infection by, reduce viral load, reduce infection-associated lung lesions, or any combination thereof, multiple subtypes of the RSV A strain. A RSV-binding antibody or antigen-binding fragment thereof may bind to, neutralize, neutralize infection by, prevent infection by, treat infection by, reduce viral load, reduce infection-associated lung lesions, or any combination thereof, multiple subtypes of the RSV B strain.

[0104] Also, for example, an MPV-binding antibody or antigen-binding fragment thereof may bind to, neutralize, neutralize infection by, prevent infection by, treat infection by, reduce viral load by, reduce infection-associated lung lesions, or any combination thereof, both MPV A strain and MPV B strain. An MPV-binding antibody may bind to, neutralize, neutralize infection by, prevent infection by, treat infection by, reduce viral load by, reduce infection-associated lung lesions, or any combination thereof, multiple subtypes of MPV A strain, such as MPV A1 strain, MPV A2 strain (including A2a, A2b, or both subtypes), or a combination thereof. The MPV-binding antibodies or antigen-binding fragments thereof may bind to, neutralize, neutralize infection by, prevent infection by, treat infection by, reduce viral load by, reduce infection-associated lung pathology by, or any combination thereof, multiple subtypes of MPV B strains, such as MPV B1 strain, MPV B2 strain, or a combination thereof.

[0105] In one embodiment, the antibodies or antigen-binding fragments thereof of the present disclosure may bind to, neutralize, neutralize infection by, prevent infection by, treat infection by, reduce viral load of, reduce infection-associated pulmonary pathology of, or any combination thereof, RSV A strain, RSV B strain, and MPV A strain.

[0106] In another embodiment, the antibodies or antigen-binding fragments thereof of the present disclosure may bind to, neutralize, neutralize infection by, prevent infection by, treat infection by, reduce viral load of, reduce infection-associated lung lesions of, or any combination thereof, RSV A strain, RSV B strain, and MPV B strain.

[0107] In another embodiment, the antibodies or antigen-binding fragments thereof of the present disclosure may bind to, neutralize, neutralize infection by, prevent infection by, treat infection by, reduce viral load of, reduce infection-associated pulmonary pathology of, or any combination thereof, RSV A strain, MPV A strain, and MPV B strain.

[0108] In another embodiment, the antibodies or antigen-binding fragments thereof of the present disclosure may bind to, neutralize, neutralize infection by, prevent infection by, treat infection by, reduce viral load of, reduce infection-associated pulmonary pathology of, or any combination thereof, RSV A strain, MPV A strain, and MPV B strain.

[0109] In another embodiment, the antibody or antigen-binding fragment thereof may bind to, neutralize, neutralize infection by, prevent infection by, treat infection by, reduce viral load of, reduce infection-associated lung lesions of, or any combination thereof, RSV B strain, MPV A strain, and MPV B strain.

[0110] In one embodiment, the antibodies or antigen-binding fragments thereof of the present disclosure may bind to, neutralize, neutralize infection by, prevent infection by, treat infection by, reduce viral load, reduce infection-associated lung pathology, or any combination of any subcombination of the following viral strains: RSV A, RSV B, MPV A1, MPV A2 (MPV A2a, MPV A2b, or both), MPV B1, and MPV B2.

[0111] In certain embodiments, the antigens or antigen-binding fragments thereof of the present disclosure may bind to, neutralize, neutralize infection by, prevent infection by, treat infection by, reduce viral load of, reduce infection-associated pulmonary pathology of, or any combination thereof, RSV A, RSV B, MPV A1, MPV A2, MPV B1, and MPV B2.

[0112] In any of the above embodiments, an antibody or antigen-binding fragment that may treat and / or attenuate (or "may be capable of treating and / or attenuating" or "may be capable of treating and / or attenuating") infection with both RSV A and RSV B strains may be administered therapeutically to a human subject without the need to identify the viral subtype of the RSV virus infecting the subject.

[0113] Similarly, an antibody or antigen-binding fragment that may treat and / or attenuate (or "may be capable of treating and / or attenuating" or "may be capable of treating and / or attenuating") infection with both MPV A and MPV B strains may be administered therapeutically to a human subject without the need to identify the viral subtype of the MPV virus infecting the subject.

[0114] Additionally, antibodies or antigen-binding fragments that may treat and / or attenuate (or may be "capable of treating and / or attenuating") infection with both RSV A and RSV B strains and MPV A and MPV B strains may be administered therapeutically to a human subject without the need to determine whether the subject is infected with RSV or MPV.

[0115] In one embodiment, the antibodies or antigen-binding fragments thereof of the present disclosure bind to site III of the RSV F protein. In a more specific embodiment, such antibodies or antigen-binding fragments thereof may bind to and treat infections caused by both RSV and MPV.

[0116] In one embodiment, the antibodies or antigen-binding fragments thereof of the present disclosure bind to site Φ of the RSV F protein. In a more specific embodiment, such antibodies or antigen-binding fragments thereof may bind to RSV and treat infection therewith.

[0117] In one embodiment, the antibodies or antigen-binding fragments thereof of the present disclosure bind to site IV of the RSV F protein. In a more specific embodiment, such antibodies or antigen-binding fragments thereof may bind to RSV and treat infection therewith.

[0118] For each of the antibody, antigen-binding fragment, and composition embodiments described above, in parallel embodiments, a combination of two or more antibodies or antigen-binding fragments thereof of the present disclosure as separate antibodies in a single composition or in a bispecific antibody may have the same RSV and MPV binding, neutralization, infection prevention and / or treatment, and other recited properties.

[0119] In certain embodiments, the antibody or antigen-binding fragment (e.g., comprising an IgG1 isotype) has an in vivo half-life in mice (e.g., tg32 mice) of about 10 days to about 17 days, about 10 days to about 16 days, about 10 days to about 15 days, about 10 days to about 14 days, about 10 days to about 13 days, about 10 days to about 12 days, about 11 days to about 17 days, about 11 days to about 16 days, about 11 days to about 16 days, about 11 days to about 17 ... ~approx. 15 days, ~approx. 11 days to ~approx. 14 days, ~approx. 11 days to ~approx. 13 days, ~approx. 11 days to ~approx. 12 days, ~approx. 12 days to ~approx. 17 days, ~approx. 12 days to ~approx. 16 days, ~approx. 12 days to ~approx. 15 days, ~approx. 12 days to ~approx. 14 days, ~approx. 12 days to ~approx. 13 days, ~approx. 12.5 days to ~approx. 16 days, ~approx. 12.5 days to ~approx. 15.5 days, ~approx. 12.5 days to ~approx. 15 days, ~approx. 12.5 days to ~approx. 14.5 days, ~approx. 12.5 days to ~approx. 14 days, ~approx. 12.5 days to ~approx. 13 days 0.5 days, about 12.5 days to about 13 days, about 13 days to about 16 days, about 13 days to about 15.5 days, about 13 days to about 15 days, about 13 days to about 14.5 days, about 13 days to about 14 days, about 13 days to about 13.5 days, about 13.5 days to about 16 days, about 13.5 days to about 15.5 days, about 13.5 days to about 15 days, about 13.5 days to about 14.5 days, about 13.5 days to about 14 days, about 14 days to about 16 days, about 14 days about 14 days to about 15.5 days, about 14 days to about 15 days, about 14 days to about 14.5 days, about 14.5 days to about 16 days, about 14.5 days to about 15.5 days, about 14.5 days to about 15 days, about 15 days to about 16 days, about 15 days to about 15.5 days, about 15.5 days to about 16 days, or about 10, 11, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, or 17 days.

[0120] In some embodiments, the antibodies or antigen-binding fragments of the present disclosure may reduce weight loss in RSV-infected mice at least to the same extent as nirsevimab when administered in a similar manner to similar mice at a similar stage of RSV infection.

[0121] In some embodiments, the antibodies or antigen-binding fragments of the present disclosure may increase survival of RSV-infected mice at least to the same extent as nirsevimab or an antibody having the same VH and VL as nicervimab when administered in a similar manner to similar mice at a similar stage of RSV infection.

[0122] Terms understood by those skilled in the art of antibody technology are each given their art-acquired meaning unless expressly defined differently herein. For example, the term "antibody" refers to an intact antibody comprising two or more heavy (H) chains and two light (L) chains interconnected by disulfide bonds, as well as any antigen-binding portion or fragment of an intact antibody (e.g., scFv, Fab, or Fab'2 fragment) that has or retains the ability to bind to the antigen target molecule recognized by the intact antibody. Thus, the term "antibody" herein is used in the broadest sense and includes polyclonal and monoclonal antibodies, including intact antibodies and functional (antigen-binding) antibody fragments, including fragment antigen-binding (Fab) fragments, F(ab')2 fragments, Fab' fragments, Fv fragments, recombinant IgG (rIgG) fragments, single-chain antibody fragments, including single-chain variable fragments (scFv), and single-domain antibody (e.g., sdAb, sdFv, nanobody) fragments. The term encompasses genetically engineered and / or otherwise modified forms of immunoglobulins, such as intrabodies, peptibodies, chimeric antibodies, fully human antibodies, humanized antibodies, and heteroconjugate antibodies, multispecific, e.g., bispecific, antibodies, diabodies, triabodies, tetrabodies, tandem di-scFvs, and tandem tri-scFvs. Unless otherwise specified, the term "antibody" should be understood to encompass functional antibody fragments. The term also encompasses intact or full-length antibodies, including antibodies of any class or subclass, including IgG and its subclasses (IgG1, IgG2, IgG3, IgG4), IgM, IgE, IgA, and IgD.

[0123] The antibody or antigen-binding fragment can be of any allotype or combination of allotypes. "Allotype" refers to the allelic diversity found among IgG subclasses. For example, allotypes may include G1m1 (or G1m(a)), G1m2 (or G1m(x)), G1m3 (or G1m(f)), G1m17 (or Gm(z))m), G1m27, and / or G1m28 (G1m27 and G1m28 are referred to as "alloallotypes").

[0124] The G1m3 and G1m17 allotypes are located at the same position in the CH1 domain (position 214 according to EU numbering). G1m3 contains R214(EU) and G1m17 contains K214(EU). The G1m1 allotype is located in the CH3 domain (positions 356 and 358(EU)) and refers to the substitutions E356D and M358L. The G1m2 allotype refers to the substitution of alanine at position 431(EU) with glycine. G1m allotypes, alloallotypes, and their characteristics are known in the art and can be found, for example, in<www.imgt.org / IMGTrepertoire / Proteins / allotypes / human / IGH / IGHC / G1m_allotypes.html> and Lefranc, M.-P. and Lefranc, G. Human Gm, Km and Am allotypes and their molecular characterization: a remarkable demonstration of polymorphism In: B. Tait, F. Christiansen (Eds.), Immunogenetics, chap. 34, Humana Press, Springer, New York, USA. Methods Mol. Biol. 2012; 882, 635-680. PMID: 22665258, LIGM: 406 (the contents of which and the allotypes and allotype information are incorporated herein by reference).

[0125] The G1m1 allotype may be combined with, for example, G1m3, G1m17, G1m27, G1m2, and / or G1m28 allotypes. In some embodiments, the allotype is G1m3 (G1m3,-1) without G1m1. In some embodiments, the allotype is G1m17,1 allotype. In some embodiments, the allotype is G1m3,1. In some embodiments, the allotype is G1m17 (G1m17,-1) without G1m1. Optionally, these allotypes may (or may not) be combined with G1m2, G1m27, or G1m28 allotypes. For example, the allotype may be G1m17,1,2.

[0126] In some embodiments, the antibody or antigen-binding fragment of the present disclosure comprises the G1m3 allotype or the G1m3,1 allotype. In some embodiments, the antibody or antigen-binding fragment of the present disclosure comprises the G1m3 allotype and includes M428L and N434S or M428L and N434A mutations, or any other mutation that enhances binding to human FcRn, such as those described herein. In some embodiments, the antibody or antigen-binding fragment of the present disclosure comprises the G1m3,1 allotype and includes M428L and N434S or M428L and N434A mutations, or any other mutation that enhances binding to human FcRn, such as those described herein. In some embodiments, the antibody or antigen-binding fragment of the present disclosure comprises the G1m17,1 allotype. In some embodiments, the antibody or antigen-binding fragment of the present disclosure comprises the G1m17,1 allotype and comprises M428L and N434S or M428L and N434A mutations, or any other mutation that enhances binding to human FcRn as further described herein.

[0127] "V L " or "VL" and "V HThe terms "VH" and "VH" refer to the variable binding regions from an antibody light chain and antibody heavy chain, respectively. In certain embodiments, the VL is of the kappa (κ) class (also referred to herein as "VK"). In certain embodiments, the VL is of the lambda (λ) class. The variable binding regions comprise separate and distinct subregions known as "complementarity determining regions" (CDRs) and "framework regions" (FRs). The terms "complementarity determining regions" and "CDRs" are synonymous with "hypervariable regions" or "HVRs" and generally refer to sequences of amino acids within an antibody variable region that together confer antigen specificity and / or binding affinity to the antibody, with consecutive CDRs (i.e., CDR1 and CDR2, CDR2 and CDR3) being separated from each other in the primary structure by framework regions. There are three CDRs in each variable region (HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3, also referred to as CDRH and CDRL, respectively). In certain embodiments, an antibody VH comprises four FRs and three CDRs as follows: FR1-HCDR1-FR2-HCDR2-FR3-HCDR3-FR4, and an antibody VL comprises four FRs and three CDRs as follows: FR1-LCDR1-FR2-LCDR2-FR3-LCDR3-FR4. Generally, the VH and VL together form an antigen-binding site via their respective CDRs. In certain embodiments, one or more CDRs do not contact the antigen and / or do not contribute energetically to antigen binding.

[0128] As used herein, a "variant" of a CDR refers to a functional variant of a CDR sequence having up to 1 to 3 amino acid substitutions (e.g., conservative or non-conservative substitutions), deletions, or a combination thereof.

[0129] Numbering of the CDRs and framework regions may be according to any known method or scheme, such as the Kabat, Chothia, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, EU, or AHo numbering schemes, or a combination of two or more of these IMGT, North, and AHo numbering schemes (see, e.g., Kabat et al., "Sequences of Proteins of Immunological Interest," U.S. Dept. Health and Human Services, Public Health Service National Institutes of Health, 1991, 5 th ed.; Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987); Lefranc et al., Dev. Comp. Immunol. 27:55, 2003; Honegger and Pluckthun, J. Mol. Biol. 309:657-670 (2001)). The Antigen Receptor Numbering and Receptor Classification (ANARCI) software tool (2016, Bioinformatics 15:298-300) can be used to annotate equivalent residue positions and compare different molecules. Thus, identifying the CDRs of a variable domain (VH or VL) sequence provided herein using one numbering scheme does not exclude antibodies containing CDRs of the same variable domain determined using a different numbering scheme.

[0130] In certain embodiments, the CDRs are numbered using any known CDR numbering method, including Kabat, Chothia, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, EU, or AHo numbering method, or a combination of two or more of these IMGT, Martin (Enhanced Chothia), Contact, North, and AHo numbering methods (including by a combination of any two or more of these numbering methods), as set forth in SEQ ID NOs: 2, 136, 146, 159, 169, 175, 181, 189, 196, 202, 210, 215, 225, 233, 243, 250, 254, 261, 271, 277, 284, 293, 300, 309, 316, 321, 327, 332, 342, 343, 350, 354, 361, 361, 371, 377, 384, 385, 393, 400, 409, 416, 421, 427, 432, 442, 443, 450, 454, 461, 471, 477, 484, 493, 500, 510, 520, 530, 542, 550, 560, 571, 580, 593, 600, 610, 620, 630, 640, 650, 660, 671, 680, 693, 700, 710, 720, 730, 740, 750 , 347, 352, 357, 362, 369, 727, 737, 746, 755, 765, 775, 784, 794, 804, 813, 817, 820, 823, 826, 828, 831, 834, 837, 840, 843, 883, 886, 889, 893, 896, 899, 901, 903, 129, 12, 38, 46, 53, 59, 69, 120, 73, 79, 86, 95, 22, 111, 30, 378, 386, 395, 404, 412, 416, 422, 426, 431, 4 40, 451, 458, 463, 470, 475, 480, 485, 491, 497, 532, 537, 539, 542, 545, 547, 550, 504, 513, 524, 527, 702, 707, 712, and 716, and / or the CDRs of the VH sequences according to any one of SEQ ID NOs: 77, 141, 150, 155, 164, 172, 178, 185, 192, 199, 205, 212, 220, 229, 238, 247, 252, 257, 266, 274, 282, 283, 284, 285, 286, 287, 288, 289, 290, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 340, 451, 458, 463, 470 8, 296, 305, 312, 319, 324, 330, 337, 345, 349, 355, 360, 367, 374, 732, 742, 751, 760, 770, 780, 789, 799, 808, 847, 851, 855, 858, 860, 862, 865, 868, 870, 873, 875, 877, 879, 881, 133, 17, 42, 50, 56, 64, 71, 125, 76, 83, 91, 98, 27, 116, 35, 382, 391, 400, 408, 414, 419,Antibodies or antigen-binding fragments that bind RSV-F are provided, including the CDRs of a VL sequence according to any one of 424, 429, 434, 436, 444, 449, 455, 461, 466, 473, 478, 483, 487, 495, 501, 509, 518, 522, 530, 553, 558, 560, 563, 567, 570, 572, 574, 704, and 710. In certain embodiments, the CDRs follow the IMGT numbering system. In certain embodiments, the CDRs follow the antibody numbering system developed by the Chemical Computing Group (CCG), for example, using Molecular Operating Environment (MOE) software.

[0131] In certain embodiments, the CDR numbering is determined using any known CDR numbering method, including Kabat, Chothia, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, EU, or AHo numbering method, or a combination of two or more of these IMGT, Martin (Enhanced Chothia), Contact, North, and AHo numbering methods (including by a combination of any two or more of these numbering methods), as set forth in SEQ ID NOs: 2, 136, 146, 159, 169, 175, 181, 189, 196, 202, 210, 215, 225, 233, 243, 250, 260, 270, 272, 280, 282, 284, 286, 290, 300, 302, 304, 306, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360 254, 261, 271, 277, 284, 293, 300, 309, 316, 321, 327, 332, 342, 347, 352, 357, 362, 369, 727, 737, 746, 755, 765, 775, 784, 794, 804, 813, 817, 820, 823, 826, 828, 831, 834, 837, 840, 843, 883, 886, 889, 893, 896, 899, 901, and 903, and / or the CDRs of the VH sequences according to any one of SEQ ID NOs: 7, 141, 150, 155, 164, 172, 178, 185, 192, 199, 205, 212, 220, 229, 238, 247, 252, 257, 266, 274, 282, 288, 296, 305, 312, 319, 324, 330, 337, 345, 346, 350, 352, 354, 356, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425 Antibodies or antigen-binding fragments that bind RSV-F are provided, including the CDRs of a VL sequence according to any one of: 49, 355, 360, 367, 374, 732, 742, 751, 760, 770, 780, 789, 799, 808, 847, 851, 855, 858, 860, 862, 865, 868, 870, 873, 875, 877, 879, and 881. In certain embodiments, the CDRs follow the IMGT numbering system. In certain embodiments, the CDRs follow the antibody numbering system developed by the Chemical Computing Group (CCG), for example, using Molecular Operating Environment (MOE) software.

[0132] In some embodiments that bind only to MPK, the CDRs comprise or consist of the CDRs of MPK15.

[0133] More specifically, the VH and VL of the antibody or antigen-binding fragment that binds RSV-F can comprise or consist of the VH and VL amino acid sequences, respectively, of the anti-RSV MPK or MPH antibodies in Table 2, with the corresponding amino acid sequences shown in Table 1 and the Sequence Listing. Specifically, the CDRs can be selected from the group consisting of MPK44, MPK65-v2, MPK161-v2, MPK163, MPK165, MPK167, MPK168, MPK169-v2, MPK170, MPK171-v1, MPK171-v2, MPK173, MPK175, MPK176, MPK177, MPK178, MPK179-v4, MPK18 0, MPK181, MPK182, MPK185, MPK186, MPK187, MPK188, MPK189, MPK191, MPK193, MPK194-v2, MPK195, MPK197, MPK198, MPK201, MPK202, MPK203, MPM10, MPM2, MPM8, MPO1, MPO7, MPP1, MPP 2, MPR16, MPR19-v2, MPM10, MPM2, MPM8, MPO1, MPO7, MPP1, MPP2, MPR16, MPR19-v2, MPK65-v (any one of 1 to 7). (any one of 1 to 2), MPK201-v (any one of 1 to 6). (any one of 1 to 2), MPK176-v (any one of 1 to 6). (any one of 5), or MPM2-v (any one of 1, 2, 4, 5). (any one of 1 to 9), for example, comprising or consisting of the CDRs of MPK176-v1.3, MPK176-v4.3, MPK201-v1.2, MPK201-v4.1, MPK65v2-v1.2, or MPK65v2-v3.1. For example, MPK201-v1.2 is understood to comprise the VH of MPK201 VH.1 (SEQ ID NO: 357) and the VL of MPK201 VL.2 (SEQ ID NO: 847).

[0134] In some embodiments, the antibody or antigen-binding fragment comprises the six CDRs of MPK176-v1.3, MPK176-v4.3, MPK201-v1.2, MPK201-v4.1, MPK65v2-v1.2, or MPK65v2-v3.1.

[0135] More specifically, the VH and VL of the antibody or antigen-binding fragment that binds RSV-F comprise or consist of the VH and VL, respectively, having the following sequences: 1) SEQ ID NOs: 2 and 6, 2) SEQ ID NOs: 136 and 141, 3) SEQ ID NOs: 146 and 150, 4) SEQ ID NOs: 146 and 155, 5) SEQ ID NOs: 159 and 164, 6) SEQ ID NOs: 169 and 172, 7) SEQ ID NOs: 175 and 178, 8) SEQ ID NOs: 181 and 185, 9) SEQ ID NOs: 189 and 192, 10) SEQ ID NOs: 196 and 199, 11) SEQ ID NO: 20. 2 and 205, 12) SEQ ID NOs: 210 and 212, 13) SEQ ID NOs: 215 and 220, 14) SEQ ID NOs: 225 and 229, 15) SEQ ID NOs: 233 and 238, 16) SEQ ID NOs: 243 and 247, 17) SEQ ID NOs: 250 and 252, 18) SEQ ID NOs: 254 and 257, 19) SEQ ID NOs: 261 and 266, 20) SEQ ID NOs: 271 and 274, 21) SEQ ID NOs: 277 and 282, 22) SEQ ID NOs: 284 and 288, 23) SEQ ID NOs: 293 and 296, 24) SEQ ID NOs: 300 and 305, 25) SEQ ID NOs: 309 and 312, 2 6) SEQ ID NOs: 316 and 319, 27) SEQ ID NOs: 321 and 324, 28) SEQ ID NOs: 327 and 330, 29) SEQ ID NOs: 332 and 337, 30) SEQ ID NOs: 342 and 345, 31) SEQ ID NOs: 347 and 349, 32) SEQ ID NOs: 352 and 355, 33) SEQ ID NOs: 357 and 360, 34) SEQ ID NOs: 362 and 367, 35) SEQ ID NOs: 369 and 374, 36) SEQ ID NOs: 883 and 742, 37) SEQ ID NOs: 737 and 742, 38) SEQ ID NOs: 727 and 732, 39) SEQ ID NOs: 746 and 751, 40) SEQ ID NO: 75 5 and 760, 41) SEQ ID NOs: 765 and 770, 42) SEQ ID NOs: 775 and 770, 43) SEQ ID NOs: 784 and 789, 44) SEQ ID NOs: 794 and 799, 45) SEQ ID NOs: 804 and 808, 46) SEQ ID NOs: 233 and 858, 47) SEQ ID NOs: 837 and 858, 48) SEQ ID NOs: 357 and 847, 49) SEQ ID NOs: 899 and 360, 50) SEQ ID NOs: 136 and 851, 51) SEQ ID NOs: 817 and 141, 52) SEQ ID NOs: 883 and 742, 53) SEQ ID NOs: 886 and 742, or 54) SEQ ID NOs: 883 and 875.

[0136] More specifically, the VH and VL of the antibody or antigen-binding fragment that binds MPV-F can comprise or consist of the VH and VL, respectively, specified for the anti-MPV MPK or MPH antibodies in Table 2, and have the corresponding amino acid sequences shown in Table 1 and the Sequence Listing.

[0137] In some embodiments, the CDRs are numbered using any known CDR numbering method, including Kabat, Chothia, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, EU, or AHo numbering methods, or their IMGT, Martin (Enhanced Chothia), Contact, North, and AHo numbering methods (including determining by a combination of any two or more of these numbering methods), and are set forth in SEQ ID NOs: 101, 129, 12, 38, 46, 53, 59, 69, 120, 73, 79, 86, 95, 22, 111, 30, 378, 386, 395, 404, 412, 416, 422, 426, 431, 440, 451, 458, 463, 470, 475, 480, 485, 491, 497, 532, 537, 539, 542, 545, 547, 550, 504, 513, 524, 527, 702, 707, 710, 712, 714, 716, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 745, 746, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 770, 771, and / or the CDRs of the VL sequence according to any one of SEQ ID NOs: 106, 133, 17, 42, 50, 56, 64, 71, 125, 76, 83, 91, 98, 27, 116, 35, 382, 391, 400, 408, 414, 419, 424, 429, 434, 436, 444, 449, 455, 461, 466, 473, 478, 483, 487, 495, 501, 509, 518, 522, 530, 553, 558, 560, 563, 567, 570, 572, 574, 704, and 710. In certain embodiments, the CDRs follow the IMGT numbering method (including by combining any two or more of these numbering methods). In certain embodiments, the CDRs follow the antibody numbering method developed by the Chemical Computing Group (CCG), which uses, for example, Molecular Operating Environment (MOE) software.

[0138] More specifically, the VH and VL of the antibody or antigen-binding fragment that binds MPV-F may comprise or consist of a VH and VL having the sequences of SEQ ID NOs: 101 and 106, respectively.

[0139] In certain embodiments, the CDR numbering is performed using any known CDR numbering method, including Kabat, Chothia, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, EU, or AHo numbering methods, or their IMGT, Martin (Enhanced Chothia), and as determined using a combination of two or more of the Contact, North, and AHo numbering methods (including determining by a combination of any two or more of these numbering methods), SEQ ID NOs: 129, 12, 38, 46, 53, 59, 69, 120, 73, 79, 86, 95, 22, 111, 30, 378, 386, 395, 404, 412, 416, 422, 426, 431, 440, 451, 458, 463, 470, 475, 480, 485, 491, 497, 532, 537, 539, 542, 545, 547, 550, 504, 513, 524, 527, and 702, 707, 712, and 716 and / or the CDRs of the VL sequence according to any one of SEQ ID NOs: 133, 17, 42, 50, 56, 64, 71, 125, 76, 83, 91, 98, 27, 116, 35, 382, 391, 400, 408, 414, 419, 424, 429, 434, 436, 444, 449, 455, 461, 466, 473, 478, 483, 487, 495, 501, 509, 518, 522, 530, 553, 558, 560, 563, 567, 570, 572, 574, 704, and 710. In certain embodiments, the CDRs follow the IMGT numbering system. In certain embodiments, the CDRs follow the antibody numbering system developed by the Chemical Computing Group (CCG), for example, using Molecular Operating Environment (MOE) software.

[0140] In certain embodiments, antibodies or antigen-binding fragments that bind RSV-F and / or MPV-F are provided that may include the CDRs of the VH sequence according to any one of SEQ ID NOs: 532, 537, 539, 542, 545, 547, and 550, and / or the CDRs of the VL sequence according to any one of SEQ ID NOs: 553, 558, 560, 563, 567, 570, 572, and 574, as determined using any known CDR numbering method, including Kabat, Chothia, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, EU, or AHo numbering, or a combination of two or more of these IMGT, Martin (Enhanced Chothia), Contact, North, and AHo numbering methods (including a combination of any two or more of these numbering methods). In certain embodiments, the CDRs are numbered according to the IMGT numbering method. In certain embodiments, the CDRs follow the antibody numbering method developed by the Chemical Computing Group (CCG), for example, using Molecular Operating Environment (MOE) software.

[0141] More specifically, the VH and VL of the antibody or antigen-binding fragment that binds RSV-F and / or MPV-F comprise or consist of any VH and any VL identified for the anti-RSV / MPV MPK or MPH antibodies in Tables 2 and 20, and have the corresponding amino acid sequences shown in Table 1 and the Sequence Listing. In some embodiments, the VH and VL are both derived from the same antibody identified in Tables 2 and 20. However, in other embodiments, the VH may be derived from a first antibody identified in Table 2 or 20, while the VL may be derived from a second, different antibody identified in Table 2 or 20. In some such instances, the first and second antibodies may both be MPK antibodies, or the first and second antibodies may both be MPH antibodies. However, a VH from an MPK antibody and a VL from an MPH antibody, and vice versa, may also be used, particularly when the V(D)J usage is the same between the MPH and MPK antibodies.

[0142] In specific embodiments, the CDRs of the antibody or antigen-binding fragment that binds RSV-F and / or MPV-F are selected from the group consisting of MPK190-v1.3, MPK9, MPK10, MPK18, MPK30-v1, MPK36-v3, MPK51, MPK51-v1.1, MPK67, MPK73, MPK77, MPK77-v1.1, MPK86, MPK92, MPK99, MPK102, MPK104, MPK104-v1.1, MPK104, v1.3, MPK108, MPK126, MPK127, MPK128, MPK129, MPK130, MPK131, MPK132, MPK133, MPK134, MPK135, MPK136, MPK137, MPK138, MPK139, MPK139-v1.1 ... The polypeptide comprises or consists of the CDRs of MPK129, MPK130, MPK132-v2, MPK133, MPK136, MPK141, MPK142-v1, MPK142-v2, MPK144, MPK145, MPK146, MPK149, MPK150-v2, MPK151, MPK152, MPK153, MPK155, MPK157, MPK158, MPK162, MPK174-v2, MPK190, MPK190-v1.1, MPK196, MPK204, MPH12, or an MPH12 variant. In some embodiments, the CDRs are all derived from the same antibody identified in Table 2 and Table 20, e.g., all derived from MPK190-v1.3, MPK190-v1.1, MPK51-v1.1, MPK77-v1.1, MPK104-v1.1, or MPK 104-v1.3. However, in other embodiments, CDRH1, CDRH2, and CDRH3 may be derived from a first antibody identified in Table 2 or Table 20, while CDRL1, CDRL2, and CDRL3 may be derived from a second, different antibody identified in Table 2 or Table 20. In some such examples, the first and second antibodies may both be MPK antibodies, or the first and second antibodies may both be MPH antibodies. However, particularly when the V(D)J usage is the same between the MPH antibody and the MPK antibody, CDRH1, CDRH2, and CDRH3 from the MPK antibody and CDRL1, CDRL2, and CDRL3 from the MPH antibody can also be used, and vice versa. In some embodiments, one or more of the first and second antibodies is MPK190-v1.3. In some embodiments, one or more of the first and second antibodies is MPK190-v1.1.In some embodiments, one or more of the first and second antibodies is MPK51-v1.1. In some embodiments, one or more of the first and second antibodies is MPK77-v1.1. In some embodiments, one or more of the first and second antibodies is MPK104-v1.1. In some embodiments, one or more of the first and second antibodies is MPK104-v1.3.

[0143] The cross-binding and / or cross-neutralizing antibodies and antigen-binding fragments of the present disclosure may also be used to bind only RSV-F or only MPV-F, and their usefulness is not limited to situations in which binding and / or neutralization of both RSV and MPV targets occurs.

[0144] More specifically, the VH and VL of the antibody or antigen-binding fragment that binds RSV-F and / or MPV-F and / or neutralizes RSV and / or MPV comprise or consist of the VH and VL having the following sequences, respectively: 1) SEQ ID NOs: 129 and 133, 2) SEQ ID NOs: 12 and 17, 3) SEQ ID NOs: 38 and 42, 4) SEQ ID NOs: 46 and 50, 5) SEQ ID NOs: 53 and 56, 6) SEQ ID NOs: 59 and 64, 7) SEQ ID NOs: 69 and 71, 8) SEQ ID NOs: 120 and 125, 9) SEQ ID NOs: 73 and 76, 10) SEQ ID NOs: 79 and 83, 11) SEQ ID NOs: 120 and 125, 12) SEQ ID NOs: 130 and 132, 13) SEQ ID NOs: 140 and 142, 14) SEQ ID NOs: 150 and 152, 15) SEQ ID NOs: 160 and 162, 16) SEQ ID NOs: 170 and 172, 17) SEQ ID NOs: 180 and 183, 18) SEQ ID NOs: 190 and 192, 19) SEQ ID NOs: 200 and 210, 20) SEQ ID NOs: 210 and 212, 21) SEQ ID NOs: 220 and 225, 22) SEQ ID NOs: 230 and 232, 23) SEQ ID NOs: 240 and 242, 24) SEQ ID NOs: 250 and ) SEQ ID NOs: 86 and 91, 12) SEQ ID NOs: 95 and 98, 13) SEQ ID NOs: 22 and 27, 14) SEQ ID NOs: 111 and 116, 15) SEQ ID NOs: 30 and 35, 16) SEQ ID NOs: 378 and 382, 17) SEQ ID NOs: 386 and 391, 18) SEQ ID NOs: 395 and 400, 19) SEQ ID NOs: 404 and 408, 20) SEQ ID NOs: 412 and 414, 21) SEQ ID NOs: 416 and 419, 22) SEQ ID NOs: 422 and 424, 23) SEQ ID NOs: 426 and 429, 24) SEQ ID NOs: 431 and 434, 25) SEQ ID NOs: 431 and 436, 26) SEQ ID NOs: 440 and 444, 2 7) SEQ ID NOs: 431 and 449, 28) SEQ ID NOs: 451 and 455, 29) SEQ ID NOs: 458 and 461, 30) SEQ ID NOs: 463 and 466, 31) SEQ ID NOs: 470 and 473, 32) SEQ ID NOs: 475 and 478, 33) SEQ ID NOs: 480 and 483, 34) SEQ ID NOs: 485 and 487, 35) SEQ ID NOs: 491 and 495, 36) SEQ ID NOs: 497 and 501, 37) SEQ ID NOs: 504 and 509, 38) SEQ ID NOs: 513 and 518, 39) SEQ ID NOs: 120 and 522, 40) SEQ ID NOs: 524 and 518, 41) SEQ ID NOs: 527 and 530, 42) SEQ ID NO: 5 32 and 553, 43) SEQ ID NOs: 532 and 558, 44) SEQ ID NOs: 532 and 577, 45) SEQ ID NOs: 532 and 563, 46) SEQ ID NOs: 532 and 567, 47) SEQ ID NOs: 532 and 570, 48) SEQ ID NOs: 532 and 572, 49) SEQ ID NOs: 532 and 574, 50) SEQ ID NOs: 537 and 553, 51) SEQ ID NOs: 537 and 558, 52) SEQ ID NOs: 537 and 577, 53) SEQ ID NOs: 537 and 563, 54) SEQ ID NOs: 537 and 567, 55) SEQ ID NOs: 537 and 570, 56) SEQ ID NOs: 537 and 572, 57) SEQ ID NOs: 537 and 574,58) SEQ ID NOs: 539 and 553, 59) SEQ ID NOs: 539 and 558, 60) SEQ ID NOs: 539 and 577, 61) SEQ ID NOs: 539 and 563, 62) SEQ ID NOs: 539 and 567, 63) SEQ ID NOs: 539 and 570, 64) SEQ ID NOs: 539 and 572, 65) SEQ ID NOs: 539 and 574, 66) SEQ ID NOs: 542 and 553, 67) SEQ ID NOs: 542 and 558, 68) SEQ ID NOs: 542 and 577, 69) SEQ ID NOs: 542 and 563, 70) SEQ ID NOs: 542 and 567, 71) SEQ ID NOs: 542 and 570, 72) SEQ ID NOs: 542 and 572, 73) SEQ ID NOs: 542 and 574, 74) SEQ ID NOs: 545 and 553, 75) SEQ ID NOs: 545 and 558, 76) SEQ ID NOs: 545 and 577, 77) SEQ ID NOs: 545 and 563, 78) SEQ ID NOs: 545 and 567, 79) SEQ ID NOs: 545 and 570, 80) SEQ ID NOs: 545 and 572, 81) SEQ ID NOs: 545 and 574, 82) SEQ ID NOs: 547 and 553, 83) SEQ ID NOs: 547 and 558, 84) SEQ ID NOs: 547 and 577, 85) SEQ ID NOs: 547 and 563, 86) SEQ ID NOs: 547 and 567, 87) SEQ ID NOs: 547 and 570, 88) SEQ ID NOs: 547 and 572, 89) SEQ ID NOs: 547 and 574, 90) SEQ ID NOs: 550 and 553, 91) SEQ ID NOs: 702 and 704, 92) SEQ ID NOs: 707 and 708, 93) SEQ ID NOs: 707 and 709, 94) SEQ ID NOs: 712 and 76, 95) SEQ ID NOs: 716 and 64, 96) SEQ ID NOs: 717 and 116.

[0145] In certain embodiments, the present disclosure provides an antibody or antigen-binding fragment that binds RSV-F, comprising a heavy chain variable domain (VH) comprising complementarity-determining regions (CDRs) H1, CDRH2, and CDRH3, and a light chain variable region (VL) comprising CDRL1, CDRL2, and CDRL3, wherein the CDRs are determined according to the IMGT numbering system, and (i) optionally, CDRH1 is selected from the group consisting of SEQ ID NOs: 3, 137, 147, 160, 170, 182, 216, 234, 244, 262, 278, 285, 301, 333, 363, 370, 13, 23, 31, 39, 401, 411, 421, 431, 441, 451, 461, 471, 481, 482, 491, 501, 511, 521, 531, 541, 551, 561, 571, 581, 591, 601, 611, 621, 631, 641, 651, 661, 671, 681, 691, 701, 711, 721, 731, 741, 751, 761, 771, 781, 791, 801, 811, 821, 831, 841, 851, 861, 871, 881, 891, 901, 911, 921, 931, 941, 951, 961, 971, 54, 60, 74, 80, 87, 112, 121, 130, 380, 387, 396, 728, 738, 747, 756, 766, 776, 785, 795, 805, 814, 887, 890, 417, 441, 452, 459, 471, 481, 492, 498, 505, 514, 528, and 533, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or relative to the germline-encoded amino acid. and (ii) optionally, CDRH2 has the amino acid sequence set forth in any one of SEQ ID NOs: 4, 138, 161, 217, 226, 235, 263, 279, 302, 334, 364, 371, 729, 739, 748, 757, 767, 777, 786, 796, 815, 818, 838, 884, 894, 897, 14, 24, 32, 40, 47, 61, 81, 88, 96, 113, 122, 388, 397, 405, 442, 453, 464, 506, 515, 534, 540, 543, and 548, or one, two, or three of the amino acid sequences set forth in SEQ ID NOs: (iii) optionally, CDRH3 comprises or consists of a functional variant thereof comprising at least one amino acid substitution, wherein one or more of the substitutions are optionally conservative and / or relative to a germline encoded amino acid; and (iv) optionally, CDRH3 comprises or consists of a functional variant thereof comprising at least one amino acid substitution selected from the group consisting of SEQ ID NOs: 5, 139, 148, 162, 176, 183, 190, 197, 203, 218, 227, 236, 245, 255, 264, 272, 280, 286, 294, 303, 310, 317, 322, 328, 335, 343, 353, 358, 365, 372, 730, 740, 749, 758, 768,778, 787, 797, 806, 821, 824, 832, 835, 841, 844, 15, 25, 33, 48, 62, 89, 114, 123, 131, 389, 398, 406, 427, 432, 476, 493, 499, 507, 516, 535, and 551, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or relative to a germline-encoded amino acid; and (iv) any Optionally, CDRL1 comprises or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 8, 142, 151, 165, 173, 186, 193, 206, 221, 230, 239, 258, 267, 289, 297, 306, 313, 338, 350, 375, 733, 743, 761, 771, 781, 790, 800, 809, 18, 65, 92, 99, 126, 383, 401, 437, 445, 456, 488, 554, 561, 564, and 568, or a functional variant thereof comprising one, two, or three amino acid substitutions. one or more of the substitutions are optionally conservative substitutions and / or substitutions relative to a germline-encoded amino acid; and (v) optionally, CDRL2 comprises an amino acid sequence set forth in any one of SEQ ID NOs: 9, 143, 152, 156, 166, 200, 207, 222, 240, 268, 290, 314, 339, 734, 752, 762, 772, 791, 801, 856, 871, 19, 43, 66, 117, 392, 409, 467, 489, 510, 519, 555, and 705, or one, two, or three amino acid substitutions. and / or (vi) optionally, CDRL3 comprises or consists of a functional variant thereof, including a nucleotide sequence selected from the group consisting of SEQ ID NOs: 10, 144, 153, 157, 167, 179, 187, 194, 208, 213, 223, 231, 241, 248, 259, 269, 275, 291, 298, 307, 325, 340, 376, 735, 744, 753, 763, 773, 782, 792, 802, 810, 848, 852, 866, 870, 880, 882, 884, 886, 888, 890, 900, 902, 910, 912, 914, 916, 918, 920, 922, 924, 926, 928, 930, 932, 934, 936, 938, 940, 942, 944, 946, 948, 950, 952, 956, 958, 960, 962, 964, 966, 970, 972, 976, 978, 980, 982, 984, 986, 988, 990, 1000, 1002, 1004, 1006, 1008, 1009, 1109, 1111, 1121, 1122, 112328, 36, 44, 51, 57, 67, 77, 84, 93, 118, 127, 134, 384, 393, 402, 410, 420, 438, 446, 468, 502, 511, 556, and 520, or a functional variant thereof having one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or relative to a germline-encoded amino acid.

[0146] In certain embodiments, the present disclosure provides an antibody or antigen-binding fragment that binds RSV-F, comprising a heavy chain variable domain (VH) comprising complementarity-determining regions (CDRs) H1, CDRH2, and CDRH3, and a light chain variable region (VL) comprising CDRL1, CDRL2, and CDRL3, wherein the CDRs are determined according to the IMGT numbering system, and (i) optionally, CDRH1 is selected from the group consisting of SEQ ID NOs: 3, 137, 147, 160, 170, 182, 216, 234, 244, 262, 278, 285, 301, 333, 363, 370, 728, 738, 747, 750, 760, 770, 780, 790, 800, 810, 820, 830, 840, 850, 860, 870, 880, 890, 900, 910, 920, 930, 940, 950, 960, 970, 980, 990, 1000, 1010, 1020, 1030, 1040, 1050, 1060, 1070, 1080, 1090, 1100, 1110, 1120, 1130, 1140, 1150, 1160, 1170, 1182, 1210, 1220, 1230, 1240, 1250, 1260, 1270, 1280, 1290, 13 and (ii) optionally, CDRH2 comprises or consists of an amino acid sequence set forth in any one of SEQ ID NOs: 4, 138, 161, 217, 226, 235, 263, 279, 302, 334, 364, 371, 729, 739, 748, 757, 767, 777, 780, 781, 782, 783, 784, 785, 795, 805, 814, 887, and 890, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or relative to a germline-encoded amino acid; 86, 796, 815, 818, 838, 884, 894, and 897, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or relative to a germline-encoded amino acid; and (iii) optionally, CDRH3 comprises or consists of an amino acid sequence set forth in any one of SEQ ID NOs: 5, 139, 148, 162, 176, 183, 190, 197, 203, 218, 227, 236, 245, 255, 264, 272, 280, 286, 290, 300, 301, 302, 303, 304, 305, 306, 307, 308, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 94, 303, 310, 317, 322, 328, 335, 343, 353, 358, 365, 372, 730, 740, 749, 758, 768, 778, 787, 797, 806, 821, 824, 832, 835, 841, and 844, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or relative to a germline-encoded amino acid; and (iv) optionally, CDRL1 is8, 142, 151, 165, 173, 186, 193, 206, 221, 230, 239, 258, 267, 289, 297, 306, 313, 338, 350, 375, 733, 743, 761, 771, 781, 790, 800, and 809, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein the substitutions one or more of which are optionally conservative substitutions and / or substitutions relative to a germline-encoded amino acid; and (v) optionally, CDRL2 has the amino acid sequence set forth in any one of SEQ ID NOs: 9, 143, 152, 156, 166, 200, 207, 222, 240, 268, 290, 314, 339, 734, 752, 762, 772, 791, 801, 856, and 871, or one, two, or three of the amino acid sequences set forth in SEQ ID NOs: and / or (vi) optionally, CDRL3 comprises or consists of a functional variant thereof comprising an amino acid substitution, wherein one or more of the substitutions are optionally conservative and / or relative to a germline encoded amino acid; and / or 307, 325, 340, 376, 735, 744, 753, 763, 773, 782, 792, 802, 810, 848, 852, and 866, or a functional variant thereof having one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or relative to a germline-encoded amino acid.

[0147] In a further embodiment, CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of the antibody or antigen-binding fragment that binds RSV-F comprise or consist of the CDRs identified for the anti-RSV MPK antibody in Table 2 and have the corresponding amino acid sequences shown in Table 1 and the Sequence Listing. Specifically, the CDRs are MPK44, MPK65-v2, MPK161-v2, MPK163, MPK165, MPK167, MPK168, MPK169- v2, MPK170, MPK171-v1, MPK171-v2, MPK173, MPK175, MPK176, MPK177, MPK178, MPK179- v4, MPK180, MPK181, MPK182, MPK185, MPK186, MPK187, MPK188, MPK189, MPK191, MPK19 3, MPK194-v2, MPK195, MPK197, MPK198, MPK201, MPK202, MPK203, MPM10, MPM2, MPM8, MP It may comprise or consist of the CDRs of O1, MPO7, MPP1, MPP2, MPR16, or MPR19-v2, MPK65-v (any one of 1 to 7). (any one of 1 to 2), MPK201-v (any one of 1 to 6). (any one of 1 to 2), MPK176-v (any one of 1 to 6). (any one of 5), or MPM2-v (any one of 1, 2, 4, 5). (any one of 1 to 9), specifically, MPK176-v1.3, MPK176-v4.3, MPK201-v1.1, MPK201-v1.2, MPK201-v4.1, MPK65v2-v1.2, or MPK65v2-v3.1.

[0148] More specifically, CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of the antibody or antigen-binding fragment that binds RSV-F comprise or consist of CDRs having the following sequences: 1) SEQ ID NOs: 3-5 and 8-10, 2) SEQ ID NOs: 137-139 and 142-144, 3) SEQ ID NOs: 147, 138, 148, and 151-153, 4) SEQ ID NOs: 147, 138, 148, 142, 156, and 157, 5) SEQ ID NOs: 160-162 and 165-167, 6) SEQ ID NOs: 170, 138, 148, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 56, and 157, 7) SEQ ID NOs: 137, 138, 176, 142, 143, and 179, 8) SEQ ID NOs: 182, 138, 183, 186, 143, and 187, 9) SEQ ID NOs: 137, 138, 190, 193, 143, and 194, 10) SEQ ID NOs: 137, 138, 197, 142, 200, and 157, 11) SEQ ID NOs: 137, 138, 203, and 206 to 208, 12) SEQ ID NOs: 137, 138, 203, 142, 143, and 213, 13) SEQ ID NOs: 216 to 218 and 221 to 223, 14) SEQ ID NOs: 137, 226, 227, 230, 143, and and 231, 15) SEQ ID NOs: 234 to 236 and 239 to 241, 16) SEQ ID NOs: 244, 138, 245, 173, 143, and 248, 17) SEQ ID NOs: 182, 138, 148, 142, 156, and 157, 18) SEQ ID NOs: 137, 138, 255, 258, 156, and 259, 19) SEQ ID NOs: 262 to 264 and 267 to 269, 20) SEQ ID NOs: 137, 138, 272, 173, 143, and 275, 21) SEQ ID NOs: 278 to 280 and 206 to 208, 22) SEQ ID NOs: 285, 138, 286, and 289 to 291, 23) SEQ ID NOs: 137, 2 26, 294, 297, 143, and 298, 24) SEQ ID NOs: 301 to 303, 306, 268, and 307, 25) SEQ ID NOs: 137, 138, 310, 313, 314, and 157, 26) 137, 138, 317, 142, 143, and 213, 27) SEQ ID NOs: 137, 138, 322, 142, 143, and 325, 28) SEQ ID NOs: 137, 138, 322, 142, 143, and 325, 29) SEQ ID NOs: 170, 138, 328, 142, 143, and 157, 30) SEQ ID NOs: 333 to 335 and 338 to 340, 31) SEQ ID NOs: 137, 138,343, 173, 143, and 213, 32) SEQ ID NOs: 301 to 303, 350, 268, and 307, 33) SEQ ID NOs: 137, 138, 353, 142, 143, and 213, 34) SEQ ID NOs: 137, 226, 358, 142, 143, and 231, 35) SEQ ID NOs: 363 to 365 and 8 to 10, 36) SEQ ID NOs: 370 to 372, 375, 143, and 376, 37) SEQ ID NO: 7 38, 884, 740, 743, 240, and 744, 38) SEQ ID NOs: 738-740, 743, 240, and 744, 39) SEQ ID NOs: 728-730 and 733-735, 40) SEQ ID NOs: 747-749, 221, and 752-753, 41) SEQ ID NOs: 756-758 and 761-763, 42) SEQ ID NOs: 766-768 and 771-773, 43) SEQ ID NOs: 776-778, 78 1, 268, and 782, 44) SEQ ID NOs: 785-787 and 790-792, 45) SEQ ID NOs: 795-797 and 800-802, 46) SEQ ID NOs: 805, 796, 806, 809, 801, and 810, 47) SEQ ID NOs: 234, 838, 236, and 239-241, 48) SEQ ID NOs: 137, 226, 358, 142, 143, and 848, 49) SEQ ID NOs: 814, 226, 358, 142, 143, and 848 58, 142, 143, and 231, 50) SEQ ID NOs: 137 to 139, 142, 143, and 852, 51) SEQ ID NOs: 814, 818, 139, and 142 to 144, 52) 738, 884, 740, 743, 240, and 744, 53) SEQ ID NOs: 887, 884, 740, 743, 240, and 744, or 54) SEQ ID NOs: 738, 884, 740, 743, 240, and 744.

[0149] In further embodiments, CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of the antibody or antigen-binding fragment that binds MPV-F comprise or consist of the CDRs identified for the anti-MPV MPK antibodies in Table 2 and have the corresponding amino acid sequences shown in Table 1 and the Sequence Listing. Specifically, the CDRs comprise or consist of the CDRs of MPK15 disclosed herein.

[0150] In certain embodiments, the present disclosure provides an antibody or antigen-binding fragment that binds MPV-F, comprising a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs) H1, CDRH2, and CDRH3, and a light chain variable region (VL) comprising CDRL1, CDRL2, and CDRL3, wherein the CDRs are determined according to the IMGT numbering system, and (i) optionally, CDRH1 is selected from the group consisting of SEQ ID NOs: 102, 13, 23, 31, 39, 54, 60, 74, 80, 87, 112, 121, 130, 380, 387, 396, 417, 441, 452, 45 9, 471, 481, 492, 498, 505, 514, 528, and 533, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or relative to a germline-encoded amino acid; and (ii) optionally, CDRH2 comprises or consists of an amino acid sequence set forth in any one of SEQ ID NOs: 103, 14, 24, 32, 40, 47, 61, 81, 88, 96, 113, 122, 388, 397, 405, 442, 453, 464, 506, , 515, 534, 540, 543, and 548, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or relative to a germline-encoded amino acid; and (iii) optionally, CDRH3 comprises or consists of an amino acid sequence set forth in any one of SEQ ID NOs: 104, 15, 25, 33, 48, 62, 89, 114, 123, 131, 389, 398, 406, 427, 432, 476, 493, 499, 507, 516, 520, 530, 541, 542, 543, and 548, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or relative to a germline-encoded amino acid; (iv) optionally, CDRL1 comprises or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 107, 18, 65, 92, 99, 126, 383, 401, 437, 445, 456, 488, 554, 561, 564, and 568, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative substitutions and / or substitutions relative to a germline encoded amino acid;or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or relative to a germline-encoded amino acid; (v) optionally, CDRL2 comprises or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 108, 19, 43, 66, 117, 392, 409, 467, 489, 510, 519, 555, and 705, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or relative to a germline-encoded amino acid; and / or (vi) optionally, CDRL3 comprises or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 109, 20, 28, 36, 44, 51, 57, 67, 77, 84, 93, 118, 127, 134, 384, 393, 402, 410, 420, 438, 446, 468, 502, 511, 556, and 520, or a functional variant thereof having one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative substitutions and / or substitutions relative to a germline-encoded amino acid.

[0151] In certain embodiments, the present disclosure provides an antibody or antigen-binding fragment that binds MPV-F, comprising: a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs) H1, CDRH2, and CDRH3; and a light chain variable region (VL) comprising CDRL1, CDRL2, and CDRL3, wherein the CDRs are determined according to the IMGT numbering system; and (i) optionally, CDRH1 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 102, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are selected from the group consisting of: (ii) optionally, CDRH2 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 103 or a functional variant thereof comprising one, two, or three amino acid substitutions, one or more of which are optionally conservative substitutions and / or substitutions relative to germline-encoded amino acids; and (iii) optionally, CDRH3 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 104 or a functional variant thereof comprising one, two, or three amino acid substitutions. (iv) optionally, CDRL1 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 107, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative substitutions and / or substitutions relative to a germline-encoded amino acid; (v) optionally, CDRL2 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 108, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative substitutions and / or substitutions relative to a germline-encoded amino acid; (vi) optionally, CDRL3 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 109 or a functional variant thereof with one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or substitutions relative to a germline-encoded amino acid; and / or

[0152] In certain embodiments, the present disclosure provides antibodies or antigen-binding fragments that bind RSV-F and / or MPV-F, comprising a heavy chain variable domain (VH) comprising complementarity-determining regions (CDRs) H1, CDRH2, and CDRH3, and a light chain variable region (VL) comprising CDRL1, CDRL2, and CDRL3, wherein the CDRs are determined according to the IMGT numbering system, and (i) optionally, CDRH1 is selected from the group consisting of SEQ ID NOs: 13, 23, 31, 39, 54, 60, 74, 80, 87, 112, 121, 130, 380, 387, 396, 417, 441, 452, 453, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 591, 592, 593, 594, 595, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621, 622, 623, 6 and (ii) optionally, CDRH2 comprises or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 14, 24, 32, 40, 47, 61, 81, 88, 96, 113, 122, 388, 397, 405, 442, 453, 464, 506, 515, 534, 542, 553, 564, 571, 581, 592, 605, 616, 621, 631, 632, 642, 653, 664, 671, 681, 692, 705, 714, 728, 733, 742, 753, 764, 771, 781, 792, 805, 814, 828, 833, 842, 853, 864, 871, 881, 892, 905, 914, 928, 933, 942, 953, 964, 971, 981, 992, 1005, 1014, 1024, 1034, 1042, 1053, 1064, 1071, 1081, 1092, 1105, 1113, 122, 1234, 1242, 1254, 1264, 1272, 1282, 1294, 1304, 1316, 1326, 1334, 1346, 1353, (iii) optionally, CDRH3 comprises or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 15, 25, 33, 48, 62, 89, 114, 123, 131, 389, 398, 406, 427, 432, 476, 493, 499, 507, 516, 535, and 551, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative substitutions and / or substitutions relative to a germline-encoded amino acid; (iv) optionally, CDRL1 comprises or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 18, 65, 92, 99, 126, 383, 401, 437, 445, 456, 488, 554, 561, 564, and 568, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or relative to a germline-encoded amino acid;or consisting of, wherein one or more of the substitutions are optionally conservative substitutions and / or substitutions relative to a germline-encoded amino acid; and (v) optionally, CDRL2 comprises or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 19, 43, 66, 117, 392, 409, 467, 489, 510, 519, 555, and 705, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative substitutions and / or substitutions relative to a germline-encoded amino acid. and / or (vi) optionally, CDRL3 comprises or consists of the amino acid sequence set forth in any one of SEQ ID NOs: 20, 28, 36, 44, 51, 57, 67, 77, 84, 93, 118, 127, 134, 384, 393, 402, 410, 420, 438, 446, 468, 502, 511, 556, and 520, or a functional variant thereof having one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative substitutions and / or substitutions relative to a germline-encoded amino acid.

[0153] In further embodiments, CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of the antibody or antigen-binding fragment that binds RSV-F and / or MPV-F comprise or consist of the CDRs identified for the anti-RSV / MPV MPK or MPH antibodies in Tables 2 and 20, and have the corresponding amino acid sequences shown in Table 1 and the Sequence Listing. Specifically, the CDRs are those of MPK190-v1.3, MPK9, MPK10, MPK18, MPK30-v1, MPK36-v3, MPK51, MPK51-v1.1, MPK67, MPK73, MPK77, MPK77-v1.1, MPK86, MPK92, MPK99, MPK102, MPK104, MPK104-v1.1, MPK104-v1.3, MPK108, MPK126, MPK127, MPK129, MPK130, MPK132, and the like, as disclosed herein. The cross-linking or cross-neutralizing antibodies may comprise or consist of the CDRs of RSV-F alone or MPV-F alone, and need not be used in situations where binding and / or neutralization of both RSV and MPV targets occurs.

[0154] The term "CL" refers to an "immunoglobulin light chain constant region" or "light chain constant region," i.e., a constant region derived from an antibody light chain. The term "CH" refers to an "immunoglobulin heavy chain constant region" or "heavy chain constant region," which can be further divided into CH1, CH2, and CH3 domains (IgA, IgD, IgG) or CH1, CH2, CH3, and CH4 domains (IgE, IgM) depending on the antibody isotype. The Fc region of an antibody heavy chain is further described herein. In any of the embodiments of the present disclosure, an antibody or antigen-binding fragment of the present disclosure comprises any one or more of CL, CH1, CH2, and CH3. In any of the embodiments of the present disclosure, an antibody or antigen-binding fragment of the present disclosure may comprise any one or more of CL, CH1, CH2, and CH3. In certain embodiments, the CL comprises an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 905. In certain embodiments, the CL comprises an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a human lambda light chain constant domain.

[0155] In certain embodiments, CH1-CH3 comprise an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 664-668.

[0156] For example, it is understood that production in mammalian cell lines may remove one or more C-terminal lysines of an antibody heavy chain (see, e.g., Liu et al. mAbs 6(5):1145-1154 (2014)). Accordingly, antibodies or antigen-binding fragments of the present disclosure can include heavy chain, CH1-CH3, CH3, or Fc polypeptides with or without a C-terminal lysine residue or C-terminal glycine-lysine; in other words, embodiments are encompassed in which the C-terminal residue of a heavy chain, CH1-CH3, or Fc polypeptide is not lysine, as well as embodiments in which lysine is the C-terminal residue. In certain embodiments, a composition comprises a plurality of antibodies and / or antigen-binding fragments of the present disclosure, wherein one or more antibodies or antigen-binding fragments do not include a lysine residue or C-terminal glycine-lysine at the C-terminus of the heavy chain, CH1-CH3, or Fc polypeptide, and one or more antibodies or antigen-binding fragments include a lysine residue at the C-terminus of the heavy chain, CH1-CH3, or Fc polypeptide.

[0157] "Fab" (Fragment Antigen Binding) is the portion of an antibody that binds to an antigen. It comprises the variable region and CH1 of a heavy chain linked to a light chain via an interchain disulfide bond. Each Fab fragment is monovalent with respect to antigen binding, i.e., it has a single antigen-binding site. Pepsin treatment of an antibody yields a single large F(ab')2 fragment, which roughly corresponds to two disulfide-linked Fab fragments with bivalent antigen-binding activity while still cross-linking antigen. Both Fab and F(ab')2 are examples of "antigen-binding fragments." Fab' fragments differ from Fab fragments by having several additional residues at the carboxy terminus of the CH1 domain, including one or more cysteines from the antibody hinge region. Fab'-SH is the designation used herein for Fab' in which the cysteine residues in the constant domains bear a free thiol group. F(ab')2 antibody fragments were originally produced as pairs of Fab' fragments, each with hinge cysteines between them. Other chemical linkages of antibody fragments are also known.

[0158] Fab fragments may be linked, for example, by peptide linkers, to form single-chain Fabs, also referred to herein as "scFabs." In these embodiments, the interchain disulfide bonds present in native Fabs may be absent, and the linker serves, in whole or in part, to link or connect the Fab fragments in a single polypeptide chain. A heavy chain-derived Fab fragment (e.g., comprising, consisting of, or consisting essentially of VH+CH1, or "Fd") and a light chain-derived Fab fragment (e.g., comprising, consisting of, or consisting essentially of VL+CL) may be linked in any configuration to form an scFab. For example, an scFab may be arranged, from N- to C-terminal, as follows: (heavy chain Fab fragment-linker-light chain Fab fragment) or (light chain Fab fragment-linker-heavy chain Fab fragment). Peptide linkers and exemplary linker sequences for use in scFabs are discussed in further detail herein.

[0159] An "Fv" is a small antibody fragment containing a complete antigen-recognition and antigen-binding site. This fragment generally consists of a dimer of one heavy- and one light-chain variable domain in tight, non-covalent association. However, even a single variable domain (or half of an Fv containing only three CDRs specific for an antigen) has the ability to recognize and bind antigen, although typically with lower affinity than the entire binding site.

[0160] "Single-chain Fv," also abbreviated as "sFv" or "scFv," is a Fv consisting of VFs linked together to form a single polypeptide chain. H and V L In some embodiments, the scFv polypeptide is an antibody fragment comprising a V H Domains and V LThe scFv may comprise a polypeptide linker disposed between and connecting the domains, which allows the scFv to maintain or form the desired structure for antigen binding. Such peptide linkers can be incorporated into the fusion polypeptide using standard techniques well known in the art. For a review of scFvs, see Pluckthun in *The Pharmacology of Monoclonal Antibodies*, vol. 113, Rosenburg and Moore eds., Springer-Verlag, New York, pp. 269-315 (1994); Borrebaeck 1995 (infra). In certain embodiments, the antibody or antigen-binding fragment comprises an scFv comprising a VH domain, a VL domain, and a peptide linker connecting the VH domain to the VL domain. In certain embodiments, the scFv comprises a VH domain connected to the VL domain by a peptide linker, which can be in a VH-linker-VL orientation or a VL-linker-VH orientation. Any scFv of the disclosure can be engineered so that the C-terminus of the VL domain is linked to the N-terminus of the VH domain by a short peptide sequence, or vice versa (i.e., (N)VL(C)-linker-(N)VH(C) or (N)VH(C)-linker-(N)VL(C)). Alternatively, in some embodiments, a linker can be linked to the N-terminal portion or terminus of the VH domain, the VL domain, or both.

[0161] Peptide linker sequences can be selected, for example, based on: (1) their ability to adopt a flexible, extended conformation; (2) their inability or lack of ability to adopt a secondary structure that can interact with a functional epitope on the first and second polypeptides and / or the target molecule; and / or (3) the absence or relative absence of hydrophobic or charged residues that can react with the polypeptides and / or the target molecule. Other considerations for linker design (e.g., length) include the conformation or range of conformations in which the VH and VL can form a functional antigen-binding site. In certain embodiments, peptide linker sequences contain, for example, Gly, Asn, and Ser residues. Other near-neutral amino acids (e.g., Thr and Ala) can also be included in the linker sequence. Other amino acid sequences that may be usefully employed as linkers include those disclosed in Maratea et al., Gene 40:39 46 (1985), Murphy et al., Proc. Natl. Acad. Sci. USA 83:8258 8262 (1986), U.S. Pat. No. 4,935,233, and U.S. Pat. No. 4,751,180. Other illustrative, non-limiting examples of linkers include, for example, Glu-Gly-Lys-Ser-Ser-Gly-Ser-Gly-Ser-Glu-Ser-Lys-Val-Asp (Chaudhary et al., Proc. Natl. Acad. Sci. USA 87:1066-1070 (1990)), and Lys-Glu-Ser-Gly-Ser-Val-Ser-Ser-Glu-Gln-Leu-Ala-Gln-Phe-Arg-Ser-Leu-Asp (Bird et al., Science 242:423-426 (1988)), as well as the pentamer Gly-Gly-Gly-Gly-Ser, when present in a single repeat or repeated 1 to 5 or more times.Any suitable linker may be used, but generally may be about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 15 23, 24, 25, 26, 27, 28, 29, 30, 40, 50, 60, 70, 80, 90, 100 amino acids in length, or less than about 200 amino acids in length. Preferably, the linker comprises a flexible structure (one that can provide flexibility and room for conformational movement between the two regions, domains, motifs, fragments, or modules connected by the linker), and preferably is biologically inert and / or has a low risk of immunogenicity in humans.

[0162] An scFv can be constructed using any combination of VH and VL sequences disclosed herein, or any combination of CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 sequences.

[0163] In some embodiments, a linker sequence is not required, such as when the first and second polypeptides have non-essential N-terminal amino acid regions that can be used to separate functional domains and prevent steric hindrance.

[0164] During antibody development, DNA at germline variable (V), joining (J), and diversity (D) loci may rearrange, resulting in the insertion and / or deletion of nucleotides in the coding sequence. Somatic mutations may be encoded by the resulting sequence and may be identified by reference to the corresponding known germline sequence. In some situations, somatic mutations that are not important for the desired properties of the antibody (e.g., binding to RSV and / or MPV fusion glycoprotein antigens) or that confer undesirable properties to the antibody (e.g., resulting in an increased risk of immunogenicity in the subject receiving the antibody), or both, may be substituted with the corresponding germline-encoded amino acid or a different amino acid such that the desired properties of the antibody are improved or maintained and the undesirable properties of the antibody are reduced or eliminated. Thus, in some embodiments, antibodies or antigen-binding fragments of the present disclosure contain one or more additional germline-encoded amino acids in the variable regions compared to a parent antibody or antigen-binding fragment, provided that the parent antibody or antigen-binding fragment contains one or more somatic mutations. The variable region and CDR amino acid sequences of exemplary anti-RSV-F, anti-MPV-F, and anti-RSV-F and / or MPV-F antibodies of the present disclosure are provided in Table 1, Table 2, and the Sequence Listing.

[0165] In certain embodiments, the antibody or antigen-binding fragment comprises amino acid modifications (e.g., substitution mutations) to eliminate the undesired risk of oxidation, deamidation, and / or isomerization.

[0166] Also provided herein are variant antibodies that contain one or more amino acid modifications in the variable regions (e.g., VH, VL, framework, or CDR) compared to a ("parent") antibody of the present disclosure, wherein the variant antibodies bind to RSV and / or MPV fusion glycoproteins.

[0167] In certain embodiments, the antibody binds to RSV-F, (i) VH is SEQ ID NO: 2, 136, 146, 159, 169, 175, 181, 189, 196, 202, 210, 215, 225, 233, 243, 250, 254, 261, 271, 277, 284, 293, 300, 309, 316, 321, 327, 332, 342, 347, 352, 357, 362, 369, 727, 737, 746, 755, 765, 775, 784, 794, 804, 813, 817, 820, 823, 826, 828, 831, 834, 837, 840, 843, 883, 886, 889, 893, 896, 899, 901, 903, 129, 12, 38, 46, 53, 59, 69, 120, 73, 79, 86, 95, 22, 111, 30, 378, 386, 395, 404, 41 2, 416, 422, 426, 431, 440, 451, 458, 463, 470, 475, 480, 485, 491, 497, 532, 537, 539, 542, 545, 547, 550, 504, 513, 524, 527, 702, 707, 712, and 716, wherein the sequence diversity is optionally limited to one or more framework regions, and / or the sequence diversity includes one or more substitutions relative to a germline-encoded amino acid, and / or (ii) VL is SEQ ID NO: 7, 141, 150, 155, 164, 172, 178, 185, 192, 199, 205, 212, 220, 229, 238, 247, 252, 257, 266, 274, 282, 288, 296, 305, 312, 319, 324, 330, 337, 345, 349, 355, 360, 367, 374, 732, 742 , 751, 760, 770, 780, 789, 799, 808, 847, 851, 855, 858, 860, 862, 865, 868, 870, 873, 875, 877, 879, 881, 133, 17, 42, 50, 56, 64, 71, 125, 76, 83, 91, 98, 27, 116, 35, 382, 391, 400, 408, 414, 419, 4 24, 429, 434, 436, 444, 449, 455, 461, 466, 473, 478, 483, 487, 495, 501, 509, 518, 522, 530, 553, 558, 560, 563, 567, 570, 572, 574, 704, and 710, wherein the sequence diversity is optionally limited to one or more framework regions and / or the sequence diversity includes one or more substitutions relative to the germline-encoded amino acid sequence.

[0168] In certain embodiments, the antibody binds to RSV-F, (i) VH is SEQ ID NO: 2, 136, 146, 159, 169, 175, 181, 189, 196, 202, 210, 215, 225, 233, 243, 250, 254, 261, 271, 277, 284, 293, 300, 309, 316, 321, 327, 332, 342, 347, 352, 357, 362, 369, 727, 737, 746, 755, 765, 775, 784, 794, 804, 813, 817, 820, 823, 826, 828, 831, 834, 837, 840, 843, 883, 88 6, 889, 893, 896, 899, 901, and 903, wherein the sequence diversity is optionally limited to one or more framework regions, and / or the sequence diversity includes one or more substitutions relative to a germline-encoded amino acid, and / or (ii) VL is SEQ ID NO: 7, 141, 150, 155, 164, 172, 178, 185, 192, 199, 205, 212, 220, 229, 238, 247, 252, 257, 266, 274, 282, 288, 296, 305, 312, 319, 324, 330, 337, 345, 349, 355, 360, 367, 374, 732, 742, 751, 760, 770, 780, 789, 799, 808, 847, 851, 855, 858, 860, 862, 865, 868, 870 , 873, 875, 877, 879, and 881, wherein the sequence diversity is optionally limited to one or more framework regions and / or the sequence diversity includes one or more substitutions relative to the germline-encoded amino acid sequence.

[0169] In certain embodiments, the antibody binds to MVP-F and (i) VH is any one of SEQ ID NOs: 101, 132, 16, 41, 49, 55, 63, 70, 124, 75, 82, 90, 97, 26, 115, 34, 381, 390, 399, 407, 413, 418, 423, 428, 433, 435, 443, 448, 454, 460, 465, 472, 477, 482, 486, 494, 500, 508, 517, 521, 525, 529, 703, 707, 712, and 716. wherein the sequence diversity is optionally limited to one or more framework regions, and / or the sequence diversity includes one or more substitutions relative to a germline-encoded amino acid; and / or (ii) VL is selected from the group consisting of SEQ ID NOs: 106, 133, 17, 42, 50, 56, 64, 71, 125, 76, 83, 91, 98, 27, 116, 35, 382, 391, 400, 408, 414, 419, 424, 429, 434, 436, 444, 449, 455, 461, 466, 473, 478, 483, 487, 495, 501, 509, 518, 522, 530, 553, 558, 560, 563, 567, 570, 572, 574, 704, and 710, wherein the sequence diversity is optionally limited to one or more framework regions and / or the sequence diversity comprises one or more substitutions relative to the germline-encoded amino acid sequence.

[0170] In certain embodiments, the antibody binds to MVP-F and (i) the VH comprises or consists of an amino acid sequence having at least 80% (e.g., 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to the amino acid sequence set forth in SEQ ID NO: 101, wherein the sequence diversity is optionally limited to one or more framework regions, and / or the sequence diversity includes one or more substitutions relative to a germline-encoded amino acid; and / or (ii) the VL comprises or consists of an amino acid sequence having at least 80% (e.g., 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to the amino acid sequence set forth in SEQ ID NO: 106, wherein the sequence diversity is optionally limited to one or more framework regions and / or the sequence diversity comprises one or more substitutions relative to a germline-encoded amino acid.

[0171] In certain embodiments, the antibody binds to RSV-F and / or MPV-F, (i) VH is selected from the group consisting of SEQ ID NOs: 129, 12, 38, 46, 53, 59, 69, 120, 73, 79, 86, 95, 22, 111, 30, 378, 386, 395, 404, 412, 416, 422, 426, 431, 440, 451, 458, 463, 470, 475, 480, 485, 491, 497, 532, 537, 539, 542, 545, 547, 550, 504, 513, 524, 527, 702, 707, 712, and 716. comprising or consisting of an amino acid sequence having at least 80% (e.g., 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to any one of the amino acid sequences set forth, wherein the sequence diversity is optionally limited to one or more framework regions, and / or the sequence diversity includes one or more substitutions relative to a germline-encoded amino acid; and / or (ii) VL is selected from the group consisting of SEQ ID NOs: 133, 17, 42, 50, 56, 64, 71, 125, 76, 83, 91, 98, 27, 116, 35, 382, 391, 400, 408, 414, 419, 424, 429, 434, 436, 444, 449, 455, 461, 466, 473, 478, 483, 487, 495, 501, 509, 518, 522, 530, 553, 558, 560, 563, 567, 570, 572, 574, 704, and 71 9, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or more) identity to any one of the amino acid sequences set forth in any one of Tables 1 to 5. 0, wherein the sequence diversity is optionally limited to one or more framework regions and / or the sequence diversity comprises one or more substitutions relative to the germline-encoded amino acid sequence.

[0172] In certain embodiments, the antibody binds to RSV-F and / or MPV-F, (i) the VH comprises or consists of an amino acid sequence having at least 80% (e.g., 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to the amino acid sequence set forth in any one of SEQ ID NOs: 532, 537, 539, 542, 545, 547, or 550, wherein the sequence diversity is optionally limited to one or more framework regions, and / or the sequence diversity includes one or more substitutions relative to a germline-encoded amino acid; and / or (ii) the VL comprises or consists of an amino acid sequence having at least 80% (e.g., 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to the amino acid sequence set forth in any one of SEQ ID NOs: 553, 558, 560, 563, 567, 570, 572, or 574, wherein the sequence diversity is optionally limited to one or more framework regions and / or the sequence diversity includes one or more substitutions relative to a germline-encoded amino acid.

[0173] In certain embodiments, the antibodies or antigen-binding fragments of the present disclosure are monospecific (e.g., bind to a single epitope) or multispecific (e.g., bind to multiple epitopes and / or target molecules). Antibodies and antigen-binding fragments can be constructed in a variety of formats.Exemplary antibody formats are disclosed in Spiess et al., Mol. Immunol. 67(2):95 (2015), and Brinkmann and Kontermann, mAbs 9(2):282-212 (2017), which formats and methods for making them are incorporated herein by reference, and include, for example, Bispecific T cell Engager (BiTE), DART, Knobs-Into-Holes (KIH) assembly, scFv-CH3-KIH assembly, KIH common light chain antibody, TandAb, triple body, TriBi minibody, Fab-scFv, scFv-CH-CL-scFv, F(ab')2-scFv2, tetravalent HCab, intrabody, CrossMab, dual acting Fab (DAF) (2-in-1 or 4-in-1), DutaMab, DT-IgG, Charge Pairs, Fab-arm exchange, SEEDbody, Triomab, LUZ-Y assembly, Fcab, κλ-body, orthogonal Fab, DVD-Ig (see, e.g., U.S. Pat. No. 8,258,268, the format of which is incorporated herein by reference in its entirety), IgG(H)-scFv, scFv-(H)IgG, IgG(L)-scFv, scFv-(L)IgG, IgG(L,H)-Fv, IgG(H)-V, V(H)-IgG, IgG(L)-V, V(L)-IgG, KIH These include IgG-scFab, 2scFv-IgG, IgG-2scFv, scFv4-Ig, Zybody, and DVI-IgG (4-in-1), as well as the so-called FIT-Ig (e.g., WO 2015 / 103072, the formats of which are incorporated herein by reference in their entireties), the so-called WuxiBody format (e.g., WO 2019 / 057122, the formats of which are incorporated herein by reference in their entireties), and the so-called in-elbow insert Ig format (IEI-Ig, e.g., WO 2019 / 024979 and WO 2019 / 025391, the formats of which are incorporated herein by reference in their entireties).

[0174] In certain embodiments, an antibody or antigen-binding fragment comprises two or more VH domains, two or more VL domains, or both (i.e., two or more VH domains and two or more VL domains). In certain embodiments, the antigen-binding fragment comprises the format (from N-terminal to C-terminal): VH-linker-VL-linker-VH-linker-VL, where the two VH sequences may be the same or different and the two VL sequences may be the same or different. Such linked scFvs can comprise any combination of VH and VL domains configured to bind a given target, and in formats comprising two or more VH and / or two or more VL, one, two, or more different epitopes or antigens may be bound. It will be understood that formats incorporating multiple antigen-binding domains may comprise VH and / or VL sequences in any combination or orientation. For example, the antigen-binding fragment can comprise the format VL-linker-VH-linker-VL-linker-VH, VH-linker-VL-linker-VL-linker-VH, or VL-linker-VH-linker-VH-linker-VH-linker-VL.

[0175] In embodiments comprising two VH domains and / or two VL domains, one or more VH domains or VL domains, or one or more CDRs therein, may be according to the sequences set forth in SEQ ID NOS: 1-574 and 701-903 of Table 1 and the Sequence Listing, and optionally according to the combinations set forth for specific antibodies in Table 2 and Table 20. In such embodiments, one or more VH or VL domains, or one or more CDRs may also be according to the sequences set forth in SEQ ID NOS: 575-655 of Table 1 and the Sequence Listing, and optionally according to the combinations set forth for specific antibodies in Table 3 for anti-RSV antibodies, or according to the combinations set forth for specific antibodies in Table 4 for anti-RSV / MPV antibodies.

[0176] More specifically, one or more VH may bind RSV-F and may comprise the CDRs in a VH sequence according to any one of SEQ ID NOs: 576, 586, 591, 600, 604, 613, and 617, and one or more VL may bind RSV-F and may comprise a VL sequence according to any one of SEQ ID NOs: 581, 588, 596, 602, 609, 615, and 622, determined using any known CDR numbering method, including Kabat, Chothia, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, EU, or AHo numbering, or a combination of two or more of these IMGT, Martin (Enhanced Chothia), Contact, North, and AHo numbering methods. In certain embodiments, the CDRs are numbered according to the IMGT numbering method. In certain embodiments, the CDRs follow the antibody numbering method developed by the Chemical Computing Group (CCG), for example, using Molecular Operating Environment (MOE) software.

[0177] In certain embodiments, CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are, respectively, SEQ ID NO: 577, 592, 605, or 618; SEQ ID NO: 578, 593, 606, or 619; SEQ ID NO: 579, 594, 607, or 620; SEQ ID NO: 582, 597, 610, or 623; SEQ ID NO: 583, 143, 268, or 624; or SEQ ID NO: 584, 598, 611, or 625; or in each case and may comprise or consist of functional variants thereof comprising one, two, or three amino acid substitutions, one or more of which are optionally conservative substitutions and / or substitutions relative to a germline-encoded amino acid or an amino acid sequence having at least 80% (e.g., 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to the amino acid sequence.

[0178] The constructed monospecific or multispecific antibodies or antigen-binding fragments of the present disclosure comprise any combination of VH and VL sequences and / or any combination of CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 sequences disclosed herein in Table 1 and SEQ ID NOs: 1-574 and 701-903 of the Sequence Listing, optionally according to the combinations set forth for specific antibodies in Table 2 and Table 20. Bispecific or multispecific antibodies or antigen-binding fragments may, in some embodiments, comprise one, two, or more antigen-binding domains (e.g., VH and VL) of the present disclosure, one or more VH or VL or one or more CDRs of which may also according to the sequences set forth in Table 1 and SEQ ID NOs: 575-655 of the Sequence Listing, and optionally, for anti-RSV antibodies, according to the combinations set forth for specific antibodies in Table 3 and the Sequence Listing, or for anti-RSV / MPV antibodies, according to the combinations set forth for specific antibodies in Table 4 and the Sequence Listing. There may be two or more binding domains that bind to the same or different RSV-F and / or MPV-F epitopes, and the bispecific or multispecific antibodies or antigen-binding fragments provided herein may, in some embodiments, include additional RSV-F and / or MPV-F specific binding domains and / or binding domains that bind to entirely different antigens or pathogens.

[0179] In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain, e.g., IgG1m3, which comprises M428L and N434S mutations in the heavy chain. In some embodiments, the antibody or antigen-binding fragment comprises a light chain, e.g., the light chain may be a kappa light chain or a lambda light chain.

[0180] In any of the embodiments of the present disclosure, the antibody or antigen-binding fragment may be multispecific, eg, bispecific, trispecific, etc.

[0181] In certain embodiments, the antibody or antigen-binding fragment is at least bispecific and comprises at least a VH and VL, or three CDRs of a VH and three CDRs of a VL, of at least one of i) MPK65-v2-v1.2, MPK65-v2-v3.1, MPK176-v1.3, MPK76-v43, MPK201-v1.2, and MPK 201-v1.4, or ii) the VH and VL amino acid sequences set forth in any one of SEQ ID NOs: 136 and 851, 814 and 141, 233 and 858, 837 and 858, 357 and 847, or 899 and 360, respectively.

[0182] In certain embodiments, the antibody or antigen-binding fragment is at least bispecific and comprises at least a VH and a VL, or the three CDRs of the VH and the three CDRs of the VL of MPK190-v1.3 or the VH and VL amino acid sequences set forth in SEQ ID NOs: 702 and 704, respectively.

[0183] In certain embodiments, the antibody or antigen-binding fragment is at least bispecific and comprises at least (A) a first VH and VL, or a first set of six CDRs (the first set of six CDRs being selected from the group consisting of: i) MPK65-v2-v1.2, MPK65-v2-v3.1, MPK176-v1.3, MPK76-v43, MPK201-v1.2, and MPK 201-v1.4, or ii) the three HCDRs and three LCDRs of at least one of the VH and VL set forth in any one of SEQ ID NOs: 136 and 851, 814 and 141, 233 and 858, 837 and 858, 357 and 847, and 899 and 360, respectively), and (B) at least a second VH and VL, or a second set of six CDRs (the second set of six CDRs are the three HCDRs and three LCDRs of the VH and VL of MPK190-v1.3 or the VH and VL set forth in SEQ ID NOs: 702 and 704).

[0184] In some embodiments, the antibody or antigen-binding fragment may further comprise an Fc polypeptide or fragment thereof comprising or consisting of an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to the amino acid sequence set forth in any one of SEQ ID NOs: 664-700, more specifically any one of SEQ ID NOs: 670-700, or comprising or consisting of the amino acid sequence set forth in any one of SEQ ID NOs: 664-700, more specifically any one of SEQ ID NOs: 670-700.

[0185] For example, it is understood that production in a mammalian cell line may remove one or more C-terminal lysines of the antibody heavy chain (see, e.g., Liu et al. mAbs 6(5):1145-1154 (2014)). Production may also remove one or more C-terminal glycines of the antibody heavy chain. Thus, an antibody or antigen-binding fragment of the present disclosure can include a heavy chain, CH1-CH3, CH3, or Fc polypeptide, with or without a C-terminal lysine and / or residue present; in other words, embodiments are encompassed in which the C-terminal residue of the heavy chain, CH1-CH3, or Fc polypeptide is not lysine or glycine, as well as embodiments in which lysine or glycine is the C-terminal residue. In certain embodiments, a composition comprises a plurality of antibodies and / or antigen-binding fragments of the present disclosure, wherein one or more of the antibodies or antigen-binding fragments do not comprise a lysine or glycine residue at the C-terminus of the heavy chain, CH1-CH3, or Fc polypeptide, and one or more of the antibodies or antigen-binding fragments comprise a lysine or glycine residue at the C-terminus of the heavy chain, CH1-CH3, or Fc polypeptide.

[0186] In certain embodiments, the antibody or antigen-binding fragment comprises an Fc polypeptide or fragment thereof. An "Fc" fragment or Fc polypeptide comprises the carboxy-terminal portions of both antibody heavy chains (i.e., the CH2 and CH3 domains of IgG) held together by disulfides. An Fc may comprise a dimer composed of two Fc polypeptides (i.e., two CH2-CH3 polypeptides). Antibody "effector functions" refer to the biological activities attributable to the Fc region of an antibody (a native-sequence Fc region or an amino acid sequence variant Fc region) and vary depending on the antibody isotype. Examples of antibody effector functions include C1q binding and complement-dependent cytotoxicity, Fc receptor binding, antibody-dependent cell-mediated cytotoxicity (ADCC), phagocytosis, down-regulation of cell surface receptors (e.g., B cell receptors), and B cell activation. As discussed herein, modifications (e.g., amino acid substitutions) can be made to the Fc domain to modify (e.g., improve, reduce, or eliminate) one or more functions of an Fc-containing polypeptide (e.g., an antibody of the disclosure), including, for example, Fc receptor (FcR) binding, antibody half-life regulation (e.g., by binding to FcRn), ADCC function, protein A binding, protein G binding, and complement fixation.Amino acid modifications that modify (e.g., improve, reduce, or eliminate) Fc function include, for example, T250Q / M428L, M252Y / S254T / T256E, H433K / N434F, M428L / N434S, M428L / N434A, E233P / L234V / L235A / G236+A327G / A330S / P331S, E333A, S239D / A330L / I332E, P257I / Q3 11, K326W / E333S, S239D / I332E / G236A, N297Q, K322A, S228P, L235E+E318A / K320A / K322A, L234A / L235A (also referred to herein as "LALA"), and L234A / L235A / P329G mutations, which are summarized and annotated in "Engineered Fc Regions" published by InvivoGen (2011), which is incorporated herein by reference.

[0187] For example, to activate the complement cascade, the C1q protein complex can bind to two or more IgG1 molecules or one IgM molecule when the immunoglobulin molecule is bound to an antigenic target (Ward, E.S., and Ghetie, V., Ther. Immunol. 2 (1995) 77-94). Burton, D.R. (Mol. Immunol. 22 (1985) 161-206) reported that the heavy chain region containing amino acid residues 318-337 is involved in complement binding. Duncan, A.R., and Winter, G. (Nature 332 (1988) 738-740) reported, using site-directed mutagenesis, that Glu318, Lys320, and Lys322 form the binding site for C1q. The role of residues Glu318, Lys320, and Lys322 in binding C1q was confirmed by the ability of short synthetic peptides containing these residues to inhibit complement-mediated lysis.

[0188] For example, FcR binding can be mediated by the interaction of the Fc portion (of an antibody) with Fc receptors (FcRs), specialized cell surface receptors on cells, including hematopoietic cells. Fc receptors belong to the immunoglobulin superfamily and have been shown to mediate both the removal of antibody-coated pathogens by phagocytosis of immune complexes via antibody-dependent cellular cytotoxicity (ADCC), as well as the lysis of corresponding antibody-coated red blood cells and various other cellular targets (e.g., tumor cells) (Van de Winkel, JG, and Anderson, CL, J. Leukoc. Biol. 49 (1991) 511-524). FcRs are defined by their specificity for immunoglobulin classes. Fc receptors for IgG antibodies are referred to as FcγRs, Fc receptors for IgE are referred to as FcεRs, Fc receptors for IgA are referred to as FcαRs, and neonatal Fc receptors are referred to as FcRn. Fc receptor binding is described, for example, in Ravetch, JV, and Kinet, JP, Annu. Rev. Immunol. 9 (1991) 457-492, Capel, PJ et al., Immunomethods 4 (1994) 25-34, de Haas, M., et al., J Lab. Clin. Med. 126 (1995) 330-341, and Gessner, JE, et al., Ann. Hematol. 76 (1998) 231-248.

[0189] Cross-linking of receptors by the Fc domains (FcγRs) of native IgG antibodies triggers a wide variety of effector functions, including phagocytosis, antibody-dependent cellular cytotoxicity, and the release of inflammatory mediators, as well as modulation of immune complex clearance and antibody production. Fc moieties that provide cross-linking of receptors (e.g., FcγRs) are contemplated herein. In humans, three classes of FcγRs have been characterized to date: (i) FcγRI (CD64), which binds monomeric IgG with high affinity and is expressed on macrophages, monocytes, neutrophils, and eosinophils; (ii) FcγRII (CD32), which binds complexed IgG with intermediate to low affinity, is widely expressed, particularly on leukocytes, and is thought to play a central role in antibody-mediated immunity and can be divided into FcγRIIA, FcγRIIB, and FcγRIIC, and is a key regulator of the immune system. (iii) FcγRIII (CD16) binds IgG with intermediate to low affinity and is found in two forms (FcγRIIIA and FcγRIIIB); FcγRIIIA is found on NK cells, macrophages, eosinophils, and some monocytes and T cells and is thought to mediate ADCC; FcγRIIIB is highly expressed on neutrophils.

[0190] FcγRIIA is found on many cells involved in death (e.g., macrophages, monocytes, neutrophils) and appears to be able to activate the death process. FcγRIIB appears to play a role in inhibitory processes and is found on B cells, macrophages, as well as mast cells and eosinophils. Importantly, 75% of all FcγRIIB has been shown to be found in the liver (Ganesan, LP et al., 2012: "FcγRIIb on liver sinusoidal endothelium clears small immune complexes", Journal of Immunology 189:4981-4988). FcγRIIB is abundantly expressed on the liver sinusoidal endothelium, called LSECs, and in the liver's Kupffer cells, which are the primary site of small immune complex clearance (Ganesan, LP et al., 2012: FcγRIIb on liver sinusoidal endothelium clears small immune complexes. Journal of Immunology 189:4981-4988).

[0191] In some embodiments, the antibodies and antigen-binding fragments thereof disclosed herein comprise an Fc polypeptide or fragment thereof for binding to FcγRIIb, particularly the Fc region, e.g., an IgG-type antibody. Furthermore, the Fc portion can be engineered to enhance FcγRIIb binding by introducing the mutations S267E and L328F, as described in Chu, S.Y. et al., 2008: Inhibition of B cell receptor-mediated activation of primary human B cells by coengagement of CD19 and FcgammaRIIb with Fc-engineered antibodies. Molecular Immunology 45, 3926-3933. This can enhance the clearance of immune complexes (Chu, S., et al., 2014: Accelerated Clearance of IgE In Chimpanzees Is Mediated By Xmab7195, An Fc-Engineered Antibody With Enhanced Affinity For Inhibitory Receptor FcγRIIb. Am J Respir Crit, American Thoracic Society International Conference Abstracts). In some embodiments, the antibody or antigen-binding fragment thereof of the present disclosure comprises an engineered Fc portion having the mutations S267E and L328F, as described in particular in Chu, S.Y. et al., 2008: Inhibition of B cell receptor-mediated activation of primary human B cells by coengagement of CD19 and FcγRIIb with Fc-engineered antibodies. Molecular Immunology 45, 3926-3933.

[0192] On B cells, FcγRIIB may function to suppress further immunoglobulin production and isotype switching, for example, to the IgE class. On macrophages, FcγRIIB is thought to inhibit phagocytosis mediated through FcγRIIA. On eosinophils and mast cells, FcγRIIB may serve to suppress activation of these cells by binding of IgE to its distinct receptor.

[0193] With respect to FcγRI binding, modifications in native IgG of one or more of E233-G236, P238, D265, N297, A327, and P329 reduce binding to FcγRI. Substitution of IgG2 residues at positions 233-236 with the corresponding IgG1 and IgG4 positions reduced IgG1 and IgG4 binding to FcγRI by 103-fold and eliminated the human monocyte response to antibody-sensitized erythrocytes (Armour, KLet et al., Eur. J. Immunol. 29 (1999) 2613-2624).

[0194] With respect to FcγRII binding, reduced binding to FcγRIIA is seen for IgG mutations such as one or more of E233-G236, P238, D265, N297, A327, P329, D270, Q295, A327, R292, and K414.

[0195] The two allelic forms of human FcγRIIA are the "H131" variant, which binds IgG1 Fc with higher affinity, and the "R131" variant, which binds IgG1 Fc with lower affinity. See, e.g., Bruhns et al., Blood 113:3716-3725 (2009).

[0196] With respect to FcγRIII binding, reduced binding to FcγRIIIA is observed for mutations in one or more of, for example, E233-G236, P238, D265, N297, A327, P329, D270, Q295, A327, S239, E269, E293, Y296, V303, A327, K338, and D376. Mapping of the binding site on human IgG1 for Fc receptors, the mutation sites described above, and methods for measuring binding to FcγRI and FcγRIIA are described in Shields, R.L., et al., J. Biol. Chem. 276 (2001) 6591-6604.

[0197] The two allelic forms of human FcγRIIIA are the "F158" variant, which binds IgG1 Fc with lower affinity, and the "V158" variant, which binds IgG1 Fc with higher affinity. See, e.g., Bruhns et al., Blood 113:3716-3725 (2009).

[0198] With regard to binding to FcγRII, two regions of native IgG Fc appear to be involved in the interaction between FcγRII and IgG: (i) the lower hinge region of IgG Fc, specifically amino acid residues L, L, G, G (234-237, EU numbering), and (ii) adjacent regions of the CH2 domain of IgG Fc, specifically loops and chains within the upper CH2 domain adjacent to the lower hinge region, e.g., the region of P331 (Wines, BD, et al., J. Immunol. 2000;164:5313-5318). Furthermore, while FcγRI appears to bind to the same site on IgG Fc, FcRn and Protein A bind to different sites on IgG Fc, which appear to be at the CH2-CH3 interface (Wines, BD, et al., J. Immunol. 2000;164:5313-5318).

[0199] Also contemplated are mutations that increase the binding affinity of an Fc polypeptide or fragment thereof of the present disclosure to (i.e., one or more) Fcγ receptors (e.g., when compared to a reference Fc polypeptide or fragment thereof that includes or does not include the mutation). See, e.g., Delillo and Ravetch, Cell 161(5):1035-1045 (2015) and Ahmed et al., J. Struc. Biol. 194(1):78 (2016). The Fc mutations and techniques are incorporated herein by reference.

[0200] In any of the embodiments disclosed herein, the antibody or antigen-binding fragment may comprise an Fc polypeptide or fragment thereof comprising mutations selected from G236A, S239D, A330L, and I332E, or a combination comprising any two or more thereof, e.g., S239D / I332E, S239D / A330L / I332E, G236A / S239D / I332E, G236A / A330L / I332E (also referred to herein as "GAALIE"), or G236A / S239D / A330L / I332E. In some embodiments, the Fc polypeptide or fragment thereof does not comprise S239D. In some embodiments, the Fc polypeptide or fragment thereof comprises an S at position 239 (EU numbering). In some embodiments, the Fc polypeptide or fragment thereof comprises the amino acid sequence set forth in SEQ ID NOs: 672-678.

[0201] In certain embodiments, an Fc polypeptide or fragment thereof may comprise or consist of at least a portion of an Fc polypeptide or fragment thereof that is involved in FcRn binding. In certain embodiments, the Fc polypeptide or fragment thereof comprises one or more amino acid modifications that improve binding affinity for FcRn (e.g., at a pH of about 6.0) (e.g., enhance binding to FcRn), which in some embodiments increases the in vivo half-life of a molecule comprising the Fc polypeptide or fragment thereof (e.g., compared to a reference Fc polypeptide or fragment thereof, or an otherwise identical antibody that does not contain the modifications). In certain embodiments, the Fc polypeptide or fragment thereof comprises or is derived from an IgG Fc, and the half-life extending mutations comprise one or more of M428L, N434S, N434H, N434A, N434S, M252Y, S254T, T256E, T250Q, P257I Q311I, D376V, T307A, and E380A (EU numbering). In certain embodiments, the half-life extending mutations comprise M428L / N434S (also referred to herein as "MLNS," "LS," "_LS," and "-LS"). In certain embodiments, the half-life extending mutations are in an Fc polypeptide or fragment thereof comprising or consisting of the amino acid sequence set forth in SEQ ID NOs: 679-684. In certain embodiments, the half-life extending mutations comprise M252Y / S254T / T256E. In certain embodiments, the half-life extending mutations comprise T250Q / M428L. In certain embodiments, the half-life extending mutations comprise P257I / Q311I. In certain embodiments, the half-life extending mutations comprise P257I / N434H. In certain embodiments, the half-life extending mutations comprise D376V / N434H. In certain embodiments, the half-life extending mutations comprise T307A / E380A / N434A. In certain embodiments, the half-life extending mutations comprise M428L / N434A (also referred to herein as "MLNA," "LA," "_LA," and "-LA"). In certain embodiments, the half-life extending mutations are in an Fc polypeptide or fragment thereof comprising or consisting of the amino acid sequence set forth in SEQ ID NOs: 685-690.

[0202] In some embodiments, the antibody or antigen-binding fragment comprises an Fc portion comprising the substitution mutations M428L / N434S or M428L / N434A. In some embodiments, the antibody or antigen-binding fragment comprises an Fc polypeptide or fragment thereof comprising the substitution mutations G236A / A330L / I332E. In certain embodiments, the antibody or antigen-binding fragment comprises an Fc portion (e.g., an IgG) comprising the G236A, A330L, and I332E mutations (GAALIE) and not comprising the S239D mutation (e.g., comprising a native S at position 239). In certain embodiments, the antibody or antigen-binding fragment comprises an Fc polypeptide or fragment thereof comprising the substitution mutations M428L / N434S and G236A / A330L / I332E (which may comprise or consist of the amino acid sequence set forth in SEQ ID NOs: 691-695), optionally not comprising S239D (e.g., comprising an S at position 239). In certain embodiments, the antibody or antigen-binding fragment comprises an Fc polypeptide or fragment thereof comprising the substitution mutations M428L / N434A and G236A / A330L / I332E (which may comprise or consist of the amino acid sequence set forth in SEQ ID NOs: 696-700), optionally excluding S239D (e.g., S at 239). In certain embodiments, the antibody or antigen-binding fragment comprises an Fc polypeptide or fragment thereof comprising the substitution mutations M428L / N434S (or M428L / N434A) and G236A / S239D / A330L / I332E.

[0203] In some embodiments, an antibody or antigen-binding fragment (further described herein) is provided that comprises any one of the amino acid mutations (i) to (xviii) in the (e.g., human) IgG1 heavy chain: (i) G236A, L328V, and Q295E, (ii) G236A, P230A, and Q295E, (iii) G236A, R292P, and I377N, (iv) G236A, K334A, and Q295E, (v) G236S, R292P, and Y300L, (vi) G236A and Y300L, (vii) G236A and Y300L, or (viii) G236A, K334A, and Q295E. 6A, R292P, and Y300L, (viii) G236S, G420V, G446E, and L309T, (ix) G236A and R292P, (x) R292P and Y300L, (xi) G236A and R292P, (xii) Y300L, (xiii) E345K, G236S, L235Y, and S267E, (xiv) E272R, L309T, S219Y, and S267E, (xv) G236Y, (xvi) G236W, (xvii) F243L, G446E, P396L, and S267E, (xviii) G236A, S239D, and H268E. The numbering of amino acid residues is according to the EU index as set forth in Kabat. In certain embodiments, the antibody or antigen-binding fragment is afucosylated. In some embodiments, the antibody or antigen-binding fragment further comprises one or more mutations that enhance binding to human FcRn, such as M428L and N434S mutations or M428L and N434A mutations (EU numbering), or any other mutation that enhances binding to human FcRn, such as those described herein. In certain embodiments, the antibody or antigen-binding fragment is afucosylated.

[0204] In specific embodiments, the antibody or antigen-binding fragment has i) a VH and VL, respectively, as set forth elsewhere herein, or (iii) a CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 as determined by any CDR determination scheme set forth elsewhere herein or disclosed herein, and (A) substitution mutations: (i) G236A, L328V, and Q295E, (ii) G236A, P230A, and Q295E, (iii) G236A, R292P, and I377N, (iv) G236A, K334A, and Q295E, 5E, (v) G236S, R292P, and Y300L, (vi) G236A and Y300L, (vii) G236A, R292P, and Y300L, (viii) G236S, G420V, G446E, and L309T, (ix) G236A and R292P, (x) R292P and Y300L, (xi) G236A and R292P, (xii) Y300L, (xiii) E345K, G236S, L235Y, and S267E, (xiv) E272R, L309T, S219Y, and S267E, (xv) G236Y, (xvi) G236W, (xvii (xviii) G236A, S239D, and H268E, (xix) M428L / N434S, (xx) M428L / N434A, (xxi) G236A / A330L / I332E / M428L / N434S, (xxii) G236A / A330L / I332E / M428L / N434A, or (xxiii) any two or more of (i) to (xxii); or (B) an Fc portion comprising at least 85%, at least 86%, or at least 90% of any one of SEQ ID NOs: 664 to 700. an Fc portion comprising or consisting of an Fc polypeptide or a fragment thereof, comprising or consisting of an amino acid sequence (optionally other than a naturally occurring variant thereof) having at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity thereto, or comprising or consisting of an amino acid sequence set forth in any one of SEQ ID NOs: 672-700;Including.

[0205] In certain embodiments, the antibody or antigen-binding fragment comprises a glycosylation-altering mutation, the glycosylation-altering mutation comprises N297A, N297Q, or N297G, and / or the antibody or antigen-binding fragment is partially or fully aglycosylated and / or partially or fully afucosylated. Host cell lines and methods for producing partially or fully aglycosylated or partially or fully afucosylated antibodies and antigen-binding fragments are known (see, e.g., WO 2016 / 181357; Suzuki et al. Clin. Cancer Res. 13(6):1875-82 (2007); Huang et al. MAbs 6:1-12 (2018)).

[0206] The antibodies or antigen-binding fragments of the present disclosure may be fucosylated (e.g., comprise one or more fucosyl moieties, typically comprising a native (wild-type) fucosylation pattern or a fucosylation pattern comprising one or more additional or fewer fucosyl moieties compared to native) or afucosylated. In particular, native IgG1 antibodies possess a glycan site at N297, which is typically the only site at which the core fucose moiety may be found in an antibody, although some glycan sites may arise through mutation (e.g., within the variable domain) during antibody development. Fucosylation of an Fc polypeptide or fragment thereof or antibody can be effected by introducing an amino acid mutation to introduce or destroy a fucosylation site (e.g., introducing a mutation at N297, such as N297Q or N297A, to disrupt the formation of glycans that may contain a core fucose moiety), although it is typically preferred to maintain N297 and its glycans by expressing the polypeptide in a host cell that has been genetically engineered to lack (or have an inhibited or impaired ability to) fucosylate polypeptides, expressing the polypeptide under conditions in which the ability of the host cell to fucosylate polypeptides is impaired (e.g., in the presence of 2-fluoro-L-fucose (2FF)), or the like. Afucosylated polypeptides may comprise a fucose moiety or may be substantially free of fucose moieties, and / or may be expressed by a host cell genetically engineered to lack (or have an inhibited or impaired ability to) fucosylate polypeptides, and / or may be expressed under conditions in which the host cell's ability to fucosylate polypeptides is impaired (e.g., in the presence of 2-fluoro-L-fucose (2FF)). In some embodiments, the polypeptide does not comprise a core fucose moiety at Asn297. In some embodiments, the afucosylated polypeptide has increased binding to FcγRIIIA. In some situations, addition of 2FF to culture medium containing host cells expressing the antibodies results in about 85% or more of the antibodies lacking a fucose moiety.Thus, antibodies may be described as "afucosylated" if produced in the presence of 2FF or a similar reagent. In some contexts, polypeptides or antibodies may be described as, for example, afucosylated, meaning that about 85% or more of the single polypeptide or antibody molecules of the polypeptides or antibodies do not contain a fucose moiety. In certain preferred embodiments, the afucosylated antibody or antigen-binding fragment, or a population or plurality thereof, contains an asparagine (N) at EU297. Fucosylation, or lack thereof, can be assessed, for example, using mass spectrometry (e.g., electrospray mass spectrometry (ESI-MS)). In some embodiments, compositions are provided comprising a plurality of any one or more of the polypeptides of the present disclosure, wherein the composition comprises an afucosylated polypeptide.

[0207] In certain embodiments, the antibody or antigen-binding fragment elicits continued protection in vivo in a subject, even after detectable levels of the antibody or antigen-binding fragment can no longer be found in the subject (i.e., when the antibody or antigen-binding fragment has disappeared from the subject after administration). Such protection is referred to herein as a vaccine effect. Without being bound by theory, it is believed that dendritic cells can internalize the antibody and antigen complex and then induce or contribute to an endogenous immune response against the antigen. In certain embodiments, the antibody or antigen-binding fragment contains one or more modifications, such as mutations in Fc, including, for example, G236A, A330L, and I332E, that activate dendritic cells, which can induce, for example, T cell immunity, against the antigen.

[0208] In certain embodiments, an antibody or antigen-binding fragment of the disclosure comprises an Fc variant selected from the Fc variants summarized in Table A (see also WO 2022 / 251119). In certain embodiments, the Fc variant or antibody or antigen-binding fragment is afucosylated. In other embodiments, the Fc variant or antibody or antigen-binding fragment is afucosylated.

[0209] [Table 1]

[0210] In some embodiments, an anti-parvovirus antibody or antigen-binding fragment is provided that includes, in a (e.g., human) IgG1 heavy chain, any one of the amino acid mutations set forth in (i) to (xviii): (i) G236A, L328V, and Q295E, (ii) G236A, P230A, and Q295E, (iii) G236A, R292P, and I377N, (iv) G236A, K334A, and Q295E, (v) G236S, R292P, and Y300L, (vi) G236A and Y300L, (vii) G236A, R292P, and and Y300L, (viii) G236S, G420V, G446E, and L309T, (ix) G236A and R292P, (x) R292P and Y300L, (xi) G236A and R292P, (xii) Y300L, (xiii) E345K, G236S, L235Y, and S267E, (xiv) E272R, L309T, S219Y, and S267E, (xv) G236Y, (xvi) G236W, (xvii) F243L, G446E, P396L, and S267E, and (xviii) G236A, S239D, and H268E. Amino acid residue numbering follows the EU index as described in Kabat. In certain embodiments, the antibody or antigen-binding fragment is afucosylated. In some embodiments, the antibody or antigen-binding fragment further comprises one or more mutations that enhance binding to human FcRn, such as M428L and N434S mutations or M428L and N434A mutations (EU numbering), or any other mutation that enhances binding to human FcRn, such as those described herein. In certain embodiments, the antibody or antigen-binding fragment is afucosylated.

[0211] In any of the embodiments of the present disclosure, the antibody or antigen-binding fragment comprises an Fc polypeptide or fragment thereof comprising a CH2 (or fragment thereof), a CH3 (or fragment thereof), or a CH2 and a CH3, where the CH2, CH3, or both may be of any isotype and may contain amino acid substitutions or other modifications compared to the corresponding wild-type CH2 or CH3, respectively. In certain embodiments, an Fc of the present disclosure comprises two CH2-CH3 polypeptides that associate to form a dimer.

[0212] In any of the embodiments of the present disclosure, the antibody or antigen-binding fragment may be monoclonal. As used herein, the term "monoclonal antibody" (mAb) refers to an antibody obtained from a substantially homogeneous population of antibodies, the individual antibodies of which are identical except for possible naturally occurring mutations that may be present in minor amounts. Monoclonal antibodies are highly specific, being directed against a single antigenic site. Furthermore, in contrast to polyclonal antibody preparations, which include different antibodies directed against different epitopes, each monoclonal antibody is directed against a single epitope on the antigen. In addition to their specificity, monoclonal antibodies are advantageous in that they may be synthesized uncontaminated by other antibodies. The term "monoclonal" should not be construed as requiring production of the antibody by any particular method. For example, monoclonal antibodies useful in the present invention can be prepared by the hybridoma method first described by Kohler et al., Nature 256:495 (1975), or can be made using recombinant DNA methodologies in bacterial, eukaryotic, or plant cells (see, e.g., U.S. Pat. No. 4,816,567). Monoclonal antibodies may also be isolated from phage antibody libraries using the techniques described, for example, in Clackson et al., Nature, 352:624-628 (1991) and Marks et al., J. Mol. Biol., 222:581-597 (1991). Monoclonal antibodies may also be obtained using the methods disclosed in WO 2004 / 076677(A2).

[0213] The antibodies and antigen-binding fragments of the present disclosure include "chimeric antibodies" in which a portion of the heavy and / or light chain is identical to or homologous to corresponding sequences in antibodies from a particular species or belonging to a particular antibody class or subclass, and the remainder of the chain is identical to or homologous to corresponding sequences in antibodies from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit the desired biological activity (see U.S. Pat. Nos. 4,816,567, 5,530,101, and 7,498,415, and Morrison et al., Proc. Natl. Acad. Sci. USA, 81:6851-6855 (1984)). For example, chimeric antibodies may contain both human and non-human residues. Furthermore, chimeric antibodies may contain residues that are not found in the recipient antibody or the donor antibody. These modifications are made to further refine antibody performance. For further details, see Jones et al., Nature 321:522-525 (1986), Riechmann et al., Nature 332:323-329 (1988), and Presta Curr. Op. Struct. Biol. 2:593-596 (1992). Chimeric antibodies also include primatized and humanized antibodies.

[0214] "Humanized antibodies" are generally considered to be human antibodies with one or more amino acid residues introduced into them from a non-human source. These non-human amino acid residues typically come from the variable domain. Humanization may be performed according to the method of Winter and coworkers (Jones et al., Nature, 321:522-525 (1986); Reichmann et al., Nature, 332:323-327 (1988); Verhoeyen et al., Science, 239:1534-1536 (1988)), by substituting non-human variable sequences for the corresponding sequences of a human antibody. Such "humanized" antibodies are therefore chimeric antibodies (U.S. Pat. Nos. 4,816,567, 5,530,101, and 7,498,415), in which substantially less than an intact human variable domain has been substituted by the corresponding sequence from the non-human species. In some instances, a "humanized" antibody is produced by a non-human cell or animal and contains human sequences, e.g., H C This includes the domain.

[0215] A "human antibody" is an antibody that contains only sequences present in antibodies produced by humans (i.e., sequences encoded by human antibody-encoding genes). However, as used herein, human antibodies may contain residues or modifications not found in naturally occurring human antibodies (e.g., antibodies isolated from humans), including the modifications and variant sequences described herein. These modifications and variant sequences are typically made to further refine or enhance antibody performance. In some instances, human antibodies are produced by transgenic animals. See, e.g., U.S. Patent Nos. 5,770,429, 6,596,541, and 7,049,426.

[0216] In certain embodiments, the antibodies or antigen-binding fragments of the present disclosure are chimeric, humanized, or human antibodies or human antigen-binding fragments.

[0217] In some embodiments, various pharmacokinetic ("PK") parameters are used to describe or characterize the antibodies or antigen-binding fragments provided herein. Details regarding the collection of antibody serum concentrations for the purpose of assessing PK parameters are described in connection with the Examples herein. 1 / 2 The term "C" or "half-life" refers to the elimination half-life of an antibody contained in a pharmaceutical composition administered to a subject. last The term "last measurable plasma concentration" generally refers to the last measurable plasma concentration (i.e., the point after which the substance is no longer present in measurable concentrations in plasma).

[0218] MPK190-v1.3 antibody In some embodiments, the antibody or antigen-binding fragment of the present disclosure is an MPK190-v1.3 antibody or antigen-binding fragment thereof. Such an antibody or antigen-binding fragment thereof may bind to and / or neutralize both RSV and MPV.

[0219] In some embodiments, the MPK190-v1.3 antibody may have a VH, VL, HC, LC, CDRH1-H3, and / or CDRL1-L3 that comprise or consist of an amino acid sequence or are encoded by a polynucleotide having the following sequence:

[0220] [Table 2]

[0221] In some embodiments, the VH and VL of the MPK190-v1.3 antibody or antigen-binding fragment that binds RSV-F and MPV-F and / or neutralizes RSV and / or MPV comprise or consist of a VH and VL having the sequences of SEQ ID NOs: 702 and 704, respectively.

[0222] In certain embodiments, the antibodies or antigen-binding fragments of the present disclosure bind RSV-F and MPV-F and / or neutralize RSV and MPV; (i) the VH comprises or consists of an amino acid sequence having at least 80% (e.g., 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to the amino acid sequence set forth in SEQ ID NO: 702, wherein the sequence diversity is optionally limited to one or more framework regions, and / or the sequence diversity includes one or more substitutions relative to a germline-encoded amino acid; and / or (ii) the VL comprises or consists of an amino acid sequence having at least 80% (e.g., 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to the amino acid sequence set forth in SEQ ID NO: 704, wherein the sequence diversity is optionally limited to one or more framework regions and / or the sequence diversity comprises one or more substitutions relative to a germline-encoded amino acid.

[0223] In some embodiments, the diversity compared to SEQ ID NO:702 or SEQ ID NO:704 is limited to one or more framework regions. In some embodiments, the diversity comprises or consists of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions (any or all of which may be conservative substitutions), insertions, or deletions in VH, VL, or both. In some embodiments, the diversity comprises one or more amino acid substitutions, insertions, and / or deletions of amino acids 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or more amino acid positions away from the N-terminal and / or C-terminal amino acids of the CDRs.

[0224] Framework regions can be identified according to a numbering scheme (e.g., IMGT, Kabat, Chothia, North, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, EU, or AHo, or a combination of two or more thereof). CDRs can be identified within a variable domain or within a heavy or light chain according to a numbering scheme or combination of numbering schemes, and preferably, FRs can be identified using the same numbering scheme or combination of numbering schemes.

[0225] For example, in some embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK190-v1.3, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 conform to IMGT (optionally an IMGT junction for CDRH3 and CDRL3), and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK190-v1.3 and / or one or more framework sequences that are variants of MPK190-v1.3 framework sequences, where one or more framework sequences of MPK190-v1.3 conform to IMGT (and if an IMGT junction is used for CDRH3 and CDRL3, this is taken into consideration).

[0226] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK190-v1.3, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to Kabat; and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK190-v1.3 and / or one or more framework sequences that are variants of MPK190-v1.3 framework sequences, where one or more framework sequences of MPK190-v1.3 are according to Kabat.

[0227] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK190-v1.3, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to Chothia, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK190-v1.3 and / or one or more framework sequences that are variants of MPK190-v1.3 framework sequences, where one or more framework sequences of MPK190-v1.3 are according to Chothia.

[0228] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK190-v1.3, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to Martin (Enhanced Chothia), and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK190-v1.3 and / or one or more framework sequences that are variants of MPK190-v1.3 framework sequences, where one or more framework sequences of MPK190-v1.3 are according to Martin (Enhanced Chothia).

[0229] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK190-v1.3, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to AbM, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK190-v1.3 and / or one or more framework sequences that are variants of MPK190-v1.3 framework sequences, where one or more framework sequences of MPK190-v1.3 are according to AbM.

[0230] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK190-v1.3, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to North, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK190-v1.3 and / or one or more framework sequences that are variants of MPK190-v1.3 framework sequences, where one or more framework sequences of MPK190-v1.3 are according to North.

[0231] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to Contact, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK190-v1.3 and / or one or more framework sequences that are variants of MPK190-v1.3 framework sequences, where one or more framework sequences of MPK190-v1.3 are according to Contact.

[0232] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK190-v1.3, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 conform to the CCG, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK190-v1.3 and / or one or more framework sequences that are variants of MPK190-v1.3 framework sequences, where one or more framework sequences of MPK190-v1.3 conform to the CCG.

[0233] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK190-v1.3, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to EU, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK190-v1.3 and / or one or more framework sequences that are variants of MPK190-v1.3 framework sequences, where one or more framework sequences of MPK190-v1.3 are according to EU.

[0234] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK190-v1.3, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to AHo, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK190-v1.3 and / or one or more framework sequences that are variants of MPK190-v1.3 framework sequences, where one or more framework sequences of MPK190-v1.3 are according to AHo.

[0235] In certain embodiments, the antibody or antigen-binding fragment comprises a VH comprising FR1, FR2, FR3, and / or FR4 of the VH amino acid sequence set forth in SEQ ID NO: 702 (or a variant of FR1, FR2, FR3, and / or FR4 comprising one, two, three, four, or five amino acid substitutions (optionally comprising or consisting of one or more conservative substitutions), insertions, and / or deletions), and a VL comprising FR1, FR2, FR3, and / or FR4 of the VL amino acid sequence set forth in SEQ ID NO: 704 (or a variant of FR1, FR2, FR3, and / or FR4 comprising one, two, three, four, or five amino acid substitutions (optionally comprising or consisting of one or more conservative substitutions), insertions, and / or deletions). In some embodiments, FRs are defined according to the IMGT, Kabat, Chothia, North, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, or AHo numbering systems, or any combination thereof.

[0236] In certain embodiments, the antibody or antigen-binding fragment comprises a FR1, FR2, FR3, and / or FR4 that has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprises or consists essentially of, a FR1, FR2, FR3, or FR4 of, the VH amino acid sequence set forth in SEQ ID NO:702; and a VL comprising FR1, FR2, FR3, and / or FR4 that have at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or consisting essentially of, or consisting of, respectively, FR1, FR2, FR3, or FR4 of the VL amino acid sequence set forth in SEQ ID NO: 704. In some embodiments, the FRs are defined according to the IMGT, Kabat, Chothia, North, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, or AHo numbering systems, or according to any combination thereof.

[0237] In certain embodiments, the antibody or antigen-binding fragment comprises a FR1, FR2, FR3, and FR4 that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or each FR1, FR2, FR3, or FR4 of, the VH amino acid sequence set forth in SEQ ID NO:702. and a VL comprising FR1, FR2, FR3, and FR4 that have at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of, respectively, FR1, FR2, FR3, or FR4 of SEQ ID NO: 704. In some embodiments, the FRs are defined according to the IMGT, Kabat, Chothia, North, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, or AHo numbering system, or according to any combination thereof.

[0238] In certain embodiments, antibodies or antigen-binding fragments of the present disclosure that bind RSV-F and MPV-F and / or neutralize RSV and MPV may comprise one or more VHs that bind RSV-F and MPV-F and may further comprise the CDRs of the VH sequence according to SEQ ID NO: 702, or may comprise one or more VLs that bind RSV-F and MPV-F and may further comprise the CDRs of the VL sequence according to SEQ ID NO: 704, wherein the CDRs are determined using any known CDR numbering method, including Kabat, Chothia, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, EU, or AHo numbering, or a combination of two or more of these IMGT, Martin (Enhanced Chothia), Contact, North, and AHo numbering methods. In certain embodiments, the CDRs are determined according to the IMGT numbering method.

[0239] An antibody or antigen-binding fragment of the disclosure that binds RSV-F and MPV-F and / or neutralizes RSV and MPV may comprise a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs) H1, CDRH2, and CDRH3, and a light chain variable domain (VL) comprising CDRL1, CDRL2, and CDRL3, wherein the CDRs are determined according to the IMGT numbering system, and (i) optionally, CDRH1 comprises or is derived from the amino acid sequence set forth in SEQ ID NO: 121, or a functional variant thereof comprising one, two, or three amino acid substitutions. wherein one or more of the substitutions are optionally conservative substitutions and / or substitutions relative to a germline-encoded amino acid; (ii) optionally, CDRH2 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 122, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative substitutions and / or substitutions relative to a germline-encoded amino acid; and (iii) optionally, CDRH3 comprises or consists of the amino acid sequence set forth in any of SEQ ID NO: 123, or a functional variant thereof comprising one, two, or three amino acid substitutions. (iv) optionally, CDRL1 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 18 or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or are substitutions relative to a germline encoded amino acid; (v) optionally, CDRL1 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 19 or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or are substitutions relative to a germline encoded amino acid; DRL2 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 705, or a functional variant thereof comprising one, two, or three amino acid substitutions, one or more of which are optionally conservative substitutions and / or substitutions relative to a germline-encoded amino acid; and / or (vi) optionally, CDRL3 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 127, or a functional variant thereof with one, two, or three amino acid substitutions, one or more of which are optionally conservative substitutions;and / or a substitution relative to a germline-encoded amino acid.

[0240] In specific embodiments, the antibody or antigen-binding fragment comprises i) a VH and VL, or CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 (either as set forth in this "MPK190-v1.3 Antibody" section, or otherwise set forth for the MPK190-v1.3 antibody, or as determined by any CDR determination scheme disclosed herein), and ii) an Fc portion. In certain embodiments, such an antibody or antigen-binding fragment comprises a CH and / or CL (potentially including a kappa light chain constant region) associated with a VH or VL, respectively, or a fragment thereof.

[0241] In specific embodiments, the antibody or antigen-binding fragment comprises a VH and VL, or a CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 (as shown in this "MPK190-v1.3 Antibody" section or otherwise referred to as MPK190-v1.3 antibodies or as determined by any CDR determination scheme disclosed herein), and (A) substitution mutations: (i) G236A, L328V, and Q295E, (ii) G236A, P230A, and Q295E, (iii) G236A, R292P, and I377N, (iv) G236A, K334A, and Q295E, (v) G236S, R292P, and Y300L, (vi) G236A and Y300L, (vii) G236A, R292P, and Y300L, (viii) G236S, G420V, G446E, and L309T, (ix) G236A and R292P, (x) R292P and Y300L, (xi) G236A and R292P, (xii) Y300L, (xiii) E345K, G236S, L235Y, and S267E, (xiv) E272R, L309T, S219Y, and S267E, (xv) G236Y, (xvi) G236W, (xvii) F243L, G446E, P396L, and S267E, (xviii) G236A, S239D, and H268E, (xix) M428L / N434S, (xx) M428L / N434A, (xxi) G236A / A330L / I332E / M428L / N434S, (xxii) G236A / A330L / I332E / M428L / N434A, or (xxiii) any two or more of (i) to (xxii), or (B) an Fc portion comprising at least 85%, at least 86%, at least 87%, at least 88%, or at least 89% of any one of SEQ ID NOs: 664 to 700. or an Fc portion comprising or consisting of an Fc polypeptide or a fragment thereof comprising or consisting of an amino acid sequence (optionally other than a naturally occurring variant thereof) having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to the Fc polypeptide or a fragment thereof, or comprising or consisting of an amino acid sequence set forth in any one of SEQ ID NOs: 672-700.

[0242] In certain embodiments, the antibody or antigen-binding fragment comprises i) a VH and VL, or CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 (either as set forth in this "MPK190-v1.3 Antibody" section, or as otherwise set forth for the MPK190-v1.3 antibody, or as determined by any CDR determination scheme disclosed herein), and ii) a sequence according to any one of SEQ ID NOs: 679-684 and 688-690, or SEQ ID NOs: 679-684 and 688-691. 690, or an Fc portion comprising or consisting of an Fc polypeptide or a fragment thereof, comprising or consisting of an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to a sequence according to any one of

[0243] In certain embodiments, the antibody or antigen-binding fragment comprises the MPK190-rIG1m3-LS antibody, the HC of which has the amino acid sequence of SEQ ID NO: 719 and may be encoded by a nucleic acid having the sequence of SEQ ID NO: 718, and the LC of which has the amino acid sequence of SEQ ID NO: 721 and may be encoded by a nucleic acid having the sequence of SEQ ID NO: 720.

[0244] In certain embodiments, the antibody or antigen-binding fragment comprises the MPK190-v1.3-rIG1m17,1-LS antibody, the HC of which has the amino acid sequence of SEQ ID NO: 723 and may be encoded by a nucleic acid having the sequence of SEQ ID NO: 722, and the LC of which has the amino acid sequence of SEQ ID NO: 725 and may be encoded by a nucleic acid having the sequence of SEQ ID NO: 724 or 904.

[0245] In certain embodiments, the antibody or antigen-binding fragment comprises a VH and VL, or CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 (either as set forth in this "MPK190-v1.3 Antibody" section, or otherwise set forth for the MPK190-v1.3 antibody, or as determined by any CDR determination scheme disclosed herein), and exhibits a synergistic effect in neutralizing or treating and / or preventing infection by RSV when co-administered with at least one of MPK65-v2-v1.2, MPK65-v2-v.3.1, MPK176-v1.3, MPK176-v4.3, MPK201-v1.2, and MPK201-v4.1.

[0246] MPK65-v2-v1.2 antibody In some embodiments, the antibody or antigen-binding fragment of the present disclosure is an MPK65-v2-v1.2 antibody or antigen-binding fragment thereof. Such an antibody or antigen-binding fragment thereof may bind and / or neutralize RSV.

[0247] In some embodiments, the MPK65-v2-v1.2 antibody may have a VH, VL, CDRH1-H3, and / or CDRL1-L3 that comprise or consist of an amino acid sequence, or that are encoded by a polynucleotide having the following sequence:

[0248] [Table 3]

[0249] In some embodiments, the VH and VL of the MPK65-v2-v1.2 antibody or antigen-binding fragment that binds RSV-F and / or neutralizes RSV and / or RSV comprises or consists of a VH and VL having the sequences of SEQ ID NOs: 136 and 851, respectively.

[0250] In certain embodiments, the antibodies or antigen-binding fragments of the present disclosure bind RSV-F and / or neutralize RSV, (i) the VH comprises or consists of an amino acid sequence having at least 80% (e.g., 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to the amino acid sequence set forth in SEQ ID NO: 136, wherein the sequence diversity is optionally limited to one or more framework regions, and / or the sequence diversity includes one or more substitutions relative to a germline-encoded amino acid; and / or (ii) the VL comprises or consists of an amino acid sequence having at least 80% (e.g., 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to the amino acid sequence set forth in SEQ ID NO: 851, wherein the sequence diversity is optionally limited to one or more framework regions and / or the sequence diversity comprises one or more substitutions relative to a germline-encoded amino acid.

[0251] In some embodiments, the diversity compared to SEQ ID NO: 136 or SEQ ID NO: 851 is limited to one or more framework regions. In some embodiments, the diversity comprises or consists of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions (any or all of which may be conservative substitutions), insertions, or deletions in VH, VL, or both. In some embodiments, the diversity comprises one or more amino acid substitutions, insertions, and / or deletions of amino acids 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or more amino acid positions away from the N-terminal and / or C-terminal amino acid of the CDR.

[0252] Framework regions can be identified according to a numbering scheme (e.g., IMGT, Kabat, Chothia, North, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, EU, or AHo, or a combination of two or more thereof). CDRs can be identified within a variable domain or within a heavy or light chain according to a numbering scheme or combination of numbering schemes, and preferably, FRs can be identified using the same numbering scheme or combination of numbering schemes.

[0253] For example, in some embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK65-v2-v1.2, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 conform to IMGT (optionally an IMGT junction for CDRH3 and CDRL3), and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK65-v2-v1.2 and / or one or more framework sequences that are variants of MPK65-v2-v1.2 framework sequences, where one or more framework sequences of MPK65-v2-v1.2 conform to IMGT (and if an IMGT junction is used for CDRH3 and CDRL3, this is taken into consideration).

[0254] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK65-v2-v1.2, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to Kabat, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK65-v2-v1.2 and / or one or more framework sequences that are variants of MPK65-v2-v1.2 framework sequences, where one or more framework sequences of MPK65-v2-v1.2 are according to Kabat.

[0255] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK65-v2-v1.2, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to Chothia, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK65-v2-v1.2 and / or one or more framework sequences that are variants of MPK65-v2-v1.2 framework sequences, where one or more framework sequences of MPK65-v2-v1.2 are according to Chothia.

[0256] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK65-v2-v1.2, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to Martin (Enhanced Chothia), and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK65-v2-v1.2 and / or one or more framework sequences that are variants of MPK65-v2-v1.2 framework sequences, where one or more framework sequences of MPK65-v2-v1.2 are according to Martin (Enhanced Chothia).

[0257] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK65-v2-v1.2, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to AbM, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK65-v2-v1.2 and / or one or more framework sequences that are variants of MPK65-v2-v1.2 framework sequences, where one or more framework sequences of MPK65-v2-v1.2 are according to AbM.

[0258] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK65-v2-v1.2, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to North, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK65-v2-v1.2 and / or one or more framework sequences that are variants of MPK65-v2-v1.2 framework sequences, where one or more framework sequences of MPK65-v2-v1.2 are according to North.

[0259] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to Contact, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK65-v2-v1.2 and / or one or more framework sequences that are variants of MPK65-v2-v1.2 framework sequences, where one or more framework sequences of MPK65-v2-v1.2 are according to Contact.

[0260] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK65-v2-v1.2, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 conform to the CCG, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK65-v2-v1.2 and / or one or more framework sequences that are variants of MPK65-v2-v1.2 framework sequences, where one or more framework sequences of MPK65-v2-v1.2 conform to the CCG.

[0261] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK65-v2-v1.2, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to EU, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK65-v2-v1.2 and / or one or more framework sequences that are variants of MPK65-v2-v1.2 framework sequences, where one or more framework sequences of MPK65-v2-v1.2 are according to EU.

[0262] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK65-v2-v1.2, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to AHo, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK65-v2-v1.2 and / or one or more framework sequences that are variants of MPK65-v2-v1.2 framework sequences, where one or more framework sequences of MPK65-v2-v1.2 are according to AHo.

[0263] In certain embodiments, the antibody or antigen-binding fragment comprises a VH comprising FR1, FR2, FR3, and / or FR4 of the VH amino acid sequence set forth in SEQ ID NO: 136 (or a variant of FR1, FR2, FR3, and / or FR4 comprising one, two, three, four, or five amino acid substitutions (optionally comprising or consisting of one or more conservative substitutions), insertions, and / or deletions), and a VL comprising FR1, FR2, FR3, and / or FR4 of the VL amino acid sequence set forth in SEQ ID NO: 851 (or a variant of FR1, FR2, FR3, and / or FR4 comprising one, two, three, four, or five amino acid substitutions (optionally comprising or consisting of one or more conservative substitutions), insertions, and / or deletions). In some embodiments, FRs are defined according to the IMGT, Kabat, Chothia, North, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, or AHo numbering systems, or any combination thereof.

[0264] In certain embodiments, the antibody or antigen-binding fragment comprises a FR1, FR2, FR3, and / or FR4 that has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprises or consists essentially of, a FR1, FR2, FR3, or FR4 of, the VH amino acid sequence set forth in SEQ ID NO: 136; and a VL comprising FR1, FR2, FR3, and / or FR4 that have at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or consisting essentially of, or consisting of, respectively, FR1, FR2, FR3, or FR4 of the VL amino acid sequence set forth in SEQ ID NO: 851. In some embodiments, the FRs are defined according to the IMGT, Kabat, Chothia, North, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, or AHo numbering systems, or according to any combination thereof.

[0265] In certain embodiments, the antibody or antigen-binding fragment comprises FR1, FR2, FR3, and FR4 that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, or comprise or consist of, the respective FR1, FR2, FR3, or FR4 of the VH amino acid sequence set forth in SEQ ID NO: 136. and a VL comprising FR1, FR2, FR3, and FR4 that have at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of, respectively, FR1, FR2, FR3, or FR4 of SEQ ID NO: 851. In some embodiments, the FRs are defined according to the IMGT, Kabat, Chothia, North, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, or AHo numbering system, or according to any combination thereof.

[0266] In certain embodiments, antibodies or antigen-binding fragments of the present disclosure that bind RSV-F and / or neutralize RSV may include one or more VHs that bind RSV-F and may further include a CDR of a VH sequence according to SEQ ID NO: 136, or may include one or more VLs that bind RSV-F and may further include a CDR of a VL sequence according to SEQ ID NO: 851, wherein the CDRs are determined using any known CDR numbering method, including Kabat, Chothia, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, EU, or AHo numbering, or a combination of two or more of these IMGT, Martin (Enhanced Chothia), Contact, North, and AHo numbering methods. In certain embodiments, the CDRs are determined according to the IMGT numbering method. In certain embodiments, the CDRs are determined according to the antibody numbering method developed by the Chemical Computing Group (CCG), for example, using Molecular Operating Environment (MOE) software. In certain embodiments, the CDRs follow the Kabat numbering system. In certain embodiments, the CDRs follow the AHo numbering system. In certain embodiments, the CDRs follow the North numbering system.

[0267] An antibody or antigen-binding fragment of the present disclosure that binds RSV-F and / or neutralizes RSV may comprise a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs) H1, CDRH2, and CDRH3, and a light chain variable domain (VL) comprising CDRL1, CDRL2, and CDRL3, wherein the CDRs are determined according to the IMGT numbering system, and (i) optionally, CDRH1 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 137, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are any (ii) optionally, CDRH2 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 138 or a functional variant thereof containing one, two, or three amino acid substitutions, one or more of which are optionally conservative substitutions and / or substitutions relative to germline-encoded amino acids; and (iii) optionally, CDRH3 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 139 or a functional variant thereof containing one, two, or three amino acid substitutions. (iv) optionally, CDRL1 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 142 or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or substitutions relative to a germline-encoded amino acid; (v) optionally, CDRL2 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 143, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or substitutions relative to a germline-encoded amino acid; or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or relative to a germline-encoded amino acid; and / or (vi) optionally, CDRL3 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 852, or a functional variant thereof having one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or relative to a germline-encoded amino acid.

[0268] In specific embodiments, the antibody or antigen-binding fragment comprises i) a VH and VL, or CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 (either as set forth in this "MPK65-v2-v1.2 Antibody" section, or otherwise set forth for the MPK65-v2-v1.2 antibody, or as determined by any CDR determination scheme disclosed herein), and ii) an Fc portion. In certain embodiments, such an antibody or antigen-binding fragment comprises a CH and / or CL (potentially including a kappa light chain constant region) associated with a VH or VL, respectively, or a fragment thereof.

[0269] In specific embodiments, the antibody or antigen-binding fragment comprises a VH and VL, or a CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 (as shown in this "MPK65-v2-v1.2 Antibody" section or otherwise referred to as MPK65-v2-v1.2 antibodies or determined by any CDR determination scheme disclosed herein), and (A) substitution mutations: (i) G236A, L328V, and Q295E, (ii) G236A, P230A, and Q295E, (iii) G236A, R292P, and I377N, (iv) G236A, K334A, and Q295E, (v) G236S, R292P, and Y300L, (vi) G236A and Y300L, (vii) G236A, R292P, and Y300L, (viii) G236S, G420V, G446E, and L309T, (ix) G236A and R292P, (x) R292P and Y300L, (xi) G236A and R292P, (xii) Y300L, (xiii) E345K, G236S, L235Y, and S267E, (xiv) E272R, L309T, S219Y, and S267E, (xv) G236Y, (xvi) G236W, (xvii) F243L, G446E, P396L, and S267E, (xviii) G236A, S239D, and H268E, (xix) M428L / N434S, (xx) M428L / N434A, (xxi) G236A / A330L / I332E / M428L / N434S, (xxii) G236A / A330L / I332E / M428L / N434A, or (xxiii) any two or more of (i) to (xxii), or (B) an Fc portion comprising at least 85%, at least 86%, at least 87%, at least 88%, or at least 89% of any one of SEQ ID NOs: 664 to 700. or an Fc portion comprising or consisting of an Fc polypeptide or a fragment thereof comprising or consisting of an amino acid sequence (optionally other than a naturally occurring variant thereof) having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to the Fc polypeptide or a fragment thereof, or comprising or consisting of an amino acid sequence set forth in any one of SEQ ID NOs: 672-700.

[0270] In certain embodiments, the antibody or antigen-binding fragment comprises i) a VH and VL, or CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 (either as set forth in this "MPK65-v2-v1.2 Antibody" section, or as otherwise set forth for the MPK65-v2-v1.2 antibody, or as determined by any CDR determination scheme disclosed herein), and ii) a sequence according to any one of SEQ ID NOs: 679-684 and 688-690, or SEQ ID NOs: 679-684 and 688-690. 8 to 690, or an Fc portion comprising or consisting of an Fc polypeptide or a fragment thereof, comprising or consisting of an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to a sequence according to any one of

[0271] In certain embodiments, the antibody or antigen-binding fragment comprises the MPK65-v2-v1.2-rIG1m3-LS antibody.

[0272] In certain embodiments, the antibody or antigen-binding fragment comprises the MPK65-v2-v1.2-rIG1m17,1-LS antibody.

[0273] MPK65-v2-v3.1 antibody In some embodiments, the antibody or antigen-binding fragment of the present disclosure is an MPK65-v2-v3.1 antibody or antigen-binding fragment thereof. Such an antibody or antigen-binding fragment thereof may bind and / or neutralize RSV.

[0274] In some embodiments, the MPK65-v2-v3.1 antibody may have a VH, VL, CDRH1-H3, and / or CDRL1-L3 that comprise or consist of an amino acid sequence, or that are encoded by a polynucleotide having the following sequence:

[0275] [Table 4]

[0276] In some embodiments, the VH and VL of the MPK65-v2-v3.1 antibody or antigen-binding fragment that binds RSV-F and / or neutralizes RSV and / or RSV comprises or consists of a VH and VL having the sequences of SEQ ID NOs: 817 and 141, respectively.

[0277] In certain embodiments, the antibodies or antigen-binding fragments of the present disclosure bind RSV-F and / or neutralize RSV, (i) the VH comprises or consists of an amino acid sequence having at least 80% (e.g., 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to the amino acid sequence set forth in SEQ ID NO: 817, wherein the sequence diversity is optionally limited to one or more framework regions, and / or the sequence diversity includes one or more substitutions relative to a germline-encoded amino acid; and / or (ii) the VL comprises or consists of an amino acid sequence having at least 80% (e.g., 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to the amino acid sequence set forth in SEQ ID NO: 141, wherein the sequence diversity is optionally limited to one or more framework regions and / or the sequence diversity comprises one or more substitutions relative to a germline-encoded amino acid.

[0278] In some embodiments, the diversity compared to SEQ ID NO:817 or SEQ ID NO:141 is limited to one or more framework regions. In some embodiments, the diversity comprises or consists of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions (any or all of which may be conservative substitutions), insertions, or deletions in VH, VL, or both. In some embodiments, the diversity comprises one or more amino acid substitutions, insertions, and / or deletions of amino acids 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or more amino acid positions away from the N-terminal and / or C-terminal amino acid of the CDR.

[0279] Framework regions can be identified according to a numbering scheme (e.g., IMGT, Kabat, Chothia, North, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, EU, or AHo, or a combination of two or more thereof). CDRs can be identified within a variable domain or within a heavy or light chain according to a numbering scheme or combination of numbering schemes, and preferably, FRs can be identified using the same numbering scheme or combination of numbering schemes.

[0280] For example, in some embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK65-v2-v3.1, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 conform to IMGT (optionally an IMGT junction for CDRH3 and CDRL3), and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK65-v2-v3.1 and / or one or more framework sequences that are variants of MPK65-v2-v3.1 framework sequences, where one or more framework sequences of MPK65-v2-v3.1 conform to IMGT (and if an IMGT junction is used for CDRH3 and CDRL3, this is taken into consideration).

[0281] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK65-v2-v3.1, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to Kabat, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK65-v2-v3.1 and / or one or more framework sequences that are variants of MPK65-v2-v3.1 framework sequences, where one or more framework sequences of MPK65-v2-v3.1 are according to Kabat.

[0282] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK65-v2-v3.1, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to Chothia, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK65-v2-v3.1 and / or one or more framework sequences that are variants of MPK65-v2-v3.1 framework sequences, where one or more framework sequences of MPK65-v2-v3.1 are according to Chothia.

[0283] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK65-v2-v3.1, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to Martin (Enhanced Chothia), and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK65-v2-v3.1 and / or one or more framework sequences that are variants of MPK65-v2-v3.1 framework sequences, where one or more framework sequences of MPK65-v2-v3.1 are according to Martin (Enhanced Chothia).

[0284] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK65-v2-v3.1, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to AbM, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK65-v2-v3.1 and / or one or more framework sequences that are variants of MPK65-v2-v3.1 framework sequences, where one or more framework sequences of MPK65-v2-v3.1 are according to AbM.

[0285] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK65-v2-v3.1, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to North, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK65-v2-v3.1 and / or one or more framework sequences that are variants of MPK65-v2-v3.1 framework sequences, where one or more framework sequences of MPK65-v2-v3.1 are according to North.

[0286] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to Contact, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK65-v2-v3.1 and / or one or more framework sequences that are variants of MPK65-v2-v3.1 framework sequences, where one or more framework sequences of MPK65-v2-v3.1 are according to Contact.

[0287] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK65-v2-v3.1, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 conform to the CCG, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK65-v2-v3.1 and / or one or more framework sequences that are variants of MPK65-v2-v3.1 framework sequences, where one or more framework sequences of MPK65-v2-v3.1 conform to the CCG.

[0288] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK65-v2-v3.1, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are in accordance with EU, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK65-v2-v3.1 and / or one or more framework sequences that are variants of MPK65-v2-v3.1 framework sequences, where one or more framework sequences of MPK65-v2-v3.1 are in accordance with EU.

[0289] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK65-v2-v3.1, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to AHo, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK65-v2-v3.1 and / or one or more framework sequences that are variants of MPK65-v2-v3.1 framework sequences, where one or more framework sequences of MPK65-v2-v3.1 are according to AHo.

[0290] In certain embodiments, the antibody or antigen-binding fragment comprises a VH comprising FR1, FR2, FR3, and / or FR4 of the VH amino acid sequence set forth in SEQ ID NO: 817 (or a variant of FR1, FR2, FR3, and / or FR4 comprising one, two, three, four, or five amino acid substitutions (optionally comprising or consisting of one or more conservative substitutions), insertions, and / or deletions) and a VL comprising FR1, FR2, FR3, and / or FR4 of the VL amino acid sequence set forth in SEQ ID NO: 141 (or a variant of FR1, FR2, FR3, and / or FR4 comprising one, two, three, four, or five amino acid substitutions (optionally comprising or consisting of one or more conservative substitutions), insertions, and / or deletions). In some embodiments, FRs are defined according to the IMGT, Kabat, Chothia, North, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, or AHo numbering systems, or any combination thereof.

[0291] In certain embodiments, the antibody or antigen-binding fragment comprises a FR1, FR2, FR3, and / or FR4 that has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprises or consists essentially of, a FR1, FR2, FR3, or FR4 of, the VH amino acid sequence set forth in SEQ ID NO:817; and a VL comprising FR1, FR2, FR3, and / or FR4 that have at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or consisting essentially of, or consisting of, respectively, FR1, FR2, FR3, or FR4 of the VL amino acid sequence set forth in SEQ ID NO: 141. In some embodiments, the FRs are defined according to the IMGT, Kabat, Chothia, North, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, or AHo numbering systems, or according to any combination thereof.

[0292] In certain embodiments, the antibody or antigen-binding fragment comprises a VH comprising FR1, FR2, FR3, and FR4 that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, respectively, FR1, FR2, FR3, or FR4 of the VH amino acid sequence set forth in SEQ ID NO: 817, and a VL comprising FR1, FR2, FR3, and FR4 that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, respectively, FR1, FR2, FR3, or FR4 of SEQ ID NO: 141. In some embodiments, FRs are defined according to the IMGT, Kabat, Chothia, North, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, or AHo numbering systems, or any combination thereof.

[0293] In certain embodiments, antibodies or antigen-binding fragments of the present disclosure that bind RSV-F and / or neutralize RSV may include one or more VHs that bind RSV-F and may further include a CDR of a VH sequence according to SEQ ID NO: 817, or may include one or more VLs that bind RSV-F and may further include a CDR of a VL sequence according to SEQ ID NO: 141, wherein the CDRs are determined using any known CDR numbering method, including Kabat, Chothia, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, EU, or AHo numbering, or a combination of two or more of these IMGT, Martin (Enhanced Chothia), Contact, North, and AHo numbering methods. In certain embodiments, the CDRs are determined according to the IMGT numbering method. In certain embodiments, the CDRs are determined according to the antibody numbering method developed by the Chemical Computing Group (CCG), for example, using Molecular Operating Environment (MOE) software. In certain embodiments, the CDRs follow the Kabat numbering system. In certain embodiments, the CDRs follow the AHo numbering system. In certain embodiments, the CDRs follow the North numbering system.

[0294] An antibody or antigen-binding fragment of the present disclosure that binds RSV-F and / or neutralizes RSV may comprise a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs) H1, CDRH2, and CDRH3, and a light chain variable domain (VL) comprising CDRL1, CDRL2, and CDRL3, wherein the CDRs are determined according to the IMGT numbering system, and (i) optionally, CDRH1 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 814, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are any (ii) optionally, CDRH2 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 818 or a functional variant thereof containing one, two, or three amino acid substitutions, one or more of which are optionally conservative substitutions and / or substitutions relative to germline-encoded amino acids; and (iii) optionally, CDRH3 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 139 or a functional variant thereof containing one, two, or three amino acid substitutions. (iv) optionally, CDRL1 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 142 or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or substitutions relative to a germline-encoded amino acid; (v) optionally, CDRL2 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 143, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or substitutions relative to a germline-encoded amino acid; or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or relative to a germline-encoded amino acid; and / or (vi) optionally, CDRL3 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 144, or a functional variant thereof having one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or relative to a germline-encoded amino acid.

[0295] In specific embodiments, the antibody or antigen-binding fragment comprises i) a VH and VL, or CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 (either as set forth in this "MPK65-v2-v3.1 Antibody" section, or otherwise set forth for the MPK65-v2-v3.1 antibody, or as determined by any CDR determination scheme disclosed herein), and ii) an Fc portion. In certain embodiments, such an antibody or antigen-binding fragment comprises a CH and / or CL (potentially including a kappa light chain constant region) associated with a VH or VL, respectively, or a fragment thereof.

[0296] In specific embodiments, the antibody or antigen-binding fragment comprises a VH and VL, or a CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 (as shown in this "MPK65-v2-v3.1 Antibody" section or otherwise referred to as MPK65-v2-v3.(i) G236A, L328V, and Q295E; (ii) G236A, P230A, and Q295E; (iii) G236A, R292P, and I377N; (iv) G236A, K334A, and Q295E; (v) G236S, R292P, and Y300L; (vi) G236A and Y300L; (vii) G236A, R292P, and Y300L; (viii) G236S, G420V, G446E, and L309T, (ix) G236A and R292P, (x) R292P and Y300L, (xi) G236A and R292P, (xii) Y300L, (xiii) E345K, G236S, L235Y, and S267E, (xiv) E272R, L309T, S219Y, and S267E, (xv) G236Y, (xvi) G236W, (xvii) F243L, G446E, P396L, and S267E, (xviii) G236A, S239D, and H268E, (xix) M428L / N434S, (xx) M428L / N434A, (xxi) G236A / A330L / I332E / M428L / N434S, (xxii) G236A / A330L / I332E / M428L / N434A, or (xxiii) any two or more of (i) to (xxii), or (B) an Fc portion comprising at least 85%, at least 86%, at least 87%, at least 88%, or at least 89% of any one of SEQ ID NOs: 664 to 700. or an Fc portion comprising or consisting of an Fc polypeptide or a fragment thereof comprising or consisting of an amino acid sequence (optionally other than a naturally occurring variant thereof) having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to the Fc polypeptide or a fragment thereof, or comprising or consisting of an amino acid sequence set forth in any one of SEQ ID NOs: 672-700.

[0297] In certain embodiments, the antibody or antigen-binding fragment comprises i) a VH and VL, or CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 (either as set forth in this "MPK65-v2-v3.1 Antibody" section, or as otherwise set forth for the MPK65-v2-v3.1 antibody, or as determined by any CDR determination scheme disclosed herein), and ii) a sequence according to any one of SEQ ID NOs: 679-684 and 688-690, or SEQ ID NOs: 679-684 and 688-690. 8 to 690, or an Fc portion comprising or consisting of an Fc polypeptide or a fragment thereof, comprising or consisting of an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to a sequence according to any one of

[0298] In certain embodiments, the antibody or antigen-binding fragment comprises the MPK65-v2-v3.1-rIG1m3-LS antibody.

[0299] In certain embodiments, the antibody or antigen-binding fragment comprises the MPK65-v2-v3.1-rIG1m17,1-LS antibody.

[0300] MPK176-v1.3 antibody In some embodiments, the antibody or antigen-binding fragment of the present disclosure is an MPK176-v1.3 antibody or antigen-binding fragment thereof. Such an antibody or antigen-binding fragment thereof may bind and / or neutralize RSV.

[0301] In some embodiments, the MPK176-v1.3 antibody may have a VH, VL, CDRH1-H3, and / or CDRL1-L3 that comprise or consist of an amino acid sequence, or that are encoded by a polynucleotide having the following sequence:

[0302] [Table 5]

[0303] In some embodiments, the VH and VL of the MPK176-v1.3 antibody or antigen-binding fragment that binds RSV-F and / or neutralizes RSV and / or RSV comprises or consists of a VH and VL having the sequences of SEQ ID NOs: 233 and 858, respectively.

[0304] In certain embodiments, the antibodies or antigen-binding fragments of the present disclosure bind RSV-F and / or neutralize RSV, (i) the VH comprises or consists of an amino acid sequence having at least 80% (e.g., 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to the amino acid sequence set forth in SEQ ID NO: 233, wherein the sequence diversity is optionally limited to one or more framework regions, and / or the sequence diversity includes one or more substitutions relative to a germline-encoded amino acid; and / or (ii) the VL comprises or consists of an amino acid sequence having at least 80% (e.g., 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity to the amino acid sequence set forth in SEQ ID NO: 858, wherein the sequence diversity is optionally limited to one or more framework regions and / or the sequence diversity comprises one or more substitutions relative to a germline-encoded amino acid.

[0305] In some embodiments, the diversity compared to SEQ ID NO:233 or SEQ ID NO:858 is limited to one or more framework regions. In some embodiments, the diversity comprises or consists of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions (any or all of which may be conservative substitutions), insertions, or deletions in VH, VL, or both. In some embodiments, the diversity comprises one or more amino acid substitutions, insertions, and / or deletions of amino acids 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or more amino acid positions away from the N-terminal and / or C-terminal amino acid of the CDR.

[0306] Framework regions can be identified according to a numbering scheme (e.g., IMGT, Kabat, Chothia, North, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, EU, or AHo, or a combination of two or more thereof). CDRs can be identified within a variable domain or within a heavy or light chain according to a numbering scheme or combination of numbering schemes, and preferably, FRs can be identified using the same numbering scheme or combination of numbering schemes.

[0307] For example, in some embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK176-v1.3, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 conform to IMGT (optionally an IMGT junction for CDRH3 and CDRL3), and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK176-v1.3 and / or one or more framework sequences that are variants of MPK176-v1.3 framework sequences, where one or more framework sequences of MPK176-v1.3 conform to IMGT (and if an IMGT junction is used for CDRH3 and CDRL3, this is taken into consideration).

[0308] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK176-v1.3, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to Kabat, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK176-v1.3 and / or one or more framework sequences that are variants of MPK176-v1.3 framework sequences, where one or more framework sequences of MPK176-v1.3 are according to Kabat.

[0309] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK176-v1.3, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to Chothia, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK176-v1.3 and / or one or more framework sequences that are variants of MPK176-v1.3 framework sequences, where one or more framework sequences of MPK176-v1.3 are according to Chothia.

[0310] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK176-v1.3, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to Martin (Enhanced Chothia), and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK176-v1.3 and / or one or more framework sequences that are variants of MPK176-v1.3 framework sequences, where one or more framework sequences of MPK176-v1.3 are according to Martin (Enhanced Chothia).

[0311] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK176-v1.3, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to AbM, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK176-v1.3 and / or one or more framework sequences that are variants of MPK176-v1.3 framework sequences, where one or more framework sequences of MPK176-v1.3 are according to AbM.

[0312] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK176-v1.3, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to North, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK176-v1.3 and / or one or more framework sequences that are variants of MPK176-v1.3 framework sequences, where one or more framework sequences of MPK176-v1.3 are according to North.

[0313] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to Contact, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK176-v1.3 and / or one or more framework sequences that are variants of MPK176-v1.3 framework sequences, where one or more framework sequences of MPK176-v1.3 are according to Contact.

[0314] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK176-v1.3, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 conform to the CCG, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK176-v1.3 and / or one or more framework sequences that are variants of MPK176-v1.3 framework sequences, where one or more framework sequences of MPK176-v1.3 conform to the CCG.

[0315] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK176-v1.3, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to EU, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK176-v1.3 and / or one or more framework sequences that are variants of MPK176-v1.3 framework sequences, where one or more framework sequences of MPK176-v1.3 are according to EU.

[0316] In other embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of MPK176-v1.3, where CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are according to AHo, and the antibody or antigen-binding fragment further comprises one or more framework sequences from MPK176-v1.3 and / or one or more framework sequences that are variants of MPK176-v1.3 framework sequences, where one or more framework sequences of MPK176-v1.3 are according to AHo.

[0317] In certain embodiments, the antibody or antigen-binding fragment comprises a VH comprising FR1, FR2, FR3, and / or FR4 of the VH amino acid sequence set forth in SEQ ID NO: 233 (or a variant of FR1, FR2, FR3, and / or FR4 comprising one, two, three, four, or five amino acid substitutions (optionally comprising or consisting of one or more conservative substitutions), insertions, and / or deletions) and a VL comprising FR1, FR2, FR3, and / or FR4 of the VL amino acid sequence set forth in SEQ ID NO: 858 (or a variant of FR1, FR2, FR3, and / or FR4 comprising one, two, three, four, or five amino acid substitutions (optionally comprising or consisting of one or more conservative substitutions), insertions, and / or deletions). In some embodiments, FRs are defined according to the IMGT, Kabat, Chothia, North, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, or AHo numbering systems, or any combination thereof.

[0318] In certain embodiments, the antibody or antigen-binding fragment comprises a FR1, FR2, FR3, and / or FR4 that has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprises or consists essentially of, a FR1, FR2, FR3, or FR4 of, the VH amino acid sequence set forth in SEQ ID NO:233; and a VL comprising FR1, FR2, FR3, and / or FR4 that have at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or consisting essentially of, or consisting of, respectively, FR1, FR2, FR3, or FR4 of the VL amino acid sequence set forth in SEQ ID NO: 858. In some embodiments, the FRs are defined according to the IMGT, Kabat, Chothia, North, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, or AHo numbering systems, or according to any combination thereof.

[0319] In certain embodiments, the antibody or antigen-binding fragment comprises a VH comprising FR1, FR2, FR3, and FR4 that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, respectively, FR1, FR2, FR3, or FR4 of the VH amino acid sequence set forth in SEQ ID NO: 233, and a VL comprising FR1, FR2, FR3, and FR4 that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to, respectively, FR1, FR2, FR3, or FR4 of SEQ ID NO: 858. In some embodiments, FRs are defined according to the IMGT, Kabat, Chothia, North, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, or AHo numbering systems, or any combination thereof.

[0320] In certain embodiments, antibodies or antigen-binding fragments of the present disclosure that bind RSV-F and / or neutralize RSV may include one or more VHs that bind RSV-F and may further include a CDR of a VH sequence according to SEQ ID NO: 233, or one or more VLs that bind RSV-F and may further include a CDR of a VL sequence according to SEQ ID NO: 858, wherein the CDRs are determined using any known CDR numbering method, including Kabat, Chothia, EU, Martin (Enhanced Chothia), Contact, AbM, CCG, EU, or AHo numbering, or a combination of two or more of these IMGT, Martin (Enhanced Chothia), Contact, North, and AHo numbering methods. In certain embodiments, the CDRs are determined according to the IMGT numbering method. In certain embodiments, the CDRs are determined according to the antibody numbering method developed by the Chemical Computing Group (CCG), for example, using Molecular Operating Environment (MOE) software. In certain embodiments, the CDRs follow the Kabat numbering system. In certain embodiments, the CDRs follow the AHo numbering system. In certain embodiments, the CDRs follow the North numbering system.

[0321] An antibody or antigen-binding fragment of the present disclosure that binds RSV-F and / or neutralizes RSV may comprise a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs) H1, CDRH2, and CDRH3, and a light chain variable domain (VL) comprising CDRL1, CDRL2, and CDRL3, wherein the CDRs are determined according to the IMGT numbering system, and (i) optionally, CDRH1 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 234, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are any (ii) optionally, CDRH2 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 235 or a functional variant thereof containing one, two, or three amino acid substitutions, one or more of which are optionally conservative substitutions and / or substitutions relative to germline-encoded amino acids; and (iii) optionally, CDRH3 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 236 or a functional variant thereof containing one, two, or three amino acid substitutions. (iv) optionally, CDRL1 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 239 or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or substitutions relative to a germline-encoded amino acid; (v) optionally, CDRL2 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 240, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or substitutions relative to a germline-encoded amino acid; or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or relative to a germline-encoded amino acid; and / or (vi) optionally, CDRL3 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 241 or a functional variant thereof having one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conservative and / or relative to a germline-encoded amino acid.

[0322] In specific embodiments, the antibody or antigen-binding...

Claims

1. An antibody or antigen-binding fragment comprising a heavy chain variable domain (VH) containing complementarity-determining regions (CDRs) H1, CDRH2, and CDRH3, and a light chain variable domain (VL) containing CDRL1, CDRL2, and CDRL3, wherein the antibody or antigen-binding fragment binds to respiratory syncytial virus (RSV) fusion glycoprotein (RSV-F), and the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are numbered according to the IMGT numbering system, and (i) Sequence IDs 121, 122, 123, 18, 705 and 127; (ii) Sequence IDs 130, 47, 131, 18, 117 and 134; (iii) Sequence IDs 13-15 and 18-20; (iv) Sequence IDs 39, 40, 25, 18, 43 and 44; (v) Sequence IDs 39, 47, 48, 18, 19 and 51; (vi) Sequence IDs 55, 24, 25, 18, 43 and 57; (vii) Sequence IDs 60-62 and 65-67; (viiii) Sequence IDs 39, 40, 25, 18, 43 and 44; (ix) Sequence IDs 121-123, 126, 117 and 127; (x) Sequence IDs 74, 24, 48, 18, 19 and 77; (xi) Sequence IDs 80, 81, 25, 18, 19 and 84; (xi) Sequence IDs 87-89, 92, 19 and 93; (xiiii) Sequence IDs 39, 96, 48, 99, 19 and 44; (xiv) Sequence IDs 23-25, 18, 19 and 28; (xv) Sequence IDs 112-114, 18, 117 and 118; (xvi) Sequence IDs 31-33, 18, 19 and 36; (xvii) Sequence IDs 380, 81, 25, 383, 19 and 384; (xviiii) Sequence IDs 387-389, 18, 392 and 393; (xix) Sequence IDs 396-398, 401, 19 and 402; (xx) Sequence IDs 80, 405, 406, 18, 409 and 410; (xxi) Sequence IDs 87-89, 401, 19 and 402; (xxii) Sequence IDs 417, 24, 48, 18, 19 and 420; (xxiii) Sequence IDs 396-398, 401, 19 and 402; (xxiv) Sequence IDs 39, 40, 427, 401, 19 and 28; (xxv) Sequence IDs 130, 47, 432, 18, 117 and 134; (xxvi) Sequence IDs 130, 47, 432, 437, 43 and 438; (xxvii) Sequence numbers 441, 442, 48, 445, 19 and 446; (xxviiii) Sequence IDs 130, 47, 432, 18, 117 and 134; (xxx) Sequence numbers 452, 453, 48, 456, 19 and 384; (xxx) Sequence IDs 459, 24, 25, 18, 19 and 402; (xxxi) Sequence IDs 87, 464, 89, 401, 467, and 468; (xxxii) Sequence IDs 471, 81, 25, 445, 19 and 384; (xxxiii) Sequence IDs 471, 40, 476, 18, 19 and 51; (xxxiv) Sequence IDs 481, 88, 48, 18, 19 and 51; (xxxv) Sequence IDs 87, 88, 25, 488, 489 and 402; (xxxvi) Sequence IDs 492, 47, 493, 18, 19 and 384; (xxxvii) Sequence IDs 498, 47, 499, 18, 467 and 502; (xxxviiii) Sequence IDs 505, 506, 507, 18, 510 and 511; (xxxix) Sequence IDs 514, 515, 516, 18, 519 and 520; (xxxx) Sequence IDs 121-123, 126, 117 and 127; (xxxxi) Sequence IDs 514-516, 18, 519 and 520; (xxxxii) Sequence IDs 528, 88, 25, 401, 19 and 402; (xxxiii) Sequence IDs 533-535 and 554-556; (xxxxiv) Sequence IDs 533-535, 561, 555 and 556; (xxxv) Sequence IDs 533-535, 564, 555 and 556; (xxxvi) Sequence IDs 533-535, 568, 555 and 556; (xxxvii) Sequence IDs 533, 540, 535 and 554-556; (xxxviiii) Sequence IDs 533, 540, 535, 561, 555 and 556; (xxxxix) Sequence numbers 533, 540, 535, 564, 555 and 556; (l) Sequence numbers 533, 540, 535, 568, 555, 556; (li) Sequence IDs 533, 543, 535 and 554-556; (lii) Sequence numbers 533, 543, 535, 561, 555 and 556; (liii) Sequence numbers 533, 543, 535, 564, 555 and 556; (liv) Sequence IDs 533, 543, 535, 568, 555 and 556; (lv) Sequence IDs 533, 548, 535 and 554-556; (lvi) Sequence numbers 533, 548, 535, 561, 555 and 556; (lvii) Sequence numbers 533, 548, 535, 564, 555 and 556; (lviiii) Sequence numbers 533, 548, 535, 564, 555 and 556; (lix) Sequence numbers 533, 548, 535, 568, 555 and 556; (lx) Sequence IDs 112-114, 18, 705 and 118; (lxi) Sequence IDs 137, 138, 139, 142, 143, 852; (lxii) Sequence numbers 814, 818, 139, 142, 143, 144; (lxiii) Sequence IDs 234, 235, 236, 239, 240, 241; (lxiv) Sequence IDs 234, 838, 236, 239, 240, 241; (lxv) Sequence IDs 137, 226, 358, 142, 143, 848; or (lxvi) Sequence IDs 814, 226, 358, 142, 143, 231 An antibody or antigen-binding fragment containing the amino acid sequence shown.

2. The VH and the VL are, (i) Sequence IDs 702 and 704, respectively; (ii) Sequence IDs 136 and 851, respectively; (iii) Sequence IDs 817 and 141, respectively; (iv) Sequence IDs 899 and 360, respectively; (v) Sequence IDs 233 and 858, respectively; (vi) Sequence IDs 837 and 858, respectively; (vii) Sequence IDs 357 and 847, respectively; (viiii) Sequence IDs 129 and 133, respectively; (ix) Sequence IDs 46 and 50, respectively; (x) Sequence IDs 53 and 56, respectively; (xi) Sequence IDs 59 and 64, respectively; (xi) Sequence IDs 69 and 71, respectively; (xiii) Sequence IDs 120 and 125, respectively; (xiv) Sequence IDs 73 and 76, respectively; (xv) Sequence IDs 79 and 83, respectively; (xvi) Sequence IDs 86 and 91, respectively; (xvii) Sequence IDs 95 and 98, respectively; (xviiii) Sequence IDs 22 and 27, respectively; (xix) Sequence IDs 111 and 116, respectively; (xx) Sequence IDs 30 and 35, respectively; (xxi) Sequence IDs 378 and 382, ​​respectively; (xxii) Sequence IDs 386 and 391, respectively; (xxiii) Sequence IDs 395 and 400, respectively; (xxiv) Sequence IDs 404 and 408, respectively; (xxv) Sequence IDs 412 and 414, respectively; (xxvi) Sequence IDs 416 and 419, respectively; (xxvii) Sequence IDs 422 and 424, respectively; (xxviiii) Sequence IDs 426 and 429, respectively; (xxix) Sequence IDs 431 and 434, respectively; (xxx) Sequence IDs 431 and 436, respectively; (xxxi) Sequence IDs 440 and 444, respectively; (xxxii) Sequence IDs 431 and 449, respectively; (xxxiii) Sequence IDs 451 and 455, respectively; (xxxiv) Sequence IDs 458 and 461, respectively; (xxxv) Sequence IDs 463 and 466, respectively; (xxxvi) Sequence IDs 470 and 473, respectively; (xxxvii) Sequence IDs 475 and 478, respectively; (xxxviiii) Sequence IDs 480 and 483, respectively; (xxxix) Sequence IDs 485 and 487, respectively; (xl) Sequence IDs 491 and 495, respectively; (xli) Sequence IDs 497 and 501, respectively; (xlii) Sequence IDs 504 and 509, respectively; (xliiii) Sequence IDs 513 and 518, respectively; (xliv) Sequence IDs 120 and 522, respectively; (xlv) Sequence IDs 524 and 518, respectively; (xlvi) Sequence IDs 527 and 530, respectively; (xlvii) Sequence IDs 532 and 553, respectively; (xlviiii) Sequence IDs 532 and 558, respectively; (xlix) Sequence IDs 532 and 577, respectively; (l) Sequence IDs 532 and 563, respectively; (li) Sequence IDs 532 and 567, respectively; (lii) Sequence IDs 532 and 570, respectively; (liiii) Sequence IDs 532 and 572, respectively; (lib) Sequence IDs 532 and 574, respectively; (lv) Sequence IDs 537 and 553, respectively; (lvi) Sequence IDs 537 and 558, respectively; (lvii) Sequence IDs 537 and 577, respectively; (lviiii) Sequence IDs 537 and 563, respectively; (lix) Sequence IDs 537 and 567, respectively; (lx) Sequence IDs 537 and 570, respectively; (lxi) Sequence IDs 537 and 572, respectively; (lxii) Sequence IDs 537 and 574, respectively; (lxiii) Sequence IDs 539 and 553, respectively; (lxiv) Sequence IDs 539 and 558, respectively; (lxv) Sequence IDs 539 and 577, respectively; (lxvi) Sequence IDs 539 and 563, respectively; (lxvii) Sequence IDs 539 and 567, respectively; (lxviiii) Sequence IDs 539 and 570, respectively; (lxix) Sequence IDs 539 and 572, respectively; (lxx) Sequence IDs 539 and 574, respectively; (lxxi) Sequence IDs 542 and 553, respectively; (lxxii) Sequence IDs 542 and 558, respectively; (lxxiii) Sequence IDs 542 and 577, respectively; (lxxiv) Sequence IDs 542 and 563, respectively; (lxxv) Sequence IDs 542 and 567, respectively; (lxxvi) Sequence IDs 542 and 570, respectively; (lxxvii) Sequence IDs 542 and 572, respectively; (lxxviiii) Sequence IDs 542 and 574, respectively; (lxxix) Sequence IDs 545 and 553, respectively; (lxxx) Sequence numbers 545 and 558, respectively; (lxxxi) Sequence IDs 545 and 577, respectively; (lxxxii) Sequence IDs 545 and 563, respectively; (lxxxiii) Sequence IDs 545 and 567, respectively; (lxxxiv) Sequence IDs 545 and 570, respectively; (lxxxv) Sequence IDs 545 and 572, respectively; (lxxxvi) Sequence IDs 545 and 574, respectively; (lxxxvii) Sequence IDs 547 and 553, respectively; (lxxxviiii) Sequence IDs 547 and 558, respectively; (lxxxix) Sequence IDs 547 and 577, respectively; (xc) Sequence IDs 547 and 563, respectively; (xci) Sequence IDs 547 and 567, respectively; (xcii) Sequence IDs 547 and 570, respectively; (xciii) Sequence IDs 547 and 572, respectively; (xciv) Sequence IDs 547 and 574, respectively; (xcv) Sequence IDs 550 and 553, respectively; (xcvi) Sequence IDs 707 and 708, respectively; (xcvii) Sequence IDs 707 and 709, respectively; (xcviiii) Sequence IDs 712 and 76, respectively; (xcix) Sequence IDs 716 and 64 respectively; or (c) The antibody or antigen-binding fragment according to claim 1, comprising an amino acid sequence having at least 90% identity with the amino acid sequences shown in SEQ ID NOs. 717 and 116, respectively, or comprising the above amino acid sequences, wherein the sequence diversity is optionally limited to one or more framework regions and / or comprises one or more substitutions for germline encoded amino acids.

3. (A) The VH and VL each contain an amino acid sequence having at least 90% identity with the amino acid sequences shown in SEQ ID NOs. 702 and 704, respectively, and the sequence diversity is optionally limited to one or more framework regions and / or the sequence diversity includes one or more substitutions of amino acids encoded in the germline. (B) The antibody or antigen-binding fragment (i) comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 amino acid sequences of the VH and VL shown in SEQ ID NOs. 702 and 704, respectively, or (C) (i) CDRH1 comprises the amino acid sequence shown in SEQ ID NO: 121, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conserved substitutions and / or substitutions for amino acids encoded in the germline; (ii) CDRH2 comprises the amino acid sequence shown in SEQ ID NO: 122, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conserved substitutions and / or substitutions for amino acids encoded in the germline; (iii) CDRH3 comprises the amino acid sequence shown in SEQ ID NO: 123, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conserved substitutions and / or substitutions for amino acids encoded in the germline; (iv) CDRL1 is The antibody or antigen-binding fragment according to claim 1, comprising the amino acid sequence shown in SEQ ID NO: 18, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conserved substitutions and / or substitutions for amino acids encoded in the germline, (v) CDRL2 comprises the amino acid sequence shown in SEQ ID NO: 705, or a functional variant thereof comprising one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conserved substitutions and / or substitutions for amino acids encoded in the germline, and / or (vi) CDRL3 comprises the amino acid sequence shown in SEQ ID NO: 127, or a functional variant thereof having one, two, or three amino acid substitutions, wherein one or more of the substitutions are optionally conserved substitutions and / or substitutions for amino acids encoded in the germline.

4. The antibody or antigen-binding fragment according to claim 1, wherein the antibody or antigen-binding fragment is an IgG isotype selected from IgG1, IgG2, IgG3, and IgG4.

5. The antibody or antigen-binding fragment according to claim 1, wherein the antibody or antigen-binding fragment comprises a human antibody, a monoclonal antibody, a purified antibody, a single-chain antibody, Fab, Fab', F(ab')2, or Fv.

6. The antibody or antigen-binding fragment is a multispecific antibody or antigen-binding fragment comprising (i) a first VH and a first VL, and (ii) a second VH and a second VL, and is optionally a bispecific antibody or antigen-binding fragment, wherein the first VH and the first VL together form a first antigen-binding site, the second VH and the second VL together form a second antigen-binding site, and the amino acid sequences of the first VH and the first VL and the amino acid sequences of the second VH and the second VL independently i) Sequence IDs 702 and 704; ii) Sequence IDs 136 and 851; iii) Sequence IDs 817 and 141; iv) Sequence IDs 899 and 360; v) Sequence IDs 233 and 858; vi) Sequence IDs 837 and 858; vii) Sequence IDs 357 and 847; viiii) Sequence IDs 129 and 133; ix) Sequence IDs 46 and 50; x) Sequence IDs 53 and 56; xi) Sequence IDs 59 and 64; xi) Sequence IDs 69 and 71; xiiii) Sequence IDs 120 and 125; xiv) Sequence IDs 73 and 76; xv) Sequence IDs 79 and 83; xvi) Sequence IDs 86 and 91; xvii) Sequence IDs 95 and 98; xviiii) Sequence IDs 22 and 27; xix) Sequence IDs 111 and 116; xx) Sequence IDs 30 and 35; xxi) Sequence IDs 378 and 382; xxii) Sequence IDs 386 and 391; xxiii) Sequence IDs 395 and 400; xxiv) Sequence IDs 404 and 408; xxv) Sequence IDs 412 and 414; xxvi) Sequence IDs 416 and 419; xxvii) Sequence IDs 422 and 424; xxviiii) Sequence IDs 426 and 429; xxx) Sequence IDs 431 and 434; xxx) Sequence IDs 431 and 436; xxxi) Sequence IDs 440 and 444; xxxii) Sequence IDs 431 and 449; xxxiii) Sequence IDs 451 and 455; xxxiv) Sequence IDs 458 and 461; xxxv) Sequence IDs 463 and 466; xxxvi) Sequence IDs 470 and 473; xxxvii) Sequence IDs 475 and 478; xxxviiii) Sequence IDs 480 and 483; xxxix) Sequence IDs 485 and 487; XL) Sequence IDs 491 and 495; xli) Sequence IDs 497 and 501; xlii) Sequence IDs 504 and 509; xliiii) Sequence IDs 513 and 518; xlv) Sequence IDs 120 and 522; xlv) Sequence IDs 524 and 518; XLVI) Sequence IDs 527 and 530; XLVII) Sequence IDs 532 and 553; XLVIIII) Sequence IDs 532 and 558; xlix) Sequence IDs 532 and 577; l) Sequence IDs 532 and 563; li) Sequence IDs 532 and 567; li) Sequence IDs 532 and 570; liiii) Sequence IDs 532 and 572; lv) Sequence IDs 532 and 574; lv) Sequence IDs 537 and 553; lvi) Sequence IDs 537 and 558; lvi) Sequence IDs 537 and 577; lviiii) Sequence IDs 537 and 563; lix) Sequence IDs 537 and 567; lx) Sequence IDs 537 and 570; lxi) Sequence IDs 537 and 572; lxii) Sequence IDs 537 and 574; lxiii) Sequence IDs 539 and 553; lxiv) Sequence IDs 539 and 558; lxv) Sequence IDs 539 and 577; lxvi) Sequence IDs 539 and 563; lxvii) Sequence IDs 539 and 567; lxviiii) Sequence IDs 539 and 570; lxix) Sequence IDs 539 and 572; lxx) Sequence IDs 539 and 574; lxxi) Sequence IDs 542 and 553; lxxii) Sequence IDs 542 and 558; lxxiii) Sequence IDs 542 and 577; lxxiv) Sequence IDs 542 and 563; lxxv) Sequence IDs 542 and 567; lxxvi) Sequence IDs 542 and 570; lxxvii) Sequence IDs 542 and 572; lxxviiii) Sequence IDs 542 and 574; lxxix) Sequence IDs 545 and 553; lxxx) Sequence IDs 545 and 558; lxxxi) Sequence IDs 545 and 577; lxxxii) Sequence IDs 545 and 563; lxxxiii) Sequence IDs 545 and 567; lxxxiv) Sequence IDs 545 and 570; lxxxv) Sequence IDs 545 and 572; lxxxvi) Sequence IDs 545 and 574; lxxxvii) Sequence IDs 547 and 553; lxxxviiii) Sequence IDs 547 and 558; lxxxix) Sequence IDs 547 and 577; xc) Sequence IDs 547 and 563; xci) Sequence IDs 547 and 567; xcii) Sequence IDs 547 and 570; xciiii) Sequence IDs 547 and 572; xciv) Sequence IDs 547 and 574; xcv) Sequence IDs 550 and 553; xcvi) Sequence IDs 707 and 708; xcvii) Sequence IDs 707 and 709; xcviiii) Sequence IDs 712 and 76; xcix) Sequence IDs 716 and 64; or c) The antibody or antigen-binding fragment according to claim 1, comprising SEQ ID NOs: 717 and 116, wherein the amino acid sequences of the first VH and the first VL are not the same as the amino acid sequences of the second VH and the second VL.

7. (A) (i) a first VH and a first VL, and (ii) a second VH and a second VL, wherein the first VH and the first VL together form a first antigen-binding site, and the second VH and the second VL together form a second antigen-binding site, wherein the first VH and the first VL each include the VH and VL shown in SEQ ID NOs: 136 and 851, 817 and 141, 233 and 858, 837 and 858, 357 and 847, and 899 and 360, (B) (i) a first VH and a first VL, and (ii) a second VH and a second VL, wherein the first VH and the first VL together form a first antigen-binding site, and the second VH and the second VL together form a second antigen-binding site, and the first VH and the first VL each include the VH and VL shown in SEQ ID NOs. 702 and 704, or (C) (i) a first VH and a first VL, and (ii) a second VH and a second VL, wherein the first VH and the first VL together form a first antigen-binding site, and the second VH and the second VL together form a second antigen-binding site, wherein the first VH and VL each include the VH and VL shown in SEQ ID NOs: 136 and 851, 817 and 141, 233 and 858, 837 and 858, 357 and 847, and 899 and 360, and the second VH and VL each include the VH and VL shown in SEQ ID NOs: 702 and 704, the antibody or antigen-binding fragment according to claim 6.

8. The antibody or antigen-binding fragment according to claim 1, wherein the antibody or antigen-binding fragment comprises an Fc polypeptide or a fragment thereof.

9. The antibody or antigen-binding fragment according to claim 8, wherein the Fc polypeptide comprises an amino acid sequence (optionally selected, other than naturally occurring variants thereof) having at least 85% identity with any one of SEQ ID NOs. 679-684 and 688-690, or comprises an amino acid sequence shown in any one of SEQ ID NOs. 679-684 and 688-690.

10. The antibody or antigen-binding fragment according to claim 9, wherein the antibody comprises a heavy chain (HC) having the amino acid sequence shown in SEQ ID NO: 723 and a light chain (LC) having the amino acid sequence shown in SEQ ID NO:

725.

11. The antibody or antigen-binding fragment according to claim 1, wherein the antibody or antigen-binding fragment binds to (a) both RSV A strain and RSV B strain, (b) both MPV A strain and MPV B strain, or (c) any combination of RSV A strain, RSV B strain, MPV A strain, and MPV B strain.

12. The antibody or antigen-binding fragment according to claim 1, wherein the antibody or antigen-binding fragment thereof (a) activates human FcγRIIa, or (b) activates human FcγRIIa.

13. (a) The antibody neutralizes infection by RSV and / or MPV, and / or (b) The antibody or antigen-binding fragment treats and / or prevents (i) RSV infection and / or (ii) MPV infection in a subject, according to claim 1.

14. An isolated polynucleotide encoding an antibody or antigen-binding fragment according to any one of claims 1 to 13, or encoding the VH, heavy chain, VL, light chain, and / or one or more CDRs of the antibody or antigen-binding fragment.

15. The isolated polynucleotide according to claim 14, wherein the polynucleotide comprises a polynucleotide having at least 50% identity with a polynucleotide sequence encoding VH represented by one or more of SEQ ID NOs: 701, 135, 816, 232, 836, 356, 898, and / or a polynucleotide sequence encoding VL represented by one or more of SEQ ID NOs: 703, 850, 140, 857, 846, 359.

16. A recombinant vector comprising the polynucleotide described in claim 14.

17. A host cell comprising the polynucleotide and / or a recombinant vector comprising the polynucleotide according to claim 14, wherein the polynucleotide is heterogeneous to the host cell, and the host cell expresses the encoded antibody or antigen-binding fragment.

18. Isolated human B cells comprising the polynucleotide and / or a recombinant vector comprising the polynucleotide according to claim 14, wherein the polynucleotide is heterologous to the human B cells and / or the human B cells are immortalized.

19. A composition comprising: (i) an antibody or antigen-binding fragment according to any one of claims 1 to 13; (ii) an isolated polynucleotide encoding the antibody or antigen-binding fragment; (iii) a recombinant vector comprising the isolated polynucleotide; (iv) a host cell comprising the polynucleotide and / or recombinant vector wherein the polynucleotide is heterogeneous to the host cell and the host cell expresses the encoded antibody or antigen-binding fragment; and / or (v) an isolated human B cell comprising the polynucleotide and / or recombinant vector wherein the polynucleotide is heterogeneous to the human B cell and / or the human B cell is immortalized; and a pharmaceutically acceptable excipient, carrier, or diluent.

20. A composition comprising a polynucleotide according to claim 14 or a recombinant vector containing the polynucleotide encapsulated in a carrier molecule, wherein the carrier molecule optionally comprises lipids, lipid-derived delivery vehicles such as liposomes, solid lipid nanoparticles, oily suspensions, submicron lipid emulsions, lipid microbubbles, reverse lipid micelles, cochlear liposomes, lipid microtubules, lipid microcylinders, lipid nanoparticles (LNPs), or nanoscale platforms.

21. A method for producing an antibody or antigen-binding fragment according to any one of claims 1 to 13, comprising culturing a host cell comprising an isolated polynucleotide and / or a recombinant vector comprising the polynucleotide encoding the antibody or antigen-binding fragment according to any one of claims 1 to 13, wherein the polynucleotide is heterogeneous to the host cell, and the host cell expresses the encoded antibody or antigen-binding fragment, or isolated human B cells comprising the polynucleotide and / or a recombinant vector comprising the polynucleotide, wherein the polynucleotide is heterogeneous to the human B cell and / or the human B cell is immortalized, for a time and under conditions sufficient to allow the host cell or human B cell to express the antibody or antigen-binding fragment, respectively.

22. (A) In methods for treating or preventing RSV infection and / or MPV infection in subjects, (B) The composition according to claim 19 for use in the preparation of a pharmaceutical for the treatment or prevention of RSV infection and / or MPV infection in a subject.

23. a) The composition according to claim 22, wherein the RSV comprises both RSV A strain and RSV B strain, b) the MPV comprises both MPV A strain and MPV B strain, and c) the RSV and MPV comprise any combination of RSV A strain, RSV B strain, MPV A strain, and MPV B strain.

24. A method for in vitro diagnosis of RSV infection and / or MPV infection, comprising: (i) contacting a sample derived from a subject with an antibody or antigen-binding fragment described in any one of claims 1 to 13; and (ii) detecting a complex comprising an antigen and the antibody, or an antigen and the antigen-binding fragment.

25. An antibody or antigen-binding fragment according to any one of claims 1 to 13; an isolated polynucleotide encoding the antibody or antigen-binding fragment; a recombinant vector comprising the isolated polynucleotide; a host cell comprising the polynucleotide and / or the recombinant vector, wherein the polynucleotide is heterogeneous to the host cell, and the host cell expresses the encoded antibody or antigen-binding fragment; or (i) an antibody or antigen-binding fragment according to any one of claims 1 to 13, (ii) an isolated polynucleotide encoding the antibody or antigen-binding fragment, (iii) a recombinant comprising the isolated polynucleotide A kit comprising a liquid composition comprising a vector, (iv) a host cell comprising the polynucleotide and / or recombinant vector wherein the polynucleotide is heterogeneous to the host cell and the host cell expresses the encoded antibody or antigen-binding fragment, and / or (v) an isolated human B cell comprising the polynucleotide and / or recombinant vector wherein the polynucleotide is heterogeneous to the human B cell and / or the human B cell is immortalized, and a composition comprising a pharmaceutically acceptable excipient, carrier or diluent, and instructions for its use in the treatment of RSV and / or MPV infection in a subject.

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