WO2024036128A2 - Anti-venom antibodies and uses thereof - Google Patents

Anti-venom antibodies and uses thereof Download PDF

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WO2024036128A2
WO2024036128A2 PCT/US2023/071814 US2023071814W WO2024036128A2 WO 2024036128 A2 WO2024036128 A2 WO 2024036128A2 US 2023071814 W US2023071814 W US 2023071814W WO 2024036128 A2 WO2024036128 A2 WO 2024036128A2
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seq
3ftx
antibody
amino acid
cdr3
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PCT/US2023/071814
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French (fr)
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WO2024036128A3 (en
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Joseph JARDINE
Irene KHALEK
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International Aids Vaccine Initiative
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/02—Antidotes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/515—Complete light chain, i.e. VL + CL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/55—Fab or Fab'
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Definitions

  • the field of the invention generally relates to anti-toxin antibodies and their use in the treatment of snake bite.
  • CROSS-REFRENCE TO RELATED APPLICATIONS [0002] This application claims the benefit of U.S. application no. 63/395,914, filed August 8, 2022, which is incorporated herein by reference in its entirety.
  • BACKGROUND [0003] Existing animal-derived antivenoms for treatment of snakebite suffer major limitations in safety, efficacy, potency, product consistency, cost of production, and coverage of snake species.
  • a cocktail of human monoclonal antibodies (mAbs) that target individual toxins present in venom with broad cross-reactivity across toxin variants found in multiple geographically diverse species would solve many of the issues inherent with current treatments. Described herein is the discovery of human mAbs that bind and neutralize multiple variants of long chain alpha-neurotoxic three finger toxins (3FTx-L) from multiple species of medically important Asian and African elapid snakes including cobras, kraits and mambas.3FTx-L is a major contributor to the lethality of elapid snake venoms and is often poorly targeted by animal-derived antivenoms thus is an excellent target for a broadly neutralizing human mAb therapy.
  • 3FTx-L long chain alpha-neurotoxic three finger toxins
  • monoclonal antibodies capable of binding to and neutralizing multiple variants of long chain alpha-neurotoxic three finger toxins (3FTx-L) from multiple species of medically important Asian and African elapid snakes BRIEF SUMMARY [0005]
  • monoclonal antibodies that monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L).
  • an antibody described herein is a bispecific, trispecific or multispecific antibody.
  • an antibody described herein specifically binds at least one 3FTx-L variant disclosed in Table 1.
  • an antibody described herein specifically binds at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15 or at least 163FTx-L variants disclosed in Table 1. In some embodiments, an antibody described herein specifically binds all 3FTx-L variants disclosed in Table 1. In some embodiments, an antibody described herein is capable of neutralizing at least one 3FTx-L variant disclosed in Table 1. In some embodiments, an antibody described herein is capable of neutralizing alpha-bungarotoxin (SEQ ID NO: 250).
  • an antibody described herein is capable of neutralizing at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15 or at least 16 3FTx-L variants disclosed in Table 1.
  • an antibody described herein is capable of neutralizing the 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, or 3FTx-L15 variants disclosed in Table 1.
  • an antibody described herein is capable of neutralizing the 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, and 3FTx- L15 variants disclosed in Table 1. In some embodiments, an antibody described herein is capable of neutralizing all 3FTx-L variants disclosed in Table 1. In some embodiments, neutralization is assessed in an in vitro cell based assay. In some embodiments, neutralization is assessed in an in vivo assay. [0006] In one aspect, provided herein are pharmaceutical compositions comprising a monoclonal antibody that specifically binds to 3FTx-L described herein.
  • provided herein are isolated polynucleotides encoding a monoclonal antibody that specifically binds to 3FTx-L described herein. [0008] In one aspect, provided herein are methods of producing a monoclonal antibody that specifically binds to 3FTx-L described herein. [0009] In one aspect, provided herein are methods of neutralizing an 3FTx-L, comprising contacting the toxin with a monoclonal antibody that specifically binds to 3FTx-L described herein. [0010] In one aspect, provided herein are methods of treating snake bite comprising administering to a subject in need thereof a monoclonal antibody that specifically binds to 3FTx-L described herein.
  • an isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein (1) the VH is a VH1-02, VH1-18, VH1-69 or VH3-07 VH and the VL is a VL2-14, VK3-20, VK1-39, VL2-14 or VL1-51 VL, and (2) wherein the VH CDR3 comprises 20 or 21 amino acid residues comprising the amino acid sequence of SEQ ID NO: 244- 248 or
  • An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises Thr28, Ser31 and Tyr32, the VH CDR3 comprises 20 or 21 amino acid residues comprising the amino acid sequence of SEQ ID NO: 244-248 or 249, the VL CDR1 comprises Tyr32, the VL CDR2 comprises Asp50 and the VL CDR3 comprises Ser91 and Tyr92, optionally wherein the VH is a VH1-02, VH1-18, VH1-69 or VH3-07 VH and the VL is a VL2-14, VK3-20, VK1-39, VL2-14 or VL1-51 VL.
  • VH heavy
  • VH CDR3 comprises an amino acid sequence of SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, 123, 133, 143 or 153 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222, or 238, optionally wherein the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153.
  • the VH CDR1 comprises the amino acid sequence of SEQ ID NO: 151
  • the VH CDR2 comprises the amino acid sequence of SEQ ID NO: 152, 213, 229, or 237
  • the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222 or 238,
  • the VL CDR1 comprises the amino acid sequence of SEQ ID NO: 154
  • the VL CDR2 comprises the amino acid sequence of SEQ ID NO: 155 or 232
  • the VL CDR3 comprises the amino acid sequence of SEQ ID NO: 156.
  • VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 151-153, respectively, SEQ ID NO: 196-198, respectively, SEQ ID NO: 204-206, respectively, SEQ ID NO: 212-214, respectively, SEQ ID NO: 220-222, respectively, SEQ ID NO: 228-230, respectively, and SEQ ID NO: 236-238, respectively.
  • VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 154-156, respectively, SEQ ID NO: 199-201, respectively, SEQ ID NO: 207-209, respectively, SEQ ID NO: 215-217, respectively, SEQ ID NO: 223-225, respectively, SEQ ID NO: 231-233, respectively, and SEQ ID NO: 239-241, respectively.
  • VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 151-156, respectively, SEQ ID NO: 196-201, respectively, SEQ ID NO: 204-209, respectively, SEQ ID NO: 212-217, respectively, SEQ ID NO: 220-225, respectively, SEQ ID NO: 228-233, respectively, and SEQ ID NO: 236-241, respectively.
  • VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 228-233, respectively.
  • VH and VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 157 and 158, respectively, SEQ ID NO: 202 and 203, respectively, SEQ ID NO: 210 and 211, respectively, SEQ ID NO: 218 and 219, respectively, SEQ ID NO: 226 and 227, respectively, SEQ ID NO: 234 and 235, respectively, or SEQ ID NO: 242 and 243, respectively.
  • VH and VL comprises an amino acid sequence of SEQ ID NO: 157 and 158, respectively, SEQ ID NO: 202 and 203, respectively, SEQ ID NO: 210 and 211, respectively, SEQ ID NO: 218 and 219, respectively, SEQ ID NO: 226 and 227, respectively, SEQ ID NO: 234 and 235, respectively, or SEQ ID NO: 242 and 243, respectively.
  • An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR3 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95.
  • VH heavy chain variable region
  • VL light chain variable region
  • An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR3 of LB5_95.
  • VH heavy chain variable region
  • VL light chain variable region
  • An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, 123, 133, 143 or 153.
  • An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 153.
  • An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the VH CDR3 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • VH heavy chain variable region
  • VL light chain variable region
  • An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the VH CDR3 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • VH heavy chain variable region
  • VL light chain variable region
  • An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, 123, 133, 143 or 153 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the VH CDR3 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6.
  • VH heavy chain variable region
  • VL light chain variable region
  • An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222 or 238.
  • VH heavy chain variable region
  • VL light chain variable region
  • VH CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR1 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95; (b) the VH CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR1 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_
  • An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein (a) the VH CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR1 of LB5_95; (b) the VH CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR2 of LB5_95; and (c) the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR3 of LB5_95.
  • VH heavy chain
  • An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein (a) the VH CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 1, 11, 21, 31, 41, 51, 61, 71, 81, 91, 101, 111, 121, 131, 141 or 151; (b) the VH CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 2, 12, 22, 32, 42, 52, 62, 72, 82, 92, 102, 112, 122, 132,
  • An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein (a) the VH CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 151; (b) the VH CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 152; and (c) the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 153.
  • An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein (a) the VH CDR1 comprises the VH CDR1 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) the VH CDR2 comprises the VH CDR2 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and (c) the VH CDR3 comprises the VH CDR3 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein (a) the VH CDR1 comprises the amino acid of SEQ ID NO: 1, 11, 21, 31, 41, 51, 61, 71, 81, 91, 101, 111, 121, 131, 141 or 151 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) the VH CDR2 comprises the amino acid of SEQ ID NO: 2, 12, 22, 32, 42, 52, 62, 72, 82, 92, 102, 112, 122, 132, 142 or 152 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and
  • An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein (a) the VH CDR1 comprises the amino acid of SEQ ID NO: 151 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) the VH CDR2 comprises the amino acid of SEQ ID NO: 152 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and (c) the VH CDR3 comprises the amino acid of SEQ ID NO: 153 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein (a) the VH CDR1 comprises the VH CDR1 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6; (b) the VH CDR2 comprises the VH CDR2 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6; and (c) the VH CDR3 comprises the VH CDR3 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6.
  • VH CDR1 comprises the VH CDR1 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6
  • the VH CDR2
  • An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein (a) the VH CDR1 comprises the amino acid of SEQ ID NO: 151; (b) the VH CDR2 comprises amino acid of SEQ ID NO: 152, 213, 229 or 237; and (c) the VH CDR3 comprises amino acid of SEQ ID NO: 153, 214, 222 or 238.
  • the VL CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VL CDR1 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95; (b) the VL CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VL CDR2 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_
  • the VL CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VL CDR1 of LB5_95;
  • the VL CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VL CDR2 of LB5_95;
  • the VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VL CDR3 of LB5_95.
  • VL CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144 or 154
  • VL CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 5, 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 125, 135, 145 or 155
  • VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 6, 16, 26, 36, 46, 56, 66, 76, 86, 96, 106, 116, 126, 136
  • VL CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 154
  • VL CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 155
  • VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 156.
  • the VL CDR1 comprises the VL CDR1 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) the VL CDR2 comprises the VL CDR2 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91,
  • VL CDR1 comprises the VL CDR1 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions
  • VL CDR2 comprises the VL CDR2 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions
  • VL CDR3 comprises the VL CDR3 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • the VL CDR1 comprises the amino acid of SEQ ID NO: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144 or 154 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions
  • the VL CDR2 comprises the amino acid of SEQ ID NO: 5, 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 125, 135, 145 or 155 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions
  • the VL CDR3 comprises the amino acid of SEQ ID NO: 6, 16, 26, 36, 46, 56, 66, 76, 86, 96, 106, 116, 126, 136, 146 or 156 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • VL CDR1 comprises the amino acid of SEQ ID NO: 154 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions
  • VL CDR2 comprises the amino acid of SEQ ID NO: 155 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions
  • VL CDR3 comprises the amino acid of SEQ ID NO: 156 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • the isolated monoclonal antibody according to any one of embodiments [12] to [31], wherein (a) the VL CDR1 comprises the VL CDR1 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6; (b) the VL CDR2 comprises the VL CDR2 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6; and (c) the VL CDR3 comprises the VL CDR3 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6.
  • VL CDR1 comprises the amino acid of SEQ ID NO: 154
  • VL CDR2 comprises the amino acid of 155, 232 or 240
  • VL CDR3 comprises the amino acid of SEQ ID NO: 156.
  • VH CDR1, VH CDR2 and VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VH CDR1, VH CDR2 and VH CDR3, respectively.
  • VH CDR1, VH CDR2 and VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_95 VH CDR1, VH CDR2 and VH CDR3, respectively.
  • VH CDR1, VH CDR2 and VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to (a) SEQ ID NO: 1, 2 and 3, respectively; (b) SEQ ID NO: 11, 12 and 13, respectively; (c) SEQ ID NO: 21, 22 and 23, respectively; (d) SEQ ID NO: 31, 32 and 33, respectively; (e) SEQ ID NO: 41, 42 and 43, respectively; (f) SEQ ID NO: 51, 52 and 53, respectively; (g) SEQ ID NO: 61, 62 and 63, respectively; (h) SEQ ID NO: 71, 72 and 73, respectively; (i) SEQ ID NO: 81, 82 and 83, respectively; (j) SEQ ID NO: 91, 92 and 93, respectively; (k) SEQ ID NO: 101, 102 and 103, respectively; (l) SEQ ID NO: 11, 12 and 13, respectively; (c) SEQ ID NO: 21, 22 and 23, respectively; (
  • VH CDR1, VH CDR2 and VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 151, 152 and 153, respectively.
  • VH CDR1, VH CDR2 and VH CDR3 comprises the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VH CDR1, VH CDR2 and VH CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • VH CDR1, VH CDR2 and VH CDR3 comprises the LB5_95 VH CDR1, VH CDR2 and VH CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of (a) SEQ ID NO: 1, 2 and 3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) SEQ ID NO: 11, 12 and 13, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (c) SEQ ID NO: 21, 22 and 23, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (d) SEQ ID NO: 31, 32 and 33, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (e) SEQ ID NO: 41, 42 and 43, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (f) SEQ ID NO: 51, 52 and 53, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions,
  • VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 151, 152 and 153, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • VH CDR1, VH CDR2 and VH CDR3 comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6.
  • VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 196-198, respectively, SEQ ID NO: 204-206, respectively, SEQ ID NO: 212-214, respectively, SEQ ID NO: 220-222, respectively, SEQ ID NO: 228-230, respectively, and SEQ ID NO: 236-238, respectively.
  • VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VL CDR1, VL CDR2 and VL CDR3, respectively.
  • VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_95 VL CDR1, VL CDR2 and VL CDR3, respectively.
  • VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to (a) SEQ ID NO: 4, 5 and 6, respectively; (b) SEQ ID NO: 14, 15 and 16, respectively; (c) SEQ ID NO: 24, 25 and 26, respectively; (d) SEQ ID NO: 34, 35 and 36, respectively; (e) SEQ ID NO: 44, 45 and 46, respectively; (f) SEQ ID NO: 54, 55 and 56, respectively; (g) SEQ ID NO: 64, 65 and 66, respectively; (h) SEQ ID NO: 74, 75 and 76, respectively; (i) SEQ ID NO: 84, 85 and 86, respectively; (j) SEQ ID NO: 94, 95 and 96, respectively; (k) SEQ ID NO: 104, 105 and 106, respectively; (l) SEQ ID NO: 4, 5 and 6, respectively; (b) SEQ ID NO: 14, 15 and 16, respectively; (c)
  • VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 154, 155 and 156, respectively.
  • VL CDR1, VL CDR2 and VL CDR3 comprises the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VL CDR1, VL CDR2 and VL CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • VL CDR1, VL CDR2 and VL CDR3 comprises the LB5_95 VL CDR1, VL CDR2 and VL CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of (a) SEQ ID NO: 4, 5 and 6, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) SEQ ID NO: 14, 15 and 16, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (c) SEQ ID NO: 24, 25 and 26, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (d) SEQ ID NO: 34, 35 and 36, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (e) SEQ ID NO: 44, 45 and 46, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (f) SEQ ID NO: 54, 55 and 56, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions; (b) SEQ ID NO: 54, 55 and 56, respectively, comprising 0, 1, 2, 3, 4, or 5 substitution
  • VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 154, 155 and 156, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • VL CDR1, VL CDR2 and VL CDR3 comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6.
  • VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 199-201, respectively, SEQ ID NO: 207-209, respectively, SEQ ID NO: 215-217, respectively, SEQ ID NO: 223-225, respectively, SEQ ID NO: 231-233, respectively, and SEQ ID NO: 239-241, respectively.
  • VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3, respectively.
  • VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_95 VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3, respectively.
  • VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to (a) SEQ ID NO: 1, 2, 3, 4, 5 and 6, respectively; (b) SEQ ID NO: 11, 12, 13, 14, 15 and 16, respectively; (c) SEQ ID NO: 21, 22, 23, 24, 25 and 26, respectively; (d) SEQ ID NO: 31, 32, 33, 34, 35 and 36, respectively; (e) SEQ ID NO: 41, 42, 43, 44, 45 and 46, respectively; (f) SEQ ID NO: 51, 52, 53, 54, 55 and 56, respectively; (g) SEQ ID NO: 61, 62, 63, 64, 65 and 66, respectively; (h) SEQ ID NO: 71, 72, 73, 74, 75 and 76, respectively; (
  • VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 151, 152, 153, 154, 155 and 156, respectively.
  • VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the LB5_95 VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of (a) SEQ ID NO: 1, 2, 3, 4, 5 and 6, respectively; (b) SEQ ID NO: 11, 12, 13, 14, 15 and 16, respectively; (c) SEQ ID NO: 21, 22, 23, 24, 25 and 26, respectively; (d) SEQ ID NO: 31, 32, 33, 34, 35 and 36, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (e) SEQ ID NO: 41, 42, 43, 44, 45 and 46, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (f) SEQ ID NO: 51, 52, 53, 54, 55 and 56, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (g) SEQ ID NO: 61, 62,
  • VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 151, 152, 153, 154, 155 and 156, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6.
  • VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 151-156, respectively, SEQ ID NO: 196-201, respectively, SEQ ID NO: 204-209, respectively, SEQ ID NO: 212-217, respectively, SEQ ID NO: 220-225, respectively, SEQ ID NO: 228-233, respectively, and SEQ ID NO: 236-241, respectively.
  • VH and VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to (a) SEQ ID NO: 7 and 8, respectively; (b) SEQ ID NO: 17 and 18, respectively; (c) SEQ ID NO: 27 and 28, respectively; (d) SEQ ID NO: 37 and 38, respectively; (e) SEQ ID NO: 47 and 48, respectively; (f) SEQ ID NO: 57 and 58, respectively; (g) SEQ ID NO: 67 and 68, respectively; (h) SEQ ID NO: 77 and 78, respectively; (i) SEQ ID NO: 87 and 88, respectively; (j) SEQ ID NO: 97 and 98, respectively; (k) SEQ ID NO: 107 and 108, respectively; (l) SEQ ID NO: 117 and 118, respectively; (m) SEQ ID NO: 127 and 128, respectively; (a) SEQ ID NO: 7 and 8, respectively; (b) SEQ ID NO: 17 and 18, respectively; (c
  • VH and VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 157 and 158, respectively.
  • VH and VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 202 and 203, respectively, SEQ ID NO: 210 and 211, respectively, SEQ ID NO: 218 and 219, respectively, SEQ ID NO: 226 and 227, respectively, SEQ ID NO: 234 and 235, respectively, or SEQ ID NO: 242 and 243, respectively.
  • VH and VL comprises the amino acid sequence of SEQ ID NO: 202 and 203, respectively, SEQ ID NO: 210 and 211, respectively, SEQ ID NO: 218 and 219, respectively, SEQ ID NO: 226 and 227, respectively, SEQ ID NO: 234 and 235, respectively, or SEQ ID NO: 242 and 243, respectively.
  • the antibody of any one of embodiments [82] to [84], wherein the heavy chain constant region comprises a native amino acid sequence.
  • the antibody of any one of embodiments [82] to [84], wherein the heavy chain constant region comprises a variant amino acid sequence.
  • a pharmaceutical composition comprising the monoclonal antibody of any one of embodiments [1] to [103] and a pharmaceutically acceptable excipient.
  • the pharmaceutical composition of any one of embodiments [104] to [106] comprising a second antibody, wherein the second antibody is capable of binding at least one toxic component of snake venom in addition to 3FTx-L.
  • the pharmaceutical composition of embodiment [107], wherein the at least one toxic component of snake venom in addition to 3FTx-L comprises a metalloprotease or a phospholipase.
  • a host cell comprising the polynucleotide of any one of embodiments [109] to [114], the vector of embodiment [115] or embodiment [116], or a first vector comprising the nucleic acid of embodiment [109] and a second vector comprising the nucleic acid of embodiment [110].
  • the host cell of embodiment [119] which is selected from the group consisting of E.
  • a method of producing an antibody that binds to 3FTx-L comprising culturing the host cell of embodiment [120] so that the polynucleotide is expressed and the antibody is produced.
  • [122.] An isolated antibody that specifically binds to 3FTx-L and is encoded by the isolated polynucleotide of any one of embodiments [109] to [114].
  • [123.] A method of neutralizing an 3FTx-L comprising contacting the 3FTx-L with a sufficient amount of the antibody of any one of embodiments [1] to [103], or the pharmaceutical composition of any one of embodiments [104] to [108].
  • [124.] A method of treating snake bite comprising administering to a subject in need thereof a therapeutically sufficient amount of the antibody of any one of embodiments [1] to [103], or the pharmaceutical composition of any one of embodiments [104] to [108].
  • a method of producing an engineered variant of an antibody comprising (a) substituting one or more amino acid residues of the VH; and/or substituting one or more amino acid residues of the VL to create an engineered variant antibody, and (b) and producing the engineered variant antibody, wherein the antibody is LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95.
  • a method of producing an engineered variant of an antibody comprising (a) substituting one or more amino acid residues of the VH; and/or substituting one or more amino acid residues of the VL to create an engineered variant antibody, and (b) and producing the engineered variant antibody, wherein the antibody is 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6.
  • a method of producing an engineered variant of a LB5_95 comprising (a) substituting one or more amino acid residues of the LB5_95 VH; and/or substituting one or more amino acid residues of the LB5_95 VL to create an engineered variant antibody, and (b) and producing the engineered variant antibody.
  • Figure 1 Isolation of cross-reactive anti-3FTx-L mAbs from naive library.
  • PSR polyspecific reagent
  • 3FTx-L variants from the selections are shown in circles and additional variants are shown as triangles.
  • 3FTx variants are classified by various known families, and the mamba-exclusive group included fasciculins, FS2 toxins, dendroaspins, and mambalgins.
  • FIG. 4 Kaplan–Meier survival curves for in vivo protection experiments.
  • the control group was injected with purified ⁇ -bungarotoxin only.
  • Groups of five mice were challenged with 2x LD50 doses of B) N. kaouthia, C) D.
  • Figure 5 Crystal structure of 95Mat5 Fab with 3FTx-L15 reveals similarity in toxin recognition of antibody and nAChR ⁇ .
  • C, D, E Molecular details of interaction for CDRs L1, L2, H1 and H3 with 3FTx-L15.
  • Asp50 from the LC of 95Mat5 interacts with and orients Arg98 in CDRH3 and is involved with an electrostatic network for toxin recognition.
  • Figure 7 Binding curves for main (A) and supplemental (B) recombinant 3FTx-L variants on yeast-displayed human nAChR ⁇ 1 subunit measured via flow cytometry. The median APC area signal was plotted for each population of streptavidin-APC stained yeast cells displaying nAChR ⁇ 1 and incubated with various concentrations of biotinylated 3FTx-L variants. Non-linear curve fitting was performed to calculate the IC50 for each variant using a one-site competitive binding model in Prism.
  • FIG. 8 Flow chart of sorts used in sorting of the naive Fab library for cross-reactive anti-3FTx-L antibodies.3 rounds of magnetic-activated cell sorts (MACS) were performed initially with Fc-conjugated 3FTx (Fc-3FTx-L2 and Fc-3FTx-L3), followed by 5 rounds of FACS that were either affinity (AFF) sorts or negative (PSR) sorts.
  • AFF affinity
  • PSR negative
  • Negative sorting antigens included recombinant rabbit Fc-tagged phospholipase A2 (Fc-PLA2) and soluble cytosolic protein extract (SCP). The concentration of antigen used is indicated in parentheses. See Methods section for further details.
  • Figure 9 Flow cytometry plots for each anti-3FTx sorting step showing the population of cells sorted for each round of FACS described in Fig S4. An example of paired chain selection is shown for AFF1, gating the population of Fabs with coordinated heavy vs. light chain display signals. Antigen-binding or non-binding cells were then sorted in the AFF or PSR sorts, respectively, as shown by the gates drawn with red outlines.
  • FIG. 10 Flow chart of sorts used in sorting the LB5_95 affinity maturation library. 4 rounds of FACS were performed with the separate heavy chain (HC) and light chain (LC) libraries prior to combining them, followed by an additional 4 rounds of FACS with the combined library. The percentage of the paired chain population that was sorted is indicated under the name of each sort, and the concentration of antigen used is indicated in parentheses. Prior to each PSR sort, the cell populations from the previous affinity sort were combined before sorting with the SCP. Sorts with dissociation conditions applied are indicated with “diss”. See Methods section for further details.
  • Figure 11 Characterization of affinity matured antibodies.
  • CHO-SMP cell soluble membrane protein extract
  • ssDNA single-stranded DNA
  • insulin insulin
  • Affinity-capture self-interaction nanoparticle spectroscopy AC-SINS
  • Figure 12 Validation of potential 95Mat5-binding 3FTx variants at the deep sequencing threshold.
  • 3FTx-L15, 95Mat5 HC, and 95Mat5 LC residues are shown in dark green, orange, and gold sticks. Two cation/amino– ⁇ interactions involve Tyr100-Arg34 and Arg34-Phe30-Tyr32.
  • Figure 15 Comparison of the binding mode for 95Mat5:3FTx-L15 with several nAChR ⁇ subunits in complex with 3FTx-L. 3FTx-L is in dark green cartoon representation. Human nAChR ⁇ 1, ⁇ 7, and ⁇ 9 are shown in lavender, pink, and wheat cartoon, respectively.
  • Figure 16 Data collection and refinement statistics of 3FTx-L15 and 95Mat5 Fab complex structure.
  • 3FTx-L is a major contributor to the lethality of elapid snake venoms and is often poorly targeted by animal-derived antivenoms thus is an excellent target for a broadly neutralizing human monoclonal antibody therapy.
  • This panel was used for human antibody discovery, downselection to identify potential bnAbs, and biophysical characterization of lead candidates.
  • 3FTx-L and 3FTx-L toxin-rich venom from distinct snakes across Asia and Africa was assessed. This work demonstrates the potential of anti-toxin bnAbs and provides a template for the discovery of bnAbs targeting additional venom toxin classes.
  • provided herein is a method for the synthetic production of a human antibody that can neutralize three-finger neurotoxins from various snakes across continents.
  • a treatment of snakebite envenoming comprising administering a therapeutically effective amount of an antibody described herein. I.
  • the term "long chain alpha-neurotoxic three finger toxin” or “3FTX_LCa” or “3FTx-L” refers to alpha-neurotoxins that can efficiently bind to nicotinic acetylcholine receptors (nAChRs). Son et al., Toxins (Basel). 13(2): 164 (2021) and Utkin, Yuri, World J Biol Chem 10(1): 17-27 (2019).
  • alpha-bungarotoxin (SEQ ID NO: 250) from krait Bungarus multicinctus venom binds muscle-type as well as neuronal alpha7 and alpha9 nAChRs with nanomolar affinities and blocks ion current through the ion channel of these receptors.
  • "Long chain alpha-neurotoxic three finger toxin” or “3FTX_LCa” or “3FTx-L” encompass, but are not limited to, native 3FTx-L, an isoform of 3FTx-L, or a recombinant variant of 3FTx-L.
  • 3FTx-L comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 161-177.
  • the 3FTx-L is the Bungarus caeruleus (South central Asia) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 161 (UniProtKB accession number D2N116). In some embodiments, the 3FTx-L is the Bungarus multicinctus (Southeastern Asia) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 162 (UniProtKB accession number P60616, 1HC9). In some embodiments, the 3FTx-L is the Dendroaspis polylepis (East central & southern Africa) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 163 (UniProtKB accession number C0HJD7, 4LFT).
  • the 3FTx-L is the Dendroaspis viridis (Western Africa) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 164 (UniProtKB accession number P01394).
  • the 3FTx-L is the Naja kaouthia, Naja siamensis (Southeastern Asia) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 165 (UniProtKB accession number P01391, 2CTX, 4AEA).
  • the 3FTx-L is the Naja nivea (Southern Africa) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 166 (UniProtKB accession number P01390).
  • the 3FTx-L is the Bungarus candidus (Southern Asia) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 167 (UniProtKB accession number A1IVR9). In some embodiments, the 3FTx-L is the Dendroaspis jamesoni (West central Africa) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 168 (UniProtKB accession number P01393). In some embodiments, the 3FTx-L is the Naja anchietae (South central Africa) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 169 (UniProtKB accession number P01389).
  • the 3FTx-L is the Naja melanoleuca (West central Africa) 3FTx- L comprising the amino acid sequence of SEQ ID NO: 170 (UniProtKB accession number P01383). In some embodiments, the 3FTx-L is the Naja naja (South central Asia) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 171 (UniProtKB accession number P25672). In some embodiments, the 3FTx-L is the Naja sputatrix (Indonesia) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 172 (UniProtKB accession number O42257).
  • the 3FTx-L is the Naja oxiana (Central Asia) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 173 (UniProtKB accession number 1NTN). In some embodiments, the 3FTx-L is the Ophiophagus hannah (Southeastern Asia) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 174 (UniProtKB accession number P01386, 1TXA). In some embodiments, the 3FTx-L is the Naja naja (South central Asia) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 175 (UniProtKB accession number P25668).
  • the 3FTx-L is the Dendroaspis viridis (Western Africa) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 176 (UniProtKB accession number P01395). In some embodiments, the 3FTx-L is the Naja melanoleuca (West central Africa) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 177 (UniProtKB accession number P01388). In some embodiments, the 3FTx-L is alpha- bungarotoxin comprising the amino acid sequence of SEQ ID NO: 250. Table 1. Selected recombinant 3FTX variants.
  • antibody means an immunoglobulin molecule (or a group of immunoglobulin molecules) that recognizes and specifically binds to a target, such as a protein, polypeptide, peptide, carbohydrate, polynucleotide, lipid, or combinations of the foregoing through at least one antigen recognition site within the variable region of the immunoglobulin molecule.
  • Antibodies can include, for example, monoclonal antibodies, recombinantly produced antibodies, human antibodies, humanized antibodies, resurfaced antibodies, chimeric antibodies, immunoglobulins, synthetic antibodies, tetrameric antibodies comprising two heavy chain and two light chain molecules, an antibody light chain monomer, an antibody heavy chain monomer, an antibody light chain dimer, an antibody heavy chain dimer, an antibody light chain- antibody heavy chain pair, intrabodies, heteroconjugate antibodies, single domain antibodies, monovalent antibodies, single chain antibodies or single-chain Fvs (scFv), affybodies, Fab fragments, F(ab')2 fragments, disulfide-linked Fvs (sdFv), anti-idiotypic (anti-Id) antibodies (including, e.g., anti-Id) antibodies (including, e.g., antigen Id).
  • antibodies described herein refer to polyclonal antibody populations.
  • Antibodies can be of any type (e.g., IgG, IgE, IgM, IgD, IgA, or IgY), any class (e.g., IgG 1 , IgG 2 , IgG 3 , IgG 4 , IgA 1 , or IgA 2 ), or any subclasses (isotypes) thereof (e.g.
  • immunoglobulin molecule based on the identity of their heavy-chain constant domains referred to as alpha, delta, epsilon, gamma, and mu, respectively.
  • the different classes of immunoglobulins have different and well known subunit structures and three-dimensional configurations.
  • Antibodies can be naked or conjugated or fused to other molecules such as toxins, radioisotopes, other polypeptides etc.
  • the terms "antigen-binding domain,” “antigen-binding region,” “antigen- binding site,” and similar terms refer to the portion of antibody molecules which comprises the amino acid residues that confer on the antibody molecule its specificity for the antigen (e.g., 3FTx- L).
  • the antigen-binding region can be derived from any animal species, such as mouse and humans.
  • the terms “variable region” or “variable domain” are used interchangeably and are common in the art. The variability in sequence is concentrated in those regions called complementarity determining regions (CDRs) while the more highly conserved regions in the variable domain are called framework regions (FR).
  • variable region is a human variable region.
  • variable region comprises human CDRs and human framework regions (FRs).
  • FRs human framework regions
  • variable region comprises human CDRs and primate (e.g., non-human primate) framework regions (FRs).
  • the IMGT unique numbering defined for the IG and TR variable regions and domains of all jawed vertebrates has allowed a redefinition of the limits of the framework (FR-IMGT) and complementarity determining regions (CDR-IMGT), leading to a standardized description of mutations, allelic polymorphisms, 2D representations (Colliers de Perles) and 3D structures, whatever the antigen receptor, the chain type, or the species.
  • FR-IMGT limits of the framework
  • CDR-IMGT complementarity determining regions
  • a third approach is based on crystallographic studies of antigen-antibody complexes (Al-lazikani et al, J. Molec. Biol. 273:927-948 (1997)). In addition, combinations of these approaches are sometimes used in the art to determine CDRs.
  • the CDR regions are determined according to Kabat. In some embodiments, the CDR regions are determined according to IMGT.
  • the Kabat numbering system is generally used when referring to a residue in the variable domain (approximately residues 1-107 of the light chain and residues 1-113 of the heavy chain) (e.g., Kabat et al., Sequences of Immunological Interest. (5th Ed., 1991, National Institutes of Health, Bethesda, Md.) ("Kabat").
  • the amino acid position numbering as in Kabat refers to the numbering system used for heavy chain variable domains or light chain variable domains of the compilation of antibodies in Kabat et al. (Sequences of Immunological Interest.
  • a heavy chain variable domain can include a single amino acid insert (residue 52a according to Kabat) after residue 52 of H2 and inserted residues (e.g. residues 82a, 82b, and 82c, etc. according to Kabat) after heavy chain FR residue 82.
  • the Kabat numbering of residues can be determined for a given antibody by alignment at regions of homology of the sequence of the antibody with a "standard" Kabat numbered sequence.
  • Chothia refers instead to the location of the structural loops (Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)).
  • the end of the Chothia CDR-H1 loop when numbered using the Kabat numbering convention varies between H32 and H34 depending on the length of the loop (this is because the Kabat numbering scheme places the insertions at H35A and H35B; if neither 35A nor 35B is present, the loop ends at 32; if only 35A is present, the loop ends at 33; if both 35A and 35B are present, the loop ends at 34).
  • the AbM hypervariable regions represent a compromise between the Kabat CDRs and Chothia structural loops, and are used by Oxford Molecular's AbM antibody modeling software.
  • the CDR regions are determined according to Kabat.
  • the CDR regions are determined according to IMGT.
  • the CDR regions are determined according to Chothia.
  • the CDR regions are determined according to AbM.
  • the VH and VL residues are numbered according to Kabat.
  • VL and VL domain are used interchangeably to refer to the light chain variable region of an antibody.
  • VH and VH domain are used interchangeably to refer to the heavy chain variable region of an antibody.
  • antibody fragment refers to a portion of an intact antibody.
  • An antigen-binding fragment refers to a portion of an intact antibody that binds to an antigen.
  • An antigen-binding fragment can contain the antigenic determining variable regions of an intact antibody. Examples of antibody fragments include, but are not limited to Fab, Fab', F(ab')2, and Fv fragments, linear antibodies, and single chain antibodies.
  • a "monoclonal” antibody or antigen-binding fragment thereof refers to a homogeneous antibody or antigen-binding fragment population involved in the highly specific recognition and binding of a single antigenic determinant, or epitope. This is in contrast to polyclonal antibodies that typically include different antibodies directed against different antigenic determinants.
  • the term "monoclonal” antibody or antigen-binding fragment thereof encompasses both intact and full- length monoclonal antibodies as well as antibody fragments (such as Fab, Fab', F(ab')2, Fv), single chain (scFv) mutants, fusion proteins comprising an antibody portion, and any other modified immunoglobulin molecule comprising an antigen recognition site.
  • “monoclonal” antibody or antigen-binding fragment thereof refers to such antibodies and antigen-binding fragments thereof made in any number of manners including but not limited to by hybridoma, phage selection, recombinant expression, and transgenic animals.
  • the term "polyclonal antibody” describes a composition of different (diverse) antibody molecules which are capable of binding to or reacting with several different specific antigenic determinants on the same or on different antigens. Usually, the variability of a polyclonal antibody is located in the so-called variable regions of the polyclonal antibody, in particular in the CDR regions.
  • a mixture of two or more polyclonal antibodies is produced in one mixture from a polyclonal polycomposition cell line, which is produced from two or more parental polyclonal cell lines each expressing antibody molecules which are capable of binding to a distinct target, but it may also be a mixture of two or more polyclonal antibodies produced separately.
  • a mixture of monoclonal antibodies providing the same antigen/epitope coverage as a polyclonal antibody described herein will be considered as an equivalent of a polyclonal antibody.
  • humanized antibody or antigen-binding fragment thereof refers to forms of non-human (e.g. murine) antibodies or antigen-binding fragments that are specific immunoglobulin chains, chimeric immunoglobulins, or fragments thereof that contain minimal non-human (e.g., murine) sequences.
  • humanized antibodies or antigen-binding fragments thereof are human immunoglobulins in which residues from the complementary determining region (CDR) are replaced by residues from the CDR of a non-human species (e.g. murine) that have the desired specificity, affinity, and capability (“CDR grafted") (Jones et al., Nature 321:522-525 (1986); Riechmann et al., Nature 332:323-327 (1988); Verhoeyen et al., Science 239:1534-1536 (1988)).
  • CDR complementary determining region
  • the Fv framework region (FR) residues of a human immunoglobulin are replaced with the corresponding residues in an antibody or fragment from a non-human species (e.g., murine) that has the desired specificity, affinity, and capability.
  • the humanized antibody or antigen-binding fragment thereof can be further modified by the substitution of additional residues either in the Fv framework region and/or within the replaced non-human residues to refine and optimize antibody or antigen-binding fragment thereof specificity, affinity, and/or capability.
  • the humanized antibody or antigen-binding fragment thereof will comprise substantially all of at least one, and typically two or three, variable domains containing all or substantially all of the CDR regions that correspond to the non-human immunoglobulin whereas all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence.
  • the humanized antibody or antigen-binding fragment thereof can also comprise at least a portion of an immunoglobulin constant region or domain (Fc), typically that of a human immunoglobulin. Examples of methods used to generate humanized antibodies are described in U.S. Pat.5,225,539; Roguska et al., Proc. Natl. Acad.
  • a "humanized antibody” is a resurfaced antibody.
  • chimeric antibodies or antigen-binding fragments thereof refers to antibodies or antigen-binding fragments thereof wherein the amino acid sequence is derived from two or more species.
  • variable region of both light and heavy chains corresponds to the variable region of antibodies or antigen-binding fragments thereof derived from one species of mammals (e.g., mouse) with the desired specificity, affinity, and capability while the constant regions are homologous to the sequences in antibodies or antigen-binding fragments thereof derived from another (usually human) to avoid eliciting an immune response in that species.
  • epipe or "antigenic determinant” are used interchangeably herein and refer to that portion of an antigen capable of being recognized and specifically bound by a particular antibody.
  • epitopes can be formed both from contiguous amino acids and noncontiguous amino acids juxtaposed by tertiary folding of a protein. Epitopes formed from contiguous amino acids are typically retained upon protein denaturing, whereas epitopes formed by tertiary folding are typically lost upon protein denaturing.
  • An epitope typically includes at least 3, and more usually, at least 5 or 8-10 amino acids in a unique spatial conformation.
  • Binding affinity generally refers to the strength of the sum total of non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen).
  • binding affinity refers to intrinsic binding affinity which reflects a 1:1 interaction between members of a binding pair (e.g., antibody and antigen).
  • the affinity of a molecule X for its partner Y can generally be represented by the dissociation constant (Kd).
  • Kd dissociation constant
  • Affinity can be measured by common methods known in the art, including those described herein. Low-affinity antibodies generally bind antigen slowly and tend to dissociate readily, whereas high-affinity antibodies generally bind antigen faster and tend to remain bound longer.
  • a variety of methods of measuring binding affinity are known in the art, any of which can be used for purposes of the present invention. Specific illustrative embodiments are described in the following.
  • binding affinity refers to a stronger binding between a molecule and its binding partner.
  • Or better when used herein refers to a stronger binding, represented by a smaller numerical Kd value.
  • an antibody which has an affinity for an antigen of "0.6 nM or better” the antibody's affinity for the antigen is ⁇ 0.6 nM, i.e. 0.59 nM, 0.58 nM, 0.57 nM etc. or any value less than 0.6 nM.
  • the terms “immunospecifically binds,” “immunospecifically recognizes,” “specifically binds,” and “specifically recognizes” are analogous terms in the context of antibodies and refer to molecules that bind to an antigen (e.g., epitope or immune complex) as such binding is understood by one skilled in the art.
  • an antigen e.g., epitope or immune complex
  • a molecule that specifically binds to an antigen can bind to other peptides or polypeptides, generally with lower affinity as determined by, e.g., immunoassays, BIAcore ® , KinExA 3000 instrument (Sapidyne Instruments, Boise, ID), or other assays known in the art.
  • molecules that immunospecifically bind to an antigen bind to the antigen with a Kd that is at least 2 logs, 2.5 logs, 3 logs, or 4 logs lower than the Kd when the molecules bind non-specifically to another antigen.
  • the antibody specifically binds to 3FTx-L1 comprising the amino acid sequence of SEQ ID NO: 161.
  • the antibody specifically binds to 3FTx-L3 comprising the amino acid sequence of SEQ ID NO: 162.
  • the antibody specifically binds to 3FTx-L4 comprising the amino acid sequence of SEQ ID NO: 163.
  • the antibody specifically binds to 3FTx-L5 comprising the amino acid sequence of SEQ ID NO: 164. In some embodiments, the antibody specifically binds to 3FTx-L6 comprising the amino acid sequence of SEQ ID NO: 165. In some embodiments, the antibody specifically binds to 3FTx-L8 comprising the amino acid sequence of SEQ ID NO: 166. In some embodiments, the antibody specifically binds to 3FTx-L9 comprising the amino acid sequence of SEQ ID NO: 167. In some embodiments, the antibody specifically binds to 3FTx-L10 comprising the amino acid sequence of SEQ ID NO: 168.
  • the antibody specifically binds to 3FTx-L11 comprising the amino acid sequence of SEQ ID NO: 169. In some embodiments, the antibody specifically binds to 3FTx-L12 comprising the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody specifically binds to 3FTx-L13 comprising the amino acid sequence of SEQ ID NO: 171. In some embodiments, the antibody specifically binds to 3FTx-L14 comprising the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody specifically binds to 3FTx-L15 comprising the amino acid sequence of SEQ ID NO: 173.
  • the antibody specifically binds to 3FTx-L1 comprising the amino acid sequence of SEQ ID NO: 174. In some embodiments, the antibody specifically binds to 3FTx-L16 comprising the amino acid sequence of SEQ ID NO: 175. In some embodiments, the antibody specifically binds to 3FTx-L17 comprising the amino acid sequence of SEQ ID NO: 176. In some embodiments, the antibody specifically binds to 3FTx-L18 comprising the amino acid sequence of SEQ ID NO: 177.
  • the antibody specifically binds to 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, and 3FTx-L15 variants listed in Table 1.
  • the antibody specifically binds to 3FTx-L2 comprising the amino acid sequence of SEQ ID NO: 162, 3FTx-L3 comprising the amino acid sequence of SEQ ID NO: 163, 3FTx-L5 comprising the amino acid sequence of SEQ ID NO: 165, 3FTx-L6 comprising the amino acid sequence of SEQ ID NO: 166, 3FTx-L8 comprising the amino acid sequence of SEQ ID NO: 167, 3FTx-L9 comprising the amino acid sequence of SEQ ID NO: 168, and 3FTx-L15 comprising the amino acid sequence of SEQ ID NO: 174, as listed in Table 1.
  • preferentially binds it is meant that the antibody specifically binds to an epitope more readily than it would bind to a related, similar, homologous, or analogous epitope.
  • an antibody which "preferentially binds" to a given epitope would more likely bind to that epitope than to a related epitope, even though such an antibody may cross-react with the related epitope.
  • An antibody is said to "competitively inhibit" binding of a reference antibody to a given epitope if it preferentially binds to that epitope or an overlapping epitope to the extent that it blocks, to some degree, binding of the reference antibody to the epitope.
  • Competitive inhibition may be determined by any method known in the art, for example, competition ELISA assays.
  • An antibody may be said to competitively inhibit binding of the reference antibody to a given epitope by at least 90%, at least 80%, at least 70%, at least 60%, or at least 50%.
  • the phrase "substantially similar,” or “substantially the same”, as used herein, denotes a sufficiently high degree of similarity between two numeric values (generally one associated with an antibody described herein and the other associated with a reference/comparator antibody) such that one of skill in the art would consider the difference between the two values to be of little or no biological and/or statistical significance within the context of the biological characteristic measured by said values (e.g., Kd values).
  • a polypeptide, antibody, polynucleotide, vector, cell, or composition which is "isolated” is a polypeptide, antibody, polynucleotide, vector, cell, or composition which is in a form not found in nature. Isolated polypeptides, antibodies, polynucleotides, vectors, cell or compositions include those which have been purified to a degree that they are no longer in a form in which they are found in nature.
  • an antibody, polynucleotide, vector, cell, or composition which is isolated is substantially pure.
  • substantially pure refers to material which is at least 50% pure (i.e., free from contaminants), at least 90% pure, at least 95% pure, at least 98% pure, or at least 99% pure.
  • polypeptide polypeptide
  • the terms also encompass an amino acid polymer that has been modified naturally or by intervention; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as conjugation with a labeling component.
  • polypeptides containing one or more analogs of an amino acid including, for example, unnatural amino acids, etc.
  • the polypeptides described herein are based upon antibodies, in certain embodiments, the polypeptides can occur as single chains or associated chains.
  • nucleic acids or polypeptides refer to two or more sequences or subsequences that are the same or have a specified percentage of nucleotides or amino acid residues that are the same, when compared and aligned (introducing gaps, if necessary) for maximum correspondence, not considering any conservative amino acid substitutions as part of the sequence identity.
  • the percent identity can be measured using sequence comparison software or algorithms or by visual inspection.
  • sequence comparison software or algorithms or by visual inspection.
  • Various algorithms and software are known in the art that can be used to obtain alignments of amino acid or nucleotide sequences.
  • One such non-limiting example of a sequence alignment algorithm is the algorithm described in Karlin et al, Proc. Natl. Acad.
  • Gapped BLAST can be used as described in Altschul et al., Nucleic Acids Res. 25:3389-3402 (1997).
  • BLAST-2 Altschul et al., Methods in Enzymology, 266:460-480 (1996)), ALIGN, ALIGN-2 (Genentech, South San Francisco, California) or Megalign (DNASTAR) are additional publicly available software programs that can be used to align sequences.
  • the percent identity between two nucleotide sequences is determined using the GAP program in GCG software (e.g., using a NWSgapdna.CMP matrix and a gap weight of 40, 50, 60, 70, or 90 and a length weight of 1, 2, 3, 4, 5, or 6).
  • the GAP program in the GCG software package which incorporates the algorithm of Needleman and Wunsch (J.
  • Mol. Biol. (48):444-453 (1970)) can be used to determine the percent identity between two amino acid sequences (e.g., using either a Blossum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5).
  • the percent identity between nucleotide or amino acid sequences is determined using the algorithm of Myers and Miller (CABIOS, 4:11-17 (1989)).
  • the percent identity can be determined using the ALIGN program (version 2.0) and using a PAM120 with residue table, a gap length penalty of 12 and a gap penalty of 4.
  • Appropriate parameters for maximal alignment by particular alignment software can be determined by one skilled in the art.
  • the default parameters of the alignment software are used.
  • the percentage identity "X" of a first amino acid sequence to a second sequence amino acid is calculated as 100 x (Y/Z), where Y is the number of amino acid residues scored as identical matches in the alignment of the first and second sequences (as aligned by visual inspection or a particular sequence alignment program) and Z is the total number of residues in the second sequence. If the length of a first sequence is longer than the second sequence, the percent identity of the first sequence to the second sequence will be longer than the percent identity of the second sequence to the first sequence.
  • whether any particular polynucleotide has a certain percentage sequence identity can, in certain embodiments, be determined using the Bestfit program (Wisconsin Sequence Analysis Package, Version 8 for Unix, Genetics Computer Group, University Research Park, 575 Science Drive, Madison, WI 53711). Bestfit uses the local homology algorithm of Smith and Waterman (Advances in Applied Mathematics 2: 482 489 (1981)) to find the best segment of homology between two sequences.
  • the parameters are set such that the percentage of identity is calculated over the full length of the reference nucleotide sequence and that gaps in homology of up to 5% of the total number of nucleotides in the reference sequence are allowed.
  • two nucleic acids or polypeptides described herein are substantially identical, meaning they have at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, and in some embodiments at least 95%, 96%, 97%, 98%, 99% nucleotide or amino acid residue identity, when compared and aligned for maximum correspondence, as measured using a sequence comparison algorithm or by visual inspection.
  • Identity can exist over a region of the sequences that is at least about 10, about 20, about 40-60 residues in length or any integral value there between, and can be over a longer region than 60-80 residues, for example, at least about 90-100 residues, and in some embodiments, the sequences are substantially identical over the full length of the sequences being compared, such as the coding region of a nucleotide sequence for example.
  • a "conservative amino acid substitution" is one in which one amino acid residue is replaced with another amino acid residue having a similar side chain.
  • Families of amino acid residues having similar side chains have been defined in the art, including basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine).
  • basic side chains e.g., lysine, arginine, histidine
  • acidic side chains e.g., aspartic acid
  • substitution of a phenylalanine for a tyrosine is a conservative substitution.
  • conservative substitutions in the sequences of the polypeptides and antibodies described herein do not abrogate the binding of the polypeptide or antibody containing the amino acid sequence, to the antigen(s).
  • Methods of identifying nucleotide and amino acid conservative substitutions which do not eliminate antigen binding are well- known in the art (see, e.g., Brummell et al., Biochem. 32: 1180-1187 (1993); Kobayashi et al., Protein Eng.12(10):879-884 (1999); and Burks et al., Proc. Natl. Acad. Sci.
  • treatment refers to treatment of a person who suffered a snake bite, is suspected of having suffered a snake bite or is likely to suffer a snake bite.
  • treating includes alleviating or reducing at least one adverse or negative effect or symptom of a condition, disease or disorder. This condition, disease or disorder can be a condition, disease or disorder associate with snake bite.
  • effective amount refers to an amount effective, at dosages, and for periods of time necessary, to achieve the desired result with respect to the treatment of the relevant disorder, condition, or side effect.
  • an "effective amount” can be determined empirically and in a routine manner, in relation to the stated purpose. It will be appreciated that the effective amount of components of the present invention will vary from patient to patient not only with the particular vaccine, component or composition selected, the route of administration, and the ability of the components to elicit a desired result in the individual, but also with factors such as the disease state or severity of the condition to be alleviated, hormone levels, age, sex, weight of the individual, the state of being of the patient, and the severity of the pathological condition being treated, concurrent medication or special diets then being followed by the particular patient, and other factors which those skilled in the art will recognize, with the appropriate dosage being at the discretion of the attending physician. Dosage regimes may be adjusted to provide the improved therapeutic response.
  • an effective amount is also one in which any toxic or detrimental effects of the components are outweighed by the therapeutically beneficial effects.
  • therapeutically effective amount refers to an amount of an antibody, immunoconjugate, or other drug effective to "treat” a disease or disorder in a subject or mammal.
  • prophylactically effective amount refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired prophylactic result. Typically but not necessarily, since a prophylactic dose is used in subjects prior to or at an earlier stage of disease, the prophylactically effective amount will be less than the therapeutically effective amount.
  • the terms "subject,” “individual,” and “patient” are used interchangeably herein, and refer to an animal, for example a human, to whom treatment, including prophylactic treatment, with the antibody or pharmaceutical composition according to the present disclosure, is provided.
  • the subject, individual, or patient has suffered a snake bite or is suspected of having suffered a snake bite.
  • the subject, individual, or patient is at risk of suffering a snake bite.
  • Administration "in combination with" one or more further therapeutic agents includes simultaneous (concurrent) or consecutive administration in any order.
  • composition refers to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem complications commensurate with a reasonable benefit/risk ratio.
  • “Pharmaceutically acceptable” or “pharmaceutical formulation” refers to a preparation which is in such form as to permit the biological activity of the active ingredient to be effective, and which contains no additional components which are unacceptably toxic to a subject to which the formulation would be administered.
  • the formulation can be sterile.
  • an antibody described herein is a monoclonal antibody. In some embodiments, an antibody described herein is a human antibody. In some embodiments, an antibody described herein specifically binds least one 3FTx-L variant listed in Table 1. In some embodiments, an antibody described herein specifically binds at least two, at least three, at least four, or at least five 3FTx-L variants listed in Table 1. In some embodiments, an antibody described herein specifically binds 1, 2, 3, 4, 5, 10, or 15 3FTX_LCa variants listed in Table 1. In some embodiments, an antibody described herein specifically binds all 3FTx-L variants listed in Table 1.
  • the antibody specifically binds to at least three of 3FTx-L1, 3FTx-L2, 3FTx-L3, 3FTx-L5, and 3FTx- L6 variants listed in Table 1. In some embodiments, the antibody specifically binds to 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, and 3FTx-L15 variants listed in Table 1.
  • the antibody specifically binds to 3FTx-L2 comprising the amino acid sequence of SEQ ID NO: 162, 3FTx-L3 comprising the amino acid sequence of SEQ ID NO: 163, 3FTx-L5 comprising the amino acid sequence of SEQ ID NO: 165, 3FTx-L6 comprising the amino acid sequence of SEQ ID NO: 166, 3FTx-L8 comprising the amino acid sequence of SEQ ID NO: 167, 3FTx-L9 comprising the amino acid sequence of SEQ ID NO: 168, and 3FTx-L15 comprising the amino acid sequence of SEQ ID NO: 174, as listed in Table 1.
  • an isolated monoclonal antibody described herein comprises a VH that is a VH1-02, VH1-18, VH1-69 or VH3-07 VH and a VL that is a VL2-14, VK3-20, VK1-39, VL2-14 or VL1-51 VL.
  • the antibody comprises a VH that is a VH1-02 VH and a VL that is a VL2-14, VK3-20, or VK1-39 VL.
  • the antibody comprises a VH that is a VH1-18 VH and a VL that is a VL2-14 or VK3-20 VL.
  • the antibody comprises a VH that is a VH1-69 VH and a VL that is a VK1-39 or VL1-51 VL. In some embodiments, the antibody comprises a VH that is a VH3-07 VH and a VL that is a VL1-51 VL.
  • an isolated monoclonal antibody described herein comprises a VH CDR3 that comprises 19 or 20 residues comprising the amino acid sequence of SEQ ID NO: 244 or 245. In some embodiments, the VH CDR3 comprises the amino acid sequence of 246, 247, 248 or 249. In some embodiments, the VH CDR3 comprises the amino acid sequence of 246 or 248.
  • the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, 123, 133, 143 or 153 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222, or 238 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222, or 238.
  • the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153.
  • the antibody further comprises VH CDR1 residues Thr28, Ser31 and Tyr32, VL CDR2 residue Asp50, and VL CDR3 residues Ser91 and Tyr92.
  • the antibody further comprises a VH that is a VH1-02, VH1-18, VH1-69 or VH3-07 VH and a VL that is a VL2-14, VK3-20, VK139, VL2-14 or VL1-51 VL.
  • the antibody further comprises a VH that is a VH1-69 VH and a VL that is a VK1-39 VL.
  • an isolated monoclonal antibody described herein comprises a VH CDR3 that comprises 19 residues comprising the amino acid sequence of SEQ ID NO: 244 or 245.
  • the VH CDR3 comprises the amino acid sequence of 248 or 249.
  • the VH CDR3 comprises the amino acid sequence of 248.
  • the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, 123, 133, 143 or 153 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222, or 238 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222, or 238. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153. In some embodiments, the antibody further comprises VH CDR1 residues Thr28, Ser31 and Tyr32, VL CDR2 residue Asp50, and VL CDR3 residues Ser91 and Tyr92.
  • the antibody further comprises a VH that is a VH1-02, VH1-18, VH1-69 or VH3-07 VH and a VL that is a VL2-14, VK3-20, VK139, VL2-14 or VL1-51 VL.
  • the antibody further comprises a VH that is a VH1-69 VH and a VL that is a VK1-39 VL.
  • the residue numbers and CDRs are according to Kabat.
  • an isolated monoclonal antibody described herein comprises a VH CDR3 that comprises 20 residues comprising the amino acid sequence of SEQ ID NO: 244 or 245.
  • the VH CDR3 comprises the amino acid sequence of 246 or 247. In some embodiments, the VH CDR3 comprises the amino acid sequence of 246. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, 123, 133, 143 or 153 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222, or 238 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222, or 238. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153. In some embodiments, the antibody further comprises VH CDR1 residues Thr28, Ser31 and Tyr32, VL CDR2 residue Asp50, and VL CDR3 residues Ser91 and Tyr92. In some embodiments, the antibody further comprises a VH that is a VH1-02, VH1-18, VH1-69 or VH3-07 VH and a VL that is a VL2-14, VK3-20, VK139, VL2-14 or VL1-51 VL.
  • the antibody further comprises a VH that is a VH1-69 VH and a VL that is a VK1-39 VL.
  • the residue numbers and CDRs are according to Kabat.
  • an isolated monoclonal antibody described herein comprises a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 153, 214, 222, or 238 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222, or 238.
  • the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153.
  • the antibody further comprises VH CDR1 residues Thr28, Ser31 and Tyr32, VL CDR2 residue Asp50, and VL CDR3 residues Ser91 and Tyr92.
  • the antibody further comprises a VH that is a VH1-02, VH1-18, VH1-69 or VH3-07 VH and a VL that is a VL2-14, VK3-20, VK139, VL2- 14 or VL1-51 VL.
  • the antibody further comprises a VH that is a VH1-69 VH and a VL that is a VK1-39 VL.
  • the residue numbers and CDRs are according to Kabat.
  • an isolated monoclonal antibody described herein comprises (1) a VH CDR1 comprising the VH CDR1 of LB5_95, (2) a VH CDR2 comprising the amino acid sequence of SEQ ID NO: LB5_95, 95MAT3, 96MAT5, or 95MAT6, (3) a VH CDR3 comprising the amino acid sequence of SEQ ID NO: LB5_95, 95MAT3, 95MAT4 or 95MAT6, (4) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: LB5_95, (5) a VL CDR2 comprising the amino acid sequence of SEQ ID NO: LB5_95 or 95MAT5, and (6) a VL CDR3 comprising the amino acid sequence of SEQ ID NO: LB5_95.
  • an isolated monoclonal antibody described herein comprises the VH CDR1, VH CDR2 and VH CDR3 of LB95_5, 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6.
  • the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of LB95_5.
  • the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT1.
  • the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT2.
  • the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT3. In some embodiments, the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT4. In some embodiments, the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT5. In some embodiments, the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT6. In some embodiments, the antibody further comprises the VL CDR1, VL CDR2 and VL CDR3 of LB95_5, 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6.
  • the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of LB95_5. In some embodiments, the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT1. In some embodiments, the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT2. In some embodiments, the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT3. In some embodiments, the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT4. In some embodiments, the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT5.
  • the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT6.
  • the CDRs are according to Kabat.
  • an isolated monoclonal antibody described herein comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of LB95_5, 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6.
  • the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of LB5_95.
  • the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT1. In some embodiments, the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT2. In some embodiments, the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT3. In some embodiments, the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT4.
  • the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT5. In some embodiments, the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT6. In some embodiments, the CDRs are according to Kabat.
  • an isolated monoclonal antibody described herein comprises (1) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 151 comprising 0, 1, 2, 3, 4, or 5 substitutions, (2) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 152, 213, 229, or 237 comprising 0, 1, 2, 3, 4, or 5 substitutions, (3) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 153, 214, 222 or 238 comprising 0, 1, 2, 3, 4, or 5 substitutions, (4) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 154 comprising 0, 1, 2, 3, 4, or 5 substitutions, (5) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 155 or 232 comprising 0, 1, 2, 3, 4, or 5 substitutions, and (6) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 156 comprising 0, 1, 2, 3, 4, or 5 substitutions.
  • the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222, or 238. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153. In some embodiments, the antibody further comprises VH CDR1 residues Thr28, Ser31 and Tyr32, VL CDR2 residue Asp50, and VL CDR3 residues Ser91 and Tyr92.
  • the antibody comprises (1) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 151, (2) a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 152, 213, 229, or 237, (3) a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 153, 214, 222 or 238, (4) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 154, (5) a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 155 or 232, and (6) a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 156.
  • the antibody further comprises a VH that is a VH1-02, VH1-18, VH1-69 or VH3-07 VH and a VL that is a VL2-14, VK3-20, VK139, VL2-14 or VL1-51 VL.
  • the antibody further comprises a VH that is a VH1-69 VH and a VL that is a VK1-39 VL.
  • the residue numbers and CDRs are according to Kabat.
  • an isolated monoclonal antibody described herein comprises (1) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 151, (2) a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 152, 213, 229, or 237, (3) a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 153, 214, 222 or 238, (4) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 154, (5) a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 155 or 232, and (6) a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 156.
  • an isolated monoclonal antibody described herein comprises a VH CDR1, VH CDR2 and VH CDR3 comprising the amino acid sequence of SEQ ID NO: 151-153, respectively, SEQ ID NO: 196-198, respectively, SEQ ID NO: 204-206, respectively, SEQ ID NO: 212-214, respectively, SEQ ID NO: 220-222, respectively, SEQ ID NO: 228-230, respectively, and SEQ ID NO: 236-238, respectively.
  • the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 151-153, respectively.
  • the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 196-198, respectively. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 204-206, respectively. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 212-214, respectively. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 220-222, respectively.
  • the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 228-230, respectively. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 236-238, respectively.
  • the antibody further comprises a VL CDR1, VL CDR2 and VL CDR3 comprising the amino acid sequence of SEQ ID NO: 154-156, respectively, SEQ ID NO: 199-201, respectively, SEQ ID NO: 207-209, respectively, SEQ ID NO: 215-217, respectively, SEQ ID NO: 223-225, respectively, SEQ ID NO: 231-233, respectively, and SEQ ID NO: 239-241, respectively.
  • the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 154-156, respectively.
  • the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 199-201, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 207- 209, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 215-217, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 223-225, respectively.
  • the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 231-233, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 239-241, respectively.
  • an isolated monoclonal antibody described herein comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprising the amino acid sequence of SEQ ID NO: 151-156, respectively, SEQ ID NO: 196-201, respectively, SEQ ID NO: 204-209, respectively, SEQ ID NO: 212-217, respectively, SEQ ID NO: 220-225, respectively, SEQ ID NO: 228-233, respectively, and SEQ ID NO: 236-241, respectively.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 151-156, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 196-201, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 204-209, respectively.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 212-217, respectively.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 220-225, respectively.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 228-233, respectively.
  • VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 236-241, respectively.
  • an isolated monoclonal antibody described herein comprises a VH comprising an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to LB95_5, 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6 VH.
  • the antibody further comprises a VL comprising an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to LB95_5, 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6 VL.
  • the antibody comprises the VH and VL of LB95_5, 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6.
  • the antibody comprises the VH and VL of LB95_5.
  • the antibody comprises the VH and VL of 95MAT1.
  • the antibody comprises the VH and VL of 95MAT2.
  • the antibody comprises the VH and VL of 95MAT3.
  • an isolated monoclonal antibody described herein comprises a VH comprising an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 157, 202, 210, 218, 226, 234, or 242.
  • the antibody further comprises a VL comprising an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 158, 203, 211, 219, 227, 235, or 243.
  • the antibody comprises a VH and VL comprising an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 157 and 158, respectively, SEQ ID NO: 202 and 203, respectively, SEQ ID NO: 210 and 211, respectively, SEQ ID NO: 218 and 219, respectively, SEQ ID NO: 226 and 227, respectively, SEQ ID NO: 234 and 235, respectively, or SEQ ID NO: 242 and 243, respectively.
  • the antibody comprises a VH and VL comprising the amino acid sequence of SEQ ID NO: 157 and 158, respectively, SEQ ID NO: 202 and 203, respectively, SEQ ID NO: 210 and 211, respectively, SEQ ID NO: 218 and 219, respectively, SEQ ID NO: 226 and 227, respectively, SEQ ID NO: 234 and 235, respectively, or SEQ ID NO: 242 and 243, respectively.
  • the antibody comprises a VH and VL comprising the amino acid sequence of SEQ ID NO: 157 and 158, respectively.
  • the antibody comprises a VH and VL comprising the amino acid sequence of SEQ ID NO: 202 and 203, respectively.
  • the antibody comprises a VH and VL comprising the amino acid sequence of SEQ ID NO: 210 and 211, respectively. In some embodiments, the antibody comprises a VH and VL comprising the amino acid sequence of SEQ ID NO: 218 and 219, respectively. In some embodiments, the antibody comprises a VH and VL comprising the amino acid sequence of SEQ ID NO: 226 and 227, respectively. In some embodiments, the antibody comprises a VH and VL comprising the amino acid sequence of SEQ ID NO: 234 and 235, respectively. In some embodiments, the antibody comprises a VH and VL comprising the amino acid sequence of SEQ ID NO: 242 and 243, respectively.
  • an isolated monoclonal antibody described herein comprises a VH, a VL, or a VH and VL sequence listed in Table 2. In some embodiments, an isolated monoclonal antibody described herein comprises a VH, a VL, or a VH and VL sequence listed in Table 3. In some embodiments, an isolated monoclonal antibody described herein comprises a VH, a VL, or a VH and VL sequence listed in Table 2 and Table 3.
  • an isolated monoclonal antibody described herein comprises one, two, three, four, five or six of the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences listed in Table 2. In some embodiments, an isolated monoclonal antibody described herein comprises one, two, three, four, five or six of the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences listed in Table 3.
  • an isolated monoclonal antibody described herein comprises one, two, three, four, five or six of the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences listed in Table 2 and Table 3. [0089] In some embodiments, an isolated monoclonal antibody described herein comprises a VH CDR3 sequence listed in Table 2. In some embodiments, an isolated monoclonal antibody described herein comprises a VH CDR3 sequence listed in Table 3. In some embodiments, an isolated monoclonal antibody described herein comprises a VH CDR3 sequence listed in Table 2 and Table 3.
  • an isolated monoclonal antibody described herein comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequence listed in Table 2. In some embodiments, an isolated monoclonal antibody described herein comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequence listed in Table 3. In some embodiments, an isolated monoclonal antibody described herein comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequence listed in Table 2 and Table 3.
  • polypeptides that comprise an amino acid sequence having at least about 80% sequence identity, at least about 85% sequence identity, at least about 90% sequence identity, at least about 95% sequence identity, at least about 96% sequence identity, at least about 97% sequence identity, at least about 98% sequence identity, or at least about 99% sequence, or is identical to a sequence listed in Table 2. Also provided herein are polypeptides that comprise an amino acid sequence having at least about 80% sequence identity, at least about 85% sequence identity, at least about 90% sequence identity, at least about 95% sequence identity, at least about 96% sequence identity, at least about 97% sequence identity, at least about 98% sequence identity, or at least about 99% sequence, or is identical to a sequence listed in Table 3.
  • an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR3 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95.
  • VH heavy chain variable region
  • VL light chain variable region
  • an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR3 of LB5_95.
  • VH heavy chain variable region
  • VL light chain variable region
  • an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, 123, 133, 143 or 153.
  • an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 153.
  • VH heavy chain variable region
  • VL light chain variable region
  • an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the VH CDR3 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • VH heavy chain variable region
  • VL light chain variable region
  • an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the VH CDR3 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • VH heavy chain variable region
  • VL light chain variable region
  • an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, 123, 133, 143 or 153 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • VH heavy chain variable region
  • VL light chain variable region
  • an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the VH CDR3 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6.
  • the VH CDR3 comprises the VH CDR3 of 95MAT1.
  • the VH CDR3 comprises the VH CDR3 of 95MAT2.
  • the VH CDR3 comprises the VH CDR3 of 95MAT3. In some embodiments, the VH CDR3 comprises the VH CDR3 of 95MAT4. In some embodiments, the VH CDR3 comprises the VH CDR3 of 95MAT5. In some embodiments, the VH CDR3 comprises the VH CDR3 of 95MAT6.
  • an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222 or 238.
  • the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153.
  • the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 214.
  • the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 222. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 238.
  • an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR1 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_
  • an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR1 of LB5_95; the VH CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR2 of LB5_95; and the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR3 of LB5_95.
  • VH heavy chain variable region
  • VL light
  • an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 1, 11, 21, 31, 41, 51, 61, 71, 81, 91, 101, 111, 121, 131, 141 or 151; the VH CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 2, 12, 22, 32, 42, 52, 62, 72, 82, 92, 102, 112, 122, 132, 142 or
  • an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 151; the VH CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 152; and the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 153.
  • VH heavy chain variable region
  • VL light chain variable region
  • an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises the VH CDR1 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; the VH CDR2 comprises the VH CDR2 of LB5_49
  • an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises the VH CDR1 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; the VH CDR2 comprises the VH CDR2 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and the VH CDR3 comprises the VH CDR3 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • VH heavy chain variable region
  • VL light chain variable region
  • an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises the amino acid of SEQ ID NO: 1, 11, 21, 31, 41, 51, 61, 71, 81, 91, 101, 111, 121, 131, 141 or 151 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; the VH CDR2 comprises the amino acid of SEQ ID NO: 2, 12, 22, 32, 42, 52, 62, 72, 82, 92, 102, 112, 122, 132, 142 or 152 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and the VH
  • an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises the amino acid of SEQ ID NO: 151 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; the VH CDR2 comprises the amino acid of SEQ ID NO: 152 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and the VH CDR3 comprises the amino acid of SEQ ID NO: 153 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • VH heavy chain variable region
  • VL light chain variable region
  • an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises the VH CDR1 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6; the VH CDR2 comprises the VH CDR2 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6; and the VH CDR3 comprises the VH CDR3 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6.
  • VH heavy chain variable region
  • VL light chain variable region
  • an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises the amino acid of SEQ ID NO: 151; the VH CDR2 comprises amino acid of SEQ ID NO: 152, 213, 229 or 237; and the VH CDR3 comprises amino acid of SEQ ID NO: 153, 214, 222 or 238.
  • VH heavy chain variable region
  • VL light chain variable region
  • the VL CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VL CDR1 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95;
  • the VL CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VL CDR2 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_
  • the VL CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VL CDR1 of LB5_95;
  • the VL CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VL CDR2 of LB5_95;
  • the VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VL CDR3 of LB5_95.
  • the VL CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144 or 154;
  • the VL CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 5, 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 125, 135, 145 or 155;
  • the VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 6, 16, 26, 36, 46, 56, 66, 76, 86, 96, 106, 116, 126, 136, 146 or 156.
  • the VL CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 154;
  • the VL CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 155;
  • the VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 156.
  • the VL CDR1 comprises the VL CDR1 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions;
  • the VL CDR2 comprises the VL CDR2 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 comprising
  • the VL CDR1 comprises the VL CDR1 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions
  • the VL CDR2 comprises the VL CDR2 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions
  • the VL CDR3 comprises the VL CDR3 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • the VL CDR1 comprises the amino acid of SEQ ID NO: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144 or 154 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions;
  • the VL CDR2 comprises the amino acid of SEQ ID NO: 5, 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 125, 135, 145 or 155 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions;
  • the VL CDR3 comprises the amino acid of SEQ ID NO: 6, 16, 26, 36, 46, 56, 66, 76, 86, 96, 106, 116, 126, 136, 146 or 156 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • the VL CDR1 comprises the amino acid of SEQ ID NO: 154 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions;
  • the VL CDR2 comprises the amino acid of SEQ ID NO: 155 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions;
  • the VL CDR3 comprises the amino acid of SEQ ID NO: 156 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • the VL CDR1 comprises the VL CDR1 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6; the VL CDR2 comprises the VL CDR2 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6; and the VL CDR3 comprises the VL CDR2 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6.
  • the VL CDR1 comprises the amino acid of SEQ ID NO: 154; the VL CDR2 comprises the amino acid of 155, 232 or 240; and the VL CDR3 comprises the amino acid of SEQ ID NO: 156.
  • the VH CDR1, VH CDR2 and VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VH CDR1, VH CDR2 and VH CDR3, respectively.
  • the VH CDR1, VH CDR2 and VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_95 VH CDR1, VH CDR2 and VH CDR3, respectively.
  • the VH CDR1, VH CDR2 and VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 1, 2 and 3, respectively; SEQ ID NO: 11, 12 and 13, respectively; SEQ ID NO: 21, 22 and 23, respectively; SEQ ID NO: 31, 32 and 33, respectively; SEQ ID NO: 41, 42 and 43, respectively; SEQ ID NO: 51, 52 and 53, respectively; SEQ ID NO: 61, 62 and 63, respectively; SEQ ID NO: 71, 72 and 73, respectively; SEQ ID NO: 81, 82 and 83, respectively; SEQ ID NO: 91, 92 and 93, respectively; SEQ ID NO: 101, 102 and 103, respectively; SEQ ID NO: 111, 112 and 113, respectively; SEQ ID NO: 121, 122 and 123, respectively; SEQ ID NO: 131, 132 and 133, respectively;
  • the VH CDR1, VH CDR2 and VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 151, 152 and 153, respectively.
  • the VH CDR1, VH CDR2 and VH CDR3 comprises the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VH CDR1, VH CDR2 and VH CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • the VH CDR1, VH CDR2 and VH CDR3 comprises the LB5_95 VH CDR1, VH CDR2 and VH CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 1, 2 and 3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 11, 12 and 13, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 21, 22 and 23, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 31, 32 and 33, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 41, 42 and 43, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 51, 52 and 53, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 61, 62 and 63, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO
  • the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 151, 152 and 153, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • the VH CDR1, VH CDR2 and VH CDR3 comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6.
  • the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT1.
  • the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT2. In some embodiments, the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT3. In some embodiments, the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT4. In some embodiments, the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT5. In some embodiments, the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT6.
  • the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 196-198, respectively, SEQ ID NO: 204-206, respectively, SEQ ID NO: 212-214, respectively, SEQ ID NO: 220-222, respectively, SEQ ID NO: 228-230, respectively, and SEQ ID NO: 236-238, respectively.
  • the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 196-198, respectively.
  • the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 204-206, respectively.
  • the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 212-214, respectively. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 220-222, respectively. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 228-230, respectively. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 236-238, respectively.
  • the VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VL CDR1, VL CDR2 and VL CDR3, respectively.
  • the VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_95 VL CDR1, VL CDR2 and VL CDR3, respectively.
  • the VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 4, 5 and 6, respectively; SEQ ID NO: 14, 15 and 16, respectively; SEQ ID NO: 24, 25 and 26, respectively; SEQ ID NO: 34, 35 and 36, respectively; SEQ ID NO: 44, 45 and 46, respectively; SEQ ID NO: 54, 55 and 56, respectively; SEQ ID NO: 64, 65 and 66, respectively; SEQ ID NO: 74, 75 and 76, respectively; SEQ ID NO: 84, 85 and 86, respectively; SEQ ID NO: 94, 95 and 96, respectively; SEQ ID NO: 104, 105 and 106, respectively; SEQ ID NO: 114, 115 and 116, respectively; SEQ ID NO: 124, 125 and 126, respectively; SEQ ID NO: 134, 135 and 136, respectively; SEQ ID NO: 4, 5 and 6, respectively; SEQ ID NO
  • the VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 154, 155 and 156, respectively.
  • the VL CDR1, VL CDR2 and VL CDR3 comprises the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VL CDR1, VL CDR2 and VL CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • the VL CDR1, VL CDR2 and VL CDR3 comprises the LB5_95 VL CDR1, VL CDR2 and VL CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 4, 5 and 6, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 14, 15 and 16, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 24, 25 and 26, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 34, 35 and 36, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 44, 45 and 46, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 54, 55 and 56, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 64, 65 and 66, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO:
  • the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 154, 155 and 156, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • the VL CDR1, VL CDR2 and VL CDR3 comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6.
  • the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT1.
  • the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT2. In some embodiments, the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT3. In some embodiments, the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT4. In some embodiments, the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT5. In some embodiments, the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT6.
  • the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 199-201, respectively, SEQ ID NO: 207-209, respectively, SEQ ID NO: 215-217, respectively, SEQ ID NO: 223-225, respectively, SEQ ID NO: 231-233, respectively, and SEQ ID NO: 239-241, respectively.
  • the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 199-201, respectively.
  • the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 207-209, respectively.
  • the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 215- 217, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 223-225, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 231-233, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 239-241, respectively.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3, respectively.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_95 VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3, respectively.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 1, 2, 3, 4, 5 and 6, respectively; SEQ ID NO: 11, 12, 13, 14, 15 and 16, respectively; SEQ ID NO: 21, 22, 23, 24, 25 and 26, respectively; SEQ ID NO: 31, 32, 33, 34, 35 and 36, respectively; SEQ ID NO: 41, 42, 43, 44, 45 and 46, respectively; SEQ ID NO: 51, 52, 53, 54, 55 and 56, respectively; SEQ ID NO: 61, 62, 63, 64, 65 and 66, respectively; SEQ ID NO: 71, 72, 73, 74, 75 and 76, respectively; SEQ ID NO: 81, 82, 83, 84, 85 and 86, respectively; SEQ ID NO: 91, 92, 93
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 151, 152, 153, 154, 155 and 156, respectively.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the LB5_95 VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 1, 2, 3, 4, 5 and 6, respectively; SEQ ID NO: 11, 12, 13, 14, 15 and 16, respectively; SEQ ID NO: 21, 22, 23, 24, 25 and 26, respectively; SEQ ID NO: 31, 32, 33, 34, 35 and 36, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 41, 42, 43, 44, 45 and 46, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 51, 52, 53, 54, 55 and 56, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 61, 62, 63, 64, 65 and 66, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 61, 62, 63, 64
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 151, 152, 153, 154, 155 and 156, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6.
  • the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT1.
  • the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT2.
  • the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT3. In some embodiments, the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT4. In some embodiments, the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT5. In some embodiments, the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT6.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 151-156, respectively, SEQ ID NO: 196-201, respectively, SEQ ID NO: 204-209, respectively, SEQ ID NO: 212-217, respectively, SEQ ID NO: 220-225, respectively, SEQ ID NO: 228-233, respectively, and SEQ ID NO: 236-241, respectively.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 151-156, respectively.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 196-201, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 204-209, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 212-217, respectively.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 220-225, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 228-233, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 236-241, respectively.
  • the VH comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 7, 17, 27, 37, 47, 57, 67, 77, 87, 97, 107, 117, 127, 137, 147 or 157. In some embodiments of the monoclonal antibody described herein, the VH comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 157.
  • the VH comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 202, 210, 218, 226, 234, or 242.
  • the VH comprises the amino acid sequence of SEQ ID NO: 202.
  • the VH comprises the amino acid sequence of SEQ ID NO: 210.
  • the VH comprises the amino acid sequence of SEQ ID NO: 218.
  • the VH comprises the amino acid sequence of SEQ ID NO: 226.
  • the VH comprises the amino acid sequence of SEQ ID NO: 234.
  • the VH comprises the amino acid sequence of SEQ ID NO: 242.
  • the VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 8, 18, 28, 38, 48, 58, 68, 78, 88, 98, 108, 118, 128, 138, 148 or 158.
  • the VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 158.
  • the VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 203, 211, 219, 227, 235, or 243.
  • the VL comprises the amino acid sequence of SEQ ID NO: 203.
  • the VL comprises the amino acid sequence of SEQ ID NO: 211.
  • the VL comprises the amino acid sequence of SEQ ID NO: 219.
  • the VL comprises the amino acid sequence of SEQ ID NO: 227.
  • the VL comprises the amino acid sequence of SEQ ID NO: 235.
  • the VL comprises the amino acid sequence of SEQ ID NO: 243.
  • the VH and VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 157 and 158, respectively. In some embodiments of the monoclonal antibody described herein, the VH and VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 202 and 203, respectively, SEQ ID NO: 210 and 211, respectively, SEQ ID NO: 218 and 219, respectively, SEQ ID NO: 226 and 227, respectively, SEQ ID NO: 234 and 235, respectively, or SEQ ID NO: 242 and 243, respectively.
  • the VH and VL comprises the amino acid sequence of SEQ ID NO: 202 and 203, respectively, SEQ ID NO: 210 and 211, respectively, SEQ ID NO: 218 and 219, respectively, SEQ ID NO: 226 and 227, respectively, SEQ ID NO: 234 and 235, respectively, or SEQ ID NO: 242 and 243, respectively.
  • the VH and VL comprises the amino acid sequence of SEQ ID NO: 202 and 203, respectively.
  • the VH and VL comprises the amino acid sequence of SEQ ID NO: 210 and 211, respectively.
  • the VH and VL comprises the amino acid sequence of SEQ ID NO: 218 and 219, respectively. In some embodiments, the VH and VL comprises the amino acid sequence of SEQ ID NO: 226 and 227, respectively. In some embodiments, the VH and VL comprises the amino acid sequence of SEQ ID NO: 234 and 235, respectively. In some embodiments, the VH and VL comprises the amino acid sequence of SEQ ID NO: 242 and 243, respectively. In some embodiments, an isolated monoclonal antibody described herein further comprises heavy and/or light chain constant regions. In some embodiments, an isolated monoclonal antibody described herein further comprises human heavy and/or light chain constant regions.
  • the heavy chain constant region is selected from the group consisting of human immunoglobulins IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. In some embodiments, the heavy chain constant region is selected from the group consisting of human immunoglobulins IgG1, IgG2, IgG3, and IgG4. In some embodiments, the heavy chain constant region comprises a native amino acid sequence. In some embodiments, the heavy chain constant region comprises a variant amino acid sequence. In some embodiments, the antibody is a recombinant antibody, a chimeric antibody, a human antibody, an antibody fragment, a bispecific antibody, a trispecific antibody, or a multispecific antibody.
  • the antibody is a bispecific antibody, a trispecific antibody or a multispecific antibody.
  • an antibody described herein is a bispecific antibody, a trispecific antibody or a multispecific antibody capable of binding at least one toxic component of snake venom in addition to 3FTx-L.
  • the at least one toxic component of snake venom in addition to 3FTx-L comprises a metalloprotease or a phospholipase.
  • an antibody described herein is a multispecific antibody, e.g. a bispecific antibody. Multispecific antibodies are monoclonal antibodies that have binding specificities for at least two different epitopes.
  • one of the binding specificities is for 3FTx-L epitope and the other is for an epitope on a different antigen, e.g., a different neurotoxin, a cytotoxin, a cardiotoxin, a hemotoxin, or a myotoxin.
  • a multispecific antibody described herein binds to 3FTx-L and to a metalloproteinase.
  • a multispecific antibody described herein binds to 3FTx-L and to a phospholipase.
  • bispecific antibodies bind to two different epitopes of 3FTx-L. Bispecific antibodies can be prepared as full length antibodies or antibody fragments.
  • Multispecific antibodies include, but are not limited to, recombinant co-expression of two immunoglobulin heavy chain-light chain pairs having different specificities (see Milstein and Cuello, Nature 305: 537 (1983)), WO 93/08829, and Traunecker et al., EMBO J. 10: 3655 (1991)), and "knob-in-hole” engineering (see, e.g., U.S. Patent No. 5,731,168).
  • Multi-specific antibodies may also be made by engineering electrostatic steering effects for making antibody Fc-heterodimeric molecules (WO 2009/089004A1); cross- linking two or more antibodies or fragments (see, e.g., US Patent No.
  • an antibody described herein is a multispecific antibody, e.g. a bispecific antibody comprising a first antigen binding domain comprising a VH domain or VH and VL domains described herein, and a second antigen binding region capable of binding a second toxin.
  • the second antigen binding region binds to a different neurotoxin, a cytotoxin, a cardiotoxin, a hemotoxin, or a myotoxin.
  • the second antigen binding region binds to a metalloproteinase.
  • the second antigen binding region binds to a phospholipase.
  • the antibody fragment comprises a single-chain Fv (scFv), F(ab) fragment, F(ab')2 fragment, or an isolated VH domain.
  • the antibody is capable of neutralizing at least two 3FTx-L variants described herein.
  • an antibody described herein specifically binds 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, and 3FTx-L15 variants listed in Table 1.
  • an antibody described herein specifically binds least one 3FTx-L variant listed in Table 1.
  • an antibody described herein specifically binds at least two, at least three, at least four, or at least five 3FTx-L variants listed in Table 1. In some embodiments, an antibody described herein specifically binds 1, 2, 3, 4, 5, 10, or 15 3FTx-L variants listed in Table 1. In some embodiments, an antibody described herein specifically binds all 3FTx-L variants listed in Table 1. In some embodiments, an antibody described herein is capable of binding more than one 3FTx-L selected from the group consisting of SEQ ID NO: 161-176 and 177.
  • an antibody described herein is capable of binding at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15 or at least 163FTx-L selected from the group consisting of SEQ ID NO: 161-176 and 177. In some embodiments, an antibody described herein is capable of binding all 173FTx-L selected from the group consisting of SEQ ID NO: 161-176 and 177.
  • an antibody described herein specifically binds 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, and 3FTx-L15 variants listed in Table 1.
  • an antibody described herein specifically binds 3FTx-L2 comprising the amino acid sequence of SEQ ID NO: 162, 3FTx-L3 comprising the amino acid sequence of SEQ ID NO: 163, 3FTx-L5 comprising the amino acid sequence of SEQ ID NO: 165, 3FTx-L6 comprising the amino acid sequence of SEQ ID NO: 166, 3FTx-L8 comprising the amino acid sequence of SEQ ID NO: 167, 3FTx-L9 comprising the amino acid sequence of SEQ ID NO: 168, and 3FTx-L15 comprising the amino acid sequence of SEQ ID NO: 174, as listed in Table 1.
  • an antibody described herein specifically binds at least three of the 3FTx-L1, 3FTx-L2, 3FTx-L3, 3FTx-L5, and 3FTx-L6 variants listed in Table 1. In some embodiments, an antibody described herein is capable of neutralizing at least one 3FTx-L variant listed in Table 1. In some embodiments, an antibody described herein is capable of neutralizing at least two, at least three, at least four, or at least five 3FTx-L variants listed in Table 1. In some embodiments, an antibody described herein is capable of neutralizing 1, 2, 3, 4, 5, 10, or 153FTx-L variants listed in Table 1. In some embodiments, an antibody described herein is capable of neutralizing all 3FTx-L variants listed in Table 1.
  • an antibody described herein is capable of neutralizing in an in vitro cell based assay at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15 or at least 163FTx-L selected from the group consisting of SEQ ID NO: 161-176 and 177.
  • an antibody described herein is capable of neutralizing alpha-bungarotoxin comprising the amino acid sequence of SEQ ID NO: 250.
  • an antibody described herein is capable of neutralizing the 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, and 3FTx-L15 variants listed in Table 1.
  • an antibody described herein is capable of neutralizing 3FTx-L2 comprising the amino acid sequence of SEQ ID NO: 162, 3FTx-L3 comprising the amino acid sequence of SEQ ID NO: 163, 3FTx-L5 comprising the amino acid sequence of SEQ ID NO: 165, 3FTx-L6 comprising the amino acid sequence of SEQ ID NO: 166, 3FTx-L8 comprising the amino acid sequence of SEQ ID NO: 167, 3FTx-L9 comprising the amino acid sequence of SEQ ID NO: 168, and 3FTx-L15 comprising the amino acid sequence of SEQ ID NO: 174, as listed in Table 1.
  • an antibody described herein is capable of neutralizing at least three of the 3FTx-L1, 3FTx-L2, 3FTx-L3, 3FTx-L5, and 3FTx-L6 variants listed in Table 1.
  • neutralization is assessed in a cell based in vitro assay.
  • neutralization is assessed in an in vivo assay.
  • provided herein are antibodies that bind the same or an overlapping epitope of 3FTx-L as an antibody described herein.
  • the epitope of an antibody can be determined by, e.g., NMR spectroscopy, X-ray diffraction crystallography studies, ELISA assays, hydrogen/deuterium exchange coupled with mass spectrometry (e.g., liquid chromatography electrospray mass spectrometry), array-based oligo-peptide scanning assays, and/or mutagenesis mapping (e.g., site-directed mutagenesis mapping).
  • crystallization may be accomplished using any of the known methods in the art (e.g., Giegé R et al., (1994) Acta Crystallogr D Biol Crystallogr 50(Pt 4): 339-350; McPherson A (1990) Eur J Biochem 189: 1-23; Chayen NE (1997) Structure 5: 1269-1274; McPherson A (1976) J Biol Chem 251: 6300-6303).
  • Antibody:antigen crystals may be studied using well known X-ray diffraction techniques and may be refined using computer software such as X-PLOR (Yale University, 1992, distributed by Molecular Simulations, Inc.; see, e.g., Meth Enzymol (1985) volumes 114 & 115, eds Wyckoff HW et al.; U.S. Patent Application No.
  • the epitope of an antibody is determined using alanine scanning mutagenesis studies. Usually, binding to the antigen is reduced or disrupted when a residue within the epitope is substituted to alanine. In some embodiments, the Kd of binding to the antigen is increased by about 5-fold, 10-fold, 20-fold, 10-fold or more when a residue within the epitope is substituted for alanine. In some embodiments, binding affinity is determined by ELISA.
  • antibodies that recognize and bind to the same or overlapping epitopes of 3FTx-L can be identified using routine techniques such as an immunoassay, for example, by showing the ability of one antibody to block the binding of another antibody to a target antigen, i.e., a competitive binding assay.
  • a competitive binding assay e.g., ELISA competitive assays or surface plasmon resonance.
  • antibodies that competitively inhibit (e.g., in a dose dependent manner) an antibody described herein from binding to 3FTx-L, as determined using assays known to one of skill in the art or described herein (e.g., ELISA competitive assays, or suspension array or surface plasmon resonance assay).
  • the epitope of an antibody described herein is used as an immunogen to produce antibodies.
  • methods for producing an engineered variant of an antibody described herein comprises directed-evolution and yeast display. Methods for producing an engineered antibody are known to those skilled in the art, for example, as described in International Appl. No.
  • an engineered antibody possesses one or more improved properties, for example, higher binding affinity to target antigen, higher binding affinity to target antigen at low pH, increased median neutralization IC50 potency, and increased breadth of neutralization compared to the parent antibody.
  • an engineered variant of an antibody comprising substituting one or more amino acid residues of the VH; and/or substituting one or more amino acid residues of the VL to create an engineered variant antibody, and producing the engineered variant antibody, wherein the antibody is LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95.
  • a method of producing an engineered variant of a LB5_95 comprising substituting one or more amino acid residues of the LB5_95 VH; and/or substituting one or more amino acid residues of the LB5_95 VL to create an engineered variant antibody, and producing the engineered variant antibody.
  • a method of producing an engineered variant of a parent antibody comprises substituting one or more amino acid residues of the VH; and/or substituting one or more amino acid residues of the VL to create an engineered variant antibody, and producing the engineered variant antibody.
  • the parent antibody is an antibody described herein.
  • the parent antibody is LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95.
  • the parent antibody is LB5_95.
  • the method further comprises determining that the engineered variant antibody has improved properties, for example, by determining the engineered variant antibody's binding affinity to target antigen, binding affinity to target antigen at low pH, median neutralization IC 50 potency, or breadth of neutralization compared to the parent antibody.
  • a method of producing an engineered variant of an antibody comprising substituting one or more amino acid residues of the VH; and/or substituting one or more amino acid residues of the VL to create an engineered variant antibody, and producing the engineered variant antibody, wherein the antibody is 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6.
  • a method of producing an engineered variant of a 95MAT5 comprising substituting one or more amino acid residues of the 95MAT5 VH; and/or substituting one or more amino acid residues of the 95MAT5 VL to create an engineered variant antibody, and producing the engineered variant antibody.
  • a method of producing an engineered variant of a parent antibody comprises substituting one or more amino acid residues of the VH; and/or substituting one or more amino acid residues of the VL to create an engineered variant antibody, and producing the engineered variant antibody.
  • the parent antibody is an antibody described herein.
  • the parent antibody is 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6.
  • the parent antibody is 95MAT5.
  • the method further comprises determining that the engineered variant antibody has improved properties, for example, by determining the engineered variant antibody's binding affinity to target antigen, binding affinity to target antigen at low pH, median neutralization IC50 potency, or breadth of neutralization compared to the parent antibody.
  • the affinity or avidity of an antibody or fusion polypeptide for an antigen can be determined experimentally using any suitable method well known in the art, e.g., flow cytometry, enzyme-linked immunoabsorbent assay (ELISA), or radioimmunoassay (RIA), or kinetics (e.g., BIACORETM analysis). Direct binding assays as well as competitive binding assay formats can be readily employed.
  • the measured affinity of a particular antibody-antigen interaction can vary if measured under different conditions (e.g., salt concentration, pH, temperature).
  • affinity and other antigen-binding parameters e.g., Kd, Kon, Koff
  • affinity and other antigen-binding parameters are made with standardized solutions of antibody and antigen, and a standardized buffer, as known in the art and such as the buffer described herein.
  • the anti-3FTx-L antibody described herein is a monoclonal antibody.
  • Monoclonal antibodies can be prepared using hybridoma methods, such as those described by Kohler and Milstein (1975) Nature 256:495. Alternatively monoclonal antibodies can also be made using recombinant DNA methods as described, for example, in U.S. Patent 4,816,567. Recombinant monoclonal antibodies or fragments thereof of the desired species can be isolated from phage display libraries expressing CDRs of the desired species as described (McCafferty et al., 1990, Nature, 348:552-554; Clackson et al., 1991, Nature, 352:624-628; and Marks et al., 1991, J.
  • the polynucleotide(s) encoding a monoclonal antibody can further be modified in a number of different manners using recombinant DNA technology to generate alternative antibodies.
  • the constant domains of the light and heavy chains of, for example, a mouse monoclonal antibody can be substituted 1) for those regions of, for example, a human antibody to generate a chimeric antibody or 2) for a non-immunoglobulin polypeptide to generate a fusion antibody.
  • the constant regions are truncated or removed to generate the desired antibody fragment of a monoclonal antibody.
  • Site-directed or high-density mutagenesis of the variable region can be used to optimize specificity, affinity, etc. of a monoclonal antibody.
  • Methods for engineering, humanizing or resurfacing non-human or human antibodies can also be used and are well known in the art.
  • a humanized, resurfaced or similarly engineered antibody can have one or more amino acid residues from a source that is non-human, e.g., but not limited to, mouse, rat, rabbit, non-human primate or other mammal. These non-human amino acid residues are replaced by residues that are often referred to as "import" residues, which are typically taken from an "import" variable, constant or other domain of a known human sequence.
  • Such imported sequences can be used to reduce immunogenicity or reduce, enhance or modify binding, affinity, on-rate, off-rate, avidity, specificity, half-life, or any other suitable characteristic, as known in the art.
  • the CDR residues are directly and most substantially involved in influencing antibody binding. Accordingly, part or all of the non-human or human CDR sequences are maintained while the non-human sequences of the variable and constant regions can be replaced with human or other amino acids.
  • Antibodies can also optionally be humanized, resurfaced, engineered or human antibodies engineered with retention of high affinity for the antigen and other favorable biological properties.
  • humanized (or human) or engineered antibodies and resurfaced antibodies can be optionally prepared by a process of analysis of the parental sequences and various conceptual humanized and engineered products using three-dimensional models of the parental, engineered, and humanized sequences.
  • Three-dimensional immunoglobulin models are commonly available and are familiar to those skilled in the art.
  • Computer programs are available which illustrate and display probable three-dimensional conformational structures of selected candidate immunoglobulin sequences. Inspection of these displays permits analysis of the likely role of the residues in the functioning of the candidate immunoglobulin sequence, i.e., the analysis of residues that influence the ability of the candidate immunoglobulin to bind its antigen.
  • framework (FR) residues can be selected and combined from the consensus and import sequences so that the desired antibody characteristic, such as increased affinity for the target antigen(s), is achieved.
  • Humanization, resurfacing or engineering of antibodies described herein can be performed using any known method, such as but not limited to those described in, Winter (Jones et al., Nature 321:522 (1986); Riechmann et al., Nature 332:323 (1988); Verhoeyen et al., Science 239:1534 (1988)), Sims et al., J. Immunol.151: 2296 (1993); Chothia and Lesk, J. Mol. Biol.196:901 (1987), Carter et al., Proc. Natl.
  • the antibody is a human antibody.
  • Human antibodies can be directly prepared using various techniques known in the art. Human antibodies can be isolated from suitable donors. Immortalized human B lymphocytes immunized in vitro or isolated from an immunized individual that produce an antibody directed against a target antigen can be generated (See, e.g., Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985); Boemer et al., 1991, J. Immunol., 147 (1):86-95; and U.S. Patent 5,750,373).
  • the human antibody can be selected from a phage library, where that phage library expresses human antibodies, as described, for example, in Vaughan et al., 1996, Nat. Biotech., 14:309-314, Sheets et al., 1998, Proc. Nat'l. Acad. Sci., 95:6157-6162, Hoogenboom and Winter, 1991, J. Mol. Biol., 227:381, and Marks et al., 1991, J. Mol. Biol., 222:581). Techniques for the generation and use of antibody phage libraries are also described in U.S. Patent Nos.
  • antibody fragments are produced recombinantly.
  • Fab, Fv, and scFv antibody fragments can all be expressed in and secreted from E. coli or other host cells, thus allowing the production of large amounts of these fragments.
  • Such antibody fragments can also be isolated from antibody phage libraries.
  • the antibody fragment can also be linear antibodies as described in U.S. Patent 5,641,870, for example, and can be monospecific or bispecific.
  • variable domains in both the heavy and light chains are altered by at least partial replacement of one or more CDRs and, if necessary, by partial framework region replacement and sequence changing.
  • the CDRs can be derived from an antibody of the same class or even subclass as the antibody from which the framework regions are derived, it is envisaged that the CDRs will be derived from an antibody of different class and in certain embodiments from an antibody from a different species. It may not be necessary to replace all of the CDRs with the complete CDRs from the donor variable region to transfer the antigen-binding capacity of one variable domain to another.
  • the modified antibodies described herein will comprise antibodies (e.g., full-length antibodies or immunoreactive fragments thereof) in which at least a fraction of one or more of the constant region domains has been deleted or otherwise altered so as to provide desired biochemical characteristics such as increased serum half-life when compared with an antibody of approximately the same immunogenicity comprising a native or unaltered constant region.
  • the constant region of the modified antibodies will comprise a human constant region.
  • Modifications to the constant region compatible with this invention comprise additions, deletions or substitutions of one or more amino acids in one or more domains.
  • the modified antibodies described herein can comprise alterations or modifications to one or more of the three heavy chain constant domains (CH1, CH2 or CH3) and/or to the light chain constant domain (CL).
  • modified constant regions wherein one or more domains are partially or entirely deleted are contemplated.
  • the modified antibodies will comprise domain deleted constructs or variants wherein the entire CH2 domain has been removed ( ⁇ CH2 constructs).
  • the omitted constant region domain will be replaced by a short amino acid spacer (e.g., 10 residues) that provides some of the molecular flexibility typically imparted by the absent constant region.
  • the modified antibodies can be engineered to fuse the CH3 domain directly to the hinge region of the respective modified antibodies.
  • a peptide spacer between the hinge region and the modified CH2 and/or CH3 domains.
  • compatible constructs could be expressed wherein the CH2 domain has been deleted and the remaining CH3 domain (modified or unmodified) is joined to the hinge region with a 5-20 amino acid spacer.
  • a spacer can be added, for instance, to ensure that the regulatory elements of the constant domain remain free and accessible or that the hinge region remains flexible.
  • amino acid spacers can, in some cases, prove to be immunogenic and elicit an unwanted immune response against the construct.
  • any spacer added to the construct will be relatively non- immunogenic, or even omitted altogether, so as to maintain the desired biochemical qualities of the modified antibodies.
  • the antibodies described herein can be provided by the partial deletion or substitution of a few or even a single amino acid.
  • Such partial deletions of the constant regions can improve selected characteristics of the antibody (serum half-life) while leaving other desirable functions associated with the subject constant region domain intact.
  • the constant regions of the disclosed antibodies can be modified through the mutation or substitution of one or more amino acids that enhances the profile of the resulting construct.
  • a conserved binding site e.g., Fc binding
  • Certain embodiments can comprise the addition of one or more amino acids to the constant region to enhance desirable characteristics such as decreasing or increasing effector function or provide for more cytotoxin or carbohydrate attachment.
  • it can be desirable to insert or replicate specific sequences derived from selected constant region domains.
  • the half-life of an IgG is mediated by its pH-dependent binding to the neonatal receptor FcRn.
  • an antibody described herein comprises a variant Fc region that has been modified to enhance binding to FcRn (see, e.g., Petkova et al., Int. Immunol.18: 1759-1769 (2006); Dall'Acqua et al., J. Immunol.169: 5171-5180 (2002); Oganesyan et al., Mol. Immunol.46: 1750-1755 (2009); Dall'Acqua et al., J. Biol. Chem. 281: 23514-23524 (2006), Hinton et al., J. Immunol.176: 346-356 (2006); Datta-Mannan et al., Drug Metab.
  • an antibody described herein comprises a variant Fc region that has been modified to have a selective affinity for FcRn at pH 6.0, but not pH 7.4.
  • the variant Fc region contains one or more of the following modifications that increase half-life: IgG1-M252Y, S254T, T256E; IgG1-T250Q, M428L; IgG1-M428L and N434S (the "LS" mutation); IgG1-H433K, N434Y; IgG1-N434A; and IgG1-T307A, E380A, N434A; wherein the numbering of the residues is that of the EU index of Kabat et al. (Kabat et al., Sequences of Proteins of Immunological Interest, 1991 Fifth edition, herein incorporated by reference).
  • an antibody described herein comprises a variant Fc region that has been modified to reduce its effector functions.
  • the variant Fc region comprises the L234A, L235A hinge region substitutions, wherein the numbering of the residues is that of the EU index of Kabat et al.
  • an antibody described herein comprises an Fc region having a carbohydrate structure that lacks fucose attached (directly or indirectly) to the Fc region or has a reduced level of fucosylation.
  • a fucosylation variant antibody has improved ADCC function. See, e.g., US Patent Publication Nos. US 2003/0157108; US 2004/0093621, each of which is incorporated by reference herein in its entirety.
  • Examples of publications related to "defucosylated” or “fucose-deficient” antibody variants include: US 2003/0157108; WO 2000/61739; WO 2001/29246; US 2003/0115614; US 2002/0164328; US 2004/0093621; US 2004/0132140; US 2004/0110704; US 2004/0110282; US 2004/0109865; WO 2003/085119; WO 2003/084570; WO 2005/035586; WO 2005/035778; WO2005/053742; WO2002/031140; Okazaki et al. J. Mol. Biol.336:1239-1249 (2004); Yamane-Ohnuki et al. Biotech.
  • Examples of cell lines capable of producing defucosylated antibodies include Lec 13 CHO cells deficient in protein fucosylation (Ripka et al. Arch. Biochem. Biophys. 249:533-545 (1986); US Pat Appl No US 2003/0157108 A1; and WO 2004/056312), and knockout cell lines, such as alpha-1,6-fucosyltransferase gene, FUT8, knockout CHO cells (see, e.g., Yamane-Ohnuki et al. Biotech. Bioeng. 87: 614 (2004); Kanda, Y. et al., Biotechnol.
  • an antibody described herein comprises bisected oligosaccharides, in which a biantennary oligosaccharide attached to the Fc region of the antibody is bisected by GlcNAc.
  • an antibody comprising bisected oligosaccharides has reduced fucosylation and/or improved ADCC function. See, e.g., WO 2003/011878; U.S. Pat. No. 6,602,684; and US 2005/0123546, each of which is incorporated by reference herein in its entirety.
  • an antibody described herein comprises at least one galactose residue in the oligosaccharide attached to the Fc region.
  • Such antibody variants may have improved CDC function. See, e.g., in WO 1997/30087; WO 1998/58964; and WO 1999/22764, each of which is incorporated by reference herein in its entirety.
  • an antibody described herein comprises a variant Fc region comprising a combination of substitutions with increased binding to FcRn and Fc gamma RIIIa. The combinations increase antibody half-life and ADCC.
  • such combination include antibodies with the following amino acid substitution in the Fc region: (1) S239D/I332E and T250Q/M428L; (2) S239D/I332E and M428L/N434S; (3) S239D/I332E and N434A; (4) S239D/I332E and T307A/E380A/N434A; (5) S239D/I332E and M252Y/S254T/T256E; (6) S239D/A330L/I332E and 250Q/M428L; (7) S239D/A330L/I332E and M428L/N434S; (8) S239D/A330L/I332E and N434A; (9) S239D/A330L/I332E and T307A/E380A/N434A; or (10) S239D/A330L/I332E and M252Y/S254T
  • an antibody comprising the variant Fc region is directly cytotoxic to infected cells, or uses natural defenses such as complement, antibody dependent cellular cytotoxicity (ADCC), or phagocytosis by macrophages.
  • the present invention further embraces variants and equivalents which are substantially homologous to the chimeric, humanized and human antibodies, or antibody fragments thereof, set forth herein. These can contain, for example, conservative substitution mutations, i.e., the substitution of one or more amino acids by similar amino acids. For example, conservative substitution refers to the substitution of an amino acid with another within the same general class such as, for example, one acidic amino acid with another acidic amino acid, one basic amino acid with another basic amino acid or one neutral amino acid by another neutral amino acid.
  • polypeptides provided herein can be recombinant polypeptides, natural polypeptides, or synthetic polypeptides comprising an antibody, or fragment thereof. It will be recognized in the art that some amino acid sequences described herein can be varied without significant effect of the structure or function of the protein.
  • the invention further includes variations of the polypeptides which show substantial activity or which include regions of an antibody, or fragment thereof, against a human folate receptor protein. Such mutants include deletions, insertions, inversions, repeats, and type substitutions.
  • the polypeptides and analogs can be further modified to contain additional chemical moieties not normally part of the protein.
  • Those derivatized moieties can improve the solubility, the biological half-life or absorption of the protein.
  • the moieties can also reduce or eliminate any desirable side effects of the proteins and the like.
  • An overview for those moieties can be found in REMINGTON'S PHARMACEUTICAL SCIENCES, 21th ed., Mack Publishing Co., Easton, PA (2005).
  • III. Polynucleotides In certain aspects, provided herein are polynucleotides comprising a nucleotide sequence or nucleotide sequences encoding an anti-3FTx-L antibody described herein or a fragment thereof and vectors, e.g., vectors comprising such polynucleotides.
  • the vectors can be used for recombinant expression of an antibody described herein in host cells (e.g., E. coli and mammalian cells). In some embodiments, the vectors can be used for administration of an antibody described herein to a patient in need thereof.
  • the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95.
  • the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5. In one aspect, provided herein are isolated polynucleotides encoding the heavy chain variable region or heavy chain of an antibody described herein.
  • the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95.
  • the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6.
  • the antibody comprises the VH and VL of LB5_95.
  • the antibody comprises the VH and VL of 95MAT5.
  • the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95.
  • the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6.
  • the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5. In one aspect, provided herein are isolated polynucleotides encoding the heavy chain variable region or heavy chain of an antibody described herein and the light chain variable region or light chain of an antibody described herein.
  • the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95.
  • the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6.
  • the antibody comprises the VH and VL of LB5_95.
  • the antibody comprises the VH and VL of 95MAT5.
  • the polynucleotide encodes a heavy chain variable region described herein.
  • the VH comprises the VH of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95.
  • the VH comprises the VH of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6.
  • the VH comprises the VH of LB5_95.
  • the VH comprises the VH of 95MAT5.
  • the polynucleotide encodes a light chain variable region described herein.
  • the VL comprises the VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95.
  • the VL comprises the VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6.
  • the VL comprises the VL of LB5_95. In some embodiments, the VL comprises the VL of 95MAT5.
  • an isolated polynucleotide described herein is a DNA. In some embodiments, an isolated polynucleotide described herein is an mRNA. In some embodiments, the mRNA comprises a modified nucleotide. In some embodiments, an isolated polynucleotide described herein encodes an antibody described herein and comprises an mRNA. In some embodiments, the mRNA comprises at least one modified nucleotide. In some embodiments, a modified mRNA encoding an antibody described herein is for administering to a subject to treat snake bite.
  • a modified mRNA encoding an antibody described herein is for administering to a subject at risk of suffering a snake bite.
  • the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95.
  • the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6.
  • the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5.
  • an "isolated" polynucleotide or nucleic acid molecule is one which is separated from other nucleic acid molecules which are present in the natural source (e.g., in a mouse or a human) of the nucleic acid molecule.
  • an "isolated" nucleic acid molecule such as a cDNA molecule, can be substantially free of other cellular material, or culture medium when produced by recombinant techniques, or substantially free of chemical precursors or other chemicals when chemically synthesized.
  • the language "substantially free” includes preparations of polynucleotide or nucleic acid molecule having less than about 15%, 10%, 5%, 2%, 1%, 0.5%, or 0.1% (in particular less than about 10%) of other material, e.g., cellular material, culture medium, other nucleic acid molecules, chemical precursors and/or other chemicals.
  • a nucleic acid molecule(s) encoding an antibody or fusion polypeptide described herein is isolated or purified.
  • the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95.
  • the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5.
  • polynucleotides comprising a nucleotide sequence encoding the light chain or heavy chain of an antibody described herein.
  • the polynucleotides can comprise nucleotide sequences encoding a light chain comprising the VL of antibodies described herein.
  • the polynucleotides can comprise nucleotide sequences encoding a heavy chain comprising the VH of antibodies described herein.
  • the antibody is a human antibody. In some embodiments, the antibody is a chimeric antibody. In some embodiments, the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6.
  • the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5.
  • polynucleotides comprising a nucleotide sequence encoding an anti-3FTx-L antibody comprising three VL chain CDRs, e.g., containing VL CDR1, VL CDR2, and VL CDR3 of any one of antibodies described herein.
  • polynucleotides comprising three VH chain CDRs, e.g., containing VH CDR1, VH CDR2, and VH CDR3 of any one of antibodies described herein.
  • polynucleotides comprising a nucleotide sequence encoding an anti-3FTx-L antibody comprising three VL CDRs, e.g., containing VL CDR1, VL CDR2, and VL CDR3 of any one of antibodies described herein and three VH chain CDRs, e.g., containing VH CDR1, VH CDR2, and VH CDR3 of any one of antibodies described herein.
  • the antibody is a human antibody.
  • polynucleotides comprising a nucleotide sequence encoding a broadly neutralizing anti-3FTx-L antibody comprising three VL chain CDRs, e.g., containing VL CDR1, VL CDR2, and VL CDR3 of any one of antibodies described herein.
  • polynucleotides comprising a nucleotide sequence encoding an anti-3FTx-L antibody comprising three VH chain CDRs, e.g., containing VH CDR1, VH CDR2, and VH CDR3 of any one of antibodies described herein.
  • polynucleotides comprising a nucleotide sequence encoding an anti-3FTx-L antibody comprising three VL CDRs, e.g., containing VL CDR1, VL CDR2, and VL CDR3 of any one of antibodies described herein and three VH chain CDRs, e.g., containing VH CDR1, VH CDR2, and VH CDR3 of any one of antibodies described herein.
  • provided herein are polynucleotides comprising a nucleotide sequence encoding a broadly neutralizing anti-3FTx-L antibody comprising the VH CDR3 of an antibody described herein.
  • the antibody is a human antibody.
  • a polynucleotide provided herein comprises a nucleotide sequence encoding an antibody or fragment thereof described herein comprising: framework regions (e.g., framework regions of the VL domain and VH domain) that are human framework regions, wherein the antibody immunospecifically binds 3FTx-L.
  • a polynucleotide provided herein comprises a nucleotide sequence encoding an antibody or fragment thereof (e.g., CDRs or variable domain) described herein.
  • provided herein is a polynucleotide comprising a nucleotide sequence encoding an antibody comprising a light chain and a heavy chain, e.g., a separate light chain and heavy chain.
  • a polynucleotide provided herein comprises a nucleotide sequence encoding a kappa light chain.
  • a polynucleotide provided herein comprises a nucleotide sequence encoding a lambda light chain.
  • a polynucleotide provided herein comprises a nucleotide sequence encoding an antibody described herein comprising a human kappa light chain or a human lambda light chain.
  • a polynucleotide provided herein comprises a nucleotide sequence encoding an antibody, which immunospecifically binds to 3FTx- L, wherein the antibody comprises a light chain, and wherein the amino acid sequence of the VL domain can comprise the amino acid sequence set forth herein, and wherein the constant region of the light chain comprises the amino acid sequence of a human kappa light chain constant region.
  • a polynucleotide provided herein comprises a nucleotide sequence encoding an antibody, which immunospecifically binds to 3FTx-L, and comprises a light chain, wherein the amino acid sequence of the VL domain can comprise the amino acid sequence set forth herein, and wherein the constant region of the light chain comprises the amino acid sequence of a human lambda light chain constant region.
  • human constant region sequences can be those described in U.S. Patent No.5,693,780.
  • a polynucleotide provided herein comprises a nucleotide sequence encoding an antibody described herein, which immunospecifically binds to 3FTx-L, wherein the antibody comprises a heavy chain, and wherein the constant region of the heavy chain comprises the amino acid sequence of a human alpha or gamma heavy chain constant region.
  • a polynucleotide provided herein comprises a nucleotide sequence encoding an antibody described herein, which immunospecifically binds 3FTx-L, wherein the antibody comprises a VL domain and a VH domain comprising any amino acid sequences described herein, and wherein the constant regions comprise the amino acid sequences of the constant regions of a human IgA1, human IgA2 ' human IgG1 (e.g., allotype 1, 17, or 3), human IgG 2 , or human IgG 4 .
  • a polynucleotide provided herein comprises nucleotide sequences encoding an anti-3FTx-L antibody or a fragment thereof that are optimized, e.g., by codon/RNA optimization, replacement with heterologous signal sequences, and elimination of mRNA instability elements.
  • Methods to generate optimized nucleic acids encoding an anti-3FTx- L antibody or a fragment thereof (e.g., light chain, heavy chain, VH domain, or VL domain) for recombinant expression by introducing codon changes and/or eliminating inhibitory regions in the mRNA can be carried out by adapting the optimization methods described in, e.g., U.S. Patent Nos.
  • RNA potential splice sites and instability elements (e.g., A/T or A/U rich elements) within the RNA can be mutated without altering the amino acids encoded by the nucleic acid sequences to increase stability of the RNA for recombinant expression.
  • the alterations utilize the degeneracy of the genetic code, e.g., using an alternative codon for an identical amino acid.
  • an optimized polynucleotide sequence encoding an anti-3FTx-L antibody described herein or a fragment thereof can hybridize to an antisense (e.g., complementary) polynucleotide of an unoptimized polynucleotide sequence encoding an anti-3FTx-L antibody described herein or a fragment thereof (e.g., VL domain or VH domain).
  • an antisense e.g., complementary
  • an optimized nucleotide sequence encoding an anti-3FTx-L antibody described herein or a fragment hybridizes under high stringency conditions to antisense polynucleotide of an unoptimized polynucleotide sequence encoding an anti-3FTx-L antibody described herein or a fragment thereof.
  • an optimized nucleotide sequence encoding an anti-3FTx-L antibody described herein or a fragment thereof hybridizes under high stringency, intermediate or lower stringency hybridization conditions to an antisense polynucleotide of an unoptimized nucleotide sequence encoding an anti-3FTx-L antibody described herein or a fragment thereof.
  • polynucleotides can be obtained, and the nucleotide sequence of the polynucleotides determined, by any method known in the art.
  • Nucleotide sequences encoding antibodies described herein, and modified versions of these antibodies can be determined using methods well known in the art, i.e., nucleotide codons known to encode particular amino acids are assembled in such a way to generate a nucleic acid that encodes the antibody.
  • Such a polynucleotide encoding the antibody can be assembled from chemically synthesized oligonucleotides (e.g., as described in Kutmeier G et al., (1994), BioTechniques 17: 242-246), which, briefly, involves the synthesis of overlapping oligonucleotides containing portions of the sequence encoding the antibody, annealing and ligating of those oligonucleotides, and then amplification of the ligated oligonucleotides by PCR.
  • chemically synthesized oligonucleotides e.g., as described in Kutmeier G et al., (1994), BioTechniques 17: 242-246
  • a polynucleotide encoding an antibody or fragment thereof described herein can be generated from nucleic acid from a suitable source (e.g., PBMCs) using methods well known in the art (e.g., PCR and other molecular cloning methods). For example, PCR amplification using synthetic primers hybridizable to the 3' and 5' ends of a known sequence can be performed using genomic DNA obtained from hybridoma cells producing the antibody of interest. Such PCR amplification methods can be used to obtain nucleic acids comprising the sequence encoding the light chain and/or heavy chain of an antibody.
  • Such PCR amplification methods can be used to obtain nucleic acids comprising the sequence encoding the variable light chain region and/or the variable heavy chain region of an antibody.
  • the amplified nucleic acids can be cloned into vectors for expression in host cells and for further cloning, for example, to generate chimeric and humanized antibodies.
  • a nucleic acid encoding the immunoglobulin or fragment can be chemically synthesized or obtained from a suitable source (e.g., an antibody cDNA library or a cDNA library generated from, or nucleic acid, preferably poly A+ RNA, isolated from, any tissue or cells expressing the antibody, such as hybridoma cells selected to express an antibody described herein) by PCR amplification using synthetic primers hybridizable to the 3' and 5' ends of the sequence or by cloning using an oligonucleotide probe specific for the particular gene sequence to identify, e.g., a cDNA clone from a cDNA library that encodes the antibody.
  • a suitable source e.g., an antibody cDNA library or a cDNA library generated from, or nucleic acid, preferably poly A+ RNA, isolated from, any tissue or cells expressing the antibody, such as hybridoma cells selected to express an antibody described herein
  • Amplified nucleic acids generated by PCR can then be cloned into replicable cloning vectors using any method well known in the art.
  • DNA encoding anti-3FTX_LCa antibodies described herein can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of the anti-3FTx-L).
  • PBMCs can serve as a source of such DNA. Once isolated, the DNA can be placed into expression vectors, which are then transfected into host cells such as E.
  • the DNA also can be modified, for example, by substituting the coding sequence for human heavy and light chain constant domains with a coding sequence for a non-immunoglobulin polypeptide, or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide.
  • polynucleotides that hybridize under high stringency, intermediate or lower stringency hybridization conditions to polynucleotides that encode an antibody described herein.
  • polynucleotides described herein hybridize under high stringency, intermediate or lower stringency hybridization conditions to polynucleotides encoding a VH domain and/or VL domain provided herein. Hybridization conditions have been described in the art and are known to one of skill in the art.
  • hybridization under stringent conditions can involve hybridization to filter- bound DNA in 6x sodium chloride/sodium citrate (SSC) at about 45°C followed by one or more washes in 0.2xSSC/0.1% SDS at about 50-65°C; hybridization under highly stringent conditions can involve hybridization to filter-bound nucleic acid in 6xSSC at about 45°C followed by one or more washes in 0.1xSSC/0.2% SDS at about 68°C.
  • Hybridization under other stringent hybridization conditions are known to those of skill in the art and have been described, see, for example, Ausubel FM et al., eds., (1989) Current Protocols in Molecular Biology, Vol. I, Green Publishing Associates, Inc.
  • cells e.g., host cells
  • vectors e.g., expression vectors
  • polynucleotides comprising nucleotide sequences encoding anti-3FTx-L antibodies or a fragment thereof described herein.
  • the vectors can be used for recombinant expression of an antibody described herein in host cells (e.g., mammalian cells). In some embodiments, the vectors can be used for administration of an antibody described herein to a patient in need thereof. Also provided herein are host cells comprising such vectors for recombinantly expressing anti-3FTx-L antibodies described herein. In a particular aspect, provided herein are methods for producing an antibody described herein, comprising expressing such antibody in a host cell.
  • the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95.
  • the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6.
  • the antibody comprises the VH and VL of LB5_95.
  • the antibody comprises the VH and VL of 95MAT5.
  • an isolated vector comprising a polynucleotide described herein.
  • the vector is a viral vector.
  • a recombinant virus comprising a polynucleotide described herein.
  • the recombinant virus encodes an antibody described herein.
  • the recombinant virus encodes a bispecific antibody described herein.
  • the recombinant virus encodes a trispecific antibody described herein.
  • the recombinant virus encodes a multispecific antibody described herein.
  • the recombinant virus is a replication defective virus.
  • Suitable replication defective viral vectors are known to those skilled in the art, for example, as disclosed in U.S. Pat. Nos. 7198784, 9408905, 9862931, 8067156, U.S. Pat. Appl. Pub. Nos. 20150291935, 20120220492, 20180291351, and 20170175137, each of which is incorporated herein by reference in its entirety.
  • the recombinant virus is a retrovirus or retroviral vector, for example, a lentivirus or lentiviral vector.
  • the recombinant virus is an adenovirus or adenoviral vector, HSV or HSV vector, or influenza virus or viral vector.
  • the recombinant virus is an adeno-associated virus (AAV). In one embodiment, the recombinant virus is for administration to a subject to treat snake bite. In one embodiment, the recombinant virus is an adeno-associated virus (AAV) for administration to a subject to treat snake bite.
  • AAV particles encoding an antibody that binds to 3FTx-L and methods for producing thereof are known to one skilled in the art, for example, as disclosed in US Patent 8,865,881 and US20190031740, each of which is incorporated by reference herein in its entirety for all purposes.
  • a host cell comprising a polynucleotide described herein, or a vector described herein.
  • the vector encodes an antibody described herein.
  • a vector described herein comprises a first vector encoding a VH described herein and a second vector encoding a VL described herein.
  • a vector described herein comprises a first nucleotide sequence encoding a VH described herein and a second nucleotide sequence encoding a VL described herein.
  • the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95.
  • the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5. In some embodiments, the host cell is selected from the group consisting of E.
  • the host cell is CHO.
  • a method of producing an antibody that binds to 3FTx-L comprising culturing a host cell described herein so that the polynucleotide is expressed and the antibody is produced.
  • the method further comprises recovering the antibody.
  • the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95.
  • the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6.
  • the antibody comprises the VH and VL of LB5_95.
  • the antibody comprises the VH and VL of 95MAT5.
  • the isolated polypeptides, i.e., anti-3FTx-L antibodies described herein can be produced by any suitable method known in the art. Such methods range from direct protein synthetic methods to constructing a DNA sequence encoding isolated polypeptide sequences and expressing those sequences in a suitable transformed host.
  • a DNA sequence is constructed using recombinant technology by isolating or synthesizing a DNA sequence encoding a wild-type protein of interest.
  • the sequence can be mutagenized by site-specific mutagenesis to provide functional analogs thereof. See, e.g., Zoeller et al., Proc. Nat'l. Acad. Sci.
  • a DNA sequence encoding a polypeptide of interest would be constructed by chemical synthesis using an oligonucleotide synthesizer.
  • Such oligonucleotides can be designed based on the amino acid sequence of the desired polypeptide and selecting those codons that are favored in the host cell in which the recombinant polypeptide of interest will be produced.
  • Standard methods can be applied to synthesize an isolated polynucleotide sequence encoding an isolated polypeptide of interest. For example, a complete amino acid sequence can be used to construct a back-translated gene.
  • a DNA oligomer containing a nucleotide sequence coding for the particular isolated polypeptide can be synthesized. For example, several small oligonucleotides coding for portions of the desired polypeptide can be synthesized and then ligated. The individual oligonucleotides typically contain 5' or 3' overhangs for complementary assembly. Once assembled (by synthesis, site-directed mutagenesis or another method), the polynucleotide sequences encoding a particular isolated polypeptide of interest will be inserted into an expression vector and operatively linked to an expression control sequence appropriate for expression of the protein in a desired host.
  • recombinant expression vectors are used to amplify and express DNA encoding antibodies or fragments thereof.
  • Recombinant expression vectors are replicable DNA constructs which have synthetic or cDNA-derived DNA fragments encoding a polypeptide chain of an antibody or fragment thereof operatively linked to suitable transcriptional or translational regulatory elements derived from mammalian, microbial, viral or insect genes.
  • a transcriptional unit generally comprises an assembly of (1) a genetic element or elements having a regulatory role in gene expression, for example, transcriptional promoters or enhancers, (2) a structural or coding sequence which is transcribed into mRNA and translated into protein, and (3) appropriate transcription and translation initiation and termination sequences.
  • a regulatory element can include an operator sequence to control transcription.
  • the ability to replicate in a host, usually conferred by an origin of replication, and a selection gene to facilitate recognition of transformants can additionally be incorporated.
  • DNA regions are operatively linked when they are functionally related to each other.
  • DNA for a signal peptide is operatively linked to DNA for a polypeptide if it is expressed as a precursor which participates in the secretion of the polypeptide; a promoter is operatively linked to a coding sequence if it controls the transcription of the sequence; or a ribosome binding site is operatively linked to a coding sequence if it is positioned so as to permit translation.
  • Structural elements intended for use in yeast expression systems include a leader sequence enabling extracellular secretion of translated protein by a host cell.
  • recombinant protein is expressed without a leader or transport sequence, it can include an N-terminal methionine residue.
  • This residue can optionally be subsequently cleaved from the expressed recombinant protein to provide a final product.
  • expression control sequence and expression vector will depend upon the choice of host.
  • a variety of host-expression vector systems can be utilized to express antibody molecules described herein (see, e.g., U.S. Patent No. 5,807,715).
  • host-expression systems represent vehicles by which the coding sequences of interest can be produced and subsequently purified, but also represent cells which can, when transformed or transfected with the appropriate nucleotide coding sequences, express an antibody molecule described herein in situ. These include but are not limited to microorganisms such as bacteria (e.g., E. coli and B.
  • subtilis transformed with recombinant bacteriophage DNA, plasmid DNA or cosmid DNA expression vectors containing antibody coding sequences; yeast (e.g., Saccharomyces Pichia) transformed with recombinant yeast expression vectors containing antibody coding sequences; insect cell systems infected with recombinant virus expression vectors (e.g., baculovirus) containing antibody coding sequences; plant cell systems (e.g., green algae such as Chlamydomonas reinhardtii) infected with recombinant virus expression vectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) or transformed with recombinant plasmid expression vectors (e.g., Ti plasmid) containing antibody coding sequences; or mammalian cell systems (e.g., COS (e.g., COS1 or COS), CHO, BHK, MDCK, HEK 293, NS0, PER.C6,
  • cells for expressing antibodies described herein are CHO cells, for example CHO cells from the CHO GS SystemTM (Lonza).
  • cells for expressing antibodies described herein are human cells, e.g., human cell lines.
  • a mammalian expression vector is pOptiVECTM or pcDNA3.3.
  • bacterial cells such as Escherichia coli, or eukaryotic cells (e.g., mammalian cells), especially for the expression of whole recombinant antibody molecule, are used for the expression of a recombinant antibody molecule.
  • mammalian cells such as Chinese hamster ovary (CHO) cells in conjunction with a vector such as the major intermediate early gene promoter element from human cytomegalovirus is an effective expression system for antibodies (Foecking MK & Hofstetter H (1986) Gene 45: 101-105; and Cockett MI et al., (1990) Biotechnology 8: 662-667).
  • antibodies described herein are produced by CHO cells or NS0 cells.
  • the expression of nucleotide sequences encoding antibodies described herein which immunospecifically bind 3FTx- L is regulated by a constitutive promoter, inducible promoter or tissue specific promoter.
  • the vector is a viral vector.
  • Viral vectors can include poxvirus (vaccinia), including vaccinia Ankara and canarypox; adenoviruses, including adenovirus type 5 (Ad5); rubella; Sendai virus; rhabdovirus; alphaviruses; and adeno-associated viruses.
  • the viral vector is an adeno-associated virus.
  • a polynucleotide encoding the antibody could be delivered as DNA or RNA to the subject for in vivo expression of the antibody.
  • Suitable host cells for expression of a polypeptide of interest such as an antibody described herein include prokaryotes, yeast, insect or higher eukaryotic cells under the control of appropriate promoters. Prokaryotes include gram negative or gram positive organisms, for example E. coli or bacilli. Higher eukaryotic cells include established cell lines of mammalian origin. Cell-free translation systems could also be employed. Appropriate cloning and expression vectors for use with bacterial, fungal, yeast, and mammalian cellular hosts are described by Pouwels et al.
  • suitable mammalian host cell lines include but are not limited to CHO, VERO, BHK, Hela, MDCK, HEK 293, NIH 3T3, W138, BT483, Hs578T, HTB2, BT2O and T47D, NS0 (a murine myeloma cell line that does not endogenously produce any immunoglobulin chains), CRL7O3O, COS (e.g., COS1 or COS), PER.C6, VERO, HsS78Bst, HEK-293T, HepG2, SP210, R1.1, B-W, L-M, BSC1, BSC40, YB/20, BMT10 and HsS78Bst cells.
  • COS e.g., COS1 or COS
  • PER.C6 VERO, HsS78Bst, HEK-293T, HepG2, SP210, R1.1, B-W, L-M, BSC1, BSC40, YB
  • Mammalian expression vectors can comprise nontranscribed elements such as an origin of replication, a suitable promoter and enhancer linked to the gene to be expressed, and other 5' or 3' flanking nontranscribed sequences, and 5' or 3' nontranslated sequences, such as necessary ribosome binding sites, a polyadenylation site, splice donor and acceptor sites, and transcriptional termination sequences.
  • nontranscribed elements such as an origin of replication, a suitable promoter and enhancer linked to the gene to be expressed, and other 5' or 3' flanking nontranscribed sequences, and 5' or 3' nontranslated sequences, such as necessary ribosome binding sites, a polyadenylation site, splice donor and acceptor sites, and transcriptional termination sequences.
  • Baculovirus systems for production of heterologous proteins in insect cells are reviewed by Luckow and Summers, Bio/Technology 6:47 (1988).
  • the proteins produced by a transformed host can be purified according to any suitable method.
  • Such standard methods include chromatography (e.g., ion exchange, affinity and sizing column chromatography), centrifugation, differential solubility, or by any other standard technique for protein purification.
  • Affinity tags such as hexahistidine, maltose binding domain, influenza coat sequence and glutathione-S-transferase can be attached to the protein to allow easy purification by passage over an appropriate affinity column.
  • Isolated proteins can also be physically characterized using such techniques as proteolysis, nuclear magnetic resonance and x-ray crystallography.
  • supernatants from systems which secrete recombinant protein, e.g., an antibody, into culture media can be first concentrated using a commercially available protein concentration filter, for example, an Amicon or Millipore Pellicon ultrafiltration unit. Following the concentration step, the concentrate can be applied to a suitable purification matrix.
  • a suitable purification matrix for example, an anion exchange resin can be employed, for example, a matrix or substrate having pendant diethylaminoethyl (DEAE) groups.
  • the matrices can be acrylamide, agarose, dextran, cellulose or other types commonly employed in protein purification.
  • a cation exchange step can be employed.
  • Suitable cation exchangers include various insoluble matrices comprising sulfopropyl or carboxymethyl groups.
  • one or more reversed-phase high performance liquid chromatography (RP-HPLC) steps employing hydrophobic RP-HPLC media, e.g., silica gel having pendant methyl or other aliphatic groups, can be employed to further an agent.
  • RP-HPLC reversed-phase high performance liquid chromatography
  • Some or all of the foregoing purification steps, in various combinations, can also be employed to provide a homogeneous recombinant protein.
  • Recombinant protein produced in bacterial culture can be isolated, for example, by initial extraction from cell pellets, followed by one or more concentration, salting-out, aqueous ion exchange or size exclusion chromatography steps.
  • High performance liquid chromatography can be employed for final purification steps.
  • Microbial cells employed in expression of a recombinant protein can be disrupted by any convenient method, including freeze-thaw cycling, sonication, mechanical disruption, or use of cell lysing agents.
  • Methods known in the art for purifying antibodies and other proteins also include, for example, those described in U.S. Patent Publication Nos. 2008/0312425, 2008/0177048, and 2009/0187005, each of which is hereby incorporated by reference herein in its entirety.
  • an antibody described herein is isolated or purified.
  • an isolated antibody is one that is substantially free of other antibodies with different antigenic specificities than the isolated antibody.
  • a preparation of an antibody described herein is substantially free of cellular material and/or chemical precursors.
  • the language "substantially free of cellular material” includes preparations of an antibody in which the antibody is separated from cellular components of the cells from which it is isolated or recombinantly produced.
  • an antibody that is substantially free of cellular material includes preparations of antibody having less than about 30%, 20%, 10%, 5%, 2%, 1%, 0.5%, or 0.1% (by dry weight) of heterologous protein (also referred to herein as a "contaminating protein”) and/or variants of an antibody, for example, different post-translational modified forms of an antibody.
  • the polypeptide e.g., antibody described herein
  • culture medium represents less than about 20%, 10%, 2%, 1%, 0.5%, or 0.1% of the volume of the protein preparation.
  • the polypeptide e.g., antibody described herein
  • such preparations of the polypeptide have less than about 30%, 20%, 10%, or 5% (by dry weight) of chemical precursors or compounds other than the polypeptide of interest.
  • compositions comprising the antibodies or antigen-binding fragments described herein are also provided. Further provided herein are compositions comprising a polynucleotide or polynucleotides encoding the antibodies or antigen-binding fragments described herein. In some embodiments, the polynucleotide comprises mRNA. In some embodiments, the composition is a pharmaceutical composition.
  • the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95.
  • the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6.
  • the antibody comprises the VH and VL of LB5_95.
  • the antibody comprises the VH and VL of 95MAT5.
  • the composition is a lyophilized composition. In some embodiments, the composition is a liquid composition. In some embodiments, the composition is formulated for topical administration, and in certain embodiments the composition is formulated for vaginal or rectal administration. In certain aspects, provided herein is a pharmaceutical composition comprising an antibody described herein and a pharmaceutically acceptable excipient. In some embodiments, the antibody is an intact antibody. In some embodiments, the antibody is an antigen binding antibody fragment.
  • the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95.
  • the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6.
  • the antibody comprises the VH and VL of LB5_95.
  • the antibody comprises the VH and VL of 95MAT5.
  • the disclosure provides a pharmaceutical composition comprising an antibody described herein.
  • the pharmaceutical composition further comprises a second antibody, wherein the second antibody is capable of binding at least one toxic component of snake venom in addition to 3FTx-L.
  • the at least one toxic component of snake venom in addition to 3FTx-L comprises a metalloprotease or a phospholipase.
  • the pharmaceutical composition further comprises a second antibody, wherein the second antibody is capable of binding and neutralizing at least two snake venom metalloprotease variants.
  • the pharmaceutical composition further comprises a second antibody, wherein the second antibody is capable of binding and neutralizing at least two snake venom phospholipase variants.
  • compositions are intended for treatment of a snake bite.
  • a composition comprising the antibody described herein can additionally be combined with other compositions for the treatment of snake bite.
  • an antibody described herein may be administered within a pharmaceutically-acceptable diluent, carrier, or excipient, in unit dose form.
  • Conventional pharmaceutical practice may be employed to provide suitable formulations or compositions to administer to individuals being treated for snake bite. Any appropriate route of administration may be employed, for example, administration may be parenteral, intravenous, intra-arterial, subcutaneous, intramuscular, intraperitoneal, intranasal, aerosol, suppository, oral administration, vaginal, or anal.
  • compositions described herein are prepared in a manner known per se, for example, by means of conventional dissolving, lyophilizing, mixing, granulating or confectioning processes.
  • the pharmaceutical compositions may be formulated according to conventional pharmaceutical practice (see for example, in Remington: The Science and Practice of Pharmacy (21st ed.), ed. A.R. Gennaro, 2005, Lippincott Williams & Wilkins, Philadelphia, PA, and Encyclopedia of Pharmaceutical Technology, eds. J. Swarbrick and J. C. Boylan, 2013, Marcel Dekker, New York, NY).
  • the injection compositions are prepared in customary manner under sterile conditions; the same applies also to introducing the compositions into ampoules or vials and sealing the containers.
  • compositions according to the invention may be, for example, in unit dose form, such as in the form of ampoules, vials, suppositories, tablets, pills, or capsules.
  • the formulations can be administered to human individuals in therapeutically or prophylactic effective amounts (e.g., amounts which prevent, eliminate, or reduce a pathological condition) to provide therapy for a disease or condition.
  • the preferred dosage of therapeutic agent to be administered is likely to depend on such variables as the type and extent of the disorder, the overall health status of the particular patient, the formulation of the compound excipients, and its route of administration.
  • a method of treating a snake bite comprising administering to a subject in need thereof an effective amount of an antibody described herein (e.g., a bispecific or multispecific antibody), a pharmaceutical composition described herein, an isolated polynucleotide described herein, or a recombinant virus described herein (e.g., recombinant AAV).
  • the method comprises administering to a subject in need thereof an effective amount of an antibody described herein.
  • the subject has suffered a snake bite.
  • the subject is at risk of being exposed to snake bite.
  • the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95.
  • the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6.
  • the antibody comprises the VH and VL of LB5_95.
  • the antibody comprises the VH and VL of 95MAT5.
  • a method of passive immunization comprising administering to a subject in need thereof an effective amount of an antibody described herein (e.g., a bispecific or multispecific antibody), a pharmaceutical composition described herein, an isolated polynucleotide described herein, or a recombinant virus described herein (e.g., recombinant AAV).
  • the method comprises administering to a subject in need thereof an effective amount of an antibody described herein.
  • the subject is at risk of being bitten by a snake.
  • the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95.
  • the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6.
  • the antibody comprises the VH and VL of LB5_95.
  • the antibody comprises the VH and VL of 95MAT5.
  • the antibody is a multispecific, such as bispecific antibody.
  • the antibody can be a chimeric antibody, engineered antibody, recombinant antibody, or a monoclonal antibody described herein.
  • the antibody is a full antibody, an F(ab) fragment, or an F(ab)2 fragment described herein.
  • the antibody is an engineered monoclonal antibody described herein.
  • the antibody is a recombinant monoclonal antibody described herein.
  • the antibody is a chimeric monoclonal antibody described herein. In a specific embodiment, the antibody is an F(ab) described herein. In a specific embodiment, the antibody is an F(ab')2 fragment described herein.
  • the administering to the subject is by at least one mode selected from oral, parenteral, subcutaneous, intramuscular, and intravenous. In some embodiments, the administering to the subject is by at least one mode selected from vaginal, rectal, buccal, sublingual, and transdermal.
  • a method of treatment described herein further comprises administering at least one additional therapeutic agent. In some embodiments, the additional therapeutic agent comprises an anti-toxin.
  • the additional therapeutic agent comprises a second monoclonal antibody capable of neutralizing a toxic component of venom. In some embodiments, the additional therapeutic agent comprises a second monoclonal antibody capable of neutralizing a snake venom metalloprotease or a phospholipase. In some embodiments, the additional therapeutic agent comprises a second monoclonal antibody capable of neutralizing at least two snake venom metalloprotease variants or phospholipase variants. In some embodiments, the additional therapeutic agent comprises a second monoclonal antibody capable of neutralizing at least two snake venom metalloprotease variants. In some embodiments, the additional therapeutic agent comprises a second monoclonal antibody capable of neutralizing at least two snake venom phospholipase variants.
  • the additional therapeutic agent comprises a second monoclonal antibody capable of neutralizing a different neurotoxin, a cytotoxin, a cardiotoxin, a hemotoxin, or a myotoxin.
  • a second monoclonal antibody capable of neutralizing a different neurotoxin, a cytotoxin, a cardiotoxin, a hemotoxin, or a myotoxin.
  • the amount of an antibody described herein, or a pharmaceutical composition described herein which will be effective in the treatment and/or prevention of a condition will depend on the nature of the disease, and can be determined by standard clinical techniques. The precise dose to be employed in a pharmaceutical composition will also depend on the route of administration, and the seriousness of the disease, and should be decided according to the judgment of the practitioner and each subject's circumstances.
  • effective doses may also vary depending upon means of administration, target site, physiological state of the patient (including age, body weight and health), whether the patient is human or an animal, other medications administered, or whether treatment is prophylactic or therapeutic.
  • the patient is a human but non-human mammals including transgenic mammals can also be treated.
  • Treatment dosages are optimally titrated to optimize safety and efficacy.
  • an in vitro assay is employed to help identify optimal dosage ranges.
  • Effective doses may be extrapolated from dose response curves derived from in vitro or animal model test systems.
  • a pharmaceutical pack or kit described herein comprises one or more containers filled with one or more of the ingredients of the pharmaceutical compositions described herein, such as one or more antibodies described herein.
  • a kit contains an antibody described herein or a pharmaceutical composition described herein, and a second prophylactic or therapeutic agent used in the treatment of snake bites.
  • the second agent is an anti-toxin.
  • a kit contains an antibody described herein or a pharmaceutical composition described herein, and a reagent used in the detection of 3FTx-L.
  • Optionally associated with such container(s) can be a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals or biological products, which notice reflects approval by the agency of manufacture, use or sale for human administration.
  • the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95.
  • the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5. In some embodiments, a kit described herein comprises an antibody described herein, or a pharmaceutical composition described herein and a notice that reflects approval for use or sale for human administration, or d) any combination thereof.
  • the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95.
  • the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6.
  • the antibody comprises the VH and VL of LB5_95.
  • the antibody comprises the VH and VL of 95MAT5.
  • Embodiments of the present disclosure can be further defined by reference to the following non-limiting examples, which describe in detail preparation of certain antibodies of the present disclosure and methods for using antibodies of the present disclosure. It will be apparent to those skilled in the art that many modifications, both to materials and methods, can be practiced without departing from the scope of the present disclosure. All documents, patent, and patent applications cited herein are hereby incorporated by reference, and may be employed in the practice described herein.
  • polyclonal immunoglobulins are purified, sometimes processed into antibody fragments (F(ab’)2 or Fabs), and formulated for intravenous delivery to snakebite victims (R3).
  • a high-quality antivenom matched to the biting snake species is effective at reducing morbidity and mortality.
  • several antivenoms have significant problems with their safety, efficacy, potency, cost, and distribution (R4, 5).
  • the immunogenicity of the heterologous proteins and impurities present in antivenoms can induce serum sickness and severe anaphylaxis (R6).
  • venoms are complex mixtures with multiple classes and isoforms of toxic proteins that exhibit highly diverse structures, functions, biological targets, and compositions between snakes (R1, 9).
  • Three-finger toxins (3FTx) are among the most abundant and lethal toxins present in the venom of elapids, a major medically relevant family of venomous snakes that includes cobras, kraits, and mambas (R10).
  • 3FTxs exhibit significant antigenic and functional diversity and, thus, are categorized into various subfamilies (R11).
  • the ⁇ -neurotoxin class of 3FTx targets the muscle-type nicotinic acetylcholine receptor (nAChR) at neuromuscular junctions, leading to paralysis and death via asphyxiation (R12). Since ⁇ -neurotoxins are abundantly produced by a wide range of elapid species, they are considered key targets for antivenom development (R12).
  • the ⁇ -neurotoxins are further categorized into short-chain (3FTx-S) and long-chain (3FTx-L) variants based on their sequence length (R11).
  • the project workflow provides a generalizable strategy for discovering antibodies that target conserved sites on antigenically variable proteins.
  • the key features of the platform include selecting and recombinantly producing toxin baits, using a synthetic yeast display library, and analyzing antibody cross-reactivity through parallel selections and deep sequencing.
  • the utilization of recombinantly produced toxins allowed for a high level of control over antigenic variability and bypassed the need to purify the necessary toxins from multiple snake species.
  • the antibody selections from a synthetic library are driven by affinity, overcoming some of the challenges in eliciting robust antibody responses against monomeric, low molecular weight toxins that are often poorly immunogenic.
  • the antibodies recovered from this library are fully human and will lack the same immunogenic side effects as current animal- derived antivenoms.
  • snake venom is a complex cocktail of toxins, it necessitates the inclusion of broadly cross-reactive antibodies against several additional major venom classes, including short-chain 3FTx and phospholipase in elapids, and metalloproteinase and serine protease in viperids (R1). Therefore, a final universal antivenom may encompass a minimum of four to five antibodies to effectively cover the additional venom classes.
  • the discovery and development of 95Mat5 is an important first step, as it effectively neutralizes one of the most diverse and toxic components of the venom.
  • this research presents an adjustable blueprint for generating antibodies that target a broad range of antigenically diverse components, providing a valuable framework for the development of additional antivenom antibodies.
  • 3FTx-L variants from a diverse range of medically relevant African and Asian elapid snakes were recombinantly expressed in mammalian cells as candidates for antibody isolation and/or downstream characterization (Table 4). These variants exhibited a broad range of antigenic diversity, with as low as 47% paired sequence identity but with two highly conserved regions: the disulphide core and the second loop that is principally responsible for nAChR binding (R12) (Fig 1A). From these 16 candidates, a smaller panel of eight functional variants was selected to capture overall antigenic diversity and prioritize variants with available published structures (Fig 1B-C, Fig 6).
  • Recombinant 3FTx-L variants used in the antibody isolation campaign were confirmed to bind the human nAChR ⁇ 1 subunit displayed on the surface of yeast and demonstrated antagonism of the acetylcholine-induced activation of human muscle-type nAChR expressed in TE671 cells (Fig 7).
  • Table 4 List of recombinant 3FTx-L variants synthesized and tested for nAChR ⁇ 1 binding. UniProt and PDB accession numbers are provided along with any names associated with the toxin variants, snake species and geographic regions. The half-maximal inhibitory concentration (IC50) measured from the curves in Fig 7 for binding to yeast-displayed human nAChR ⁇ 1 subunit is indicated for each variant.
  • DNB did not bind.
  • Variant Accession Othe nACR ⁇ 1 name r name Species Region IC50 , . 3 FTx-L3 C0HJD7, 4LFT Alpha-elapitoxin-Dpp2d Dendroaspis polylepis s E o a u s t t h e c r e n nt A ra f l r i & 781 nM c a 3FTx-L5 P01391, 2CTX, Alpha-cobrat Naja kaouthia, Naja 4 AEA oxin siamensis Southeastern Asia 42 nM 3FTx-L6 P01390 Neurotoxin alpha Naja nivea Southern Africa 81 nM 3FTx-L8 A1IVR9 Alpha-elapitoxin-Bc2b Bungarus candidus Southern Asia 0.21 nM 3 FTx-L9 P01393 Alpha-elap
  • MCS magnetic-activated cell sorting
  • FACS fluorescence-activated cell sorting
  • the enriched cells were then subjected to five rounds of FACS: two rounds using decreasing concentrations of 3FTx-L2 to enrich high-affinity clones, interspersed with two rounds of negative selections using detergent- solubilized membrane proteins to deplete sticky clones (Fig 9). Following this fourth round of FACS, all cells displayed affinity for 3FTx-L2 and exhibited minimal off-target specificity.
  • the library was split into five fractions and screened each against a different 3FTx-L variant to identify the subset of binding Fabs (Fig 1D, Fig 8). At the conclusion of these selections, cells recovered from each round of FACS were harvested, and the Fab-encoding portions of the plasmids were deep sequenced.
  • Toxin binding was further validated via surface plasmon resonance (SPR) with a panel of seven 3FTx-L variants (Fig 2B).
  • the antibodies were also evaluated for neutralization of nAChR antagonism by the native 3FTx-L ⁇ -bungarotoxin using TE671 cells (Fig 2C).
  • Antibody clone LB5_95 was among the most potent neutralizing antibodies and had the highest affinity across all recombinant variants, thus was chosen as the lead candidate for affinity maturation.
  • Table 2 CDR sequences of cross-reactive mAbs.
  • variable domain genes for the heavy chain (HC) and light chain (LC) are listed for each cross-reactive mAb along with the SEQ ID NO for the 6 CDR, HV and VL sequences.
  • Antibody clone 95Mat5 displayed affinity gains across all seven 3FTx-L variants, primarily due to decreased dissociation rates (Fig. 2E) and had a favorable biochemical profile (Fig 11B-E).
  • 95Mat5 was further evaluated for blocking of 3FTx-L binding to yeast-displayed nAChR ⁇ 1 and exhibited inhibition against all variants tested (Fig 2F). Additionally, 95Mat5 demonstrated enhanced functional neutralization of nAChR antagonism in TE671 cells by both native ⁇ -bungarotoxin and recombinant 3FTx-L variants (Fig 2G).
  • Table 3 CDR sequences of cross-reactive mAbs.
  • variable domain genes for the heavy chain (HC) and light chain (LC) are listed for each cross-reactive mAb along with the SEQ ID NO for the 6 CDR, HV and VL sequences.
  • mAb 1 2 3 H H H 1 L 2 L 3 L VH VL 3 1 9 95Mat4 220 221 222 223 224 225 226 227 95Mat5 228 229 230 231 232 233 234 235 3
  • a yeast display library containing 8283FTx variants was constructed, sorted via FACS with 95Mat5, and deep sequenced.
  • the final sort showed exclusive enrichment with 753FTx-L variants (Fig 3A), with SPR-validated 3FTx-L8 at the end of the deep sequencing ranking (Fig 3B).
  • Other 3FTx-L variants at the binding threshold of the final sorts were synthesized and validated for 95Mat5-binding via ELISA, whereas three 3FTx-S variants that were enriched in the first 2 sorts failed to either express or bind 95Mat5 when tested (Fig 12).
  • a diverse range of 36 elapid species from 15 genera was represented in the 95Mat5- binding set of 3FTx-L variants and spread to geographic regions and alignment nodes that were not encompassed by the characterization panel of 3FTx-L variants (Fig 3C, Table 5).
  • the eluent was then concentrated to > 1 mg/ml and exchanged into PBS using a 10 kDa centrifugal filter unit (Millipore Sigma).
  • the resin was transferred to 20 mM Tris, 150 mM NaCl, pH 7.4 after washing with PBS.
  • WELQut protease (Thermo Fisher) was added to the resin and incubated with rotation for 3 hours at 30°C.
  • the supernatant was harvested from the resin and incubated with HisPurTM Ni-NTA resin (Thermo Fisher) for 30 minutes at room temperature to remove the His-tagged protease, followed by a second incubation with rProtein A resin for 30 minutes to remove any residual Fc tag.
  • the final supernatant was concentrated to >1 mg/ml using a 3 kDa centrifugal filter unit (Millipore Sigma). Toxin-Fc conjugates and cleaved toxins were frozen in aliquots stored at -80°C. Biotinylation of the purified toxins was confirmed using the Pierce biotin quantitation kit (Thermo Fisher).
  • native ⁇ - bungarotoxin purified from B. multicinctus venom was purchased from Thermo Fisher (cat #B1601).
  • the venoms of N. kaouthia and O. hannah were collected from the wild with appropriate permission from the respective forest departments (Kolkata, West Bengal #386/WL/4R-6/2017; 12/02/2018 and Mysore, Karnataka PCCF(WL)/E2/CR-06/2018-19).
  • the D. polylepis venom was a kind gift from Premium Serums and Vaccine Pvt. Ltd. (PSVPL).
  • Antibody library construction and validation A human antibody library was constructed using the common light chain strategy (R42) and displayed as molecular Fab on the surface of Saccharomyces cerevisiae in the pYDSI2 Fab display vector, which included a V5 tag for detection of HC display and a c-Myc tag for detection of LC pairing.
  • the library contains 8 human variable heavy (VH) genes (VH1-02, VH1- 18, VH1-69, VH3-07, VH3-15, VH3-23, VH3-30 and VH5-51) and 4 human variable light (VL) genes (VK1-39, VK3-20, VL1-51, VL2-14) that were selected based on high-frequency in the human memory compartment, canonical complementary determining region (CDR) structural diversity and favorable developability properties.
  • Library diversity was localized to the CDRH3 using oligonucleotides synthesized with trimer amidite mixtures based on the frequency of amino acids found in antibody CDRH3 loops, excluding methionines and cysteines.
  • the library included CDRH3 lengths between 10 and 20, using a distribution centered on length 15 but skewed to favor longer CDRH3s to avoid oversampling the shorter loops.
  • the VH and VL genes used germline CDR1 and CDR2 loops without any additional diversity, and the CDRH3 loop was fixed based on the most frequently occurring VJ rearrangement for each VL gene.
  • the heavy chains were designed to have a conserved stretch of nucleotides in the framework 2 region of the VH gene and in the J gene-encoding region just after the CDRH3. Further, each VH gene was codon-optimized in four different ways, and each unique VH gene was paired with a fixed light chain.
  • This overall design allows for deep sequencing preparation of a ⁇ 250 bp stretch of DNA that can be prepared from bulk-sorted cells and encodes the VH gene (identified by the CDRH2 loop sequence), the CDRH3 and the corresponding light chain (from the codon optimization of the VH region).
  • DNA for the library was prepared, and cells were transformed using 1,152 replicates of a high-throughput yeast transformation protocol. In total, a library with a diversity of 6x10 10 across all VH/VL pairs, estimated by colony-forming unit assay, was produced. Upon completion of the library, DNA was harvested from a subset of the expanded cells for deep sequencing analysis of the constructed antibodies. Overall, the CDRH3 length and amino acid distributions closely agree with the targeted distributions.
  • a test selection campaign was next run with 5 clinically relevant targets: ICOS-L, TNFalpha, PD1L2, IL-6R and SARS- CoV2-RBD. Briefly, 3 rounds of MACS followed by 5 rounds of FACS (3 positive selections interspersed with 2 negative selections) were used to enrich antigen-specific clones from the library. A subset of selected cells was archived after each round of FACS enrichment, and at the completion of the selection campaigns DNA was prepared for deep sequencing to monitor the enrichment process throughout. Strong enrichments were observed for each target antigen, and 6- 12 highly enriched antibodies were selected for production and characterization. At least 50% of the selected mAbs were binding for each target antigen, and most exhibited a KD in the nM range when tested via SPR.
  • Table 6 Binding affinity of mAbs for 3FTX variants The equilibrium dissociation constant (KD) measured via SPR for each mAb on each selected 3FTx-L variant is listed in nanomolar units.
  • KD equilibrium dissociation constant
  • NB not binding Snake Bungarus Dendroaspis Naja Bungarus Dendroaspis Ophiophagus 5 LB5_90 6.8 13 10 6.5 NB 6.9 14 LB5 91 11 4.8 6.6 4 1300 12 6.3 Magnetic activated cell sorting Frozen aliquots of the naive library were thawed and approximately 2.5*10 11 cells were expanded in SD-Ura medium (Sunrise Science) and grown at 30 ⁇ C overnight.
  • ⁇ 10 12 induced cells were pelleted and washed in PBS, then rotated overnight at 4°C with 20 nM of biotinylated, Fc-conjugated 3FTx-L2 and 3FTx-L3 as antigen baits in 120 mL PBS with 1% BSA (PBSA).
  • Labeled cells were washed with PBSA in batches of ⁇ 4.2*10 10 cells, incubated with 200 ⁇ L streptavidin MicroBeads (Miltenyi Biotec) for 20 min at 4°C, and then selected for positive binding using an autoMACS® Pro Separator (Miltenyi Biotec).
  • the recovered cells were subsequently grown and induced for negative sorting (MACS2) with the streptavidin MicroBeads and anti-biotin MicroBeads in the absence of the antigens (Fig 8).
  • the streptavidin binders that were enriched from the first round of MACS were discarded.
  • the non-binders were labeled again with the antigens (20 nM Fc-3FTx- L2 and 20 nM Fc-3FTx-L3) for 60 min at 4°C, washed and labeled with anti-biotin MicroBeads, and sorted for positive binding (MACS3).
  • the selected cells were then grown and induced again for FACS.
  • Fluorescence-activated cell sorting Yeast cells were alternatively selected for 3FTx binding (affinity sorts), or depleted against polyreactive clones (PSR sorts) by labeling cells with biotinylated polyspecificity reagent (R43, 44) and selecting the low binding population. After each round of selection, the collected cells were expanded and reinduced prior to the next selection. A subset of the expanded cells were also frozen for future deep sequencing analysis. During affinity sorting, 1-5*10 7 induced yeast cells were incubated for 60 min rotating at 4°C with monomeric biotinylated 3FTx variants in PBSA.
  • induced yeast cells were incubated with 20 ⁇ g/mL biotinylated HEK-cell soluble cytosolic protein extracts (SCP) (R43) and 1 ⁇ M rabbit Fc-conjugated PLA 2 in PBSA to deplete non-specific and Fc-binding Fab clones.
  • SCP biotinylated HEK-cell soluble cytosolic protein extracts
  • FITC signal (heavy chain vs light chain), which was subsequently sorted for antigen-binding on a plot of APC vs. FITC signal (Fig 9).
  • Selected yeast cells were grown in SD-Ura medium shaking overnight at 30°C and induced for consecutive rounds of selection.
  • AFF1 and AFF2 sorts cells were labeled with 100 nM and 20 nM 3FTx-L2, respectively (Fig 8).
  • AFF3 the induced library was split into five fractions, each sorted against a different toxin.
  • Yeast cells were then spun down; the cell pellet was resuspended with 250 ⁇ L of buffer P1 (with RNAse added) (Qiagen) by pipetting up and down. 5 ⁇ L of Zymolyase (Zymo Research) was added to digest yeast cell walls and incubated at 37°C for 1 h. Cells were then lysed, neutralized, and DNA was purified according to manufacturer’s instructions (Qiagen). A 240-290 bp amplicon was prepared via PCR using primers to amplify the HC region of the Fab sequence attached to partial Illumina® adapters.
  • a subsequent round of PCR was performed to attach unique indexing barcodes for each sample library using xGenTM UDI primers (Integrated DNA Technologies). Once barcoded, all library samples were pooled together, cleaned via column purification (Qiagen) and gel purification, and then measured with a Qubit DNA concentration assay (Thermo Fisher). The amplicon sample was denatured in 0.1N NaOH, combined with 20% denatured PhiX control library (Illumina) and loaded at 7 pM concentration onto a NovaSeq 6000 System (Illumina Inc) with a paired-end NovaSeq v1.5500 bp kit.
  • Paired-end FASTQ files were analyzed using the FastQC package (FastQC v0.11.9) to ensure high sequence quality and low contamination (R45).
  • FastQC v0.11.9 high sequence quality and low contamination
  • BBMerge version 38.87
  • R47 VSEARCH
  • FASTA files were written, including the abundance of each unique sequence in the FASTA header. This step substantially improved the performance of downstream FASTA parsing, as each unique sequence was only analyzed once.
  • Python code (Python 3.7) was written to parse the clustered fasta output, remove primer sequences, identify the base heavy and light chains, and translate the DNA sequences to amino acid sequences. The script then counted the unique CDR3 sequences separately associated with each heavy and light chain.
  • Affinity maturation of LB5_95 Library generation and screening Oligo pools for each of the 6 CDRs in LB5_95 were generated with combinatorial point mutations at each site in the CDR using the SAMPLER strategy (R27) and synthesized by IDT. The mutations were predefined so that the introduction of liabilities such as cysteines, methionines, N-linked glycan motifs, integrin binding sites, and aspartate isomerization sites was avoided.
  • the 3 CDRH oligo pools were stitched together with the framework regions of VH1-69 to form a heavy chain (HC) library of 5.4x10 6 diversity while the 3 CDRL oligo pools were assembled with the framework regions of VK1-39 to form a light chain (LC) library of 1.4x10 6 diversity.
  • Two additional LC libraries were also generated to combine with the first.
  • the HC library was transformed into yeast with the pYDSI2 Fab display vector containing VK1-39 as the fixed LC.
  • the three LC libraries were transformed into yeast with the same vector containing VH1-69 and the original LB5_95 CDRH3 as the fixed HC.
  • the HC and combined LC libraries were sorted separately with 3FTx-L2 and 3FTx-L3 for the first 3 affinity sorts (AFF1- AFF3), with a negative PSR sort (PSR1) performed between AFF2 and AFF3 using 20 ⁇ g/mL SCP (Fig 10).
  • AFF1 4 nM and 1 nM of each 3FTx variant were used for the HC and LC libraries, respectively.
  • Both libraries were then sorted with 200 and 40 pM of both 3FTx variants in AFF2, which were combined in PSR1 (Fig 10).
  • the separate HC and LC PSR1 libraries were each sorted with 3FTx-L2 (40 pM) and 3FTx-L3 (40 pM).
  • AFF4 the combined library was sorted with 1 nM, 200 pM and 40 pM of both 3FTx-L2 and 3FTx-L3. These populations were combined together during PSR2 and sorted with 20 ⁇ g/mL SCP.
  • AFF5 the library was split again and sorted with 3FTx-L2 (40 pM), 3FTx-L3 (200 pM), 3FTx-L5 (40 pM), 3FTx-L8 (1 nM), and 3FTx-L15 (40 pM).
  • An additional affinity sort (AFF6) was performed for the populations sorted with 3FTx-L2, 3FTx-L8, and 3FTx-L15 (Fig 10).
  • Dissociation conditions were used for 3FTx-L2 and 3FTx-L15 during AFF6. Briefly, cells were incubated with 10 nM of biotinylated toxin, washed in PBSA, and then incubated overnight with 10 nM of non-biotinylated toxin at 4°C. The following day, cells were washed, incubated with secondaries, and sorted to select antibody variants that had retained binding to the biotinylated toxin overnight. For sequencing of the affinity maturation library, a 570 bp amplicon containing all 6 CDR sites was prepared from a circularized PCR product that ligated the CDR3 end of the HC to the CDR3 end of the LC.
  • the amplicon was processed as described above and sequenced on a MiSeq System (Illumina Inc) with a paired-end MiSeq v3600 bp kit.
  • IgG expression, purification, screening, and characterization Initial cross-reactive antibody candidates
  • the selected antibodies were reformatted as IgG1 and synthesized by GenScript into a mammalian expression vector containing both the heavy and light chain separated by a P2A self- cleaving motif.
  • Antibody encoding plasmids were transfected into Expi293 cells and purified using Protein A magnetic beads (Thermo Scientific) and elution with acidic IgG elution buffer.
  • ELISA was used to screen for the cross-reactive binding of the antibodies against 3FTx-L variants. Briefly, polystyrene high-bind microplates (Corning, cat # 3690) were coated with anti-rabbit IgG Fc antibody (Sigma, cat # SAB3700849) overnight at 4°C, washed 3X with PBS containing 0.5% tween (PBST), blocked with PBS containing 3% BSA, incubated with recombinant rabbit Fc- tagged 3FTx-L for 1 hour at room temperature, and washed again 3X with PBST.
  • PBST PBS containing 0.5% tween
  • Antibodies that did not bind CHO-SMP were then screened for binding against additional 3FTx variants (3FTx-L1, 3FTx-L3, 3FTx-L5, and 3FTx-L6). 16 of the 30 antibodies selected for cross-reactivity via deep sequencing screened positive for cross-reactive binding to all 5 toxin variants (LCa-1, LCa-2, LCa-3, LCa-5 and LCa- 6) (Fig 2A).
  • Non-specific binding of these antibodies was further evaluated with the HEp-2 assay (Hemagen) using methods provided by the manufacturer and compared to reactive (bococizumab) and non-reactive (adalimumab) antibody controls.
  • Affinity matured antibodies 6 cross-reactive antibody candidates were selected from the affinity maturation library for synthesis and testing.
  • the antibodies were expressed as IgG1 using a 1:2.5 ratio of HC:LC DNA and purified as previously described.
  • the antibodies were first tested for non-specific binding on ELISA plates coated with CHO-SMP, single-stranded DNA, or insulin (Fig 11B) and subsequently tested for self-association using affinity-capture self-interaction nanoparticle spectroscopy (AC- SINS, Fig 11C).
  • the maturation antibody candidates were then incubated with the concentrated nanoparticles at a 15:1 volume ratio for 1 hr with a final Ab concentration of 41 ⁇ g/ml.
  • the average plasmon wavelength was calculated as the maximum absorption at 510-570 nm for each antibody sample, and the absorption from a blank control was subtracted to determine the wavelength shift caused by antibody self-association.
  • a non-self-interacting antibody (adalimumab) and a self- interacting antibody (bococizumab) were utilized as controls for comparison.
  • the antibodies were additionally characterized via analytical SEC and HEp-2 assay as previously described (Fig 11D, Fig 11E).
  • the lead maturation candidate (95Mat5) was also expressed and purified from Expi293 cells in a His-tagged Fab format (VH conjugated to constant CH1-only) for use in the structural studies. Briefly, harvested supernatant was incubated with HisPurTM Ni-NTA resin (Thermo Fisher) and eluted using 500 mM imidazole, then run over SEC using a HiLoad 16/600 Superdex 200 pg column (Cytiva) on an AKTA pure protein purification system (Cytiva). Surface plasmon resonance SPR measurements were carried out on a Biacore 8K instrument at 25°C.
  • a concentration series of 3FTx-L variants (or clinically relevant antigens) were injected across the antibody and control surface for 2 min, followed by a 20 min dissociation phase using a multi-cycle method. Regeneration of the surface in between injections of analyte was achieved with two, 120s injections of 3 M MgCl2. Kinetic analysis of each reference subtracted injection series was performed using the BIAEvaluation software (Cytiva). All sensorgram series were fit to a 1:1 (Langmuir) binding model of interaction. In vitro binding and inhibition assays Flow cytometry nAChR blocking assay The construct for the ⁇ 1 subunit of nAChR was based on a sequence used previously (R48) and displayed on the surface of S.
  • Biotinylated, cleaved 3FTx-L variants were pre- coupled with 95Mat5 antibody in various ratios for 1 hour at 4°C prior to incubating with induced yeast cells displaying nAChR for an additional hour in volumes avoiding depletion conditions.
  • TE671 cell-based assay of nAChR antagonism A fluorescence assay measuring the activation of fetal ( ⁇ -subunit-containing) muscle- type nAChRs natively expressed in the TE671 cell line (RRID: CVCL_1756) using a membrane potential dye (FLIPR membrane potential dye blue, Explorer Kit, R8042, Molecular Devices, San Jose, CA, USA) was employed as described in Patel et al. (R49). All further reagents in this section were acquired from Gibco, Thermo Fisher Scientific, Paisley, UK, unless stated otherwise.
  • TE671 cells were cultured in a culture medium consisting of DMEM with GlutaMAX supplement further supplemented with 10% FBS and 1% penicillin-streptomycin solution, and incubated at 37 °C/5% CO 2 until ⁇ 90% confluence was reached. Cells were dislodged from cell culture flasks with TrypLE express enzyme, and the resulting suspension was added to a 10 mL culture medium, followed by centrifugation for 5 minutes at 300 x g.
  • Assay buffer was also used to create all solutions containing toxin, antibody, or acetylcholine. The culture medium was removed and replaced with 50 ⁇ L of dye solution and incubated for 30 min at 37 °C/5% CO2.
  • the cell plate was acclimatized at room temperature for 15 min then recorded using a FlexStation 3 multi-mode microplate reader (Molecular Devices, San Jose, CA, USA) controlled by SoftMax Pro 7.1 software (Molecular Devices, San Jose, CA, USA). Excitation, cut-off, and emission wavelengths were set at 530, 550, and 565 nm, respectively, and recordings were carried out at room temperature with a read time of 214 s and an interval time of 2 s.
  • toxin-only and antibody-only controls were also included, with all data points normalized to the mean of the acetylcholine-only and toxin-only control. This was achieved by subtracting the toxin only control from the antibody + toxin and acetylcholine- only responses before normalizing to the acetylcholine response. To ensure a maximal signal window, varying concentrations of antibody were incubated with toxin concentrations that gave final concentrations of 30 nM ⁇ -bungarotoxin (as used in Patel et al.) and 380 nM 3FTx-L6 (calculated after IC 50 analysis of toxin in Fig 7).
  • 3FTx oligo pool contained three different codon versions of each protein sequence (2,484 total oligos) with homology regions at both ends and was displayed on the surface of S. cerevisiae in the pYDSI2u_SiDi1 vector.
  • a series of 3 affinity sorts were performed using 95Mat5 antibody at a concentration of 20 nM on a FACS Melody (BD Biosciences).
  • Yeast cells were incubated with antibody in PBSA for 1 hour at 4°C prior to washing and incubation with 1 ⁇ g/mL anti-V5-AF405 conjugate and 1 ⁇ g/mL anti-human IgG Fc-phycoerythrin (PE) conjugate (Southern Biotech cat #9040-09) for 20 min to select for cells displaying toxin and binding to antibody.
  • Isolated yeast cells were grown in SD-Ura medium shaking overnight at 30°C and induced for consecutive rounds of selection. Reserved cells from each sort were prepared for deep sequencing of the toxin-encoding plasmid region using a 330-360 bp amplicon attached to partial Illumina® adapters and methods described previously.
  • Deep sequencing was performed using a MiSeq System (Illumina Inc) with the paired-end MiSeq v3600 bp kit.
  • a composite reference of the 2,484 3FTx nucleotide sequences was constructed in FASTA format and indexed using Burrows-Wheeler Transform (R54). Forward and reverse reads were merged using BBMerge (version 38.87) from the BBTools suite with default parameters (R46). Merged reads were aligned to the reference and quantified using SAMtools (R55) without removing duplicates. Clones that were enriched and expressed through at least 2 of the codon versions in the final sort were considered to be antibody- binding.
  • the 3FTx-L2-binding Fab clones quantified in Fig 1E-1I were filtered from the deep sequencing data of the naive library sorted with 3FTx-L2 based on a total of 100 or more counts across the AFF2, PSR2, and AFF3 sorts. PCR sequencing artifacts and any sequence with a stop codon were removed.
  • mice received 2x IV LD 50 ⁇ -bungarotoxin alone or preincubated with 95Mat5 at molar ratios of 1:8 or 1:25 toxin:antibody. All animals in the control group rapidly exhibited signs of systemic neurotoxicity and succumbed to envenoming within four hours, while those receiving 95Mat5 exhibited significantly prolonged survival (Fig 4A).
  • Table 7 Intravenous and subcutaneous median lethal dose (LD 50 ) measured for ⁇ - bungarotoxin and crude venoms.
  • Toxin/venom Intravenous LD 50 Subcutaneous LD 50 Not tested 13.8 ⁇ g/mouse (0.688 Ophiophagus hannah 17.9 ⁇ g/mouse (0.890 mg/kg) 21.5 ⁇ g/mouse (1.08 mg/kg) Dendroaspis polylepis 6.99 ⁇ g/mouse (0.349 mg/kg) 7.17 ⁇ g/mouse (0.358 mg/kg)
  • the cross-neutralizing efficacy of 95Mat5 against 2x IV LD50 challenge doses of N. kaouthia, D. polylepis and O. hannah crude venoms was assessed.
  • mice were also treated with conventional equine-derived commercial antivenoms specific to each of the challenge venoms. These were tested at two concentrations: a high dose equivalent to their marketed neutralizing potency (Table 8) and a fixed lower dose of 25 mg/kg, matched for direct comparison with 95Mat5.
  • Table 8 a high dose equivalent to their marketed neutralizing potency
  • a fixed lower dose of 25 mg/kg matched for direct comparison with 95Mat5.
  • Mice IV dosed with whole N. kaouthia venom succumbed to death within one hour, while treatment with 95Mat5 or an equivalent dose of antivenom provided complete protection for 24 hours (Fig 4B).
  • 95Mat5 and the higher dose of antivenom protected mice from the lethal effects of D. polylepis venom, though the dose-matched antivenom resulted in only 20% survival (Fig 4C).
  • the marketed neutralization potency for each commercial antivenom is listed in units of mg venom that could be neutralized by one ml of undiluted antivenom, while the antivenom concentration is listed in units of mg serum protein (based on the dry weight of antivenom product contained in a vial) per ml of reconstituted antivenom solution.
  • the antivenom dosage is then converted to mg of serum protein per kg of animal weight.
  • Manufacturer Batch Specie Venom Antivenom Antivenom Antivenom Antivenom n umber s Type dosage potency concentration dosage two- step rescue assay where treatment is delivered after venom challenge was also evaluated. N. kaouthia and D.
  • polylepis venoms SC were used to better enable the evaluation of delayed treatment, which consisted of 25 mg/kg of 95Mat5 IV at 0, 10 and 20 minutes post-venom dosing. In both groups, control animals died within 3 hours of the venom challenge. In contrast, animals receiving 95Mat5, irrespective of treatment delay, survived the full 24-hour observation period without signs of neurotoxicity (Fig 4E-F).
  • mice Male CD-1; 18–22 g
  • mice Male CD-1; 18–22 g
  • mice Male CD-1; 18–22 g
  • mice Male CD-1; 18–22 g
  • mice Male CD-1; 18–22 g
  • mice Male CD-1; 18–22 g
  • mice Male CD-1; 18–22 g
  • mice Male CD-1; 18–22 g
  • mice Male CD-1; 18–22 g
  • mice Male CD-1; 18–22 g
  • R56 WHO-recommended approach
  • Five concentrations of toxin/venom were diluted in PBS to a volume of 200 ⁇ l and then intravenously (caudal vein) or subcutaneously injected into groups of five mice.
  • the mortality rate was recorded every one hour for a total of 24 hours post-venom injection, and the LD50 was estimated using Probit statistics (R57).
  • a 2x LD 50 dose of ⁇ -bungarotoxin 22 ⁇ g/mouse was incubated with 95Mat5 antibody in toxin:antibody molar ratios of 1:8 and 1:25 (27 and 85 mg/kg antibody) at 37 °C for 30 min.
  • the preincubated mixture (200 ⁇ l volume) was then intravenously injected into the caudal vein of a group of five mice, and the animals were continuously monitored over a 24-hour period. The time taken for the appearance of pathophysiological symptoms (e.g., hindlimb paralysis, loss of righting reflex, etc.) and death was noted. Kaplan–Meier plots were generated to depict the percentage survival over time. Similar experiments were conducted with 2x LD50 doses of each crude venom preincubated with 25 mg/kg of 95Mat5 antibody. The efficacy of 95MatAb was evaluated in comparison with the conventional monovalent antivenoms marketed by Queen Saovabha Memorial Institute (QSMI), Thailand, for treating N. kaouthia and O.
  • QSMI Queen Saovabha Memorial Institute
  • CDRH3 Trp99 makes an indole NH hydrogen bond with 3FTx-L15 Pro7 carbonyl oxygen and a carbonyl oxygen-hydrogen bond with the Ile38 backbone amide.
  • Glu100a hydrogen bonds with 3FTx-L15 Arg34 and Lys36.
  • the side chain of Tyr100 makes hydrogen bonds with 3FTx-L15 Arg34 while Thr28 and Ser31 from CDRH1 make side-chain hydrogen bonds with 3FTx-L15 Asp8 (Fig 5C-E and Table 9).
  • CDRH3 Trp99, Tyr100, Glu100a, and Tyr100e are involved in a hydrophobic interaction with a hydrophobic pocket formed by 3FTx-L15 Ala9, Phe30, Arg34, Arg37, Ile38, Phe66, and Thr68 (Fig 13 and Table 10).
  • Table 10 Contacts between nAChR ⁇ 1: ⁇ -bungarotoxin (PDB:2qc1) and 95Mat5:3FTx-L15.
  • the binding mode of 95Mat5 with 3FTx-L15 is similar to previously determined structures of ⁇ -bungarotoxin with nAChR ⁇ 1, ⁇ 7, and ⁇ 9 (Fig 15) (32-33).
  • CDRH3 of 95Mat5 Fab approximates "loop C" of nAChR ⁇ 1 (Fig 5G) that wrap around fingers I, II and the C-terminal loop of 3FTx-L toxins; the tip of the 3FTx-L finger II inserts into the binding site and is surrounded by loops A, B and C of nAChR ⁇ (Fig 5G and Table 10) (R33).
  • the antibody and receptor interact with similar toxin residues (Fig 5G and Table 10).
  • the antibody-antigen complex was screened for crystallization using the 384 conditions of the Joint Center for Structural Genomics (JCSG) Core Suite (Qiagen) using the sitting drop vapor diffusion method on the automated CrystalMation robotic system (Rigaku) at The Scripps Research Institute. Within 3–7 days, diffraction-quality crystals were obtained using 100mM sodium citrate pH 3.75, and 26% PEG6000 as precipitant at 20 °C. Data collection, processing, and structure determination Crystals were cryoprotected with 15-25% ethylene glycol and flash-cooled and stored in liquid nitrogen until data collection.
  • JCSG Joint Center for Structural Genomics
  • Refinement was carried out in Refmac (R62) and Phenix (R63), alternating with manual rebuilding and adjustment in COOT (R64).
  • Detailed data collection and refinement statistics are summarized in Fig. 16.
  • Structure validation was performed with The Protein Data Bank validation server and MolProbity (R65). Before Protein Data Bank (PDB) deposition, PDB-REDO (R66) was performed to complete the structures.
  • the coordinates and structure factors for the 95Mat5:3FTx-L15 are available under accession codes 8SXP.
  • Bailon Calderon et al., Development of Nanobodies Against Hemorrhagic and Myotoxic Components of Bothrops atrox Snake Venom. Front. Immunol.11, 655 (2020).

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Abstract

In one aspect, provided herein is a method for the synthetic production of a human antibody that can neutralize three-finger neurotoxins from various snakes across continents. In one aspect, provided herein is an antibody that binds long-chain three-finger α-neurotoxins from diverse species of snakes with high affinity, blocks toxin binding to the nicotinic acetylcholine receptor in vitro, and protects mice from lethal venom challenge. In one aspect, provided herein is a treatment of snakebite envenoming comprising administering a therapeutically effective amount of an antibody described herein.

Description

ANTI-VENOM ANTIBODIES AND USES THEREOF FIELD OF THE INVENTION [0001] The field of the invention generally relates to anti-toxin antibodies and their use in the treatment of snake bite. CROSS-REFRENCE TO RELATED APPLICATIONS [0002] This application claims the benefit of U.S. application no. 63/395,914, filed August 8, 2022, which is incorporated herein by reference in its entirety. BACKGROUND [0003] Existing animal-derived antivenoms for treatment of snakebite suffer major limitations in safety, efficacy, potency, product consistency, cost of production, and coverage of snake species. A cocktail of human monoclonal antibodies (mAbs) that target individual toxins present in venom with broad cross-reactivity across toxin variants found in multiple geographically diverse species would solve many of the issues inherent with current treatments. Described herein is the discovery of human mAbs that bind and neutralize multiple variants of long chain alpha-neurotoxic three finger toxins (3FTx-L) from multiple species of medically important Asian and African elapid snakes including cobras, kraits and mambas.3FTx-L is a major contributor to the lethality of elapid snake venoms and is often poorly targeted by animal-derived antivenoms thus is an excellent target for a broadly neutralizing human mAb therapy. [0004] There is a need for monoclonal antibodies capable of binding to and neutralizing multiple variants of long chain alpha-neurotoxic three finger toxins (3FTx-L) from multiple species of medically important Asian and African elapid snakes BRIEF SUMMARY [0005] In one aspect, provided herein are monoclonal antibodies that monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L). In some embodiments, an antibody described herein is a bispecific, trispecific or multispecific antibody. In some embodiments, an antibody described herein specifically binds at least one 3FTx-L variant disclosed in Table 1. In some embodiments, an antibody described herein specifically binds at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15 or at least 163FTx-L variants disclosed in Table 1. In some embodiments, an antibody described herein specifically binds all 3FTx-L variants disclosed in Table 1. In some embodiments, an antibody described herein is capable of neutralizing at least one 3FTx-L variant disclosed in Table 1. In some embodiments, an antibody described herein is capable of neutralizing alpha-bungarotoxin (SEQ ID NO: 250). In some embodiments, an antibody described herein is capable of neutralizing at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15 or at least 16 3FTx-L variants disclosed in Table 1. In some embodiments, an antibody described herein is capable of neutralizing the 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, or 3FTx-L15 variants disclosed in Table 1. In some embodiments, an antibody described herein is capable of neutralizing the 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, and 3FTx- L15 variants disclosed in Table 1. In some embodiments, an antibody described herein is capable of neutralizing all 3FTx-L variants disclosed in Table 1. In some embodiments, neutralization is assessed in an in vitro cell based assay. In some embodiments, neutralization is assessed in an in vivo assay. [0006] In one aspect, provided herein are pharmaceutical compositions comprising a monoclonal antibody that specifically binds to 3FTx-L described herein. [0007] In one aspect, provided herein are isolated polynucleotides encoding a monoclonal antibody that specifically binds to 3FTx-L described herein. [0008] In one aspect, provided herein are methods of producing a monoclonal antibody that specifically binds to 3FTx-L described herein. [0009] In one aspect, provided herein are methods of neutralizing an 3FTx-L, comprising contacting the toxin with a monoclonal antibody that specifically binds to 3FTx-L described herein. [0010] In one aspect, provided herein are methods of treating snake bite comprising administering to a subject in need thereof a monoclonal antibody that specifically binds to 3FTx-L described herein. [0011] In one aspect, provided herein are methods of producing an engineered variant of a monoclonal antibody that specifically binds to 3FTx-L described herein. [0012] In some embodiments, the disclosure provides: [1.] An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein (1) the VH is a VH1-02, VH1-18, VH1-69 or VH3-07 VH and the VL is a VL2-14, VK3-20, VK1-39, VL2-14 or VL1-51 VL, and (2) wherein the VH CDR3 comprises 20 or 21 amino acid residues comprising the amino acid sequence of SEQ ID NO: 244- 248 or 249. [2.] An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises Thr28, Ser31 and Tyr32, the VH CDR3 comprises 20 or 21 amino acid residues comprising the amino acid sequence of SEQ ID NO: 244-248 or 249, the VL CDR1 comprises Tyr32, the VL CDR2 comprises Asp50 and the VL CDR3 comprises Ser91 and Tyr92, optionally wherein the VH is a VH1-02, VH1-18, VH1-69 or VH3-07 VH and the VL is a VL2-14, VK3-20, VK1-39, VL2-14 or VL1-51 VL. [3.] The antibody of embodiment [1] or embodiment [2], wherein the VH CDR3 comprises an amino acid sequence of SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, 123, 133, 143 or 153 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [4.] The antibody of embodiment [1] or embodiment [2], wherein the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222, or 238, optionally wherein the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153. [5.] The antibody of embodiment [1] or embodiment [2], wherein (1) the VH CDR1 comprises the amino acid sequence of SEQ ID NO: 151, (2) the VH CDR2 comprises the amino acid sequence of SEQ ID NO: 152, 213, 229, or 237, (3) the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222 or 238, (4) the VL CDR1 comprises the amino acid sequence of SEQ ID NO: 154, (5) the VL CDR2 comprises the amino acid sequence of SEQ ID NO: 155 or 232, and (6) the VL CDR3 comprises the amino acid sequence of SEQ ID NO: 156. [6.] The antibody of any one of embodiments [1] to [5], wherein the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 151-153, respectively, SEQ ID NO: 196-198, respectively, SEQ ID NO: 204-206, respectively, SEQ ID NO: 212-214, respectively, SEQ ID NO: 220-222, respectively, SEQ ID NO: 228-230, respectively, and SEQ ID NO: 236-238, respectively. [7.] The antibody of any one of embodiments [1] to [6], wherein the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 154-156, respectively, SEQ ID NO: 199-201, respectively, SEQ ID NO: 207-209, respectively, SEQ ID NO: 215-217, respectively, SEQ ID NO: 223-225, respectively, SEQ ID NO: 231-233, respectively, and SEQ ID NO: 239-241, respectively. [8.] The antibody of any one of embodiments [1] to [7], wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 151-156, respectively, SEQ ID NO: 196-201, respectively, SEQ ID NO: 204-209, respectively, SEQ ID NO: 212-217, respectively, SEQ ID NO: 220-225, respectively, SEQ ID NO: 228-233, respectively, and SEQ ID NO: 236-241, respectively. [9.] The antibody of embodiment [8], wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 228-233, respectively. [10.] The isolated monoclonal antibody according to any one of embodiments [1] to [9], wherein the VH and VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 157 and 158, respectively, SEQ ID NO: 202 and 203, respectively, SEQ ID NO: 210 and 211, respectively, SEQ ID NO: 218 and 219, respectively, SEQ ID NO: 226 and 227, respectively, SEQ ID NO: 234 and 235, respectively, or SEQ ID NO: 242 and 243, respectively. [11.] The isolated monoclonal antibody of embodiment [10], wherein the VH and VL comprises an amino acid sequence of SEQ ID NO: 157 and 158, respectively, SEQ ID NO: 202 and 203, respectively, SEQ ID NO: 210 and 211, respectively, SEQ ID NO: 218 and 219, respectively, SEQ ID NO: 226 and 227, respectively, SEQ ID NO: 234 and 235, respectively, or SEQ ID NO: 242 and 243, respectively. [12.] An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR3 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. [13.] An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR3 of LB5_95. [14.] An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, 123, 133, 143 or 153. [15.] An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 153. [16.] An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the VH CDR3 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [17.] An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the VH CDR3 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [18.] An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, 123, 133, 143 or 153 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [19.] An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [20.] An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the VH CDR3 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6. [21.] An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222 or 238. [22.] An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein (a) the VH CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR1 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95; (b) the VH CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR2 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95; and (c) the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR3 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. [23.] An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein (a) the VH CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR1 of LB5_95; (b) the VH CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR2 of LB5_95; and (c) the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR3 of LB5_95. [24.] An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein (a) the VH CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 1, 11, 21, 31, 41, 51, 61, 71, 81, 91, 101, 111, 121, 131, 141 or 151; (b) the VH CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 2, 12, 22, 32, 42, 52, 62, 72, 82, 92, 102, 112, 122, 132, 142 or 152; and (c) the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, 123, 133, 143 or 153. [25.] An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein (a) the VH CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 151; (b) the VH CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 152; and (c) the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 153. [26.] An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein (a) the VH CDR1 comprises the VH CDR1 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) the VH CDR2 comprises the VH CDR2 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and (c) the VH CDR3 comprises the VH CDR3 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [27.] An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein (a) the VH CDR1 comprises the VH CDR1 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) the VH CDR2 comprises the VH CDR2 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and (c) the VH CDR3 comprises the VH CDR3 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [28.] An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein (a) the VH CDR1 comprises the amino acid of SEQ ID NO: 1, 11, 21, 31, 41, 51, 61, 71, 81, 91, 101, 111, 121, 131, 141 or 151 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) the VH CDR2 comprises the amino acid of SEQ ID NO: 2, 12, 22, 32, 42, 52, 62, 72, 82, 92, 102, 112, 122, 132, 142 or 152 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and (c) the VH CDR3 comprises the amino acid of SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, 123, 133, 143 or 153 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [29.] An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein (a) the VH CDR1 comprises the amino acid of SEQ ID NO: 151 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) the VH CDR2 comprises the amino acid of SEQ ID NO: 152 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and (c) the VH CDR3 comprises the amino acid of SEQ ID NO: 153 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [30.] An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein (a) the VH CDR1 comprises the VH CDR1 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6; (b) the VH CDR2 comprises the VH CDR2 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6; and (c) the VH CDR3 comprises the VH CDR3 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6. [31.] An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein (a) the VH CDR1 comprises the amino acid of SEQ ID NO: 151; (b) the VH CDR2 comprises amino acid of SEQ ID NO: 152, 213, 229 or 237; and (c) the VH CDR3 comprises amino acid of SEQ ID NO: 153, 214, 222 or 238. [32.] The isolated monoclonal antibody according to any one of embodiments [12] to [31], wherein (a) the VL CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VL CDR1 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95; (b) the VL CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VL CDR2 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95; and (c) the VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VL CDR3 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. [33.] The isolated monoclonal antibody according to any one of embodiments [12] to [31], wherein (a) the VL CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VL CDR1 of LB5_95; (b) the VL CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VL CDR2 of LB5_95; and (c) the VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VL CDR3 of LB5_95. [34.] The isolated monoclonal antibody according to any one of embodiments [12] to [31], wherein (a) the VL CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144 or 154; (b) the VL CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 5, 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 125, 135, 145 or 155; and (c) the VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 6, 16, 26, 36, 46, 56, 66, 76, 86, 96, 106, 116, 126, 136, 146 or 156. [35.] The isolated monoclonal antibody according to any one of embodiments [12] to [31], wherein (a) the VL CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 154; (b) the VL CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 155; and (c) the VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 156. [36.] The isolated monoclonal antibody according to any one of embodiments [12] to [31], wherein (a) the VL CDR1 comprises the VL CDR1 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) the VL CDR2 comprises the VL CDR2 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and (c) the VL CDR3 comprises the VL CDR3 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [37.] The isolated monoclonal antibody according to any one of embodiments [12] to [31], wherein (a) the VL CDR1 comprises the VL CDR1 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) the VL CDR2 comprises the VL CDR2 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and (c) the VL CDR3 comprises the VL CDR3 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [38.] The isolated monoclonal antibody according to any one of embodiments [12] to [31], wherein (a) the VL CDR1 comprises the amino acid of SEQ ID NO: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144 or 154 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) the VL CDR2 comprises the amino acid of SEQ ID NO: 5, 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 125, 135, 145 or 155 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and (c) the VL CDR3 comprises the amino acid of SEQ ID NO: 6, 16, 26, 36, 46, 56, 66, 76, 86, 96, 106, 116, 126, 136, 146 or 156 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [39.] The isolated monoclonal antibody according to any one of embodiments [12] to [31], wherein (a) the VL CDR1 comprises the amino acid of SEQ ID NO: 154 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) the VL CDR2 comprises the amino acid of SEQ ID NO: 155 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and (c) the VL CDR3 comprises the amino acid of SEQ ID NO: 156 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [40.] The isolated monoclonal antibody according to any one of embodiments [12] to [31], wherein (a) the VL CDR1 comprises the VL CDR1 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6; (b) the VL CDR2 comprises the VL CDR2 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6; and (c) the VL CDR3 comprises the VL CDR3 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6. [41.] The isolated monoclonal antibody according to any one of embodiments [12] to [31], wherein (a) the VL CDR1 comprises the amino acid of SEQ ID NO: 154; (b) the VL CDR2 comprises the amino acid of 155, 232 or 240; and (c) the VL CDR3 comprises the amino acid of SEQ ID NO: 156. [42.] The isolated monoclonal antibody according to any one of embodiments [12] to [41], wherein the VH CDR1, VH CDR2 and VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VH CDR1, VH CDR2 and VH CDR3, respectively. [43.] The isolated monoclonal antibody according to any one of embodiments [12] to [41], wherein the VH CDR1, VH CDR2 and VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_95 VH CDR1, VH CDR2 and VH CDR3, respectively. [44.] The isolated monoclonal antibody according to any one of embodiments [12] to [41], wherein the VH CDR1, VH CDR2 and VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to (a) SEQ ID NO: 1, 2 and 3, respectively; (b) SEQ ID NO: 11, 12 and 13, respectively; (c) SEQ ID NO: 21, 22 and 23, respectively; (d) SEQ ID NO: 31, 32 and 33, respectively; (e) SEQ ID NO: 41, 42 and 43, respectively; (f) SEQ ID NO: 51, 52 and 53, respectively; (g) SEQ ID NO: 61, 62 and 63, respectively; (h) SEQ ID NO: 71, 72 and 73, respectively; (i) SEQ ID NO: 81, 82 and 83, respectively; (j) SEQ ID NO: 91, 92 and 93, respectively; (k) SEQ ID NO: 101, 102 and 103, respectively; (l) SEQ ID NO: 111, 112 and 113, respectively; (m) SEQ ID NO: 121, 122 and 123, respectively; (n) SEQ ID NO: 131, 132 and 133, respectively; (o) SEQ ID NO: 141, 142 and 143, respectively; or (p) SEQ ID NO: 151, 152 and 153, respectively. [45.] The isolated monoclonal antibody according to any one of embodiments [12] to [41], wherein the VH CDR1, VH CDR2 and VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 151, 152 and 153, respectively. [46.] The isolated monoclonal antibody according to any one of embodiments [12] to [41], wherein the VH CDR1, VH CDR2 and VH CDR3 comprises the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VH CDR1, VH CDR2 and VH CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [47.] The isolated monoclonal antibody according to any one of embodiments [12] to [41], wherein the VH CDR1, VH CDR2 and VH CDR3 comprises the LB5_95 VH CDR1, VH CDR2 and VH CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [48.] The isolated monoclonal antibody according to any one of embodiments [12] to [41], wherein the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of (a) SEQ ID NO: 1, 2 and 3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) SEQ ID NO: 11, 12 and 13, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (c) SEQ ID NO: 21, 22 and 23, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (d) SEQ ID NO: 31, 32 and 33, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (e) SEQ ID NO: 41, 42 and 43, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (f) SEQ ID NO: 51, 52 and 53, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (g) SEQ ID NO: 61, 62 and 63, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (h) SEQ ID NO: 71, 72 and 73, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (i) SEQ ID NO: 81, 82 and 83, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (j) SEQ ID NO: 91, 92 and 93, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (k) SEQ ID NO: 101, 102 and 103, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (l) SEQ ID NO: 111, 112 and 113, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (m) SEQ ID NO: 121, 122 and 123, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (n) SEQ ID NO: 131, 132 and 133, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (o) SEQ ID NO: 141, 142 and 143, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; or (p) SEQ ID NO: 151, 152 and 153, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [49.] The isolated monoclonal antibody according to any one of embodiments [12] to [41], wherein the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 151, 152 and 153, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [50.] The isolated monoclonal antibody according to any one of embodiments [12] to [41], wherein the VH CDR1, VH CDR2 and VH CDR3 comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6. [51.] The isolated monoclonal antibody according to any one of embodiments [12] to [21], wherein the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 196-198, respectively, SEQ ID NO: 204-206, respectively, SEQ ID NO: 212-214, respectively, SEQ ID NO: 220-222, respectively, SEQ ID NO: 228-230, respectively, and SEQ ID NO: 236-238, respectively. [52.] The isolated monoclonal antibody according to any one of embodiments [12] to [51], wherein the VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VL CDR1, VL CDR2 and VL CDR3, respectively. [53.] The isolated monoclonal antibody according to any one of embodiments [12] to [51], wherein the VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_95 VL CDR1, VL CDR2 and VL CDR3, respectively. [54.] The isolated monoclonal antibody according to any one of embodiments [12] to [51], wherein the VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to (a) SEQ ID NO: 4, 5 and 6, respectively; (b) SEQ ID NO: 14, 15 and 16, respectively; (c) SEQ ID NO: 24, 25 and 26, respectively; (d) SEQ ID NO: 34, 35 and 36, respectively; (e) SEQ ID NO: 44, 45 and 46, respectively; (f) SEQ ID NO: 54, 55 and 56, respectively; (g) SEQ ID NO: 64, 65 and 66, respectively; (h) SEQ ID NO: 74, 75 and 76, respectively; (i) SEQ ID NO: 84, 85 and 86, respectively; (j) SEQ ID NO: 94, 95 and 96, respectively; (k) SEQ ID NO: 104, 105 and 106, respectively; (l) SEQ ID NO: 114, 115 and 116, respectively; (m) SEQ ID NO: 124, 125 and 126, respectively; (n) SEQ ID NO: 134, 135 and 136, respectively; (o) SEQ ID NO: 144, 145 and 146, respectively; or (p) SEQ ID NO: 154, 155 and 156, respectively. [55.] The isolated monoclonal antibody according to any one of embodiments [12] to [51], wherein the VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 154, 155 and 156, respectively. [56.] The isolated monoclonal antibody according to any one of embodiments [12] to [51], wherein the VL CDR1, VL CDR2 and VL CDR3 comprises the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VL CDR1, VL CDR2 and VL CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [57.] The isolated monoclonal antibody according to any one of embodiments [12] to [51], wherein the VL CDR1, VL CDR2 and VL CDR3 comprises the LB5_95 VL CDR1, VL CDR2 and VL CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [58.] The isolated monoclonal antibody according to any one of embodiments [12] to [51], wherein the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of (a) SEQ ID NO: 4, 5 and 6, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) SEQ ID NO: 14, 15 and 16, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (c) SEQ ID NO: 24, 25 and 26, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (d) SEQ ID NO: 34, 35 and 36, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (e) SEQ ID NO: 44, 45 and 46, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (f) SEQ ID NO: 54, 55 and 56, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (g) SEQ ID NO: 64, 65 and 66, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (h) SEQ ID NO: 74, 75 and 76, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (i) SEQ ID NO: 84, 85 and 86, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (j) SEQ ID NO: 94, 95 and 96, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (k) SEQ ID NO: 104, 105 and 106, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (l) SEQ ID NO: 114, 115 and 116, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (m) SEQ ID NO: 124, 125 and 126, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (n) SEQ ID NO: 134, 135 and 136, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (o) SEQ ID NO: 144, 145 and 146, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; or (p) SEQ ID NO: 154, 155 and 156, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [59.] The isolated monoclonal antibody according to any one of embodiments [12] to [51], wherein the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 154, 155 and 156, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [60.] The isolated monoclonal antibody according to any one of embodiments [12] to [51], wherein the VL CDR1, VL CDR2 and VL CDR3 comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6. [61.] The isolated monoclonal antibody according to any one of embodiments [12] to [51], wherein the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 199-201, respectively, SEQ ID NO: 207-209, respectively, SEQ ID NO: 215-217, respectively, SEQ ID NO: 223-225, respectively, SEQ ID NO: 231-233, respectively, and SEQ ID NO: 239-241, respectively. [62.] The isolated monoclonal antibody according to any one of embodiments [12] to [61], wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3, respectively. [63.] The isolated monoclonal antibody according to any one of embodiments [12] to [61], wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_95 VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3, respectively. [64.] The isolated monoclonal antibody according to any one of embodiments [12] to [61], wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to (a) SEQ ID NO: 1, 2, 3, 4, 5 and 6, respectively; (b) SEQ ID NO: 11, 12, 13, 14, 15 and 16, respectively; (c) SEQ ID NO: 21, 22, 23, 24, 25 and 26, respectively; (d) SEQ ID NO: 31, 32, 33, 34, 35 and 36, respectively; (e) SEQ ID NO: 41, 42, 43, 44, 45 and 46, respectively; (f) SEQ ID NO: 51, 52, 53, 54, 55 and 56, respectively; (g) SEQ ID NO: 61, 62, 63, 64, 65 and 66, respectively; (h) SEQ ID NO: 71, 72, 73, 74, 75 and 76, respectively; (i) SEQ ID NO: 81, 82, 83, 84, 85 and 86, respectively; (j) SEQ ID NO: 91, 92, 93, 94, 95 and 96, respectively; (k) SEQ ID NO: 101, 102, 103, 104, 105 and 106, respectively; (l) SEQ ID NO: 111, 112, 113, 114, 115 and 116, respectively; (m) SEQ ID NO: 121, 122, 123, 124, 125 and 126, respectively; (n) SEQ ID NO: 131, 132, 133, 134, 135 and 136, respectively; (o) SEQ ID NO: 141, 142, 143, 144, 145 and 146, respectively; or (p) SEQ ID NO: 151, 152, 153, 154, 155 and 156, respectively. [65.] The isolated monoclonal antibody according to any one of embodiments [12] to [61], wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 151, 152, 153, 154, 155 and 156, respectively. [66.] The isolated monoclonal antibody according to any one of embodiments [12] to [61], wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [67.] The isolated monoclonal antibody according to any one of embodiments [12] to [61], wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the LB5_95 VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [68.] The isolated monoclonal antibody according to any one of embodiments [12] to [61], wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of (a) SEQ ID NO: 1, 2, 3, 4, 5 and 6, respectively; (b) SEQ ID NO: 11, 12, 13, 14, 15 and 16, respectively; (c) SEQ ID NO: 21, 22, 23, 24, 25 and 26, respectively; (d) SEQ ID NO: 31, 32, 33, 34, 35 and 36, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (e) SEQ ID NO: 41, 42, 43, 44, 45 and 46, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (f) SEQ ID NO: 51, 52, 53, 54, 55 and 56, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (g) SEQ ID NO: 61, 62, 63, 64, 65 and 66, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (h) SEQ ID NO: 71, 72, 73, 74, 75 and 76, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (i) SEQ ID NO: 81, 82, 83, 84, 85 and 86, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (j) SEQ ID NO: 91, 92, 93, 94, 95 and 96, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (k) SEQ ID NO: 101, 102, 103, 104, 105 and 106, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (l) SEQ ID NO: 111, 112, 113, 114, 115 and 116, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (m) SEQ ID NO: 121, 122, 123, 124, 125 and 126, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (n) SEQ ID NO: 131, 132, 133, 134, 135 and 136, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (o) SEQ ID NO: 141, 142, 143, 144, 145 and 146, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; or (p) SEQ ID NO: 151, 152, 153, 154, 155 and 156, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [69.] The isolated monoclonal antibody according to any one of embodiments [12] to [61], wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 151, 152, 153, 154, 155 and 156, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [70.] The isolated monoclonal antibody according to any one of embodiments [12] to [61], wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6. [71.] The isolated monoclonal antibody according to any one of embodiments [12] to [61], wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 151-156, respectively, SEQ ID NO: 196-201, respectively, SEQ ID NO: 204-209, respectively, SEQ ID NO: 212-217, respectively, SEQ ID NO: 220-225, respectively, SEQ ID NO: 228-233, respectively, and SEQ ID NO: 236-241, respectively. [72.] The isolated monoclonal antibody according to any one of embodiments [12] to [71], wherein the VH comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 7, 17, 27, 37, 47, 57, 67, 77, 87, 97, 107, 117, 127, 137, 147 or 157. [73.] The isolated monoclonal antibody according to any one of embodiments [12] to [71], wherein the VH comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 157. [74.] The isolated monoclonal antibody according to any one of embodiments [12] to [71], wherein the VH comprises the amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 202, 210, 218, 226, 234, or 242. [75.] The isolated monoclonal antibody according to any one of embodiments [12] to [74], wherein the VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 8, 18, 28, 38, 48, 58, 68, 78, 88, 98, 108, 118, 128, 138, 148 or 158. [76.] The isolated monoclonal antibody according to any one of embodiments [12] to [74], wherein the VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 158. [77.] The isolated monoclonal antibody according to any one of embodiments [12] to [74], wherein the VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 203, 211, 219, 227, 235, or 243. [78.] The isolated monoclonal antibody according to any one of embodiments [12] to [77], wherein the VH and VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to (a) SEQ ID NO: 7 and 8, respectively; (b) SEQ ID NO: 17 and 18, respectively; (c) SEQ ID NO: 27 and 28, respectively; (d) SEQ ID NO: 37 and 38, respectively; (e) SEQ ID NO: 47 and 48, respectively; (f) SEQ ID NO: 57 and 58, respectively; (g) SEQ ID NO: 67 and 68, respectively; (h) SEQ ID NO: 77 and 78, respectively; (i) SEQ ID NO: 87 and 88, respectively; (j) SEQ ID NO: 97 and 98, respectively; (k) SEQ ID NO: 107 and 108, respectively; (l) SEQ ID NO: 117 and 118, respectively; (m) SEQ ID NO: 127 and 128, respectively; (n) SEQ ID NO: 137 and 138, respectively; (o) SEQ ID NO: 147 and 148, respectively; or (p) SEQ ID NO: 157 and 158, respectively. [79.] The isolated monoclonal antibody according to any one of embodiments [12] to [77], wherein the VH and VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 157 and 158, respectively. [80.] The isolated monoclonal antibody according to any one of embodiments [12] to [77], wherein the VH and VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 202 and 203, respectively, SEQ ID NO: 210 and 211, respectively, SEQ ID NO: 218 and 219, respectively, SEQ ID NO: 226 and 227, respectively, SEQ ID NO: 234 and 235, respectively, or SEQ ID NO: 242 and 243, respectively. [81.] The isolated monoclonal antibody according to any one of embodiments [12] to [77], wherein the VH and VL comprises the amino acid sequence of SEQ ID NO: 202 and 203, respectively, SEQ ID NO: 210 and 211, respectively, SEQ ID NO: 218 and 219, respectively, SEQ ID NO: 226 and 227, respectively, SEQ ID NO: 234 and 235, respectively, or SEQ ID NO: 242 and 243, respectively. [82.] The monoclonal antibody of any one of embodiments [1] to [81], further comprising a heavy and/or light chain constant region. [83.] The monoclonal antibody of any one of embodiments [1] to [81], further comprising a human heavy and/or light chain constant region. [84.] The antibody of embodiment [82] or embodiment [83], wherein the heavy chain constant region is selected from the group consisting of a human immunoglobulin IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2 constant region. [85.] The antibody of any one of embodiments [82] to [84], wherein the heavy chain constant region comprises a native amino acid sequence. [86.] The antibody of any one of embodiments [82] to [84], wherein the heavy chain constant region comprises a variant amino acid sequence. [87.] The isolated monoclonal antibody of any one of embodiments [1] to [86], wherein the antibody is a recombinant antibody, a chimeric antibody, a human antibody, an antibody fragment, a bispecific antibody, a trispecific antibody or a multispecific antibody. [88.] The isolated monoclonal antibody of embodiment [87], wherein the antibody is a bispecific antibody, a trispecific antibody or a multispecific antibody. [89.] The isolated monoclonal antibody of embodiment [87], wherein the antibody is a bispecific antibody, a trispecific antibody or a multispecific antibody capable of binding at least one toxic component of snake venom in addition to 3FTx-L. [90.] The isolated monoclonal antibody of embodiment [89], wherein the at least one toxic component of snake venom in addition to 3FTx-L comprises a metalloprotease or a phospholipase. [91.] The isolated monoclonal antibody of embodiment [87], wherein the antibody fragment comprises a single-chain Fv (scFv), F(ab) fragment, F(ab’)2 fragment, or an isolated VH domain. [92.] The monoclonal antibody of any one of embodiments [1] to [91], wherein the antibody is capable of neutralizing at least two 3FTx-L variants listed in Table 1. [93.] The monoclonal antibody of any one of embodiments [1] to [91], wherein the antibody is capable of neutralizing the 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, and 3FTx- L15 variants listed in Table 1. [94.] The isolated monoclonal antibody of any one of embodiments [1] to [93], wherein the 3FTx-L comprises the amino acid sequence of SEQ ID NO: 161-176 or 177. [95.] The monoclonal antibody of any one of embodiments [1] to [93], wherein the 3FTx-L comprises 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, or 3FTx-L15 variants listed in Table 1. [96.] The isolated monoclonal antibody of any one of embodiments [1] to [95], wherein the antibody is capable of binding more than one 3FTx-L selected from the group consisting of SEQ ID NO: 161-176 and 177. [97.] The isolated monoclonal antibody of any one of embodiments [1] to [95], wherein the antibody is capable of binding at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15 or at least 163FTx-L selected from the group consisting of SEQ ID NO: 161-176 and 177. [98.] The isolated monoclonal antibody of any one of embodiments [1] to [95], wherein the antibody is capable of binding all 173FTx-L selected from the group consisting of SEQ ID NO: 161-176 and 177. [99.] The isolated monoclonal antibody of any one of embodiments [1] to [95], wherein the antibody is capable of binding the 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, and 3FTx-L15 variants listed in Table 1. [100.] The monoclonal antibody of any one of embodiments [1] to [99], wherein the antibody is capable of neutralizing in an in vitro cell based assay at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15 or at least 163FTx-L selected from the group consisting of SEQ ID NO: 161- 176 and 177. [101.] The monoclonal antibody of any one of embodiments [1] to [99], wherein the antibody is capable of neutralizing in an in vitro cell based assay all 17 3FTx-L selected from the group consisting of SEQ ID NO: 161-176 and 177. [102.] The monoclonal antibody of any one of embodiments [1] to [99], wherein the antibody is capable of neutralizing in an in vitro cell based assay alpha-bungarotoxin (SEQ ID NO: 250). [103.] The monoclonal antibody of any one of embodiments [1] to [99], wherein the antibody is capable of neutralizing in an in vitro cell based assay the 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, and 3FTx-L15 variants listed in Table 1. [104.] A pharmaceutical composition comprising the monoclonal antibody of any one of embodiments [1] to [103] and a pharmaceutically acceptable excipient. [105.] The pharmaceutical composition of embodiment [104], which is a lyophilized composition. [106.] The pharmaceutical composition of embodiment [104], which is liquid composition. [107.] The pharmaceutical composition of any one of embodiments [104] to [106] comprising a second antibody, wherein the second antibody is capable of binding at least one toxic component of snake venom in addition to 3FTx-L. [108.] The pharmaceutical composition of embodiment [107], wherein the at least one toxic component of snake venom in addition to 3FTx-L comprises a metalloprotease or a phospholipase. [109.] An isolated polynucleotide encoding the heavy chain variable region or heavy chain of the antibody of any one of embodiments [1] to [103]. [110.] An isolated polynucleotide encoding the light chain variable region or light chain of the antibody of any one of embodiments [1] to [103]. [111.] An isolated polynucleotide encoding the heavy chain variable region or heavy chain of the antibody of any one of embodiments [1] to [103] and the light chain variable region or light chain of the antibody of any one of embodiments [1] to [103]. [112.] The isolated polynucleotide of any one of embodiments [109] to [111], which is a DNA. [113.] The isolated polynucleotide of any one of embodiments [109] to [111], which is an mRNA. [114.] The isolated polynucleotide of embodiment [113], wherein the mRNA comprises a modified nucleotide. [115.] An isolated vector comprising the polynucleotide of any one of embodiments [109] to [111]. [116.] The isolated vector of embodiment [115], wherein the vector is a viral vector. [117.] A recombinant virus comprising the polynucleotide of any one of embodiments [109] to [111]. [118.] The recombinant virus of embodiment [117], which is a recombinant adeno-associated virus (AAV). [119.] A host cell comprising the polynucleotide of any one of embodiments [109] to [114], the vector of embodiment [115] or embodiment [116], or a first vector comprising the nucleic acid of embodiment [109] and a second vector comprising the nucleic acid of embodiment [110]. [120.] The host cell of embodiment [119], which is selected from the group consisting of E. coli, Pseudomonas, Bacillus, Streptomyces, yeast, CHO, YB/20, NS0, PER-C6, HEK-293T, NIH-3T3, HeLa, BHK, Hep G2, SP2/0, R1.1, B-W, L-M, COS 1, COS 7, BSC1, BSC40, BMT10 cell, plant cell, insect cell, and human cell in tissue culture. [121.] A method of producing an antibody that binds to 3FTx-L comprising culturing the host cell of embodiment [120] so that the polynucleotide is expressed and the antibody is produced. [122.] An isolated antibody that specifically binds to 3FTx-L and is encoded by the isolated polynucleotide of any one of embodiments [109] to [114]. [123.] A method of neutralizing an 3FTx-L comprising contacting the 3FTx-L with a sufficient amount of the antibody of any one of embodiments [1] to [103], or the pharmaceutical composition of any one of embodiments [104] to [108]. [124.] A method of treating snake bite comprising administering to a subject in need thereof a therapeutically sufficient amount of the antibody of any one of embodiments [1] to [103], or the pharmaceutical composition of any one of embodiments [104] to [108]. [125.] The method of embodiment [124], wherein the administering to the subject is by at least one mode selected from oral, parenteral, subcutaneous, intramuscular, intravenous, vaginal, rectal, buccal, sublingual, and transdermal. [126.] The method of any one of embodiments [124 or embodiment [125], further comprising administering at least one additional therapeutic agent. [127.] The method of embodiment [126], wherein the additional therapeutic agent is an antitoxin. [128.] A method of passive immunization comprising administering to a subject in need thereof a therapeutically sufficient amount of the antibody of any one of embodiments [1] to [103], or the pharmaceutical composition of any one of embodiments [104] to [108]. [129.] The method of embodiment [128], wherein the administering to the subject is by at least one mode selected from oral, parenteral, subcutaneous, intramuscular, intravenous, vaginal, rectal, buccal, sublingual, and transdermal. [130.] A method of producing an engineered variant of an antibody comprising (a) substituting one or more amino acid residues of the VH; and/or substituting one or more amino acid residues of the VL to create an engineered variant antibody, and (b) and producing the engineered variant antibody, wherein the antibody is LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. [131.] A method of producing an engineered variant of an antibody comprising (a) substituting one or more amino acid residues of the VH; and/or substituting one or more amino acid residues of the VL to create an engineered variant antibody, and (b) and producing the engineered variant antibody, wherein the antibody is 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6. [132.] A method of producing an engineered variant of a LB5_95 comprising (a) substituting one or more amino acid residues of the LB5_95 VH; and/or substituting one or more amino acid residues of the LB5_95 VL to create an engineered variant antibody, and (b) and producing the engineered variant antibody. BRIEF DESCRIPTION OF THE DRAWINGS [0013] Figure 1: Isolation of cross-reactive anti-3FTx-L mAbs from naive library. A) Structure of 3FTx-L2 (1hc9, (R39)) shown as surface (left) and cartoon with the disulfide bonds shown as sticks. The structures are colored by site-specific Shannon Entropy values calculated from 149 unique 3FTx-L sequences and mapped onto 1hc9. Red denotes high entropy (sites with significant antigenic diversity) and blue denotes low entropy (highly conserved positions). B) List of recombinant 3FTx-L variants used in sorting and characterization of mAbs along with corresponding UniProt and PDB accession numbers. C) Sequence alignment of 3FTx-L variants listed in (B) aligned to 3FTx-L2, with dots indicating conserved residues. D) Sorting strategy for selection of cross-reactive Fabs. Fc-fused 3FTx-L2 and 3FTx-L3 were used as baits in MACS. FACS iterated between positive selections with 3FTx-L2 and depletions with polyspecific reagent (PSR) to remove non-specific antibodies. Final sorts were performed with five different 3FTx-L variants to select for universally enriched cross-reactive clones through deep sequencing. Frequencies of the 8 different VH genes (E), 4 different VL genes (F), and CDRH3 lengths (G) in the naive (unsorted) library, the 3FTx-L2-reactive Fabs, and Fabs that were cross-reactive across all five 3FTx-L variants. H) Percentage of Fab clones present in 3FTx-L2 affinity sort populations also present in the final populations of the 4 other sort variants as determined by deep sequencing. I) Venn diagram depicting the cross-reactive profile of 3FTx-L2-reactive Fabs. The bold numbers listed in parentheses denote the number of Fabs that bound each 3FTx-L variant, while the italic numbers denote the percentage present in each quadrant of the diagram (R40). J) Frequency logos constructed with WebLogo (R41) for 20 AA CDRH3s present in the naive library, the set of 3FTx- L2-reactive Fabs, and the set of cross-reactive Fabs. [0014] Figure 2: Binding and neutralization of cross-reactive and affinity-matured antibodies against 3FTx-L variants. A) Alignment of CDRH3 sequences for the 16 cross-reactive anti-3FTx-L antibodies isolated and validated from the naive Fab library. B) Binding affinities (SPR) across an expanded characterization panel of 3FTx-L variants for each of the cross-reactive antibodies. 3FTx-L variants from the selections are shown in circles and additional variants are shown as triangles. C) Functional neutralization of native ⍺-bungarotoxin nAChR-antagonism for each cross-reactive antibody evaluated in acetylcholine-induced TE671 cells. Each response was normalized to the maximum (10 μM acetylcholine only) and minimum (10 μM acetylcholine with 30 nM ⍺-bungarotoxin) control responses. Error bars represent the standard deviation from 3 replicate experiments. D) CDR sequences listed for the 6 broadly enriched antibodies selected via deep sequencing from the affinity maturation library and the parental antibody (LB5_95). E) Isoaffinity plot of LB5_95 vs. affinity-matured 95Mat5 binding to 3FTx-L variants. The measurement of dissociation rate (kd) has an instrument limit of 10-5 s-1, and two points were placed at ≤ 10-5 as they fell below the functional range. F) Blocking of 3FTx-L variant binding to nAChR⍺1-displaying yeast by 95Mat5 assayed via flow cytometry. The median APC area signal was normalized to maximum and minimum signals from toxin-only and nAChR⍺1-only controls to calculate % neutralization. Error bars represent the standard deviation from 3-5 replicate experiments. Functional neutralization of (G) native ⍺-bungarotoxin (30 nM) and (H) recombinant 3FTx-L6 (380 nM) nAChR-antagonism for LB5_95 vs.95Mat5 evaluated in acetylcholine-induced TE671 cells. Each response was normalized to the control responses as described in (C), with error bars representing the standard deviation of 3 replicate experiments. [0015] Figure 3: Breadth determination of mAb:3FTx affinity. A) Composition of the unsorted 3FTx library as compared to the three sequential affinity sorts performed with 95Mat5. 3FTx variants are classified by various known families, and the mamba-exclusive group included fasciculins, FS2 toxins, dendroaspins, and mambalgins. B) List of the deep sequencing ranking and read counts in Sort 3 for the seven 3FTx-L variants used in the characterization panel, along with their respective picomolar dissociation constant (KD) as measured by SPR. C) Unrooted tree constructed using the neighbor-joining method with the Jukes-Cantor genetic distance model (Geneious version 2023.1 created by Biomatters) from the alignment of the 95Mat5-binding 3FTx- L variants. The genera of the species for the variants in each node are indicated and color- categorized based on the geographic region of the snakes. The node locations of the variants used in antibody characterization are indicated in bold black text. A scale bar to represent the degree of genetic change is provided at the lower right. [0016] Figure 4: Kaplan–Meier survival curves for in vivo protection experiments. A) ⍺- bungarotoxin (2x LD50 dose) was preincubated with 95Mat5 and injected intravenously into groups of experimental animals (n=5) at 1:8 and 1:25 toxin:antibody molar ratios (27 mg/kg and 85 mg/kg antibody). The control group was injected with purified ⍺-bungarotoxin only. Groups of five mice were challenged with 2x LD50 doses of B) N. kaouthia, C) D. polylepis or D) O. hannah whole venoms. Mice received either no antibody (control), 25 mg/kg of 95Mat5, the manufacturer- recommended dose of commercial antivenom, or an equivalent 25 mg/kg dose of antivenom for direct potency comparison between 95Mat5 and the antivenom. Commercial antivenoms were matched to the appropriate snake. Groups of five mice were injected subcutaneously with 2x LD50 doses of whole venoms from (E) N. kaouthia or (F) D. polylepis prior to intravenous treatment with 95Mat5 (25 mg/kg) at 0, 10 and 20 min post-venom injection. The control groups were injected with venom alone. [0017] Figure 5: Crystal structure of 95Mat5 Fab with 3FTx-L15 reveals similarity in toxin recognition of antibody and nAChR⍺. A) Overall structure of 95Mat5 Fab with 3FTx-L15 in cartoon representation. Orange and gold denote the heavy chain (HC) and light chain (LC) of the Fab, respectively. B) Interaction interface of 95Mat5 with 3FTx-L15 epitope residues in dark green sticks. C, D, E) Molecular details of interaction for CDRs L1, L2, H1 and H3 with 3FTx-L15. F) Asp50 from the LC of 95Mat5 interacts with and orients Arg98 in CDRH3 and is involved with an electrostatic network for toxin recognition. Hydrogen bonds, salt bridges, and van der Waals interactions are represented in black, red, and light blue dashed lines, respectively. G) Comparison of interactions for 95Mat5:3FTx-L15 and nAChR⍺1:α-bungarotoxin (PDB ID: 2qc1). 3FTx-L15 CDRH3 and nAChR⍺1 loop C both insert into 3FTx-L in a similar way using two Tyr residues that are structurally conserved (black box). The 95Mat5 Tyr residues are in orange, and the Tyr residues from the receptor are in lavender. Frequency logos comparing 20 AA-long cross-reactive CDRH3 sequences with loop C in nAChR⍺1 from amphibian, bird, fish, human, lizard, marsupial, rodent, and snake were constructed with WebLogo (R41). [0018] Figure 6: Sequence alignments of 3FTx-L variants from the full collection (A) and those used in the characterization panel (B). The alignment distances (% sequence similarity between each variant) are shown plotted in heat map form for both the full collection (C) and the characterization panel (D). [0019] Figure 7: Binding curves for main (A) and supplemental (B) recombinant 3FTx-L variants on yeast-displayed human nAChR⍺1 subunit measured via flow cytometry. The median APC area signal was plotted for each population of streptavidin-APC stained yeast cells displaying nAChR⍺1 and incubated with various concentrations of biotinylated 3FTx-L variants. Non-linear curve fitting was performed to calculate the IC50 for each variant using a one-site competitive binding model in Prism. C) Concentration-inhibition plots demonstrating the antagonism of 3FTx-L variants from the characterization panel on the acetylcholine-induced activation of nAChRs expressed in TE671 cells. Each point represents the mean ± SD of 3 replicate experiments. [0020] Figure 8: Flow chart of sorts used in sorting of the naive Fab library for cross-reactive anti-3FTx-L antibodies.3 rounds of magnetic-activated cell sorts (MACS) were performed initially with Fc-conjugated 3FTx (Fc-3FTx-L2 and Fc-3FTx-L3), followed by 5 rounds of FACS that were either affinity (AFF) sorts or negative (PSR) sorts. Negative sorting antigens included recombinant rabbit Fc-tagged phospholipase A2 (Fc-PLA2) and soluble cytosolic protein extract (SCP). The concentration of antigen used is indicated in parentheses. See Methods section for further details. [0021] Figure 9: Flow cytometry plots for each anti-3FTx sorting step showing the population of cells sorted for each round of FACS described in Fig S4. An example of paired chain selection is shown for AFF1, gating the population of Fabs with coordinated heavy vs. light chain display signals. Antigen-binding or non-binding cells were then sorted in the AFF or PSR sorts, respectively, as shown by the gates drawn with red outlines. The percentage of the paired chain population that was sorted is indicated next to the sorted population, and the concentration of antigen used is indicated in parentheses. [0022] Figure 10: Flow chart of sorts used in sorting the LB5_95 affinity maturation library. 4 rounds of FACS were performed with the separate heavy chain (HC) and light chain (LC) libraries prior to combining them, followed by an additional 4 rounds of FACS with the combined library. The percentage of the paired chain population that was sorted is indicated under the name of each sort, and the concentration of antigen used is indicated in parentheses. Prior to each PSR sort, the cell populations from the previous affinity sort were combined before sorting with the SCP. Sorts with dissociation conditions applied are indicated with “diss”. See Methods section for further details. [0023] Figure 11: Characterization of affinity matured antibodies. A) Binding affinities for the 6 matured antibodies with the toxin panel variants in comparison to the parent antibody (LB5_95). B) ELISA to assess polyreactivity of antibodies on PSR reagents: cell soluble membrane protein extract (CHO-SMP), single-stranded DNA (ssDNA) and insulin. LB5_95 and the lead matured antibody (95Mat5) are compared to adalilumab (good developability) and bococizumab (poor developability) controls. C) Affinity-capture self-interaction nanoparticle spectroscopy (AC-SINS) characterization of LB5_95 and 95Mat5 comparing wavelength shifts (nm) to control antibodies. D) Analytical size exclusion chromatography performed for LB5_95 and 95Mat5 in comparison to controls. E) Images of HEp-2 cells stained with antibodies in comparison to controls. [0024] Figure 12: Validation of potential 95Mat5-binding 3FTx variants at the deep sequencing threshold. A) List of 3FTx-L and 3FTx-S variants present at the bottom of the deep sequencing count rankings in the final sorts of the 3FTx library. Variant names are listed along with species and corresponding UniProt accession numbers. The outcome of the ELISA results (binding or non- binding) or the inability of the variant to express from mammalian cells is listed in the final column. B) ELISA results for 95Mat5 binding to the expressed threshold 3FTx variants listed in A as compared to 3FTx-L2. [0025] Figure 13: 95Mat5 Fab recognizes hydrophobic pockets of 3FTx-L15. 3FTx-L15 is presented by a hydrophobic surface with red for high levels of hydrophobicity and gray for high levels of hydrophilicity. [0026] Figure 14: 95Mat5:3FTx-L15 interfaces show cation/amino-π interaction. 3FTx-L15, 95Mat5 HC, and 95Mat5 LC residues are shown in dark green, orange, and gold sticks. Two cation/amino–π interactions involve Tyr100-Arg34 and Arg34-Phe30-Tyr32. [0027] Figure 15: Comparison of the binding mode for 95Mat5:3FTx-L15 with several nAChR⍺ subunits in complex with 3FTx-L. 3FTx-L is in dark green cartoon representation. Human nAChR⍺1, ⍺7, and ⍺9 are shown in lavender, pink, and wheat cartoon, respectively. [0028] Figure 16: Data collection and refinement statistics of 3FTx-L15 and 95Mat5 Fab complex structure. DETAILED DESCRIPTION [0029] Snakebite envenoming is a significant public health concern worldwide, and improved therapies are urgently needed. The antigenic diversity within snake venom toxins poses a significant challenge to the development of monoclonal antibody-based treatments. A synthetic discovery strategy was developed to produce bnAbs against α-neurotoxin 3FTx-L. Briefly, a panel of diverse 3FTx-L variants was assembled to represent the diversity across medically relevant Asian and African elapid snakes including cobras, kraits and mambas. 3FTx-L is a major contributor to the lethality of elapid snake venoms and is often poorly targeted by animal-derived antivenoms thus is an excellent target for a broadly neutralizing human monoclonal antibody therapy. This panel was used for human antibody discovery, downselection to identify potential bnAbs, and biophysical characterization of lead candidates. Finally, in vivo protection against purified native 3FTx-L and 3FTx-L toxin-rich venom from distinct snakes across Asia and Africa was assessed. This work demonstrates the potential of anti-toxin bnAbs and provides a template for the discovery of bnAbs targeting additional venom toxin classes. [0030] In one aspect, provided herein is a method for the synthetic production of a human antibody that can neutralize three-finger neurotoxins from various snakes across continents. In one aspect, provided herein is an antibody that binds long-chain three-finger α-neurotoxins from diverse species of snakes with high affinity, blocks toxin binding to the nicotinic acetylcholine receptor in vitro, and protects mice from lethal venom challenge. Structural analysis of the antibody/toxin complex revealed a binding mode that mimics the receptor/toxin interaction. In one aspect, provided herein is a treatment of snakebite envenoming comprising administering a therapeutically effective amount of an antibody described herein. I. Definitions [0031] To facilitate an understanding of the present invention, a number of terms and phrases are defined below. [0032] As used herein, the term "long chain alpha-neurotoxic three finger toxin" or "3FTX_LCa" or "3FTx-L" refers to alpha-neurotoxins that can efficiently bind to nicotinic acetylcholine receptors (nAChRs). Son et al., Toxins (Basel). 13(2): 164 (2021) and Utkin, Yuri, World J Biol Chem 10(1): 17-27 (2019). For example, alpha-bungarotoxin (SEQ ID NO: 250) from krait Bungarus multicinctus venom binds muscle-type as well as neuronal alpha7 and alpha9 nAChRs with nanomolar affinities and blocks ion current through the ion channel of these receptors. "Long chain alpha-neurotoxic three finger toxin" or "3FTX_LCa" or "3FTx-L" encompass, but are not limited to, native 3FTx-L, an isoform of 3FTx-L, or a recombinant variant of 3FTx-L. In one embodiment, 3FTx-L comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 161-177. In some embodiments, the 3FTx-L is the Bungarus caeruleus (South central Asia) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 161 (UniProtKB accession number D2N116). In some embodiments, the 3FTx-L is the Bungarus multicinctus (Southeastern Asia) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 162 (UniProtKB accession number P60616, 1HC9). In some embodiments, the 3FTx-L is the Dendroaspis polylepis (East central & southern Africa) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 163 (UniProtKB accession number C0HJD7, 4LFT). In some embodiments, the 3FTx-L is the Dendroaspis viridis (Western Africa) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 164 (UniProtKB accession number P01394). In some embodiments, the 3FTx-L is the Naja kaouthia, Naja siamensis (Southeastern Asia) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 165 (UniProtKB accession number P01391, 2CTX, 4AEA). In some embodiments, the 3FTx-L is the Naja nivea (Southern Africa) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 166 (UniProtKB accession number P01390). In some embodiments, the 3FTx-L is the Bungarus candidus (Southern Asia) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 167 (UniProtKB accession number A1IVR9). In some embodiments, the 3FTx-L is the Dendroaspis jamesoni (West central Africa) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 168 (UniProtKB accession number P01393). In some embodiments, the 3FTx-L is the Naja anchietae (South central Africa) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 169 (UniProtKB accession number P01389). In some embodiments, the 3FTx-L is the Naja melanoleuca (West central Africa) 3FTx- L comprising the amino acid sequence of SEQ ID NO: 170 (UniProtKB accession number P01383). In some embodiments, the 3FTx-L is the Naja naja (South central Asia) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 171 (UniProtKB accession number P25672). In some embodiments, the 3FTx-L is the Naja sputatrix (Indonesia) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 172 (UniProtKB accession number O42257). In some embodiments, the 3FTx-L is the Naja oxiana (Central Asia) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 173 (UniProtKB accession number 1NTN). In some embodiments, the 3FTx-L is the Ophiophagus hannah (Southeastern Asia) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 174 (UniProtKB accession number P01386, 1TXA). In some embodiments, the 3FTx-L is the Naja naja (South central Asia) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 175 (UniProtKB accession number P25668). In some embodiments, the 3FTx-L is the Dendroaspis viridis (Western Africa) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 176 (UniProtKB accession number P01395). In some embodiments, the 3FTx-L is the Naja melanoleuca (West central Africa) 3FTx-L comprising the amino acid sequence of SEQ ID NO: 177 (UniProtKB accession number P01388). In some embodiments, the 3FTx-L is alpha- bungarotoxin comprising the amino acid sequence of SEQ ID NO: 250. Table 1. Selected recombinant 3FTX variants. Names of selected 3FTx-L variants that were synthesized are listed along with their NCBI and/or PDB accession numbers, snake species, geographic regions, and native toxin sequences. Variant name Accession Species Region SEQ ID NO
Figure imgf000034_0001
3FTx-L8 A1IVR9 Bungarus Southern Asia 167 candidus
Figure imgf000035_0001
[0033] The term "antibody" means an immunoglobulin molecule (or a group of immunoglobulin molecules) that recognizes and specifically binds to a target, such as a protein, polypeptide, peptide, carbohydrate, polynucleotide, lipid, or combinations of the foregoing through at least one antigen recognition site within the variable region of the immunoglobulin molecule. As used herein, the terms "antibody" and "antibodies" are terms of art and can be used interchangeably herein and refer to a molecule with an antigen-binding site that specifically binds an antigen. [0034] Antibodies can include, for example, monoclonal antibodies, recombinantly produced antibodies, human antibodies, humanized antibodies, resurfaced antibodies, chimeric antibodies, immunoglobulins, synthetic antibodies, tetrameric antibodies comprising two heavy chain and two light chain molecules, an antibody light chain monomer, an antibody heavy chain monomer, an antibody light chain dimer, an antibody heavy chain dimer, an antibody light chain- antibody heavy chain pair, intrabodies, heteroconjugate antibodies, single domain antibodies, monovalent antibodies, single chain antibodies or single-chain Fvs (scFv), affybodies, Fab fragments, F(ab')2 fragments, disulfide-linked Fvs (sdFv), anti-idiotypic (anti-Id) antibodies (including, e.g., anti-anti- Id antibodies), bispecific antibodies, and multi-specific antibodies. In certain embodiments, antibodies described herein refer to polyclonal antibody populations. Antibodies can be of any type (e.g., IgG, IgE, IgM, IgD, IgA, or IgY), any class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, or IgA2), or any subclasses (isotypes) thereof (e.g. IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2), of immunoglobulin molecule, based on the identity of their heavy-chain constant domains referred to as alpha, delta, epsilon, gamma, and mu, respectively. The different classes of immunoglobulins have different and well known subunit structures and three-dimensional configurations. Antibodies can be naked or conjugated or fused to other molecules such as toxins, radioisotopes, other polypeptides etc. [0035] As used herein, the terms "antigen-binding domain," "antigen-binding region," "antigen- binding site," and similar terms refer to the portion of antibody molecules which comprises the amino acid residues that confer on the antibody molecule its specificity for the antigen (e.g., 3FTx- L). The antigen-binding region can be derived from any animal species, such as mouse and humans. [0036] As used herein, the terms "variable region" or "variable domain" are used interchangeably and are common in the art. The variability in sequence is concentrated in those regions called complementarity determining regions (CDRs) while the more highly conserved regions in the variable domain are called framework regions (FR). Without wishing to be bound by any particular mechanism or theory, it is believed that the CDRs of the light and heavy chains are primarily responsible for the interaction and specificity of the antibody with antigen (e.g., 3FTx-L). In certain embodiments, the variable region is a human variable region. In certain embodiments, the variable region comprises human CDRs and human framework regions (FRs). In certain embodiments, the variable region comprises human CDRs and primate (e.g., non-human primate) framework regions (FRs). [0037] There are several approaches for determining CDRs. One approach is based on cross- species sequence variability (i.e., Kabat et al., Sequences of Proteins of Immunological Interest, (5th ed., 1991, National Institutes of Health, Bethesda Md.), "Kabat"). A second approach was developed by the MGT, the international ImMunoGeneTics database (imgt.cines.fr) as a high quality integrated information system specializing in immunoglobulins (IG), T cell receptors (TR) and major histocompatibility complex (MHC) of human and other vertebrates. Lefranc, M.-P., The Immunologist, 7, 132-136 (1999). The IMGT unique numbering defined for the IG and TR variable regions and domains of all jawed vertebrates has allowed a redefinition of the limits of the framework (FR-IMGT) and complementarity determining regions (CDR-IMGT), leading to a standardized description of mutations, allelic polymorphisms, 2D representations (Colliers de Perles) and 3D structures, whatever the antigen receptor, the chain type, or the species. A third approach is based on crystallographic studies of antigen-antibody complexes (Al-lazikani et al, J. Molec. Biol. 273:927-948 (1997)). In addition, combinations of these approaches are sometimes used in the art to determine CDRs. In some embodiments, the CDR regions are determined according to Kabat. In some embodiments, the CDR regions are determined according to IMGT. [0038] The Kabat numbering system is generally used when referring to a residue in the variable domain (approximately residues 1-107 of the light chain and residues 1-113 of the heavy chain) (e.g., Kabat et al., Sequences of Immunological Interest. (5th Ed., 1991, National Institutes of Health, Bethesda, Md.) ("Kabat"). [0039] The amino acid position numbering as in Kabat, refers to the numbering system used for heavy chain variable domains or light chain variable domains of the compilation of antibodies in Kabat et al. (Sequences of Immunological Interest. (5th Ed., 1991, National Institutes of Health, Bethesda, Md.), "Kabat"). Using this numbering system, the actual linear amino acid sequence can contain fewer or additional amino acids corresponding to a shortening of, or insertion into, a FR or CDR of the variable domain. For example, a heavy chain variable domain can include a single amino acid insert (residue 52a according to Kabat) after residue 52 of H2 and inserted residues (e.g. residues 82a, 82b, and 82c, etc. according to Kabat) after heavy chain FR residue 82. The Kabat numbering of residues can be determined for a given antibody by alignment at regions of homology of the sequence of the antibody with a "standard" Kabat numbered sequence. Chothia refers instead to the location of the structural loops (Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)). The end of the Chothia CDR-H1 loop when numbered using the Kabat numbering convention varies between H32 and H34 depending on the length of the loop (this is because the Kabat numbering scheme places the insertions at H35A and H35B; if neither 35A nor 35B is present, the loop ends at 32; if only 35A is present, the loop ends at 33; if both 35A and 35B are present, the loop ends at 34). The AbM hypervariable regions represent a compromise between the Kabat CDRs and Chothia structural loops, and are used by Oxford Molecular's AbM antibody modeling software. In some embodiments, the CDR regions are determined according to Kabat. In some embodiments, the CDR regions are determined according to IMGT. In some embodiments, the CDR regions are determined according to Chothia. In some embodiments, the CDR regions are determined according to AbM. In some embodiments, the VH and VL residues are numbered according to Kabat.
[0040] The terms "VL" and "VL domain" are used interchangeably to refer to the light chain variable region of an antibody. [0041] The terms "VH" and "VH domain" are used interchangeably to refer to the heavy chain variable region of an antibody. [0042] The term "antibody fragment" refers to a portion of an intact antibody. An "antigen-binding fragment" refers to a portion of an intact antibody that binds to an antigen. An antigen-binding fragment can contain the antigenic determining variable regions of an intact antibody. Examples of antibody fragments include, but are not limited to Fab, Fab', F(ab')2, and Fv fragments, linear antibodies, and single chain antibodies. [0043] A "monoclonal" antibody or antigen-binding fragment thereof refers to a homogeneous antibody or antigen-binding fragment population involved in the highly specific recognition and binding of a single antigenic determinant, or epitope. This is in contrast to polyclonal antibodies that typically include different antibodies directed against different antigenic determinants. The term "monoclonal" antibody or antigen-binding fragment thereof encompasses both intact and full- length monoclonal antibodies as well as antibody fragments (such as Fab, Fab', F(ab')2, Fv), single chain (scFv) mutants, fusion proteins comprising an antibody portion, and any other modified immunoglobulin molecule comprising an antigen recognition site. Furthermore, "monoclonal" antibody or antigen-binding fragment thereof refers to such antibodies and antigen-binding fragments thereof made in any number of manners including but not limited to by hybridoma, phage selection, recombinant expression, and transgenic animals. [0044] The term "polyclonal antibody" describes a composition of different (diverse) antibody molecules which are capable of binding to or reacting with several different specific antigenic determinants on the same or on different antigens. Usually, the variability of a polyclonal antibody is located in the so-called variable regions of the polyclonal antibody, in particular in the CDR regions. In the present disclosure a mixture of two or more polyclonal antibodies (a polycomposition) is produced in one mixture from a polyclonal polycomposition cell line, which is produced from two or more parental polyclonal cell lines each expressing antibody molecules which are capable of binding to a distinct target, but it may also be a mixture of two or more polyclonal antibodies produced separately. A mixture of monoclonal antibodies providing the same antigen/epitope coverage as a polyclonal antibody described herein will be considered as an equivalent of a polyclonal antibody. When stating that a member of a polyclonal antibody binds to an antigen, it is herein meant to be binding with a binding constant below 100 nM, preferably below 10 nM, even more preferred below 1 nM. [0045] The term "humanized" antibody or antigen-binding fragment thereof refers to forms of non-human (e.g. murine) antibodies or antigen-binding fragments that are specific immunoglobulin chains, chimeric immunoglobulins, or fragments thereof that contain minimal non-human (e.g., murine) sequences. Typically, humanized antibodies or antigen-binding fragments thereof are human immunoglobulins in which residues from the complementary determining region (CDR) are replaced by residues from the CDR of a non-human species (e.g. murine) that have the desired specificity, affinity, and capability ("CDR grafted") (Jones et al., Nature 321:522-525 (1986); Riechmann et al., Nature 332:323-327 (1988); Verhoeyen et al., Science 239:1534-1536 (1988)). In some instances, the Fv framework region (FR) residues of a human immunoglobulin are replaced with the corresponding residues in an antibody or fragment from a non-human species (e.g., murine) that has the desired specificity, affinity, and capability. The humanized antibody or antigen-binding fragment thereof can be further modified by the substitution of additional residues either in the Fv framework region and/or within the replaced non-human residues to refine and optimize antibody or antigen-binding fragment thereof specificity, affinity, and/or capability. In general, the humanized antibody or antigen-binding fragment thereof will comprise substantially all of at least one, and typically two or three, variable domains containing all or substantially all of the CDR regions that correspond to the non-human immunoglobulin whereas all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody or antigen-binding fragment thereof can also comprise at least a portion of an immunoglobulin constant region or domain (Fc), typically that of a human immunoglobulin. Examples of methods used to generate humanized antibodies are described in U.S. Pat.5,225,539; Roguska et al., Proc. Natl. Acad. Sci., USA, 91(3):969-973 (1994), and Roguska et al., Protein Eng. 9(10):895-904 (1996). In some embodiments, a "humanized antibody" is a resurfaced antibody. [0046] The term "chimeric" antibodies or antigen-binding fragments thereof refers to antibodies or antigen-binding fragments thereof wherein the amino acid sequence is derived from two or more species. Typically, the variable region of both light and heavy chains corresponds to the variable region of antibodies or antigen-binding fragments thereof derived from one species of mammals (e.g., mouse) with the desired specificity, affinity, and capability while the constant regions are homologous to the sequences in antibodies or antigen-binding fragments thereof derived from another (usually human) to avoid eliciting an immune response in that species. [0047] The term "epitope" or "antigenic determinant" are used interchangeably herein and refer to that portion of an antigen capable of being recognized and specifically bound by a particular antibody. When the antigen is a polypeptide, epitopes can be formed both from contiguous amino acids and noncontiguous amino acids juxtaposed by tertiary folding of a protein. Epitopes formed from contiguous amino acids are typically retained upon protein denaturing, whereas epitopes formed by tertiary folding are typically lost upon protein denaturing. An epitope typically includes at least 3, and more usually, at least 5 or 8-10 amino acids in a unique spatial conformation. [0048] "Binding affinity" generally refers to the strength of the sum total of non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen). Unless indicated otherwise, as used herein, "binding affinity" refers to intrinsic binding affinity which reflects a 1:1 interaction between members of a binding pair (e.g., antibody and antigen). The affinity of a molecule X for its partner Y can generally be represented by the dissociation constant (Kd). Affinity can be measured by common methods known in the art, including those described herein. Low-affinity antibodies generally bind antigen slowly and tend to dissociate readily, whereas high-affinity antibodies generally bind antigen faster and tend to remain bound longer. A variety of methods of measuring binding affinity are known in the art, any of which can be used for purposes of the present invention. Specific illustrative embodiments are described in the following. [0049] "Or better" when used herein to refer to binding affinity refers to a stronger binding between a molecule and its binding partner. "Or better" when used herein refers to a stronger binding, represented by a smaller numerical Kd value. For example, an antibody which has an affinity for an antigen of "0.6 nM or better", the antibody's affinity for the antigen is <0.6 nM, i.e. 0.59 nM, 0.58 nM, 0.57 nM etc. or any value less than 0.6 nM. [0050] As used herein, the terms "immunospecifically binds," "immunospecifically recognizes," "specifically binds," and "specifically recognizes" are analogous terms in the context of antibodies and refer to molecules that bind to an antigen (e.g., epitope or immune complex) as such binding is understood by one skilled in the art. For example, a molecule that specifically binds to an antigen can bind to other peptides or polypeptides, generally with lower affinity as determined by, e.g., immunoassays, BIAcore®, KinExA 3000 instrument (Sapidyne Instruments, Boise, ID), or other assays known in the art. In a specific embodiment, molecules that immunospecifically bind to an antigen bind to the antigen with a Kd that is at least 2 logs, 2.5 logs, 3 logs, or 4 logs lower than the Kd when the molecules bind non-specifically to another antigen. In some embodiments, the antibody specifically binds to 3FTx-L1 comprising the amino acid sequence of SEQ ID NO: 161. In some embodiments, the antibody specifically binds to 3FTx-L3 comprising the amino acid sequence of SEQ ID NO: 162. In some embodiments, the antibody specifically binds to 3FTx-L4 comprising the amino acid sequence of SEQ ID NO: 163. In some embodiments, the antibody specifically binds to 3FTx-L5 comprising the amino acid sequence of SEQ ID NO: 164. In some embodiments, the antibody specifically binds to 3FTx-L6 comprising the amino acid sequence of SEQ ID NO: 165. In some embodiments, the antibody specifically binds to 3FTx-L8 comprising the amino acid sequence of SEQ ID NO: 166. In some embodiments, the antibody specifically binds to 3FTx-L9 comprising the amino acid sequence of SEQ ID NO: 167. In some embodiments, the antibody specifically binds to 3FTx-L10 comprising the amino acid sequence of SEQ ID NO: 168. In some embodiments, the antibody specifically binds to 3FTx-L11 comprising the amino acid sequence of SEQ ID NO: 169. In some embodiments, the antibody specifically binds to 3FTx-L12 comprising the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody specifically binds to 3FTx-L13 comprising the amino acid sequence of SEQ ID NO: 171. In some embodiments, the antibody specifically binds to 3FTx-L14 comprising the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody specifically binds to 3FTx-L15 comprising the amino acid sequence of SEQ ID NO: 173. In some embodiments, the antibody specifically binds to 3FTx-L1 comprising the amino acid sequence of SEQ ID NO: 174. In some embodiments, the antibody specifically binds to 3FTx-L16 comprising the amino acid sequence of SEQ ID NO: 175. In some embodiments, the antibody specifically binds to 3FTx-L17 comprising the amino acid sequence of SEQ ID NO: 176. In some embodiments, the antibody specifically binds to 3FTx-L18 comprising the amino acid sequence of SEQ ID NO: 177. In some embodiments, the antibody specifically binds to 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, and 3FTx-L15 variants listed in Table 1. In some embodiments, the antibody specifically binds to 3FTx-L2 comprising the amino acid sequence of SEQ ID NO: 162, 3FTx-L3 comprising the amino acid sequence of SEQ ID NO: 163, 3FTx-L5 comprising the amino acid sequence of SEQ ID NO: 165, 3FTx-L6 comprising the amino acid sequence of SEQ ID NO: 166, 3FTx-L8 comprising the amino acid sequence of SEQ ID NO: 167, 3FTx-L9 comprising the amino acid sequence of SEQ ID NO: 168, and 3FTx-L15 comprising the amino acid sequence of SEQ ID NO: 174, as listed in Table 1. [0051] By "preferentially binds," it is meant that the antibody specifically binds to an epitope more readily than it would bind to a related, similar, homologous, or analogous epitope. Thus, an antibody which "preferentially binds" to a given epitope would more likely bind to that epitope than to a related epitope, even though such an antibody may cross-react with the related epitope. [0052] An antibody is said to "competitively inhibit" binding of a reference antibody to a given epitope if it preferentially binds to that epitope or an overlapping epitope to the extent that it blocks, to some degree, binding of the reference antibody to the epitope. Competitive inhibition may be determined by any method known in the art, for example, competition ELISA assays. An antibody may be said to competitively inhibit binding of the reference antibody to a given epitope by at least 90%, at least 80%, at least 70%, at least 60%, or at least 50%. [0053] The phrase "substantially similar," or "substantially the same", as used herein, denotes a sufficiently high degree of similarity between two numeric values (generally one associated with an antibody described herein and the other associated with a reference/comparator antibody) such that one of skill in the art would consider the difference between the two values to be of little or no biological and/or statistical significance within the context of the biological characteristic measured by said values (e.g., Kd values). The difference between said two values can be less than about 50%, less than about 40%, less than about 30%, less than about 20%, or less than about 10% as a function of the value for the reference/comparator antibody. [0054] A polypeptide, antibody, polynucleotide, vector, cell, or composition which is "isolated" is a polypeptide, antibody, polynucleotide, vector, cell, or composition which is in a form not found in nature. Isolated polypeptides, antibodies, polynucleotides, vectors, cell or compositions include those which have been purified to a degree that they are no longer in a form in which they are found in nature. In some embodiments, an antibody, polynucleotide, vector, cell, or composition which is isolated is substantially pure. [0055] As used herein, "substantially pure" refers to material which is at least 50% pure (i.e., free from contaminants), at least 90% pure, at least 95% pure, at least 98% pure, or at least 99% pure. [0056] The terms "polypeptide," "peptide," and "protein" are used interchangeably herein to refer to polymers of amino acids of any length. The polymer can be linear or branched, it can comprise modified amino acids, and it can be interrupted by non-amino acids. The terms also encompass an amino acid polymer that has been modified naturally or by intervention; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as conjugation with a labeling component. Also included within the definition are, for example, polypeptides containing one or more analogs of an amino acid (including, for example, unnatural amino acids, etc.), as well as other modifications known in the art. It is understood that, because the polypeptides described herein are based upon antibodies, in certain embodiments, the polypeptides can occur as single chains or associated chains. [0057] The terms "identical" or percent "identity" in the context of two or more nucleic acids or polypeptides, refer to two or more sequences or subsequences that are the same or have a specified percentage of nucleotides or amino acid residues that are the same, when compared and aligned (introducing gaps, if necessary) for maximum correspondence, not considering any conservative amino acid substitutions as part of the sequence identity. The percent identity can be measured using sequence comparison software or algorithms or by visual inspection. Various algorithms and software are known in the art that can be used to obtain alignments of amino acid or nucleotide sequences. One such non-limiting example of a sequence alignment algorithm is the algorithm described in Karlin et al, Proc. Natl. Acad. Sci., 87:2264-2268 (1990), as modified in Karlin et al., Proc. Natl. Acad. Sci., 90:5873-5877 (1993), and incorporated into the NBLAST and XBLAST programs (Altschul et al., Nucleic Acids Res., 25:3389-3402 (1991)). In certain embodiments, Gapped BLAST can be used as described in Altschul et al., Nucleic Acids Res. 25:3389-3402 (1997). BLAST-2, WU-BLAST-2 (Altschul et al., Methods in Enzymology, 266:460-480 (1996)), ALIGN, ALIGN-2 (Genentech, South San Francisco, California) or Megalign (DNASTAR) are additional publicly available software programs that can be used to align sequences. In certain embodiments, the percent identity between two nucleotide sequences is determined using the GAP program in GCG software (e.g., using a NWSgapdna.CMP matrix and a gap weight of 40, 50, 60, 70, or 90 and a length weight of 1, 2, 3, 4, 5, or 6). In certain alternative embodiments, the GAP program in the GCG software package, which incorporates the algorithm of Needleman and Wunsch (J. Mol. Biol. (48):444-453 (1970)) can be used to determine the percent identity between two amino acid sequences (e.g., using either a Blossum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5). Alternatively, in certain embodiments, the percent identity between nucleotide or amino acid sequences is determined using the algorithm of Myers and Miller (CABIOS, 4:11-17 (1989)). For example, the percent identity can be determined using the ALIGN program (version 2.0) and using a PAM120 with residue table, a gap length penalty of 12 and a gap penalty of 4. Appropriate parameters for maximal alignment by particular alignment software can be determined by one skilled in the art. In certain embodiments, the default parameters of the alignment software are used. In certain embodiments, the percentage identity "X" of a first amino acid sequence to a second sequence amino acid is calculated as 100 x (Y/Z), where Y is the number of amino acid residues scored as identical matches in the alignment of the first and second sequences (as aligned by visual inspection or a particular sequence alignment program) and Z is the total number of residues in the second sequence. If the length of a first sequence is longer than the second sequence, the percent identity of the first sequence to the second sequence will be longer than the percent identity of the second sequence to the first sequence. [0058] As a non-limiting example, whether any particular polynucleotide has a certain percentage sequence identity (e.g., is at least 80% identical, at least 85% identical, at least 90% identical, and in some embodiments, at least 95%, 96%, 97%, 98%, or 99% identical) to a reference sequence can, in certain embodiments, be determined using the Bestfit program (Wisconsin Sequence Analysis Package, Version 8 for Unix, Genetics Computer Group, University Research Park, 575 Science Drive, Madison, WI 53711). Bestfit uses the local homology algorithm of Smith and Waterman (Advances in Applied Mathematics 2: 482 489 (1981)) to find the best segment of homology between two sequences. When using Bestfit or any other sequence alignment program to determine whether a particular sequence is, for instance, 95% identical to a reference sequence described herein, the parameters are set such that the percentage of identity is calculated over the full length of the reference nucleotide sequence and that gaps in homology of up to 5% of the total number of nucleotides in the reference sequence are allowed. [0059] In some embodiments, two nucleic acids or polypeptides described herein are substantially identical, meaning they have at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, and in some embodiments at least 95%, 96%, 97%, 98%, 99% nucleotide or amino acid residue identity, when compared and aligned for maximum correspondence, as measured using a sequence comparison algorithm or by visual inspection. Identity can exist over a region of the sequences that is at least about 10, about 20, about 40-60 residues in length or any integral value there between, and can be over a longer region than 60-80 residues, for example, at least about 90-100 residues, and in some embodiments, the sequences are substantially identical over the full length of the sequences being compared, such as the coding region of a nucleotide sequence for example. [0060] A "conservative amino acid substitution" is one in which one amino acid residue is replaced with another amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art, including basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). For example, substitution of a phenylalanine for a tyrosine is a conservative substitution. In some embodiments, conservative substitutions in the sequences of the polypeptides and antibodies described herein do not abrogate the binding of the polypeptide or antibody containing the amino acid sequence, to the antigen(s). Methods of identifying nucleotide and amino acid conservative substitutions which do not eliminate antigen binding are well- known in the art (see, e.g., Brummell et al., Biochem. 32: 1180-1187 (1993); Kobayashi et al., Protein Eng.12(10):879-884 (1999); and Burks et al., Proc. Natl. Acad. Sci. USA 94:.412-417 (1997)). [0061] As used herein, the terms "treatment" or "therapy" (as well as different forms thereof, including curative or palliative) refer to treatment of a person who suffered a snake bite, is suspected of having suffered a snake bite or is likely to suffer a snake bite. As used herein, the term "treating" includes alleviating or reducing at least one adverse or negative effect or symptom of a condition, disease or disorder. This condition, disease or disorder can be a condition, disease or disorder associate with snake bite. [0062] As employed above and throughout the disclosure the term "effective amount" refers to an amount effective, at dosages, and for periods of time necessary, to achieve the desired result with respect to the treatment of the relevant disorder, condition, or side effect. An "effective amount" can be determined empirically and in a routine manner, in relation to the stated purpose. It will be appreciated that the effective amount of components of the present invention will vary from patient to patient not only with the particular vaccine, component or composition selected, the route of administration, and the ability of the components to elicit a desired result in the individual, but also with factors such as the disease state or severity of the condition to be alleviated, hormone levels, age, sex, weight of the individual, the state of being of the patient, and the severity of the pathological condition being treated, concurrent medication or special diets then being followed by the particular patient, and other factors which those skilled in the art will recognize, with the appropriate dosage being at the discretion of the attending physician. Dosage regimes may be adjusted to provide the improved therapeutic response. An effective amount is also one in which any toxic or detrimental effects of the components are outweighed by the therapeutically beneficial effects. [0063] The term "therapeutically effective amount" refers to an amount of an antibody, immunoconjugate, or other drug effective to "treat" a disease or disorder in a subject or mammal. A "prophylactically effective amount" refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired prophylactic result. Typically but not necessarily, since a prophylactic dose is used in subjects prior to or at an earlier stage of disease, the prophylactically effective amount will be less than the therapeutically effective amount. [0064] The terms "subject," "individual," and "patient" are used interchangeably herein, and refer to an animal, for example a human, to whom treatment, including prophylactic treatment, with the antibody or pharmaceutical composition according to the present disclosure, is provided. In some embodiments, the subject, individual, or patient has suffered a snake bite or is suspected of having suffered a snake bite. In some embodiments, the subject, individual, or patient is at risk of suffering a snake bite. [0065] Administration "in combination with" one or more further therapeutic agents includes simultaneous (concurrent) or consecutive administration in any order. [0066] The terms "pharmaceutically composition," "pharmaceutical formulation," "pharmaceutically acceptable formulation," or "pharmaceutically acceptable composition" all of which are used interchangeably, refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem complications commensurate with a reasonable benefit/risk ratio. "Pharmaceutically acceptable" or "pharmaceutical formulation" refers to a preparation which is in such form as to permit the biological activity of the active ingredient to be effective, and which contains no additional components which are unacceptably toxic to a subject to which the formulation would be administered. The formulation can be sterile. [0067] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to "a cell" includes a combination of two or more cells, and the like. [0068] The term "and/or" as used in a phrase such as "A and/or B" herein is intended to include both "A and B," "A or B," "A," and "B." Likewise, the term "and/or" as used in a phrase such as "A, B, and/or C" is intended to encompass each of the following embodiments: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone). [0069] The term "about" as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of up to ±20% from the specified value, as such variations are appropriate to perform the disclosed methods. Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term "about." Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. [0070] Notwithstanding that the numerical ranges and parameters setting forth the broad scope described herein are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements. [0071] It is understood that wherever embodiments are described herein with the language "comprising," otherwise analogous embodiments described in terms of "consisting of" and/or "consisting essentially of" are also provided. II. Anti-FTX_L antibodies [0072] In one aspect, provided herein are antibodies that bind to 3FTx-L. In some embodiments, an antibody described herein is a monoclonal antibody. In some embodiments, an antibody described herein is a human antibody. In some embodiments, an antibody described herein specifically binds least one 3FTx-L variant listed in Table 1. In some embodiments, an antibody described herein specifically binds at least two, at least three, at least four, or at least five 3FTx-L variants listed in Table 1. In some embodiments, an antibody described herein specifically binds 1, 2, 3, 4, 5, 10, or 15 3FTX_LCa variants listed in Table 1. In some embodiments, an antibody described herein specifically binds all 3FTx-L variants listed in Table 1. In some embodiments, the antibody specifically binds to at least three of 3FTx-L1, 3FTx-L2, 3FTx-L3, 3FTx-L5, and 3FTx- L6 variants listed in Table 1. In some embodiments, the antibody specifically binds to 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, and 3FTx-L15 variants listed in Table 1. In some embodiments, the antibody specifically binds to 3FTx-L2 comprising the amino acid sequence of SEQ ID NO: 162, 3FTx-L3 comprising the amino acid sequence of SEQ ID NO: 163, 3FTx-L5 comprising the amino acid sequence of SEQ ID NO: 165, 3FTx-L6 comprising the amino acid sequence of SEQ ID NO: 166, 3FTx-L8 comprising the amino acid sequence of SEQ ID NO: 167, 3FTx-L9 comprising the amino acid sequence of SEQ ID NO: 168, and 3FTx-L15 comprising the amino acid sequence of SEQ ID NO: 174, as listed in Table 1. [0073] In some embodiments, an isolated monoclonal antibody described herein comprises a VH that is a VH1-02, VH1-18, VH1-69 or VH3-07 VH and a VL that is a VL2-14, VK3-20, VK1-39, VL2-14 or VL1-51 VL. In some embodiments, the antibody comprises a VH that is a VH1-02 VH and a VL that is a VL2-14, VK3-20, or VK1-39 VL. In some embodiments, the antibody comprises a VH that is a VH1-18 VH and a VL that is a VL2-14 or VK3-20 VL. In some embodiments, the antibody comprises a VH that is a VH1-69 VH and a VL that is a VK1-39 or VL1-51 VL. In some embodiments, the antibody comprises a VH that is a VH3-07 VH and a VL that is a VL1-51 VL. [0074] In some embodiments, an isolated monoclonal antibody described herein comprises a VH CDR3 that comprises 19 or 20 residues comprising the amino acid sequence of SEQ ID NO: 244 or 245. In some embodiments, the VH CDR3 comprises the amino acid sequence of 246, 247, 248 or 249. In some embodiments, the VH CDR3 comprises the amino acid sequence of 246 or 248. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, 123, 133, 143 or 153 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222, or 238 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222, or 238. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153. In some embodiments, the antibody further comprises VH CDR1 residues Thr28, Ser31 and Tyr32, VL CDR2 residue Asp50, and VL CDR3 residues Ser91 and Tyr92. In some embodiments, the antibody further comprises a VH that is a VH1-02, VH1-18, VH1-69 or VH3-07 VH and a VL that is a VL2-14, VK3-20, VK139, VL2-14 or VL1-51 VL. In some embodiments, the antibody further comprises a VH that is a VH1-69 VH and a VL that is a VK1-39 VL. In some embodiments, the residue numbers and CDRs are according to Kabat. [0075] In some embodiments, an isolated monoclonal antibody described herein comprises a VH CDR3 that comprises 19 residues comprising the amino acid sequence of SEQ ID NO: 244 or 245. In some embodiments, the VH CDR3 comprises the amino acid sequence of 248 or 249. In some embodiments, the VH CDR3 comprises the amino acid sequence of 248. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, 123, 133, 143 or 153 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222, or 238 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222, or 238. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153. In some embodiments, the antibody further comprises VH CDR1 residues Thr28, Ser31 and Tyr32, VL CDR2 residue Asp50, and VL CDR3 residues Ser91 and Tyr92. In some embodiments, the antibody further comprises a VH that is a VH1-02, VH1-18, VH1-69 or VH3-07 VH and a VL that is a VL2-14, VK3-20, VK139, VL2-14 or VL1-51 VL. In some embodiments, the antibody further comprises a VH that is a VH1-69 VH and a VL that is a VK1-39 VL. In some embodiments, the residue numbers and CDRs are according to Kabat. [0076] In some embodiments, an isolated monoclonal antibody described herein comprises a VH CDR3 that comprises 20 residues comprising the amino acid sequence of SEQ ID NO: 244 or 245. In some embodiments, the VH CDR3 comprises the amino acid sequence of 246 or 247. In some embodiments, the VH CDR3 comprises the amino acid sequence of 246. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, 123, 133, 143 or 153 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222, or 238 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222, or 238. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153. In some embodiments, the antibody further comprises VH CDR1 residues Thr28, Ser31 and Tyr32, VL CDR2 residue Asp50, and VL CDR3 residues Ser91 and Tyr92. In some embodiments, the antibody further comprises a VH that is a VH1-02, VH1-18, VH1-69 or VH3-07 VH and a VL that is a VL2-14, VK3-20, VK139, VL2-14 or VL1-51 VL. In some embodiments, the antibody further comprises a VH that is a VH1-69 VH and a VL that is a VK1-39 VL. In some embodiments, the residue numbers and CDRs are according to Kabat. [0077] In some embodiments, an isolated monoclonal antibody described herein comprises a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 153, 214, 222, or 238 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222, or 238. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153. In some embodiments, the antibody further comprises VH CDR1 residues Thr28, Ser31 and Tyr32, VL CDR2 residue Asp50, and VL CDR3 residues Ser91 and Tyr92. In some embodiments, the antibody further comprises a VH that is a VH1-02, VH1-18, VH1-69 or VH3-07 VH and a VL that is a VL2-14, VK3-20, VK139, VL2- 14 or VL1-51 VL. In some embodiments, the antibody further comprises a VH that is a VH1-69 VH and a VL that is a VK1-39 VL. In some embodiments, the residue numbers and CDRs are according to Kabat. [0078] In some embodiments, an isolated monoclonal antibody described herein comprises (1) a VH CDR1 comprising the VH CDR1 of LB5_95, (2) a VH CDR2 comprising the amino acid sequence of SEQ ID NO: LB5_95, 95MAT3, 96MAT5, or 95MAT6, (3) a VH CDR3 comprising the amino acid sequence of SEQ ID NO: LB5_95, 95MAT3, 95MAT4 or 95MAT6, (4) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: LB5_95, (5) a VL CDR2 comprising the amino acid sequence of SEQ ID NO: LB5_95 or 95MAT5, and (6) a VL CDR3 comprising the amino acid sequence of SEQ ID NO: LB5_95. In some embodiments, the CDRs are according to Kabat. [0079] In some embodiments, an isolated monoclonal antibody described herein comprises the VH CDR1, VH CDR2 and VH CDR3 of LB95_5, 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6. In some embodiments, the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of LB95_5. In some embodiments, the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT1. In some embodiments, the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT2. In some embodiments, the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT3. In some embodiments, the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT4. In some embodiments, the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT5. In some embodiments, the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT6. In some embodiments, the antibody further comprises the VL CDR1, VL CDR2 and VL CDR3 of LB95_5, 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6. In some embodiments, the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of LB95_5. In some embodiments, the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT1. In some embodiments, the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT2. In some embodiments, the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT3. In some embodiments, the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT4. In some embodiments, the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT5. In some embodiments, the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT6. In some embodiments, the CDRs are according to Kabat. [0080] In some embodiments, an isolated monoclonal antibody described herein comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of LB95_5, 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6. In some embodiments, the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of LB5_95. In some embodiments, the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT1. In some embodiments, the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT2. In some embodiments, the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT3. In some embodiments, the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT4. In some embodiments, the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT5. In some embodiments, the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT6. In some embodiments, the CDRs are according to Kabat. [0081] In some embodiments, an isolated monoclonal antibody described herein comprises (1) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 151 comprising 0, 1, 2, 3, 4, or 5 substitutions, (2) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 152, 213, 229, or 237 comprising 0, 1, 2, 3, 4, or 5 substitutions, (3) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 153, 214, 222 or 238 comprising 0, 1, 2, 3, 4, or 5 substitutions, (4) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 154 comprising 0, 1, 2, 3, 4, or 5 substitutions, (5) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 155 or 232 comprising 0, 1, 2, 3, 4, or 5 substitutions, and (6) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 156 comprising 0, 1, 2, 3, 4, or 5 substitutions. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222, or 238. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153. In some embodiments, the antibody further comprises VH CDR1 residues Thr28, Ser31 and Tyr32, VL CDR2 residue Asp50, and VL CDR3 residues Ser91 and Tyr92. In some embodiments, the antibody comprises (1) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 151, (2) a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 152, 213, 229, or 237, (3) a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 153, 214, 222 or 238, (4) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 154, (5) a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 155 or 232, and (6) a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 156. In some embodiments, the antibody further comprises a VH that is a VH1-02, VH1-18, VH1-69 or VH3-07 VH and a VL that is a VL2-14, VK3-20, VK139, VL2-14 or VL1-51 VL. In some embodiments, the antibody further comprises a VH that is a VH1-69 VH and a VL that is a VK1-39 VL. In some embodiments, the residue numbers and CDRs are according to Kabat. [0082] In some embodiments, an isolated monoclonal antibody described herein comprises (1) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 151, (2) a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 152, 213, 229, or 237, (3) a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 153, 214, 222 or 238, (4) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 154, (5) a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 155 or 232, and (6) a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 156. [0083] In some embodiments, an isolated monoclonal antibody described herein comprises a VH CDR1, VH CDR2 and VH CDR3 comprising the amino acid sequence of SEQ ID NO: 151-153, respectively, SEQ ID NO: 196-198, respectively, SEQ ID NO: 204-206, respectively, SEQ ID NO: 212-214, respectively, SEQ ID NO: 220-222, respectively, SEQ ID NO: 228-230, respectively, and SEQ ID NO: 236-238, respectively. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 151-153, respectively. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 196-198, respectively. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 204-206, respectively. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 212-214, respectively. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 220-222, respectively. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 228-230, respectively. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 236-238, respectively. In some embodiments, the antibody further comprises a VL CDR1, VL CDR2 and VL CDR3 comprising the amino acid sequence of SEQ ID NO: 154-156, respectively, SEQ ID NO: 199-201, respectively, SEQ ID NO: 207-209, respectively, SEQ ID NO: 215-217, respectively, SEQ ID NO: 223-225, respectively, SEQ ID NO: 231-233, respectively, and SEQ ID NO: 239-241, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 154-156, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 199-201, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 207- 209, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 215-217, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 223-225, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 231-233, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 239-241, respectively. [0084] In some embodiments, an isolated monoclonal antibody described herein comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprising the amino acid sequence of SEQ ID NO: 151-156, respectively, SEQ ID NO: 196-201, respectively, SEQ ID NO: 204-209, respectively, SEQ ID NO: 212-217, respectively, SEQ ID NO: 220-225, respectively, SEQ ID NO: 228-233, respectively, and SEQ ID NO: 236-241, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 151-156, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 196-201, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 204-209, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 212-217, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 220-225, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 228-233, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 236-241, respectively. [0085] In some embodiments, an isolated monoclonal antibody described herein comprises a VH comprising an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to LB95_5, 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6 VH. In some embodiments, the antibody further comprises a VL comprising an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to LB95_5, 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6 VL. In some embodiments, the antibody comprises the VH and VL of LB95_5, 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6. In some embodiments, the antibody comprises the VH and VL of LB95_5. In some embodiments, the antibody comprises the VH and VL of 95MAT1. In some embodiments, the antibody comprises the VH and VL of 95MAT2. In some embodiments, the antibody comprises the VH and VL of 95MAT3. In some embodiments, the antibody comprises the VH and VL of 95MAT4. In some embodiments, the antibody comprises the VH and VL of 95MAT5. In some embodiments, the antibody comprises the VH and VL of 95MAT6. [0086] In some embodiments, an isolated monoclonal antibody described herein comprises a VH comprising an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 157, 202, 210, 218, 226, 234, or 242. In some embodiments, the antibody further comprises a VL comprising an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 158, 203, 211, 219, 227, 235, or 243. In some embodiments, the antibody comprises a VH and VL comprising an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 157 and 158, respectively, SEQ ID NO: 202 and 203, respectively, SEQ ID NO: 210 and 211, respectively, SEQ ID NO: 218 and 219, respectively, SEQ ID NO: 226 and 227, respectively, SEQ ID NO: 234 and 235, respectively, or SEQ ID NO: 242 and 243, respectively. In some embodiments, the antibody comprises a VH and VL comprising the amino acid sequence of SEQ ID NO: 157 and 158, respectively, SEQ ID NO: 202 and 203, respectively, SEQ ID NO: 210 and 211, respectively, SEQ ID NO: 218 and 219, respectively, SEQ ID NO: 226 and 227, respectively, SEQ ID NO: 234 and 235, respectively, or SEQ ID NO: 242 and 243, respectively. In some embodiments, the antibody comprises a VH and VL comprising the amino acid sequence of SEQ ID NO: 157 and 158, respectively. In some embodiments, the antibody comprises a VH and VL comprising the amino acid sequence of SEQ ID NO: 202 and 203, respectively. In some embodiments, the antibody comprises a VH and VL comprising the amino acid sequence of SEQ ID NO: 210 and 211, respectively. In some embodiments, the antibody comprises a VH and VL comprising the amino acid sequence of SEQ ID NO: 218 and 219, respectively. In some embodiments, the antibody comprises a VH and VL comprising the amino acid sequence of SEQ ID NO: 226 and 227, respectively. In some embodiments, the antibody comprises a VH and VL comprising the amino acid sequence of SEQ ID NO: 234 and 235, respectively. In some embodiments, the antibody comprises a VH and VL comprising the amino acid sequence of SEQ ID NO: 242 and 243, respectively. [0087] In some embodiments, an isolated monoclonal antibody described herein comprises a VH, a VL, or a VH and VL sequence listed in Table 2. In some embodiments, an isolated monoclonal antibody described herein comprises a VH, a VL, or a VH and VL sequence listed in Table 3. In some embodiments, an isolated monoclonal antibody described herein comprises a VH, a VL, or a VH and VL sequence listed in Table 2 and Table 3. [0088] In some embodiments, an isolated monoclonal antibody described herein comprises one, two, three, four, five or six of the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences listed in Table 2. In some embodiments, an isolated monoclonal antibody described herein comprises one, two, three, four, five or six of the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences listed in Table 3. In some embodiments, an isolated monoclonal antibody described herein comprises one, two, three, four, five or six of the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences listed in Table 2 and Table 3. [0089] In some embodiments, an isolated monoclonal antibody described herein comprises a VH CDR3 sequence listed in Table 2. In some embodiments, an isolated monoclonal antibody described herein comprises a VH CDR3 sequence listed in Table 3. In some embodiments, an isolated monoclonal antibody described herein comprises a VH CDR3 sequence listed in Table 2 and Table 3. [0090] In some embodiments, an isolated monoclonal antibody described herein comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequence listed in Table 2. In some embodiments, an isolated monoclonal antibody described herein comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequence listed in Table 3. In some embodiments, an isolated monoclonal antibody described herein comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequence listed in Table 2 and Table 3. [0091] Also provided herein are polypeptides that comprise an amino acid sequence having at least about 80% sequence identity, at least about 85% sequence identity, at least about 90% sequence identity, at least about 95% sequence identity, at least about 96% sequence identity, at least about 97% sequence identity, at least about 98% sequence identity, or at least about 99% sequence, or is identical to a sequence listed in Table 2. Also provided herein are polypeptides that comprise an amino acid sequence having at least about 80% sequence identity, at least about 85% sequence identity, at least about 90% sequence identity, at least about 95% sequence identity, at least about 96% sequence identity, at least about 97% sequence identity, at least about 98% sequence identity, or at least about 99% sequence, or is identical to a sequence listed in Table 3. [0092] In some embodiments, an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR3 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. [0093] In some embodiments, an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR3 of LB5_95. [0094] In some embodiments, an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, 123, 133, 143 or 153. [0095] In some embodiments, an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 153. [0096] In some embodiments, an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the VH CDR3 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [0097] In some embodiments, an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the VH CDR3 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [0098] In some embodiments, an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, 123, 133, 143 or 153 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. [0099] In some embodiments, an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the VH CDR3 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6. In some embodiments, the VH CDR3 comprises the VH CDR3 of 95MAT1. In some embodiments, the VH CDR3 comprises the VH CDR3 of 95MAT2. In some embodiments, the VH CDR3 comprises the VH CDR3 of 95MAT3. In some embodiments, the VH CDR3 comprises the VH CDR3 of 95MAT4. In some embodiments, the VH CDR3 comprises the VH CDR3 of 95MAT5. In some embodiments, the VH CDR3 comprises the VH CDR3 of 95MAT6. In some embodiments, an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222 or 238. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 214. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 222. In some embodiments, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 238. In some embodiments, an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR1 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95; the VH CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR2 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95; and the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR3 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In some embodiments, an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR1 of LB5_95; the VH CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR2 of LB5_95; and the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VH CDR3 of LB5_95. In some embodiments, an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 1, 11, 21, 31, 41, 51, 61, 71, 81, 91, 101, 111, 121, 131, 141 or 151; the VH CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 2, 12, 22, 32, 42, 52, 62, 72, 82, 92, 102, 112, 122, 132, 142 or 152; and the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, 123, 133, 143 or 153. In some embodiments, an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 151; the VH CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 152; and the VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 153. In some embodiments, an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises the VH CDR1 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; the VH CDR2 comprises the VH CDR2 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and the VH CDR3 comprises the VH CDR3 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises the VH CDR1 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; the VH CDR2 comprises the VH CDR2 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and the VH CDR3 comprises the VH CDR3 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises the amino acid of SEQ ID NO: 1, 11, 21, 31, 41, 51, 61, 71, 81, 91, 101, 111, 121, 131, 141 or 151 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; the VH CDR2 comprises the amino acid of SEQ ID NO: 2, 12, 22, 32, 42, 52, 62, 72, 82, 92, 102, 112, 122, 132, 142 or 152 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and the VH CDR3 comprises the amino acid of SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, 123, 133, 143 or 153 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises the amino acid of SEQ ID NO: 151 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; the VH CDR2 comprises the amino acid of SEQ ID NO: 152 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and the VH CDR3 comprises the amino acid of SEQ ID NO: 153 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises the VH CDR1 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6; the VH CDR2 comprises the VH CDR2 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6; and the VH CDR3 comprises the VH CDR3 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6. In some embodiments, an isolated monoclonal antibody described herein specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises the amino acid of SEQ ID NO: 151; the VH CDR2 comprises amino acid of SEQ ID NO: 152, 213, 229 or 237; and the VH CDR3 comprises amino acid of SEQ ID NO: 153, 214, 222 or 238. In some embodiments of the monoclonal antibody described herein, the VL CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VL CDR1 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95; the VL CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VL CDR2 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95; and the VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VL CDR3 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In some embodiments of the monoclonal antibody described herein, the VL CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VL CDR1 of LB5_95; the VL CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VL CDR2 of LB5_95; and the VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the VL CDR3 of LB5_95. In some embodiments of the monoclonal antibody described herein, the VL CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144 or 154; the VL CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 5, 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 125, 135, 145 or 155; and the VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 6, 16, 26, 36, 46, 56, 66, 76, 86, 96, 106, 116, 126, 136, 146 or 156. In some embodiments of the monoclonal antibody described herein, the VL CDR1 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 154; the VL CDR2 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 155; and the VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 156. In some embodiments of the monoclonal antibody described herein, the VL CDR1 comprises the VL CDR1 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; the VL CDR2 comprises the VL CDR2 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and the VL CDR3 comprises the VL CDR3 of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments of the monoclonal antibody described herein, the VL CDR1 comprises the VL CDR1 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; the VL CDR2 comprises the VL CDR2 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and the VL CDR3 comprises the VL CDR3 of LB5_95 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments of the monoclonal antibody described herein, the VL CDR1 comprises the amino acid of SEQ ID NO: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144 or 154 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; the VL CDR2 comprises the amino acid of SEQ ID NO: 5, 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 125, 135, 145 or 155 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and the VL CDR3 comprises the amino acid of SEQ ID NO: 6, 16, 26, 36, 46, 56, 66, 76, 86, 96, 106, 116, 126, 136, 146 or 156 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments of the monoclonal antibody described herein, the VL CDR1 comprises the amino acid of SEQ ID NO: 154 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; the VL CDR2 comprises the amino acid of SEQ ID NO: 155 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and the VL CDR3 comprises the amino acid of SEQ ID NO: 156 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments of the monoclonal antibody described herein, the VL CDR1 comprises the VL CDR1 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6; the VL CDR2 comprises the VL CDR2 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6; and the VL CDR3 comprises the VL CDR2 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6. In some embodiments of the monoclonal antibody described herein, the VL CDR1 comprises the amino acid of SEQ ID NO: 154; the VL CDR2 comprises the amino acid of 155, 232 or 240; and the VL CDR3 comprises the amino acid of SEQ ID NO: 156. In some embodiments of the monoclonal antibody described herein, the VH CDR1, VH CDR2 and VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VH CDR1, VH CDR2 and VH CDR3, respectively. In some embodiments of the monoclonal antibody described herein, the VH CDR1, VH CDR2 and VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_95 VH CDR1, VH CDR2 and VH CDR3, respectively. In some embodiments of the monoclonal antibody described herein, the VH CDR1, VH CDR2 and VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 1, 2 and 3, respectively; SEQ ID NO: 11, 12 and 13, respectively; SEQ ID NO: 21, 22 and 23, respectively; SEQ ID NO: 31, 32 and 33, respectively; SEQ ID NO: 41, 42 and 43, respectively; SEQ ID NO: 51, 52 and 53, respectively; SEQ ID NO: 61, 62 and 63, respectively; SEQ ID NO: 71, 72 and 73, respectively; SEQ ID NO: 81, 82 and 83, respectively; SEQ ID NO: 91, 92 and 93, respectively; SEQ ID NO: 101, 102 and 103, respectively; SEQ ID NO: 111, 112 and 113, respectively; SEQ ID NO: 121, 122 and 123, respectively; SEQ ID NO: 131, 132 and 133, respectively; SEQ ID NO: 141, 142 and 143, respectively; or SEQ ID NO: 151, 152 and 153, respectively. In some embodiments of the monoclonal antibody described herein, the VH CDR1, VH CDR2 and VH CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 151, 152 and 153, respectively. In some embodiments of the monoclonal antibody described herein, the VH CDR1, VH CDR2 and VH CDR3 comprises the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VH CDR1, VH CDR2 and VH CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments of the monoclonal antibody described herein, the VH CDR1, VH CDR2 and VH CDR3 comprises the LB5_95 VH CDR1, VH CDR2 and VH CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments of the monoclonal antibody described herein, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 1, 2 and 3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 11, 12 and 13, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 21, 22 and 23, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 31, 32 and 33, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 41, 42 and 43, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 51, 52 and 53, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 61, 62 and 63, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 71, 72 and 73, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 81, 82 and 83, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 91, 92 and 93, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 101, 102 and 103, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 111, 112 and 113, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 121, 122 and 123, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 131, 132 and 133, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 141, 142 and 143, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; or SEQ ID NO: 151, 152 and 153, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments of the monoclonal antibody described herein, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 151, 152 and 153, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments of the monoclonal antibody described herein, the VH CDR1, VH CDR2 and VH CDR3 comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6. In some embodiments, the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT1. In some embodiments, the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT2. In some embodiments, the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT3. In some embodiments, the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT4. In some embodiments, the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT5. In some embodiments, the antibody comprises the VH CDR1, VH CDR2 and VH CDR3 of 95MAT6. In some embodiments of the monoclonal antibody described herein, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 196-198, respectively, SEQ ID NO: 204-206, respectively, SEQ ID NO: 212-214, respectively, SEQ ID NO: 220-222, respectively, SEQ ID NO: 228-230, respectively, and SEQ ID NO: 236-238, respectively. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 196-198, respectively. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 204-206, respectively. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 212-214, respectively. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 220-222, respectively. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 228-230, respectively. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 236-238, respectively. In some embodiments of the monoclonal antibody described herein, the VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VL CDR1, VL CDR2 and VL CDR3, respectively. In some embodiments of the monoclonal antibody described herein, the VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_95 VL CDR1, VL CDR2 and VL CDR3, respectively. In some embodiments of the monoclonal antibody described herein, the VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 4, 5 and 6, respectively; SEQ ID NO: 14, 15 and 16, respectively; SEQ ID NO: 24, 25 and 26, respectively; SEQ ID NO: 34, 35 and 36, respectively; SEQ ID NO: 44, 45 and 46, respectively; SEQ ID NO: 54, 55 and 56, respectively; SEQ ID NO: 64, 65 and 66, respectively; SEQ ID NO: 74, 75 and 76, respectively; SEQ ID NO: 84, 85 and 86, respectively; SEQ ID NO: 94, 95 and 96, respectively; SEQ ID NO: 104, 105 and 106, respectively; SEQ ID NO: 114, 115 and 116, respectively; SEQ ID NO: 124, 125 and 126, respectively; SEQ ID NO: 134, 135 and 136, respectively; SEQ ID NO: 144, 145 and 146, respectively; or SEQ ID NO: 154, 155 and 156, respectively. In some embodiments of the monoclonal antibody described herein, the VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 154, 155 and 156, respectively. In some embodiments of the monoclonal antibody described herein, the VL CDR1, VL CDR2 and VL CDR3 comprises the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VL CDR1, VL CDR2 and VL CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments of the monoclonal antibody described herein, the VL CDR1, VL CDR2 and VL CDR3 comprises the LB5_95 VL CDR1, VL CDR2 and VL CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments of the monoclonal antibody described herein, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 4, 5 and 6, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 14, 15 and 16, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 24, 25 and 26, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 34, 35 and 36, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 44, 45 and 46, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 54, 55 and 56, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 64, 65 and 66, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 74, 75 and 76, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 84, 85 and 86, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 94, 95 and 96, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 104, 105 and 106, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 114, 115 and 116, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 124, 125 and 126, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 134, 135 and 136, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 144, 145 and 146, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 154, 155 and 156, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments of the monoclonal antibody described herein, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 154, 155 and 156, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments of the monoclonal antibody described herein, the VL CDR1, VL CDR2 and VL CDR3 comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6. In some embodiments, the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT1. In some embodiments, the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT2. In some embodiments, the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT3. In some embodiments, the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT4. In some embodiments, the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT5. In some embodiments, the antibody comprises the VL CDR1, VL CDR2 and VL CDR3 of 95MAT6. In some embodiments of the monoclonal antibody described herein, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 199-201, respectively, SEQ ID NO: 207-209, respectively, SEQ ID NO: 215-217, respectively, SEQ ID NO: 223-225, respectively, SEQ ID NO: 231-233, respectively, and SEQ ID NO: 239-241, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 199-201, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 207-209, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 215- 217, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 223-225, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 231-233, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 239-241, respectively. In some embodiments of the monoclonal antibody described herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3, respectively. In some embodiments of the monoclonal antibody described herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the LB5_95 VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3, respectively. In some embodiments of the monoclonal antibody described herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 1, 2, 3, 4, 5 and 6, respectively; SEQ ID NO: 11, 12, 13, 14, 15 and 16, respectively; SEQ ID NO: 21, 22, 23, 24, 25 and 26, respectively; SEQ ID NO: 31, 32, 33, 34, 35 and 36, respectively; SEQ ID NO: 41, 42, 43, 44, 45 and 46, respectively; SEQ ID NO: 51, 52, 53, 54, 55 and 56, respectively; SEQ ID NO: 61, 62, 63, 64, 65 and 66, respectively; SEQ ID NO: 71, 72, 73, 74, 75 and 76, respectively; SEQ ID NO: 81, 82, 83, 84, 85 and 86, respectively; SEQ ID NO: 91, 92, 93, 94, 95 and 96, respectively; SEQ ID NO: 101, 102, 103, 104, 105 and 106, respectively; SEQ ID NO: 111, 112, 113, 114, 115 and 116, respectively; SEQ ID NO: 121, 122, 123, 124, 125 and 126, respectively; SEQ ID NO: 131, 132, 133, 134, 135 and 136, respectively; SEQ ID NO: 141, 142, 143, 144, 145 and 146, respectively; or SEQ ID NO: 151, 152, 153, 154, 155 and 156, respectively. In some embodiments of the monoclonal antibody described herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 151, 152, 153, 154, 155 and 156, respectively. In some embodiments of the monoclonal antibody described herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95 VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments of the monoclonal antibody described herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the LB5_95 VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments of the monoclonal antibody described herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 1, 2, 3, 4, 5 and 6, respectively; SEQ ID NO: 11, 12, 13, 14, 15 and 16, respectively; SEQ ID NO: 21, 22, 23, 24, 25 and 26, respectively; SEQ ID NO: 31, 32, 33, 34, 35 and 36, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 41, 42, 43, 44, 45 and 46, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 51, 52, 53, 54, 55 and 56, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 61, 62, 63, 64, 65 and 66, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 71, 72, 73, 74, 75 and 76, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 81, 82, 83, 84, 85 and 86, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 91, 92, 93, 94, 95 and 96, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 101, 102, 103, 104, 105 and 106, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 111, 112, 113, 114, 115 and 116, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 121, 122, 123, 124, 125 and 126, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 131, 132, 133, 134, 135 and 136, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; SEQ ID NO: 141, 142, 143, 144, 145 and 146, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; or SEQ ID NO: 151, 152, 153, 154, 155 and 156, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments of the monoclonal antibody described herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 151, 152, 153, 154, 155 and 156, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments of the monoclonal antibody described herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6. In some embodiments, the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT1. In some embodiments, the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT2. In some embodiments, the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT3. In some embodiments, the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT4. In some embodiments, the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT5. In some embodiments, the antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of 95MAT6. In some embodiments of the monoclonal antibody described herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 151-156, respectively, SEQ ID NO: 196-201, respectively, SEQ ID NO: 204-209, respectively, SEQ ID NO: 212-217, respectively, SEQ ID NO: 220-225, respectively, SEQ ID NO: 228-233, respectively, and SEQ ID NO: 236-241, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 151-156, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 196-201, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 204-209, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 212-217, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 220-225, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 228-233, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 236-241, respectively. In some embodiments of the monoclonal antibody described herein, the VH comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 7, 17, 27, 37, 47, 57, 67, 77, 87, 97, 107, 117, 127, 137, 147 or 157. In some embodiments of the monoclonal antibody described herein, the VH comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 157. In some embodiments of the monoclonal antibody described herein, the VH comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 202, 210, 218, 226, 234, or 242. In some embodiments, the VH comprises the amino acid sequence of SEQ ID NO: 202. In some embodiments, the VH comprises the amino acid sequence of SEQ ID NO: 210. In some embodiments, the VH comprises the amino acid sequence of SEQ ID NO: 218. In some embodiments, the VH comprises the amino acid sequence of SEQ ID NO: 226. In some embodiments, the VH comprises the amino acid sequence of SEQ ID NO: 234. In some embodiments, the VH comprises the amino acid sequence of SEQ ID NO: 242. In some embodiments of the monoclonal antibody described herein, the VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 8, 18, 28, 38, 48, 58, 68, 78, 88, 98, 108, 118, 128, 138, 148 or 158. In some embodiments of the monoclonal antibody described herein, the VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 158. In some embodiments of the monoclonal antibody described herein, the VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 203, 211, 219, 227, 235, or 243. In some embodiments, the VL comprises the amino acid sequence of SEQ ID NO: 203. In some embodiments, the VL comprises the amino acid sequence of SEQ ID NO: 211. In some embodiments, the VL comprises the amino acid sequence of SEQ ID NO: 219. In some embodiments, the VL comprises the amino acid sequence of SEQ ID NO: 227. In some embodiments, the VL comprises the amino acid sequence of SEQ ID NO: 235. In some embodiments, the VL comprises the amino acid sequence of SEQ ID NO: 243. In some embodiments of the monoclonal antibody described herein, the VH and VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 7 and 8, respectively; SEQ ID NO: 17 and 18, respectively; SEQ ID NO: 27 and 28, respectively; SEQ ID NO: 37 and 38, respectively; SEQ ID NO: 47 and 48, respectively; SEQ ID NO: 57 and 58, respectively; SEQ ID NO: 67 and 68, respectively; SEQ ID NO: 77 and 78, respectively; SEQ ID NO: 87 and 88, respectively; SEQ ID NO: 97 and 98, respectively; SEQ ID NO: 107 and 108, respectively; SEQ ID NO: 117 and 118, respectively; SEQ ID NO: 127 and 128, respectively; SEQ ID NO: 137 and 138, respectively; SEQ ID NO: 147 and 148, respectively; or SEQ ID NO: 157 and 158, respectively. In some embodiments of the monoclonal antibody described herein, the VH and VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 157 and 158, respectively. In some embodiments of the monoclonal antibody described herein, the VH and VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 202 and 203, respectively, SEQ ID NO: 210 and 211, respectively, SEQ ID NO: 218 and 219, respectively, SEQ ID NO: 226 and 227, respectively, SEQ ID NO: 234 and 235, respectively, or SEQ ID NO: 242 and 243, respectively. In some embodiments of the monoclonal antibody described herein, the VH and VL comprises the amino acid sequence of SEQ ID NO: 202 and 203, respectively, SEQ ID NO: 210 and 211, respectively, SEQ ID NO: 218 and 219, respectively, SEQ ID NO: 226 and 227, respectively, SEQ ID NO: 234 and 235, respectively, or SEQ ID NO: 242 and 243, respectively. In some embodiments, the VH and VL comprises the amino acid sequence of SEQ ID NO: 202 and 203, respectively. In some embodiments, the VH and VL comprises the amino acid sequence of SEQ ID NO: 210 and 211, respectively. In some embodiments, the VH and VL comprises the amino acid sequence of SEQ ID NO: 218 and 219, respectively. In some embodiments, the VH and VL comprises the amino acid sequence of SEQ ID NO: 226 and 227, respectively. In some embodiments, the VH and VL comprises the amino acid sequence of SEQ ID NO: 234 and 235, respectively. In some embodiments, the VH and VL comprises the amino acid sequence of SEQ ID NO: 242 and 243, respectively. In some embodiments, an isolated monoclonal antibody described herein further comprises heavy and/or light chain constant regions. In some embodiments, an isolated monoclonal antibody described herein further comprises human heavy and/or light chain constant regions. In some embodiments, the heavy chain constant region is selected from the group consisting of human immunoglobulins IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. In some embodiments, the heavy chain constant region is selected from the group consisting of human immunoglobulins IgG1, IgG2, IgG3, and IgG4. In some embodiments, the heavy chain constant region comprises a native amino acid sequence. In some embodiments, the heavy chain constant region comprises a variant amino acid sequence. In some embodiments, the antibody is a recombinant antibody, a chimeric antibody, a human antibody, an antibody fragment, a bispecific antibody, a trispecific antibody, or a multispecific antibody. In some embodiments, the antibody is a bispecific antibody, a trispecific antibody or a multispecific antibody. In some embodiments, an antibody described herein is a bispecific antibody, a trispecific antibody or a multispecific antibody capable of binding at least one toxic component of snake venom in addition to 3FTx-L. In some embodiments, the at least one toxic component of snake venom in addition to 3FTx-L comprises a metalloprotease or a phospholipase. In some embodiments, an antibody described herein is a multispecific antibody, e.g. a bispecific antibody. Multispecific antibodies are monoclonal antibodies that have binding specificities for at least two different epitopes. In some embodiments, one of the binding specificities is for 3FTx-L epitope and the other is for an epitope on a different antigen, e.g., a different neurotoxin, a cytotoxin, a cardiotoxin, a hemotoxin, or a myotoxin. In some embodiments, a multispecific antibody described herein binds to 3FTx-L and to a metalloproteinase. In some embodiments, a multispecific antibody described herein binds to 3FTx-L and to a phospholipase. In some embodiments, bispecific antibodies bind to two different epitopes of 3FTx-L. Bispecific antibodies can be prepared as full length antibodies or antibody fragments. Techniques for making multispecific antibodies, e.g., bispecific antibodies include, but are not limited to, recombinant co-expression of two immunoglobulin heavy chain-light chain pairs having different specificities (see Milstein and Cuello, Nature 305: 537 (1983)), WO 93/08829, and Traunecker et al., EMBO J. 10: 3655 (1991)), and "knob-in-hole" engineering (see, e.g., U.S. Patent No. 5,731,168). Multi-specific antibodies may also be made by engineering electrostatic steering effects for making antibody Fc-heterodimeric molecules (WO 2009/089004A1); cross- linking two or more antibodies or fragments (see, e.g., US Patent No. 4,676,980, and Brennan et al., Science, 229: 81 (1985)); using leucine zippers to produce bi-specific antibodies (see, e.g., Kostelny et al., J. Immunol., 148(5):1547-1553 (1992)); using "diabody" technology for making bispecific antibody fragments (see, e.g., Hollinger et al., Proc. Natl. Acad. Sci. USA, 90:6444-6448 (1993)); and using single-chain Fv (scFv) dimers (see, e.g. Gruber et al., J. Immunol., 152:5368 (1994)); and preparing trispecific antibodies as described, e.g., in Tutt et al. J. Immunol. 147: 60 (1991). Engineered antibodies with three or more functional antigen binding sites, including "Octopus antibodies" and dual variable domain (DVD) immunoglobulins are also included herein (see, e.g. US 2006/0025576A1 and US Patent 10,093,733). The antibody or fragment described herein also includes a "Dual Acting Fab" or "DAF" comprising an antigen binding site that binds to different epitopes (see, US 2008/0069820, for example). In some embodiments, an antibody described herein is a multispecific antibody, e.g. a bispecific antibody comprising a first antigen binding domain comprising a VH domain or VH and VL domains described herein, and a second antigen binding region capable of binding a second toxin. In one embodiment, the second antigen binding region binds to a different neurotoxin, a cytotoxin, a cardiotoxin, a hemotoxin, or a myotoxin. In one embodiment, the second antigen binding region binds to a metalloproteinase. In one embodiment, the second antigen binding region binds to a phospholipase. In some embodiments, the antibody fragment comprises a single-chain Fv (scFv), F(ab) fragment, F(ab')2 fragment, or an isolated VH domain. In some embodiments, the antibody is capable of neutralizing at least two 3FTx-L variants described herein. In some embodiments, an antibody described herein specifically binds 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, and 3FTx-L15 variants listed in Table 1. In some embodiments, an antibody described herein specifically binds least one 3FTx-L variant listed in Table 1. In some embodiments, an antibody described herein specifically binds at least two, at least three, at least four, or at least five 3FTx-L variants listed in Table 1. In some embodiments, an antibody described herein specifically binds 1, 2, 3, 4, 5, 10, or 15 3FTx-L variants listed in Table 1. In some embodiments, an antibody described herein specifically binds all 3FTx-L variants listed in Table 1. In some embodiments, an antibody described herein is capable of binding more than one 3FTx-L selected from the group consisting of SEQ ID NO: 161-176 and 177. In some embodiments, an antibody described herein is capable of binding at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15 or at least 163FTx-L selected from the group consisting of SEQ ID NO: 161-176 and 177. In some embodiments, an antibody described herein is capable of binding all 173FTx-L selected from the group consisting of SEQ ID NO: 161-176 and 177. In some embodiments, an antibody described herein specifically binds 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, and 3FTx-L15 variants listed in Table 1. In some embodiments, an antibody described herein specifically binds 3FTx-L2 comprising the amino acid sequence of SEQ ID NO: 162, 3FTx-L3 comprising the amino acid sequence of SEQ ID NO: 163, 3FTx-L5 comprising the amino acid sequence of SEQ ID NO: 165, 3FTx-L6 comprising the amino acid sequence of SEQ ID NO: 166, 3FTx-L8 comprising the amino acid sequence of SEQ ID NO: 167, 3FTx-L9 comprising the amino acid sequence of SEQ ID NO: 168, and 3FTx-L15 comprising the amino acid sequence of SEQ ID NO: 174, as listed in Table 1. In some embodiments, an antibody described herein specifically binds at least three of the 3FTx-L1, 3FTx-L2, 3FTx-L3, 3FTx-L5, and 3FTx-L6 variants listed in Table 1. In some embodiments, an antibody described herein is capable of neutralizing at least one 3FTx-L variant listed in Table 1. In some embodiments, an antibody described herein is capable of neutralizing at least two, at least three, at least four, or at least five 3FTx-L variants listed in Table 1. In some embodiments, an antibody described herein is capable of neutralizing 1, 2, 3, 4, 5, 10, or 153FTx-L variants listed in Table 1. In some embodiments, an antibody described herein is capable of neutralizing all 3FTx-L variants listed in Table 1. In some embodiments, an antibody described herein is capable of neutralizing in an in vitro cell based assay at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15 or at least 163FTx-L selected from the group consisting of SEQ ID NO: 161-176 and 177. In some embodiments, an antibody described herein is capable of neutralizing alpha-bungarotoxin comprising the amino acid sequence of SEQ ID NO: 250. In some embodiments, an antibody described herein is capable of neutralizing the 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, and 3FTx-L15 variants listed in Table 1. In some embodiments, an antibody described herein is capable of neutralizing 3FTx-L2 comprising the amino acid sequence of SEQ ID NO: 162, 3FTx-L3 comprising the amino acid sequence of SEQ ID NO: 163, 3FTx-L5 comprising the amino acid sequence of SEQ ID NO: 165, 3FTx-L6 comprising the amino acid sequence of SEQ ID NO: 166, 3FTx-L8 comprising the amino acid sequence of SEQ ID NO: 167, 3FTx-L9 comprising the amino acid sequence of SEQ ID NO: 168, and 3FTx-L15 comprising the amino acid sequence of SEQ ID NO: 174, as listed in Table 1. In some embodiments, an antibody described herein is capable of neutralizing at least three of the 3FTx-L1, 3FTx-L2, 3FTx-L3, 3FTx-L5, and 3FTx-L6 variants listed in Table 1. In some embodiments, neutralization is assessed in a cell based in vitro assay. In some embodiments, neutralization is assessed in an in vivo assay. In another aspect, provided herein are antibodies that bind the same or an overlapping epitope of 3FTx-L as an antibody described herein. In certain embodiments, the epitope of an antibody can be determined by, e.g., NMR spectroscopy, X-ray diffraction crystallography studies, ELISA assays, hydrogen/deuterium exchange coupled with mass spectrometry (e.g., liquid chromatography electrospray mass spectrometry), array-based oligo-peptide scanning assays, and/or mutagenesis mapping (e.g., site-directed mutagenesis mapping). For X-ray crystallography, crystallization may be accomplished using any of the known methods in the art (e.g., Giegé R et al., (1994) Acta Crystallogr D Biol Crystallogr 50(Pt 4): 339-350; McPherson A (1990) Eur J Biochem 189: 1-23; Chayen NE (1997) Structure 5: 1269-1274; McPherson A (1976) J Biol Chem 251: 6300-6303). Antibody:antigen crystals may be studied using well known X-ray diffraction techniques and may be refined using computer software such as X-PLOR (Yale University, 1992, distributed by Molecular Simulations, Inc.; see, e.g., Meth Enzymol (1985) volumes 114 & 115, eds Wyckoff HW et al.; U.S. Patent Application No. 2004/0014194), and BUSTER (Bricogne G (1993) Acta Crystallogr D Biol Crystallogr 49(Pt 1): 37-60; Bricogne G (1997) Meth Enzymol 276A: 361-423, ed Carter CW; Roversi P et al., (2000) Acta Crystallogr D Biol Crystallogr 56(Pt 10): 1316-1323). Mutagenesis mapping studies may be accomplished using any method known to one of skill in the art. See, e.g., Champe M et al., (1995) supra and Cunningham BC & Wells JA (1989) supra for a description of mutagenesis techniques, including alanine scanning mutagenesis techniques. In a specific embodiment, the epitope of an antibody is determined using alanine scanning mutagenesis studies. Usually, binding to the antigen is reduced or disrupted when a residue within the epitope is substituted to alanine. In some embodiments, the Kd of binding to the antigen is increased by about 5-fold, 10-fold, 20-fold, 10-fold or more when a residue within the epitope is substituted for alanine. In some embodiments, binding affinity is determined by ELISA. In addition, antibodies that recognize and bind to the same or overlapping epitopes of 3FTx-L can be identified using routine techniques such as an immunoassay, for example, by showing the ability of one antibody to block the binding of another antibody to a target antigen, i.e., a competitive binding assay. In another aspect, provided herein are antibodies that compete (e.g., in a dose dependent manner) for binding to 3FTx-L with an antibody described herein, as determined using assays known to one of skill in the art or described herein (e.g., ELISA competitive assays or surface plasmon resonance). In another aspect, provided herein are antibodies that competitively inhibit (e.g., in a dose dependent manner) an antibody described herein from binding to 3FTx-L, as determined using assays known to one of skill in the art or described herein (e.g., ELISA competitive assays, or suspension array or surface plasmon resonance assay). In certain embodiments, the epitope of an antibody described herein is used as an immunogen to produce antibodies. In one aspect, provided herein are methods for producing an engineered variant of an antibody described herein. In some embodiments, a method for producing an engineered variant comprises directed-evolution and yeast display. Methods for producing an engineered antibody are known to those skilled in the art, for example, as described in International Appl. No. PCT/US2019/43578, filed on July 26, 2016, which is incorporated herein by reference in its entirety for all purposes. In some embodiments, an engineered antibody possesses one or more improved properties, for example, higher binding affinity to target antigen, higher binding affinity to target antigen at low pH, increased median neutralization IC50 potency, and increased breadth of neutralization compared to the parent antibody. In one aspect, provided herein is a method of producing an engineered variant of an antibody comprising substituting one or more amino acid residues of the VH; and/or substituting one or more amino acid residues of the VL to create an engineered variant antibody, and producing the engineered variant antibody, wherein the antibody is LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In one aspect, provided herein is a method of producing an engineered variant of a LB5_95 comprising substituting one or more amino acid residues of the LB5_95 VH; and/or substituting one or more amino acid residues of the LB5_95 VL to create an engineered variant antibody, and producing the engineered variant antibody. In some embodiments, a method of producing an engineered variant of a parent antibody comprises substituting one or more amino acid residues of the VH; and/or substituting one or more amino acid residues of the VL to create an engineered variant antibody, and producing the engineered variant antibody. In some embodiments, the parent antibody is an antibody described herein. In some embodiments, the parent antibody is LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In some embodiments, the parent antibody is LB5_95. In some embodiments, the method further comprises determining that the engineered variant antibody has improved properties, for example, by determining the engineered variant antibody's binding affinity to target antigen, binding affinity to target antigen at low pH, median neutralization IC50 potency, or breadth of neutralization compared to the parent antibody. In one aspect, provided herein is a method of producing an engineered variant of an antibody comprising substituting one or more amino acid residues of the VH; and/or substituting one or more amino acid residues of the VL to create an engineered variant antibody, and producing the engineered variant antibody, wherein the antibody is 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In one aspect, provided herein is a method of producing an engineered variant of a 95MAT5 comprising substituting one or more amino acid residues of the 95MAT5 VH; and/or substituting one or more amino acid residues of the 95MAT5 VL to create an engineered variant antibody, and producing the engineered variant antibody. In some embodiments, a method of producing an engineered variant of a parent antibody comprises substituting one or more amino acid residues of the VH; and/or substituting one or more amino acid residues of the VL to create an engineered variant antibody, and producing the engineered variant antibody. In some embodiments, the parent antibody is an antibody described herein. In some embodiments, the parent antibody is 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the parent antibody is 95MAT5. In some embodiments, the method further comprises determining that the engineered variant antibody has improved properties, for example, by determining the engineered variant antibody's binding affinity to target antigen, binding affinity to target antigen at low pH, median neutralization IC50 potency, or breadth of neutralization compared to the parent antibody. The affinity or avidity of an antibody or fusion polypeptide for an antigen can be determined experimentally using any suitable method well known in the art, e.g., flow cytometry, enzyme-linked immunoabsorbent assay (ELISA), or radioimmunoassay (RIA), or kinetics (e.g., BIACORE™ analysis). Direct binding assays as well as competitive binding assay formats can be readily employed. (See, for example, Berzofsky, et al., "Antibody-Antigen Interactions," In Fundamental Immunology, Paul, W. E., Ed., Raven Press: New York, N.Y. (1984); Kuby, Janis Immunology, W. H. Freeman and Company: New York, N.Y. (1992); and methods described herein. The measured affinity of a particular antibody-antigen interaction can vary if measured under different conditions (e.g., salt concentration, pH, temperature). Thus, measurements of affinity and other antigen-binding parameters (e.g., Kd, Kon, Koff) are made with standardized solutions of antibody and antigen, and a standardized buffer, as known in the art and such as the buffer described herein. In some embodiments, the anti-3FTx-L antibody described herein is a monoclonal antibody. Monoclonal antibodies can be prepared using hybridoma methods, such as those described by Kohler and Milstein (1975) Nature 256:495. Alternatively monoclonal antibodies can also be made using recombinant DNA methods as described, for example, in U.S. Patent 4,816,567. Recombinant monoclonal antibodies or fragments thereof of the desired species can be isolated from phage display libraries expressing CDRs of the desired species as described (McCafferty et al., 1990, Nature, 348:552-554; Clackson et al., 1991, Nature, 352:624-628; and Marks et al., 1991, J. Mol. Biol., 222:581-597). The polynucleotide(s) encoding a monoclonal antibody can further be modified in a number of different manners using recombinant DNA technology to generate alternative antibodies. In some embodiments, the constant domains of the light and heavy chains of, for example, a mouse monoclonal antibody can be substituted 1) for those regions of, for example, a human antibody to generate a chimeric antibody or 2) for a non-immunoglobulin polypeptide to generate a fusion antibody. In some embodiments, the constant regions are truncated or removed to generate the desired antibody fragment of a monoclonal antibody. Site-directed or high-density mutagenesis of the variable region can be used to optimize specificity, affinity, etc. of a monoclonal antibody. Methods for engineering, humanizing or resurfacing non-human or human antibodies can also be used and are well known in the art. A humanized, resurfaced or similarly engineered antibody can have one or more amino acid residues from a source that is non-human, e.g., but not limited to, mouse, rat, rabbit, non-human primate or other mammal. These non-human amino acid residues are replaced by residues that are often referred to as "import" residues, which are typically taken from an "import" variable, constant or other domain of a known human sequence. Such imported sequences can be used to reduce immunogenicity or reduce, enhance or modify binding, affinity, on-rate, off-rate, avidity, specificity, half-life, or any other suitable characteristic, as known in the art. In general, the CDR residues are directly and most substantially involved in influencing antibody binding. Accordingly, part or all of the non-human or human CDR sequences are maintained while the non-human sequences of the variable and constant regions can be replaced with human or other amino acids. Antibodies can also optionally be humanized, resurfaced, engineered or human antibodies engineered with retention of high affinity for the antigen and other favorable biological properties. To achieve this goal, humanized (or human) or engineered antibodies and resurfaced antibodies can be optionally prepared by a process of analysis of the parental sequences and various conceptual humanized and engineered products using three-dimensional models of the parental, engineered, and humanized sequences. Three-dimensional immunoglobulin models are commonly available and are familiar to those skilled in the art. Computer programs are available which illustrate and display probable three-dimensional conformational structures of selected candidate immunoglobulin sequences. Inspection of these displays permits analysis of the likely role of the residues in the functioning of the candidate immunoglobulin sequence, i.e., the analysis of residues that influence the ability of the candidate immunoglobulin to bind its antigen. In this way, framework (FR) residues can be selected and combined from the consensus and import sequences so that the desired antibody characteristic, such as increased affinity for the target antigen(s), is achieved. Humanization, resurfacing or engineering of antibodies described herein can be performed using any known method, such as but not limited to those described in, Winter (Jones et al., Nature 321:522 (1986); Riechmann et al., Nature 332:323 (1988); Verhoeyen et al., Science 239:1534 (1988)), Sims et al., J. Immunol.151: 2296 (1993); Chothia and Lesk, J. Mol. Biol.196:901 (1987), Carter et al., Proc. Natl. Acad. Sci. U.S.A. 89:4285 (1992); Presta et al., J. Immunol. 151:2623 (1993), U.S. Pat. Nos. 5,639,641, 5,723,323; 5,976,862; 5,824,514; 5,817,483; 5,814,476; 5,763,192; 5,723,323; 5,766,886; 5,714,352; 6,204,023; 6,180,370; 5,693,762; 5,530,101; 5,585,089; 5,225,539; 4,816,567; PCT/: US98/16280; US96/18978; US91/09630; US91/05939; US94/01234; GB89/01334; GB91/01134; GB92/01755; WO90/14443; WO90/14424; WO90/14430; EP 229246; 7,557,189; 7,538,195; and 7,342,110, each of which is entirely incorporated herein by reference, including the references cited therein. In certain alternative embodiments, the antibody is a human antibody. Human antibodies can be directly prepared using various techniques known in the art. Human antibodies can be isolated from suitable donors. Immortalized human B lymphocytes immunized in vitro or isolated from an immunized individual that produce an antibody directed against a target antigen can be generated (See, e.g., Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985); Boemer et al., 1991, J. Immunol., 147 (1):86-95; and U.S. Patent 5,750,373). Also, the human antibody can be selected from a phage library, where that phage library expresses human antibodies, as described, for example, in Vaughan et al., 1996, Nat. Biotech., 14:309-314, Sheets et al., 1998, Proc. Nat'l. Acad. Sci., 95:6157-6162, Hoogenboom and Winter, 1991, J. Mol. Biol., 227:381, and Marks et al., 1991, J. Mol. Biol., 222:581). Techniques for the generation and use of antibody phage libraries are also described in U.S. Patent Nos. 5,969,108, 6,172,197, 5,885,793, 6,521,404; 6,544,731; 6,555,313; 6,582,915; 6,593,081; 6,300,064; 6,653,068; 6,706,484; and 7,264,963; and Rothe et al., 2007, J. Mol. Bio., doi:10.1016/j.jmb.2007.12.018 (each of which is incorporated by reference in its entirety). Affinity maturation strategies and chain shuffling strategies (Marks et al., 1992, Bio/Technology 10:779-783, incorporated by reference in its entirety) are known in the art and can be employed to generate high affinity human antibodies. In certain embodiments an antibody fragment is provided. Various techniques are known for the production of antibody fragments. Traditionally, these fragments are derived via proteolytic digestion of intact antibodies (for example Morimoto et al., 1993, Journal of Biochemical and Biophysical Methods 24:107-117; Brennan et al., 1985, Science, 229:81). In certain embodiments, antibody fragments are produced recombinantly. Fab, Fv, and scFv antibody fragments can all be expressed in and secreted from E. coli or other host cells, thus allowing the production of large amounts of these fragments. Such antibody fragments can also be isolated from antibody phage libraries. The antibody fragment can also be linear antibodies as described in U.S. Patent 5,641,870, for example, and can be monospecific or bispecific. Other techniques for the production of antibody fragments will be apparent to the skilled practitioner. In certain embodiments, the variable domains in both the heavy and light chains are altered by at least partial replacement of one or more CDRs and, if necessary, by partial framework region replacement and sequence changing. Although the CDRs can be derived from an antibody of the same class or even subclass as the antibody from which the framework regions are derived, it is envisaged that the CDRs will be derived from an antibody of different class and in certain embodiments from an antibody from a different species. It may not be necessary to replace all of the CDRs with the complete CDRs from the donor variable region to transfer the antigen-binding capacity of one variable domain to another. Rather, it may only be necessary to transfer those residues that are necessary to maintain the activity of the antigen-binding site. Given the explanations set forth in U.S. Pat. Nos. 5,585,089, 5,693,761 and 5,693,762, it will be well within the competence of those skilled in the art, either by carrying out routine experimentation or by trial and error testing to obtain a functional antibody with reduced immunogenicity. Alterations to the variable region notwithstanding, those skilled in the art will appreciate that the modified antibodies described herein will comprise antibodies (e.g., full-length antibodies or immunoreactive fragments thereof) in which at least a fraction of one or more of the constant region domains has been deleted or otherwise altered so as to provide desired biochemical characteristics such as increased serum half-life when compared with an antibody of approximately the same immunogenicity comprising a native or unaltered constant region. In some embodiments, the constant region of the modified antibodies will comprise a human constant region. Modifications to the constant region compatible with this invention comprise additions, deletions or substitutions of one or more amino acids in one or more domains. That is, the modified antibodies described herein can comprise alterations or modifications to one or more of the three heavy chain constant domains (CH1, CH2 or CH3) and/or to the light chain constant domain (CL). In some embodiments, modified constant regions wherein one or more domains are partially or entirely deleted are contemplated. In some embodiments, the modified antibodies will comprise domain deleted constructs or variants wherein the entire CH2 domain has been removed (ΔCH2 constructs). In some embodiments, the omitted constant region domain will be replaced by a short amino acid spacer (e.g., 10 residues) that provides some of the molecular flexibility typically imparted by the absent constant region. It will be noted that in certain embodiments, the modified antibodies can be engineered to fuse the CH3 domain directly to the hinge region of the respective modified antibodies. In other constructs it may be desirable to provide a peptide spacer between the hinge region and the modified CH2 and/or CH3 domains. For example, compatible constructs could be expressed wherein the CH2 domain has been deleted and the remaining CH3 domain (modified or unmodified) is joined to the hinge region with a 5-20 amino acid spacer. Such a spacer can be added, for instance, to ensure that the regulatory elements of the constant domain remain free and accessible or that the hinge region remains flexible. However, it should be noted that amino acid spacers can, in some cases, prove to be immunogenic and elicit an unwanted immune response against the construct. Accordingly, in certain embodiments, any spacer added to the construct will be relatively non- immunogenic, or even omitted altogether, so as to maintain the desired biochemical qualities of the modified antibodies. Besides the deletion of whole constant region domains, it will be appreciated that the antibodies described herein can be provided by the partial deletion or substitution of a few or even a single amino acid. For example, it may be desirable to simply delete that part of one or more constant region domains that control the effector function (e.g., complement C1Q binding) to be modulated. Such partial deletions of the constant regions can improve selected characteristics of the antibody (serum half-life) while leaving other desirable functions associated with the subject constant region domain intact. Moreover, as alluded to above, the constant regions of the disclosed antibodies can be modified through the mutation or substitution of one or more amino acids that enhances the profile of the resulting construct. In this respect it may be possible to disrupt the activity provided by a conserved binding site (e.g., Fc binding) while substantially maintaining the configuration and immunogenic profile of the modified antibody. Certain embodiments can comprise the addition of one or more amino acids to the constant region to enhance desirable characteristics such as decreasing or increasing effector function or provide for more cytotoxin or carbohydrate attachment. In such embodiments it can be desirable to insert or replicate specific sequences derived from selected constant region domains. The half-life of an IgG is mediated by its pH-dependent binding to the neonatal receptor FcRn. In some embodiments, an antibody described herein comprises a variant Fc region that has been modified to enhance binding to FcRn (see, e.g., Petkova et al., Int. Immunol.18: 1759-1769 (2006); Dall'Acqua et al., J. Immunol.169: 5171-5180 (2002); Oganesyan et al., Mol. Immunol.46: 1750-1755 (2009); Dall'Acqua et al., J. Biol. Chem. 281: 23514-23524 (2006), Hinton et al., J. Immunol.176: 346-356 (2006); Datta-Mannan et al., Drug Metab. Dispos.35: 86-94 (2007); Datta- Mannan et al., J. Biol. Chem.282: 1709-1717 (2007); WO 06/130834; Strohl, Curr. Op. Biotechnol. 20: 685-691 (2009); and Yeung et al., J. Immunol.182: 7663-7671 (2009), the contents of each of which is herein incorporated by reference in its entirety). In some embodiments, an antibody described herein comprises a variant Fc region that has been modified to have a selective affinity for FcRn at pH 6.0, but not pH 7.4. By way of example, the variant Fc region contains one or more of the following modifications that increase half-life: IgG1-M252Y, S254T, T256E; IgG1-T250Q, M428L; IgG1-M428L and N434S (the "LS" mutation); IgG1-H433K, N434Y; IgG1-N434A; and IgG1-T307A, E380A, N434A; wherein the numbering of the residues is that of the EU index of Kabat et al. (Kabat et al., Sequences of Proteins of Immunological Interest, 1991 Fifth edition, herein incorporated by reference). In some embodiments, an antibody described herein comprises a variant Fc region that has been modified to reduce its effector functions. In some embodiments, the variant Fc region comprises the L234A, L235A hinge region substitutions, wherein the numbering of the residues is that of the EU index of Kabat et al. In some embodiments, an antibody described herein comprises an Fc region having a carbohydrate structure that lacks fucose attached (directly or indirectly) to the Fc region or has a reduced level of fucosylation. In some embodiments, a fucosylation variant antibody has improved ADCC function. See, e.g., US Patent Publication Nos. US 2003/0157108; US 2004/0093621, each of which is incorporated by reference herein in its entirety. Examples of publications related to "defucosylated" or "fucose-deficient" antibody variants include: US 2003/0157108; WO 2000/61739; WO 2001/29246; US 2003/0115614; US 2002/0164328; US 2004/0093621; US 2004/0132140; US 2004/0110704; US 2004/0110282; US 2004/0109865; WO 2003/085119; WO 2003/084570; WO 2005/035586; WO 2005/035778; WO2005/053742; WO2002/031140; Okazaki et al. J. Mol. Biol.336:1239-1249 (2004); Yamane-Ohnuki et al. Biotech. Bioeng.87: 614 (2004), each of which is incorporated by reference herein in its entirety. Examples of cell lines capable of producing defucosylated antibodies include Lec 13 CHO cells deficient in protein fucosylation (Ripka et al. Arch. Biochem. Biophys. 249:533-545 (1986); US Pat Appl No US 2003/0157108 A1; and WO 2004/056312), and knockout cell lines, such as alpha-1,6-fucosyltransferase gene, FUT8, knockout CHO cells (see, e.g., Yamane-Ohnuki et al. Biotech. Bioeng. 87: 614 (2004); Kanda, Y. et al., Biotechnol. Bioeng., 94(4):680-688 (2006); and WO2003/085107), each of which is incorporated by reference herein in its entirety. In some embodiment, an antibody described herein comprises bisected oligosaccharides, in which a biantennary oligosaccharide attached to the Fc region of the antibody is bisected by GlcNAc. In some embodiment, an antibody comprising bisected oligosaccharides has reduced fucosylation and/or improved ADCC function. See, e.g., WO 2003/011878; U.S. Pat. No. 6,602,684; and US 2005/0123546, each of which is incorporated by reference herein in its entirety. In some embodiment, an antibody described herein comprises at least one galactose residue in the oligosaccharide attached to the Fc region. Such antibody variants may have improved CDC function. See, e.g., in WO 1997/30087; WO 1998/58964; and WO 1999/22764, each of which is incorporated by reference herein in its entirety. In some embodiments, an antibody described herein comprises a variant Fc region comprising a combination of substitutions with increased binding to FcRn and Fc gamma RIIIa. The combinations increase antibody half-life and ADCC. For example, such combination include antibodies with the following amino acid substitution in the Fc region: (1) S239D/I332E and T250Q/M428L; (2) S239D/I332E and M428L/N434S; (3) S239D/I332E and N434A; (4) S239D/I332E and T307A/E380A/N434A; (5) S239D/I332E and M252Y/S254T/T256E; (6) S239D/A330L/I332E and 250Q/M428L; (7) S239D/A330L/I332E and M428L/N434S; (8) S239D/A330L/I332E and N434A; (9) S239D/A330L/I332E and T307A/E380A/N434A; or (10) S239D/A330L/I332E and M252Y/S254T/T256E, wherein the numbering of the residues is that of the EU index of Kabat et al. In some embodiments, an antibody comprising the variant Fc region is directly cytotoxic to infected cells, or uses natural defenses such as complement, antibody dependent cellular cytotoxicity (ADCC), or phagocytosis by macrophages. The present invention further embraces variants and equivalents which are substantially homologous to the chimeric, humanized and human antibodies, or antibody fragments thereof, set forth herein. These can contain, for example, conservative substitution mutations, i.e., the substitution of one or more amino acids by similar amino acids. For example, conservative substitution refers to the substitution of an amino acid with another within the same general class such as, for example, one acidic amino acid with another acidic amino acid, one basic amino acid with another basic amino acid or one neutral amino acid by another neutral amino acid. What is intended by a conservative amino acid substitution is well known in the art. The polypeptides provided herein can be recombinant polypeptides, natural polypeptides, or synthetic polypeptides comprising an antibody, or fragment thereof. It will be recognized in the art that some amino acid sequences described herein can be varied without significant effect of the structure or function of the protein. Thus, the invention further includes variations of the polypeptides which show substantial activity or which include regions of an antibody, or fragment thereof, against a human folate receptor protein. Such mutants include deletions, insertions, inversions, repeats, and type substitutions. The polypeptides and analogs can be further modified to contain additional chemical moieties not normally part of the protein. Those derivatized moieties can improve the solubility, the biological half-life or absorption of the protein. The moieties can also reduce or eliminate any desirable side effects of the proteins and the like. An overview for those moieties can be found in REMINGTON'S PHARMACEUTICAL SCIENCES, 21th ed., Mack Publishing Co., Easton, PA (2005). III. Polynucleotides In certain aspects, provided herein are polynucleotides comprising a nucleotide sequence or nucleotide sequences encoding an anti-3FTx-L antibody described herein or a fragment thereof and vectors, e.g., vectors comprising such polynucleotides. In some embodiments, the vectors can be used for recombinant expression of an antibody described herein in host cells (e.g., E. coli and mammalian cells). In some embodiments, the vectors can be used for administration of an antibody described herein to a patient in need thereof. In some embodiments, the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5. In one aspect, provided herein are isolated polynucleotides encoding the heavy chain variable region or heavy chain of an antibody described herein. In some embodiments, the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5. In one aspect, provided herein are isolated polynucleotides encoding the light chain variable region or light chain of an antibody described herein. In some embodiments, the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5. In one aspect, provided herein are isolated polynucleotides encoding the heavy chain variable region or heavy chain of an antibody described herein and the light chain variable region or light chain of an antibody described herein. In some embodiments, the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5. In some embodiments, the polynucleotide encodes a heavy chain variable region described herein. In some embodiments, the VH comprises the VH of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In some embodiments, the VH comprises the VH of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the VH comprises the VH of LB5_95. In some embodiments, the VH comprises the VH of 95MAT5. In some embodiments, the polynucleotide encodes a light chain variable region described herein. In some embodiments, the VL comprises the VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In some embodiments, the VL comprises the VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the VL comprises the VL of LB5_95. In some embodiments, the VL comprises the VL of 95MAT5. In some embodiments, an isolated polynucleotide described herein is a DNA. In some embodiments, an isolated polynucleotide described herein is an mRNA. In some embodiments, the mRNA comprises a modified nucleotide. In some embodiments, an isolated polynucleotide described herein encodes an antibody described herein and comprises an mRNA. In some embodiments, the mRNA comprises at least one modified nucleotide. In some embodiments, a modified mRNA encoding an antibody described herein is for administering to a subject to treat snake bite. In some embodiments, a modified mRNA encoding an antibody described herein is for administering to a subject at risk of suffering a snake bite. In some embodiments, the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5. As used herein, an "isolated" polynucleotide or nucleic acid molecule is one which is separated from other nucleic acid molecules which are present in the natural source (e.g., in a mouse or a human) of the nucleic acid molecule. Moreover, an "isolated" nucleic acid molecule, such as a cDNA molecule, can be substantially free of other cellular material, or culture medium when produced by recombinant techniques, or substantially free of chemical precursors or other chemicals when chemically synthesized. For example, the language "substantially free" includes preparations of polynucleotide or nucleic acid molecule having less than about 15%, 10%, 5%, 2%, 1%, 0.5%, or 0.1% (in particular less than about 10%) of other material, e.g., cellular material, culture medium, other nucleic acid molecules, chemical precursors and/or other chemicals. In a specific embodiment, a nucleic acid molecule(s) encoding an antibody or fusion polypeptide described herein is isolated or purified. In particular aspects, provided herein are polynucleotides comprising nucleotide sequences encoding antibodies described herein, as well as antibodies that compete with such antibodies for binding to 3FTx-L, or which binds to the same epitope as that of such antibodies. In some embodiments, the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5. In certain aspects, provided herein are polynucleotides comprising a nucleotide sequence encoding the light chain or heavy chain of an antibody described herein. The polynucleotides can comprise nucleotide sequences encoding a light chain comprising the VL of antibodies described herein. The polynucleotides can comprise nucleotide sequences encoding a heavy chain comprising the VH of antibodies described herein. In some embodiments, the antibody is a human antibody. In some embodiments, the antibody is a chimeric antibody. In some embodiments, the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5. In particular embodiments, provided herein are polynucleotides comprising a nucleotide sequence encoding an anti-3FTx-L antibody comprising three VL chain CDRs, e.g., containing VL CDR1, VL CDR2, and VL CDR3 of any one of antibodies described herein. In specific embodiments, provided herein are polynucleotides comprising three VH chain CDRs, e.g., containing VH CDR1, VH CDR2, and VH CDR3 of any one of antibodies described herein. In specific embodiments, provided herein are polynucleotides comprising a nucleotide sequence encoding an anti-3FTx-L antibody comprising three VL CDRs, e.g., containing VL CDR1, VL CDR2, and VL CDR3 of any one of antibodies described herein and three VH chain CDRs, e.g., containing VH CDR1, VH CDR2, and VH CDR3 of any one of antibodies described herein. In some embodiments, the antibody is a human antibody. In particular embodiments, provided herein are polynucleotides comprising a nucleotide sequence encoding a broadly neutralizing anti-3FTx-L antibody comprising three VL chain CDRs, e.g., containing VL CDR1, VL CDR2, and VL CDR3 of any one of antibodies described herein. In particular embodiments, provided herein are polynucleotides comprising a nucleotide sequence encoding an anti-3FTx-L antibody comprising three VH chain CDRs, e.g., containing VH CDR1, VH CDR2, and VH CDR3 of any one of antibodies described herein. In particular embodiments, provided herein are polynucleotides comprising a nucleotide sequence encoding an anti-3FTx-L antibody comprising three VL CDRs, e.g., containing VL CDR1, VL CDR2, and VL CDR3 of any one of antibodies described herein and three VH chain CDRs, e.g., containing VH CDR1, VH CDR2, and VH CDR3 of any one of antibodies described herein. In some embodiments, provided herein are polynucleotides comprising a nucleotide sequence encoding a broadly neutralizing anti-3FTx-L antibody comprising the VH CDR3 of an antibody described herein. In some embodiments, the antibody is a human antibody. In specific embodiments, a polynucleotide provided herein comprises a nucleotide sequence encoding an antibody or fragment thereof described herein comprising: framework regions (e.g., framework regions of the VL domain and VH domain) that are human framework regions, wherein the antibody immunospecifically binds 3FTx-L. In certain embodiments, a polynucleotide provided herein comprises a nucleotide sequence encoding an antibody or fragment thereof (e.g., CDRs or variable domain) described herein. In specific aspects, provided herein is a polynucleotide comprising a nucleotide sequence encoding an antibody comprising a light chain and a heavy chain, e.g., a separate light chain and heavy chain. With respect to the light chain, in a specific embodiment, a polynucleotide provided herein comprises a nucleotide sequence encoding a kappa light chain. In another specific embodiment, a polynucleotide provided herein comprises a nucleotide sequence encoding a lambda light chain. In yet another specific embodiment, a polynucleotide provided herein comprises a nucleotide sequence encoding an antibody described herein comprising a human kappa light chain or a human lambda light chain. In a particular embodiment, a polynucleotide provided herein comprises a nucleotide sequence encoding an antibody, which immunospecifically binds to 3FTx- L, wherein the antibody comprises a light chain, and wherein the amino acid sequence of the VL domain can comprise the amino acid sequence set forth herein, and wherein the constant region of the light chain comprises the amino acid sequence of a human kappa light chain constant region. In another particular embodiment, a polynucleotide provided herein comprises a nucleotide sequence encoding an antibody, which immunospecifically binds to 3FTx-L, and comprises a light chain, wherein the amino acid sequence of the VL domain can comprise the amino acid sequence set forth herein, and wherein the constant region of the light chain comprises the amino acid sequence of a human lambda light chain constant region. For example, human constant region sequences can be those described in U.S. Patent No.5,693,780. In a particular embodiment, a polynucleotide provided herein comprises a nucleotide sequence encoding an antibody described herein, which immunospecifically binds to 3FTx-L, wherein the antibody comprises a heavy chain, and wherein the constant region of the heavy chain comprises the amino acid sequence of a human alpha or gamma heavy chain constant region. In yet another specific embodiment, a polynucleotide provided herein comprises a nucleotide sequence encoding an antibody described herein, which immunospecifically binds 3FTx-L, wherein the antibody comprises a VL domain and a VH domain comprising any amino acid sequences described herein, and wherein the constant regions comprise the amino acid sequences of the constant regions of a human IgA1, human IgA2 ' human IgG1 (e.g., allotype 1, 17, or 3), human IgG2, or human IgG4. In yet another specific embodiment, a polynucleotide provided herein comprises nucleotide sequences encoding an anti-3FTx-L antibody or a fragment thereof that are optimized, e.g., by codon/RNA optimization, replacement with heterologous signal sequences, and elimination of mRNA instability elements. Methods to generate optimized nucleic acids encoding an anti-3FTx- L antibody or a fragment thereof (e.g., light chain, heavy chain, VH domain, or VL domain) for recombinant expression by introducing codon changes and/or eliminating inhibitory regions in the mRNA can be carried out by adapting the optimization methods described in, e.g., U.S. Patent Nos. 5,965,726; 6,174,666; 6,291,664; 6,414,132; and 6,794,498, accordingly. For example, potential splice sites and instability elements (e.g., A/T or A/U rich elements) within the RNA can be mutated without altering the amino acids encoded by the nucleic acid sequences to increase stability of the RNA for recombinant expression. The alterations utilize the degeneracy of the genetic code, e.g., using an alternative codon for an identical amino acid. In some embodiments, it can be desirable to alter one or more codons to encode a conservative mutation, e.g., a similar amino acid with similar chemical structure and properties and/or function as the original amino acid. In certain embodiments, an optimized polynucleotide sequence encoding an anti-3FTx-L antibody described herein or a fragment thereof (e.g., VL domain or VH domain) can hybridize to an antisense (e.g., complementary) polynucleotide of an unoptimized polynucleotide sequence encoding an anti-3FTx-L antibody described herein or a fragment thereof (e.g., VL domain or VH domain). In specific embodiments, an optimized nucleotide sequence encoding an anti-3FTx-L antibody described herein or a fragment hybridizes under high stringency conditions to antisense polynucleotide of an unoptimized polynucleotide sequence encoding an anti-3FTx-L antibody described herein or a fragment thereof. In a specific embodiment, an optimized nucleotide sequence encoding an anti-3FTx-L antibody described herein or a fragment thereof hybridizes under high stringency, intermediate or lower stringency hybridization conditions to an antisense polynucleotide of an unoptimized nucleotide sequence encoding an anti-3FTx-L antibody described herein or a fragment thereof. Information regarding hybridization conditions has been described, see, e.g., U.S. Patent Application Publication No. US 2005/0048549 (e.g., paragraphs 72-73), which is incorporated herein by reference. The polynucleotides can be obtained, and the nucleotide sequence of the polynucleotides determined, by any method known in the art. Nucleotide sequences encoding antibodies described herein, and modified versions of these antibodies can be determined using methods well known in the art, i.e., nucleotide codons known to encode particular amino acids are assembled in such a way to generate a nucleic acid that encodes the antibody. Such a polynucleotide encoding the antibody can be assembled from chemically synthesized oligonucleotides (e.g., as described in Kutmeier G et al., (1994), BioTechniques 17: 242-246), which, briefly, involves the synthesis of overlapping oligonucleotides containing portions of the sequence encoding the antibody, annealing and ligating of those oligonucleotides, and then amplification of the ligated oligonucleotides by PCR. Alternatively, a polynucleotide encoding an antibody or fragment thereof described herein can be generated from nucleic acid from a suitable source (e.g., PBMCs) using methods well known in the art (e.g., PCR and other molecular cloning methods). For example, PCR amplification using synthetic primers hybridizable to the 3' and 5' ends of a known sequence can be performed using genomic DNA obtained from hybridoma cells producing the antibody of interest. Such PCR amplification methods can be used to obtain nucleic acids comprising the sequence encoding the light chain and/or heavy chain of an antibody. Such PCR amplification methods can be used to obtain nucleic acids comprising the sequence encoding the variable light chain region and/or the variable heavy chain region of an antibody. The amplified nucleic acids can be cloned into vectors for expression in host cells and for further cloning, for example, to generate chimeric and humanized antibodies. If a clone containing a nucleic acid encoding a particular antibody or fragment thereof is not available, but the sequence of the antibody molecule or fragment thereof is known, a nucleic acid encoding the immunoglobulin or fragment can be chemically synthesized or obtained from a suitable source (e.g., an antibody cDNA library or a cDNA library generated from, or nucleic acid, preferably poly A+ RNA, isolated from, any tissue or cells expressing the antibody, such as hybridoma cells selected to express an antibody described herein) by PCR amplification using synthetic primers hybridizable to the 3' and 5' ends of the sequence or by cloning using an oligonucleotide probe specific for the particular gene sequence to identify, e.g., a cDNA clone from a cDNA library that encodes the antibody. Amplified nucleic acids generated by PCR can then be cloned into replicable cloning vectors using any method well known in the art. DNA encoding anti-3FTX_LCa antibodies described herein can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of the anti-3FTx-L). PBMCs can serve as a source of such DNA. Once isolated, the DNA can be placed into expression vectors, which are then transfected into host cells such as E. coli cells, simian COS cells, Chinese hamster ovary (CHO) cells (e.g., CHO cells from the CHO GS System™ (Lonza)), or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of anti-3FTx-L antibodies in the recombinant host cells. The DNA also can be modified, for example, by substituting the coding sequence for human heavy and light chain constant domains with a coding sequence for a non-immunoglobulin polypeptide, or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide. Also provided are polynucleotides that hybridize under high stringency, intermediate or lower stringency hybridization conditions to polynucleotides that encode an antibody described herein. In specific embodiments, polynucleotides described herein hybridize under high stringency, intermediate or lower stringency hybridization conditions to polynucleotides encoding a VH domain and/or VL domain provided herein. Hybridization conditions have been described in the art and are known to one of skill in the art. For example, hybridization under stringent conditions can involve hybridization to filter- bound DNA in 6x sodium chloride/sodium citrate (SSC) at about 45°C followed by one or more washes in 0.2xSSC/0.1% SDS at about 50-65°C; hybridization under highly stringent conditions can involve hybridization to filter-bound nucleic acid in 6xSSC at about 45°C followed by one or more washes in 0.1xSSC/0.2% SDS at about 68°C. Hybridization under other stringent hybridization conditions are known to those of skill in the art and have been described, see, for example, Ausubel FM et al., eds., (1989) Current Protocols in Molecular Biology, Vol. I, Green Publishing Associates, Inc. and John Wiley & Sons, Inc., New York at pages 6.3.1-6.3.6 and 2.10.3. IV. Vectors, Cells, and Methods of Producing a Neutralizing Agent In certain aspects, provided herein are cells (e.g., host cells) expressing (e.g., recombinantly) antibodies described herein which specifically bind to 3FTx-L and related polynucleotides and expression vectors. Provided herein are vectors (e.g., expression vectors) comprising polynucleotides comprising nucleotide sequences encoding anti-3FTx-L antibodies or a fragment thereof described herein. In some embodiments, the vectors can be used for recombinant expression of an antibody described herein in host cells (e.g., mammalian cells). In some embodiments, the vectors can be used for administration of an antibody described herein to a patient in need thereof. Also provided herein are host cells comprising such vectors for recombinantly expressing anti-3FTx-L antibodies described herein. In a particular aspect, provided herein are methods for producing an antibody described herein, comprising expressing such antibody in a host cell. In some embodiments, the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5. In certain aspects, provided herein is an isolated vector comprising a polynucleotide described herein. In some embodiments, the vector is a viral vector. In certain aspects, provided herein is a recombinant virus comprising a polynucleotide described herein. In some embodiments, the recombinant virus encodes an antibody described herein. In one embodiment, the recombinant virus encodes a bispecific antibody described herein. In one embodiment, the recombinant virus encodes a trispecific antibody described herein. In one embodiment, the recombinant virus encodes a multispecific antibody described herein. In one embodiment, the recombinant virus is a replication defective virus. Suitable replication defective viral vectors are known to those skilled in the art, for example, as disclosed in U.S. Pat. Nos. 7198784, 9408905, 9862931, 8067156, U.S. Pat. Appl. Pub. Nos. 20150291935, 20120220492, 20180291351, and 20170175137, each of which is incorporated herein by reference in its entirety. In one embodiment, the recombinant virus is a retrovirus or retroviral vector, for example, a lentivirus or lentiviral vector. In one embodiment, the recombinant virus is an adenovirus or adenoviral vector, HSV or HSV vector, or influenza virus or viral vector. In one embodiment, the recombinant virus is an adeno-associated virus (AAV). In one embodiment, the recombinant virus is for administration to a subject to treat snake bite. In one embodiment, the recombinant virus is an adeno-associated virus (AAV) for administration to a subject to treat snake bite. Recombinant AAV particles encoding an antibody that binds to 3FTx-L and methods for producing thereof are known to one skilled in the art, for example, as disclosed in US Patent 8,865,881 and US20190031740, each of which is incorporated by reference herein in its entirety for all purposes. See also, Lin and Balazs, Retrovirology 15:66 (2018) and van den berg et al., Molecular Therapy: methods & Clinical Development 14:100-112 (2019), each of which is incorporated by reference herein in its entirety for all purposes. In certain aspects, provided herein is a host cell comprising a polynucleotide described herein, or a vector described herein. In some embodiments, the vector encodes an antibody described herein. In some embodiments, a vector described herein comprises a first vector encoding a VH described herein and a second vector encoding a VL described herein. In some embodiments, a vector described herein comprises a first nucleotide sequence encoding a VH described herein and a second nucleotide sequence encoding a VL described herein. In some embodiments, the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5. In some embodiments, the host cell is selected from the group consisting of E. coli, Pseudomonas, Bacillus, Streptomyces, yeast, CHO, YB/20, NS0, PER-C6, HEK-293T, NIH-3T3, Helga, BHK, Hep G2, SP2/0, R1.1, B-W, L-M, COS 1, COS 7, BSC1, BSC40, BMT10 cell, plant cell, insect cell, and human cell in tissue culture. In some embodiments, the host cell is CHO. In certain aspects, provided herein is a method of producing an antibody that binds to 3FTx-L comprising culturing a host cell described herein so that the polynucleotide is expressed and the antibody is produced. In some embodiments, the method further comprises recovering the antibody. In some embodiments, the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5. The isolated polypeptides, i.e., anti-3FTx-L antibodies described herein can be produced by any suitable method known in the art. Such methods range from direct protein synthetic methods to constructing a DNA sequence encoding isolated polypeptide sequences and expressing those sequences in a suitable transformed host. In some embodiments, a DNA sequence is constructed using recombinant technology by isolating or synthesizing a DNA sequence encoding a wild-type protein of interest. Optionally, the sequence can be mutagenized by site-specific mutagenesis to provide functional analogs thereof. See, e.g., Zoeller et al., Proc. Nat'l. Acad. Sci. USA 81:5662- 5066 (1984) and U.S. Pat. No.4,588,585. In some embodiments a DNA sequence encoding a polypeptide of interest would be constructed by chemical synthesis using an oligonucleotide synthesizer. Such oligonucleotides can be designed based on the amino acid sequence of the desired polypeptide and selecting those codons that are favored in the host cell in which the recombinant polypeptide of interest will be produced. Standard methods can be applied to synthesize an isolated polynucleotide sequence encoding an isolated polypeptide of interest. For example, a complete amino acid sequence can be used to construct a back-translated gene. Further, a DNA oligomer containing a nucleotide sequence coding for the particular isolated polypeptide can be synthesized. For example, several small oligonucleotides coding for portions of the desired polypeptide can be synthesized and then ligated. The individual oligonucleotides typically contain 5' or 3' overhangs for complementary assembly. Once assembled (by synthesis, site-directed mutagenesis or another method), the polynucleotide sequences encoding a particular isolated polypeptide of interest will be inserted into an expression vector and operatively linked to an expression control sequence appropriate for expression of the protein in a desired host. Proper assembly can be confirmed by nucleotide sequencing, restriction mapping, and expression of a biologically active polypeptide in a suitable host. As is well known in the art, in order to obtain high expression levels of a transfected gene in a host, the gene must be operatively linked to transcriptional and translational expression control sequences that are functional in the chosen expression host. In certain embodiments, recombinant expression vectors are used to amplify and express DNA encoding antibodies or fragments thereof. Recombinant expression vectors are replicable DNA constructs which have synthetic or cDNA-derived DNA fragments encoding a polypeptide chain of an antibody or fragment thereof operatively linked to suitable transcriptional or translational regulatory elements derived from mammalian, microbial, viral or insect genes. A transcriptional unit generally comprises an assembly of (1) a genetic element or elements having a regulatory role in gene expression, for example, transcriptional promoters or enhancers, (2) a structural or coding sequence which is transcribed into mRNA and translated into protein, and (3) appropriate transcription and translation initiation and termination sequences. Such regulatory elements can include an operator sequence to control transcription. The ability to replicate in a host, usually conferred by an origin of replication, and a selection gene to facilitate recognition of transformants can additionally be incorporated. DNA regions are operatively linked when they are functionally related to each other. For example, DNA for a signal peptide (secretory leader) is operatively linked to DNA for a polypeptide if it is expressed as a precursor which participates in the secretion of the polypeptide; a promoter is operatively linked to a coding sequence if it controls the transcription of the sequence; or a ribosome binding site is operatively linked to a coding sequence if it is positioned so as to permit translation. Structural elements intended for use in yeast expression systems include a leader sequence enabling extracellular secretion of translated protein by a host cell. Alternatively, where recombinant protein is expressed without a leader or transport sequence, it can include an N-terminal methionine residue. This residue can optionally be subsequently cleaved from the expressed recombinant protein to provide a final product. The choice of expression control sequence and expression vector will depend upon the choice of host. A variety of host-expression vector systems can be utilized to express antibody molecules described herein (see, e.g., U.S. Patent No. 5,807,715). Such host-expression systems represent vehicles by which the coding sequences of interest can be produced and subsequently purified, but also represent cells which can, when transformed or transfected with the appropriate nucleotide coding sequences, express an antibody molecule described herein in situ. These include but are not limited to microorganisms such as bacteria (e.g., E. coli and B. subtilis) transformed with recombinant bacteriophage DNA, plasmid DNA or cosmid DNA expression vectors containing antibody coding sequences; yeast (e.g., Saccharomyces Pichia) transformed with recombinant yeast expression vectors containing antibody coding sequences; insect cell systems infected with recombinant virus expression vectors (e.g., baculovirus) containing antibody coding sequences; plant cell systems (e.g., green algae such as Chlamydomonas reinhardtii) infected with recombinant virus expression vectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) or transformed with recombinant plasmid expression vectors (e.g., Ti plasmid) containing antibody coding sequences; or mammalian cell systems (e.g., COS (e.g., COS1 or COS), CHO, BHK, MDCK, HEK 293, NS0, PER.C6, VERO, CRL7O3O, HsS78Bst, Helga, and NIH 3T3, HEK-293T, HepG2, SP210, R1.1, B-W, L-M, BSC1, BSC40, YB/20 and BMT10 cells) harboring recombinant expression constructs containing promoters derived from the genome of mammalian cells (e.g., metallothionein promoter) or from mammalian viruses (e.g., the adenovirus late promoter; the vaccinia virus 7.5K promoter). In a specific embodiment, cells for expressing antibodies described herein are CHO cells, for example CHO cells from the CHO GS System™ (Lonza). In a particular embodiment, cells for expressing antibodies described herein are human cells, e.g., human cell lines. In a specific embodiment, a mammalian expression vector is pOptiVEC™ or pcDNA3.3. In a particular embodiment, bacterial cells such as Escherichia coli, or eukaryotic cells (e.g., mammalian cells), especially for the expression of whole recombinant antibody molecule, are used for the expression of a recombinant antibody molecule. For example, mammalian cells such as Chinese hamster ovary (CHO) cells in conjunction with a vector such as the major intermediate early gene promoter element from human cytomegalovirus is an effective expression system for antibodies (Foecking MK & Hofstetter H (1986) Gene 45: 101-105; and Cockett MI et al., (1990) Biotechnology 8: 662-667). In certain embodiments, antibodies described herein are produced by CHO cells or NS0 cells. In a specific embodiment, the expression of nucleotide sequences encoding antibodies described herein which immunospecifically bind 3FTx- L is regulated by a constitutive promoter, inducible promoter or tissue specific promoter. For applications where it is desired that the antibodies described herein be expressed in vivo, for example in a subject in need of treatment with an antibody described herein, any vector that allows for the expression of the antibodies and is safe for use in vivo may be used. In some embodiments, the vector is a viral vector. Viral vectors can include poxvirus (vaccinia), including vaccinia Ankara and canarypox; adenoviruses, including adenovirus type 5 (Ad5); rubella; Sendai virus; rhabdovirus; alphaviruses; and adeno-associated viruses. In some embodiments, the viral vector is an adeno-associated virus. Alternatively, a polynucleotide encoding the antibody could be delivered as DNA or RNA to the subject for in vivo expression of the antibody. Suitable host cells for expression of a polypeptide of interest such as an antibody described herein include prokaryotes, yeast, insect or higher eukaryotic cells under the control of appropriate promoters. Prokaryotes include gram negative or gram positive organisms, for example E. coli or bacilli. Higher eukaryotic cells include established cell lines of mammalian origin. Cell-free translation systems could also be employed. Appropriate cloning and expression vectors for use with bacterial, fungal, yeast, and mammalian cellular hosts are described by Pouwels et al. (Cloning Vectors: A Laboratory Manual, Elsevier, N.Y., 1985), the relevant disclosure of which is hereby incorporated by reference. Additional information regarding methods of protein production, including antibody production, can be found, e.g., in U.S. Patent Publication No. 2008/0187954, U.S. Patent Nos.6,413,746 and 6,660,501, and International Patent Publication No. WO 04009823, each of which is hereby incorporated by reference herein in its entirety. Various mammalian or insect cell culture systems are also advantageously employed to express a recombinant protein such as an antibody described herein. Expression of recombinant proteins in mammalian cells can be performed because such proteins are generally correctly folded, appropriately modified and completely functional. Examples of suitable mammalian host cell lines include but are not limited to CHO, VERO, BHK, Hela, MDCK, HEK 293, NIH 3T3, W138, BT483, Hs578T, HTB2, BT2O and T47D, NS0 (a murine myeloma cell line that does not endogenously produce any immunoglobulin chains), CRL7O3O, COS (e.g., COS1 or COS), PER.C6, VERO, HsS78Bst, HEK-293T, HepG2, SP210, R1.1, B-W, L-M, BSC1, BSC40, YB/20, BMT10 and HsS78Bst cells. Mammalian expression vectors can comprise nontranscribed elements such as an origin of replication, a suitable promoter and enhancer linked to the gene to be expressed, and other 5' or 3' flanking nontranscribed sequences, and 5' or 3' nontranslated sequences, such as necessary ribosome binding sites, a polyadenylation site, splice donor and acceptor sites, and transcriptional termination sequences. Baculovirus systems for production of heterologous proteins in insect cells are reviewed by Luckow and Summers, Bio/Technology 6:47 (1988). The proteins produced by a transformed host can be purified according to any suitable method. Such standard methods include chromatography (e.g., ion exchange, affinity and sizing column chromatography), centrifugation, differential solubility, or by any other standard technique for protein purification. Affinity tags such as hexahistidine, maltose binding domain, influenza coat sequence and glutathione-S-transferase can be attached to the protein to allow easy purification by passage over an appropriate affinity column. Isolated proteins can also be physically characterized using such techniques as proteolysis, nuclear magnetic resonance and x-ray crystallography. For example, supernatants from systems which secrete recombinant protein, e.g., an antibody, into culture media can be first concentrated using a commercially available protein concentration filter, for example, an Amicon or Millipore Pellicon ultrafiltration unit. Following the concentration step, the concentrate can be applied to a suitable purification matrix. Alternatively, an anion exchange resin can be employed, for example, a matrix or substrate having pendant diethylaminoethyl (DEAE) groups. The matrices can be acrylamide, agarose, dextran, cellulose or other types commonly employed in protein purification. Alternatively, a cation exchange step can be employed. Suitable cation exchangers include various insoluble matrices comprising sulfopropyl or carboxymethyl groups. Finally, one or more reversed-phase high performance liquid chromatography (RP-HPLC) steps employing hydrophobic RP-HPLC media, e.g., silica gel having pendant methyl or other aliphatic groups, can be employed to further an agent. Some or all of the foregoing purification steps, in various combinations, can also be employed to provide a homogeneous recombinant protein. Recombinant protein produced in bacterial culture can be isolated, for example, by initial extraction from cell pellets, followed by one or more concentration, salting-out, aqueous ion exchange or size exclusion chromatography steps. High performance liquid chromatography (HPLC) can be employed for final purification steps. Microbial cells employed in expression of a recombinant protein can be disrupted by any convenient method, including freeze-thaw cycling, sonication, mechanical disruption, or use of cell lysing agents. Methods known in the art for purifying antibodies and other proteins also include, for example, those described in U.S. Patent Publication Nos. 2008/0312425, 2008/0177048, and 2009/0187005, each of which is hereby incorporated by reference herein in its entirety. In specific embodiments, an antibody described herein is isolated or purified. Generally, an isolated antibody is one that is substantially free of other antibodies with different antigenic specificities than the isolated antibody. For example, in a particular embodiment, a preparation of an antibody described herein is substantially free of cellular material and/or chemical precursors. The language "substantially free of cellular material" includes preparations of an antibody in which the antibody is separated from cellular components of the cells from which it is isolated or recombinantly produced. Thus, an antibody that is substantially free of cellular material includes preparations of antibody having less than about 30%, 20%, 10%, 5%, 2%, 1%, 0.5%, or 0.1% (by dry weight) of heterologous protein (also referred to herein as a "contaminating protein") and/or variants of an antibody, for example, different post-translational modified forms of an antibody. When the polypeptide (e.g., antibody described herein) is recombinantly produced, it is also generally substantially free of culture medium, i.e., culture medium represents less than about 20%, 10%, 2%, 1%, 0.5%, or 0.1% of the volume of the protein preparation. When the polypeptide (e.g., antibody described herein) is produced by chemical synthesis, it is generally substantially free of chemical precursors or other chemicals, i.e., it is separated from chemical precursors or other chemicals which are involved in the synthesis of the protein. Accordingly, such preparations of the polypeptide (e.g., antibody described herein) have less than about 30%, 20%, 10%, or 5% (by dry weight) of chemical precursors or compounds other than the polypeptide of interest. In some embodiments, antibodies described herein are isolated or purified. V. Pharmaceutical Compositions Compositions comprising the antibodies or antigen-binding fragments described herein are also provided. Further provided herein are compositions comprising a polynucleotide or polynucleotides encoding the antibodies or antigen-binding fragments described herein. In some embodiments, the polynucleotide comprises mRNA. In some embodiments, the composition is a pharmaceutical composition. In some embodiments, the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5. In some embodiments, the composition is a lyophilized composition. In some embodiments, the composition is a liquid composition. In some embodiments, the composition is formulated for topical administration, and in certain embodiments the composition is formulated for vaginal or rectal administration. In certain aspects, provided herein is a pharmaceutical composition comprising an antibody described herein and a pharmaceutically acceptable excipient. In some embodiments, the antibody is an intact antibody. In some embodiments, the antibody is an antigen binding antibody fragment. In some embodiments, the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5. In another embodiment, the disclosure provides a pharmaceutical composition comprising an antibody described herein. In some embodiments, the pharmaceutical composition further comprises a second antibody, wherein the second antibody is capable of binding at least one toxic component of snake venom in addition to 3FTx-L. In some embodiments, the at least one toxic component of snake venom in addition to 3FTx-L comprises a metalloprotease or a phospholipase. In some embodiments, the pharmaceutical composition further comprises a second antibody, wherein the second antibody is capable of binding and neutralizing at least two snake venom metalloprotease variants. In some embodiments, the pharmaceutical composition further comprises a second antibody, wherein the second antibody is capable of binding and neutralizing at least two snake venom phospholipase variants. Such compositions are intended for treatment of a snake bite. In further embodiments of the present disclosure, a composition comprising the antibody described herein can additionally be combined with other compositions for the treatment of snake bite. In some embodiments, an antibody described herein may be administered within a pharmaceutically-acceptable diluent, carrier, or excipient, in unit dose form. Conventional pharmaceutical practice may be employed to provide suitable formulations or compositions to administer to individuals being treated for snake bite. Any appropriate route of administration may be employed, for example, administration may be parenteral, intravenous, intra-arterial, subcutaneous, intramuscular, intraperitoneal, intranasal, aerosol, suppository, oral administration, vaginal, or anal. The pharmaceutical compositions described herein are prepared in a manner known per se, for example, by means of conventional dissolving, lyophilizing, mixing, granulating or confectioning processes. The pharmaceutical compositions may be formulated according to conventional pharmaceutical practice (see for example, in Remington: The Science and Practice of Pharmacy (21st ed.), ed. A.R. Gennaro, 2005, Lippincott Williams & Wilkins, Philadelphia, PA, and Encyclopedia of Pharmaceutical Technology, eds. J. Swarbrick and J. C. Boylan, 2013, Marcel Dekker, New York, NY). The injection compositions are prepared in customary manner under sterile conditions; the same applies also to introducing the compositions into ampoules or vials and sealing the containers. Pharmaceutical compositions according to the invention may be, for example, in unit dose form, such as in the form of ampoules, vials, suppositories, tablets, pills, or capsules. The formulations can be administered to human individuals in therapeutically or prophylactic effective amounts (e.g., amounts which prevent, eliminate, or reduce a pathological condition) to provide therapy for a disease or condition. The preferred dosage of therapeutic agent to be administered is likely to depend on such variables as the type and extent of the disorder, the overall health status of the particular patient, the formulation of the compound excipients, and its route of administration. VI. Therapeutic Uses and Methods In one aspect, provided herein is a method of treating a snake bite, comprising administering to a subject in need thereof an effective amount of an antibody described herein (e.g., a bispecific or multispecific antibody), a pharmaceutical composition described herein, an isolated polynucleotide described herein, or a recombinant virus described herein (e.g., recombinant AAV). In some embodiments, the method comprises administering to a subject in need thereof an effective amount of an antibody described herein. In some embodiments, the subject has suffered a snake bite. In some embodiments, the subject is at risk of being exposed to snake bite. In some embodiments, the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5. Further provided herein is a method of passive immunization comprising administering to a subject in need thereof an effective amount of an antibody described herein (e.g., a bispecific or multispecific antibody), a pharmaceutical composition described herein, an isolated polynucleotide described herein, or a recombinant virus described herein (e.g., recombinant AAV). In some embodiments, the method comprises administering to a subject in need thereof an effective amount of an antibody described herein. In some embodiments, the subject is at risk of being bitten by a snake. In some embodiments, the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5. Further provided herein is a method of neutralizing 3FTx-L comprising contacting the toxin with an effective amount of an antibody described herein. In one embodiment, the antibody is a multispecific, such as bispecific antibody. In some embodiments of a method described herein, the antibody can be a chimeric antibody, engineered antibody, recombinant antibody, or a monoclonal antibody described herein. In some embodiments, the antibody is a full antibody, an F(ab) fragment, or an F(ab)2 fragment described herein. In a specific embodiment, the antibody is an engineered monoclonal antibody described herein. In a specific embodiment, the antibody is a recombinant monoclonal antibody described herein. In a specific embodiment, the antibody is a chimeric monoclonal antibody described herein. In a specific embodiment, the antibody is an F(ab) described herein. In a specific embodiment, the antibody is an F(ab')2 fragment described herein. In some embodiments, the administering to the subject is by at least one mode selected from oral, parenteral, subcutaneous, intramuscular, and intravenous. In some embodiments, the administering to the subject is by at least one mode selected from vaginal, rectal, buccal, sublingual, and transdermal In some embodiments, a method of treatment described herein further comprises administering at least one additional therapeutic agent. In some embodiments, the additional therapeutic agent comprises an anti-toxin. In some embodiments, the additional therapeutic agent comprises a second monoclonal antibody capable of neutralizing a toxic component of venom. In some embodiments, the additional therapeutic agent comprises a second monoclonal antibody capable of neutralizing a snake venom metalloprotease or a phospholipase. In some embodiments, the additional therapeutic agent comprises a second monoclonal antibody capable of neutralizing at least two snake venom metalloprotease variants or phospholipase variants. In some embodiments, the additional therapeutic agent comprises a second monoclonal antibody capable of neutralizing at least two snake venom metalloprotease variants. In some embodiments, the additional therapeutic agent comprises a second monoclonal antibody capable of neutralizing at least two snake venom phospholipase variants. In some embodiments, the additional therapeutic agent comprises a second monoclonal antibody capable of neutralizing a different neurotoxin, a cytotoxin, a cardiotoxin, a hemotoxin, or a myotoxin. The amount of an antibody described herein, or a pharmaceutical composition described herein which will be effective in the treatment and/or prevention of a condition will depend on the nature of the disease, and can be determined by standard clinical techniques. The precise dose to be employed in a pharmaceutical composition will also depend on the route of administration, and the seriousness of the disease, and should be decided according to the judgment of the practitioner and each subject's circumstances. For example, effective doses may also vary depending upon means of administration, target site, physiological state of the patient (including age, body weight and health), whether the patient is human or an animal, other medications administered, or whether treatment is prophylactic or therapeutic. Usually, the patient is a human but non-human mammals including transgenic mammals can also be treated. Treatment dosages are optimally titrated to optimize safety and efficacy. In certain embodiments, an in vitro assay is employed to help identify optimal dosage ranges. Effective doses may be extrapolated from dose response curves derived from in vitro or animal model test systems. VII. Kits Provided herein are kits comprising one or more antibodies described herein. In some embodiments, a pharmaceutical pack or kit described herein comprises one or more containers filled with one or more of the ingredients of the pharmaceutical compositions described herein, such as one or more antibodies described herein. In some embodiments, a kit contains an antibody described herein or a pharmaceutical composition described herein, and a second prophylactic or therapeutic agent used in the treatment of snake bites. In some embodiments, the second agent is an anti-toxin. In some embodiments, a kit contains an antibody described herein or a pharmaceutical composition described herein, and a reagent used in the detection of 3FTx-L. Optionally associated with such container(s) can be a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals or biological products, which notice reflects approval by the agency of manufacture, use or sale for human administration. In some embodiments, the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5. In some embodiments, a kit described herein comprises an antibody described herein, or a pharmaceutical composition described herein and a notice that reflects approval for use or sale for human administration, or d) any combination thereof. In some embodiments, the antibody comprises the VH and VL of LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5, or 95MAT6. In some embodiments, the antibody comprises the VH and VL of LB5_95. In some embodiments, the antibody comprises the VH and VL of 95MAT5. Embodiments of the present disclosure can be further defined by reference to the following non-limiting examples, which describe in detail preparation of certain antibodies of the present disclosure and methods for using antibodies of the present disclosure. It will be apparent to those skilled in the art that many modifications, both to materials and methods, can be practiced without departing from the scope of the present disclosure. All documents, patent, and patent applications cited herein are hereby incorporated by reference, and may be employed in the practice described herein. EXAMPLES Example 1. Isolation of cross-reactive human monoclonal antibodies that bind and neutralize multiple variants of long chain alpha-neurotoxic three finger toxins. Snakebite envenoming is estimated to cause 81,000-138,000 deaths annually, with an additional 400,000 or more people left with permanent disabilities (R1). The impact is particularly severe in low- and middle-income countries in Africa and Asia due to the alarmingly large number of snakebites and limited access to modern medical resources. These significant global public health costs warranted the designation of snakebite as a neglected tropical disease by the World Health Organization (WHO) in 2018 (R2). Animal-derived polyclonal antibody-based antivenom therapy is the primary medical countermeasure used to treat snakebites and has been in use for over a century. Currently available antivenoms are produced by the hyperimmunization of large animals (e.g., equines and ovines) until they produce a robust anti-venom antibody response. From there, polyclonal immunoglobulins (IgGs) are purified, sometimes processed into antibody fragments (F(ab’)2 or Fabs), and formulated for intravenous delivery to snakebite victims (R3). A high-quality antivenom matched to the biting snake species is effective at reducing morbidity and mortality. However, in practice, several antivenoms have significant problems with their safety, efficacy, potency, cost, and distribution (R4, 5). The immunogenicity of the heterologous proteins and impurities present in antivenoms can induce serum sickness and severe anaphylaxis (R6). Furthermore, only a fraction of the antibodies therapeutically target the venom toxins, thus requiring large doses of a product with high batch-to-batch variability and limited shelf life to effect a cure (R7, 8). Development of effective antivenom is challenging, as venoms are complex mixtures with multiple classes and isoforms of toxic proteins that exhibit highly diverse structures, functions, biological targets, and compositions between snakes (R1, 9). Three-finger toxins (3FTx) are among the most abundant and lethal toxins present in the venom of elapids, a major medically relevant family of venomous snakes that includes cobras, kraits, and mambas (R10). Despite their structural similarity, 3FTxs exhibit significant antigenic and functional diversity and, thus, are categorized into various subfamilies (R11). The α-neurotoxin class of 3FTx targets the muscle-type nicotinic acetylcholine receptor (nAChR) at neuromuscular junctions, leading to paralysis and death via asphyxiation (R12). Since α-neurotoxins are abundantly produced by a wide range of elapid species, they are considered key targets for antivenom development (R12). The α-neurotoxins are further categorized into short-chain (3FTx-S) and long-chain (3FTx-L) variants based on their sequence length (R11). One of the primary challenges in the development of targeted therapy is the significant antigenic diversity within a given toxin class. Elapid α-neurotoxins have been documented to evolve under a strong influence of positive selection, resulting in considerable sequence diversity even across closely related species (R10). In practice, this toxin variant diversity has resulted in antivenoms that are relatively species-specific, prompting manufacturers to immunize animals with venoms from multiple species of medically relevant snakes to expand the functional breadth of coverage (R9), but in doing so, generating a need for higher therapeutic doses due to reduced dose efficacy (R13). Many of the current safety, efficacy and reproducibility limitations with animal- derived polyclonal antivenoms could be addressed with the development of a recombinant antibody cocktail (R14). Of late, many studies have demonstrated the effectiveness of monoclonal antibodies (mAbs) or nanobodies (Nbs) in neutralizing a particular snake venom toxin to protect envenomed experimental animals (R15-22). However, like the animal-derived polyclonal antivenoms, nearly all the mAbs and Nbs reported to date have a narrow breadth of coverage outside the initial target venom. Thus, a broad-spectrum recombinant antivenom would require an unrealistic number of antibodies to cover the multiple toxin variants found across diverse snake species. Despite the large amount of overall antigenic diversity within a toxin class, the functionally active region of the protein tends to be highly conserved to preserve functionality (R23). It was hypothesized that the development of antibodies targeting these functionally conserved regions could achieve two objectives: 1) broad recognition across a toxin class and 2) disruption of toxin functionality. Broadly neutralizing antibodies (bnAbs) are well studied in the field of viral infections, most notably HIV, and strategies have been developed to isolate these highly desirable but extremely rare bnAbs from the abundant strain-specific antibodies (R24-26). Described herein is the discovery, optimization, and characterization of a broadly neutralizing 3FTx-L antibody that demonstrated protective efficacy against lethal venom challenge in mice from a range of medically relevant snakes. The project workflow provides a generalizable strategy for discovering antibodies that target conserved sites on antigenically variable proteins. The key features of the platform include selecting and recombinantly producing toxin baits, using a synthetic yeast display library, and analyzing antibody cross-reactivity through parallel selections and deep sequencing. The utilization of recombinantly produced toxins allowed for a high level of control over antigenic variability and bypassed the need to purify the necessary toxins from multiple snake species. The antibody selections from a synthetic library are driven by affinity, overcoming some of the challenges in eliciting robust antibody responses against monomeric, low molecular weight toxins that are often poorly immunogenic. Lastly, the antibodies recovered from this library are fully human and will lack the same immunogenic side effects as current animal- derived antivenoms. In vivo protection studies revealed the cross-neutralization potential of 95Mat5, which not only protected against purified ⍺-bungarotoxin (B. multicinctus, krait), but also completely neutralized the neurotoxin-rich whole venoms of N. kaouthia (cobra) and D. polylepis (mamba), and prolonged animal survival against O. hannah (king cobra). The inability of 95Mat5 to fully protect against O. hannah venom could be attributed to this venom’s complexity, being enriched with high proportions of various α-neurotoxin variants, in addition to other 3FTxs and non-3FTx components (R35). Structural characterization of 95Mat5 in complex with 3FTx-L15 revealed that the antibody mimics the binding mode of nAChR to the toxin. Receptor mimicry is commonly observed in antiviral bnAbs (R24, 36), as the receptor recognition site of the viral Env protein tends to be both highly conserved and critical for viral entry. Given the parallels here, it is not surprising that bnAbs against 3FTx-L adopted a similar strategy, however, it was striking that this solution was shared across all 3FTx-L bnAbs. After screening the naive library, which contained over 60 billion unique antibodies, only 16 antibodies were recovered that bound all the toxins in the panel. All the cross-reactive antibodies utilized a 19 or 20 AA CDRH3 loop containing the R[W/Y]YxxGxY (SEQ ID NO: 244 and 245) motif, suggesting that the experiment did not recover 16 unique specificities, but that all the mAbs likely utilize the same overall mode of binding. This result matches previous findings with bnAbs against HIV and influenza, where nearly identical antibodies are recovered from multiple donors (R37, 38), suggesting that there are a limited number of approaches to achieve broad recognition. Although 95Mat5 demonstrated successful protection of mice against lethal venom challenge from diverse snake species, it should be emphasized that this antibody alone does not constitute the definitive product for universal snake antivenom development. As snake venom is a complex cocktail of toxins, it necessitates the inclusion of broadly cross-reactive antibodies against several additional major venom classes, including short-chain 3FTx and phospholipase in elapids, and metalloproteinase and serine protease in viperids (R1). Therefore, a final universal antivenom may encompass a minimum of four to five antibodies to effectively cover the additional venom classes. However, the discovery and development of 95Mat5 is an important first step, as it effectively neutralizes one of the most diverse and toxic components of the venom. Moreover, this research presents an adjustable blueprint for generating antibodies that target a broad range of antigenically diverse components, providing a valuable framework for the development of additional antivenom antibodies. Development and validation of cross-reactive 3FTx antibodies Sixteen 3FTx-L variants from a diverse range of medically relevant African and Asian elapid snakes were recombinantly expressed in mammalian cells as candidates for antibody isolation and/or downstream characterization (Table 4). These variants exhibited a broad range of antigenic diversity, with as low as 47% paired sequence identity but with two highly conserved regions: the disulphide core and the second loop that is principally responsible for nAChR binding (R12) (Fig 1A). From these 16 candidates, a smaller panel of eight functional variants was selected to capture overall antigenic diversity and prioritize variants with available published structures (Fig 1B-C, Fig 6). Recombinant 3FTx-L variants used in the antibody isolation campaign were confirmed to bind the human nAChR⍺1 subunit displayed on the surface of yeast and demonstrated antagonism of the acetylcholine-induced activation of human muscle-type nAChR expressed in TE671 cells (Fig 7). Table 4. List of recombinant 3FTx-L variants synthesized and tested for nAChR⍺1 binding. UniProt and PDB accession numbers are provided along with any names associated with the toxin variants, snake species and geographic regions. The half-maximal inhibitory concentration (IC50) measured from the curves in Fig 7 for binding to yeast-displayed human nAChR⍺1 subunit is indicated for each variant. DNB = did not bind. Variant Accession Othe nACR⍺1 name r name Species Region IC50
Figure imgf000107_0001
, . 3FTx-L3 C0HJD7, 4LFT Alpha-elapitoxin-Dpp2d Dendroaspis polylepis s E oa us tt he c re nnt Ara fl ri & 781 nM ca 3FTx-L5 P01391, 2CTX, Alpha-cobrat Naja kaouthia, Naja 4AEA oxin siamensis Southeastern Asia 42 nM 3FTx-L6 P01390 Neurotoxin alpha Naja nivea Southern Africa 81 nM 3FTx-L8 A1IVR9 Alpha-elapitoxin-Bc2b Bungarus candidus Southern Asia 0.21 nM 3FTx-L9 P01393 Alpha-elapitoxin-Djk2a Dendroaspis jamesoni West central Africa 49 nM 3FTx-L10 P01389 Toxin III Naja anchietae South central Africa 779 nM 3FTx-L11 P01383 Neurotoxin 3.9.4 Naja melanoleuca West central Africa DNB 3FTx-L13 O42257 Long neurotoxin 7 Naja sputatrix Indonesia 122 nM 3FTx-L14 1NTN Neurotoxin 1 Naja oxiana Central Asia DNB 3FTx-L15 P01386, 1TXA Toxin B Ophiophagus hannah Southeastern Asia 113 nM 3FTx-L17 P01395 Alpha-elapitoxin-Dv2a Dendroaspis viridis Western Africa 15 nM 3FTx-L18 P01388 Neurotoxin B Naja melanoleuca West central Africa 162 nM 3FTx-L21 P25674 Toxin CM-5 Naja haje Northern Africa 11 nM 3FTx-L22 P34074 Long neurotoxin 1 Naja annulata West central Africa 106 nM Antibodies against the 3FTx-L variants were isolated from a synthetic human library containing 6x1010 unique antibodies displayed as Fabs on the surface of Saccharomyces cerevisiae. To efficiently sample the diversity of the library, a dual approach of magnetic-activated cell sorting (MACS) followed by fluorescence-activated cell sorting (FACS) was employed to isolate clones with high affinity and specificity (Fig 1D, Fig 8). Following each selection, the enriched cells were expanded and induced for further rounds of selection. A subset of these cells was reserved for deep sequencing analysis. Two rounds of MACS were performed using 3FTx-L2 and 3FTx-L3 as pooled baits to bulk-enrich anti-3FTx-L reactive Fabs from the naive library. The enriched cells were then subjected to five rounds of FACS: two rounds using decreasing concentrations of 3FTx-L2 to enrich high-affinity clones, interspersed with two rounds of negative selections using detergent- solubilized membrane proteins to deplete sticky clones (Fig 9). Following this fourth round of FACS, all cells displayed affinity for 3FTx-L2 and exhibited minimal off-target specificity. To identify broadly cross-reactive Fabs, the library was split into five fractions and screened each against a different 3FTx-L variant to identify the subset of binding Fabs (Fig 1D, Fig 8). At the conclusion of these selections, cells recovered from each round of FACS were harvested, and the Fab-encoding portions of the plasmids were deep sequenced. In total, 3873 unique Fab sequences that were enriched for binding 3FTx-L2 were observed. The overall composition of these Fabs was still relatively diverse, with a slight preference for VH1 and no VL bias (Fig 1E, 1F), however, a notable shift towards 20 amino acid (AA) CDRH3 loops was observed (Fig 1G). The parallel selections with 3FTx-L variants showed a strong correlation between percent identity to 3FTx-L2 and cross-reactivity.3FTx-L1, sharing 85% identity with 3FTx-L2, bound 42% of the L2-binding Fabs. The more antigenically distant variants, 3FTx-L3, L5, and L6 (50-54% identity to L2), cross-reacted with only 3.3%, 6.2% and 6.6% of Fabs that bound 3FTx-L2, respectively (Fig 1H). In total, 52 Fabs (1.3%) were observed to bind all five 3FTx-L variants (Fig 1I). A 71% majority of cross-reactive Fabs utilized a 20 AA CDRH3 loop (Fig 1G). Examination of this subset showed a predominant R[W/Y]YxxGxY motif (SEQ ID NO: 244 and 245) (Fig 1J), suggesting that the breadth of reactivity was achieved through a conserved mode of binding. A total of 30 Fabs that were highly enriched in the cross-reactive deep sequencing datasets were selected for validation. The Fabs were reformatted as human IgG and screened for binding to 3FTx-L variants and for polyreactivity via ELISA. Sixteen of these antibodies bound to all five 3FTx-L variants without reactivity on a polyspecific reagent (PSR). These antibodies were primarily VH1 HC, and all had long (19-20 residue) CDRH3s, with several displaying the conserved R[W/Y]YxxGxY motif (SEQ ID NO: 244 and 245) (Fig 2A, Table 2). Toxin binding was further validated via surface plasmon resonance (SPR) with a panel of seven 3FTx-L variants (Fig 2B). The antibodies were also evaluated for neutralization of nAChR antagonism by the native 3FTx-L α-bungarotoxin using TE671 cells (Fig 2C). Antibody clone LB5_95 was among the most potent neutralizing antibodies and had the highest affinity across all recombinant variants, thus was chosen as the lead candidate for affinity maturation. Table 2: CDR sequences of cross-reactive mAbs. The variable domain genes for the heavy chain (HC) and light chain (LC) are listed for each cross-reactive mAb along with the SEQ ID NO for the 6 CDR, HV and VL sequences. mAb HC LC 1 2 3 H H H 1 L 2 3 VH VL R L L R R R R R D D D D D D 8 8 8 8 8 8 8 8 8 8 8
Figure imgf000109_0001
LB5_91 VH1-02 VK3-20 121 122 123 124 125 126 127 128 or 1 2 8 8 8
Figure imgf000110_0001
_ gy (R27), adapted for multistate optimization. Initial sorting of the separate heavy chain (HC) and light chain (LC) libraries was performed with both 3FTx-L2 and 3FTx-L3 to maintain cross-reactivity while also decreasing antigen concentrations in successive sorts to select for affinity (Fig 10). The final sorts were performed in parallel with 5 variants (3FTx-L2, L3, L5, L8 & L15) at sub-nanomolar concentrations or with competition sorting (R28). Deep sequencing analysis of the most broadly enriched clones revealed a highly prevalent aspartic or glutamic acid substituted for alanine in the CDR-L2 (Fig 2D). Six highly enriched clones were selected for evaluation, expressed well and showed increased affinity to most of the 3FTx-L variants (Fig 11A, Table 3). Antibody clone 95Mat5 displayed affinity gains across all seven 3FTx-L variants, primarily due to decreased dissociation rates (Fig. 2E) and had a favorable biochemical profile (Fig 11B-E). 95Mat5 was further evaluated for blocking of 3FTx-L binding to yeast-displayed nAChR⍺1 and exhibited inhibition against all variants tested (Fig 2F). Additionally, 95Mat5 demonstrated enhanced functional neutralization of nAChR antagonism in TE671 cells by both native α-bungarotoxin and recombinant 3FTx-L variants (Fig 2G). Table 3: CDR sequences of cross-reactive mAbs. The variable domain genes for the heavy chain (HC) and light chain (LC) are listed for each cross-reactive mAb along with the SEQ ID NO for the 6 CDR, HV and VL sequences. mAb 1 2 3 H H H 1 L 2 L 3 L VH VL 3 1 9
Figure imgf000110_0002
95Mat4 220 221 222 223 224 225 226 227 95Mat5 228 229 230 231 232 233 234 235 3 To
Figure imgf000111_0001
ider range of 3FTx- L variants and against other classes of 3FTx, a yeast display library containing 8283FTx variants was constructed, sorted via FACS with 95Mat5, and deep sequenced. The final sort showed exclusive enrichment with 753FTx-L variants (Fig 3A), with SPR-validated 3FTx-L8 at the end of the deep sequencing ranking (Fig 3B). Other 3FTx-L variants at the binding threshold of the final sorts were synthesized and validated for 95Mat5-binding via ELISA, whereas three 3FTx-S variants that were enriched in the first 2 sorts failed to either express or bind 95Mat5 when tested (Fig 12). A diverse range of 36 elapid species from 15 genera was represented in the 95Mat5- binding set of 3FTx-L variants and spread to geographic regions and alignment nodes that were not encompassed by the characterization panel of 3FTx-L variants (Fig 3C, Table 5). Collectively, these findings emphasize that the breadth of 3FTx-L binding extends across the medically important elapid snake family. Table 5. List of 95Mat5-binding 3FTx-L variants identified through deep sequencing. Verified binding/verified non-binding indicated for select toxins. Sort NGS Variant name Species Snake Accession Ref. order class name x- x- x-
Figure imgf000111_0002
10 AUSSU_Alpha- Austrelaps Australian A8S6B0.1 elapitoxin-As2a superbus 11 Alh l i i A 2 Hd hi S k P01380 x- x-
Figure imgf000112_0001
et al., Science 2021 x- x- x-
Figure imgf000113_0001
48 Alpha- Bungarus Krait P60616, 3FTx- bungarotoxin_V31 multicinctus 1HC9, 2 Vrifid bindin 4H P x- x- x- x-
Figure imgf000114_0001
66 NAJNU_T1284 Naja nubiae African T.D. cobra Kazandijian t l x- r x- r x- x- r x- r x- r x- r x- r x- r x-
Figure imgf000115_0001
S2 94 Long_neurotoxin_ Ophiophagus King A8N285 LNTX-2_homolog hannah cobra S2 95 L i OH O hi h Ki 53B53 x- r
Figure imgf000116_0001
Toxin preparation Long chain ⍺-neurotoxin three-finger toxin (3FTx-L) variant sequences from various snake species were selected from NCBI databases (Table 4), codon optimized for mammalian expression and cloned into a variant of pcDNA3.4 containing an N-terminal signal sequence (VH1- 2 leader), a C-terminal Avitag followed by a WELQut cleavage tag and a rabbit Fc tag by Genscript. A group I phospholipase A2 (PLA2) from Naja mossambica venom (UniProt accession # P00602) was also cloned into the same vector for use in the negative FACS steps. Plasmid DNA was prepped and co-transfected with a BirA expression plasmid into Expi293 cells (Thermo Fisher) using FectoPRO® (Polyplus Transfection). Cells were grown for 5 days shaking at 240 RPM, 37°C with 8% CO2 in Expi293 expression medium (Thermo Fisher). Approximately 24 hours after transfection, cells were fed D-(+)- glucose solution, 3 mM of sterile sodium valproic acid solution, and 20 nM d-biotin. Five days post-transfection, the supernatant was harvested from cell cultures, filtered through 0.45 µm, and incubated overnight, rotating at 4°C with rProtein A Sepharose affinity resin (Cytiva). The affinity resin was washed once with 500 mM NaCl in 1X PBS and twice with 1X PBS. For toxin-Fc conjugate purification, elution of the resin was performed with acidic IgG elution buffer (Thermo Fisher), followed by immediate neutralization to pH 7 using Tris base. The eluent was then concentrated to > 1 mg/ml and exchanged into PBS using a 10 kDa centrifugal filter unit (Millipore Sigma). For cleaved toxin purification, the resin was transferred to 20 mM Tris, 150 mM NaCl, pH 7.4 after washing with PBS. WELQut protease (Thermo Fisher) was added to the resin and incubated with rotation for 3 hours at 30°C. The supernatant was harvested from the resin and incubated with HisPur™ Ni-NTA resin (Thermo Fisher) for 30 minutes at room temperature to remove the His-tagged protease, followed by a second incubation with rProtein A resin for 30 minutes to remove any residual Fc tag. The final supernatant was concentrated to >1 mg/ml using a 3 kDa centrifugal filter unit (Millipore Sigma). Toxin-Fc conjugates and cleaved toxins were frozen in aliquots stored at -80°C. Biotinylation of the purified toxins was confirmed using the Pierce biotin quantitation kit (Thermo Fisher). For use in the in vitro neutralization and in vivo protection studies, native ⍺- bungarotoxin purified from B. multicinctus venom was purchased from Thermo Fisher (cat #B1601). The venoms of N. kaouthia and O. hannah were collected from the wild with appropriate permission from the respective forest departments (Kolkata, West Bengal #386/WL/4R-6/2017; 12/02/2018 and Mysore, Karnataka PCCF(WL)/E2/CR-06/2018-19). The D. polylepis venom was a kind gift from Premium Serums and Vaccine Pvt. Ltd. (PSVPL). Antibody library construction and validation A human antibody library was constructed using the common light chain strategy (R42) and displayed as molecular Fab on the surface of Saccharomyces cerevisiae in the pYDSI2 Fab display vector, which included a V5 tag for detection of HC display and a c-Myc tag for detection of LC pairing. The library contains 8 human variable heavy (VH) genes (VH1-02, VH1- 18, VH1-69, VH3-07, VH3-15, VH3-23, VH3-30 and VH5-51) and 4 human variable light (VL) genes (VK1-39, VK3-20, VL1-51, VL2-14) that were selected based on high-frequency in the human memory compartment, canonical complementary determining region (CDR) structural diversity and favorable developability properties. Library diversity was localized to the CDRH3 using oligonucleotides synthesized with trimer amidite mixtures based on the frequency of amino acids found in antibody CDRH3 loops, excluding methionines and cysteines. The library included CDRH3 lengths between 10 and 20, using a distribution centered on length 15 but skewed to favor longer CDRH3s to avoid oversampling the shorter loops. The VH and VL genes used germline CDR1 and CDR2 loops without any additional diversity, and the CDRH3 loop was fixed based on the most frequently occurring VJ rearrangement for each VL gene. To facilitate deep sequencing analysis of selected antibodies, the heavy chains were designed to have a conserved stretch of nucleotides in the framework 2 region of the VH gene and in the J gene-encoding region just after the CDRH3. Further, each VH gene was codon-optimized in four different ways, and each unique VH gene was paired with a fixed light chain. This overall design allows for deep sequencing preparation of a ~250 bp stretch of DNA that can be prepared from bulk-sorted cells and encodes the VH gene (identified by the CDRH2 loop sequence), the CDRH3 and the corresponding light chain (from the codon optimization of the VH region). DNA for the library was prepared, and cells were transformed using 1,152 replicates of a high-throughput yeast transformation protocol. In total, a library with a diversity of 6x1010 across all VH/VL pairs, estimated by colony-forming unit assay, was produced. Upon completion of the library, DNA was harvested from a subset of the expanded cells for deep sequencing analysis of the constructed antibodies. Overall, the CDRH3 length and amino acid distributions closely agree with the targeted distributions. A test selection campaign was next run with 5 clinically relevant targets: ICOS-L, TNFalpha, PD1L2, IL-6R and SARS- CoV2-RBD. Briefly, 3 rounds of MACS followed by 5 rounds of FACS (3 positive selections interspersed with 2 negative selections) were used to enrich antigen-specific clones from the library. A subset of selected cells was archived after each round of FACS enrichment, and at the completion of the selection campaigns DNA was prepared for deep sequencing to monitor the enrichment process throughout. Strong enrichments were observed for each target antigen, and 6- 12 highly enriched antibodies were selected for production and characterization. At least 50% of the selected mAbs were binding for each target antigen, and most exhibited a KD in the nM range when tested via SPR. Table 6: Binding affinity of mAbs for 3FTX variants The equilibrium dissociation constant (KD) measured via SPR for each mAb on each selected 3FTx-L variant is listed in nanomolar units. NB: not binding Snake Bungarus Dendroaspis Naja Bungarus Dendroaspis Ophiophagus 5
Figure imgf000118_0001
LB5_90 6.8 13 10 6.5 NB 6.9 14 LB5 91 11 4.8 6.6 4 1300 12 6.3
Figure imgf000119_0001
Magnetic activated cell sorting Frozen aliquots of the naive library were thawed and approximately 2.5*1011 cells were expanded in SD-Ura medium (Sunrise Science) and grown at 30˚C overnight. The following day, the cultures were passaged to an OD600 ≈ 1*106 into SD-Ura and grown at 30˚C until reaching an OD600 = 1*107. Cells were then pelleted and resuspended in induction media (20 g/L galactose, 1 g/L glucose, 6.7 g/L yeast nitrogen base, 5 g/L bacto-cassamino acids, 38 mM disodium phosphate, 72 mM monosodium phosphate, and 419 µM L-tryptophan) and induced at 18°C for 3 days. For the first round of MACS (MACS1), ~1012 induced cells were pelleted and washed in PBS, then rotated overnight at 4°C with 20 nM of biotinylated, Fc-conjugated 3FTx-L2 and 3FTx-L3 as antigen baits in 120 mL PBS with 1% BSA (PBSA). Labeled cells were washed with PBSA in batches of ~4.2*1010 cells, incubated with 200 µL streptavidin MicroBeads (Miltenyi Biotec) for 20 min at 4°C, and then selected for positive binding using an autoMACS® Pro Separator (Miltenyi Biotec). The recovered cells were subsequently grown and induced for negative sorting (MACS2) with the streptavidin MicroBeads and anti-biotin MicroBeads in the absence of the antigens (Fig 8). For this negative selection step, the streptavidin binders that were enriched from the first round of MACS were discarded. The non-binders were labeled again with the antigens (20 nM Fc-3FTx- L2 and 20 nM Fc-3FTx-L3) for 60 min at 4°C, washed and labeled with anti-biotin MicroBeads, and sorted for positive binding (MACS3). The selected cells were then grown and induced again for FACS. Fluorescence-activated cell sorting Yeast cells were alternatively selected for 3FTx binding (affinity sorts), or depleted against polyreactive clones (PSR sorts) by labeling cells with biotinylated polyspecificity reagent (R43, 44) and selecting the low binding population. After each round of selection, the collected cells were expanded and reinduced prior to the next selection. A subset of the expanded cells were also frozen for future deep sequencing analysis. During affinity sorting, 1-5*107 induced yeast cells were incubated for 60 min rotating at 4°C with monomeric biotinylated 3FTx variants in PBSA. For PSR sorting, induced yeast cells were incubated with 20 µg/mL biotinylated HEK-cell soluble cytosolic protein extracts (SCP) (R43) and 1 µM rabbit Fc-conjugated PLA2 in PBSA to deplete non-specific and Fc-binding Fab clones. Cells were then washed with PBSA and incubated with 1 µg/mL of streptavidin-allophycocyanin (APC) conjugate (Thermo Fisher, cat #SA1005), 1 µg/mL anti-V5 antibody conjugated with Alexa Fluor 405 conjugate and 1 µg/mL anti-C-Myc antibody conjugated with fluorescein isothiocyanate (Immunology Consultants Laboratory, cat #CMYC- 45F) in PBSA for 20 min. Yeast cells were then washed once and resuspended in PBSA for sorting on a FACS Melody (BD Biosciences). Paired Fab chains were gated from a plot of AF405 vs. FITC signal (heavy chain vs light chain), which was subsequently sorted for antigen-binding on a plot of APC vs. FITC signal (Fig 9). Selected yeast cells were grown in SD-Ura medium shaking overnight at 30°C and induced for consecutive rounds of selection. In the AFF1 and AFF2 sorts, cells were labeled with 100 nM and 20 nM 3FTx-L2, respectively (Fig 8). In AFF3, the induced library was split into five fractions, each sorted against a different toxin. Cells that received 3FTx-L2 or 3FTx- L1 were sorted at 4 nM, cells that received 3FTx-L3, 3FTx-L5 and 3FTx-L6 were sorted at 100 nM. AFF4 was also performed using 20 nM 3FTx-L3, 4 nM 3FTx-L5 and 4 nM 3FTx-L6 on the binding populations sorted with those variants during AFF3. Negative PSR sorts were performed between AFF1 & AFF2 and between AFF2 & AFF3 (Fig 8). Deep sequencing and analysis of selected Fab populations The archived cells from the FACS selections were thawed and grown in 2 ml SD-Ura medium overnight shaking at 30°C. Yeast cells were then spun down; the cell pellet was resuspended with 250 µL of buffer P1 (with RNAse added) (Qiagen) by pipetting up and down. 5 µL of Zymolyase (Zymo Research) was added to digest yeast cell walls and incubated at 37°C for 1 h. Cells were then lysed, neutralized, and DNA was purified according to manufacturer’s instructions (Qiagen). A 240-290 bp amplicon was prepared via PCR using primers to amplify the HC region of the Fab sequence attached to partial Illumina® adapters. A subsequent round of PCR was performed to attach unique indexing barcodes for each sample library using xGen™ UDI primers (Integrated DNA Technologies). Once barcoded, all library samples were pooled together, cleaned via column purification (Qiagen) and gel purification, and then measured with a Qubit DNA concentration assay (Thermo Fisher). The amplicon sample was denatured in 0.1N NaOH, combined with 20% denatured PhiX control library (Illumina) and loaded at 7 pM concentration onto a NovaSeq 6000 System (Illumina Inc) with a paired-end NovaSeq v1.5500 bp kit. Paired-end FASTQ files were analyzed using the FastQC package (FastQC v0.11.9) to ensure high sequence quality and low contamination (R45). To create one merged contig for each pair of reads, BBMerge (version 38.87) from the BBTools suite was used to join the forward and reverse reads using the default parameters (R46). To efficiently quantify the number of identical sequences, the merged reads were clustered using VSEARCH (v2.15.1) (R47). Clustering was done using the "cluster_fast" method, and FASTA files were written, including the abundance of each unique sequence in the FASTA header. This step substantially improved the performance of downstream FASTA parsing, as each unique sequence was only analyzed once. Python code (Python 3.7) was written to parse the clustered fasta output, remove primer sequences, identify the base heavy and light chains, and translate the DNA sequences to amino acid sequences. The script then counted the unique CDR3 sequences separately associated with each heavy and light chain. Affinity maturation of LB5_95 Library generation and screening Oligo pools for each of the 6 CDRs in LB5_95 were generated with combinatorial point mutations at each site in the CDR using the SAMPLER strategy (R27) and synthesized by IDT. The mutations were predefined so that the introduction of liabilities such as cysteines, methionines, N-linked glycan motifs, integrin binding sites, and aspartate isomerization sites was avoided. The 3 CDRH oligo pools were stitched together with the framework regions of VH1-69 to form a heavy chain (HC) library of 5.4x106 diversity while the 3 CDRL oligo pools were assembled with the framework regions of VK1-39 to form a light chain (LC) library of 1.4x106 diversity. Two additional LC libraries were also generated to combine with the first. One contained combinatorial point mutations in each of the 3 CDRs of VK3-20 and was assembled with the framework regions of VK3-20 with a diversity of 1.6x106. The other contained the combinatorial oligo pools for CDRL1 and CDRL2 of VK1-39 along with a pool of 3,500 CDRL3 of lengths varying from 7-12 residues retrieved from human naive VK sequences listed on the Observed Antibody Space database (Olsen et al., Protein Sci. 31(1): 141–146 (2022)) with a diversity of 3.9x107. The HC library was transformed into yeast with the pYDSI2 Fab display vector containing VK1-39 as the fixed LC. The three LC libraries were transformed into yeast with the same vector containing VH1-69 and the original LB5_95 CDRH3 as the fixed HC. The HC and combined LC libraries were sorted separately with 3FTx-L2 and 3FTx-L3 for the first 3 affinity sorts (AFF1- AFF3), with a negative PSR sort (PSR1) performed between AFF2 and AFF3 using 20 µg/mL SCP (Fig 10). In AFF1, 4 nM and 1 nM of each 3FTx variant were used for the HC and LC libraries, respectively. Both libraries were then sorted with 200 and 40 pM of both 3FTx variants in AFF2, which were combined in PSR1 (Fig 10). In AFF3, the separate HC and LC PSR1 libraries were each sorted with 3FTx-L2 (40 pM) and 3FTx-L3 (40 pM). To avoid depletion conditions, the binding of 107 cells at low antigen concentrations was performed in larger volumes (5 ml, 30 ml, and 140 ml for 1 nM, 200 pM, and 40 pM, respectively). After the first rounds of sorting with the separate HC and LC libraries, the VH and VK DNA from the enriched Fab clones were extracted and assembled together to form a combined HC/LC library (Fig 10). This library was transformed into yeast with the dual vector for subsequent rounds of sorting. Affinity sorts 4-6 were performed with the combined HC & LC library, with a negative PSR sort (PSR2) between AFF4 and AFF5 (Fig 10). In AFF4, the combined library was sorted with 1 nM, 200 pM and 40 pM of both 3FTx-L2 and 3FTx-L3. These populations were combined together during PSR2 and sorted with 20 µg/mL SCP. In AFF5, the library was split again and sorted with 3FTx-L2 (40 pM), 3FTx-L3 (200 pM), 3FTx-L5 (40 pM), 3FTx-L8 (1 nM), and 3FTx-L15 (40 pM). An additional affinity sort (AFF6) was performed for the populations sorted with 3FTx-L2, 3FTx-L8, and 3FTx-L15 (Fig 10). Dissociation conditions were used for 3FTx-L2 and 3FTx-L15 during AFF6. Briefly, cells were incubated with 10 nM of biotinylated toxin, washed in PBSA, and then incubated overnight with 10 nM of non-biotinylated toxin at 4°C. The following day, cells were washed, incubated with secondaries, and sorted to select antibody variants that had retained binding to the biotinylated toxin overnight. For sequencing of the affinity maturation library, a 570 bp amplicon containing all 6 CDR sites was prepared from a circularized PCR product that ligated the CDR3 end of the HC to the CDR3 end of the LC. The amplicon was processed as described above and sequenced on a MiSeq System (Illumina Inc) with a paired-end MiSeq v3600 bp kit. IgG expression, purification, screening, and characterization Initial cross-reactive antibody candidates The selected antibodies were reformatted as IgG1 and synthesized by GenScript into a mammalian expression vector containing both the heavy and light chain separated by a P2A self- cleaving motif. Antibody encoding plasmids were transfected into Expi293 cells and purified using Protein A magnetic beads (Thermo Scientific) and elution with acidic IgG elution buffer. ELISA was used to screen for the cross-reactive binding of the antibodies against 3FTx-L variants. Briefly, polystyrene high-bind microplates (Corning, cat # 3690) were coated with anti-rabbit IgG Fc antibody (Sigma, cat # SAB3700849) overnight at 4°C, washed 3X with PBS containing 0.5% tween (PBST), blocked with PBS containing 3% BSA, incubated with recombinant rabbit Fc- tagged 3FTx-L for 1 hour at room temperature, and washed again 3X with PBST. Plates were then incubated with serial dilutions of the eluted antibodies for 1 hour, washed 3X with PBST, and incubated for 1 hour with alkaline phosphatase-conjugated anti-human IgG Fc-specific antibody (Jackson ImmunoResearch, cat # 109-055-098), and washed a final 3X with PBST before incubating with phosphatase substrate (Sigma cat # S0942) and reading absorbance at 405 nm. Antibodies that showed positive binding to 3FTx-L2 were then tested for non-specific binding on ELISA plates coated with Chinese hamster ovary cell soluble membrane protein extract (CHO- SMP). Antibodies that did not bind CHO-SMP were then screened for binding against additional 3FTx variants (3FTx-L1, 3FTx-L3, 3FTx-L5, and 3FTx-L6). 16 of the 30 antibodies selected for cross-reactivity via deep sequencing screened positive for cross-reactive binding to all 5 toxin variants (LCa-1, LCa-2, LCa-3, LCa-5 and LCa- 6) (Fig 2A). These antibodies were recloned into mammalian expression vectors just the heavy chain and co-transfected with the corresponding light chain for using a 1:2.5 ratio of HC:LC DNA, and purified from Expi293 cells with rProtein A Sepharose affinity resin (Cytiva) and elution with acidic buffer. The purity and monomeric content of the antibodies were analyzed using SDS-PAGE and analytical size exclusion chromatography on a 1260 Infinity II preparative LC system (Agilent) using a TSKgel® SuperSW mAb HR HPLC column (Tosoh Bioscience). Non-specific binding of these antibodies was further evaluated with the HEp-2 assay (Hemagen) using methods provided by the manufacturer and compared to reactive (bococizumab) and non-reactive (adalimumab) antibody controls. Affinity matured antibodies 6 cross-reactive antibody candidates were selected from the affinity maturation library for synthesis and testing. The antibodies were expressed as IgG1 using a 1:2.5 ratio of HC:LC DNA and purified as previously described. The antibodies were first tested for non-specific binding on ELISA plates coated with CHO-SMP, single-stranded DNA, or insulin (Fig 11B) and subsequently tested for self-association using affinity-capture self-interaction nanoparticle spectroscopy (AC- SINS, Fig 11C). Briefly, 20 nm gold nanoparticles (Ted Pella) were coated for 1 hr at room temperature with a 4:1 mixture of anti-human IgG Fc-specific capture antibodies (Jackson ImmunoResearch, cat #109-005-098) and polyclonal goat IgG non-capture antibodies (Jackson ImmunoResearch, cat #005-000-003) that had been buffer-exchanged into 20 mM sodium acetate, pH 4.3 and normalized to a concentration of 0.4 mg/ml. The coated nanoparticles were then blocked with 0.1 μM thiolated poly(ethylene glycol) for 1 hr and then concentrated and buffer-exchanged into PBS. The maturation antibody candidates were then incubated with the concentrated nanoparticles at a 15:1 volume ratio for 1 hr with a final Ab concentration of 41 μg/ml. The average plasmon wavelength was calculated as the maximum absorption at 510-570 nm for each antibody sample, and the absorption from a blank control was subtracted to determine the wavelength shift caused by antibody self-association. A non-self-interacting antibody (adalimumab) and a self- interacting antibody (bococizumab) were utilized as controls for comparison. The antibodies were additionally characterized via analytical SEC and HEp-2 assay as previously described (Fig 11D, Fig 11E). The lead maturation candidate (95Mat5) was also expressed and purified from Expi293 cells in a His-tagged Fab format (VH conjugated to constant CH1-only) for use in the structural studies. Briefly, harvested supernatant was incubated with HisPur™ Ni-NTA resin (Thermo Fisher) and eluted using 500 mM imidazole, then run over SEC using a HiLoad 16/600 Superdex 200 pg column (Cytiva) on an AKTA pure protein purification system (Cytiva). Surface plasmon resonance SPR measurements were carried out on a Biacore 8K instrument at 25°C. All experiments were performed with a flow rate of 30 µL/min in a mobile phase of HBS-EP+ [0.01 M HEPES (pH 7.6), 0.15 M NaCl, 3 mM EDTA, 0.0005% (v/v) Surfactant P20]. Anti-Human IgG (Fc specific) antibody (Cytiva) was immobilized to a density of ~3000-5000 RU via standard NHS/EDc coupling to a Series S CM-3 (Cytiva) sensor chip. A reference surface was generated through the same method. For conventional kinetic/dose-response experiments, listed antibodies were captured to ~50-100 RU via Fc-capture on the active flow cell prior to analyte injection. A concentration series of 3FTx-L variants (or clinically relevant antigens) were injected across the antibody and control surface for 2 min, followed by a 20 min dissociation phase using a multi-cycle method. Regeneration of the surface in between injections of analyte was achieved with two, 120s injections of 3 M MgCl2. Kinetic analysis of each reference subtracted injection series was performed using the BIAEvaluation software (Cytiva). All sensorgram series were fit to a 1:1 (Langmuir) binding model of interaction. In vitro binding and inhibition assays Flow cytometry nAChR blocking assay The construct for the ⍺1 subunit of nAChR was based on a sequence used previously (R48) and displayed on the surface of S. cerevisiae in the pYDSI2u_SiDi1 vector, a variant of the pYDSI2 vector used for the antibody display but modified to only express a single protein per cell rather than both a heavy chain and light chain. Biotinylated, cleaved 3FTx-L variants were pre- coupled with 95Mat5 antibody in various ratios for 1 hour at 4°C prior to incubating with induced yeast cells displaying nAChR for an additional hour in volumes avoiding depletion conditions. Cells were then washed with PBSA and coupled with 1 µg/mL of streptavidin-APC and 1 µg/mL anti-V5-AF405 for 20 min prior to flow cytometry on a ZE5 Cell Analyzer (BioRad). Non-linear curve-fitting to determine the IC50 for each 3FTx-L variant binding to the displayed nAChR subunit was performed via Prism (GraphPad) using a one-site competitive binding model (Table 4), and the IC50 concentration of each variant was applied in the blocking assay. TE671 cell-based assay of nAChR antagonism A fluorescence assay measuring the activation of fetal (^-subunit-containing) muscle- type nAChRs natively expressed in the TE671 cell line (RRID: CVCL_1756) using a membrane potential dye (FLIPR membrane potential dye blue, Explorer Kit, R8042, Molecular Devices, San Jose, CA, USA) was employed as described in Patel et al. (R49). All further reagents in this section were acquired from Gibco, Thermo Fisher Scientific, Paisley, UK, unless stated otherwise. TE671 cells were cultured in a culture medium consisting of DMEM with GlutaMAX supplement further supplemented with 10% FBS and 1% penicillin-streptomycin solution, and incubated at 37 °C/5% CO2 until ~90% confluence was reached. Cells were dislodged from cell culture flasks with TrypLE express enzyme, and the resulting suspension was added to a 10 mL culture medium, followed by centrifugation for 5 minutes at 300 x g. The supernatant was removed, the pellet was resuspended in a 5 mL culture medium and then counted using an automated cell counter (Luna II, Logos Biosystems, Villeneuve-d'Ascq, France), and medium was added to reach a count of (5x104-6x104 cells/100 µL).100 µL of cell suspension was then seeded into a clear-bottom, black-walled 96 well plate then incubated overnight at 37 °C/5% CO2. One vial of membrane potential dye was reconstituted in 36 mL assay buffer, which consisted of HBSS (created from 10x solution as per manufacturer’s instructions) supplemented with 20 mM HEPES and 0.5 µM atropine (A0132, Sigma-Aldrich, Gillingham, UK) and sterile filtered. Assay buffer was also used to create all solutions containing toxin, antibody, or acetylcholine. The culture medium was removed and replaced with 50 µL of dye solution and incubated for 30 min at 37 °C/5% CO2. For antibody neutralization experiments, solutions of toxin, antibody, toxin + antibody or assay buffer alone were concurrently incubated in a clear v-bottom 96-well plate (‘reagent plate’) (651201, Greiner Bio One, Stonehouse, UK). Reagent plates were not incubated for toxin IC50 experiments. After incubation, 50 µL solution from the reagent plate was transferred to the cell plate, and the cell plate was incubated for a further 15 min at 37 °C/5% CO2. Following incubation, the cell plate was acclimatized at room temperature for 15 min then recorded using a FlexStation 3 multi-mode microplate reader (Molecular Devices, San Jose, CA, USA) controlled by SoftMax Pro 7.1 software (Molecular Devices, San Jose, CA, USA). Excitation, cut-off, and emission wavelengths were set at 530, 550, and 565 nm, respectively, and recordings were carried out at room temperature with a read time of 214 s and an interval time of 2 s. A compound transfer of 50 µL of either 30 µM acetylcholine solution (to give 10 µM final concentration) or assay buffer alone from a separate clear v-bottom 96-well plate loaded into the reader was set after 20 s baseline recording to induce nAChR activation. Fluorescent responses were measured by the software in relative fluorescence units (RFUs), and the response for each well was determined by calculating the baseline (mean of the first 20 s of recording) and subtracting this from the maximum response from the remainder of the recording. For experiments with toxins only, 10 µM acetylcholine and assay buffer alone were used as controls, with all data points normalized to the mean of the acetylcholine-only responses. For experiments with antibodies and toxins, toxin-only and antibody-only controls were also included, with all data points normalized to the mean of the acetylcholine-only and toxin-only control. This was achieved by subtracting the toxin only control from the antibody + toxin and acetylcholine- only responses before normalizing to the acetylcholine response. To ensure a maximal signal window, varying concentrations of antibody were incubated with toxin concentrations that gave final concentrations of 30 nM ⍺-bungarotoxin (as used in Patel et al.) and 380 nM 3FTx-L6 (calculated after IC50 analysis of toxin in Fig 7). All experiments had 2-4 replicates per plate, and experiments were repeated on 3 separate days using different cell passage numbers. The mean of the replicates for each plate was calculated and combined with the means from the 2 other plates to give n=3. The means of these combined values were then calculated and plotted as the mean ± SD. Prism 9 (GraphPad, San Diego, CA, USA) was used for all graph plotting and application of non- linear regression equations to determine IC50 values. Screening and selection of antibody-binding toxins A yeast display library containing 8283FTx variants was constructed and synthesized as an oligo pool by Twist Bioscience. These variants were picked from NCBI databases and transcriptome sequencing (R50-53) to cover a broader range of snake species and encompass other 3FTx families beyond ⍺-neurotoxins, including muscarinic neurotoxins, cytotoxins, and anticoagulants, while containing 149 3FTx-L and 272 3FTx-S variants. The 3FTx oligo pool contained three different codon versions of each protein sequence (2,484 total oligos) with homology regions at both ends and was displayed on the surface of S. cerevisiae in the pYDSI2u_SiDi1 vector. A series of 3 affinity sorts were performed using 95Mat5 antibody at a concentration of 20 nM on a FACS Melody (BD Biosciences). Yeast cells were incubated with antibody in PBSA for 1 hour at 4°C prior to washing and incubation with 1 µg/mL anti-V5-AF405 conjugate and 1 µg/mL anti-human IgG Fc-phycoerythrin (PE) conjugate (Southern Biotech cat #9040-09) for 20 min to select for cells displaying toxin and binding to antibody. Isolated yeast cells were grown in SD-Ura medium shaking overnight at 30°C and induced for consecutive rounds of selection. Reserved cells from each sort were prepared for deep sequencing of the toxin-encoding plasmid region using a 330-360 bp amplicon attached to partial Illumina® adapters and methods described previously. Deep sequencing was performed using a MiSeq System (Illumina Inc) with the paired-end MiSeq v3600 bp kit. To analyze the results, a composite reference of the 2,484 3FTx nucleotide sequences was constructed in FASTA format and indexed using Burrows-Wheeler Transform (R54). Forward and reverse reads were merged using BBMerge (version 38.87) from the BBTools suite with default parameters (R46). Merged reads were aligned to the reference and quantified using SAMtools (R55) without removing duplicates. Clones that were enriched and expressed through at least 2 of the codon versions in the final sort were considered to be antibody- binding. An enrichment threshold of 10 total counts from the top 2 codon versions was applied in the 3 sorts (Fig 5A), and clones were filtered from the set of variants present in the previous sort. Nine 3FTx-L variants and three 3FTx-S variants present near the thresholds were selected for synthesis and 95Mat5 binding validation via ELISA (Fig 12). Recombinant expression and ELISA were performed using the rabbit Fc-conjugated toxin construct and methods previously described. Analysis performed for Fig 1 The Shannon entropy used in Fig 1A was calculated for each position in the alignment of 3FTx-L library variants using the equation H(x) = ^∑^ ^^^ p(xi) log2 p(xi) where p(xi) is the frequency of each amino acid residue occurring
Figure imgf000127_0001
the collection of 149 variants. The 3FTx-L2-binding Fab clones quantified in Fig 1E-1I were filtered from the deep sequencing data of the naive library sorted with 3FTx-L2 based on a total of 100 or more counts across the AFF2, PSR2, and AFF3 sorts. PCR sequencing artifacts and any sequence with a stop codon were removed. Cross-reactive Fab clones were filtered out of the 3,873 Fabs that bound 3FTx-L2 based on their presence in all four of the final affinity sorts for 3FTx-L1, L3, L5 and L6 above a threshold of 10 counts (Table 4). Example 2. In vivo protection To determine whether in vitro binding and inhibitory activities translated into preclinical protection against envenoming, the ability of 95Mat5 to protect against the lethal effects of α-bungarotoxin (purified 3FTx-L from Bungarus multicinctus venom) and 3FTx-L-rich whole snake venoms (Naja kaouthia, Dendroaspis polylepis and Ophiophagus hannah) were measured (R29-31). First, the median lethal dose (LD50) of α-bungarotoxin and the crude venoms was determined for both the intravenous (IV) and subcutaneous (SC) routes (Table 7). Next, groups of five mice received 2x IV LD50 α-bungarotoxin alone or preincubated with 95Mat5 at molar ratios of 1:8 or 1:25 toxin:antibody. All animals in the control group rapidly exhibited signs of systemic neurotoxicity and succumbed to envenoming within four hours, while those receiving 95Mat5 exhibited significantly prolonged survival (Fig 4A). Table 7: Intravenous and subcutaneous median lethal dose (LD50) measured for α- bungarotoxin and crude venoms. Toxin/venom Intravenous LD50 Subcutaneous LD50 Not tested
Figure imgf000128_0001
13.8 μg/mouse (0.688
Figure imgf000128_0002
Ophiophagus hannah 17.9 μg/mouse (0.890 mg/kg) 21.5 μg/mouse (1.08 mg/kg) Dendroaspis polylepis 6.99 μg/mouse (0.349 mg/kg) 7.17 μg/mouse (0.358 mg/kg) Next, the cross-neutralizing efficacy of 95Mat5 against 2x IV LD50 challenge doses of N. kaouthia, D. polylepis and O. hannah crude venoms was assessed. As a positive control and comparator to 95Mat5, mice were also treated with conventional equine-derived commercial antivenoms specific to each of the challenge venoms. These were tested at two concentrations: a high dose equivalent to their marketed neutralizing potency (Table 8) and a fixed lower dose of 25 mg/kg, matched for direct comparison with 95Mat5. Mice IV dosed with whole N. kaouthia venom succumbed to death within one hour, while treatment with 95Mat5 or an equivalent dose of antivenom provided complete protection for 24 hours (Fig 4B). 95Mat5 and the higher dose of antivenom protected mice from the lethal effects of D. polylepis venom, though the dose-matched antivenom resulted in only 20% survival (Fig 4C). The efficacy of 95Mat5 was reduced against O. hannah venom (20% survival at 24 hours), though increased animal survival times compared to dose-matched antivenom were observed (Fig 4D). Table 8: Neutralization potencies and dosages of monovalent antivenoms marketed by Queen Saovabha Memorial Institute (QSMI) for treating N. kaouthia and O. hannah envenoming, and African polyvalent antivenom marketed by Premium Serums and Vaccine Pvt. Ltd. (PSVPL) for treating D. polylepis bites. The marketed neutralization potency for each commercial antivenom is listed in units of mg venom that could be neutralized by one ml of undiluted antivenom, while the antivenom concentration is listed in units of mg serum protein (based on the dry weight of antivenom product contained in a vial) per ml of reconstituted antivenom solution. The antivenom dosage is then converted to mg of serum protein per kg of animal weight. Manufacturer Batch Specie Venom Antivenom Antivenom Antivenom number s Type dosage potency concentration dosage
Figure imgf000129_0001
two- step rescue assay where treatment is delivered after venom challenge was also evaluated. N. kaouthia and D. polylepis venoms SC were used to better enable the evaluation of delayed treatment, which consisted of 25 mg/kg of 95Mat5 IV at 0, 10 and 20 minutes post-venom dosing. In both groups, control animals died within 3 hours of the venom challenge. In contrast, animals receiving 95Mat5, irrespective of treatment delay, survived the full 24-hour observation period without signs of neurotoxicity (Fig 4E-F). Collectively, these data demonstrate that a single monoclonal antibody (95Mat5) provides broad preclinical protection against 3FTx-L-rich snake venoms and exhibits superior dose efficacy than commercial monovalent and polyvalent antivenoms. In vivo protection studies Animal ethics and biosafety clearances Approvals to perform in vivo neutralization assays in the murine model of envenoming were obtained from the Institutional Animal Ethics Committee, Indian Institute of Science, Bangalore (CAF/Ethics/904/2022 and CAF/Ethics/947/2023). Experimental protocols were designed following the guidelines issued by the Committee for Control and Supervision of Experiments on Animals (CCSEA), Government of India. The Institutional Biosafety Committee (IBSC) permission was also obtained as these experiments involved the use of snake venoms and recombinant proteins. Determination of median lethal dose The intravenous and/or subcutaneous median lethal doses (LD50) of α-bungarotoxin and crude venoms from N. kaouthia, D. polylepis and O. hannah were determined in mice (male CD-1; 18–22 g) using the WHO-recommended approach (R56) (Table 7). Five concentrations of toxin/venom were diluted in PBS to a volume of 200 μl and then intravenously (caudal vein) or subcutaneously injected into groups of five mice. The mortality rate was recorded every one hour for a total of 24 hours post-venom injection, and the LD50 was estimated using Probit statistics (R57). Preincubation neutralization experiments The in vivo neutralizing efficacy of 95Mat5 against α-bungarotoxin and N. kaouthia, D. polylepis and O. hannah venoms was evaluated in mice (male CD-1; 18–22 g; n=5 per group) using an established preincubation and intravenous co-administration approach (R56). A 2x LD50 dose of α-bungarotoxin (22 µg/mouse) was incubated with 95Mat5 antibody in toxin:antibody molar ratios of 1:8 and 1:25 (27 and 85 mg/kg antibody) at 37 °C for 30 min. The preincubated mixture (200 μl volume) was then intravenously injected into the caudal vein of a group of five mice, and the animals were continuously monitored over a 24-hour period. The time taken for the appearance of pathophysiological symptoms (e.g., hindlimb paralysis, loss of righting reflex, etc.) and death was noted. Kaplan–Meier plots were generated to depict the percentage survival over time. Similar experiments were conducted with 2x LD50 doses of each crude venom preincubated with 25 mg/kg of 95Mat5 antibody. The efficacy of 95MatAb was evaluated in comparison with the conventional monovalent antivenoms marketed by Queen Saovabha Memorial Institute (QSMI), Thailand, for treating N. kaouthia and O. hannah envenoming, and African polyvalent antivenom marketed by PSVPL for treating D. polylepis bites. The contents of the commercial antivenom vial were weighed and reconstituted in 10 ml sterile water provided by the manufacturer. These conventional antivenoms were tested both at 25 mg/kg and at doses equivalent to their marketed neutralization potencies (Table 8). In all of the aforementioned experiments, a group of five mice injected with α-bungarotoxin/crude venom served as a positive control. Rescue experiments The ability of 95Mat5 to rescue experimental animals injected with crude snake venom was assessed using a two-step rescue strategy. To better reflect a clinical envenoming scenario (58), crude snake venom was first injected into mice via the subcutaneous route, followed by the intravenous administration of 95Mat5 at 0, 10 and 20 minutes post-venom injection. Since 95Mat5 exhibited reduced efficacy against O. hannah venom in the preincubation studies, only N. kaouthia and D. polylepis venoms were selected for rescue experiments. In these experiments, a 2x LD50 dose of each venom (27.52 and 14.34 µg/mouse for N. kaouthia and D. polylepis, respectively), diluted in PBS to 100 μl, was subcutaneously injected into groups of five mice, followed by the intravenous administration of 95Mat5 (25 mg/kg in 100 μl volume). For comparison, the conventional monovalent antivenom against N. kaouthia (QSMI) was also estimated at the same 25 mg/kg dose and injection time points (0, 10 and 20 minutes). Mice were observed over a 24- hour period, and the percentage survival over time was plotted as Kaplan–Meier curves. Example 3. Structural analysis of 95Mat5 with 3FTx-L15 To provide a molecular explanation for its broad reactivity, a crystal structure of 95Mat5 Fab in complex with 3FTx-L15 was determined to 2.9Å resolution (Fig 5A and Fig 16). 95Mat5 targets the middle of the toxin through CDRs H1, H3, L1, and L2 (Fig 5B). The interaction surface is contributed primarily by CDRH3, although CDRs H1, L1 and L2 provide hydrophobic interactions and H-bonds (Fig 5B and Table 9). The buried surface area on 3FTx-L15 is 787 Å2, with 82.7% and 17.3% from the HC and LC, respectively. Specifically, residues Thr6-Ala9, Thr25- Ile38, and Phe66-Thr68 from 3FTx-L15 are involved (Fig 5B) with Asp28, Phe30, and Arg34 interacting with both HC and LC (Fig 5B-E). Table 9: Interactions between 95Mat5 and 3FTx-L15 by PISA web server. Hydrogen Bonds Ionic Interactions Distance (Å)
Figure imgf000131_0001
Figure imgf000131_0002
]
Figure imgf000131_0003
CDRs H1 and H3 of 95Mat5 participate in a polar network, where CDRH3 makes six hydrogen bonds with 3FTx-L15 (Fig 5C-E and Table 9) that are crucial for antigen recognition. CDRH3 Trp99 makes an indole NH hydrogen bond with 3FTx-L15 Pro7 carbonyl oxygen and a carbonyl oxygen-hydrogen bond with the Ile38 backbone amide. Glu100a hydrogen bonds with 3FTx-L15 Arg34 and Lys36. Additionally, the side chain of Tyr100 makes hydrogen bonds with 3FTx-L15 Arg34 while Thr28 and Ser31 from CDRH1 make side-chain hydrogen bonds with 3FTx-L15 Asp8 (Fig 5C-E and Table 9). CDRH3 Trp99, Tyr100, Glu100a, and Tyr100e are involved in a hydrophobic interaction with a hydrophobic pocket formed by 3FTx-L15 Ala9, Phe30, Arg34, Arg37, Ile38, Phe66, and Thr68 (Fig 13 and Table 10). Table 10: Contacts between nAChRα1:α-bungarotoxin (PDB:2qc1) and 95Mat5:3FTx-L15. nAChRα1 α-bungarotoxin Trp187 Ser9
Figure imgf000132_0001
3FTx-L15 and α-bungarotoxin residues involved in H-bonds and ionic interactions are shown in bold; van der Waals interactions are in the normal font; hydrophobic interactions are underlined. The 95Mat5 CDRL1 Tyr32 hydrogen bonds with Phe30 backbone amide (Fig 5E and Table 9). Tyr32 and Tyr92 LC interact with Phe30 in a hydrophobic pocket on 3FTx-L15 (Fig 11 and Table 10). 3FTx-L15 Arg34 guanidium group stacks in a cation-π interaction between aromatic residues Tyr100, Tyr100e HC, and Phe30 from its own Finger II. Phe30 also packs again with 95Mat5 Tyr32 and Tyr92 LC (Fig 13, Fig 14 and Table 10). Interestingly, this binding network resembles an interaction of nAChR⍺1 Tyr190 and Tyr198-3FTx-L with Arg36-3FTx- L_Phe30 (R32). 95Mat5 CDRL2 Asp50 is involved in a patch of electrostatic interactions that involves two arginines and two aspartic acids. In the Pisa interaction interface analysis, Asp50 makes three hydrogen bonds/salt bridges with CDRH3 Arg98 and a long-range electrostatic interaction with 3FTx-L15 Arg37 (Fig 5E, 5F and Table 9).95Mat5 Arg98 is also involved in four van der Waals and polar interactions with 3FTx-L15 Arg37 and 1 longer-range electrostatic interaction with 3FTx-L15 Asp28 (5.3 Å) (Table 9). 95Mat5 Asp50 therefore appears to play an important role in the stabilization and orientation of CDRH3 Arg98 for antigen recognition as well as the in longer range electrostatic interactions with 3FTx-L15, thus explaining its strong selection in the affinity maturation of LB5_95 (Fig.2D). The binding mode of 95Mat5 with 3FTx-L15 is similar to previously determined structures of ⍺-bungarotoxin with nAChR⍺1, ⍺7, and ⍺9 (Fig 15) (32-33). CDRH3 of 95Mat5 Fab approximates "loop C" of nAChR⍺1 (Fig 5G) that wrap around fingers I, II and the C-terminal loop of 3FTx-L toxins; the tip of the 3FTx-L finger II inserts into the binding site and is surrounded by loops A, B and C of nAChR⍺ (Fig 5G and Table 10) (R33). The antibody and receptor interact with similar toxin residues (Fig 5G and Table 10). Tyr100 and Tyr100e in 95Mat5 align with Tyr190 and Tyr198 of nAChR⍺1, respectively (Fig 5G), while Tyr100 is conserved among the cross-reactive antibodies (Fig 5G). Furthermore, 95Mat5 Fab recognizes 3FTx-L15 residues that include Asp28, Phe30, Arg34, Gly35, and Lys36 on finger II, and Pro67 on the C-terminus (Fig 5B and Table 10). These equivalent ⍺-bungarotoxin residues Asp30, Phe32, Arg36, Gly37, Lys38, and Pro69 also play an important role in nAChR binding (Table 10) (R34). Thus, the findings suggest antibody mimicry of nAChR⍺1 that facilitates broad recognition of 3FTx-L variants. Structural studies Crystallization 3FTx-L15 was mixed with 95Mat5 Fab fragment at a 1:1.3 molar ratio of toxin: Fab. The mixture was incubated overnight at 4 ºC before further purification by gel filtration (Superdex 200 column) to remove uncomplexed toxin or Fab. The peak corresponding to the complex was pooled and adjusted to 12 mg/mL in 20 mM Tris pH 8.0, and 150-mM NaCl buffer. The complex between toxin and Fab was confirmed by SDS-PAGE and used immediately for crystallization trials. The antibody-antigen complex was screened for crystallization using the 384 conditions of the Joint Center for Structural Genomics (JCSG) Core Suite (Qiagen) using the sitting drop vapor diffusion method on the automated CrystalMation robotic system (Rigaku) at The Scripps Research Institute. Within 3–7 days, diffraction-quality crystals were obtained using 100mM sodium citrate pH 3.75, and 26% PEG6000 as precipitant at 20 °C. Data collection, processing, and structure determination Crystals were cryoprotected with 15-25% ethylene glycol and flash-cooled and stored in liquid nitrogen until data collection. Data were collected from a crystal cryocooled to 100K using a Rigaku MicroMax-007 generator at 1.5418 Å wavelength with a Mar345dtb area detector. Diffraction data were processed with HKL-2000 (R59). The initial models for 95Mat5 Fab were generated by Repertoire Builder (sysimm.ifrec.osaka-u.ac.jp/rep_builder/) (R60). The model template for 3FTx-L15 was derived from α-bungarotoxin V31 (PDB: 1HC9). Initial phases were determined by molecular replacement using Phaser (R61). Refinement was carried out in Refmac (R62) and Phenix (R63), alternating with manual rebuilding and adjustment in COOT (R64). Detailed data collection and refinement statistics are summarized in Fig. 16. Structure validation was performed with The Protein Data Bank validation server and MolProbity (R65). Before Protein Data Bank (PDB) deposition, PDB-REDO (R66) was performed to complete the structures. The coordinates and structure factors for the 95Mat5:3FTx-L15 are available under accession codes 8SXP. Structural analysis Epitope and paratope residues, as well as their interactions, were identified by accessing PISA at the European Bioinformatics Institute (ww w ebi.ac.uk/pdbe/pisa/) (R67). Structure figures were generated by MacPyMol (DeLano Scientific LLC). While the invention has been described in connection with what is presently considered to be the most practical and preferred embodiments, it is to be understood that the invention is not to be limited to the disclosed embodiments, but on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims. All publications, patents, patent applications, internet sites, and accession numbers/database sequences including both polynucleotide and polypeptide sequences cited herein are hereby incorporated by reference herein in their entirety for all purposes to the same extent as if each individual publication, patent, patent application, internet site, or accession number/database sequence were specifically and individually indicated to be so incorporated by reference. REFERENCES R1. J. M. Gutiérrez, et al., Snakebite envenoming. Nat Rev Dis Primers.3, 17063 (2017). R2. J.-P. Chippaux, Snakebite envenomation turns again into a neglected tropical disease! J. Venom. Anim. Toxins Incl. Trop. Dis.23, 38 (2017). R3. G. León, et al., Current technology for the industrial manufacture of snake antivenoms. Toxicon.151, 63–73 (2018). R4. R. A. Harrison & J. M. Gutiérrez, Priority Actions and Progress to Substantially and Sustainably Reduce the Mortality, Morbidity and Socioeconomic Burden of Tropical Snakebite. Toxins .8 (2016), doi:10.3390/toxins8120351. R5. A. H. Laustsen, et al., From Fangs to Pharmacology: The Future of Snakebite Envenoming Therapy. Curr. Pharm. Des.22, 5270–5293 (2016). R6. G. León et al., Pathogenic mechanisms underlying adverse reactions induced by intravenous administration of snake antivenoms. Toxicon.76, 63–76 (2013). R7. A. H. Laustsen, et al., Pros and cons of different therapeutic antibody formats for recombinant antivenom development. Toxicon.146, 151–175 (2018). R8. M. B. Pucca, et al., History of Envenoming Therapy and Current Perspectives. Front. Immunol. 10, 1598 (2019). R9. N. R. Casewell, et al., Causes and Consequences of Snake Venom Variation. Trends Pharmacol. Sci.41 (2020), doi:10.1016/j.tips.2020.05.006. R10. K. Sunagar, et al., Three-fingered RAVERs: Rapid Accumulation of Variations in Exposed Residues of snake venom toxins. Toxins .5 (2013), doi:10.3390/toxins5112172. R11. R. M. Kini & R. Doley, Structure, function and evolution of three-finger toxins: mini proteins with multiple targets. Toxicon.56, 855–867 (2010). R12. S. Nirthanan, Snake three-finger α-neurotoxins and nicotinic acetylcholine receptors: molecules, mechanisms and medicine. Biochem. Pharmacol.181, 114168 (2020). R13. I. S. Abubakar, et al., Randomised controlled double-blind non-inferiority trial of two antivenoms for saw-scaled or carpet viper (Echis ocellatus) envenoming in Nigeria. PLoS Negl. Trop. Dis.4, e767 (2010). R14. R. M. Kini, et al., Biosynthetic Oligoclonal Antivenom (BOA) for Snakebite and Next- Generation Treatments for Snakebite Victims. Toxins .10 (2018), doi:10.3390/toxins10120534. R15. H. Bailon Calderon, et al., Development of Nanobodies Against Hemorrhagic and Myotoxic Components of Bothrops atrox Snake Venom. Front. Immunol.11, 655 (2020). R16. W. Danpaiboon, et al., Ophiophagus hannah venom: proteome, components bound by Naja kaouthia antivenin and neutralization by N. kaouthia neurotoxin-specific human ScFv. Toxins .6, 1526–1558 (2014). R17. A. H. Laustsen, et al., In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies. Nat. Commun.9, 3928 (2018). R18. N. D. R. Prado, et al., Inhibition of the Myotoxicity Induced by Bothrops jararacussu Venom and Isolated Phospholipases A2 by Specific Camelid Single-Domain Antibody Fragments. PLoS One.11, e0151363 (2016). R19. L. C. Silva, et al., Discovery of human scFvs that cross-neutralize the toxic effects of B. jararacussu and C. d. terrificus venoms. Acta Trop.177, 66–73 (2018). R20. L. Ledsgaard, et al., Discovery and optimization of a broadly-neutralizing human monoclonal antibody against long-chain α-neurotoxins from snakes. Nat. Commun.14, 682 (2023). R21. C.-H. Lee, et al., Chicken antibodies against venom proteins of Trimeresurus stejnegeri in Taiwan. J. Venom. Anim. Toxins Incl. Trop. Dis.26, e20200056 (2020). R22. F. Kazemi-Lomedasht, et al., Development of a human scFv antibody targeting the lethal Iranian cobra (Naja oxiana) snake venom. Toxicon.171, 78–85 (2019). R23. K. Sunagar & Y. Moran, The Rise and Fall of an Evolutionary Innovation: Contrasting Strategies of Venom Evolution in Ancient and Young Animals. PLoS Genet.11, e1005596 (2015). R24. X. Wu, et al., Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science.329, 856–861 (2010). R25. L. M. Walker, et al., et al., Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature.477, 466–470 (2011). R26. D. Sok, et al., Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex. Proc. Natl. Acad. Sci. U. S. A.111, 17624–17629 (2014). R27. F. Zhao, et al., Broadening a SARS-CoV-1 neutralizing antibody for potent SARS-CoV-2 neutralization through directed evolution. bioRxiv (2021), p.2021.05.29.443900. R28. E. T. Boder, et al., Directed evolution of antibody fragments with monovalent femtomolar antigen-binding affinity. Proc. Natl. Acad. Sci. U. S. A.97, 10701–10705 (2000). R29. U. Rashmi, et al., Remarkable intrapopulation venom variability in the monocellate cobra (Naja kaouthia) unveils neglected aspects of India’s snakebite problem. J. Proteomics.242, 104256 (2021). R30. A. H. Laustsen, et al., Unveiling the nature of black mamba (Dendroaspis polylepis) venom through venomics and antivenom immunoprofiling: Identification of key toxin targets for antivenom development. J. Proteomics.119, 126–142 (2015). R31. C. H. Tan, et al., Venom-gland transcriptome and venom proteome of the Malaysian king cobra (Ophiophagus hannah). BMC Genomics.16, 687 (2015). R32. M. M. Rahman, et al., Structure of the Native Muscle-type Nicotinic Receptor and Inhibition by Snake Venom Toxins. Neuron.106, 952–962.e5 (2020). R33. C. D. Dellisanti, et al., Crystal structure of the extracellular domain of nAChR alpha1 bound to alpha-bungarotoxin at 1.94 A resolution. Nat. Neurosci.10, 953–962 (2007). R34. C. Fruchart-Gaillard, et al., Experimentally based model of a complex between a snake toxin and the α7 nicotinic receptor. Proceedings of the National Academy of Sciences. 99, 3216–3221 (2002). R35. F. J. Vonk,. et al., The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system. Proc. Natl. Acad. Sci. U. S. A.110, 20651–20656 (2013). R36. P. S. Lee, et al., Receptor mimicry by antibody F045-092 facilitates universal binding to the H3 subtype of influenza virus. Nat. Commun.5, 3614 (2014). R37. A. P. West Jr, et al., Structural basis for germ-line gene usage of a potent class of antibodies targeting the CD4-binding site of HIV-1 gp120. Proc. Natl. Acad. Sci. U. S. A. 109, E2083–90 (2012). R38. F. Chen, N. Tzarum, I. A. Wilson, M. Law, V1-69 antiviral broadly neutralizing antibodies: genetics, structures, and relevance to rational vaccine design. Curr. Opin. Virol. 34, 149–159 (2019). R39. M. Harel, R. Kasher, A. Nicolas, J. M. Guss, M. Balass, M. Fridkin, A. B. Smit, K. Brejc, T. K. Sixma, E. Katchalski-Katzir, J. L. Sussman, S. Fuchs, The Binding Site of Acetylcholine Receptor as Visualized in the X-Ray Structure of a Complex between α-Bungarotoxin and a Mimotope Peptide. Neuron.32, 265–275 (2001). R40. H. Heberle, G. V. Meirelles, F. R. da Silva, G. P. Telles, R. Minghim, InteractiVenn: a web- based tool for the analysis of sets through Venn diagrams. BMC Bioinformatics. 16 (2015), , doi:10.1186/s12859-015-0611-3. R41. G. E. Crooks, G. Hon, J.-M. Chandonia, S. E. Brenner, WebLogo: a sequence logo generator. Genome Res.14, 1188–1190 (2004). R42. T. Van Blarcom, K. Lindquist, Z. Melton, W. L. Cheung, C. Wagstrom, D. McDonough, C. Valle Oseguera, S. Ding, A. Rossi, S. Potluri, P. Sundar, S. Pitts, M. Sirota, M. Galindo Casas, Y. Yan, J. Jones, Z. Roe-Zurz, S. Srivatsa Srinivasan, W. Zhai, J. Pons, A. Rajpal, J. Chaparro- Riggers, Productive common light chain libraries yield diverse panels of high affinity bispecific antibodies. MAbs.10, 256–268 (2018). R43. Y. Xu, W. Roach, T. Sun, T. Jain, B. Prinz, T.-Y. Yu, J. Torrey, J. Thomas, P. Bobrowicz, M. Vásquez, K. D. Wittrup, E. Krauland, Addressing polyspecificity of antibodies selected from an in vitro yeast presentation system: a FACS-based, high-throughput selection and analytical tool. Protein Eng. Des. Sel.26, 663–670 (2013). R44. R. L. Kelly, J. Zhao, D. Le, K. D. Wittrup, Nonspecificity in a nonimmune human scFv repertoire. MAbs.9, 1029–1035 (2017). R45. Babraham Bioinformatics - FastQC A Quality Control tool for High Throughput Sequence Data, (available at http://www.bioinformatics.babraham.ac.uk/projects/fastqc/). R46. B. Bushnell, J. Rood, E. Singer, BBMerge – Accurate paired shotgun read merging via overlap. PLoS One.12, e0185056 (2017). R47. T. Rognes, T. Flouri, B. Nichols, C. Quince, F. Mahé, VSEARCH: a versatile open source tool for metagenomics. PeerJ.4, e2584 (2016). R48. K. Noridomi, G. Watanabe, M. N. Hansen, G. W. Han, L. Chen, Structural insights into the molecular mechanisms of myasthenia gravis and their therapeutic implications. Elife. 6 (2017), doi:10.7554/eLife.23043. R49. R. N. Patel, R. H. Clare, L. Ledsgaard, M. Nys, J. Kool, A. H. Laustsen, C. Ulens, N. R. Casewell, An in vitro assay to investigate venom neurotoxin activity on muscle-type nicotinic acetylcholine receptor activation and for the discovery of toxin-inhibitory molecules. bioRxiv (2023), p.2023.04.28.538762. R50. T. D. Kazandjian, D. Petras, S. D. Robinson, J. van Thiel, H. W. Greene, K. Arbuckle, A. Barlow, D. A. Carter, R. M. Wouters, G. Whiteley, S. C. Wagstaff, A. S. Arias, L.-O. Albulescu, A. Plettenberg Laing, C. Hall, A. Heap, S. Penrhyn-Lowe, C. V. McCabe, S. Ainsworth, R. R. da Silva, P. C. Dorrestein, M. K. Richardson, J. M. Gutiérrez, J. J. Calvete, R. A. Harrison, I. Vetter, E. A. B. Undheim, W. Wüster, N. R. Casewell, Convergent evolution of pain-inducing defensive venom components in spitting cobras. Science.371, 386–390 (2021). R51. S. Ainsworth, D. Petras, M. Engmark, R. D. Süssmuth, G. Whiteley, L.-O. Albulescu, T. D. Kazandjian, S. C. Wagstaff, P. Rowley, W. Wüster, P. C. Dorrestein, A. S. Arias, J. M. Gutiérrez, R. A. Harrison, N. R. Casewell, J. J. Calvete, The medical threat of mamba envenoming in sub- Saharan Africa revealed by genus-wide analysis of venom composition, toxicity and antivenomics profiling of available antivenoms. J. Proteomics.172, 173–189 (2018). R52. K. Sunagar, S. Khochare, R. R. Senji Laxme, S. Attarde, P. Dam, V. Suranse, A. Khaire, G. Martin, A. Captain, A Wolf in Another Wolf’s Clothing: Post-Genomic Regulation Dictates Venom Profiles of Medically-Important Cryptic Kraits in India. Toxins . 13 (2021), doi:10.3390/toxins13010069. R53. G. Whiteley, N. R. Casewell, D. Pla, S. Quesada-Bernat, R. A. E. Logan, F. M. S. Bolton, S. C. Wagstaff, J. M. Gutiérrez, J. J. Calvete, R. A. Harrison, Defining the pathogenic threat of envenoming by South African shield-nosed and coral snakes (genus Aspidelaps), and revealing the likely efficacy of available antivenom. J. Proteomics.198, 186–198 (2019). R54. H. Li, R. Durbin, Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics.25, 1754–1760 (2009). R55. G. Abecasis, R. Durbin, … Genome Project Data Processing Subgroup (2009) The Sequence alignment/map (SAM) format and SAMtools. Bioinformatics 25: 20782079Marshall HD …. Züchter Genet. Breed. Res. R56. World Health Organization, WHO expert committee on biological standardization: Sixty- seventh report (World Health Organization, Genève, Switzerland, 2017). R57. D. J. Finney, A statistical treatment of the sigmoid response curve. Probit analysis. Cambridge University Press, London. 633 (1971) (available at https://www.researchgate.net/profile/Milan- Arambasic/post/Any_biostatisticians_who_can_perform_Probit_analysis/attachment/63ce571c23 e35630acdcd5e4/AS%3A11431281114361226%401674467098438/download/P+R+O+B+I+T++ ++++A+N+A+L+Y+S+E+S%2C+Finney%2C+D.J.pdf). R58. C. Knudsen, N. R. Casewell, B. Lomonte, J. M. Gutiérrez, S. Vaiyapuri, A. H. Laustsen, Novel Snakebite Therapeutics Must Be Tested in Appropriate Rescue Models to Robustly Assess Their Preclinical Efficacy. Toxins .12 (2020), doi:10.3390/toxins12090528. R59. Z. Otwinowski, W. Minor, "[20] Processing of X-ray diffraction data collected in oscillation mode" in Methods in Enzymology (Academic Press, 1997), vol.276, pp.307–326. R60. D. Schritt, S. Li, J. Rozewicki, K. Katoh, K. Yamashita, W. Volkmuth, G. Cavet, D. M. Standley, Repertoire Builder: high-throughput structural modeling of B and T cell receptors. Molecular Systems Design & Engineering.4, 761–768 (2019). R61. A. J. McCoy, R. W. Grosse-Kunstleve, P. D. Adams, M. D. Winn, L. C. Storoni, R. J. Read, Phaser crystallographic software. J. Appl. Crystallogr.40, 658–674 (2007). R62. P. Skubák, G. N. Murshudov, N. S. Pannu, Direct incorporation of experimental phase information in model refinement. Acta Crystallogr. D Biol. Crystallogr.60, 2196–2201 (2004). R63. P. D. Adams, R. W. Grosse-Kunstleve, L. W. Hung, T. R. Ioerger, A. J. McCoy, N. W. Moriarty, R. J. Read, J. C. Sacchettini, N. K. Sauter, T. C. Terwilliger, PHENIX: building new software for automated crystallographic structure determination. Acta Crystallogr. D Biol. Crystallogr.58, 1948–1954 (2002). R64. P. Emsley, K. Cowtan, Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr.60, 2126–2132 (2004). R65. V. B. Chen, W. B. Arendall 3rd, J. J. Headd, D. A. Keedy, R. M. Immormino, G. J. Kapral, L. W. Murray, J. S. Richardson, D. C. Richardson, MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D Biol. Crystallogr.66, 12–21 (2010). R66. R. P. Joosten, J. Salzemann, V. Bloch, H. Stockinger, A.-C. Berglund, C. Blanchet, E. Bongcam-Rudloff, C. Combet, A. L. Da Costa, G. Deleage, M. Diarena, R. Fabbretti, G. Fettahi, V. Flegel, A. Gisel, V. Kasam, T. Kervinen, E. Korpelainen, K. Mattila, M. Pagni, M. Reichstadt, V. Breton, I. J. Tickle, G. Vriend, PDB_REDO: automated re-refinement of X-ray structure models in the PDB. J. Appl. Crystallogr.42, 376–384 (2009). R67. E. Krissinel, K. Henrick, Inference of macromolecular assemblies from crystalline state. J. Mol. Biol.372, 774–797 (2007).
SEQUENCES SEQ ID NO: 1: LB5_49 VH CDR1 GYTFTGYY SEQ ID NO: 2: LB5_49 VH CDR2 INPNSGGT SEQ ID NO: 3: LB5_49 VH CDR3 CARSGGAWYVTGFYAQGNFDY SEQ ID NO: 4: LB5_49 VL CDR1 SSDVGGYNY SEQ ID NO: 5: LB5_49 VL CDR2 EVS SEQ ID NO: 6: LB5_49 VL CDR3 SSYTSSSTL SEQ ID NO: 7: LB5_49 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTM TRDTSISTAYMELSRLRSDDTAVYYCARSGGAWYVTGFYAQGNFDYWGQGTLVTVSS SEQ ID NO: 8: LB5_49 VL QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSNRPSGVSNRFSGSKSG NTASLTISGLQAEDEADYYCSSYTSSSTLVVFGGGTKLTVLGQ SEQ ID NO: 9: intentionally left open SEQ ID NO: 10: intentionally left open SEQ ID NO: 11: LB5_53 VH CDR1 GYTFTGYY SEQ ID NO: 12: LB5_53 VH CDR2 INPNSGGT SEQ ID NO: 13: LB5_53 VH CDR3 CARDVLVHYVSGRYPYYVFDY SEQ ID NO: 14: LB5_53 VL CDR1 QSVSSSY SEQ ID NO: 15: LB5_53 VL CDR2 GAS SEQ ID NO: 16: LB5_53 VL CDR3 QQYGSSP SEQ ID NO: 17: LB5_53 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTM TRDTSISTAYMELSRLRSDDTAVYYCARDVLVHYVSGRYPYYVFDYWGQGTLVTVSS SEQ ID NO: 18: LB5_53 VL EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT DFTLTISRLEPEDFAVYYCQQYGSSPLTFGQGTKLEIK SEQ ID NO: 19: intentionally left open SEQ ID NO: 20: intentionally left open SEQ ID NO: 21: LB5_54 VH CDR1 GYTFTGYY SEQ ID NO: 22: LB5_54 VH CDR2 INPNSGGT SEQ ID NO: 23: LB5_54 VH CDR3 CARTYFKWYSRGAYPADYFDY SEQ ID NO: 24: LB5_54 VL CDR1 SSDVGGYNY SEQ ID NO: 25: LB5_54 VL CDR2 EVS SEQ ID NO: 26: LB5_54 VL CDR3 SSYTSSSTL SEQ ID NO: 27: LB5_54 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTM TRDTSISTAYMELSRLRSDDTAVYYCARTYFKWYSRGAYPADYFDYWGQGTLVTVSS SEQ ID NO: 28: LB5_54 VL QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSNRPSGVSNRFSGSKSG NTASLTISGLQAEDEADYYCSSYTSSSTLVVFGGGTKLTVLGQ SEQ ID NO: 29: intentionally left open SEQ ID NO: 30: intentionally left open SEQ ID NO: 31: LB5_55 VH CDR1 GYTFTGYY SEQ ID NO: 32: LB5_55 VH CDR2 INPNSGGT SEQ ID NO: 33: LB5_55 VH CDR3 CARWWYRYYEYGVWYDGPFDY SEQ ID NO: 34: LB5_55 VL CDR1 QSVSSSY SEQ ID NO: 35: LB5_55 VL CDR2 GAS SEQ ID NO: 36: LB5_55 VL CDR3 QQYGSSP SEQ ID NO: 37: LB5_55 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTM TRDTSISTAYMELSRLRSDDTAVYYCARWWYRYYEYGVWYDGPFDYWGQGTLVTVSS SEQ ID NO: 38: LB5_55 VL EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT DFTLTISRLEPEDFAVYYCQQYGSSPLTFGQGTKLEIK SEQ ID NO: 39: intentionally left open SEQ ID NO: 40: intentionally left open SEQ ID NO: 41: LB5_57 VH CDR1 GYTFTSYG SEQ ID NO: 42: LB5_57 VH CDR2 ISAYNGNT SEQ ID NO: 43: LB5_57 VH CDR3 CARVPVRTYETGYYSDG-FDY SEQ ID NO: 44: LB5_57 VL CDR1 QSVSSSY SEQ ID NO: 45: LB5_57 VL CDR2 GAS SEQ ID NO: 46: LB5_57 VL CDR3 QQYGSSP SEQ ID NO: 47: LB5_57 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTM TTDTSTSTAYMELRSLRSDDTAVYYCARVPVRTYETGYYSDGFDYWGQGTLVTVSS SEQ ID NO: 48: LB5_57 VL EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT DFTLTISRLEPEDFAVYYCQQYGSSPLTFGQGTKLEIK SEQ ID NO: 49: intentionally left open SEQ ID NO: 50: intentionally left open SEQ ID NO: 51: LB5_59 VH CDR1 GYTFTSYG SEQ ID NO: 52: LB5_59 VH CDR2 ISAYNGNT SEQ ID NO: 53: LB5_59 VH CDR3 CARTPFTYYEFGGYPSDVFDY SEQ ID NO: 54: LB5_59 VL CDR1 QSVSSSY SEQ ID NO: 55: LB5_59 VL CDR2 GAS SEQ ID NO: 56: LB5_59 VL CDR3 QQYGSSP SEQ ID NO: 57: LB5_59 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTM TTDTSTSTAYMELRSLRSDDTAVYYCARTPFTYYEFGGYPSDVFDYWGQGTLVTVSS SEQ ID NO: 58: LB5_59 VL EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT DFTLTISRLEPEDFAVYYCQQYGSSPLTFGQGTKLEIK SEQ ID NO: 59: intentionally left open SEQ ID NO: 60: intentionally left open SEQ ID NO: 61: LB5_62 VH CDR1 GYTFTGYY SEQ ID NO: 62: LB5_62 VH CDR2 INPNSGGT SEQ ID NO: 63: LB5_62 VH CDR3 CARSANIVYQTGYYQSSLFDY SEQ ID NO: 64: LB5_62 VL CDR1 QSVSSSY SEQ ID NO: 65: LB5_62 VL CDR2 GAS SEQ ID NO: 66: LB5_62 VL CDR3 QQYGSSP SEQ ID NO: 67: LB5_62 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTM TRDTSISTAYMELSRLRSDDTAVYYCARSANIVYQTGYYQSSLFDYWGQGTLVTVSS SEQ ID NO: 68: LB5_62 VL EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT DFTLTISRLEPEDFAVYYCQQYGSSPLTFGQGTKLEIK SEQ ID NO: 69: intentionally left open SEQ ID NO: 70: intentionally left open SEQ ID NO: 71: LB5_64 VH CDR1 GGTFSSYA SEQ ID NO: 72: LB5_64 VH CDR2 IIPIFGTA SEQ ID NO: 73: LB5_64 VH CDR3 CARLTFALYVTGYYFAY-FDY SEQ ID NO: 74: LB5_64 VL CDR1 SSNIGNNY SEQ ID NO: 75: LB5_64 VL CDR2 DNN SEQ ID NO: 76: LB5_64 VL CDR3 GTWDSSLSA SEQ ID NO: 77: LB5_64 VH QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTI TADESTSTAYMELSSLRSEDTAVYYCARLTFALYVTGYYFAYFDYWGQGTLVTVSS SEQ ID NO: 78: LB5_64 VL QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGT SATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLGQ SEQ ID NO: 79: intentionally left open SEQ ID NO: 80: intentionally left open SEQ ID NO: 81: LB5_65 VH CDR1 GYTFTSYG SEQ ID NO: 82: LB5_65 VH CDR2 ISAYNGNT SEQ ID NO: 83: LB5_65 VH CDR3 CARLFYALYELDYYDLDYFDY SEQ ID NO: 84: LB5_65 VL CDR1 QSVSSSY SEQ ID NO: 85: LB5_65 VL CDR2 GAS SEQ ID NO: 86: LB5_65 VL CDR3 QQYGSSP SEQ ID NO: 87: LB5_65 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTM TTDTSTSTAYMELRSLRSDDTAVYYCARLFYALYELDYYDLDYFDYWGQGTLVTVSS SEQ ID NO: 88: LB5_65 VL EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT DFTLTISRLEPEDFAVYYCQQYGSSPLTFGQGTKLEIK SEQ ID NO: 89: intentionally left open SEQ ID NO: 90: intentionally left open SEQ ID NO: 91: LB5_66 VH CDR1 GFTFSSYW SEQ ID NO: 92: LB5_66 VH CDR2 IKQDGSEK SEQ ID NO: 93: LB5_66 VH CDR3 CARPTSYEYYTGTYADW-FDY SEQ ID NO: 94: LB5_66 VL CDR1 SSNIGNNY SEQ ID NO: 95: LB5_66 VL CDR2 DNN SEQ ID NO: 96: LB5_66 VL CDR3 GTWDSSLSA SEQ ID NO: 97: LB5_66 VH EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLEWVANIKQDGSEKYYVDSVKGRFTI SRDNAKNSLYLQMNSLRAEDTAVYYCARPTSYEYYTGTYADWFDYWGQGTLVTVSS SEQ ID NO: 98: LB5_66 VL QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGT SATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGTKLTVLGQ SEQ ID NO: 99: intentionally left open SEQ ID NO: 100: intentionally left open SEQ ID NO: 101: LB5_67 VH CDR1 GYTFTSYG SEQ ID NO: 102: LB5_67 VH CDR2 ISAYNGNT SEQ ID NO: 103: LB5_67 VH CDR3 CARGQLQAYVNGYWPTYRFDY SEQ ID NO: 104: LB5_67 VL CDR1 SSDVGGYNY SEQ ID NO: 105: LB5_67 VL CDR2 EVS SEQ ID NO: 106: LB5_67 VL CDR3 SSYTSSSTL SEQ ID NO: 107: LB5_67 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTM TTDTSTSTAYMELRSLRSDDTAVYYCARGQLQAYVNGYWPTYRFDYWGQGTLVTVSS SEQ ID NO: 108: LB5_67 VL QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSNRPSGVSNRFSGSKSG NTASLTISGLQAEDEADYYCSSYTSSSTLVVFGGGTKLTVLGQ SEQ ID NO: 109: intentionally left open SEQ ID NO: 110: intentionally left open SEQ ID NO: 111: LB5_90 VH CDR1 GYTFTGYY SEQ ID NO: 112: LB5_90 VH CDR2 INPNSGGT SEQ ID NO: 113: LB5_90 VH CDR3 CARSYFVWYTRGSYPDYSFDY SEQ ID NO: 114: LB5_90 VL CDR1 QSISSY SEQ ID NO: 115: LB5_90 VL CDR2 AAS SEQ ID NO: 116: LB5_90 VL CDR3 QQSYSTP SEQ ID NO: 117: LB5_90 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTM TRDTSISTAYMELSRLRSDDTAVYYCARSYFVWYTRGSYPDYSFDYWGQGTLVTVSS SEQ ID NO: 118: LB5_90 VL DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTD FTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK SEQ ID NO: 119: intentionally left open SEQ ID NO: 120: intentionally left open SEQ ID NO: 121: LB5_91 VH CDR1 GYTFTGYY SEQ ID NO: 122: LB5_91 VH CDR2 INPNSGGT SEQ ID NO: 123: LB5_91 VH CDR3 CARHHIGWYVTGPYVDNYFDY SEQ ID NO: 124: LB5_91 VL CDR1 QSVSSSY SEQ ID NO: 125: LB5_91 VL CDR2 GAS SEQ ID NO: 126: LB5_91 VL CDR3 QQYGSSP SEQ ID NO: 127: LB5_91 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTM TRDTSISTAYMELSRLRSDDTAVYYCARHHIGWYVTGPYVDNYFDYWGQGTLVTVSS SEQ ID NO: 128: LB5_91 VL EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT DFTLTISRLEPEDFAVYYCQQYGSSPLTFGQGTKLEIK SEQ ID NO: 129: intentionally left open SEQ ID NO: 130: intentionally left open SEQ ID NO: 131: LB5_93 VH CDR1 GGTFSSYA SEQ ID NO: 132: LB5_93 VH CDR2 IIPIFGTA SEQ ID NO: 133: LB5_93 VH CDR3 CARHEYRWYQLGPYGSDIFDY SEQ ID NO: 134: LB5_93 VL CDR1 QSISSY SEQ ID NO: 135: LB5_93 VL CDR2 AAS SEQ ID NO: 136: LB5_93 VL CDR3 QQSYSTP SEQ ID NO: 137: LB5_93 VH QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTI TADESTSTAYMELSSLRSEDTAVYYCARHEYRWYQLGPYGSDIFDYWGQGTLVTVSS SEQ ID NO: 138: LB5_93 VL DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTD FTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK SEQ ID NO: 139: intentionally left open SEQ ID NO: 140: intentionally left open SEQ ID NO: 141: LB5_94 VH CDR1 GGTFSSYA SEQ ID NO: 142: LB5_94 VH CDR2 IIPIFGTA SEQ ID NO: 143: LB5_94 VH CDR3 CAREGIVYYTTGPYRDYAFDY SEQ ID NO: 144: LB5_94 VL CDR1 QSISSY SEQ ID NO: 145: LB5_94 VL CDR2 AAS SEQ ID NO: 146: LB5_94 VL CDR3 QQSYSTP SEQ ID NO: 147: LB5_94 VH QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTI TADESTSTAYMELSSLRSEDTAVYYCAREGIVYYTTGPYRDYAFDYWGQGTLVTVSS SEQ ID NO: 148: LB5_94 VL DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTD FTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK SEQ ID NO: 149: intentionally left open SEQ ID NO: 150: intentionally left open SEQ ID NO: 151: LB5_95 VH CDR1 GGTFSSYA SEQ ID NO: 152: LB5_95 VH CDR2 IIPIFGTA SEQ ID NO: 153: LB5_95 VH CDR3 CARIPLRWYESGPYESGVFDY SEQ ID NO: 154: LB5_95 VL CDR1 QSISSY SEQ ID NO: 155: LB5_95 VL CDR2 AAS SEQ ID NO: 156: LB5_95 VL CDR3 QQSYSTP SEQ ID NO: 157: LB5_95 VH QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTI TADESTSTAYMELSSLRSEDTAVYYCARIPLRWYESGPYESGVFDYWGQGTLVTVSS SEQ ID NO: 158: LB5_95 VL DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTD FTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK SEQ ID NO: 159: intentionally left open SEQ ID NO: 160: intentionally left open SEQ ID NO: 161: 3FTX_LCa-1 Bungarus caeruleus LLCHTTSTSPISTVTCPSGENLCYTKMWCDAFCSSRGKVIELGCVATCPQPKPYEEVTCCSTDKCNPHPK QRPG SEQ ID NO: 162: 3FTX_LCa-2 Bungarus multicinctus IVCHTTATSPISAVTCPPGENLCYRKMWCDVFCSSRGKVVELGCAATCPSKKPYEEVTCCSTDKCNPHPK QRPG SEQ ID NO: 163: 3FTX_LCa-3 Dendroaspis polylepis RTCNKTFSDQSKICPPGENICYTKTWCDAFCSQRGKRVELGCAATCPKVKAGVEIKCCSTDNCNKFQFGK PR SEQ ID NO: 164: 3FTX_LCa-4 Dendroaspis viridis RTCYKTPSVKPETCPHGENICYTETWCDAWCSQRGKREELGCAATCPKVKAGVGIKCCSTDNCDPFPVKN PR SEQ ID NO: 165: 3FTX_LCa-5 Naja kaouthia, Naja siamensis IRCFITPDITSKDCPNGHVCYTKTWCDAFCSIRGKRVDLGCAATCPTVKTGVDIQCCSTDNCNPFPTRKR P SEQ ID NO: 166: 3FTX_LCa-6 Naja nivea IRCFITPDVTSQACPDGHVCYTKMWCDNFCGMRGKRVDLGCAATCPKVKPGVNIKCCSRDNCNPFPTRKR S SEQ ID NO: 167: 3FTX_LCa-8 Bungarus candidus LLCYKTPIPINAETCPPGENLCYTKMWCDIWCSSRGKVVELGCAATCPSKKPYEEVTCCSTDKCNPHPKQ RPD SEQ ID NO: 168: 3FTX_LCa-9 Dendroaspis jamesoni RTCYKTYSDKSKTCPRGEDICYTKTWCDGFCSQRGKRVELGCAATCPKVKTGVEIKCCSTDYCNPFPVWN PR SEQ ID NO: 169: 3FTX_LCa-10 Naja anchietae IRCFITPDVTSQACPDGQNICYTKTWCDNFCGMRGKRVDLGCAATCPTVKPGVDIKCCSTDNCNPFPTRE RS SEQ ID NO: 170: 3FTX_LCa-11 Naja melanoleuca KRCYRTPDLKSQTCPPGEDLCYTKKWCADWCTSRGKVIELGCVATCPKVKPYEQITCCSTDNCNPHPKMK P SEQ ID NO: 171: 3FTX_LCa-12 Naja naja IRCFITPDITSKDCPNGHVCYTKTWCDGFCRIRGERVDLGCAATCPTVKTGVDIQCCSTDDCDPFPTRKR P SEQ ID NO: 172: 3FTX_LCa-13 Naja sputatrix IRCFITPDVTSTDCPNGHVCYTKTWCDGFCSSRGRRVELGCAATCPTVKPGVDIQCCSTDNCNPFPTRP SEQ ID NO: 173: 3FTX_LCa-14 Naja oxiana ITCYKTPIITSETCAPGQNLCYTKTWCDAWCGSRGKVIELGCAATCPTVESYQDIKCCSTDNCNPHPKQK RP SEQ ID NO: 174: 3FTX_LCa-15 Ophiophagus hannah TKCYVTPDATSQTCPDGQDICYTKTWCDGFCSSRGKRIDLGCAATCPKVKPGVDIKCCSTDNCNPFPTWK RKH SEQ ID NO: 175: 3FTX_LCa-16 Naja naja IRCFITPDITSKDCPNGHVCYTKTWCDGFCSIRGKRVDLGCAATCPTVRTGVDIQCCSTDDCDPFPTRKR P SEQ ID NO: 176: 3FTX_LCa-17 Dendroaspis viridis RTCYKTPSVKPETCPHGENICYTETWCDAWCSQRGKRVELGCAATCPKVKAGVGIKCCSTDNCNPFPVWN PRG SEQ ID NO: 177: 3FTX_LCa-18 Naja melanoleuca IRCFITPDVTSQICADGHVCYTKTWCDNFCASRGKRVDLGCAATCPTVKPGVNIKCCSTDNCNPFPTRNR P SEQ ID NO: 178: 3FTX_LCa-21 IRCFITPDVTSQACPDGHVCYTKMWCDNFCGMRGKRVDLGCAATCPTVKPGVDIKCCSTDNCNPFPTRKR S SEQ ID NO: 179: 3FTX_LCa-22 IRCFITPRVSSQACPDGHVCYTKTWCDNFCGINGKRVDLGCAATCPTVKPGVDIKCCSTDNCNPFPTRKR P SEQ ID NO: 180: LB5_49 VL CDR2v2 EVSNRP SEQ ID NO: 181: LB5_53 VL CDR2v2 GASSRA SEQ ID NO: 182: LB5_54 VL CDR2v2 EVSNRP SEQ ID NO: 183: LB5_55 VL CDR2v2 GASSRA SEQ ID NO: 184: LB5_57 VL CDR2v2 GASSRA SEQ ID NO: 185 LB5_59 VL CDR2v2 GASSRA SEQ ID NO: 186: LB5_62 VL CDR2v2 GASSRA SEQ ID NO: 187: LB5_64 VL CDR2v2 DNNKRP SEQ ID NO: 188: LB5_65 VL CDR2v2 GASSRA SEQ ID NO: 189: LB5_66 VL CDR2v2 DNNKRP SEQ ID NO: 190: LB5_67 VL CDR2v2 EVSNRP SEQ ID NO: 191: LB5_90 VL CDR2v2 AASSLQ SEQ ID NO: 192: LB5_91 VL CDR2v2 GASSRA SEQ ID NO: 193: LB5_93 VL CDR2v2 AASSLQ SEQ ID NO: 194: LB5_94 VL CDR2v2 AASSLQ SEQ ID NO: 195: LB5_95 VL CDR2v2 AASSLQ SEQ ID NO: 196: 95MAT1 VH CDR1 GGTFSSYA SEQ ID NO: 197: 95MAT1 VH CDR2 IIPIFGTA SEQ ID NO: 198: 95MAT1 VH CDR3 CARIPLRWYESGPYESGVFDY SEQ ID NO: 199: 95MAT1 VL CDR1 QSISSY SEQ ID NO: 200: 95MAT1 VL CDR2 DASSLQ SEQ ID NO: 201: 95MAT1 VL CDR3 QQSYSTP SEQ ID NO: 202: 95MAT1 VH QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTI TADESTSTAYMELSSLRSEDTAVYYCARIPLRWYESGPYESGVFDYWGQGTLVTVSS SEQ ID NO: 203: 95MAT1 VL DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYDASSLQSGVPSRFSGSGSGTD FTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK SEQ ID NO: 204: 95MAT2 VH CDR1 GGTFSSYA SEQ ID NO: 205: 95MAT2 VH CDR2 IIPIFGTA SEQ ID NO: 206: 95MAT2 VH CDR3 CARIPLVWYESGPYESGVFDY SEQ ID NO: 207: 95MAT2 VL CDR1 QSISSY SEQ ID NO: 208: 95MAT2 VL CDR2 DASSLQ SEQ ID NO: 209: 95MAT2 VL CDR3 QQSYSTP SEQ ID NO: 210: 95MAT2 VH QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTI TADESTSTAYMELSSLRSEDTAVYYCARIPLVWYESGPYESGVFDYWGQGTLVTVSS SEQ ID NO: 211: 95MAT2 VL DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYDASSLQSGVPSRFSGSGSGTD FTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK SEQ ID NO: 212: 95MAT3 VH CDR1 GGTFSSYA SEQ ID NO: 213: 95MAT3 VH CDR2 IIPIFGPA SEQ ID NO: 214: 95MAT3 VH CDR3 CARIPLVWYESGPYESGVFDY SEQ ID NO: 215: 95MAT3 VL CDR1 QSISSY SEQ ID NO: 216: 95MAT3 VL CDR2 DASSLQ SEQ ID NO: 217: 95MAT3 VL CDR3 QQSYSTP SEQ ID NO: 218: 95MAT3 VH QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGPANYAQKFQGRVTI TADESTSTAYMELSSLRSEDTAVYYCARIPLVWYESGPYESGVFDYWGQGTLVTVSS SEQ ID NO: 219: 95MAT3 VL DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYDASSLQSGVPSRFSGSGSGTD FTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK SEQ ID NO: 220: 95MAT4 VH CDR1 GGTFSSYA SEQ ID NO: 221: 95MAT4 VH CDR2 IIPIFGTA SEQ ID NO: 222: 95MAT4 VH CDR3 CARIPLHWYESGPYESGVFDY SEQ ID NO: 223: 95MAT4 VL CDR1 QSISSY SEQ ID NO: 224: 95MAT4 VL CDR2 DASSLQ SEQ ID NO: 225: 95MAT4 VL CDR3 QQSYSTP SEQ ID NO: 226: 95MAT4 VH QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTI TADESTSTAYMELSSLRSEDTAVYYCARIPLHWYESGPYESGVFDYWGQGTLVTVSS SEQ ID NO: 227: 95MAT4 VL DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYDASSLQSGVPSRFSGSGSGTD FTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK SEQ ID NO: 228: 95MAT5 VH CDR1 GGTFSSYA SEQ ID NO: 229: 95MAT5 VH CDR2 YIPIFGTA SEQ ID NO: 230: 95MAT5 VH CDR3 CARIPLRWYESGPYESGVFDY SEQ ID NO: 231: 95MAT5 VL CDR1 QSISSY SEQ ID NO: 232: 95MAT5 VL CDR2 DASSLQ SEQ ID NO: 233: 95MAT5 VL CDR3 QQSYSTP SEQ ID NO: 234: 95MAT5 VH QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGYIPIFGTANYAQKFQGRVTI TADESTSTAYMELSSLRSEDTAVYYCARIPLRWYESGPYESGVFDYWGQGTLVTVSS SEQ ID NO: 235: 95MAT5 VL DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYDASSLQSGVPSRFSGSGSGTD FTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK SEQ ID NO: 236: 95MAT6 VH CDR1 GGTFSSYA SEQ ID NO: 237: 95MAT6 VH CDR2 IIPIFGHA SEQ ID NO: 238: 95MAT6 VH CDR3 CARIPLIWYESGPYESGVFDY SEQ ID NO: 239: 95MAT6 VL CDR1 QSISSY SEQ ID NO: 240: 95MAT6 VL CDR2 DASSLQ SEQ ID NO: 241: 95MAT6 VL CDR3 QQSYSTP SEQ ID NO: 242: 95MAT6 VH QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGHANYAQKFQGRVTI TADESTSTAYMELSSLRSEDTAVYYCARIPLIWYESGPYESGVFDYWGQGTLVTVSS SEQ ID NO: 243: 95MAT6 VL DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYDASSLQSGVPSRFSGSGSGTD FTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK SEQ ID NO: 244: VHCDR3 MOTIF1A RWYXXGXY SEQ ID NO: 245: VHCDR3 MOTIF1B RYYXXGXY SEQ ID NO: 246: VHCDR3 MOTIF2A 20 CARXXXRWYXXGXYXXXXFDY SEQ ID NO: 247: VHCDR3 MOTIF2B 20 CARXXXRYYXXGXYXXXXFDY SEQ ID NO: 248: VHCDR3 MOTIF2A 19 CARXXXRWYXXGXYXXXFDY SEQ ID NO: 249: VHCDR3 MOTIF2B 19 CARXXXRYYXXGXYXXXFDY SEQ ID NO: 250: alpha-bungarotoxin IVCHTTATSPISAVTCPPGENLCYRKMWCDAFCSSRGKVVELGCAATCPSKKPYEEVTCCSTDKCNPHPK QRPG

Claims

CLAIMS What is claimed is: 1. An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises 20 or 21 amino acid residues comprising the amino acid sequence of SEQ ID NO: 244-248 or 249, optionally wherein the VH is a VH1-02, VH1-18, VH1-69 or VH3-07 VH and the VL is a VL2-14, VK3-20, VK139, VL2- 14 or VL1-51 VL, optionally wherein the 3FTx-L comprises the amino acid sequence of SEQ ID NO: 161-176 or 177, and optionally wherein the 3FTx-L comprises 3FTx-L2, 3FTx-L3, 3FTx- L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, or 3FTx-L15 variants listed in Table 1.
2. An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein (1) the VH CDR1 comprises the amino acid sequence of SEQ ID NO: 151, (2) the VH CDR2 comprises the amino acid sequence of SEQ ID NO: 152, 213, 229, or 237, (3) the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 153, 214, 222 or 238, (4) the VL CDR1 comprises the amino acid sequence of SEQ ID NO: 154, (5) the VL CDR2 comprises the amino acid sequence of SEQ ID NO: 155 or 232, and (6) the VL CDR3 comprises the amino acid sequence of SEQ ID NO: 156, optionally wherein the 3FTx-L comprises the amino acid sequence of SEQ ID NO: 161-176 or 177, optionally wherein the 3FTx-L comprises 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, or 3FTx-L15 variants listed in Table 1.
3. The antibody of any one of claim 1 or claim 2, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 151- 156, respectively, SEQ ID NO: 196-201, respectively, SEQ ID NO: 204-209, respectively, SEQ ID NO: 212-217, respectively, SEQ ID NO: 220-225, respectively, SEQ ID NO: 228-233, respectively, and SEQ ID NO: 236-241, respectively.
4. The isolated monoclonal antibody according to any one of claims 1 to 3, wherein the VH and VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 157 and 158, respectively, SEQ ID NO: 202 and 203, respectively, SEQ ID NO: 210 and 211, respectively, SEQ ID NO: 218 and 219, respectively, SEQ ID NO: 226 and 227, respectively, SEQ ID NO: 234 and 235, respectively, or SEQ ID NO: 242 and 243, respectively.
5. An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of (a) SEQ ID NO: 1, 2 and 3, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) SEQ ID NO: 11, 12 and 13, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (c) SEQ ID NO: 21, 22 and 23, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (d) SEQ ID NO: 31, 32 and 33, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (e) SEQ ID NO: 41, 42 and 43, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (f) SEQ ID NO: 51, 52 and 53, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (g) SEQ ID NO: 61, 62 and 63, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (h) SEQ ID NO: 71, 72 and 73, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (i) SEQ ID NO: 81, 82 and 83, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (j) SEQ ID NO: 91, 92 and 93, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (k) SEQ ID NO: 101, 102 and 103, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (l) SEQ ID NO: 111, 112 and 113, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (m) SEQ ID NO: 121, 122 and 123, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (n) SEQ ID NO: 131, 132 and 133, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (o) SEQ ID NO: 141, 142 and 143, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; or (p) SEQ ID NO: 151, 152 and 153, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; optionally wherein the 3FTx-L comprises the amino acid sequence of SEQ ID NO: 161-176 or 177, optionally wherein the 3FTx-L comprises 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx- L8, 3FTx-L9, or 3FTx-L15 variants listed in Table 1.
6. An isolated monoclonal antibody that specifically binds to a long chain alpha-neurotoxic three finger toxin (3FTx-L) and comprises a heavy chain variable region (VH) comprising a VH CDR1, VH CDR2 and VH CDR3, and a light chain variable region (VL) comprising a VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1, VH CDR2 and VH CDR3 comprises the amino acid sequence of SEQ ID NO: 196-198, respectively, SEQ ID NO: 204-206, respectively, SEQ ID NO: 212-214, respectively, SEQ ID NO: 220-222, respectively, SEQ ID NO: 228-230, respectively, and SEQ ID NO: 236-238, respectively, optionally wherein the 3FTx-L comprises the amino acid sequence of SEQ ID NO: 161-176 or 177, optionally wherein the 3FTx-L comprises 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, or 3FTx-L15 variants listed in Table 1.
7. The isolated monoclonal antibody of claim 5 or claim 6, wherein the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of (a) SEQ ID NO: 4, 5 and 6, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) SEQ ID NO: 14, 15 and 16, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (c) SEQ ID NO: 24, 25 and 26, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (d) SEQ ID NO: 34, 35 and 36, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (e) SEQ ID NO: 44, 45 and 46, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (f) SEQ ID NO: 54, 55 and 56, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (g) SEQ ID NO: 64, 65 and 66, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (h) SEQ ID NO: 74, 75 and 76, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (i) SEQ ID NO: 84, 85 and 86, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (j) SEQ ID NO: 94, 95 and 96, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (k) SEQ ID NO: 104, 105 and 106, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (l) SEQ ID NO: 114, 115 and 116, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (m) SEQ ID NO: 124, 125 and 126, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (n) SEQ ID NO: 134, 135 and 136, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (o) SEQ ID NO: 144, 145 and 146, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (p) SEQ ID NO: 154, 155 and 156, respectively, comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions.
8. The isolated monoclonal antibody of claim 5 or claim 6, wherein the VL CDR1, VL CDR2 and VL CDR3 comprises the amino acid sequence of SEQ ID NO: 199-201, respectively, SEQ ID NO: 207-209, respectively, SEQ ID NO: 215-217, respectively, SEQ ID NO: 223-225, respectively, SEQ ID NO: 231-233, respectively, and SEQ ID NO: 239-241, respectively.
9. The isolated monoclonal antibody according to any one of claims 5 to 8, wherein (a) the VH comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 7, 17, 27, 37, 47, 57, 67, 77, 87, 97, 107, 117, 127, 137, 147 or 157, (b) the VH comprises the amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 202, 210, 218, 226, 234, or 242, (c) the VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 8, 18, 28, 38, 48, 58, 68, 78, 88, 98, 108, 118, 128, 138, 148 or 158, and/or (d) the VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 203, 211, 219, 227, 235, or 243.
10. The monoclonal antibody of any one of claims 1 to 9, further comprising a heavy and/or light chain constant region, optionally wherein the heavy and/or light chain constant region is a human heavy and/or light chain constant region, optionally wherein the heavy chain constant region is selected from the group consisting of a human immunoglobulin IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2 constant region.
11. The isolated monoclonal antibody of any one of claims 1 to 10, wherein the antibody is characterized by one or mor of (a) the antibody is a recombinant antibody, a chimeric antibody, a human antibody, an antibody fragment, a bispecific antibody, a trispecific antibody or a multispecific antibody, (b) the antibody is a bispecific antibody, a trispecific antibody or a multispecific antibody, (c) the antibody is a bispecific antibody, a trispecific antibody or a multispecific antibody capable of binding at least one toxic component of snake venom in addition to 3FTx-L, optionally wherein the at least one toxic component of snake venom in addition to 3FTx-L comprises a metalloprotease or a phospholipase, (d) the antibody is an antibody fragment, wherein the antibody fragment comprises a single- chain Fv (scFv), F(ab) fragment, F(ab’)2 fragment, or an isolated VH domain, (e) the antibody is capable of neutralizing at least two 3FTx-L variants listed in Table 1, (f) the antibody is capable of neutralizing the 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, and 3FTx-L15 variants listed in Table 1, (g) the antibody is capable of binding more than one 3FTx-L selected from the group consisting of SEQ ID NO: 161-176 and 177, (h) the antibody is capable of binding the 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx- L8, 3FTx-L9, and 3FTx-L15 variants listed in Table 1, (i) the antibody is capable of neutralizing in an in vitro cell based assay at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15 or at least 163FTx-L selected from the group consisting of SEQ ID NO: 161-176 and 177, (j) the antibody is capable of neutralizing in an in vitro cell based assay alpha-bungarotoxin (SEQ ID NO: 250), and /or (k) the antibody is capable of neutralizing in an in vitro cell based assay the 3FTx-L2, 3FTx-L3, 3FTx-L5, 3FTx-L6, 3FTx-L8, 3FTx-L9, and 3FTx-L15 variants listed in Table 1.
12. A pharmaceutical composition comprising the monoclonal antibody of any one of claims 1 to 11 and a pharmaceutically acceptable excipient, optionally wherein the pharmaceutical composition further comprises a second antibody that is capable of binding at least one toxic component of snake venom in addition to 3FTx-L, optionally wherein the at least one toxic component of snake venom in addition to 3FTx-L comprises a metalloprotease or a phospholipase.
13. An isolated polynucleotide encoding the heavy chain variable region or heavy chain of the antibody of any one of claims 1 to 11 and/or the light chain variable region or light chain of the antibody of any one of claims 1 to 11, optionally wherein the isolated polynucleotide is an RNA comprising a modified nucleotide.
14. A host cell comprising the polynucleotide of claim 13.
15. A method of producing an antibody that binds to 3FTx-L comprising culturing the host cell of claim 14 so that the polynucleotide is expressed and the antibody is produced.
16. A method of neutralizing an 3FTx-L comprising contacting the 3FTx-L with a sufficient amount of the antibody of any one of claims 1 to 11, or the pharmaceutical composition of claim 12.
17. A method of treating snake bite or passive immunization comprising administering to a subject in need thereof a therapeutically sufficient amount of the antibody of any one of claims 1 to 11, or the pharmaceutical composition of claim 12.
18. The method of claim 17, further comprising administering at least one additional therapeutic agent, optionally wherein the additional therapeutic agent is an antitoxin.
19. A method of producing an engineered variant of an antibody comprising (a) substituting one or more amino acid residues of the VH; and/or substituting one or more amino acid residues of the VL to create an engineered variant antibody, and (b) and producing the engineered variant antibody, wherein the antibody is LB5_49, LB5_53, LB5_54, LB5_55, LB5_57, LB5_59, LB5_62, LB5_64, LB5_65, LB5_66, LB5_67, LB5_90, LB5_91, LB5_93, LB5_94 or LB5_95, or wherein the antibody is 95MAT1, 95MAT2, 95MAT3, 95MAT4, 95MAT5 or 95MAT6.
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