Compositions and methods for treating and inhibiting allergic reactions

Abstract

Disclosed herein are antibodies, compositions and methods for treating allergic reactions.In some embodiments, the compositions are combination treatments of more than one antibody.In some embodiments, the antibody binds to Ara h 2 and / or Ara h 6 and is useful for treating peanut allergy.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 382,963, filed November 9, 2022, which is incorporated herein by reference in its entirety. Summary of the Invention

[0002] Disclosed herein is a composition comprising a first binding domain that binds to Ara h 2 and Ara h 6, wherein the first binding domain comprises a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences of HC-CDR1: SEQ ID NO: 1, HC-CDR2: SEQ ID NO: 2 or SEQ ID NO: 3, and HC-CDR-3: SEQ ID NO: 4 or SEQ ID NO: 5; and the first binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequence of LC-CDR1: SEQ ID NO: 6, LC-CDR2: SEQ ID NO: 7, and LC-CDR-3: SEQ ID NO: 8. and a second binding domain that binds to Ara h, wherein the second binding domain comprises a VH comprising CDRs: HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequence of SEQ ID NO: 18, the amino acid sequence of SEQ ID NO: 19, and the amino acid sequence of SEQ ID NO: 20 or SEQ ID NO: 21; and the second binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences of SEQ ID NO: 22, SEQ ID NO: 23, and SEQ ID NO: 24. 2, the third binding domain comprises a VH comprising CDRs: HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise: HC-CDR1: an amino acid sequence according to SEQ ID NO: 35, HC-CDR2: an amino acid sequence according to SEQ ID NO: 36 or SEQ ID NO: 37, HC-CDR-3: an amino acid sequence according to SEQ ID NO: 38; and the third binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2,LC-CDR3 comprises the amino acid sequence according to LC-CDR1: SEQ ID NO: 39, LC-CDR2: SEQ ID NO: 40, LC-CDR3: SEQ ID NO: 41. In some embodiments, the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 9 or SEQ ID NO: 10. In some embodiments, the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 11. In some embodiments, the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:9 or SEQ ID NO:10, and the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:11. In some embodiments, the first binding domain comprises a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the first binding domain is a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the first binding domain comprises an scFv. In some embodiments, the VH of the first binding domain and the VL of the first binding domain are connected by an scFv linker sequence. In some embodiments, the scFv linker sequence of the first binding domain comprises an amino acid sequence according to SEQ ID NO: 12. In some embodiments, the scFv of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 13 or SEQ ID NO: 14. In some embodiments, the first binding domain comprises a constant domain. In some embodiments, the constant domain of the first binding domain comprises a human IgG4 sequence. In some embodiments, the human IgG4 sequence of the first binding domain comprises a S228P point mutation, where the amino acid numbering is according to the EU index of Kabat et al. In some embodiments, the human IgG4 sequence of the first binding domain isIn some embodiments, the constant domain of the first binding domain comprises a human IgG1 sequence. In some embodiments, the constant domain of the first binding domain comprises a C, H 1. C H 2. C H 3, or C L In some embodiments, the first binding domain comprises the amino acid sequence C H 1. C H 2. C H 3, and C LIn some embodiments, the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 72, or SEQ ID NO: 73, and the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 17. In some embodiments, the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 25 or SEQ ID NO: 26. In some embodiments, the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 27 or SEQ ID NO: 28. In some embodiments, the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:25 or SEQ ID NO:26, and the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:27 or SEQ ID NO:28. In some embodiments, the second binding domain comprises a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the second binding domain is a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the second binding domain comprises an scFv. In some embodiments, the VH of the second binding domain and the VL of the second binding domain are connected by an scFv linker sequence. In some embodiments, the scFv linker sequence of the second binding domain comprises an amino acid sequence according to SEQ ID NO: 29. In some embodiments, the scFv of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 30 or SEQ ID NO: 31. In some embodiments, the second binding domain comprises a constant domain.In some embodiments, the constant domain of the second binding domain comprises a human IgG4 sequence. In some embodiments, the human IgG4 sequence of the second binding domain comprises a S228P point mutation, amino acid numbering according to the EU index of Kabat et al. In some embodiments, the human IgG4 sequence of the second binding domain does not have a C-terminal lysine residue. In some embodiments, the constant domain of the second binding domain comprises a human IgG1 sequence. In some embodiments, the constant domain of the second binding domain is C. H 1. C H 2. C H 3, or C L In some embodiments, the second binding domain comprises the amino acid sequence C H 1. C H 2. C H 3, and C LIn some embodiments, the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:74, or SEQ ID NO:75, and the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:34 or SEQ ID NO:76. In some embodiments, the VH of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:42 or SEQ ID NO:43. In some embodiments, the VL of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:44. In some embodiments, the VH of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 42 or SEQ ID NO: 43, and the VL of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 44. In some embodiments, the third binding domain comprises a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the third binding domain is a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the third binding domain comprises an scFv. In some embodiments, the VH of the third binding domain and the VL of the third binding domain are connected by an scFv linker sequence. In some embodiments, the scFv linker sequence of the third binding domain comprises an amino acid sequence according to SEQ ID NO: 45. In some embodiments, the scFv of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 46 or SEQ ID NO: 47. In some embodiments, the third binding domain comprises a constant domain.In some embodiments, the constant domain of the third binding domain comprises a human IgG4 sequence. In some embodiments, the human IgG4 sequence of the third binding domain comprises a S228P point mutation, and the amino acid numbering is according to the EU index of Kabat et al. In some embodiments, the human IgG4 sequence of the third binding domain does not have a C-terminal lysine residue. In some embodiments, the constant domain of the third binding domain comprises a human IgG1 sequence. In some embodiments, the constant domain of the third binding domain is C. H 1. C H 2. C H 3, or C L In some embodiments, the third binding domain comprises the amino acid sequence C H 1. C H 2. C H 3, and C L In some embodiments, the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78, and the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50. In some embodiments, the first binding domain, the second binding domain, and the third binding domain The domains are connected within the same molecule. In some embodiments, the first binding domain, the second binding domain, and the third binding domain are separate molecules. In some embodiments, the first binding domain and the second binding domain are within the same molecule, and the third binding domain is a separate molecule from the molecule comprising the first binding domain and the second binding domain. In some embodiments, the first binding domain and the third binding domain are within the same molecule, and the second binding domain is a separate molecule from the molecule comprising the first binding domain and the third binding domain. In some embodiments, the second binding domain and the third binding domain are within the same molecule, and the first binding domain is a separate molecule from the molecule comprising the second binding domain and the third binding domain. In some embodiments, the first binding domain comprises an scFv, and the second binding domain comprises a C H 1. C H 2. C H 3, and C L In some embodiments, the second binding domain comprises an scFv and the first binding domain comprises a C H 1. C H 2. C H 3, and C L In some embodiments, the first binding domain and the second binding domain are connected by a linking moiety. In some embodiments, the linking moiety is an amino acid sequence. In some embodiments, the linking moiety is at least 4 amino acids in length. In some embodiments, the linking moiety is between 4 and 20 amino acids in length. In some embodiments, the linking moiety is connected to the C of the second binding domain. Ha linking moiety comprising an amino acid sequence of at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:53 and an amino acid sequence of at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:52; a third binding domain comprising an amino acid sequence of at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78; and a third binding domain comprising an amino acid sequence of at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50. In some embodiments, the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:55 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:54; the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78; and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50.In some embodiments, the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:65 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:64; the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78; and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50. In some embodiments, the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:67 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:66; the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78; and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50.In some embodiments, the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:69 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:68; the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78; and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50. In some embodiments, the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:71 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:70, the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78, and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50. In some embodiments, the composition comprises a pharmaceutically acceptable excipient.

[0003] Disclosed herein is an isolated, recombinant nucleic acid sequence that encodes the amino acid sequence of the composition according to any one of the above embodiments.

[0004] Disclosed herein are vectors comprising the isolated recombinant nucleic acid sequences described in the above embodiments.

[0005] Disclosed herein is a kit comprising at least one of the composition according to any one of the above embodiments, the vector according to the above embodiments, or the nucleic acid molecule according to the above embodiments.

[0006] Disclosed herein is a method of treating a food allergy in a subject in need thereof, comprising administering to the subject a composition described in any one of the above embodiments.

[0007] Disclosed herein is a method for treating a food allergy in a subject in need thereof, comprising administering to the subject a composition according to any one of the above-described embodiments. In some embodiments, the food allergy comprises a peanut allergy. [Brief explanation of the drawings]

[0008] The novel features of the present disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the disclosure are utilized, and the accompanying drawings.

[0009] [Figure 1] 1 shows the distribution of peanut antigen specificity of mAbs discovered from individuals with peanut allergy. [Figure 2] Figure 1 shows epitope binning of Ara h 2-specific mAbs. [Figure 3A] A simplified ELISA for assessing the ability of IgG mAbs to block the binding of allergic plasma IgE to tagged allergens is shown. [Figure 3B] 1 shows the inhibition of recombinant Ara h 2 binding to peanut-allergic plasma IgE by one or more molecule 2 mAbs. [Figure 3C] Binding of molecule 1 and molecule 2 mAbs to recombinant Ara h 2 is shown. [Figure 3D]Molecule 1 and Molecule 2 mAbs inhibit binding of recombinant Ara h 2 to peanut-allergic plasma IgE. [Figure 4A] 1 shows an outline of the mast cell activation test (MAT). [Figure 4B] Percent inhibition of peanut- and Ara h 2-mediated mast cell activation by IgG1 and IgG4 mAbs alone or in combination is shown. [Figure 5A] Combination 1 containing two molecules is shown. [Figure 5B] 1 shows the blocking of recombinant Ara h 2 binding to peanut allergic plasma IgE by Combination 1. [Figure 5C] Figure 1 shows the inhibition of peanut-mediated mast cell activation by Combination 1 and its components. [Figure 6A] This paper presents the protocol for a mouse model of peanut allergy oral sensitization / oral peanut challenge. [Figure 6B] Figure 1 shows the dose-dependent effect of Combination 1 and its components on the hypothermic response in peanut-allergic animals when administered 25 mg of peanut protein delivered by oral gavage. [Figure 6C] Figure 1 shows the dose-dependent effect of Combination 1 and its components on serum MCPT-1 in peanut-allergic animals when administered 25 mg of peanut protein delivered by oral gavage. DETAILED DESCRIPTION OF THE INVENTION

[0010] Allergies are characterized by a number of illnesses caused by hypersensitivity of the immune system to typically harmless substances in the environment. Generally, allergic reactions occur when aspects of the immune system overreact to the presence of substances (allergens) that would not otherwise provoke a reaction. Foods, insect stings, and medications are common causes of severe allergic reactions. In addition, there are many significant non-food allergies, including, but not limited to, pollens (e.g., ragweed, trees, and grasses), animals (e.g., animal dander), mold, metals, and latex.

[0011] As commonly understood, an allergen is a type of antigen that elicits an abnormally vigorous immune response, causing the immune system to fight off an otherwise harmless perceived threat. In technical terms, an allergen is an antigen capable of stimulating a type I hypersensitivity reaction in atopic individuals via an immunoglobulin E (IgE) response. Most humans exhibit a significant IgE response only as a defense against parasitic infections. However, some individuals can react to many common environmental antigens. This genetic predisposition is called atopy. In atopic individuals, non-parasitic antigens stimulate inappropriate IgE production, resulting in type I hypersensitivity.

[0012] Some foods, such as peanuts (legumes), tree nuts, seafood, and shellfish, are the cause of serious allergies in many people. The U.S. Food and Drug Administration officially recognizes nine foods as common in terms of allergic reactions in large portions of susceptible populations. These include peanuts, tree nuts, eggs, milk, shellfish, fish, sesame, wheat and their derivatives, and soybeans and their derivatives, as well as sulfites (chemical-based, often found in flavors and colors in foods).

[0013] An allergic reaction can be caused by some form of contact with a sensitive food or drink that causes the allergen to be ingested (ingestion), breathing pollen, fragrances, or pet dander (inhalation), or brushing a body part against an allergy-causing plant (direct contact). An extremely severe form of allergic reaction is called anaphylaxis.

[0014] Immunoglobulin E (IgE) antibodies mediate allergic responses. They bind to specific receptors on inflammatory immune cells, including mast cells in mucosal tissues lining body surfaces and cavities, and basophils in the circulation. These cells mediate allergic responses triggered by specific antigens (allergens) recognized by IgE through the release of inflammatory molecules such as histamine. The inflammatory response is responsible for symptoms such as sneezing, runny or stuffy nose, itchy eyes, and difficulty breathing, and in extreme cases, can even cause anaphylactic shock and death.

[0015] Food allergies have increased over time. The most common food allergens include soy products, tree nuts (almonds, cashews, walnuts, pecans, pistachios, Brazil nuts, macadamias, etc.), peanuts, eggs, shellfish, fish, milk, sesame, and wheat. Food allergies adversely affect quality of life and also result in significant economic burdens. For example, allergy sufferers may become hypervigilant and avoid situations, including social interactions, that may lead to an allergic reaction. Furthermore, people with multiple food allergies are at increased risk of severe reactions and anaphylaxis. Currently, there is no cure for many allergies, and individuals must practice lifelong avoidance strategies. Treatment of allergies involves avoiding known allergens and the use of medications such as steroids and antihistamines. In severe reactions, injectable adrenaline (epinephrine) is recommended as a rescue treatment. One approach to treating allergies is immunotherapy, which involves repeated injections or exposure to allergen extracts to desensitize patients to the allergen. However, immunotherapy is time-consuming, usually requiring several years of treatment, and often fails to achieve its goal of desensitizing patients to allergens. Furthermore, immunotherapy carries the risk of potentially serious adverse events, including anaphylaxis. Therefore, improved therapies for treating allergic reactions are needed.

[0016] Disclosed herein are compositions for preventing, treating, and suppressing allergic reactions associated with specific allergens. The compositions provide formulations of high-affinity, allergen-specific antibodies designed to reduce and / or prevent allergic reactions associated with specific allergens.

[0017] composition Antibodies that bind to Ara h 2 and Ara h 6 Disclosed herein is an isolated antibody that binds to Ara h 2 and Ara h 6, the isolated antibody comprising a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences of HC-CDR1: SEQ ID NO: 1, HC-CDR2: SEQ ID NO: 2 or SEQ ID NO: 3, and HC-CDR-3: SEQ ID NO: 4 or SEQ ID NO: 5; and the isolated antibody comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 6, LC-CDR2: SEQ ID NO: 7, and LC-CDR-3: SEQ ID NO: 8. Disclosed herein is an isolated antibody that binds to Ara h 2 and Ara h 6, the isolated antibody comprising a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences according to SEQ ID NO: 1 for HC-CDR1, SEQ ID NO: 2 for HC-CDR2, and SEQ ID NO: 4 for HC-CDR3; and the isolated antibody comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences according to SEQ ID NO: 6 for LC-CDR1, SEQ ID NO: 7 for LC-CDR2, and SEQ ID NO: 8 for LC-CDR3. In some embodiments, the VH comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 9 or SEQ ID NO: 10. In some embodiments, the VL comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 11.In some embodiments, the VH comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:9 or SEQ ID NO:10, and the VL comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:11. In some embodiments, the isolated antibody comprises a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the isolated antibody is a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the isolated antibody comprises an scFv. In some embodiments, the VH and VL are connected by an scFv linker sequence. In some embodiments, the scFv linker sequence comprises an amino acid sequence according to SEQ ID NO:12. In some embodiments, the scFv comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 13 or SEQ ID NO: 14. In some embodiments, the isolated antibody comprises a constant domain. In some embodiments, the constant domain comprises a human IgG4 sequence. In some embodiments, the human IgG4 sequence comprises a S228P point mutation, and the amino acid numbering is according to the EU index of Kabat et al. In some embodiments, the human IgG4 sequence does not have a C-terminal lysine residue. In some embodiments, the constant domain comprises a human IgG1 sequence. In some embodiments, the constant domain is a C. H 1. C H 2. C H 3, and C L In some embodiments, the isolated antibody comprises the amino acid sequence C H 1. C H 2. C H 3, and C LIn some embodiments, the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 72, or SEQ ID NO: 73, and the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 17.

[0018] [Table 1-1] [Table 1-2] [Table 1-3]

[0019] Disclosed herein is an antibody that binds to Ara h 2 and Ara h 6, the antibody comprising a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences of HC-CDR1: SEQ ID NO: 18, HC-CDR2: SEQ ID NO: 19, and HC-CDR-3: SEQ ID NO: 20 or SEQ ID NO: 21; and the isolated antibody comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 22, LC-CDR2: SEQ ID NO: 23, and LC-CDR-3: SEQ ID NO: 24. Disclosed herein is an antibody that binds to Ara h 2 and Ara h 6, the antibody comprising a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences of HC-CDR1: SEQ ID NO: 18, HC-CDR2: SEQ ID NO: 19, and HC-CDR-3: SEQ ID NO: 20; and the isolated antibody comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 22, LC-CDR2: SEQ ID NO: 23, and LC-CDR-3: SEQ ID NO: 24. In some embodiments, the VH comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 25 or SEQ ID NO: 26. In some embodiments, the VL comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 27 or SEQ ID NO: 28.In some embodiments, the VH comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:25 or SEQ ID NO:26, and the VL comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:27 or SEQ ID NO:28. In some embodiments, the isolated antibody comprises a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the isolated antibody is a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the isolated antibody comprises an scFv. In some embodiments, the VH and VL are connected by an scFv linker sequence. In some embodiments, the scFv linker sequence comprises an amino acid sequence according to SEQ ID NO:29. In some embodiments, the scFv comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 30 or SEQ ID NO: 31. In some embodiments, the isolated antibody comprises a constant domain. In some embodiments, the constant domain comprises a human IgG4 sequence. In some embodiments, the human IgG4 sequence comprises a S228P point mutation, and the amino acid numbering is according to the EU index of Kabat et al. In some embodiments, the human IgG4 sequence does not have a C-terminal lysine residue. In some embodiments, the constant domain comprises a human IgG1 sequence. In some embodiments, the constant domain is a C. H 1. C H 2. C H 3, and C L In some embodiments, the isolated antibody comprises the amino acid sequence C H 1. C H 2. C H 3, and C LIn some embodiments, the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:74, or SEQ ID NO:75, and the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:34 or SEQ ID NO:76.

[0020] [Table 2-1] [Table 2-2] [Table 2-3]

[0021] Antibodies that bind to Ara h 2 Disclosed herein is an isolated antibody that binds to Ara h 2, the isolated antibody comprising a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences according to HC-CDR1: SEQ ID NO: 35, HC-CDR2: SEQ ID NO: 36 or SEQ ID NO: 37, and HC-CDR-3: SEQ ID NO: 38; and the isolated antibody comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences according to LC-CDR1: SEQ ID NO: 39, LC-CDR2: SEQ ID NO: 40, and LC-CDR-3: SEQ ID NO: 41. Disclosed herein is an isolated antibody that binds to Ara h 2, the isolated antibody comprising a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences according to HC-CDR1: SEQ ID NO: 35, HC-CDR2: SEQ ID NO: 36, and HC-CDR-3: SEQ ID NO: 38; and wherein said isolated antibody comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein said LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences according to LC-CDR1: SEQ ID NO: 39, LC-CDR2: SEQ ID NO: 40, and LC-CDR-3: SEQ ID NO: 41. In some embodiments, the VH comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 42 or SEQ ID NO: 43. In some embodiments, the VL comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 44. In some embodiments, the VH comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 42 or SEQ ID NO: 43, and the VL comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 44.In some embodiments, the isolated antibody comprises a Fab, Fab', F(ab')2, or single-chain variable fragment (scFv). In some embodiments, the isolated antibody is a Fab, Fab', F(ab')2, or single-chain variable fragment (scFv). In some embodiments, the isolated antibody comprises an scFv. In some embodiments, the VH and VL are connected by an scFv linker sequence. In some embodiments, the scFv linker sequence comprises an amino acid sequence according to SEQ ID NO: 45. In some embodiments, the scFv comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 46 or SEQ ID NO: 47. In some embodiments, the isolated antibody comprises a constant domain. In some embodiments, the constant domain comprises a human IgG4 sequence. In some embodiments, the human IgG4 sequence comprises a S228P point mutation, and the amino acid numbering is according to the EU index of Kabat et al. In some embodiments, the human IgG4 sequence does not have a C-terminal lysine residue. In some embodiments, the constant domain comprises a human IgG1 sequence. H 1. C H 2. C H 3, and C L In some embodiments, the isolated antibody comprises the amino acid sequence C H 1. C H 2. C H 3, and C L In some embodiments, the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78, and the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50.

[0022] [Table 3-1] [Table 3-2] [Table 3-3]

[0023] Antibodies having a first binding domain and a second binding domain Disclosed herein is an isolated antibody comprising a first binding domain that binds to Ara h 2 and Ara h 6, wherein the first binding domain comprises a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences according to HC-CDR1: SEQ ID NO: 1, HC-CDR2: SEQ ID NO: 2 or SEQ ID NO: 3, and HC-CDR-3: SEQ ID NO: 4 or SEQ ID NO: 5; and the first binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences according to LC-CDR1: SEQ ID NO: 6, LC-CDR2: SEQ ID NO: 7, and LC-CDR-3: SEQ ID NO: 8; and the isolated antibody binds to Ara h 2 and Ara h 6. 6, wherein the second binding domain comprises a VH comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences of HC-CDR1: SEQ ID NO: 18, HC-CDR2: SEQ ID NO: 19, and HC-CDR-3: SEQ ID NO: 20 or SEQ ID NO: 21; and the second binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 22, LC-CDR2: SEQ ID NO: 23, and LC-CDR-3: SEQ ID NO: 24.Disclosed herein is an isolated antibody comprising a first binding domain that binds to Ara h 2 and Ara h 6, wherein the first binding domain comprises a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences according to HC-CDR1: SEQ ID NO: 1, HC-CDR2: SEQ ID NO: 2, and HC-CDR-3: SEQ ID NO: 4; and the first binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences according to LC-CDR1: SEQ ID NO: 6, LC-CDR2: SEQ ID NO: 7, and LC-CDR-3: SEQ ID NO: 8. 6, wherein the second binding domain comprises a VH comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences of HC-CDR1: SEQ ID NO: 18, HC-CDR2: SEQ ID NO: 19, and HC-CDR-3: SEQ ID NO: 20; and the second binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 22, LC-CDR2: SEQ ID NO: 23, and LC-CDR-3: SEQ ID NO: 24. In some embodiments, the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 9 or SEQ ID NO: 10. In some embodiments, the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 11.In some embodiments, the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:9 or SEQ ID NO:10, and the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:11. In some embodiments, the first binding domain comprises a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the first binding domain is a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the first binding domain comprises an scFv. In some embodiments, the VH of the first binding domain and the VL of the first binding domain are connected by an scFv linker sequence. In some embodiments, the scFv linker sequence of the first binding domain comprises an amino acid sequence according to SEQ ID NO: 12. In some embodiments, the scFv of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 13 or SEQ ID NO: 14. In some embodiments, the first binding domain comprises a constant domain. In some embodiments, the constant domain of the first binding domain comprises a human IgG4 sequence. In some embodiments, the human IgG4 sequence of the first binding domain comprises a S228P point mutation, where the amino acid numbering is according to the EU index of Kabat et al. In some embodiments, the human IgG4 sequence of the first binding domain does not have a C-terminal lysine residue. In some embodiments, the constant domain of the first binding domain comprises a human IgG1 sequence. In some embodiments, the constant domain of the first binding domain is C. H 1. C H 2. C H 3, or C L In some embodiments, the first binding domain comprises the amino acid sequence C H 1. C H 2. C H 3, and C LIn some embodiments, the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 72, or SEQ ID NO: 73, and the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 17. In some embodiments, the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 25 or SEQ ID NO: 26. In some embodiments, the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 27 or SEQ ID NO: 28. In some embodiments, the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:25 or SEQ ID NO:26, and the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:27 or SEQ ID NO:28. In some embodiments, the second binding domain comprises a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the second binding domain is a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the second binding domain comprises an scFv. In some embodiments, the VH of the second binding domain and the VL of the second binding domain are connected by an scFv linker sequence. In some embodiments, the scFv linker sequence of the second binding domain comprises an amino acid sequence according to SEQ ID NO: 29. In some embodiments, the scFv of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 30 or SEQ ID NO: 31. In some embodiments, the second binding domain comprises a constant domain.In some embodiments, the constant domain of the second binding domain comprises a human IgG4 sequence. In some embodiments, the human IgG4 sequence of the second binding domain comprises a S228P point mutation, and the amino acid numbering is according to the EU index of Kabat et al. In some embodiments, the human IgG4 sequence of the second binding domain does not have a C-terminal lysine residue. In some embodiments, the constant domain of the second binding domain comprises a human IgG1 sequence. In some embodiments, the constant domain of the second binding domain is C. H 1. C H 2. C H 3, or C L In some embodiments, the second binding domain comprises the amino acid sequence C H 1. C H 2. C H 3, and C L In some embodiments, the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:74, or SEQ ID NO:75, and the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:34 or SEQ ID NO:76. In some embodiments, the first binding domain comprises an scFv and the second binding domain comprises a C H 1. C H 2. C H 3, and C L In some embodiments, the second binding domain comprises an scFv and the first binding domain comprises a C H 1. C H 2. C H 3, and C LIn some embodiments, the first binding domain and the second binding domain are connected by a linking moiety. In some embodiments, the linking moiety is an amino acid sequence. In some embodiments, the linking moiety is at least 4 amino acids in length. In some embodiments, the linking moiety is between 4 and 20 amino acids in length. In some embodiments, the linking moiety is connected to the C of the second binding domain. H a linking moiety comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 53 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 52. In some embodiments, the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 55 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 54. In some embodiments, the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 65 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 64. In some embodiments, the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 67 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 66. In some embodiments, the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 66. The antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 69, and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 68. In some embodiments, the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 71, and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 70.

[0024] Disclosed herein is an isolated antibody comprising a first binding domain that binds to Ara h 2 and Ara h 6, wherein the first binding domain comprises a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, and HC-CDR3, wherein the HC-CDR1, HC-CDR2, and HC-CDR3 comprise the amino acid sequences of HC-CDR1: SEQ ID NO: 1, HC-CDR2: SEQ ID NO: 2 or SEQ ID NO: 3, and HC-CDR-3: SEQ ID NO: 4 or SEQ ID NO: 5; and the first binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, and LC-CDR3, wherein the LC-CDR1, LC-CDR2, and LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 6, LC-CDR2: SEQ ID NO: 7, and LC-CDR-3: SEQ ID NO: 8. and a second binding domain that binds to IgG1A-B12, wherein the second binding domain comprises a VH comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, and HC-CDR3, wherein the HC-CDR1, HC-CDR2, and HC-CDR3 comprise the amino acid sequences of HC-CDR1: SEQ ID NO: 35, HC-CDR2: SEQ ID NO: 36 or SEQ ID NO: 37, and HC-CDR-3: SEQ ID NO: 38. The isolated antibody comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, and LC-CDR3, wherein the LC-CDR1, LC-CDR2, and LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 39, LC-CDR2: SEQ ID NO: 40, and LC-CDR-3: SEQ ID NO: 41.Disclosed herein is an isolated antibody comprising a first binding domain that binds to Ara h 2 and Ara h 6, wherein the first binding domain comprises a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, and HC-CDR3, wherein the HC-CDR1, HC-CDR2, and HC-CDR3 comprise the amino acid sequences according to SEQ ID NO: 1 for HC-CDR1, SEQ ID NO: 2 for HC-CDR2, and SEQ ID NO: 4 for HC-CDR3; and the first binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, and LC-CDR3, wherein the LC-CDR1, LC-CDR2, and LC-CDR3 comprise the amino acid sequences according to SEQ ID NO: 6 for LC-CDR1, SEQ ID NO: 7 for LC-CDR2, and SEQ ID NO: 8 for LC-CDR3; and the isolated antibody binds to Ara h 2 and Ara h 6. and a second binding domain that binds to IgG1A-B12, the second binding domain comprising a VH comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences of HC-CDR1: SEQ ID NO: 35, HC-CDR2: SEQ ID NO: 36, and HC-CDR-3: SEQ ID NO: 38. The isolated antibody comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 39, LC-CDR2: SEQ ID NO: 40, and LC-CDR-3: SEQ ID NO: 41. In some embodiments, the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 9 or SEQ ID NO: 10. In some embodiments, the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 11.In some embodiments, the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:9 or SEQ ID NO:10, and the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:11. In some embodiments, the first binding domain comprises a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the first binding domain is a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the first binding domain comprises an scFv. In some embodiments, the VH of the first binding domain and the VL of the first binding domain are connected by an scFv linker sequence. In some embodiments, the scFv linker sequence of the first binding domain comprises an amino acid sequence according to SEQ ID NO: 12. In some embodiments, the scFv of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 13 or SEQ ID NO: 14. In some embodiments, the first binding domain comprises a constant domain. In some embodiments, the constant domain of the first binding domain comprises a human IgG4 sequence. In some embodiments, the human IgG4 sequence of the first binding domain comprises a S228P point mutation, where the amino acid numbering is according to the EU index of Kabat et al. In some embodiments, the human IgG4 sequence of the first binding domain does not have a C-terminal lysine residue. In some embodiments, the constant domain of the first binding domain comprises a human IgG1 sequence. In some embodiments, the constant domain of the first binding domain is C. H 1. C H 2. C H 3, or C L In some embodiments, the first binding domain comprises the amino acid sequence C H 1. C H 2. C H 3, and C LIn some embodiments, the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 72, or SEQ ID NO: 73, and the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 17. In some embodiments, the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 42 or SEQ ID NO: 43. In some embodiments, the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 44. In some embodiments, the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 42 or SEQ ID NO: 43, and the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 44. In some embodiments, the second binding domain comprises a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the second binding domain is a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the second binding domain comprises an scFv. In some embodiments, the VH of the second binding domain and the VL of the second binding domain are connected by an scFv linker sequence. In some embodiments, the scFv linker sequence of the second binding domain comprises an amino acid sequence according to SEQ ID NO: 45. In some embodiments, the scFv of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 46 or SEQ ID NO: 47. In some embodiments, the second binding domain comprises a constant domain.In some embodiments, the constant domain of the second binding domain comprises a human IgG4 sequence. In some embodiments, the human IgG4 sequence of the second binding domain comprises a S228P point mutation, and the amino acid numbering is according to the EU index of Kabat et al. In some embodiments, the human IgG4 sequence of the second binding domain does not have a C-terminal lysine residue. In some embodiments, the constant domain of the second binding domain comprises a human IgG1 sequence. In some embodiments, the constant domain of the second binding domain is C. H 1. C H 2. C H 3, or C L In some embodiments, the second binding domain comprises the amino acid sequence C H 1. C H 2. C H 3, and C L In some embodiments, the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78, and the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50. In some embodiments, the first binding domain comprises an scFv and the second binding domain comprises a C H 1. C H 2. C H 3, and C L In some embodiments, the second binding domain comprises an scFv and the first binding domain comprises a C H 1. C H 2. C H 3, and C LIn some embodiments, the first binding domain and the second binding domain are connected by a linking moiety. In some embodiments, the linking moiety is an amino acid sequence. In some embodiments, the linking moiety is at least 4 amino acids in length. In some embodiments, the linking moiety is between 4 and 20 amino acids in length. In some embodiments, the linking moiety is connected to the C of the second binding domain. H a linking moiety comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 57 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 56; an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 59 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 58;

[0025] Disclosed herein is an isolated antibody comprising a first binding domain that binds to Ara h 2 and Ara h 6, wherein the first binding domain comprises a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences of HC-CDR1: SEQ ID NO: 18, HC-CDR2: SEQ ID NO: 19, and HC-CDR-3: SEQ ID NO: 20 or SEQ ID NO: 21; and the first binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 22, LC-CDR2: SEQ ID NO: 23, and LC-CDR-3: SEQ ID NO: 24; and the isolated antibody binds to Ara h 2 and Ara h 6. and a second binding domain that binds to IgG1A-B12, wherein the second binding domain comprises a VH comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, and HC-CDR3, wherein the HC-CDR1, HC-CDR2, and HC-CDR3 comprise the amino acid sequences of HC-CDR1: SEQ ID NO: 35, HC-CDR2: SEQ ID NO: 36 or SEQ ID NO: 37, and HC-CDR-3: SEQ ID NO: 38. The isolated antibody comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, and LC-CDR3, wherein the LC-CDR1, LC-CDR2, and LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 39, LC-CDR2: SEQ ID NO: 40, and LC-CDR-3: SEQ ID NO: 41.Disclosed herein is an isolated antibody comprising a first binding domain that binds to Ara h 2 and Ara h 6, wherein the first binding domain comprises a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences according to HC-CDR1: SEQ ID NO: 18, HC-CDR2: SEQ ID NO: 19, and HC-CDR-3: SEQ ID NO: 20; and the first binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences according to LC-CDR1: SEQ ID NO: 22, LC-CDR2: SEQ ID NO: 23, and LC-CDR-3: SEQ ID NO: 24. and a second binding domain that binds to IgG1A-B12, the second binding domain comprising a VH comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences of HC-CDR1: SEQ ID NO: 35, HC-CDR2: SEQ ID NO: 36, and HC-CDR-3: SEQ ID NO: 38. The isolated antibody comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 39, LC-CDR2: SEQ ID NO: 40, and LC-CDR-3: SEQ ID NO: 41. In some embodiments, the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 25 or SEQ ID NO: 26. In some embodiments, the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 27 or SEQ ID NO: 28.In some embodiments, the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:25 or SEQ ID NO:26, and the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:27 or SEQ ID NO:28. In some embodiments, the first binding domain comprises a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the first binding domain is a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the first binding domain comprises an scFv. In some embodiments, the VH of the first binding domain and the VL of the first binding domain are connected by an scFv linker sequence. In some embodiments, the scFv linker sequence of the first binding domain comprises an amino acid sequence according to SEQ ID NO: 29. In some embodiments, the scFv of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 30 or SEQ ID NO: 31. In some embodiments, the first binding domain comprises a constant domain. In some embodiments, the constant domain of the first binding domain comprises a human IgG4 sequence. In some embodiments, the human IgG4 sequence of the first binding domain comprises a S228P point mutation, where the amino acid numbering is according to the EU index of Kabat et al. In some embodiments, the human IgG4 sequence of the first binding domain does not have a C-terminal lysine residue. In some embodiments, the constant domain of the first binding domain comprises a human IgG1 sequence. In some embodiments, the constant domain of the first binding domain is a C. H 1. C H 2. C H 3, or C L In some embodiments, the first binding domain comprises the amino acid sequence C H 1. C H 2. C H 3, and C LIn some embodiments, the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:74, or SEQ ID NO:75, and the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:34 or SEQ ID NO:76. In some embodiments, the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:42 or SEQ ID NO:43. In some embodiments, the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:44. In some embodiments, the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 42 or SEQ ID NO: 43, and the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 44. In some embodiments, the second binding domain comprises a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the second binding domain is a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the second binding domain comprises an scFv. In some embodiments, the VH of the second binding domain and the VL of the second binding domain are connected by an scFv linker sequence. In some embodiments, the scFv linker sequence of the second binding domain comprises an amino acid sequence according to SEQ ID NO: 45. In some embodiments, the scFv of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 46 or SEQ ID NO: 47. In some embodiments, the second binding domain comprises a constant domain.In some embodiments, the constant domain of the second binding domain comprises a human IgG4 sequence. In some embodiments, the human IgG4 sequence of the second binding domain comprises a S228P point mutation, and the amino acid numbering is according to the EU index of Kabat et al. In some embodiments, the human IgG4 sequence of the second binding domain does not have a C-terminal lysine residue. In some embodiments, the constant domain of the second binding domain comprises a human IgG1 sequence. In some embodiments, the constant domain of the second binding domain is C. H 1. C H 2. C H 3, or C L In some embodiments, the second binding domain comprises the amino acid sequence C H 1. C H 2. C H 3, and C L In some embodiments, the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78, and the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50. In some embodiments, the first binding domain comprises an scFv and the second binding domain comprises a C H 1. C H 2. C H 3, and C L In some embodiments, the second binding domain comprises an scFv and the first binding domain comprises a C H 1. C H 2. C H 3, and C LIn some embodiments, the first binding domain and the second binding domain are connected by a linking moiety. In some embodiments, the linking moiety is an amino acid sequence. In some embodiments, the linking moiety is at least 4 amino acids in length. In some embodiments, the linking moiety is between 4 and 20 amino acids in length. In some embodiments, the linking moiety is connected to the C of the second binding domain. H a linking moiety comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 61 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 60; a linking moiety comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 63 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 62;

[0026] [Table 4-1] [Table 4-2] [Table 4-3] [Table 4-4] [Table 4-5] [Table 4-6] [Table 4-7] [Table 4-8]

[0027] A first binding domain, a second binding domain, and a third binding domain Disclosed herein is a composition comprising a first binding domain that binds to Ara h 2 and Ara h 6, wherein the first binding domain comprises a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, and HC-CDR3, wherein the HC-CDR1, HC-CDR2, and HC-CDR3 comprise the amino acid sequences of HC-CDR1: SEQ ID NO: 1, HC-CDR2: SEQ ID NO: 2 or SEQ ID NO: 3, and HC-CDR-3: SEQ ID NO: 4 or SEQ ID NO: 5; the first binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, and LC-CDR3, wherein the LC-CDR1, LC-CDR2, and LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 6, LC-CDR2: SEQ ID NO: 7, and LC-CDR-3: SEQ ID NO: 8; and the composition is capable of binding to Ara h 2 and Ara h 6. and a second binding domain that binds to Ara h, wherein the second binding domain comprises a VH comprising CDRs: HC-CDR1, HC-CDR2, HC-CDR3, wherein HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences according to HC-CDR1: SEQ ID NO: 18, HC-CDR2: SEQ ID NO: 19, and HC-CDR-3: SEQ ID NO: 20 or SEQ ID NO: 21; and the second binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences according to LC-CDR1: SEQ ID NO: 22, LC-CDR2: SEQ ID NO: 23, and LC-CDR-3: SEQ ID NO: 24; and the composition is and a third binding domain that binds to IgG1A-2, wherein the third binding domain comprises a VH comprising CDRs: HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences of HC-CDR1: SEQ ID NO: 35, HC-CDR2: SEQ ID NO: 36 or SEQ ID NO: 37, and HC-CDR-3: SEQ ID NO: 38; and the third binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 39, LC-CDR2: SEQ ID NO: 40,LC-CDR-3: comprises the amino acid sequence according to SEQ ID NO: 41. Disclosed herein is a composition comprising a first binding domain that binds to Ara h 2 and Ara h 6, wherein the first binding domain comprises a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences according to SEQ ID NO: 1 for HC-CDR1, SEQ ID NO: 2 for HC-CDR2, and SEQ ID NO: 4 for HC-CDR3, and the first binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences according to SEQ ID NO: 6 for LC-CDR1, SEQ ID NO: 7 for LC-CDR2, and SEQ ID NO: 8 for LC-CDR3, and the composition is capable of binding to Ara h 2 and Ara h 6. and a second binding domain that binds to Ara h, wherein the second binding domain comprises a VH comprising CDRs: HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences according to HC-CDR1: SEQ ID NO: 18, HC-CDR2: SEQ ID NO: 19, and HC-CDR-3: SEQ ID NO: 20; and the second binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences according to LC-CDR1: SEQ ID NO: 22, LC-CDR2: SEQ ID NO: 23, and LC-CDR-3: SEQ ID NO: 24. and a third binding domain that binds to IgG1A-2, wherein the third binding domain comprises a VH comprising CDRs: HC-CDR1, HC-CDR2, and HC-CDR3, wherein the HC-CDR1, HC-CDR2, and HC-CDR3 comprise the amino acid sequences of HC-CDR1: SEQ ID NO: 35, HC-CDR2: SEQ ID NO: 36, and HC-CDR3: SEQ ID NO: 38; and the third binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, and LC-CDR3, wherein the LC-CDR1, LC-CDR2, and LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 39, and LC-CDR2: SEQ ID NO: 40.LC-CDR-3: comprises an amino acid sequence according to SEQ ID NO: 41. In some embodiments, the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 9 or SEQ ID NO: 10. In some embodiments, the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 11. In some embodiments, the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 9 or SEQ ID NO: 10, and the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 11. In some embodiments, the first binding domain comprises a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the first binding domain is a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the first binding domain comprises an scFv. In some embodiments, the VH of the first binding domain and the VL of the first binding domain are connected by an scFv linker sequence. In some embodiments, the scFv linker sequence of the first binding domain comprises an amino acid sequence according to SEQ ID NO: 12. In some embodiments, the scFv of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 13 or SEQ ID NO: 14. In some embodiments, the first binding domain comprises a constant domain. In some embodiments, the constant domain of the first binding domain comprises a human IgG4 sequence. In some embodiments, the human IgG4 sequence of the first binding domain comprises a S228P point mutation, with amino acid numbering according to the EU index of Kabat et al. In some embodiments, the human IgG4 sequence of the first binding domain does not have a C-terminal lysine residue. In some embodiments, the constant domain of the first binding domain comprises:In some embodiments, the constant domain of the first binding domain comprises a human IgG1 sequence. H 1. C H 2. C H 3, or C L In some embodiments, the first binding domain comprises the amino acid sequence C H 1. C H 2. C H 3, and C LIn some embodiments, the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 72, or SEQ ID NO: 73, and the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 17. In some embodiments, the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 25 or SEQ ID NO: 26. In some embodiments, the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 27 or SEQ ID NO: 28. In some embodiments, the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:25 or SEQ ID NO:26, and the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:27 or SEQ ID NO:28. In some embodiments, the second binding domain comprises a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the second binding domain is a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the second binding domain comprises an scFv. In some embodiments, the VH of the second binding domain and the VL of the second binding domain are connected by an scFv linker sequence. In some embodiments, the scFv linker sequence of the second binding domain comprises an amino acid sequence according to SEQ ID NO: 29. In some embodiments, the scFv of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 30 or SEQ ID NO: 31. In some embodiments, the second binding domain comprises a constant domain.In some embodiments, the constant domain of the second binding domain comprises a human IgG4 sequence. In some embodiments, the human IgG4 sequence of the second binding domain comprises a S228P point mutation, and the amino acid numbering is according to the EU index of Kabat et al. In some embodiments, the human IgG4 sequence of the second binding domain does not have a C-terminal lysine residue. In some embodiments, the constant domain of the second binding domain comprises a human IgG1 sequence. In some embodiments, the constant domain of the second binding domain is C. H 1. C H 2. C H 3, or C L In some embodiments, the second binding domain comprises the amino acid sequence C H 1. C H 2. C H 3, and C LIn some embodiments, the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:74, or SEQ ID NO:75, and the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:34 or SEQ ID NO:76. In some embodiments, the VH of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:42 or SEQ ID NO:43. In some embodiments, the VL of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:44. In some embodiments, the VH of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 42 or SEQ ID NO: 43, and the VL of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 44. In some embodiments, the third binding domain comprises a Fab, Fab', F(ab')2, or single chain variable fragment (scFv). In some embodiments, the third binding domain comprises a Fab, Fab', F(ab')2, or single chain variable fragment (scFv). The binding domain is a Fab, Fab', F(ab')2, or single-chain variable fragment (scFv). In some embodiments, the third binding domain comprises an scFv. In some embodiments, the VH of the third binding domain and the VL of the third binding domain are connected by an scFv linker sequence. In some embodiments, the scFv linker sequence of the third binding domain comprises the amino acid sequence of SEQ ID NO: 45. In some embodiments, the scFv of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 46 or SEQ ID NO: 47. In some embodiments, the third binding domain comprises a constant domain. In some embodiments, the constant domain of the third binding domain comprises a human IgG4 sequence. In some embodiments, the human IgG4 sequence of the third binding domain comprises a S228P point mutation, and the amino acid numbering is according to the EU index of Kabat et al. In some embodiments, the human IgG4 sequence of the third binding domain does not have a C-terminal lysine residue. In some embodiments, the constant domain of the third binding domain comprises a human IgG1 sequence. In some embodiments, the constant domain of the third binding domain comprises a C H 1. C H 2. C H 3, or C L In some embodiments, the third binding domain comprises the amino acid sequence C H 1. C H 2. C H 3, and C LIn some embodiments, the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78, and the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50. In some embodiments, the first binding domain, the second binding domain, and the third binding domain are connected within the same molecule. In some embodiments, the first binding domain, the second binding domain, and the third binding domain are separate molecules. In some embodiments, the first binding domain and the second binding domain are within the same molecule, and the third binding domain is a separate molecule from the molecule comprising the first binding domain and the second binding domain. In some embodiments, the first binding domain and the third binding domain are in the same molecule, and the second binding domain is a separate molecule from the molecule comprising the first binding domain and the third binding domain. In some embodiments, the second binding domain and the third binding domain are in the same molecule, and the first binding domain is a separate molecule from the molecule comprising the second binding domain and the third binding domain. In some embodiments, the first binding domain comprises an scFv and the second binding domain comprises a C H 1. C H 2. C H 3, and C L In some embodiments, the second binding domain comprises an scFv and the first binding domain comprises a C H 1. C H 2. C H 3, and C L In some embodiments, the first binding domain and the second binding domain are connected by a linking moiety. In some embodiments, the linking moiety is an amino acid sequence. In some embodiments, the linking moiety is at least 4 amino acids in length. In some embodiments, the linking moiety is between 4 and 20 amino acids in length. In some embodiments, the linking moiety is connected to the C of the second binding domain.Ha linking moiety comprising an amino acid sequence of at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:53 and an amino acid sequence of at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:52; a third binding domain comprising an amino acid sequence of at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78; and a third binding domain comprising an amino acid sequence of at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50. In some embodiments, the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:55 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:54; the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78; and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50.In some embodiments, the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:65 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:64; the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78; and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50. In some embodiments, the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:67 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:66; the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78; and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50.In some embodiments, the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:69 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:68; the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78; and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50. In some embodiments, the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:71 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:70; the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78; and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50.

[0028] Disclosed herein is a composition comprising a first molecule comprising a first binding domain that binds Ara h 2 and Ara h 6 and a second binding domain that binds Ara h 2 and Ara h 6, wherein the first binding domain comprises an scFv, and the second binding domain comprises a heavy chain variable domain, a light chain variable domain, and a constant region, wherein the scFv of the first binding domain is connected to the constant domain of the second binding domain by a linking moiety; and the composition comprises a second molecule comprising a third binding domain that binds Ara h 2.In some embodiments, the first binding domain comprises a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences according to HC-CDR1: SEQ ID NO: 1, HC-CDR2: SEQ ID NO: 2 or SEQ ID NO: 3, HC-CDR3: SEQ ID NO: 4 or SEQ ID NO: 5, and the first binding domain comprises a light chain variable domain (VH) comprising the CDRs: LC-CDR1, LC-CDR2, LC-CDR3. The second binding domain comprises a VH comprising CDRs: HC-CDR1, HC-CDR2, and HC-CDR3, and the HC-CDR1, HC-CDR2, and HC-CDR3 are selected from the group consisting of HC-CDR1: SEQ ID NO: 18, HC-CDR2: SEQ ID NO: 19, and HC-CDR-3: SEQ ID NO: 20, or SEQ ID NO: No. 21, wherein the second binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences according to SEQ ID NO: 22 for LC-CDR1, SEQ ID NO: 23, and SEQ ID NO: 24 for LC-CDR-3, and the third binding domain comprises a VH comprising CDRs: HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, and HC-CDR3 comprise the amino acid sequences according to SEQ ID NO: 25, SEQ ID NO: 26, and SEQ ID NO: 27. 2. HC-CDR3 comprises the amino acid sequences of HC-CDR1: SEQ ID NO: 35, HC-CDR2: SEQ ID NO: 36 or SEQ ID NO: 37, HC-CDR-3: SEQ ID NO: 38, and the third binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, and the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 39, LC-CDR2: SEQ ID NO: 40, LC-CDR-3: SEQ ID NO: 41.In some embodiments, the first binding domain comprises a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein said HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences according to HC-CDR1: SEQ ID NO: 1, HC-CDR2: SEQ ID NO: 2, HC-CDR3: SEQ ID NO: 4, and the first binding domain comprises a light chain variable (VL) domain comprising the CDRs: LC-CDR1, LC-CDR2, LC-CDR3. the second binding domain comprises a VH comprising CDRs: HC-CDR1, HC-CDR2, HC-CDR3, and the HC-CDR1, HC-CDR2, HC-CDR3, and the HC-CDR1, HC-CDR2, HC-CDR3, and the HC-CDR1, HC-CDR2, HC-CDR3, and the HC-CDR1, HC-CDR2, HC-CDR3, and the HC-CDR1, HC-CDR2, HC-CDR3, and the HC-CDR3, HC-CDR1, HC-CDR2, HC-CDR3, and the HC-CDR3, HC-CDR3, and the ...3, HC-CDR4, HC-CDR5, HC-CDR6, HC-CDR7, HC-CDR8, HC-CDR9, HC-CDR10, HC-CDR11, HC-CDR12, HC-CDR13, HC-CDR14, HC-CDR15, HC-CDR16, HC-CDR17, HC-CDR1 and the second binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 22, LC-CDR2: SEQ ID NO: 23, and LC-CDR3: SEQ ID NO: 24; and the third binding domain comprises a VH comprising CDRs: HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR 2. HC-CDR3 comprises the amino acid sequence of HC-CDR1: SEQ ID NO: 35, HC-CDR2: SEQ ID NO: 36, HC-CDR-3: SEQ ID NO: 38, and the third binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein said LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequence of LC-CDR1: SEQ ID NO: 39, LC-CDR2: SEQ ID NO: 40, LC-CDR-3: SEQ ID NO: 41. In some embodiments, the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 9 or SEQ ID NO: 10.In some embodiments, the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 11. In some embodiments, the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 9 or SEQ ID NO: 10, and the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 11. In some embodiments, the VH of the first binding domain and the VL of the first binding domain are connected by an scFv linker sequence. In some embodiments, the scFv linker sequence of the first binding domain comprises an amino acid sequence according to SEQ ID NO: 12. In some embodiments, the scFv of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 13 or SEQ ID NO: 14. In some embodiments, the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 25 or SEQ ID NO: 26. In some embodiments, the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:27 or SEQ ID NO:28. In some embodiments, the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:25 or SEQ ID NO:26, and the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:27 or SEQ ID NO:28. In some embodiments, the second binding domain comprises a Fab, Fab', or F(ab')2. In some embodiments, the second binding domain is a Fab, Fab', or F(ab')2.In some embodiments, the constant domain of the second binding domain comprises a human IgG4 sequence. In some embodiments, the human IgG4 sequence of the second binding domain comprises a S228P point mutation, and the amino acid numbering is according to the EU index of Kabat et al. In some embodiments, the human IgG4 sequence of the second binding domain does not have a C-terminal lysine residue. In some embodiments, the constant domain of the second binding domain comprises a human IgG1 sequence. In some embodiments, the constant domain of the second binding domain is C. H 1. C H 2. C H 3, or C L In some embodiments, the second binding domain comprises the amino acid sequence C H 1. C H 2. C H 3, and C LIn some embodiments, the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:74, or SEQ ID NO:75, and the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:34 or SEQ ID NO:76. In some embodiments, the VH of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:42 or SEQ ID NO:43. In some embodiments, the VL of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:44. In some embodiments, the VH of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 42 or SEQ ID NO: 43, and the VL of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 44. In some embodiments, the third binding domain comprises a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the third binding domain is a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv). In some embodiments, the third binding domain comprises an scFv. In some embodiments, the VH of the third binding domain and the VL of the third binding domain are connected by an scFv linker sequence. In some embodiments, the scFv linker sequence of the third binding domain comprises an amino acid sequence according to SEQ ID NO: 45. In some embodiments, the scFv of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 46 or SEQ ID NO: 47. In some embodiments, the third binding domain comprises a constant domain.In some embodiments, the constant domain of the third binding domain comprises a human IgG4 sequence. In some embodiments, the human IgG4 sequence of the third binding domain comprises a S228P point mutation, and the amino acid numbering is according to the EU index of Kabat et al. In some embodiments, the human IgG4 sequence of the third binding domain does not have a C-terminal lysine residue. In some embodiments, the constant domain of the third binding domain comprises a human IgG1 sequence. In some embodiments, the constant domain of the third binding domain is C. H 1. C H 2. C H 3, or C L In some embodiments, the third binding domain comprises the amino acid sequence C H 1. C H 2. C H 3, and C L In some embodiments, the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78, and the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50. In some embodiments, the first binding domain and the second binding domain are connected by a linking moiety. In some embodiments, the linking moiety is an amino acid sequence. In some embodiments, the linking moiety is at least 4 amino acids in length. In some embodiments, the linking moiety is between 4 and 20 amino acids in length. In some embodiments, the linking moiety is The binding portion is C of the second binding domain. Ha linking moiety comprising an amino acid sequence of at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:53 and an amino acid sequence of at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:52; a third binding domain comprising an amino acid sequence of at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78; and a third binding domain comprising an amino acid sequence of at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50. In some embodiments, the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:65 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:64; the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78; and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50.In some embodiments, the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:67 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:66; the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78; and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50.

[0029] Pharmaceutical Composition Disclosed herein, in some embodiments, are pharmaceutical compositions comprising: (a) the antibodies and compositions disclosed herein; and (b) a pharmaceutically acceptable excipient.

[0030] In some embodiments, the antibody further comprises a detectable label, a therapeutic agent, or a pharmacokinetic-modifying moiety, hi some embodiments, the detectable label comprises a fluorescent label, a radiolabel, an enzyme, a nucleic acid probe, or an imaging agent.

[0031] For administration to a subject, the antibodies disclosed herein can be provided in a pharmaceutical composition together with one or more pharmaceutically acceptable carriers or excipients. The term "pharmaceutically acceptable carrier" includes, but is not limited to, a carrier that does not interfere with the effectiveness of the biological activity of the components and is not toxic to the patient to whom it is administered. Examples of suitable pharmaceutical carriers are well known in the art and include phosphate-buffered saline, water, emulsions such as oil / water emulsions, various types of wetting agents, sterile solutions, etc. Such carriers can be formulated by conventional methods and administered to a subject in an appropriate dosage. Preferably, the compositions are sterilized. These compositions can also contain adjuvants such as preservatives, emulsifiers, and dispersing agents. Prevention of microbial attack can be ensured by including various antibacterial and antifungal agents.

[0032] The pharmaceutical composition may be in any suitable form (depending on the desired method of administration). It may be provided in a unit dosage form, in a sealed container, or as part of a kit. Such a kit may include instructions for use. It may include a plurality of the above unit dosage forms.

[0033] The pharmaceutical compositions can be adapted for administration by any suitable route, including parenteral (e.g., subcutaneous, intramuscular, or intravenous) routes. Such compositions can be prepared by any method known in the art of pharmacy, for example, by mixing the active ingredient with the carrier or excipient under sterile conditions.

[0034] The dosage of the substances of the present disclosure can vary within wide limits depending on the disorder being treated, the age and condition of the individual being treated, etc., and the physician will ultimately determine the appropriate dosage to be used.

[0035] antibody production In some embodiments, the polypeptides (e.g., antibodies and binding fragments thereof) described herein are produced using any method known in the art to be useful for synthesizing polypeptides (e.g., antibodies), in particular by chemical synthesis or recombinant expression, preferably by recombinant expression techniques.

[0036] In some examples, antibodies or binding fragments thereof are recombinantly expressed, and nucleic acids encoding the antibodies or binding fragments thereof are assembled from chemically synthesized oligonucleotides (e.g., as described in Kutmeier et al., 1994, BioTechniques 17:242), which involves synthesizing overlapping oligonucleotides containing portions of the antibody-encoding sequence, annealing and ligating those oligonucleotides, and then amplifying the ligated oligonucleotides by PCR.

[0037] Alternatively, nucleic acid molecules encoding antibodies are optionally produced from an appropriate source (e.g., an antibody cDNA library, or a cDNA library generated from any tissue or cell that expresses immunoglobulins) by PCR amplification using synthetic primers hybridizable to the 3' and 5' ends of the sequence, or by cloning using oligonucleotide probes specific for particular gene sequences.

[0038] In some cases, the antibody or binding entity thereof is optionally produced by immunizing an animal such as a rabbit to produce polyclonal antibodies, or more preferably, by producing monoclonal antibodies, e.g., as described by Kohler and Milstein (1975, Nature 256:495-497), or by Kozbor et al. (1983, Immunology Today 4:72) or Cole et al. (1985 in Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., pp. 77-96). Alternatively, clones encoding at least the Fab portion of the antibody are optionally obtained by screening Fab expression libraries for clones of Fab fragments that bind to a specific antigen (e.g., as described in Huse et al., 1989, Science 246:1275-181) or by screening antibody libraries (see, e.g., Clackson et al., 1991, Nature 352:624; Hane et al., 1997 Proc. Natl. Acad. Sci. USA 94:4937).

[0039] In some embodiments, techniques developed for producing "chimeric antibodies" by splicing together the genes from a mouse antibody molecule of appropriate antigen specificity with the genes from a human antibody molecule of appropriate biological activity (Morrison et al., 1984, Proc. Natl. Acad. Sci. 81:851-855; Neuberger et al., 1984, Nature 312:604-608; Takeda et al., 1985, Nature 314:452-454) are used. Chimeric antibodies are molecules in which different portions are derived from different animal species, such as those having a variable region derived from a mouse monoclonal antibody and a human immunoglobulin constant region.

[0040] In some embodiments, techniques described for producing single-chain antibodies (U.S. Patent 4,694,778; Bird, 1988, Science 242:423-42; Huston et al., 1988, Proc. Natl. Acad. Sci. USA 85:5879-5883; Ward et al., 1989, Nature 334:544-54) are adapted to produce single-chain antibodies. Single-chain antibodies are formed by linking the heavy and light chain fragments of the Fv region via an amino acid bridge, resulting in a single-chain polypeptide. Techniques for the assembly of functional Fv fragments in E. coli are also optionally used (Skerra et al., 1988, Science 242:1038-1041).

[0041] In some embodiments, an expression vector containing the antibody nucleotide sequence or the antibody nucleotide sequence is transferred into host cells by conventional techniques (e.g., electroporation, liposome transfection, and calcium phosphate precipitation), and the transfected cells are then cultured by conventional techniques to produce the antibody. In certain embodiments, antibody expression is regulated by a constitutive, inducible, or tissue-specific promoter.

[0042] In some embodiments, various host-expression vector systems are utilized to express the antibodies or binding fragments thereof described herein. Such host-expression systems refer not only to vehicles by which antibody coding sequences are produced and subsequently purified, but also to cells that, when transformed or transfected with the appropriate nucleotide coding sequences, express the antibody or binding fragment thereof 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 the antibody or binding fragment coding sequences; yeast (e.g., Saccharomyces cerevisiae) transformed with recombinant yeast expression vectors containing the antibody or binding fragment coding sequences; and yeast (e.g., Saccharomyces cerevisiae) transformed with recombinant yeast expression vectors containing the antibody or binding fragment coding sequences. Pichia; insect cell systems infected with recombinant viral expression vectors (e.g., baculovirus) containing antibody or binding fragment coding sequences; plant cell systems infected with recombinant viral expression vectors (e.g., cauliflower mosaic virus (CaMV) and tobacco mosaic virus (TMV)) or transformed with recombinant plasmid expression vectors (e.g., Ti plasmid) containing antibody or binding fragment coding sequences; or mammalian cell systems (e.g., COS, CHO, BH, 293, 293T, and 3T3 cells) harboring recombinant expression constructs containing promoters derived from the genomes of mammalian cells (e.g., the metallothionein promoter) or mammalian viruses (e.g., the adenovirus late promoter; the vaccinia virus 7.5K promoter).

[0043] Stable expression is preferred for long-term, high-yield production of recombinant proteins. In some cases, cell lines that stably express antibodies are optionally engineered. Rather than using expression vectors containing viral origins of replication, host cells are transformed with DNA controlled by appropriate expression control elements (e.g., promoter, enhancer, sequences, transcription terminators, polyadenylation sites, etc.) and a selectable marker. After introduction of the foreign DNA, engineered cells are grown in enriched medium for 1-2 days and then switched to selective medium. The selectable marker in the recombinant plasmid confers resistance to selection, allowing the cells to stably integrate the plasmid into their chromosomes and grow to form foci, which are cloned and expanded into cell lines. This method can be advantageously used to engineer cell lines that express antibodies or binding fragments thereof.

[0044] In some examples, a number of selection systems are used, including but not limited to, genes for herpes simplex virus thymidine kinase (Wigler et al., 1977, Cell 11:223), hypoxanthine guanine phosphoribosyltransferase (Szybalska & Szybalski, 192, Proc. Natl. Acad. Sci. USA 48:202), and adenine phosphoribosyltransferase (Lowy et al., 1980, Cell 22:817), in tk-, hgprt-, or aprt- cells, respectively. Additionally, antimetabolite resistance is used as the principle of selection for the following genes: dhfr, which confers resistance to methotrexate (Wigler et al., 1980, Proc. Natl. Acad. Sci. USA 77:357; O'Hare et al., 1981, Proc. Natl. Acad. Sci. USA 78:1527); gpt, which confers resistance to mycophenolic acid (Mulligan & Berg, 1981, Proc. Natl. Acad. Sci. USA 78:2072); neo, which confers resistance to the aminoglycoside G-418 (Clinical Pharmacy 12:488-505; Wu and Wu, 1991, Biotherapy). 3:87-95, Tolstoshev, 1993, Ann. Rev. Pharmacol. Toxicol. 32:573-596, Mulligan, 1993, Science 260:926-932, and Morgan and Anderson, 1993, Ann. Rev. Biochem. 62:191-217, May 1993, TIB TECH 11(5):155-215), and hygro, which confers resistance to hygromycin (Santerre et al., 1984, Gene 30:147).Methods well known in the field of recombinant DNA technology that can be used are described in Ausubel et al. (eds., 1993, Current Protocols in Molecular Biology, John Wiley & Sons, NY; Kriegler, 1990, Gene Transfer and Expression, A Laboratory Manual, Stockton Press, NY, Chapters 12 and 13, Dracopoli et al. (eds), 1994, Current Protocols in Human Genetics, John Wiley & Sons, NY; Colberre-Garapin et al., 1981, J. Mol. Biol. 150:1).

[0045] In some instances, antibody expression levels are increased by vector amplification (for a review, see Bebbington and Hentschel, "The Use of Vectors Based on Gene Amplification for the Expression of Cloned Genes in Mammalian Cells in DNA Cloning," Vol. 3 (Academic Press, New York, 1987)). If the marker in the antibody expression vector system is amplifiable, increasing the level of inhibitor present in the host cell culture will increase the copy number of the marker gene. Because the amplified region will be linked to the antibody nucleotide sequence, antibody production will also be increased (Crouse et al., 1983, Mol. Cell Biol. 3:257).

[0046] Optionally, any method known in the art for purification of antibodies is used, such as chromatography (e.g., ion exchange chromatography, affinity chromatography, particularly affinity chromatography for specific antigens followed by Protein A, sizing column chromatography), centrifugation, differential solubility, or any other standard technique for purification of proteins.

[0047] Expression vector In some embodiments, the vector comprises any suitable vector derived from a eukaryotic or prokaryotic source. In some cases, the vector is derived from a bacterial (e.g., E. coli), insect, yeast (e.g., Pichia pastoris), algae, or mammalian source. Exemplary bacterial vectors include pACYC177, pASK75, pBAD vector series, pBADM vector series, pET vector series, pETM vector series, pGEX vector series, pHAT, pHAT2, pMal-c2, pMal-p2, pQE vector series, pRSET A, pRSET B, pRSET C, pTrcHis2 series, pZA31-Luc, pZE21-MCS-1, pFLAG ATS, pFLAG CTS, pFLAG MAC, pFLAG Shift-12c, pTAC-MAT-1, pFLAG CTC, or pTAC-MAT-2.

[0048] Exemplary insect vectors include pFastBac1, pFastBac DUAL, pFastBac ET, pFastBac HTa, pFastBac HTb, pFastBac HTc, pFastBac M30a, pFastBact M30b, pFastBac, M30c, pVL1392, pVL1393, pVL1393 M10, pVL1393 M11, pVL1393 M12, a FLAG vector such as pPolh-FLAG1 or pPolh-MAT2, or a MAT vector such as pPolh-MAT1 or pPolh-MAT2.

[0049] Optionally, the yeast vector includes a Gateway® pDEST™ 14 vector, a Gateway® pDEST™ 15 vector, a Gateway® pDEST™ 17 vector, a Gateway® pDEST™ 24 vector, a Gateway® pYES-DEST52 vector, a pBAD-DEST49 Gateway® destination vector, a pAO815 Pichia vector, a pFLD1 Pichi pastoris vector, a pGAPZA,B, & C Pichia pastoris vector, a pPIC3.5K Pichia vector, a pPIC6 A,B, & C Pichia vector, a pPIC9K Pichia vector, pTEF1 / Zeo, a pYES2 yeast vector, a pYES2 / CT yeast vector, a pYES2 / NT A,B, & C yeast vector, or a pYES3 / CT yeast vector. Exemplary algae vectors include the pChlamy-4 vector or the MCS vector.

[0050] Examples of mammalian vectors include transient expression vectors or stable expression vectors.Mammalian transient expression vectors can include pRK5, p3xFLAG-CMV 8, pFLAG-Myc-CMV 19, pFLAG-Myc-CMV 23, pFLAG-CMV 2, pFLAG-CMV 6a,b,c, pFLAG-CMV 5.1, pFLAG-CMV 5a,b,c, p3xFLAG-CMV 7.1, pFLAG-CMV 20, p3xFLAG-Myc-CMV 24, pCMV-FLAG-MAT1, pCMV-FLAG-MAT2, pBICEP-CMV 3, pcDNA3.4 or pBICEP-CMV 4. Mammalian stable expression vectors may include pFLAG-CMV 3, p3xFLAG-CMV 9, p3xFLAG-CMV 13, pFLAG-Myc-CMV 21, p3xFLAG-Myc-CMV 25, pFLAG-CMV 4, p3xFLAG-CMV 10, p3xFLAG-CMV 14, pFLAG-Myc-CMV 22, p3xFLAG-Myc-CMV 26, pBICEP-CMV 1, or pBICEP-CMV 2.

[0051] In some instances, the cell-free system is a mixture of cytoplasmic and / or nuclear components from cells and is used for in vitro nucleic acid synthesis. In some cases, the cell-free system utilizes either prokaryotic or eukaryotic components. Sometimes, nucleic acid synthesis is achieved in a cell-free system based on, for example, Drosophila cells, Xenopus eggs, or HeLa cells. Exemplary cell-free systems include, but are not limited to, the E. coli S30 Extract system, the E. coli T7 S30 system, or PURExpress®.

[0052] host cell In some embodiments, the host cell includes any suitable cell, such as a naturally occurring cell or a genetically modified cell. In some examples, the host cell is a production host cell. In some examples, the host cell is a eukaryotic cell. In other examples, the host cell is a prokaryotic cell. In some cases, the eukaryotic cell includes a fungus (e.g., a yeast cell), an animal cell, or a plant cell. In some cases, the prokaryotic cell is a bacterial cell. Examples of bacterial cells include gram-positive bacteria or gram-negative bacteria. Gram-negative bacteria are anaerobic, rod-shaped, or both.

[0053] In some examples, the Gram-positive bacteria include Actinobacteria, Firmicutes, or Tenericutes. In some cases, the Gram-negative bacteria include Aquificae, Deinococcus-Thermus, Fibrobacteres-Chlorobi / Bacteroidetes (FCB group), Fusobacteria, Gemmatimonadetes, Nitrospirae, Planctomycetes-Verrucomicrobia / Chlamydiae (PVC group), Proteobacteria, Spirochaetes, or Synergistetes. Other bacteria can be Acidobacteria, Chloroflexi, Chrysiogenetes, Cyanobacteria, Deferribacteres, Dictyoglomi, Thermodesulfobacteria, or Thermotogae. The bacterial cell can be Escherichia coli, Clostridium botulinum, or Coli bacilli.

[0054] Exemplary prokaryotic host cells include BL21, Mach1™, DH10B™, TOP10, DH5α, DH10Bac™, OmniMax™, MegaX™, DH12S™, INV110, TOP10F′, INVαF, TOP10 / P3, ccdB Survival, PIR1, PIR2, Stbl2™, Stbl3™, or Stbl4™.

[0055] In some examples, the animal cell comprises a cell from a vertebrate or invertebrate. In some cases, the animal cell comprises a cell from a marine invertebrate, a fish, an insect, an amphibian, a reptile, or a mammal. In some cases, the fungal cell comprises a yeast, such as brewer's yeast, baker's yeast, or wine yeast.

[0056] Fungi include ascomycetes, such as yeasts, molds, filamentous fungi, basidiomycetes, or zygomycetes. In some examples, yeasts include Ascomycota or Basidiomycota. In some cases, Ascomycota includes Saccharomycotina (true yeasts, e.g., Saccharomyces cerevisiae (baker's yeast)) or Taphrinomycotina (e.g., Schizosaccharomycetes (fission yeasts)). In some cases, Basidiomycota includes Agaricomycotina (e.g., Tremellomycetes) or Pucciniomycotina (e.g., Microbotryomycetes).

[0057] Exemplary yeasts or filamentous fungi include, for example, the following genera: Saccharomyces, Schizosaccharomyces, Candida, Pichia, Hansenula, Kluyveromyces, Zygosaccharomyces, Yarrowia, Trichosporon, Rhodosporidi, Aspergillus, Fusarium, or Trichoderma.The main strains are the following strains: Saccharomyces cerevisiae and Schizosaccharomyces pombe、Candida utilis、Candida boidini、Candida albicans、Candida tropicalis、Candida stellatoidea、Candida glabrata、Candida krusei、Candida parapsilosis、Candida guilliermondii、Candida viswanathii、Candida lusitaniae、Rhodotorula mucilaginosa、Methanolic pichia、Angusta pichia pastoris、Anomal pichia、Hansenula polymorpha、Kluyveromyces lactis、Zygosaccharomyces rouxii、Yarrowia lipolytica、Trichosporon pullulans, Rhodosporidium toru-Aspergillus niger, Aspergillus nidulans, Aspergillus awamori, Aspergillus oryzae,Trichoderma reesei, Yarrowia lipolytica, Brettanomyces bruxellensis, Candida stellata, Schizosaccharomyces pombe, Torulaspora delbrueckii, Zygosaccharomyces bailii, Cryptococcus neoformans, Cryptococcus gattii, Saccharomyces boulardii.

[0058] Exemplary yeast host cells include, but are not limited to, Pichia pastoris yeast strains such as GS115, KM71H, SMD1168, SMD1168H, and X-33, and Saccharomyces cerevisiae yeast strains such as INVSc1.

[0059] In some examples, the additional animal cells include cells obtained from a mollusk, arthropod, annelid, or sponge. Optionally, the additional animal cells are mammalian cells derived from, for example, a primate, ape, horse, cow, pig, dog, cat, or rodent. Optionally, the rodent includes a mouse, rat, hamster, gerbil, hamster, chinchilla, fancy rat, or guinea pig.

[0060] Exemplary mammalian host cells include 293A cell line, 293FT cell line, 293F cells, 293H cells, CHO DG44 cells, CHO-S cells, CHO-K1 cells, FUT8KO cells. CHO-K1, Expi293F(TM) cells, Flp-In(TM) T-REx(TM) 293 cell line, Flp-In(TM)-293 cell line, Flp-In(TM)-3T3 cell line, Flp-In(TM)-BHK cell line, Flp-In (Trademark)-CHO cell line, Flp-In(TM)-CV-1 cell line, Flp-In(TM)-Jurkat cell line, FreeStyle(TM) 293F cells, FreeStyle(TM) CHO-S cells, GripTite(TM) 293 These include, but are not limited to, the MSR cell line, the GS-CHO cell line, HepaRG™ cells, the T-REx™ Jurkat cell line, Per.C6 cells, the T-REx™-293 cell line, the T-REx™-CHO cell line, and the T-REx™-HeLa cell line.

[0061] In some instances, the mammalian host cell is a stable cell line, or a cell line that has integrated the genetic material of interest into its genome and is capable of expressing the products of the genetic material after many generations of cell division. In some instances, the mammalian host cell is a transient cell line, or a cell line that has not integrated the genetic material of interest into its genome and is not capable of expressing the products of the genetic material after many generations of cell division.

[0062] Exemplary insect host cells include, but are not limited to, Drosophila S2 cells, Sf9 cells, Sf21 cells, High Five™, and expressSF+® cells.

[0063] In some examples, the plant cells include cells derived from algae. Exemplary algal cell lines include, but are not limited to, strains derived from Chlamydomonas reinhardtii 137c, or Synechococcus elongatus PPC 7942.

[0064] Treatment method Disclosed herein are methods for treating food allergies in a subject in need thereof, the methods comprising administering to the subject an isolated antibody and / or composition disclosed herein. In some embodiments, the food allergy comprises peanut allergy. In some embodiments, the subject exhibits symptoms of peanut allergy. In some embodiments, the symptoms of peanut allergy comprise hives, vomiting, abdominal pain, coughing, wheezing, or anaphylaxis. In some embodiments, the isolated antibody or composition administered to the subject is administered intravenously (IV), intramuscularly (IM), or subcutaneously.

[0065] In some embodiments, the composition comprises a first binding domain that binds Ara h 2 and Ara h 6, wherein the first binding domain comprises a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences according to SEQ ID NO: 1 for HC-CDR1, SEQ ID NO: 2 for HC-CDR2, and SEQ ID NO: 4 for HC-CDR3; the first binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences according to SEQ ID NO: 6 for LC-CDR1, SEQ ID NO: 7 for LC-CDR2, and SEQ ID NO: 8 for LC-CDR3; and the composition binds Ara h 2 and Ara h 6. and a second binding domain that binds to Ara h, wherein the second binding domain comprises a VH comprising CDRs: HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences according to HC-CDR1: SEQ ID NO: 18, HC-CDR2: SEQ ID NO: 19, and HC-CDR-3: SEQ ID NO: 20; and the second binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences according to LC-CDR1: SEQ ID NO: 22, LC-CDR2: SEQ ID NO: 23, and LC-CDR-3: SEQ ID NO: 24; and and a third binding domain that binds to IgG1A-2, wherein the third binding domain comprises a VH comprising CDRs: HC-CDR1, HC-CDR2, and HC-CDR3, wherein the HC-CDR1, HC-CDR2, and HC-CDR3 comprise the amino acid sequences of HC-CDR1: SEQ ID NO: 35, HC-CDR2: SEQ ID NO: 36, and HC-CDR-3: SEQ ID NO: 38; and the third binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, and LC-CDR3, wherein the LC-CDR1, LC-CDR2, and LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 39, LC-CDR2: SEQ ID NO: 40, and LC-CDR-3: SEQ ID NO: 41.In some embodiments, the first binding domain and the second binding domain are in the same molecule, and the third binding domain is a separate molecule from the molecule having the first binding domain and the second binding domain. In some embodiments, the first binding domain comprises an scFv and the second binding domain comprises a C. H 1. C H 2. C H 3, and C L The third binding domain comprises an amino acid sequence, and the first binding domain and the second binding domain are connected to the Fc region of the second binding domain by a linking moiety. In some embodiments, the third binding domain, which is a separate molecule from the first binding domain and the second binding domain, is a monoclonal antibody. In some embodiments, the molecule comprising the first binding domain and the second binding domain is administered to a subject before the molecule comprising the third binding domain. In some embodiments, the molecule comprising the first binding domain and the second binding domain is administered to a subject simultaneously with the molecule comprising the third binding domain. In some embodiments, the molecule comprising the first binding domain and the second binding domain is administered to a subject after the molecule comprising the third binding domain.

[0066] product In another aspect of the present disclosure, an article of manufacture is provided that contains materials useful for the treatment, prevention, and / or diagnosis of the aforementioned disorders. The article of manufacture includes a container and a label or package insert on or associated with the container. Suitable containers include, for example, bottles, vials, syringes, IV solution bags, etc. The container may be formed from a variety of materials, such as glass or plastic. The container holds a composition effective for treating, preventing, and / or diagnosing a condition, alone or in combination with another composition, and may have a sterile access port (e.g., the container may be an intravenous solution bag or vial with a stopper pierceable by a hypodermic needle). At least one active agent in the composition is an antibody that specifically binds to Ara h 2 and / or Ara h 6.

[0067] The label or package insert indicates that the composition is used to treat a selected disease. Additionally, the article of manufacture may include (a) a first container containing a composition therein, the composition comprising a bispecific antibody of the present disclosure, and (b) a second container containing a composition therein, the composition comprising an additional cytotoxic or other therapeutic agent. The article of manufacture in this embodiment of the present disclosure may further include a package insert indicating that the composition can be used to treat a particular disease.

[0068] Alternatively, or additionally, the article of manufacture may further comprise a second (or third) container containing a pharmaceutically acceptable buffer, such as bacteriostatic water for injection (BWFI), phosphate-buffered saline, Ringer's solution, and dextrose solution, and it may further include other materials desirable from a commercial and user standpoint, including other buffers, diluents, filters, needles, and syringes.

[0069] definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the subject matter belongs. It is understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not intended to be limiting of any subject matter. The section headings used herein are for organizational purposes only and are not to be construed as limiting the specific inventions described. In this application, the use of the singular includes the plural unless expressly stated otherwise. It is noted that, as used in the specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. In this application, the use of "or" means "and / or" unless expressly stated otherwise. Furthermore, the use of the term "including," as well as other forms such as "include," "includes," and "included," is non-limiting.

[0070] As used herein, ranges and amounts can be expressed as "about" a particular value or range. "About" also includes the exact amount. Thus, "about 5 μL" also means "about 5 μL" and "5 μL." In general, the term "about" includes amounts that would be expected to be within experimental error.

[0071] The section headings used herein are for organizational purposes only and should not be construed as limiting the specific subject matter described.

[0072] "Antibodies" and "immunoglobulins" (Ig) are glycoproteins with the same structural characteristics. The terms are used interchangeably. In some instances, the antigen specificity of an immunoglobulin is known.

[0073] The term "antibody" is used in the broadest sense and includes fully assembled antibodies, antibody fragments capable of binding antigen (e.g., Fab, F(ab)2, Fv, single-chain antibodies, single-chain variable fragments (scFv), diabodies, antibody chimeras, hybrid antibodies, bispecific antibodies, etc.), and recombinant peptides containing the foregoing. "Antibody" can refer to monospecific antibodies, bispecific antibodies, or multispecific antibodies.

[0074] As used herein, the terms "monoclonal antibody" and "mAb" refer to an antibody obtained from a substantially homogeneous population of antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring variants that may be present in minor amounts.

[0075] "Native antibodies" and "native immunoglobulins" are typically heterotetrameric glycoproteins of approximately 150,000 daltons, composed of two identical light (L) chains and two identical heavy (H) chains. Each light chain is linked to a heavy chain by one covalent disulfide bond, while the number of disulfide bonds varies among the heavy chains of different immunoglobulin isotypes. Each heavy and light chain also has regularly spaced intrachain disulfide bridges. Each heavy chain has a variable domain (VH) at one end followed by a number of constant domains. Each light chain has a variable domain (VL) at one end and a constant domain at the other end, with the light-chain constant domain aligned with the first constant domain of the heavy chain and the light-chain variable domain aligned with the variable domain of the heavy chain. Particular amino acid residues are believed to form an interface between the light- and heavy-chain variable domains.

[0076] The term "variable" refers to the fact that certain portions of the variable domains differ greatly in sequence among antibodies. The variable regions confer antigen-binding specificity. However, variability is not evenly distributed throughout the variable domains of antibodies. The variability is concentrated in three regions called complementarity-determining regions (CDRs) or hypervariable regions, both in the light- and heavy-chain variable domains. The more highly conserved portions of the variable domains are called framework (FR) regions. Naturally occurring heavy- and light-chain variable domains each contain four FR regions, most of which adopt a β-pleated-sheet configuration, connected by three CDRs that form loops connecting, and in some cases forming part of, the β-pleated-sheet configuration. The CDRs in each chain are held together in close proximity by the FR regions and, together with the CDRs of the other chain, contribute to the formation of the antigen-binding site of antibodies (see Kabat et al. (1991) NIH PubL. No. 91-3242, Vol. I, pages 647-669). The constant domains are not directly involved in binding the antibody to an antigen, but exhibit various effector functions, such as Fc receptor (FcR) binding, participation of the antibody in antibody-dependent cellular cytotoxicity, induction of complement-dependent cytotoxicity, and mast cell degranulation.

[0077] As used herein, the term "hypervariable region" when used herein refers to the amino acid residues of an antibody which are responsible for antigen-binding. The hypervariable region comprises amino acid residues from the "complementarity determining regions" or "CDRs" (i.e., residues 24-34 (L1), 50-56 (L2), and 89-97 (L3) in the light chain variable domain and 31-35 (H1), 50-65 (H2), and 95-102 (H3) in the heavy chain variable domain; Kabat et al. (1991) Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md.), and / or amino acid residues from the "hypervariable loops" (i.e., residues 26-32 (L1), 50-52 (L2), and 91-96 (L3) in the light chain variable domain and (H1), 53-55 (H2), and 96-101 (H3) in the heavy chain variable domain; Clothia and Lesk, (1987) J. Mol. Biol., 196:901-917). "Framework" or "FR" residues are those variable domain residues other than the hypervariable region residues as herein considered.

[0078] An "Fv" is the minimum antibody fragment that contains a complete antigen-recognition and -binding site. This region consists of a dimer of one heavy- and one light-chain variable domain in tight, non-covalent association. It is in this configuration that the three CDRs of each variable domain interact to define an antigen-binding site on the surface of the VH-VL dimer. Collectively, the six CDRs confer antigen-binding specificity to the antibody. However, even a single variable domain (or half of an Fv containing only three CDRs specific for an antigen) has the ability to recognize and bind antigen, albeit with lower affinity than the entire binding site.

[0079] Fab fragments further contain the constant domain of the light chain and the first constant domain (CH1) of the heavy chain. Fab fragments differ from Fab' fragments by the addition of a few residues at the carboxy terminus of the heavy chain CH1 domain, including one or more cysteines from the antibody hinge region. Fab'-SH is the designation used herein for Fab' in which the cysteine ​​residues of the constant domains bear a free thiol group. Fab' fragments are generated by reduction of the heavy chain disulfide bridges of the F(ab')2 fragment. Other chemical linkages of antibody fragments are also known.

[0080] The "light chains" of antibodies (immunoglobulins) from any vertebrate species can be assigned to one of two clearly distinct types, called kappa (κ) and lambda (λ), based on the amino acid sequences of their constant domains.

[0081] "Single-chain variable fragment" or "scFv" refers to a fusion protein of the variable region of a light chain and the variable region of a heavy chain. The light chain variable region may be N-terminal to the variable region of the heavy chain, or the heavy chain variable region may be N-terminal to the variable region of the light chain.

[0082] Depending on the amino acid sequence of the constant domain of the heavy chain, immunoglobulins can be assigned to different classes. There are five major classes of human immunoglobulins: IgA, IgD, IgE, IgG, and IgM, and some of these can be further divided into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. The heavy chain constant domains corresponding to different classes of immunoglobulins are called alpha, delta, epsilon, gamma, and mu, respectively. The subunit structures and three-dimensional configurations of various classes of immunoglobulins are well known. Different isotypes have different effector functions. For example, human IgG1 and IgG3 isotypes have ADCC (antibody-dependent cell-mediated cytotoxicity) activity.

[0083] In some examples, the CDRs of an antibody can be numbered according to (i) the Kabat numbering system (Kabat et al. (1977) Ann. NY Acad. Sci. 190:382-391 and Kabat et al. (1991) Sequences of Proteins of Immunological Interest Fifth Edition, USDapartment of Health and Human Services, NIH Publication No. 91-3242), (ii) the Chothia numbering scheme, herein referred to as "Chothia CDRs" (e.g., Chothia and Lesk, 1987, J. Mol. Biol., 196:901-917; Al-Lazikani et al., 1997, J. Mol. Biol., 273:927-948; Chothia et al., 1992, J. Mol. Biol., 227:799-817; Tramontano A et al., 1992, J. Mol. Biol., 227:799-817). al., 1990, J. Mol. Biol. 215(1):175-82, and U.S. Patent No. 7,709,226), (iii) the ImMunoGeneTics (IMGT) numbering system (e.g., as described in Lefranc, M.-P., 1999, The Immunologist, 7:132-136, and Lefranc, M.-P. et al., 1999, Nucleic Acids Res., 27:209-212 ("IMGT CDRs")), or (iv) MacCallum et al., 1996, J. Mol. Biol., 262:732-745. See also, for example, Martin, A., "Protein Sequence and Structure Analysis of Antibody Variable Domains," in Antibody Engineering, Kontermann and Diibel, eds., Chapter 31, pp. 422-439, Springer-Verlag, Berlin (2001).

[0084] With respect to the Kabat numbering system, the CDRs within an antibody heavy chain molecule are typically located at amino acid positions 31-35 (which can optionally include one or two additional amino acids after 35, designated 35A and 35B in the Kabat numbering scheme) (CDR1), 50-65 (CDR2), and 95-102 (CDR3). Using the Kabat numbering system, the CDRs within an antibody light chain molecule are typically located at amino acid positions 24-34 (CDR1), 50-56 (CDR2), and 89-97 (CDR3). As is well known to those skilled in the art, using the Kabat numbering system, the actual linear amino acid sequence of an antibody variable domain may contain fewer or additional amino acids due to shortening or elongation of FRs and / or CDRs, and therefore the Kabat number of an amino acid may not necessarily be the same as its linear amino acid number.

[0085] The term "chimeric" antibody refers to an antibody in which a portion of the heavy and / or light chain is derived from a particular source or species, and the remainder of the heavy and / or light chain is derived from a different source or species.

[0086] The term "recombinant human antibody," as used herein, is intended to include all human antibodies prepared, expressed, generated, or isolated by recombinant means, such as antibodies isolated from host cells, such as NSO or CHO cells, or from animals (e.g., mice) transgenic for human immunoglobulin genes, or antibodies expressed using a recombinant expression vector transfected into a host cell. Such recombinant human antibodies have variable and constant regions in a rearranged form. In some cases, the recombinant human antibody has been subjected to in vivo somatic hypermutation. Thus, the amino acid sequences of the VH and VL regions of the recombinant antibody are derived from and related to human germline VH and VL sequences, but are sequences that may not naturally occur within the human antibody germline repertoire in vivo.

[0087] The terms "individual," "subject," and "patient" are used interchangeably herein and refer to any mammal. In some embodiments, the mammal is a human. In some embodiments, the mammal is a non-human. No term is limited to situations characterized by the supervision (e.g., full-time or intermittent) of a health care professional (e.g., a physician, registered nurse, bedside nurse, physician assistant, nursing assistant, or hospice worker).

[0088] As used herein, the term "percent (%) amino acid sequence identity" for a sequence is defined as the percentage of amino acid residues in a candidate sequence that are identical to the amino acid residues in a specific sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and without considering any conservative substitutions as part of the sequence identity.Alignment for the purpose of determining percent amino acid sequence identity can be obtained in various ways within the art, for example, using publicly available computer software such as EMBOSS MATCHER, EMBOSS WATER, EMBOSS STRETCHER, EMBOSS NEEDLE, EMBOSS LALIGN, BLAST, BLAST-2, ALIGN, or Megalign (DNASTAR) software.Those skilled in the art can determine the appropriate parameters for measuring alignment, including any algorithms required to achieve maximum alignment across the full length of the sequences being compared.

[0089] In situations where ALIGN-2 is used for amino acid sequence comparison, the % amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B (alternatively, it may be referred to as a given amino acid sequence A having or containing a particular % amino acid sequence identity with a given amino acid sequence B) is calculated as follows: 100 times the fraction X / Y, where X is the number of residues scored as matches by the ALIGN-2 sequence alignment program in the program's alignment identity between A and B, and Y is the total number of residues in B. It is understood that if the length of amino acid sequence A is not equal to the length of amino acid sequence B, the % amino acid sequence identity of A to B will not equal the % amino acid sequence identity of B to A. Unless specifically stated otherwise, all % amino acid sequence identity values ​​used herein are obtained using the ALIGN-2 computer program as described in the immediately preceding paragraph.

[0090] As used herein, "treatment" (and grammatical variations thereof, e.g., "treat" or "treating") refers to clinical intervention in an attempt to alter the natural course of the individual being treated and can be performed for prophylaxis or during the course of clinical pathology. Desirable effects of treatment include, but are not limited to, prevention of the occurrence or recurrence of an allergic reaction, alleviation of symptoms, reduction of any direct or indirect pathological consequences of an allergic reaction, prevention of metastasis, slowing the rate of an allergic reaction, amelioration or alleviation of an allergic reaction, and remission or improved prognosis. In some embodiments, molecules of the present disclosure are used to delay the onset of a disease or slow an allergic reaction.

[0091] Embodiment Embodiment A1. An isolated antibody that binds to Ara h 2 and Ara h 6, wherein the isolated antibody comprises a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein said HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences according to HC-CDR1: SEQ ID NO: 1, HC-CDR2: SEQ ID NO: 2 or SEQ ID NO: 3, and HC-CDR-3: SEQ ID NO: 4 or SEQ ID NO: 5; and wherein said isolated antibody comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein said LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences according to LC-CDR1: SEQ ID NO: 6, LC-CDR2: SEQ ID NO: 7, and LC-CDR-3: SEQ ID NO: 8.

[0092] Embodiment A2. The isolated antibody of embodiment A1, wherein the VH comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:9 or SEQ ID NO:10.

[0093] Embodiment A3. The isolated antibody of embodiment A1 or A2, wherein the VL comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:11.

[0094] Embodiment A4. The isolated antibody of any one of embodiments A1-A3, wherein the VH comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:9 or SEQ ID NO:10, and the VL comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:11.

[0095] Embodiment A5. The isolated antibody of any one of embodiments A1 to A4, wherein the isolated antibody comprises a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv).

[0096] Embodiment A6. The isolated antibody of any one of embodiments A1 to A5, wherein the isolated antibody is a Fab, Fab', F(ab')2, or single-chain variable fragment (scFv).

[0097] Embodiment A7. The isolated antibody of embodiment A5 or A6, wherein the isolated antibody comprises an scFv.

[0098] Embodiment A8. The isolated antibody of any one of embodiments A1 to A7, wherein the VH and VL are connected by an scFv linker sequence.

[0099] Embodiment A9. The isolated antibody of embodiment A8, wherein the scFv linker sequence comprises an amino acid sequence according to SEQ ID NO: 12.

[0100] Embodiment A10. The isolated antibody of any one of embodiments A5 to A9, wherein the scFv comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:13 or SEQ ID NO:14.

[0101] Embodiment A11. The isolated antibody of any one of embodiments A1 to A6, wherein the isolated antibody comprises a constant domain.

[0102] Embodiment A12. The isolated antibody of embodiment A11, wherein the constant domain comprises a human IgG4 sequence.

[0103] Embodiment A13. The isolated antibody of embodiment A12, wherein said human IgG4 sequence comprises a S228P point mutation, and wherein amino acid numbering is according to the EU index of Kabat et al.

[0104] Embodiment A14. The isolated antibody of embodiment A12 or A13, wherein the human IgG4 sequence does not have a C-terminal lysine residue.

[0105] Embodiment A15. The isolated antibody of any one of embodiments A11 to A14, wherein the constant domain comprises a human IgG1 sequence.

[0106] Embodiment A16. The constant domain is C H 1. C H 2. C H 3, or C L The isolated antibody of any one of embodiments A11 to A15, comprising the amino acid sequence

[0107] Embodiment A17. The isolated antibody is H 1. C H 2. C H 3, and C L The isolated antibody of any one of embodiments A1 to A15, comprising the amino acid sequence

[0108] Embodiment A18. The isolated antibody of any one of embodiments A1 to A17, wherein the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:72, or SEQ ID NO:73, and wherein the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:17.

[0109] Embodiment A19. An isolated, recombinant nucleic acid sequence encoding the amino acid sequence of the isolated antibody of any one of embodiments A1 to A18.

[0110] Embodiment A20. A vector comprising the isolated recombinant nucleic acid sequence of embodiment A19.

[0111] Embodiment A21. A pharmaceutical composition comprising (a) an isolated antibody of any one of embodiments A1-A18, and (b) a pharmaceutically acceptable excipient.

[0112] Embodiment A22. A method of treating a food allergy in a subject in need thereof, comprising administering to the subject an isolated antibody of any one of embodiments A1 to A18.

[0113] Embodiment A23. The method of embodiment A22, wherein said food allergy comprises a peanut allergy.

[0114] Embodiment B1. An isolated antibody that binds to Ara h 2 and Ara h 6, wherein the isolated antibody comprises a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein said HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences according to HC-CDR1: SEQ ID NO: 18, HC-CDR2: SEQ ID NO: 19, HC-CDR-3: SEQ ID NO: 20 or SEQ ID NO: 21, and wherein said isolated antibody comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein said LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences according to LC-CDR1: SEQ ID NO: 22, LC-CDR2: SEQ ID NO: 23, LC-CDR-3: SEQ ID NO: 24.

[0115] Embodiment B2. The isolated antibody of embodiment B1, wherein the VH comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:25 or SEQ ID NO:26.

[0116] Embodiment B3. The isolated antibody of embodiment B1 or B2, wherein the VL comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:27 or SEQ ID NO:28.

[0117] Embodiment B4. The isolated antibody of any one of embodiments B1-B3, wherein the VH comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:25 or SEQ ID NO:26, and the VL comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:27 or SEQ ID NO:28.

[0118] Embodiment B5. The isolated antibody of any one of embodiments B1-B4, wherein the isolated antibody comprises a Fab, a Fab', a F(ab')2, or a single-chain variable fragment (scFv).

[0119] Embodiment B6. The isolated antibody of any one of embodiments B1-B5, wherein the isolated antibody is a Fab, Fab', F(ab')2, or single-chain variable fragment (scFv).

[0120] Embodiment B7. The isolated antibody of embodiment B6 or B7, wherein the isolated antibody comprises an scFv.

[0121] Embodiment B8. The isolated antibody of any one of embodiments B1 to B7, wherein the VH and VL are connected by an scFv linker sequence.

[0122] Embodiment B9. The isolated antibody of embodiment B8, wherein the scFv linker sequence comprises an amino acid sequence according to SEQ ID NO:29.

[0123] Embodiment B10. The isolated antibody of any one of embodiments B5-B9, wherein the scFv comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:30 or SEQ ID NO:31.

[0124] Embodiment B11. The isolated antibody of any one of embodiments B1-B6, wherein said isolated antibody comprises a constant domain.

[0125] Embodiment B12. The isolated antibody of embodiment B11, wherein the constant domain comprises a human IgG4 sequence.

[0126] Embodiment B13. The isolated antibody of embodiment B12, wherein said human IgG4 sequence comprises a S228P point mutation, and wherein amino acid numbering is according to the EU index of Kabat et al.

[0127] Embodiment B14. The isolated antibody of embodiment B12 or B13, wherein the human IgG4 sequence does not have a C-terminal lysine residue.

[0128] Embodiment B15. The isolated antibody of any one of embodiments B11-B14, wherein the constant domain comprises a human IgG1 sequence.

[0129] Embodiment B16. The constant domain is C H 1. C H 2. C H 3, or C L The isolated antibody of any one of embodiments B11 to B15, comprising the amino acid sequence:

[0130] Embodiment B17. The isolated antibody is H 1. C H 2. C H 3, and C L The isolated antibody of any one of embodiments B1 to B15, comprising the amino acid sequence:

[0131] Embodiment B18. The isolated antibody of any one of embodiments B1 to B17, wherein the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:74, or SEQ ID NO:75, and wherein the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:34 or SEQ ID NO:76.

[0132] Embodiment B19. An isolated, recombinant nucleic acid sequence encoding the amino acid sequence of the isolated antibody of any one of embodiments B1 to B18.

[0133] Embodiment B20. A vector comprising the isolated recombinant nucleic acid sequence of embodiment B19.

[0134] Embodiment B21. A pharmaceutical composition comprising (a) an isolated antibody of any one of embodiments B1-B18, and (b) a pharmaceutically acceptable excipient.

[0135] Embodiment B22. A method of treating a food allergy in a subject in need thereof, comprising administering to the subject an isolated antibody of any one of embodiments B1 to B18.

[0136] Embodiment B23. The method of embodiment B22, wherein said food allergy comprises a peanut allergy.

[0137] Embodiment C1. An isolated antibody that binds to Ara h 2, wherein the isolated antibody comprises a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein said HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences according to HC-CDR1: SEQ ID NO: 35, HC-CDR2: SEQ ID NO: 36 or SEQ ID NO: 37, HC-CDR-3: SEQ ID NO: 38, and wherein said isolated antibody comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein said LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences according to LC-CDR1: SEQ ID NO: 39, LC-CDR2: SEQ ID NO: 40, LC-CDR-3: SEQ ID NO: 41.

[0138] Embodiment C2. The isolated antibody of embodiment C1, wherein the VH comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:42 or SEQ ID NO:43.

[0139] Embodiment C3. The isolated antibody of embodiment C1 or C2, wherein the VL comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:44.

[0140] Embodiment C4. The isolated antibody of any one of embodiments C1-C3, wherein the VH comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 42 or SEQ ID NO: 43, and the VL comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 44.

[0141] Embodiment C5. The isolated antibody of any one of embodiments C1-C4, wherein the isolated antibody comprises a Fab, a Fab', a F(ab')2, or a single-chain variable fragment (scFv).

[0142] Embodiment C6. The isolated antibody of any one of embodiments C1 to C5, wherein the isolated antibody is a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv).

[0143] Embodiment C7. The isolated antibody of embodiment C5 or C6, wherein the isolated antibody comprises an scFv.

[0144] Embodiment C8. The isolated antibody of any one of embodiments C1 to C7, wherein the VH and VL are connected by an scFv linker sequence.

[0145] Embodiment C9. The isolated antibody of embodiment C8, wherein the scFv linker sequence comprises an amino acid sequence according to SEQ ID NO:45.

[0146] Embodiment C10. The isolated antibody of any one of embodiments C5 to C9, wherein the scFv comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:46 or SEQ ID NO:47.

[0147] Embodiment C11. The isolated antibody of any one of embodiments C1 to C6, wherein said isolated antibody comprises a constant domain.

[0148] Embodiment C12. The isolated antibody of embodiment C11, wherein the constant domain comprises a human IgG4 sequence.

[0149] Embodiment C13. The isolated antibody of embodiment C12, wherein said human IgG4 sequence comprises a S228P point mutation, and wherein amino acid numbering is according to the EU index of Kabat et al.

[0150] Embodiment C14. The isolated antibody of embodiment C12 or C13, wherein the human IgG4 sequence does not have a C-terminal lysine residue.

[0151] Embodiment C15. The isolated antibody of any one of embodiments C11 to C14, wherein said constant domain comprises a human IgG1 sequence.

[0152] Embodiment C16. The constant domain is C H 1. C H 2. C H 3, or C L The isolated antibody of any one of embodiments C11 to C15, comprising the amino acid sequence

[0153] Embodiment C17. The isolated antibody is H 1. C H 2. C H 3, and C LThe isolated antibody of any one of embodiments C1 to C16, comprising the amino acid sequence

[0154] Embodiment C18. The isolated antibody of any one of embodiments C1 to C17, wherein the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78, and wherein the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50.

[0155] Embodiment C19. An isolated, recombinant nucleic acid sequence encoding the amino acid sequence of the isolated antibody of any one of embodiments C1 to C18.

[0156] Embodiment C20. A vector comprising the isolated recombinant nucleic acid sequence of embodiment C19.

[0157] Embodiment C21. A pharmaceutical composition comprising (a) an isolated antibody of any one of embodiments C1-C18, and (b) a pharmaceutically acceptable excipient.

[0158] Embodiment C22. A method of treating a food allergy in a subject in need thereof, comprising administering to the subject an isolated antibody of any one of embodiments C1 to C18.

[0159] Embodiment C23. The method of embodiment C22, wherein said food allergy comprises a peanut allergy.

[0160] Embodiment D1. An isolated antibody comprising a first binding domain that binds Ara h 2 and Ara h 6, wherein the first binding domain comprises a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences according to HC-CDR1: SEQ ID NO: 1, HC-CDR2: SEQ ID NO: 2 or SEQ ID NO: 3, and HC-CDR-3: SEQ ID NO: 4 or SEQ ID NO: 5; and the first binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences according to LC-CDR1: SEQ ID NO: 6, LC-CDR2: SEQ ID NO: 7, and LC-CDR-3: SEQ ID NO: 8; and wherein the isolated antibody binds to Ara h 2 and Ara h 6. 6, wherein the second binding domain comprises a VH comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences of HC-CDR1: SEQ ID NO: 18, HC-CDR2: SEQ ID NO: 19, and HC-CDR-3: SEQ ID NO: 20 or SEQ ID NO: 21; and the second binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 22, LC-CDR2: SEQ ID NO: 23, and LC-CDR-3: SEQ ID NO: 24.

[0161] Embodiment D2. The isolated antibody of embodiment D1, wherein the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:9 or SEQ ID NO:10.

[0162] Embodiment D3. The isolated antibody of embodiment D1 or D2, wherein the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:11.

[0163] Embodiment D4. The isolated antibody of any one of embodiments D1-D3, wherein the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:9 or SEQ ID NO:10, and the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:11.

[0164] Embodiment D5. The isolated antibody of any one of embodiments D1-D4, wherein the first binding domain comprises a Fab, a Fab', a F(ab')2, or a single-chain variable fragment (scFv).

[0165] Embodiment D6. The isolated antibody of any one of embodiments D1-D5, wherein the first binding domain is a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv).

[0166] Embodiment D7. The isolated antibody of embodiment D5 or D6, wherein the first binding domain comprises an scFv.

[0167] Embodiment D8. The isolated antibody of any one of embodiments D1-D7, wherein the VH of the first binding domain and the VL of the first binding domain are connected by an scFv linker sequence.

[0168] Embodiment D9. The isolated antibody of embodiment D8, wherein the scFv linker sequence of the first binding domain comprises an amino acid sequence according to SEQ ID NO: 12.

[0169] Embodiment D10. The isolated antibody of any one of embodiments D5-D9, wherein the scFv of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:13 or SEQ ID NO:14.

[0170] Embodiment D11. The isolated antibody of any one of embodiments D1-D6, wherein the first binding domain comprises a constant domain.

[0171] Embodiment D12. The isolated antibody of embodiment D11, wherein the constant domain of the first binding domain comprises a human IgG4 sequence.

[0172] Embodiment D13. The isolated antibody of embodiment D12, wherein the human IgG4 sequence of said first binding domain comprises a S228P point mutation, and wherein amino acid numbering is according to the EU index of Kabat et al.

[0173] Embodiment D14. The isolated antibody of embodiment D12 or D13, wherein the human IgG4 sequence of the first binding domain does not have a C-terminal lysine residue.

[0174] Embodiment D15. The isolated antibody of any one of embodiments D11 to D14, wherein the constant domain of the first binding domain comprises a human IgG1 sequence.

[0175] Embodiment D16. The constant domain of the first binding domain is C H 1. C H 2. C H 3, or C L The isolated antibody of any one of embodiments D11 to D15, comprising the amino acid sequence

[0176] Embodiment D17. The first binding domain comprises C H 1. C H 2. C H 3, and C LThe isolated antibody of any one of embodiments D1 to D15, comprising the amino acid sequence

[0177] Embodiment D18. The isolated antibody of any one of embodiments D1-D17, wherein the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:72, or SEQ ID NO:73, and the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:17.

[0178] Embodiment D19. The isolated antibody of any one of embodiments D1-D18, wherein the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:25 or SEQ ID NO:26.

[0179] Embodiment D20. The isolated antibody of any one of embodiments D1 to D19, wherein the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:27 or SEQ ID NO:28.

[0180] Embodiment D21. The isolated antibody of any one of embodiments D1-D20, wherein the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:25 or SEQ ID NO:26, and the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:27 or SEQ ID NO:28.

[0181] Embodiment D22. The isolated antibody of any one of embodiments D1-D21, wherein the second binding domain comprises a Fab, a Fab', a F(ab')2, or a single-chain variable fragment (scFv).

[0182] Embodiment D23. The isolated antibody of any one of embodiments D1-D22, wherein the second binding domain is a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv).

[0183] Embodiment D24. The isolated antibody of embodiment D22 or D23, wherein the second binding domain comprises an scFv.

[0184] Embodiment D25. The isolated antibody of any one of embodiments D1 to D24, wherein the VH of the second binding domain and the VL of the second binding domain are connected by an scFv linker sequence.

[0185] Embodiment D26. The isolated antibody of embodiment D25, wherein the scFv linker sequence of the second binding domain comprises an amino acid sequence according to SEQ ID NO:29.

[0186] Embodiment D27. The isolated antibody of any one of embodiments D1-D26, wherein the scFv of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:30 or SEQ ID NO:31.

[0187] Embodiment D28. The isolated antibody of any one of embodiments D1 to D27, wherein the second binding domain comprises a constant domain.

[0188] Embodiment D29. The isolated antibody of embodiment D28, wherein the constant domain of the second binding domain comprises a human IgG4 sequence.

[0189] Embodiment D30. The isolated antibody of embodiment D29, wherein the human IgG4 sequence of said second binding domain comprises a S228P point mutation, and wherein amino acid numbering is according to the EU index of Kabat et al.

[0190] Embodiment D31. The isolated antibody of embodiment D29 or D30, wherein the human IgG4 sequence of the second binding domain does not have a C-terminal lysine residue.

[0191] Embodiment D32. The isolated antibody of any one of embodiments D28 to D31, wherein the constant domain of the second binding domain comprises a human IgG1 sequence.

[0192] Embodiment D33. The constant domain of the second binding domain is C H 1. C H 2. C H 3, or C L The isolated antibody of any one of embodiments D28 to D32, comprising the amino acid sequence

[0193] Embodiment D34. The second binding domain is C H 1. C H 2. C H 3, and C L The isolated antibody of any one of embodiments D1 to D32, comprising the amino acid sequence

[0194] Embodiment D35. The isolated antibody of any one of embodiments D1-D34, wherein the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:74, or SEQ ID NO:75, and the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:34 or SEQ ID NO:76.

[0195] Embodiment D36. The first binding domain comprises an scFv and the second binding domain comprises a C H1. C H 2. C H 3, and C L The isolated antibody of any one of embodiments D1 to D35, comprising the amino acid sequence

[0196] Embodiment D37. The second binding domain comprises an scFv and the first binding domain comprises C H 1. C H 2. C H 3, and C L The isolated antibody of any one of embodiments D1 to D35, comprising the amino acid sequence

[0197] Embodiment D38. The isolated antibody of any one of embodiments D1 to D37, wherein the first binding domain and the second binding domain are connected by a linking moiety.

[0198] Embodiment D39. The isolated antibody of embodiment D38, wherein the linking moiety is an amino acid sequence.

[0199] Embodiment D40. The isolated antibody of embodiment D38 or D39, wherein the linking moiety is at least 4 amino acids in length.

[0200] Embodiment D41. The isolated antibody of any one of embodiments D38 to D40, wherein the linking moiety is between 4 and 20 amino acids in length.

[0201] Embodiment D42. The linking moiety is C of the second binding domain H The isolated antibody of any one of embodiments D38 to D41, wherein the three amino acid sequences are joined to the scFv of the first binding domain.

[0202] Embodiment D43. The isolated antibody of any one of embodiments D38 to D42, wherein the linking moiety comprises the amino acid sequence of SEQ ID NO:51.

[0203] Embodiment D44. The isolated antibody of any one of embodiments D1-D43, wherein the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 53 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 52.

[0204] Embodiment D45. The isolated antibody of any one of embodiments D1-D43, wherein the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 55 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 54.

[0205] Embodiment D46. The isolated antibody of any one of embodiments D1-D43, wherein the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 65 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 64.

[0206] Embodiment D47. The isolated antibody of any one of embodiments D1-D43, wherein the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 67 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 66.

[0207] Embodiment D48. The isolated antibody of any one of embodiments D1-D43, wherein the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 69 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 68.

[0208] Embodiment D49. The isolated antibody of any one of embodiments D1-D43, wherein the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 71 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 70.

[0209] Embodiment D50. An isolated, recombinant nucleic acid sequence encoding the amino acid sequence of the isolated antibody of any one of embodiments D1-D49.

[0210] Embodiment D51. A vector comprising the isolated recombinant nucleic acid sequence of embodiment D50.

[0211] Embodiment D52. A pharmaceutical composition comprising (a) an isolated antibody of any one of embodiments D1-D49, and (b) a pharmaceutically acceptable excipient.

[0212] Embodiment D53. A method of treating a food allergy in a subject in need thereof, comprising administering to the subject an isolated antibody of any one of embodiments D1-D49.

[0213] Embodiment D54 The method of embodiment D53, wherein said food allergy comprises a peanut allergy.

[0214] Embodiment E1. An isolated antibody comprising a first binding domain that binds to Ara h 2 and Ara h 6, wherein the first binding domain comprises a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences according to HC-CDR1: SEQ ID NO: 1, HC-CDR2: SEQ ID NO: 2 or SEQ ID NO: 3, and HC-CDR-3: SEQ ID NO: 4 or SEQ ID NO: 5; and the first binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences according to LC-CDR1: SEQ ID NO: 6, LC-CDR2: SEQ ID NO: 7, and LC-CDR-3: SEQ ID NO: 8; and wherein the isolated antibody binds to Ara h 2 and Ara h 6. 2, wherein the second binding domain comprises a VH comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences of HC-CDR1: SEQ ID NO: 35, HC-CDR2: SEQ ID NO: 36 or SEQ ID NO: 37, and HC-CDR-3: SEQ ID NO: 38; and wherein the isolated antibody comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 39, LC-CDR2: SEQ ID NO: 40, and LC-CDR-3: SEQ ID NO: 41.

[0215] Embodiment E2. The isolated antibody of embodiment E1, wherein the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:9 or SEQ ID NO:10.

[0216] Embodiment E3. The isolated antibody of embodiment E1 or E2, wherein the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:11.

[0217] Embodiment E4. The isolated antibody of any one of embodiments E1-E3, wherein the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:9 or SEQ ID NO:10, and the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:11.

[0218] Embodiment E5. The isolated antibody of any one of embodiments E1-E4, wherein the first binding domain comprises a Fab, a Fab', a F(ab')2, or a single-chain variable fragment (scFv).

[0219] Embodiment E6. The isolated antibody of any one of embodiments E1 to E5, wherein the first binding domain is a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv).

[0220] Embodiment E7. The isolated antibody of embodiment E5 or E6, wherein the first binding domain comprises an scFv.

[0221] Embodiment E8. The isolated antibody of any one of embodiments E1 to E7, wherein the VH of the first binding domain and the VL of the first binding domain are connected by an scFv linker sequence.

[0222] Embodiment E9. The isolated antibody of embodiment E8, wherein the scFv linker sequence of the first binding domain comprises an amino acid sequence according to SEQ ID NO: 12.

[0223] Embodiment E10. The isolated antibody of embodiment E7, wherein the scFv of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:13 or SEQ ID NO:14.

[0224] Embodiment E11. The isolated antibody of any one of embodiments E1 to E6, wherein the first binding domain comprises a constant domain.

[0225] Embodiment E12. The isolated antibody of embodiment E11, wherein the constant domain of the first binding domain comprises a human IgG4 sequence.

[0226] Embodiment E13. The isolated antibody of embodiment E12, wherein the human IgG4 sequence of said first binding domain comprises a S228P point mutation, and wherein amino acid numbering is according to the EU index of Kabat et al.

[0227] Embodiment E14. The isolated antibody of embodiment E12 or E13, wherein the human IgG4 sequence of the first binding domain does not have a C-terminal lysine residue.

[0228] Embodiment E15. The isolated antibody of any one of embodiments E11 to E14, wherein the constant domain of the first binding domain comprises a human IgG1 sequence.

[0229] Embodiment E16. The constant domain of the first binding domain is C H 1. C H 2. C H 3, or C L The isolated antibody of any one of embodiments E11 to E15, comprising the amino acid sequence

[0230] Embodiment E17. The first binding domain is C H 1. C H 2. C H 3, and C L The isolated antibody of any one of embodiments E1 to E15, comprising the amino acid sequence

[0231] Embodiment E18. The isolated antibody of any one of embodiments E1 to E17, wherein the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:72, or SEQ ID NO:73, and the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:17.

[0232] Embodiment E19. The isolated antibody of any one of embodiments E1 to E18, wherein the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 42 or SEQ ID NO: 43.

[0233] Embodiment E20. The isolated antibody of any one of embodiments E1 to E19, wherein the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:44.

[0234] Embodiment E21. The isolated antibody of any one of embodiments E1-E20, wherein the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 42 or SEQ ID NO: 43, and the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 44.

[0235] Embodiment E22. The isolated antibody of any one of embodiments E1 to E21, wherein the second binding domain comprises a Fab, a Fab', a F(ab')2, or a single-chain variable fragment (scFv).

[0236] Embodiment E23. The isolated antibody of any one of embodiments E1 to E22, wherein the second binding domain is a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv).

[0237] Embodiment E24. The isolated antibody of embodiment E22 or E23, wherein the second binding domain comprises an scFv.

[0238] Embodiment E25. The isolated antibody of any one of embodiments E1 to E24, wherein the VH of the second binding domain and the VL of the second binding domain are connected by an scFv linker sequence.

[0239] Embodiment E26. The isolated antibody of embodiment E25, wherein the scFv linker sequence of the second binding domain comprises an amino acid sequence according to SEQ ID NO:45.

[0240] Embodiment E27. The isolated antibody of any one of embodiments E1 to E26, wherein the scFv of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:46 or SEQ ID NO:47.

[0241] Embodiment E28. The isolated antibody of any one of embodiments E1 to E23, wherein the second binding domain comprises a constant domain.

[0242] Embodiment E29. The isolated antibody of embodiment E28, wherein the constant domain of the second binding domain comprises a human IgG4 sequence.

[0243] Embodiment E30. The isolated antibody of embodiment E29, wherein the human IgG4 sequence of said second binding domain comprises a S228P point mutation, and wherein amino acid numbering is according to the EU index of Kabat et al.

[0244] Embodiment E31. The isolated antibody of embodiment E28 or E29, wherein the human IgG4 sequence of the second binding domain does not have a C-terminal lysine residue.

[0245] Embodiment E32. The isolated antibody of any one of embodiments E28 to E31, wherein the constant domain of the second binding domain comprises a human IgG1 sequence.

[0246] Embodiment E33. The constant domain of the second binding domain is C H 1. C H 2. C H 3, or C L The isolated antibody of any one of embodiments E28 to E32, comprising the amino acid sequence

[0247] Embodiment E34. The second binding domain is C H 1. C H 2. C H 3, and C L The isolated antibody of any one of embodiments E1 to E32, comprising the amino acid sequence

[0248] Embodiment E35. The isolated antibody of any one of embodiments E1-E34, wherein the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78, and wherein the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50.

[0249] Embodiment E36. The first binding domain comprises an scFv and the second binding domain comprises a C H 1. C H 2. C H 3, and C L The isolated antibody of any one of embodiments E1 to E35, comprising the amino acid sequence

[0250] Embodiment E37. The second binding domain comprises an scFv and the first binding domain comprises C H 1. C H 2. C H 3, and C L The isolated antibody of any one of embodiments E1 to E35, comprising the amino acid sequence

[0251] Embodiment E38. The isolated antibody of any one of embodiments E1 to E37, wherein the first binding domain and the second binding domain are connected by a linking moiety.

[0252] Embodiment E39. The isolated antibody of embodiment E38, wherein the linking moiety is an amino acid sequence.

[0253] Embodiment E40. The isolated antibody of embodiment E38 or E39, wherein the linking moiety is at least 4 amino acids in length.

[0254] Embodiment E41. The isolated antibody of any one of embodiments E38 to E41, wherein the linking moiety is between 4 and 20 amino acids in length.

[0255] Embodiment E42. The linking moiety is C of the second binding domain H The isolated antibody of any one of embodiments E38 to E41, wherein the three amino acid sequences are joined to the scFv of the first binding domain.

[0256] Embodiment E43. The isolated antibody of any one of embodiments E38 to E42, wherein the linking moiety comprises the amino acid sequence of SEQ ID NO:51.

[0257] Embodiment E44. The isolated antibody of any one of embodiments E1 to E43, wherein the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 57 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 56.

[0258] Embodiment E45. The isolated antibody of any one of embodiments E1 to E43, wherein the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 59 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 58.

[0259] Embodiment E46. An isolated, recombinant nucleic acid sequence encoding the amino acid sequence of the isolated antibody of any one of embodiments E1 to E45.

[0260] Embodiment E47. A vector comprising the isolated recombinant nucleic acid sequence of embodiment E46.

[0261] Embodiment E48. A pharmaceutical composition comprising (a) an isolated antibody of any one of embodiments E1-E45, and (b) a pharmaceutically acceptable excipient.

[0262] Embodiment E49. A method of treating a food allergy in a subject in need thereof, comprising administering to the subject an isolated antibody of any one of embodiments E1 to E45.

[0263] Embodiment E50. The method of embodiment E49, wherein said food allergy comprises a peanut allergy.

[0264] Embodiment F1. An isolated antibody comprising a first binding domain that binds Ara h 2 and Ara h 6, wherein the first binding domain comprises a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences according to HC-CDR1: SEQ ID NO: 18, HC-CDR2: SEQ ID NO: 19, HC-CDR-3: SEQ ID NO: 20 or SEQ ID NO: 21; and the first binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences according to LC-CDR1: SEQ ID NO: 22, LC-CDR2: SEQ ID NO: 23, LC-CDR-3: SEQ ID NO: 24; and wherein the isolated antibody binds to Ara h 2 and Ara h 6. 2, wherein the second binding domain comprises a VH comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences of HC-CDR1: SEQ ID NO: 35, HC-CDR2: SEQ ID NO: 36 or SEQ ID NO: 37, and HC-CDR-3: SEQ ID NO: 38; and wherein the isolated antibody comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 39, LC-CDR2: SEQ ID NO: 40, and LC-CDR-3: SEQ ID NO: 41.

[0265] Embodiment F2. The isolated antibody of embodiment F1, wherein the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:25 or SEQ ID NO:26.

[0266] Embodiment F3. The isolated antibody of embodiment F1 or F2, wherein the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:27 or SEQ ID NO:28.

[0267] Embodiment F4. The isolated antibody of any one of embodiments F1-F3, wherein the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:25 or SEQ ID NO:26, and the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:27 or SEQ ID NO:28.

[0268] Embodiment F5. The isolated antibody of any one of embodiments F1-F4, wherein the first binding domain comprises a Fab, a Fab', a F(ab')2, or a single-chain variable fragment (scFv).

[0269] Embodiment F6. The isolated antibody of any one of embodiments F1 to F5, wherein the first binding domain is a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv).

[0270] Embodiment F7. The isolated antibody of embodiment F5 or F6, wherein the first binding domain comprises an scFv.

[0271] Embodiment F8. The isolated antibody of any one of embodiments F1 to F7, wherein the VH of the first binding domain and the VL of the first binding domain are connected by an scFv linker sequence.

[0272] Embodiment F9. The isolated antibody of embodiment F8, wherein the scFv linker sequence of the first binding domain comprises an amino acid sequence according to SEQ ID NO:29.

[0273] Embodiment F10. The isolated antibody of any one of embodiments F1 to F9, wherein the scFv of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 30 or SEQ ID NO: 31.

[0274] Embodiment F11. The isolated antibody of any one of embodiments F1 to F6, wherein the first binding domain comprises a constant domain.

[0275] Embodiment F12. The isolated antibody of embodiment F11, wherein the constant domain of the first binding domain comprises a human IgG4 sequence.

[0276] Embodiment F13. The isolated antibody of embodiment F12, wherein the human IgG4 sequence of said first binding domain comprises a S228P point mutation, and wherein amino acid numbering is according to the EU index of Kabat et al.

[0277] Embodiment F14. The isolated antibody of embodiment F12 or F13, wherein the human IgG4 sequence of the first binding domain does not have a C-terminal lysine residue.

[0278] Embodiment F15. The isolated antibody of any one of embodiments F11 to F14, wherein the constant domain of the first binding domain comprises a human IgG1 sequence.

[0279] Embodiment F16. The constant domain of the first binding domain is C H 1. C H 2. C H 3, or C L The isolated antibody of any one of embodiments F11 to F15, comprising the amino acid sequence

[0280] Embodiment F17. The first binding domain comprises C H 1. C H 2. C H 3, and C LThe isolated antibody of any one of embodiments F1 to F15, comprising the amino acid sequence

[0281] Embodiment F18. The isolated antibody of any one of embodiments F1 to F17, wherein the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:74, or SEQ ID NO:75, and wherein the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:34 or SEQ ID NO:76.

[0282] Embodiment F19. The isolated antibody of any one of embodiments F1 to F18, wherein the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 42 or SEQ ID NO: 43.

[0283] Embodiment F20. The isolated antibody of any one of embodiments F1 to F19, wherein the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:44.

[0284] Embodiment F21. The isolated antibody of any one of embodiments F1 to F20, wherein the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 42 or SEQ ID NO: 43, and the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 44.

[0285] Embodiment F22. The isolated antibody of any one of embodiments F1 to F21, wherein the second binding domain comprises a Fab, a Fab', a F(ab')2, or a single-chain variable fragment (scFv).

[0286] Embodiment F23. The isolated antibody of any one of embodiments F1 to F22, wherein the second binding domain is a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv).

[0287] Embodiment F24. The isolated antibody of embodiment F22 or F23, wherein the second binding domain comprises an scFv.

[0288] Embodiment F25. The isolated antibody of any one of embodiments F1 to F24, wherein the VH of the second binding domain and the VL of the second binding domain are connected by an scFv linker sequence.

[0289] Embodiment F26. The isolated antibody of embodiment F25, wherein the scFv linker sequence of said second binding domain comprises an amino acid sequence according to SEQ ID NO:45.

[0290] Embodiment F27. The isolated antibody of any one of embodiments F1 to F26, wherein the scFv of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:46 or SEQ ID NO:47.

[0291] Embodiment F28. The isolated antibody of any one of embodiments F1 to F23, wherein the second binding domain comprises a constant domain.

[0292] Embodiment F29. The isolated antibody of embodiment F28, wherein the constant domain of the second binding domain comprises a human IgG4 sequence.

[0293] Embodiment F30. The isolated antibody of embodiment F29, wherein the human IgG4 sequence of said second binding domain comprises a S228P point mutation, and wherein amino acid numbering is according to the EU index of Kabat et al.

[0294] Embodiment F31. The isolated antibody of embodiment F29 or F30, wherein the human IgG4 sequence of the second binding domain does not have a C-terminal lysine residue.

[0295] Embodiment F32. The isolated antibody of any one of embodiments F28 to F31, wherein the constant domain of the second binding domain comprises a human IgG1 sequence.

[0296] Embodiment F33. The constant domain of the second binding domain is C H 1. C H 2. C H 3, or C L The isolated antibody of any one of embodiments F28 to F32, comprising the amino acid sequence

[0297] Embodiment F34. The second binding domain comprises C H 1. C H 2. C H 3, and C L The isolated antibody of any one of embodiments F1 to F32, comprising the amino acid sequence

[0298] Embodiment F35. The isolated antibody of any one of embodiments F1 to F34, wherein the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78, and the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50.

[0299] Embodiment F36. The first binding domain comprises an scFv and the second binding domain comprises a C H 1. CH 2. C H 3, and C L The isolated antibody of any one of embodiments F1 to F35, comprising the amino acid sequence

[0300] Embodiment F37. The second binding domain comprises an scFv and the first binding domain comprises C H 1. C H 2. C H 3, and C L The isolated antibody of any one of embodiments F1 to F35, comprising the amino acid sequence

[0301] Embodiment F38. The isolated antibody of any one of embodiments F1 to F37, wherein the first binding domain and the second binding domain are connected by a linking moiety.

[0302] Embodiment F39. The isolated antibody of embodiment F38, wherein the linking moiety is an amino acid sequence.

[0303] Embodiment F40. The isolated antibody of embodiment F38 or F39, wherein the linking moiety is at least 4 amino acids in length.

[0304] Embodiment F41. The isolated antibody of any one of embodiments F38 to F40, wherein the linking moiety is between 4 and 20 amino acids in length.

[0305] Embodiment F42. The linking moiety is C of the second binding domain. H The isolated antibody of any one of embodiments F38 to F41, wherein the three amino acid sequence is joined to the scFv of the first binding domain.

[0306] Embodiment F43. The isolated antibody of any one of embodiments F38 to F42, wherein the linking moiety comprises the amino acid sequence of SEQ ID NO:51.

[0307] Embodiment F44. The isolated antibody of any one of embodiments F1 to F43, wherein the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 61 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 60.

[0308] Embodiment F45. The isolated antibody of any one of embodiments F1 to F43, wherein the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 63 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 62.

[0309] Embodiment F46. An isolated, recombinant nucleic acid sequence encoding the amino acid sequence of the isolated antibody of any one of embodiments F1 to F45.

[0310] Embodiment F47. A vector comprising the isolated recombinant nucleic acid sequence of embodiment F46.

[0311] Embodiment F48. A pharmaceutical composition comprising (a) an isolated antibody of any one of embodiments F1-F47, and (b) a pharmaceutically acceptable excipient.

[0312] Embodiment F49. A method of treating a food allergy in a subject in need thereof, comprising administering to the subject an isolated antibody of any one of embodiments F1-F47.

[0313] Embodiment F50. The method of embodiment F49, wherein said food allergy comprises a peanut allergy.

[0314] Embodiment G1. A composition comprising a first binding domain that binds to Ara h 2 and Ara h 6, wherein the first binding domain comprises a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences according to HC-CDR1: SEQ ID NO: 1, HC-CDR2: SEQ ID NO: 2 or SEQ ID NO: 3, and HC-CDR-3: SEQ ID NO: 4 or SEQ ID NO: 5; and the first binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences according to LC-CDR1: SEQ ID NO: 6, LC-CDR2: SEQ ID NO: 7, and LC-CDR-3: SEQ ID NO: 8; and wherein the composition binds to Ara h 2 and Ara h 6. and a second binding domain that binds to Ara h, wherein the second binding domain comprises a VH comprising CDRs: HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences according to HC-CDR1: SEQ ID NO: 18, HC-CDR2: SEQ ID NO: 19, and HC-CDR-3: SEQ ID NO: 20 or SEQ ID NO: 21; the second binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences according to LC-CDR1: SEQ ID NO: 22, LC-CDR2: SEQ ID NO: 23, and LC-CDR-3: SEQ ID NO: 24; and the composition isand a third binding domain that binds to IgG1A-2, wherein the third binding domain comprises a VH comprising CDRs: HC-CDR1, HC-CDR2, and HC-CDR3, wherein the HC-CDR1, HC-CDR2, and HC-CDR3 comprise the amino acid sequences of HC-CDR1: SEQ ID NO: 35, HC-CDR2: SEQ ID NO: 36 or SEQ ID NO: 37, and HC-CDR-3: SEQ ID NO: 38; and the third binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, and LC-CDR3, wherein the LC-CDR1, LC-CDR2, and LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 39, LC-CDR2: SEQ ID NO: 40, and LC-CDR-3: SEQ ID NO: 41.

[0315] Embodiment G2. The composition of embodiment G1, wherein the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:9 or SEQ ID NO:10.

[0316] Embodiment G3. The composition of embodiment G1 or G2, wherein the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:11.

[0317] Embodiment G4. The composition of any one of embodiments G1 to G3, wherein the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:9 or SEQ ID NO:10, and the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:11.

[0318] Embodiment G5. The composition of any one of embodiments G1 to G4, wherein the first binding domain comprises a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv).

[0319] Embodiment G6. The composition of any one of embodiments G1 to G5, wherein the first binding domain is a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv).

[0320] Embodiment G7. The composition of embodiment G5 or G6, wherein the first binding domain comprises an scFv.

[0321] Embodiment G8. The composition of any one of embodiments G1 to G7, wherein the VH of the first binding domain and the VL of the first binding domain are connected by an scFv linker sequence.

[0322] Embodiment G9. The composition of embodiment G8, wherein the scFv linker sequence of the first binding domain comprises an amino acid sequence according to SEQ ID NO: 12.

[0323] Embodiment G10. The composition of any one of embodiments G5 to G9, wherein the scFv of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 13 or SEQ ID NO: 14.

[0324] Embodiment G11. The composition of any one of embodiments G1 to G6, wherein the first binding domain comprises a constant domain.

[0325] Embodiment G12. The composition of embodiment G11, wherein the constant domain of the first binding domain comprises a human IgG4 sequence.

[0326] Embodiment G13. The composition of embodiment G12, wherein the human IgG4 sequence of said first binding domain comprises a S228P point mutation, and wherein amino acid numbering is according to the EU index of Kabat et al.

[0327] Embodiment G14. The composition of embodiment G12 or G13, wherein the human IgG4 sequence of the first binding domain does not have a C-terminal lysine residue.

[0328] Embodiment G15. The composition of any one of embodiments G11 to G14, wherein the constant domain of the first binding domain comprises a human IgG1 sequence.

[0329] Embodiment G16. The constant domain of the first binding domain is C H 1. C H 2. C H 3, or C L The composition of any one of embodiments G11 to G15, comprising an amino acid sequence.

[0330] Embodiment G17. The first binding domain is C H 1. C H 2. C H 3, and C L The composition of any one of embodiments G1 to G15, comprising an amino acid sequence.

[0331] Embodiment G18. The composition of any one of embodiments G1 to G17, wherein the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 72, or SEQ ID NO: 73, and the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 17.

[0332] Embodiment G19. The composition of any one of embodiments G1 to G18, wherein the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 25 or SEQ ID NO: 26.

[0333] Embodiment G20. The composition of any one of embodiments G1 to G19, wherein the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:27 or SEQ ID NO:28.

[0334] Embodiment G21. The composition of any one of embodiments G1 to G20, wherein the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:25 or SEQ ID NO:26, and the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:27 or SEQ ID NO:28.

[0335] Embodiment G22. The composition of any one of embodiments G1 to G21, wherein the second binding domain comprises a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv).

[0336] Embodiment G23. The composition of any one of embodiments G1 to G22, wherein the second binding domain is a Fab, Fab', F(ab')2, or a single chain variable fragment (scFv).

[0337] Embodiment G24. The composition of embodiment G22 or G23, wherein the second binding domain comprises an scFv.

[0338] Embodiment G25. The composition of any one of embodiments G1 to G24, wherein the VH of the second binding domain and the VL of the second binding domain are connected by an scFv linker sequence.

[0339] Embodiment G26. The composition of embodiment G25, wherein the scFv linker sequence of the second binding domain comprises an amino acid sequence according to SEQ ID NO:29.

[0340] Embodiment G27. The composition of any one of embodiments G22 to G26, wherein the scFv of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 30 or SEQ ID NO: 31.

[0341] Embodiment G28. The composition of any one of embodiments G1 to G23, wherein said second binding domain comprises a constant domain.

[0342] Embodiment G29. The composition of embodiment G28, wherein the constant domain of the second binding domain comprises a human IgG4 sequence.

[0343] Embodiment G30. The composition of embodiment G29, wherein the human IgG4 sequence of said second binding domain comprises a S228P point mutation, and wherein amino acid numbering is according to the EU index of Kabat et al.

[0344] Embodiment G31. The composition of embodiment G29 or G30, wherein the human IgG4 sequence of the second binding domain does not have a C-terminal lysine residue.

[0345] Embodiment G32. The composition of any one of embodiments G28 to G31, wherein the constant domain of the second binding domain comprises a human IgG1 sequence.

[0346] Embodiment G33. The constant domain of the second binding domain is C H 1. C H 2. C H 3, or C L The composition of any one of embodiments G28 to G32, comprising an amino acid sequence.

[0347] Embodiment G34. The second binding domain comprises C H 1. C H 2. C H 3, and C L The composition of any one of embodiments G1 to G32, comprising an amino acid sequence.

[0348] Embodiment G35. The composition of any one of embodiments G1 to G34, wherein the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:74, or SEQ ID NO:75, and the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:34 or SEQ ID NO:76.

[0349] Embodiment G36. The composition of any one of embodiments G1 to G35, wherein the VH of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 42 or SEQ ID NO: 43.

[0350] Embodiment G37. The composition of any one of embodiments G1 to G36, wherein the VL of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 44.

[0351] Embodiment G38. The composition of any one of embodiments G1 to G37, wherein the VH of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 42 or SEQ ID NO: 43, and the VL of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 44.

[0352] Embodiment G39. The composition of any one of embodiments G1 to G38, wherein the third binding domain comprises a Fab, Fab', F(ab')2, or a single-chain variable fragment (scFv).

[0353] Embodiment G40. The composition of any one of embodiments G1 to G39, wherein the third binding domain is a Fab, Fab', F(ab')2, or a single chain variable fragment (scFv).

[0354] Embodiment G41. The composition of embodiment G39 or G40, wherein the third binding domain comprises an scFv.

[0355] Embodiment G42. The composition of any one of embodiments G1 to G41, wherein the VH of the third binding domain and the VL of the third binding domain are connected by an scFv linker sequence.

[0356] Embodiment G43. The composition of embodiment G42, wherein the scFv linker sequence of said third binding domain comprises an amino acid sequence according to SEQ ID NO: 45.

[0357] Embodiment G44. The composition of any one of embodiments G39 to G43, wherein the scFv of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 46 or SEQ ID NO: 47.

[0358] Embodiment G45. The composition of any one of embodiments G1 to G40, wherein said third binding domain comprises a constant domain.

[0359] Embodiment G46. The composition of embodiment G45, wherein the constant domain of the third binding domain comprises a human IgG4 sequence.

[0360] Embodiment G47. The composition of embodiment G46, wherein the human IgG4 sequence of said third binding domain comprises a S228P point mutation, and wherein amino acid numbering is according to the EU index of Kabat et al.

[0361] Embodiment G48. The composition of embodiment G46 or G47, wherein the human IgG4 sequence of said third binding domain does not have a C-terminal lysine residue.

[0362] Embodiment G49. The composition of any one of embodiments G45 to G48, wherein the constant domain of the third binding domain comprises a human IgG1 sequence.

[0363] Embodiment G50. The constant domain of the third binding domain is C H 1. C H 2. C H 3, or C L The composition of any one of embodiments G45 to G49, comprising an amino acid sequence.

[0364] Embodiment G51. The third binding domain comprises C H 1. C H 2. C H 3, and C L The composition of any one of embodiments G1 to G49, comprising an amino acid sequence.

[0365] Embodiment G52. The composition of any one of embodiments G1 to G51, wherein the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78, and the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50.

[0366] Embodiment G53. The composition of any one of embodiments G1 to G52, wherein the first binding domain, second binding domain, and third binding domain are connected within the same molecule.

[0367] Embodiment G54. The composition of any one of embodiments G1 to G52, wherein the first binding domain, second binding domain, and third binding domain are separate molecules.

[0368] Embodiment G55. The composition of any one of embodiments G1-G52, wherein the first binding domain and the second binding domain are in the same molecule, and the third binding domain is a separate molecule from the molecule bearing the first binding domain and the second binding domain.

[0369] Embodiment G56. The composition of any one of embodiments G1-G52, wherein the first binding domain and the third binding domain are in the same molecule, and the second binding domain is a separate molecule from the molecule bearing the first binding domain and the third binding domain.

[0370] Embodiment G57. The composition of any one of embodiments G1-G52, wherein the second binding domain and the third binding domain are in the same molecule, and the first binding domain is a separate molecule from the molecule bearing the second binding domain and the third binding domain.

[0371] Embodiment G58. The first binding domain comprises an scFv and the second binding domain comprises a C H 1. C H 2. C H 3, and C L The composition of any one of embodiments G5 to G57, comprising an amino acid sequence.

[0372] Embodiment G59. The second binding domain comprises an scFv and the first binding domain comprises C H 1. C H 2. C H 3, and C L The composition of any one of embodiments G22 to G58, comprising an amino acid sequence.

[0373] Embodiment G60. The composition of any one of embodiments G1 to G59, wherein the first binding domain and second binding domain are connected by a linking moiety.

[0374] Embodiment G61. The composition of embodiment G60, wherein the linking moiety is an amino acid sequence.

[0375] Embodiment G62. The composition of embodiment G60 or G61, wherein the linking moiety is at least 4 amino acids in length.

[0376] Embodiment G63. The composition of any one of embodiments G60 to G62, wherein the linking moiety is between 4 and 20 amino acids in length.

[0377] Embodiment G64. The linking moiety is C of the second binding domain. H The composition of any one of embodiments G60 to G63, wherein the three amino acid sequences are joined to the scFv of the first binding domain.

[0378] Embodiment G65. The composition of any one of embodiments G60 to G64, wherein the linking moiety comprises the amino acid sequence of SEQ ID NO:51.

[0379] Embodiment G66. The composition of any one of embodiments G1 to G65, wherein the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:53 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:52, and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78, and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50.

[0380] Embodiment G67. The composition of any one of embodiments G1 to G65, wherein the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:55 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:54, and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78, and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50.

[0381] Embodiment G68. The composition of any one of embodiments G1 to G65, wherein the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 65 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 64, the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 77, or SEQ ID NO: 78, and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 50.

[0382] Embodiment G69. The composition of any one of embodiments G1 to G65, wherein the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 67 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 66, the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 77, or SEQ ID NO: 78, and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 50.

[0383] Embodiment G70. The composition of any one of embodiments G1 to G65, wherein the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 69 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 68, and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 77, or SEQ ID NO: 78, and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 50.

[0384] Embodiment G71. The composition of any one of embodiments G1 to G65, wherein the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 71 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 70, the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 77, or SEQ ID NO: 78, and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 50.

[0385] Embodiment G72. The composition of any one of embodiments G1-G71, wherein the composition comprises a pharmaceutically acceptable excipient.

[0386] Embodiment G73. An isolated, recombinant nucleic acid sequence encoding the amino acid sequence of the composition of any one of embodiments G1 to G71.

[0387] Embodiment G74. A vector comprising the isolated recombinant nucleic acid sequence of embodiment G73.

[0388] Embodiment G75. A kit comprising at least one of: (a) a composition according to any one of embodiments G1 to 72; (b) a vector according to embodiment G74; or (b) a nucleic acid molecule according to embodiment G73.

[0389] Embodiment G76. A method of treating a food allergy in a subject in need thereof, comprising administering to said subject a composition of any one of embodiments G1 to G72.

[0390] Embodiment G77. The method of embodiment G76, wherein said food allergy comprises a peanut allergy.

[0391] Embodiment H1. A composition comprising a first molecule comprising a first binding domain that binds Ara h 2 and Ara h 6 and a second binding domain that binds Ara h 2 and Ara h 6, wherein the first binding domain comprises an scFv, the second binding domain comprises a heavy chain variable domain, a light chain variable domain, and a constant region, wherein the scFv of the first binding domain is connected to the constant domain of the second binding domain by a linking moiety, and the composition comprises a second molecule comprising a third binding domain that binds Ara h 2.

[0392] Embodiment H2. The first binding domain comprises a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences according to HC-CDR1: SEQ ID NO: 1, HC-CDR2: SEQ ID NO: 2 or SEQ ID NO: 3, HC-CDR-3: SEQ ID NO: 4 or SEQ ID NO: 5, and the first binding domain comprises a light chain variable (VL) domain comprising the CDRs: LC-CDR1, LC-CDR2, LC-CDR3. the LC-CDR1, LC-CDR2, and LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 6, LC-CDR2: SEQ ID NO: 7, and LC-CDR-3: SEQ ID NO: 8; the second binding domain comprises a VH comprising CDRs: HC-CDR1, HC-CDR2, and HC-CDR3; the HC-CDR1, HC-CDR2, and HC-CDR3 comprise the amino acid sequences of HC-CDR1: SEQ ID NO: 18, HC-CDR2: SEQ ID NO: 19, and HC-CDR-3: SEQ ID NO: 20 or SEQ ID NO: 21; The second binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences of LC-CDR1: SEQ ID NO: 22, LC-CDR2: SEQ ID NO: 23, and LC-CDR3: SEQ ID NO: 24; the third binding domain comprises a VH comprising CDRs: HC-CDR1, HC-CDR2, HC-CDR3, wherein the HC-CDR1, HC-CDR2, HC-CDR3 comprise the amino acid sequences of H The composition of embodiment H1, wherein C-CDR1: comprises the amino acid sequence of SEQ ID NO: 35, HC-CDR2: comprises the amino acid sequence of SEQ ID NO: 36 or SEQ ID NO: 37, and HC-CDR-3: comprises the amino acid sequence of SEQ ID NO: 38, and the third binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, and LC-CDR3, and the LC-CDR1, LC-CDR2, and LC-CDR3 comprise the amino acid sequences: LC-CDR1: comprises the amino acid sequence of SEQ ID NO: 39, LC-CDR2: comprises the amino acid sequence of SEQ ID NO: 40, and LC-CDR-3: comprises the amino acid sequence of SEQ ID NO: 41.

[0393] Embodiment H3. The composition of embodiment H2, wherein the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:9 or SEQ ID NO:10.

[0394] Embodiment H4. The composition of any one of embodiments H2 or H3, wherein the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:11.

[0395] Embodiment H5. The composition of any one of embodiments H2-H4, wherein the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:9 or SEQ ID NO:10, and the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:11.

[0396] Embodiment H6. The composition of any one of embodiments H2 to H5, wherein the VH of the first binding domain and the VL of the first binding domain are connected by an scFv linker sequence.

[0397] Embodiment H7. The composition of embodiment H6, wherein the scFv linker sequence of the first binding domain comprises an amino acid sequence according to SEQ ID NO: 12.

[0398] Embodiment H8. The composition of any one of embodiments H1-H7, wherein the scFv of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:13 or SEQ ID NO:14.

[0399] Embodiment H9. The composition of any one of embodiments H2 to H8, wherein the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:25 or SEQ ID NO:26.

[0400] Embodiment H10. The composition of any one of embodiments H2-H9, wherein the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:27 or SEQ ID NO:28.

[0401] Embodiment H11. The composition of any one of embodiments H1-H10, wherein the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:25 or SEQ ID NO:26, and the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:27 or SEQ ID NO:28.

[0402] Embodiment H12. The composition of any one of embodiments H1-H11, wherein the second binding domain comprises a Fab, a Fab', or a F(ab')2.

[0403] Embodiment H13. The composition of any one of embodiments H1 to H12, wherein the second binding domain is a Fab, Fab', or F(ab')2.

[0404] Embodiment H14. The composition of any one of embodiments H1 to H13, wherein the constant domain of the second binding domain comprises a human IgG4 sequence.

[0405] Embodiment H15. The composition of embodiment H14, wherein the human IgG4 sequence of said second binding domain comprises a S228P point mutation, and wherein amino acid numbering is according to the EU index of Kabat et al.

[0406] Embodiment H16. The composition of embodiment H14 or H15, wherein the human IgG4 sequence of the second binding domain does not have a C-terminal lysine residue.

[0407] Embodiment H17. The composition of any one of embodiments H1 to H16, wherein the constant domain of the second binding domain comprises a human IgG1 sequence.

[0408] Embodiment H18. The constant domain of the second binding domain is C H 1. C H 2. C H 3, or C L The composition of any one of embodiments H1 to H17, comprising an amino acid sequence.

[0409] Embodiment H19. The second binding domain is C H 1. C H 2. C H 3, and C L The composition of any one of embodiments H1 to H18, comprising an amino acid sequence.

[0410] Embodiment H20. The composition of any one of embodiments H1-H19, wherein the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:74, or SEQ ID NO:75, and the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:34 or SEQ ID NO:76.

[0411] Embodiment H21. The composition of any one of embodiments H2 to H20, wherein the VH of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 42 or SEQ ID NO: 43.

[0412] Embodiment H22. The composition of any one of embodiments H2 to H21, wherein the VL of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:44.

[0413] Embodiment H23. The composition of any one of embodiments H2 to H22, wherein the VH of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 42 or SEQ ID NO: 43, and the VL of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 44.

[0414] Embodiment H24. The composition of any one of embodiments H1 to H23, wherein the third binding domain comprises a Fab, Fab', F(ab')2, or a single chain variable fragment (scFv).

[0415] Embodiment H25. The composition of any one of embodiments H1 to H24, wherein the third binding domain is a Fab, Fab', F(ab')2, or a single chain variable fragment (scFv).

[0416] Embodiment H26. The composition of embodiment H24 or H25, wherein the third binding domain comprises an scFv.

[0417] Embodiment H27. The composition of any one of embodiments H2 to H26, wherein the VH of the third binding domain and the VL of the third binding domain are connected by an scFv linker sequence.

[0418] Embodiment H28. The composition of embodiment H27, wherein the scFv linker sequence of the third binding domain comprises an amino acid sequence according to SEQ ID NO:45.

[0419] Embodiment H29. The composition of embodiment H26, wherein the scFv of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:46 or SEQ ID NO:47.

[0420] Embodiment H30. The composition of any one of embodiments H1 to H25, wherein the third binding domain comprises a constant domain.

[0421] Embodiment H31. The composition of embodiment H30, wherein the constant domain of the third binding domain comprises a human IgG4 sequence.

[0422] Embodiment H32. The composition of embodiment H31, wherein the human IgG4 sequence of said third binding domain comprises a S228P point mutation, and wherein amino acid numbering is according to the EU index of Kabat et al.

[0423] Embodiment H33. The composition of embodiment H31 or H32, wherein the human IgG4 sequence of the third binding domain does not have a C-terminal lysine residue.

[0424] Embodiment H34. The composition of any one of embodiments H30 to H33, wherein the constant domain of the third binding domain comprises a human IgG1 sequence.

[0425] The constant domain of the third binding domain is C H 1. C H 2. C H 3, or C L The composition of any one of embodiments H30-H34, embodiment H35, comprising an amino acid sequence.

[0426] Embodiment H36. The third binding domain is C H 1. C H 2. C H 3, and C L The composition of any one of embodiments H1 to H35, comprising an amino acid sequence.

[0427] Embodiment H37. The composition of any one of embodiments H1 to H36, wherein the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78, and the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50.

[0428] Embodiment H38. The composition of any one of embodiments H1 to H37, wherein the first binding domain and second binding domain are connected by a linking moiety.

[0429] Embodiment H39. The composition of embodiment H38, wherein the linking moiety is an amino acid sequence.

[0430] Embodiment H40. The composition of embodiment H38 or H39, wherein the linking moiety is at least 4 amino acids in length.

[0431] Embodiment H41. The composition of any one of embodiments H38 to H40, wherein the linking moiety is between 4 and 20 amino acids in length.

[0432] Embodiment H42. The linking moiety is C of the second binding domain. H The composition of any one of embodiments H38 to H41, wherein three amino acid sequences are joined to the scFv of the first binding domain.

[0433] Embodiment H43. The composition of any one of embodiments H38 to H42, wherein the linking moiety comprises the amino acid sequence of SEQ ID NO:51.

[0434] Embodiment H44. The composition of any one of embodiments H1-H43, wherein the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:53 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:52, and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78, and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50.

[0435] Embodiment H45. The composition of any one of embodiments H1-H43, wherein the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:65 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:64, the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78, and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50.

[0436] Embodiment H46. The composition of any one of embodiments H1-H43, wherein the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:67 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:66, the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78, and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:50.

[0437] Embodiment H47. The composition of any one of Embodiments H1-H46, wherein the composition comprises a pharmaceutically acceptable excipient.

[0438] Embodiment H48. An isolated, recombinant nucleic acid sequence encoding the amino acid sequence of the isolated antibody of any one of embodiments H1-H46.

[0439] Embodiment H49. A vector comprising the isolated recombinant nucleic acid sequence of embodiment H48.

[0440] Embodiment H50. A kit comprising at least one of: (a) the composition of any one of embodiments H1-H47; (b) the vector of embodiment H49; or (b) the nucleic acid molecule of embodiment H48.

[0441] Embodiment H51. A method of treating a food allergy in a subject in need thereof, comprising administering to the subject a composition of any one of embodiments H1-H47.

[0442] Embodiment H52. The method of embodiment H51, wherein said food allergy comprises a peanut allergy. [Example]

[0443] Example 1: Discovery of IgE monoclonal antibodies from peanut-allergic individuals. Blood samples were collected from numerous highly peanut-allergic individuals (peanut-specific IgE > 15 kU / A) across the United States under informed consent in an Institutional Review Board (IRB)-approved observational study. The SEQ SIFTER™ platform for single-cell sorting and transcriptomics was then applied to capture extremely rare circulating IgE-producing B cells in an unbiased manner (Croote et al. "High affinity allergen-specific human antibodies cloned from single IgE B cell transcriptomes," Science 362.6420(2018):1306-1309). A high-throughput, cloud-based bioinformatics pipeline was then used to reconstruct full-length, paired heavy and light chain sequences, including monoclonal IgE antibodies, thus providing insight into the IgE repertoire of allergic individuals.

[0444] IgE variable region sequences from peanut-allergic individuals were recombinantly expressed with the constant region of IgG4, rather than IgE. Monoclonal antibodies (mAbs) were generated with the specificity of the original IgE antibody, which now blocks rather than initiates the allergic cascade. Because this discovery process is unbiased regarding the specificity of IgE antibodies produced by circulating B cells, the distribution of Ara h allergen specificities naturally reflects the repertoire of circulating IgE-producing B cells. The majority of peanut-specific antibodies were found to be specific for Ara h 2 and / or the homologous allergen Ara h 6 (Figure 1). Notably, several mAbs against Ara h 1 were discovered, but these were primarily derived from a single individual and had lower affinity than mAbs specific for Ara h 2 and Ara h 6; only 13% were Ara h 1-specific mAbs, in the subnanomolar range. For this reason, we focused on Ara h 2. Figure 1 shows the specificity distribution of 158 mAbs discovered in 27 peanut-allergic individuals in an unbiased manner. "Other" includes mAbs specific for Ara h 3, Ara h 8, and Ara h 9, as well as mAbs with no detectable binding to Ara h 1, Ara h 2, Ara h 3, Ara h 6, Ara h 8, or Ara h 9 on ImmunoCAP.

[0445] Example 2. Monoclonal antibody affinity determination and epitope binning. We used the Carterra LSA, a surface plasmon resonance (SPR)-based instrument, for both antibody affinity measurements and epitope binning, a pairwise competition assay that groups antibodies by the epitopes to which they bind. The goal was to understand the number of epitopes (linear and / or conformational) on an antigen recognized by monoclonal IgE antibodies (expressed as IgG4) and the distribution of monoclonal antibody epitope specificity (i.e., is there a bias toward immunodominant epitopes?). Grouping antibodies by epitope bins, combined with affinity data, then allows for the informed selection of monoclonal antibodies for further evaluation in functional assays such as blocking ELISA, basophil activation test (BAT), or mast cell activation test (MAT).

[0446] To measure kinetic parameters, antibodies were first bound to an HC30M sensor chip, which was then activated. Antibodies were bound to the activated surface at multiple concentrations, after which the remaining reactive groups were deactivated. Native Ara h 2 or Ara h 6 (InBio) was injected sequentially over the antibody-bound chip at multiple concentrations using a Carterra LSA single flow cell, without regeneration between injections. Association and dissociation curves were fitted using a 1:1 Langmuir binding model in Kinetics software (Carterra) to obtain kd, ka, and KD.

[0447] For epitope binning, surfaces were functionalized with antibodies as described above. Each binding cycle consisted of native Ara h 2 or Ara h 6, followed by antibody, then regeneration, injected using a Carterra LSA single flow cell. Epitope binning analysis was performed using Epitope software (Carterra). Antibody binding was normalized to the signal from the antigen injection followed by a buffer-only injection. Antibody pairs were classified as blocking or sandwich according to whether they met a binding signal threshold above the buffer injection background.

[0448] Using SPR, we found that over 90% of the 64 Ara h 2-specific mAbs had high affinity in the subnanomolar range. Furthermore, we found that 90% of these mAbs belonged to epitope bins 1, 2, or 3 (Figure 2). This led to the selection and engineering of mAbs belonging to these three epitope bins for in vitro characterization. Figure 2 illustrates the distribution of the 64 mAbs by Ara h 2 epitope bin and highlights the three immunodominant epitope bins.

[0449] Example 3. In vitro characterization by ELISA An in vitro ELISA was used to characterize the binding and blocking capabilities of IgG mAbs. An in vitro blocking ELISA was used to assess the ability of one or more IgG monoclonal antibodies to block the binding of allergic plasma IgE to recombinant Ara h 2. In this assay, a simplified version of which is shown in Figure 3A, a human FcεRIα-IgG Fc fusion protein captures human IgE from peanut-allergic plasma. Following capture, a preincubated mixture of His-tagged recombinant Ara h 2 and a titrated panel of antibodies is added. Recombinant Ara h 2 binding to plasma IgE was measured using an anti-His HRP-conjugated detection antibody and TMB. Inhibition was calculated relative to no-antibody control wells.

[0450] Independently, molecules 2d, 2e, and 2f inhibited the binding of allergic plasma IgE to recombinant Ara h 2 to varying degrees (Figure 3B), but the combination of molecules 2d and 2e was found to have stronger and more consistent inhibition, achieving an average inhibition of 91% across nine peanut-allergic plasmas. Molecules 2d, 2e, and 2f are high-affinity IgG4 antibodies with the S228P hinge-stabilizing mutation, belonging to epitope bins 1, 2, and 3, respectively.

[0451] [Table 5]

[0452] Subsequently, several human IgG4-scFv antibodies derived from molecules 2d, 2e, and 2f were engineered based on the combination of binding domains, optionally further modified to eliminate chemistry, manufacturing, and control (CMC) liabilities, and named with the prefix "molecule 1." These engineered molecules are bispecific, or more specifically, have bi-epitopic specificity. These bi-epitopic antibodies bind to one Ara h 2 epitope, either "bin1," "bin2," or "bin3," via the Fab domain and to a different epitope selected from the same set via the scFv domain. The bin1 and bin2 epitopes are conserved in the homologous peanut protein, Ara h 6, whereas the "bin3" epitope is unique to Ara h 2.

[0453] [Table 6]

[0454] The ability of four molecule 1 mAbs to bind to recombinant Ara h 2 was evaluated. All showed concentration-dependent binding, similar to each other and to molecule 2d, molecule 2e, and their combination (Figure 3C). Next, the ability of these molecules to inhibit the binding of recombinant Ara h 2 to polyclonal peanut-allergic plasma IgE was evaluated. All four molecule 1 mAbs showed greater inhibition than either molecule 2d or molecule 2e alone, and with lower IC50s than the combination of molecule 2d and molecule 2e (Figure 3D).

[0455] Figure 3A shows a simplified ELISA to assess the ability of IgG mAbs to block the binding of allergic plasma IgE to tagged allergens. Figure 3B shows the inhibition of recombinant Ara h 2 binding to peanut-allergic plasma IgE by one or more molecule 2 mAbs in a blocking ELISA. Isotype control = F080-F1, an IgG4 mAb specific for a non-peanut allergen. Data are from individual peanut-allergic plasma samples (n = 9), and bars represent the mean ± SD. Figure 3C shows the binding of molecule 1 and molecule 2 mAbs to recombinant Ara h 2. Figure 3D illustrates the inhibition of peanut-allergic plasma IgE binding to recombinant Ara h 2 by molecule 1 mAb compared with molecule 2 mAb alone or in combination for one peanut-allergic plasma sample. Isotype control = F080-F1, an IgG4 mAb specific for a non-peanut allergen.

[0456] Example 4. In vitro characterization by Mast Cell Activation Assay (MAT). An outline of the MAT experimental design is shown in Figure 4A. Murine Hoxb8 mast cells expressing human FcεRIα were first sensitized with patient plasma, allowing them to capture polyclonal IgE via the high-affinity FcεRI. The cells were then washed and incubated with IgG4 antibody for 30 minutes. Then, without washing, a predetermined optimal concentration of Ara h 2 or peanut protein was added. This optimal concentration of Ara h 2 or peanut protein required for slightly greater than half-maximal activation was previously determined separately for each plasma. Activation was assessed by CD107a expression using flow cytometry, and percent inhibition was calculated relative to the activation of no-antibody control wells.

[0457] MAbs bearing both human IgG1 and human IgG4S228P constant regions were evaluated in the MAT using seven peanut-allergic plasma samples. The constant region was found to have little effect when comparing otherwise identical molecule 2 mAbs, such as molecule 2g with molecule 2d, molecule 2h with molecule 2e, and molecule 2i with molecule 2f (Figure 4B). Compared with individual molecule 2 mAbs, combinations of two or three mAbs had improved levels of inhibition, with maximal inhibition of peanut-mediated mast cell activation achieved by the combination of molecule 2f (IgG4S228P) and dual-epitope molecule 1g (IgG4S228P).

[0458] Figure 4A shows an overview of the mast cell activation test (MAT). Figure 4B shows the percent inhibition of peanut- and Ara h 2-mediated mast cell activation by human IgG1 and human IgG4 S228P mAbs. The total antibody concentration was 10 μg / mL for all test articles. Isotype control (IgG1 and IgG4 S228P) = G010-F5, a mAb specific for a non-peanut allergen. Mean ± SEM of n = 7 peanut-allergic plasma samples is shown.

[0459] Example 5. In vitro characterization of combination therapy. Based on the experiments in the previous examples, a combination therapy was developed (Combination 1). Combination 1 consists of a 1:1 mass ratio mixture of molecule 1a and molecule 2c, as shown in Figure 5A. Molecule 1a is an IgG4 antibody with a stabilized hinge region (S228P) in which an scFv domain is fused to the c-terminus of each heavy chain. Binder 1 of molecule 1 binds to epitope bin 1 on Ara h 2 and Ara h 6. Binder 2 of molecule 1 binds to epitope bin 2 on Ara h 2 and Ara h 6. Binding is bivalent for both epitopes. Molecule 2 is an IgG4 S228P antibody lacking the c-terminal lysine of the heavy chain constant region. Binder 3 binds to epitope bin 3, which is present only on Ara h 2. Binding is bivalent for this epitope.

[0460] Monoclonal antibodies were produced by transient transfection of mammalian cells. Heavy and light chain variable region genes from each mAb were synthesized after codon optimization, cloned into pcDNA3.4 vectors containing the appropriate constant region (IgG1 or IgG4 S228P, and either λ or kappa, as appropriate), and transiently cotransfected into Chinese hamster ovary (CHO) cells. After approximately 7 days of culture, antibodies were purified from the supernatant by one-step Protein A purification. After washing and elution, the eluted fractions were pooled and buffer-exchanged into the appropriate formulation buffer. Antibodies were characterized by, at a minimum, SDS-PAGE under reducing and non-reducing conditions.

[0461] For larger-scale monoclonal antibody production, stable cell lines were generated using appropriate retroviral systems. Characterized CHO cell lines were transfected with cDNAs corresponding to the heavy and light chains, and stable cell lines were selected after single-cell subcloning and characterization of clones in shake flasks and small-scale bioreactors. To produce each mAb, CHO cells were grown in bioreactors, and the mAb secreted into the culture medium was harvested using conventional IgG purification techniques.

[0462] Multiple experiments were performed to evaluate the potency and activity of Combination 1. Using the blocking ELISA format described in Example 3, Combination 1 completely inhibited recombinant Ara h2 binding to IgE across five peanut-allergic plasma samples, whereas no inhibition was observed with the isotype control (Figure 5B). Combination 1 was then evaluated against the components of molecules 1a and 2c using the MAT described in Example 4. Compared to the isotype control, Combination 1 significantly inhibited peanut-mediated mast cell activation in 19 peanut-allergic plasma samples (Figure 5C). Combination 1 achieved a mean inhibition of 82.6%, with a maximum inhibition of 97.5%, compared to a mean inhibition of 5.8% for the isotype control (IgG4 trastuzumab). The mean inhibition was 61.4% for molecule 1a alone and 48.7% for molecule 2c alone, both significantly lower than Combination 1. The coefficients of variation were also larger for molecules 1a and 2c alone compared to Combination 1.

[0463] Figure 5A shows Combination 1, which contains two molecules. Figure 5B shows blocking of rAra h 2 binding to peanut-allergic plasma IgE by Combination 1. Isotype control = F080-F1, an IgG4 mAb specific for a non-peanut allergen. Mean ± SEM of n = 5 plasmas is shown. Figure 5C shows inhibition of peanut-mediated mast cell activation by Combination 1 and its components for n = 19 peanut-allergic plasmas. Total antibody concentration is 10 μg / mL for all test articles. Isotype control = IgG4 trastuzumab. Mean ± SEM is shown. ****P<0.001 by one-way ANOVA followed by Bonferroni's multiple comparison test.

[0464] Example 6. In vivo characterization of combination treatments in a mouse model of peanut allergy. Combination 1 was evaluated in a mouse model of peanut allergy based on a protocol adapted from Landers et al. [Immunotherapy. 2022 May;14(7):539-552. doi:10.2217 / imt-2021-0206. Epub 2022 Feb 24]. Briefly, naive C3H / HeJ female mice were sensitized at weeks 0–5 with 2 mg of peanut protein plus 10 μg of cholera toxin (CTx) delivered via oral gavage. The peanut challenge protocol began on day 49. The administration protocol consisted of seven doses of 25 mg of peanut protein administered by oral gavage every other day for 2 weeks. On day 61, 48 hours before the seventh peanut protein challenge, mice were treated with either the test substance or vehicle buffer by subcutaneous injection (Figure 6A). Responses to the seventh peanut protein challenge, administered 48 hours after the test substance challenge, were recorded. Mice were monitored for core body temperature; observers were blinded to treatment. Sixty minutes after the final peanut protein challenge, mice were euthanized, and blood was collected by cardiac puncture. Serum was collected and analyzed for levels of human IgG and mast cell protease 1 (MCPT-1), an indicator of mast cell degranulation.

[0465] Unless otherwise stated, all data were analyzed using one-way ANOVA followed by Dunnett's multiple comparison test to compare each treatment group with the vehicle buffer treatment group. Statistical significance is noted as * P<0.05, ** P<0.01, and *** P<0.001, and values ​​are reported as mean ± SEM.

[0466] In this study, animals were administered either the test article (Combination 1, Molecule 1a, or Molecule 2c at doses of 0.625, 1.25, 2.5, or 5.0 mg / kg), isotype control (IgG4 trastuzumab at 5.0 mg / kg), or vehicle buffer 48 hours prior to the seventh dose. The seventh peanut protein dose resulted in a severe anaphylactic reaction, as measured by a 3.9 ± 0.5°C decrease in rectal temperature in animals treated with vehicle buffer (Figure 6A). This hypothermic response to peanut challenge was dose-dependently reversed in animals treated with Combination 1, and the reduced response in the Combination 1, 2.5, and 5.0 mg / kg groups was statistically significant compared to that measured in the group treated with vehicle buffer. In animals pretreated with molecule 1a alone, there was a dose-dependent decrease in the hypothermic response to peanut protein challenge; however, the response at all dose levels was not statistically different from that seen in the vehicle buffer-treated group. Direct comparison (unpaired Student's t-test) between the highest dose of combination 1 and molecule 1a showed a significant difference between the two treatments. Molecule 2c alone did not significantly decrease the hypothermic response to peanut protein challenge at any of the doses tested. An isotype control antibody (IgG4 trastuzumab) had no effect on the hypothermic response.

[0467] At the end of the 60-minute post-dose observation period, the animals were euthanized and a terminal blood sample was collected. A fraction of this sample was assayed for MCPT-1 as a direct measure of mast cell degranulation. Combination 1 dose-dependently reduced MCPT-1 compared to animals treated with vehicle buffer, achieving levels at 5 mg / kg equivalent to those seen in non-sensitized animals. Molecule 1a alone resulted in a significant reduction in MCPT-1 serum levels, which was significantly lower than those associated with Combination 1 at an equivalent dose (5.0 mg / kg). Neither the isotype control antibody (IgG4 trastuzumab) nor molecule 2c significantly reduced MCPT-1 levels.

[0468] Figure 6A shows the protocol for the peanut allergy oral sensitization / oral peanut challenge mouse model. On day 61, 48 hours before the seventh peanut protein challenge, mice were treated with either the test article or excipient buffer (vehicle) by subcutaneous (sc) injection. Six minutes after the final peanut protein challenge on day 63, mice were euthanized, and blood was collected by cardiac puncture. Serum was collected and analyzed for human IgG and MCPT-1 levels. Figure 6B shows the dose-dependent effects of Combination 1 and its components on the hypothermic response in peanut-allergic animals administered 25 mg of peanut protein delivered by oral gavage. Isotype control = IgG4 trastuzumab. All data were compared to the effects of excipient buffer. The effects of Combination 1 and Molecule 1a (5.0 mg / kg) were compared using an unpaired Student's t-test (#P<0.05). Figure 6C shows the dose-dependent effects of Combination 1, Molecule 1a, and Molecule 2c on serum MCPT-1, as a direct measure of mast cell degranulation in peanut-allergic animals, when administered 25 mg of peanut protein delivered by oral gavage. Isotype control = IgG4 trastuzumab. All data are compared to the effect of vehicle buffer. The effects of Combination 1 and Molecule 1a (5.0 mg / kg) were compared using an unpaired Student's t-test (###). Note that serum levels of MCPT-1 in animals treated with Combination 1 at 5 mg / kg were comparable to those in non-sensitized animals.

Claims

1. A composition comprising a first binding domain that binds to Ara h 2 and Ara h 6, wherein the first binding domain comprises a heavy chain variable domain (VH) comprising complementarity determining regions (CDRs): HC-CDR1, HC-CDR2, and HC-CDR3, wherein HC-CDR1: SEQ ID NO: 1, HC-CDR2: SEQ ID NO: 2 or SEQ ID NO: 3, and HC-CDR-3: SEQ ID NO:

4. and wherein the first binding domain comprises an amino acid sequence according to SEQ ID NO: 4 or SEQ ID NO: 5, wherein the first binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, wherein the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences according to SEQ ID NO: 6 for LC-CDR1, SEQ ID NO: 7 for LC-CDR2, and SEQ ID NO: 8 for LC-CDR3, and wherein the composition comprises Ara h 2 and Ara h 3. 6, and a VH comprising the CDRs: HC-CDR1, HC-CDR2, and HC-CDR3. The second binding domain comprises a VH comprising CDRs: HC-CDR1, HC-CDR2, and HC-CDR3. The second binding domain comprises a VH comprising CDRs: HC-CDR1, HC-CDR2, and HC-CDR3, and the HC-CDR1, HC-CDR2, and HC-CDR3 are as follows: HC-CDR1: SEQ ID NO: 18, HC-CDR2: and wherein the second binding domain comprises an amino acid sequence according to SEQ ID NO: 19, HC-CDR-3: SEQ ID NO: 20 or SEQ ID NO: 21, and the second binding domain comprises a light chain variable (VL) domain comprising CDRs: LC-CDR1, LC-CDR2, LC-CDR3, and the LC-CDR1, LC-CDR2, LC-CDR3 comprise the amino acid sequences according to SEQ ID NO: 22, LC-CDR2: SEQ ID NO: 23, LC-CDR-3: SEQ ID NO: 24, and the composition comprises Ara h 2 and Ara h 3.6, wherein the third binding domain comprises a VH comprising CDRs HC-CDR1, HC-CDR2, and HC-CDR3, wherein the HC-CDR1, HC-CDR2, and HC-CDR3 comprise the amino acid sequences according to SEQ ID NO: 35 for HC-CDR1, SEQ ID NO: 36 or SEQ ID NO: 37 for HC-CDR-3, and SEQ ID NO: 38 for HC-CDR-3; and the third binding domain comprises a light chain variable (VL) domain comprising CDRs LC-CDR1, LC-CDR2, and LC-CDR3, wherein the LC-CDR1, LC-CDR2, and LC-CDR3 comprise the amino acid sequences according to SEQ ID NO: 39 for LC-CDR1, SEQ ID NO: 40 for LC-CDR-3, and SEQ ID NO: 41 for LC-CDR-3.

2. 2. The composition of claim 1, wherein the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:9 or SEQ ID NO:

10.

3. 2. The composition of claim 1, wherein the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:

11.

4. 2. The composition of claim 1, wherein the VH of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:9 or SEQ ID NO:10, and the VL of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:

11.

5. The first binding domain is Fab, Fab', F(ab') ２ 10. The composition of claim 1, comprising a single chain variable fragment (scFv).

6. The first binding domain is Fab, Fab', F(ab') ２ 10. The composition of claim 1, wherein the antibody is a single-chain variable fragment (scFv).

7. The composition of claim 5 , wherein the first binding domain comprises the scFv.

8. 2. The composition of claim 1, wherein the VH of the first binding domain and the VL of the first binding domain are connected by an scFv linker sequence.

9. 9. The composition of claim 8, wherein the scFv linker sequence of the first binding domain comprises an amino acid sequence according to SEQ ID NO:

12.

10. 8. The composition of claim 7, wherein the scFv of the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 13 or SEQ ID NO:

14.

11. The composition of claim 1 , wherein the first binding domain comprises a constant domain.

12. The composition of claim 11 , wherein the constant domain of the first binding domain comprises a human IgG4 sequence.

13. 13. The composition of claim 12, wherein the human IgG4 sequence of the first binding domain comprises a S228P point mutation, and the amino acid numbering is according to the EU index of Kabat et al.

14. The composition of claim 12, wherein the human IgG4 sequence of the first binding domain does not have a C-terminal lysine residue.

15. The composition of claim 11 , wherein the constant domain of the first binding domain comprises a human IgG1 sequence.

16. The constant domain of the first binding domain is C Ｈ 1. C Ｈ 2. C Ｈ 3 or C Ｌ The composition of claim 11 comprising an amino acid sequence.

17. The first binding domain is C Ｈ 1. C Ｈ 2. C Ｈ 3, and C Ｌ The composition of claim 11 comprising an amino acid sequence.

18. 2. The composition of claim 1, wherein the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 72, or SEQ ID NO: 73, and the first binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:

17.

19. 2. The composition of claim 1, wherein the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:25 or SEQ ID NO:

26.

20. 2. The composition of claim 1, wherein the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:27 or SEQ ID NO:

28.

21. 2. The composition of claim 1, wherein the VH of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:25 or SEQ ID NO:26, and the VL of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:27 or SEQ ID NO:

28.

22. The second binding domain is Fab, Fab', F(ab') ２ 10. The composition of claim 1, comprising a single chain variable fragment (scFv).

23. The second binding domain is Fab, Fab', F(ab') ２ 10. The composition of claim 1, wherein the antibody is a single-chain variable fragment (scFv).

24. 23. The composition of claim 22, wherein the second binding domain comprises the scFv.

25. 25. The composition of claim 24, wherein the VH of the second binding domain and the VL of the second binding domain are connected by an scFv linker sequence.

26. 26. The composition of claim 25, wherein the scFv linker sequence of the second binding domain comprises an amino acid sequence according to SEQ ID NO:

29.

27. 23. The composition of claim 22, wherein the scFv of the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 30 or SEQ ID NO:

31.

28. The composition of claim 1 , wherein the second binding domain comprises a constant domain.

29. 29. The composition of claim 28, wherein the constant domain of the second binding domain comprises a human IgG4 sequence.

30. 30. The composition of claim 29, wherein the human IgG4 sequence of the second binding domain comprises a S228P point mutation, and the amino acid numbering is according to the EU index of Kabat et al.

31. 30. The composition of claim 29, wherein the human IgG4 sequence of the second binding domain does not have a C-terminal lysine residue.

32. 29. The composition of claim 28, wherein the constant domain of the second binding domain comprises a human IgG1 sequence.

33. The constant domain of the second binding domain is C Ｈ 1. C Ｈ 2. C Ｈ 3 or C Ｌ 29. The composition of claim 28, comprising an amino acid sequence.

34. The second binding domain is C Ｈ 1. C Ｈ 2. C Ｈ 3, and C Ｌ 29. The composition of claim 28, comprising an amino acid sequence.

35. 2. The composition of claim 1, wherein the second binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:74, or SEQ ID NO:75, and the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:34 or SEQ ID NO:

76.

36. 2. The composition of claim 1, wherein the VH of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 42 or SEQ ID NO:

43.

37. 2. The composition of claim 1, wherein the VL of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:

44.

38. 2. The composition of claim 1, wherein the VH of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 42 or SEQ ID NO: 43, and the VL of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:

44.

39. The third binding domain is Fab, Fab', F(ab') ２ 10. The composition of claim 1, comprising a single chain variable fragment (scFv).

40. The third binding domain is Fab, Fab', F(ab') ２ 10. The composition of claim 1, wherein the antibody is a single-chain variable fragment (scFv).

41. 40. The composition of claim 39, wherein the third binding domain comprises the scFv.

42. 40. The composition of claim 39, wherein the VH of the third binding domain and the VL of the third binding domain are connected by an scFv linker sequence.

43. 43. The composition of claim 42, wherein the scFv linker sequence of the third binding domain comprises an amino acid sequence according to SEQ ID NO:

45.

44. 40. The composition of claim 39, wherein the scFv of the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 46 or SEQ ID NO:

47.

45. The composition of claim 1 , wherein the third binding domain comprises a constant domain.

46. 46. ​​The composition of claim 45, wherein the constant domain of the third binding domain comprises a human IgG4 sequence.

47. 47. The composition of claim 46, wherein the human IgG4 sequence of the third binding domain comprises a S228P point mutation, and the amino acid numbering is according to the EU index of Kabat et al.

48. 47. The composition of claim 46, wherein the human IgG4 sequence of the third binding domain does not have a C-terminal lysine residue.

49. 46. ​​The composition of claim 45, wherein the constant domain of the third binding domain comprises the human IgG1 sequence.

50. The constant domain of the third binding domain is C Ｈ 1. C Ｈ 2. C Ｈ 3 or C Ｌ 46. ​​The composition of claim 45, comprising an amino acid sequence.

51. The third binding domain is C Ｈ 1. C Ｈ 2. C Ｈ 3, and C Ｌ 46. ​​The composition of claim 45, comprising an amino acid sequence.

52. 2. The composition of claim 1, wherein the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78, and the isolated antibody comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:

50.

53. The composition of claim 1 , wherein the first binding domain, the second binding domain, and the third binding domain are connected within the same molecule.

54. The composition of claim 1 , wherein the first binding domain, the second binding domain, and the third binding domain are separate molecules.

55. 2. The composition of claim 1, wherein the first binding domain and the second binding domain are in the same molecule, and the third binding domain is a separate molecule from the molecule having the first binding domain and the second binding domain.

56. 2. The composition of claim 1, wherein the first binding domain and the third binding domain are in the same molecule, and the second binding domain is a separate molecule from the molecule having the first binding domain and the third binding domain.

57. 2. The composition of claim 1, wherein the second binding domain and the third binding domain are in the same molecule and the first binding domain is a separate molecule from the molecule having the second binding domain and the third binding domain.

58. The first binding domain comprises the scFv and the second binding domain comprises C Ｈ 1. C Ｈ 2. C Ｈ 3, and C Ｌ The composition of claim 1 comprising an amino acid sequence.

59. The second binding domain comprises an scFv and the first binding domain comprises a C Ｈ 1. C Ｈ 2. C Ｈ 3, and C Ｌ The composition of claim 1 comprising an amino acid sequence.

60. The composition of claim 1 , wherein the first binding domain and the second binding domain are connected by a linking moiety.

61. The composition of claim 1 , wherein the linking moiety is an amino acid sequence.

62. The composition of claim 1 , wherein the linking moiety is at least four amino acids in length.

63. 2. The composition of claim 1, wherein the linking moiety is between 4 and 20 amino acids in length.

64. The linking moiety is C of the second binding domain Ｈ The composition of claim 1 , wherein a three amino acid sequence is connected to the scFv of the first binding domain.

65. The composition of claim 1 , wherein the linking portion comprises the amino acid sequence of SEQ ID NO:

51.

66. 2. The composition of claim 1, wherein the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:53 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:52; the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78; and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:

50.

67. 2. The composition of claim 1, wherein the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:55 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:54; the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78; and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:

50.

68. 2. The composition of claim 1, wherein the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:65 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:64; the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78; and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:

50.

69. 2. The composition of claim 1, wherein the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:67 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:66; the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78; and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:

50.

70. 2. The composition of claim 1, wherein the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:69 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:68; the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:77, or SEQ ID NO:78; and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:

50.

71. 2. The composition of claim 1, wherein the first binding domain and the second binding domain comprise an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 71 and an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 70; the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 77, or SEQ ID NO: 78; and the third binding domain comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO:

50.

72. The composition of claim 1 , wherein the composition comprises a pharmaceutically acceptable excipient.

73. 73. An isolated recombinant nucleic acid sequence encoding the amino acid sequence of the composition of any one of claims 1 to 72.

74. 74. A vector comprising the isolated recombinant nucleic acid sequence of claim 73.

75. a. the composition of any one of claims 1 to 72; b. The vector of claim 74, or c. The nucleic acid molecule of claim 73 A kit comprising at least one of the following:

76. 73. A method of treating a food allergy in a subject in need thereof, comprising administering to said subject a composition of any one of claims 1 to 72.

77. 77. The method of claim 76, wherein the food allergy comprises a peanut allergy.

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