Anti-allergen antibodies and uses thereof

Abstract

The present invention provides antibodies that bind to peanut allergens, in particular antibodies that bind to Ara h 2 and Ara h 3 or Ara h 6. The present invention also provides compositions and kits comprising different antibodies that bind to different non-overlapping epitopes of Ara h 2 and multispecific antibodies that bind to different non-overlapping epitopes of Ara h 2. In addition, the invention also relates to application of the antibodies, the compositions and the kits, for example, the application for preventing or treating peanut allergy.

Description

[0001] The present invention relates to antibodies that bind to peanut allergens, particularly antibodies that bind to Ara h 2 and Ara h 3 or Ara h 6. The present invention also relates to compositions and kits comprising different antibodies that bind to different, non-overlapping epitopes of Ara h 2 and multispecific antibodies that bind to different, non-overlapping epitopes of Ara h 2. Furthermore, the present invention relates to uses of these antibodies, compositions, and kits, for example, for preventing or treating peanut allergies.

[0002] Allergies are diseases caused by a hypersensitivity of the immune system. Encountering an allergen leads to the production of immunoglobulin E (IgE) antibodies that bind to the allergen. These antibodies are pre-bound to FcεRI receptors on mast cells and basophils, where they trigger the release of inflammatory compounds such as histamine, leukotrienes, and lipid mediators.

[0003] Peanut allergy is one of the most severe food allergies due to its prevalence, persistence, and potential severity of the allergic reaction. Allergic reactions can range from skin, respiratory, and gastrointestinal symptoms to severe and life-threatening reactions such as anaphylaxis. Peanut allergy is the most common cause of food-induced allergic reactions.

[0004] To date, at least 16 peanut proteins have been identified as allergens. Among these peanut allergens, Ara h 1, Ara h 2, Ara h 3, and Ara h 6 are considered major allergens, meaning they trigger an immune response in more than 50% of allergic people. In particular, Ara h 2 is reported to be the major peanut allergen (Hemmings, Oliver et al. Arah 2 is the dominant peanut allergen despite similarities with Ara h 6. The Journal of allergy and clinical immunology Vol. 146(3) (2020): 621-630.e5, doi:10.1016 / j.jaci.2020.03.026). In addition, Ara h 6 is a common and potent peanut allergen (Blanc, F et al. (2009), Capacity of purified peanut allergens to induce degranulation in a functional in vitro assay: Ara h 2 and Ara h 6 are the most efficient elicitors. Clinical & Experimental Allergy, 39: 1277-1285.). Furthermore, Ara h 3 accounts for 19% of the total protein in peanut extract and is classified as a major peanut allergen because it can cause sensitization in patients with this allergy.

[0005] Despite the prevalence of peanut allergies, to date, there is no cure for peanut allergy other than strict avoidance of peanuts and peanut-containing foods. However, complete avoidance can be complicated, especially if ingredient declarations are unavailable. While allergen immunotherapy, also known as desensitization, attempts to reduce allergic sensitivity through repeated exposure to the allergen, it has recently been shown to increase rather than decrease the risk of severe allergies (Chu DK, Wood RA, French S, et al. (April 2019). "Oral immunotherapy for peanut allergy (PACE): a systematic review and meta-analysis of efficacy and safety". The Lancet. 393 (10187): 2222-2232).

[0006] Recently, antibodies against peanut allergens have emerged as a promising option for treating peanut allergies. For example, WO 2018 / 234383 describes various human monoclonal antibodies against peanut allergens.

[0007] In view of the foregoing, it is an object of the present invention to provide improved human antibodies against peanut allergens. Another object of the present invention is to provide a composition comprising at least three different potent antibodies that bind to different, non-overlapping epitopes on the major peanut allergen, Ara h 2. Furthermore, another object of the present invention is to provide potent multispecific antibodies that bind to different, non-overlapping epitopes on the major peanut allergen, Ara h 2.

[0008] This object is achieved by the subject matter set out below and in the appended claims.

[0009] Although the present invention is described in detail below, it should be understood that the present invention is not limited to the specific methods, protocols and reagents described herein, as they may vary. It should also be understood that the terms used herein are not intended to limit the scope of the present invention, which is limited only by the appended claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those of ordinary skill in the art.

[0010] Hereinafter, elements of the present invention will be described. These elements are listed together with specific embodiments, however, it should be understood that they can be combined in any manner and in any quantity to create additional embodiments. The various described embodiments and selected embodiments should not be interpreted as limiting the present invention to only the embodiments clearly described. This description should be understood to support and encompass embodiments that combine the embodiments clearly described with any number of disclosed elements. In addition, unless the context otherwise indicates, any arrangement and combination of elements described in this application should be considered to be disclosed in the description of this application.

[0011] Throughout the specification and the claims that follow, unless the context requires otherwise, the term "comprise" and variations such as "comprising" and "including" will be understood to imply the inclusion of stated members, integers, or steps, but not the exclusion of any other unstated members, integers, or steps. The term "consisting of is a specific embodiment of the term "comprising" in which any other unstated members, integers, or steps are excluded. In the context of the present invention, the term "comprising" encompasses the term "consisting of." Thus, the term "comprising" encompasses "including" as well as "consisting of. For example, a composition "comprising" X may consist solely of X, or may include other contents, such as X+Y.

[0012] In the context of describing the present invention (particularly in the context of the claims), the use of terms without quantifiers and similar references should be interpreted as covering single and multiple, unless otherwise stated herein or clearly contradicted by the context. Reference to numerical ranges herein is intended only to be used as a shorthand method of individually referring to each individual value falling within the range. Unless otherwise stated herein, each individual value is incorporated into this specification as if it were individually quoted herein. No language in the specification should be construed as indicating any unclaimed element essential to the practice of the present invention.

[0013] The word "substantially" does not exclude "completely", for example a composition "substantially free" of Y may be completely free of Y. If necessary, the word "substantially" may be omitted from the definition of the present invention.

[0014] The term "about" with respect to a value x refers to x±10%, for example, x±5%, or x±7%, or x±10%, or x±12%, or x±15%, or x±20%.

[0015] As used herein, the term "disease" is intended to be generally synonymous with the terms "disorder" and "symptom" (as in medical condition) and to be used interchangeably, as all of these reflect an abnormal condition of the human or animal body or a part thereof that impairs the normal functioning and is generally manifested by distinct signs and symptoms and results in a human or animal having a shortened lifespan or sometimes a reduced quality of life.

[0016] As used herein, "treatment" of a subject or patient is intended to include prevention, prophylaxis, attenuation, amelioration, and treatment. The terms "subject" or "patient" are used interchangeably herein to refer to all mammals, including humans. Examples of subjects include humans, cows, dogs, cats, horses, goats, sheep, pigs, and rabbits. In some embodiments, the subject or patient is a human.

[0017] Doses are usually expressed in relation to body weight. Thus, a dose expressed in [g, mg, or other units] / kg (or g, mg, etc.) usually means [g, mg, or other units] "per kg (or g, mg, etc.) of body weight" even if the term "body weight" is not explicitly mentioned.

[0018] The term "binding" and similar designations generally refer to "specific binding" and do not include non-specific adhesion. Specifically, specific binding of an antibody means that the antibody recognizes its target antigen and binds to its target with a higher affinity (or at a lower antibody concentration, e.g., EC50) than it binds to a structurally different antigen and / or an antigen with a modified or mutated sequence. Thus, "higher" affinity can be at least 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 15-fold, 20-fold, 25-fold, 50-fold, 75-fold, 100-fold, 150-fold, 200-fold, 500-fold, 750-fold, 1000-fold, 1500-fold, 2000-fold, 5000-fold, 7500-fold, 10,000-fold, or even greater than 10,000-fold affinity compared to binding to a control antigen. In some cases, antibody binding to a control antigen may be undetectable (below the detection threshold), while antibody binding to a specific antigen can be well detected / determined.

[0019] As used herein, the term "antibody" encompasses various forms of antibodies, including but not limited to complete antibodies, antibody fragments (e.g., antigen binding fragments), human antibodies, chimeric antibodies, humanized antibodies, recombinant antibodies, and genetically engineered antibodies (e.g., variants or mutant antibodies), as long as the characteristic properties of the present invention are retained. In some embodiments, the antibody is a human antibody. In some embodiments, the antibody is a monoclonal antibody. For example, the antibody can be a human monoclonal antibody.

[0020] As mentioned above, the term "antibody" generally also includes antibody fragments. Fragments of antibodies can retain the antigen-binding activity of antibodies. Such fragments are referred to as "antigen-binding fragments." Antigen-binding fragments include, but are not limited to, single-chain antibodies, Fab, Fab', F(ab')2, Fv, or scFv. Antibody fragments can be obtained from antibodies by methods including digestion with enzymes such as pepsin or papain and / or by chemical reduction to cleave disulfide bonds. Alternatively, antibody fragments can be obtained by recombinant means, such as by cloning and expressing a portion (fragment) of the heavy and / or light chain sequences. The present invention also includes single-chain Fv fragments (scFv) derived from the heavy and light chains of the antibodies of the present invention. For example, the present invention includes scFv comprising the CDRs from the antibodies of the present invention. Also included are monomers and dimers of heavy or light chains, single-domain heavy chain antibodies, single-domain light chain antibodies, and single-chain antibodies, such as single-chain Fv, in which the variable domains of the heavy and light chains are connected by a peptide linker. The antibody fragments of the present invention can be included in a variety of structures known to those skilled in the art. In addition, the sequences of the invention may be components of multispecific molecules, wherein the sequences of the invention target the epitopes of the invention, and other regions of the molecule bind other targets. Although the specification, including the claims, may explicitly refer to one or more antigen-binding fragments, one or more antibody fragments, one or more variants and / or one or more derivatives of an antibody in some places, it is to be understood that the term "antibody" includes all classes of antibodies, i.e., one or more antigen-binding fragments, one or more antibody fragments, one or more variants and one or more derivatives of an antibody.

[0021] Human antibodies are well known in the art (van Dijk, MA, and van de Winkel, JG, Curr. Opin. Chem. Biol. 5 (2001) 368-374). Human antibodies can also be produced in transgenic animals (e.g., mice or chickens) that, after immunization, are able to produce a complete repertoire of human antibodies or selectable human antibodies in the absence of endogenous immunoglobulins. Transferring the human germline immunoglobulin gene array in these germline mutant mice will result in the production of human antibodies upon antigen challenge (see, e.g., Jakobovits, A., et al., Proc. Natl. Acad. Sci. USA 90 (1993) 2551-2555; Jakobovits, A., et al., Nature 362 (1993) 255-258; Bruggemann, M., et al., Year Immunol. 7 (1993) 3340). Human antibodies can also be produced in phage display libraries (Hoogenboom, HR, and Winter, G., J. Mol. Biol. 227 (1992) 381-388; Marks, JD, et al., J. Mol. Biol. 222 (1991) 581-597). The techniques of Cole et al. and Boerner et al. can also be used to prepare human monoclonal antibodies (Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985); and Boerner, P., et al., J. Immunol. 147 (1991) 86-95). As used herein, the expression "human antibody" includes non-naturally occurring sequence variants of human antibodies, which are generally obtained by introducing one or more mutations into (naturally occurring) human antibodies. These mutations include one or more mutations in the CDR or framework regions, and Fc modifications (e.g., specific functions as known in the art).

[0022] As used herein, the term "variable region" (light chain variable region (V L ), heavy chain variable region (V H )) represents each of a pair of light and heavy chains directly involved in binding the antibody to the antigen.

[0023] The antibodies of the present invention can be of any isotype (e.g., IgA, IgG, IgM, i.e., α heavy chain, γ heavy chain, or μ heavy chain). Preferably, the antibody is of IgG type or IgA type. Within the IgG isotype, the antibody can be of IgG1, IgG2, IgG3, or IgG4 subclass, preferably IgG1 or IgG4. The antibodies of the present invention can have a kappa light chain or a lambda light chain.

[0024] Antibodies according to the present invention can be provided in purified form. Typically, the antibody will be present in a composition that is substantially free of other polypeptides, for example, wherein less than 90% by weight, typically less than 60% by weight, more typically less than 50% by weight of the composition is constituted by other polypeptides.

[0025] Antibodies according to the present invention can be immunogenic in human hosts and / or non-human (or heterologous) hosts, such as mice. For example, an antibody can have a unique site that is immunogenic in a non-human host but not in a human host. Antibodies of the present invention for human use include antibodies that cannot be easily isolated from hosts such as mice, goats, rabbits, rats, non-primate mammals, etc., and cannot generally be obtained by humanization or from xenogeneic mice.

[0026] As used herein, the term "antigen" refers to any structural substance that serves as a target of a receptor for an adaptive immune response, particularly a target of an antibody, T cell receptor, and / or B cell receptor. An "epitope", also referred to as an "antigenic determinant", is an antigenic portion (or fragment) that is recognized by the immune system, particularly by an antibody, T cell receptor, and / or B cell receptor. Thus, an antigen has at least one epitope, i.e., a single antigen has one or more than one epitope. An antigen can be (i) a peptide, polypeptide, or protein, (ii) a polysaccharide, (iii) a lipid, (iv) a lipoprotein, or a lipopeptide, (v) a glycolipid, (vi) a nucleic acid, or (vii) a small molecule drug or toxin. Thus, an antigen can be a peptide, protein, polysaccharide, lipid, a combination thereof including lipoproteins and glycolipids, a nucleic acid (e.g., DNA, siRNA, shRNA, antisense oligonucleotides, decoy DNA, plasmid), or a small molecule drug (e.g., cyclosporine A, paclitaxel, doxorubicin, methotrexate, 5-aminolevulinic acid), or any combination thereof. Preferably, the antigen is selected from (i) a peptide, polypeptide or protein, (ii) a polysaccharide, (iii) a lipid, (iv) a lipoprotein or lipopeptide, and (v) a glycolipid; more preferably, the antigen is a peptide, polypeptide or protein.

[0027] As used herein, the term "mutation" refers to a change in a nucleic acid sequence and / or an amino acid sequence compared to a reference sequence, such as a corresponding genomic sequence. Mutations, for example, compared to a genomic sequence, may be, for example, (naturally occurring) somatic mutations, spontaneous mutations, induced mutations, such as mutations induced by enzymes, chemicals or radiation, or mutations obtained by site-directed mutagenesis (a molecular biological method for making specific and intentional changes in nucleic acid sequences and / or amino acid sequences). Therefore, the term "mutation" should be understood to also include mutations in a physical manner, such as mutations in a nucleic acid sequence or an amino acid sequence. Mutations include substitutions, deletions and insertions of one or more nucleotides or amino acids, and inversions of several consecutive nucleotides or amino acids. In order to achieve mutations in an amino acid sequence, mutations can be introduced into the nucleotide sequence encoding the amino acid sequence to express (recombinant) mutated polypeptides. Mutations can be achieved, for example, by changing the codons of a nucleic acid molecule encoding one amino acid to produce codons encoding a different amino acid, such as by site-directed mutagenesis, or by synthesizing sequence variants, such as by knowing the nucleotide sequence of a nucleic acid molecule encoding a polypeptide and by designing the synthesis of a nucleic acid molecule comprising a nucleotide sequence encoding the polypeptide variant without the need to mutate one or more nucleotides of the nucleic acid molecule.

[0028] As used herein (i.e., throughout this specification), the term "sequence variant" refers to any change compared to a reference sequence. The term "sequence variant" includes nucleotide sequence variants and amino acid sequence variants. Preferably, the reference sequence is any sequence listed in the "Sequence Listing and SEQ ID Number Table" (Sequence Listing), i.e., SEQ ID NO: 1 to SEQ ID NO: 99. In particular, the sequence variant shares (relative to the entire length of the sequence) at least 70% or at least 75%, preferably at least 80% or at least 85%, more preferably at least 90% or at least 93%, even more preferably at least 95% or at least 96%, still more preferably at least 97% or at least 98%, particularly preferably at least 99% sequence identity with its reference sequence. In some embodiments, the sequence variants share at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity. Thus, the higher the % identity of a sequence variant, the more preferred it is. For example, a sequence variant having at least 84% sequence identity is more preferred than a sequence variant having at least 75% but less than 84% sequence identity compared to the reference sequence. In some embodiments, the sequence variant retains the (biological) function of the reference sequence. For example, sequence variants associated with the antibodies of the present invention preferably retain specific binding to peanut allergens, particularly Ara h 2 (and optionally, Ara h 3 or Ara h 6).

[0029] Sequence identity can be calculated as described below.Usually, sequence variants can retain the specific function of the reference sequence.In some embodiments, amino acid sequence variants have the sequence of change, wherein by one or more than one (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more than 10) amino acid deletion or replacement in the reference sequence, or by one or more than one (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more than 10) amino acid insertion or addition in the sequence of the reference amino acid sequence.As the result of change, compared with the reference sequence, amino acid sequence variants have an amino acid sequence of at least 70% or at least 75%, preferably at least 80% or at least 85%, more preferably at least 90% or at least 93%, even more preferably at least 95% or at least 96%, also more preferably at least 97% or at least 98%, particularly preferably at least 99% identity. For example, a variant sequence with at least 90% identity has no more than 10 changes, i.e., any combination of deletions, insertions, or substitutions, per every 100 amino acids of the reference sequence. Of course, the same applies to nucleic acid sequences.

[0030] The "% identity" of a sequence variant is typically determined relative to a reference sequence. It is typically calculated over the entire length of the reference sequence (i.e., the sequence cited in the application). Percent identity as referred to herein can be determined, for example, by methods known in the art, such as the BLASR (National Center for Biotechnology Information; http: / / www.ncbi.nlm.nih.gov / ) Blosum 62 matrix using the default parameters specified by NCBI; gap opening penalty = 11 and gap extension penalty = 1].

[0031] In general, although non-conservative amino acid substitutions are possible, preferably, the substitution is a conservative amino acid substitution, in which the substituted amino acid has similar structural or chemical properties to the corresponding amino acid in the reference sequence. For example, conservative amino acid substitutions involve replacing one aliphatic or hydrophobic amino acid, such as alanine, valine, leucine, and isoleucine, with another aliphatic or hydrophobic amino acid; replacing one hydroxyl-containing amino acid, such as serine and threonine, with another hydroxyl-containing amino acid; replacing one acidic residue, such as glutamic acid or aspartic acid, with another acidic residue; replacing one amide-containing residue, such as asparagine and glutamine, with another amide-containing residue; replacing one aromatic residue, such as phenylalanine and tyrosine, with another aromatic residue; replacing one basic residue, such as lysine, arginine, and histidine, with another basic residue; and replacing one small amino acid, such as alanine, serine, threonine, cysteine, and glycine, with another small amino acid.

[0032] Several documents are cited throughout this specification. Each document cited herein, whether supra or infra, including all patents, patent applications, scientific publications, manufacturer's specifications, instructions, etc., is hereby incorporated by reference in its entirety. Nothing herein should be construed as an admission that the present invention is not entitled to antedate such disclosure by virtue of prior invention.

[0033] It should be understood that the present invention is not limited to the specific methods, protocols and reagents described herein, as they may vary. It should also be understood that the terminology used herein is for the purpose of describing specific embodiments only and is not intended to limit the scope of the present invention, which is limited only by the appended claims. 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.

[0034] Antibodies and their antigen-binding fragments

[0035] In a first aspect, the present invention provides (isolated) antibodies or antigen-binding fragments thereof that (specifically) bind to peanut allergens, in particular Ara h 2 (peanut (Arachis hypogaea) allergen 2). Ara h 2 is the major peanut allergen that is recognized by serum IgE in more than 90% of peanut-allergic patients. Ara h 2 is a 2S albumin storage protein of approximately 17.5 kDa. Two Ara h 2 isoforms have been described, Ara h 2.0101 (SEQ ID NO: 55) and Ara h 2.0201 (SEQ ID NO: 56), wherein Ara h 2.0201 contains 12 additional amino acids (Hales, Belinda et al. (2004). Isoforms of the Major Peanut Allergen Ara h 2: IgE Binding in Children with Peanut Allergy. International archives of allergy and immunology. 135. 101-7. 10.1159 / 000080652). Thus, the antibodies or antigen-binding fragments thereof of the present invention specifically bind to polypeptides or proteins having an amino acid sequence according to SEQ ID NO: 55 and / or SEQ ID NO: 56.

[0036] Preferably, an (isolated) antibody or antigen-binding fragment thereof that (specifically) binds to Ara h 2 also binds to Ara h 3 (peanut allergen 3; also known as "Ara h 3.0101"; SEQ ID NO: 57) or Ara h 6 (peanut allergen 6; also known as "Ara h 6.0101"; SEQ ID NO: 58). Ara h 3 and Ara h 6 are further major peanut allergens. Therefore, the antibody or antigen-binding fragment thereof of the present invention preferably binds to a polypeptide or protein having an amino acid sequence according to SEQ ID NO: 57 or SEQ ID NO: 58. Preferably, the antibody or antigen-binding fragment thereof of the present invention (i) binds to Ara h 2 and Ara h 3; or (ii) binds to Ara h 2 and Ara h 6 (specifically).

[0037] The peanut allergens, in particular Ara h 2, Ara h 3 and / or Ara h 6, may be peanut-derived, recombinantly expressed or synthetic peanut peptides.

[0038] Standard methods for evaluating the binding of antibodies or antigen-binding fragments thereof according to the present invention are known to those skilled in the art and include, for example, ELISA (enzyme-linked immunosorbent assay). Thus, the relative affinity of antibody binding can be determined by measuring the antibody concentration required for maximal binding to achieve 50% saturation (EC 50 Specific examples of ELISAs that can be used to assess antibody binding are described in the Examples section of this specification.

[0039] In general, the antibodies or antigen-binding fragments thereof according to the present invention may comprise (at least) three complementary determining regions (CDRs) on the heavy chain and (at least) three CDRs on the light chain. Typically, complementary determining regions (CDRs) are hypervariable regions present in the heavy chain variable domain and the light chain variable domain. Typically, the heavy chain of an antibody and the CDRs of the light chain to which it is attached together form an antigen receptor. Typically, three CDRs (CDR1, CDR2, and CDR3) are arranged non-continuously in the variable domain. Since antigen receptors are typically composed of two variable domains (on two different polypeptide chains, i.e., heavy chain and light chain: heavy chain variable region (VH) and light chain variable region (VL)), each antigen receptor typically has six CDRs (heavy chain: CDRH1, CDRH2, and CDRH3; light chain: CDRL1, CDRL2, and CDRL3). For example, a typical IgG antibody molecule typically has two antigen receptors and therefore comprises 12 CDRs. The CDRs on the heavy and / or light chains can be separated by framework regions, wherein the framework region (FR) is a region in the variable domain that is less "variable" than the CDRs. For example, the variable region (or each variable region, respectively) may consist of four framework regions, separated by three CDRs.

[0040] The sequences of the heavy and light chains of exemplary antibodies of the present invention were determined, including three different CDRs on the heavy chain and three different CDRs on the light chain. The CDR amino acid sequences of the heavy chain CDR1 (CDRH1), heavy chain CDR2 (CDRH2), heavy chain CDR3 (CDRH3), light chain CDR1 (CDRL1), light chain CDR2 (CDRL2), and light chain CDR3 (CDRL3) of exemplary antibodies 17H9, 15E3, 2F8, and 7G6, and exemplary variants thereof, are shown in Table 1 below.

[0041] The CDRs identified as described herein, in particular the three different CDRs on the heavy chain (CDR1, CDR2 and CDR3) and the three different CDRs on the light chain (CDR1, CDR2 and CDR3) can be grafted into any variable framework region, in particular any variable human framework region, without abolishing their specificity.

[0042] The human variable framework region (VH) of the heavy chain can be retrieved from the following website: "https: / / www.imgt.org / genedb / resultPage.action;jsessionid=49EB34C22C79EAC51862C76108963216?gene.id.species=Homo+sapiens&molComponent=IG&geneTypeLike=variable&allele.fcode=functional&cloneName=&locusLike=IGH&mainLocusLike=IGH+locus&cosLocusLike=any&groupLike=any&subgroup=-1&geneLike=&selection=any", the content of which is incorporated herein by reference. Thus, the VH chain may be selected from the amino acid sequences encoded by the following genes: IGHV1-18, IGHV1-2, IGHV1-24, IGHV1-3, IGHV1-45, IGHV1-46, IGHV1-58, IGHV1-69, IGHV1-69-2, IGHV1-69D, IGHV1-8, IGHV2-26, IGHV2-5, IGHV2-70, IGHV2-70D, IGHV3-11, IGHV3-13, IGHV3-15, IGHV3-20, IGHV3-21, IGHV3-23, IGHV3-23D, IGHV3-30, IGHV3-31. 0-3, IGHV3-30-5, IGHV3-33, IGHV3-35, IGHV3-43, IGHV3-43D, IGHV3-48, IGHV3-49, IGHV3-53, IGHV3-62, IGHV3-64, IGHV3-64D, IGHV3-66, IGHV3-7, IGHV3-72, IGHV3-73, IGHV3-74, IGHV3-9, IGHV3-NL1, IGHV4-28, IGHV4-30-1, IGHV4-30-2, IGHV4-30-4, IGHV4-31, IGHV4-34 and IGHV4-38-2.

[0043] The human variable framework regions (VK, κ) of the light and heavy chains can be retrieved from the following website: "https: / / www.imgt.org / genedb / resultPage.action;jsessionid=49EB34C22C79EAC51862C76108963216?gene.id.species=Homo+sapiens&molComponent=IG&geneTypeLike=variable&allele.fcode=functional&cloneName=&locusLike=IGK&mainLocusLike=IGK+locus&cosLocusLike=any&groupLike=any&subgroup=-1&geneLike=&selection=any", the contents of which are incorporated herein by reference. Thus, the VK(κ) chain can be selected from the amino acid sequences encoded by the following genes: IGKV1-12, IGKV1-13, IGKV1-16, IGKV1-17, IGKV1-27, IGKV1-33, IGKV1-39, IGKV1-5, IGKV1-6, IGKV1-8, IGKV1-9, IGKV1-NL1, IGKV1D-12, IGKV1D-13, IGKV1D-16, IGKV1D-17, IGKV1D-33, IGKV1D-39, IGKV1D-43, IGKV1D-54 ... GKV1D-8, IGKV2-24, IGKV2-28, IGKV2-29, IGKV2-30, IGKV2-40, IGKV2D-26, IGKV2D-28, IGKV2D-29, IGKV2D-30, IGKV2D-40 , IGKV3-11, IGKV3-15, IGKV3-20, IGKV3D-11, IGKV3D-15, IGKV3D-20, IGKV3D-7, IGKV4-1, IGKV5-2, IGKV6-21 and IGKV6D-21.

[0044] The human variable framework regions (VL, λ) of the light and heavy chains can be retrieved from the following website: "https: / / www.imgt.org / genedb / resultPage.action;jsessionid=49EB34C22C79EAC51862C76108963216?gene.id.species=Homo+sapiens&molComponent=IG&geneTypeLike=variable&allele.fcode=functional&cloneName=&locusLike=IGL&mainLocusLike=IGL+locus&cosLocusLike=any&groupLike=any&subgroup=-1&geneLike=&selection=any", the content of which is incorporated herein by reference. Thus, the VL(λ) chain can be selected from the amino acid sequences encoded by the following genes: IGLV1-36, IGLV1-40, IGLV1-44, IGLV1-47, IGLV1-51, IGLV10-54, IGLV2-11, IGLV2-14, IGLV2-18, IGLV2-23, IGLV2-8, IGLV3-1, IGLV3-10, IGLV3-12, IGLV3-16 ,IGLV3-19,IGLV3-21,IGLV3-22,IGLV3-25,IGLV3-27,IGLV3-9,IGLV4-3,IGLV4-60,IGLV4-69, IGLV5-37, IGLV5-39, IGLV5-45, IGLV5-52, IGLV6-57, IGLV7-43, IGLV7-46, IGLV8-61 and IGLV9-49.

[0045] The human variable framework regions of the heavy and light chains may also comprise respective human HJ (heavy chain) sequences and light chain KJ (κ) sequences or light chain LJ (λ) sequences.

[0046] HJ sequences can be retrieved from the following website: "https: / / www.imgt.org / genedb / resultPage.action?gene.id.species=Homo+sapiens&molComponent=IG&geneTypeLike=any&allele.fcode=functional&cloneName=&locusLike=IGH&mainLocusLike=IGH+locus&cosLocusLike=any&groupLike=IGHJ&subgroup=-1&geneLike=&selection=any", the contents of which are incorporated herein by reference. In particular, the HJ sequence can be selected from the amino acid sequences encoded by the following genes: IGHJ1, IGHJ2, IGHJ3, IGHJ4, IGHJ5, and IGHJ6.

[0047] KJ sequences can be retrieved from the following website: "https: / / www.imgt.org / genedb / resultPage.action?gene.id.species=Homo+sapiens&molComponent=IG&geneTypeLike=any&allele.fcode=functional&cloneName=&locusLike=IGK&mainLocusLike=IGK+locus&cosLocusLike=any&groupLike=IGKJ&subgroup=-1&geneLike=&selection=any", the contents of which are incorporated herein by reference. In particular, the KJ sequence can be selected from the amino acid sequences encoded by the following genes: IGKJ1, IGKJ2, IGKJ3, IGKJ4 and IGKJ5.

[0048] LJ sequences can be retrieved from the following website: "https: / / www.imgt.org / genedb / resultPage.action?gene.id.species=Homo+sapiens&molComponent=IG&geneTypeLike=any&allele.fcode=functional&cloneName=&locusLike=IGL&mainLocusLike=IGL+locus&cosLocusLike=any&groupLike=IGLJ&subgroup=-1&geneLike=&selection=any", the contents of which are incorporated herein by reference. In particular, the LJ sequence can be selected from the amino acid sequences encoded by the following genes: IGLJ1, IGLJ2, IGLJ3, IGLJ6 and IGLJ7.

[0049] The heavy chain CDR sequences (CDRH1, CDRH2 and CDRH3) of the present invention can be composed of human heavy chain variable framework sequences, which are defined by the combination of human VH sequences described herein and human HJ sequences described herein. Similarly, the light chain CDR sequences (CDRL1, CDRL2 and CDRL3) of the present invention can be composed of human light chain variable framework sequences, which are defined by the combination of human VL sequences or VK sequences described herein and human LJ sequences or KJ sequences described herein.

[0050] Therefore, the variable framework regions and binding regions of the antibodies according to the present invention may be characterized by (i) a combination of a human VH sequence (including a CDRH1 sequence, a CDRH2 sequence, and a CDRH3 sequence according to the present invention, respectively) and a human VL sequence (including a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence according to the present invention, respectively), or (ii) a combination of a human VH sequence (including a CDRH1 sequence, a CDRH2 sequence, and a CDRH3 sequence according to the present invention, respectively) and a human VK sequence (including a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence according to the present invention, respectively). In addition, the variable framework regions may be characterized by (i) a combination of a human VH sequence and a human HJ sequence with a human VL sequence and a human LJ sequence, or (ii) a combination of a human VH sequence and a human HJ sequence with a human VK sequence and a human KJ sequence, thereby forming the variable framework regions and binding regions of the antibodies according to the present invention.

[0051] The CDR sequences of the present invention are inserted into the sites of the variable framework sequences that provide the CDR sequences, e.g. Figure 18 B. Figure 19 D. Figure 20 C and Figure 21Shown in the grey box in B.

[0052] The variable region residues are numbered according to the IMGT numbering system (IMGT: http: / / www.imgt.org / ; cf. Lefranc, M.-P. et al. (2009) Nucleic Acids Res. 37, D1006-D1012). To define the CDR regions, the Kabat CDR definition was applied (Tai Te Wu, Elvin A. Kabat; An analysis of thesequences of the variable regions of Bence Jones proteins and myeloma lightchains and their implications for antibody complementarity. J Exp Med 1 August 1970; 132 (2): 211-250; George Johnson, Tai Te Wu, Kabat Database and its applications: 30 years after the first variability plot, Nucleic Acids Research, Volume 28, Issue 1, 1 January 2000, Pages 214-218).

[0053]

[0054] Table 1: SEQ ID NOs. of CDR sequences of antibodies 17H9, 15E3, 2F8 and 7G6

[0055] In addition, the amino acid sequences of the heavy chain variable regions (VH) and light chain variable regions (VL) of exemplary antibodies 17H9, 15E3, 2F8, and 7G6 and exemplary variants thereof are shown in Table 2 below:

[0056]

[0057] Table 2: SEQ ID NOs of wild-type (wt) sequences and engineered VH sequences / VL sequences of antibodies 17H9, 15E3, 2F8 and 7G6

[0058] Preferably, the antibodies or antigen-binding fragments thereof of the present invention comprise a combination of the six CDR sequences of the exemplary antibodies shown in Table 1 (optionally, the VH sequences and VL sequences of the exemplary antibodies shown in Table 2) or sequence variants thereof as defined herein.

[0059] In some embodiments, the antibody or antigen-binding fragment thereof comprises a CDRH1 at least 70% identical to SEQ ID NO: 1, a CDRH2 at least 70% identical to SEQ ID NO: 2, a CDRH3 at least 70% identical to SEQ ID NO: 3, a CDRL1 at least 70% identical to SEQ ID NO: 4, a CDRL2 at least 70% identical to SEQ ID NO: 5, and a CDRL3 at least 70% identical to SEQ ID NO: 6. Preferably, the antibody or antigen-binding fragment thereof comprises:

[0060] - a heavy chain CDR1 sequence according to SEQ ID NO: 1;

[0061] - a heavy chain CDR2 sequence according to SEQ ID NO: 2;

[0062] - a heavy chain CDR3 sequence according to SEQ ID NO: 3;

[0063] - a light chain CDR1 sequence according to SEQ ID NO: 4;

[0064] - a light chain CDR2 sequence according to SEQ ID NO: 5; and

[0065] - a light chain CDR3 sequence according to SEQ ID NO: 6.

[0066] As shown in the accompanying Examples, this antibody (eg, 17H9) specifically binds to Ara h 2 and Ara h 3.

[0067] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 7 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 8 have a light chain variable region (VL) having an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, respectively).

[0068] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 7 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 76, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, respectively).

[0069] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 7 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 77, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, respectively).

[0070] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 7 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 78, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, respectively).

[0071] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 7 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 79, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, respectively).

[0072] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 44 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 44. 8 have a light chain variable region (VL) having an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, respectively).

[0073] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 44 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 44. 76, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, respectively).

[0074] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 44 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 44. 77, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, respectively).

[0075] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 44 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 44. 78, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, respectively).

[0076] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 44 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 44. 79, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, respectively).

[0077] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 45 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 45. 8 have a light chain variable region (VL) having an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, respectively).

[0078] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 45 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 45. 76, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, respectively).

[0079] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 45 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 45. 77, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, respectively).

[0080] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 45 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 45. 78, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, respectively).

[0081] Preferably, such antibodies or antigen-binding fragments thereof of the present invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99%) identical to SEQ ID NO: 45 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99%) identical to SEQ ID NO: 45. 79, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, respectively).

[0082] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 7 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 8.

[0083] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 7 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 46.

[0084] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 7 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 47.

[0085] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 7 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 48.

[0086] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 7 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 49.

[0087] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 44 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 8.

[0088] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 44 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 46.

[0089] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 44 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 47.

[0090] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 44 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 48.

[0091] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 44 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 49.

[0092] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 45 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 8.

[0093] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 45 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 46.

[0094] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 45 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 47.

[0095] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 45 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 48.

[0096] Preferably, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 45 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 49.

[0097] In some embodiments, the antibody or antigen-binding fragment thereof comprises a CDRH1 that is at least 70% identical to SEQ ID NO: 9, a CDRH2 that is at least 70% identical to SEQ ID NO: 10, a CDRH3 that is at least 70% identical to SEQ ID NO: 11, a CDRL1 that is at least 70% identical to SEQ ID NO: 12, a CDRL2 that is at least 70% identical to SEQ ID NO: 13, and a CDRL3 that is at least 70% identical to SEQ ID NO: 14. Preferably, the antibody or antigen-binding fragment thereof comprises:

[0098] - a heavy chain CDR1 sequence according to SEQ ID NO: 9;

[0099] - a heavy chain CDR2 sequence according to SEQ ID NO: 10;

[0100] - a heavy chain CDR3 sequence according to SEQ ID NO: 11;

[0101] - a light chain CDR1 sequence according to SEQ ID NO: 12;

[0102] - a light chain CDR2 sequence according to SEQ ID NO: 13; and

[0103] - a light chain CDR3 sequence according to SEQ ID NO: 14.

[0104] As shown in the accompanying Examples, such antibodies (eg, 15E3) specifically bind to Ara h 2 and Ara h 6.

[0105] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 15 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 16 have a light chain variable region (VL) having an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14, respectively).

[0106] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 15 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 79, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to 39. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14, respectively).

[0107] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 15 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: In some embodiments, the present invention comprises a light chain variable region (VL) having an amino acid sequence that is 70% or more identical (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) to the amino acid sequence. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14, respectively).

[0108] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 37 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 16 have a light chain variable region (VL) having an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14, respectively).

[0109] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 37 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 79, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to 39. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14, respectively).

[0110] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 37 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: In some embodiments, the present invention comprises a light chain variable region (VL) having an amino acid sequence that is 70% or more identical (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) to the amino acid sequence. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14, respectively).

[0111] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 38 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 16 have a light chain variable region (VL) having an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14, respectively).

[0112] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 38 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: In some embodiments, the present invention comprises a light chain variable region (VL) having an amino acid sequence that is 70% or more identical (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) to the amino acid sequence. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14, respectively).

[0113] Preferably, such antibodies or antigen-binding fragments thereof of the present invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99%) identical to SEQ ID NO: 38 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99%) identical to SEQ ID NO: 38. 79, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to 39. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14, respectively).

[0114] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 15 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 16.

[0115] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 15 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 39.

[0116] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 15 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 40.

[0117] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 37 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 16.

[0118] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 37 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 39.

[0119] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 37 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 40.

[0120] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 38 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 16.

[0121] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 38 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 40.

[0122] Preferably, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 38 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 39.

[0123] In some embodiments, the antibody or antigen-binding fragment thereof comprises a CDRH1 at least 70% identical to SEQ ID NO: 17, a CDRH2 at least 70% identical to SEQ ID NO: 18, a CDRH3 at least 70% identical to SEQ ID NO: 51, a CDRL1 at least 70% identical to SEQ ID NO: 20, a CDRL2 at least 70% identical to SEQ ID NO: 21, and a CDRL3 at least 70% identical to SEQ ID NO: 22. Preferably, the antibody or antigen-binding fragment thereof comprises:

[0124] - a heavy chain CDR1 sequence according to SEQ ID NO: 17;

[0125] - a heavy chain CDR2 sequence according to SEQ ID NO: 18;

[0126] - a heavy chain CDR3 sequence according to SEQ ID NO: 51;

[0127] - a light chain CDR1 sequence according to SEQ ID NO: 20;

[0128] - a light chain CDR2 sequence according to SEQ ID NO: 21; and

[0129] - a light chain CDR3 sequence according to SEQ ID NO: 22.

[0130] As shown in the accompanying Examples, such antibodies (e.g., 2F8 CDRH3 variants) specifically bind to Ara h 2 and Ara h 6. Furthermore, as shown in the accompanying Examples, variant 2F8 containing an engineered CDRH3 produces a more homogeneous product compared to wild-type 2F8, thereby increasing the manufacturability of the antibody.

[0131] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 53 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to 24. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 17, SEQ ID NO: 18 and SEQ ID NO: 51, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 20, SEQ ID NO: 21 and SEQ ID NO: 22, respectively).

[0132] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 53 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 17, SEQ ID NO: 18 and SEQ ID NO: 51, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 20, SEQ ID NO: 21 and SEQ ID NO: 22, respectively).

[0133] Preferably, such antibodies or antigen-binding fragments thereof of the present invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 53 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 73, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 17, SEQ ID NO: 18 and SEQ ID NO: 51, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 20, SEQ ID NO: 21 and SEQ ID NO: 22, respectively).

[0134] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 53 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 24.

[0135] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 53 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 42.

[0136] Preferably, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 53 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 43.

[0137] The present invention also provides an antibody or antigen-binding fragment thereof that specifically binds to Ara h 2 and / or Ara h 6, comprising a VH that is at least 70% identical to SEQ ID NO: 23; and a VL that is at least 70% identical to SEQ ID NO: 42 or SEQ ID NO: 43. Thus, it is preferred to retain the heavy chain CDR1 sequence, heavy chain CDR2 sequence, and heavy chain CDR3 sequence as shown in SEQ ID NO: 17, SEQ ID NO: 18, and SEQ ID NO: 19, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence, and light chain CDR3 sequence as shown in SEQ ID NO: 20, SEQ ID NO: 21, and SEQ ID NO: 22, respectively. In some embodiments, such an antibody or antigen-binding fragment thereof comprises a VH according to SEQ ID NO: 23; and a VL according to SEQ ID NO: 42 or SEQ ID NO: 43.

[0138] The present invention also provides an antibody or antigen-binding fragment thereof that specifically binds to Ara h 2 and / or Ara h 6, comprising a VH that is at least 70% identical to SEQ ID NO: 41 or SEQ ID NO: 50; and a VL that is at least 70% identical to SEQ ID NO: 24. Thus, it is preferred that the heavy chain CDR1 sequence, heavy chain CDR2 sequence, and heavy chain CDR3 sequence as shown in SEQ ID NO: 17, SEQ ID NO: 18, and SEQ ID NO: 19, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence, and light chain CDR3 sequence as shown in SEQ ID NO: 20, SEQ ID NO: 21, and SEQ ID NO: 22, respectively, be retained. In some embodiments, such an antibody or antigen-binding fragment thereof comprises a VH according to SEQ ID NO: 41 or SEQ ID NO: 50; and a VL according to SEQ ID NO: 24.

[0139] The present invention also provides an antibody or antigen-binding fragment thereof that specifically binds to Ara h 2 and / or Ara h 6, comprising a VH that is at least 70% identical to SEQ ID NO: 41 or SEQ ID NO: 50; and a VL that is at least 70% identical to SEQ ID NO: 42 or SEQ ID NO: 43. Therefore, it is preferred to retain the heavy chain CDR1 sequence, heavy chain CDR2 sequence, and heavy chain CDR3 sequence shown in SEQ ID NO: 17, SEQ ID NO: 18, and SEQ ID NO: 19, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence, and light chain CDR3 sequence shown in SEQ ID NO: 20, SEQ ID NO: 21, and SEQ ID NO: 22, respectively.

[0140] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 41 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 41. 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 17, SEQ ID NO: 18 and SEQ ID NO: 19, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 20, SEQ ID NO: 21 and SEQ ID NO: 22, respectively).

[0141] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 41 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 41. 73, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 17, SEQ ID NO: 18 and SEQ ID NO: 19, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 20, SEQ ID NO: 21 and SEQ ID NO: 22, respectively).

[0142] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 50 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 17, SEQ ID NO: 18 and SEQ ID NO: 19, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 20, SEQ ID NO: 21 and SEQ ID NO: 22, respectively).

[0143] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 50 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 73, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 17, SEQ ID NO: 18 and SEQ ID NO: 19, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 20, SEQ ID NO: 21 and SEQ ID NO: 22, respectively).

[0144] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 41 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 42.

[0145] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 41 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 43.

[0146] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 50 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 42.

[0147] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 50 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 43.

[0148] In some embodiments, the antibody or antigen-binding fragment thereof comprises a CDRH1 that is at least 70% identical to SEQ ID NO: 25, a CDRH2 that is at least 70% identical to SEQ ID NO: 26, a CDRH3 that is at least 70% identical to SEQ ID NO: 27, a CDRL1 that is at least 70% identical to SEQ ID NO: 28, a CDRL2 that is at least 70% identical to SEQ ID NO: 52, and a CDRL3 that is at least 70% identical to SEQ ID NO: 30. Preferably, the antibody or antigen-binding fragment thereof comprises:

[0149] - a heavy chain CDR1 sequence according to SEQ ID NO: 25;

[0150] - a heavy chain CDR2 sequence according to SEQ ID NO: 26;

[0151] - a heavy chain CDR3 sequence according to SEQ ID NO: 27;

[0152] - a light chain CDR1 sequence according to SEQ ID NO: 28;

[0153] - a light chain CDR2 sequence according to SEQ ID NO: 52; and

[0154] - a light chain CDR3 sequence according to SEQ ID NO: 30.

[0155] As shown in the accompanying Examples, such antibodies (e.g., 7G6 CDRL2 variants) specifically bind to Ara h 2 and Ara h 6. Furthermore, as shown in the accompanying Examples, the variant 7G6 containing the engineered CDRL2 exhibits less nonspecific binding compared to wild-type 7G6, thereby increasing the manufacturability of the antibody.

[0156] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 31 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 54 have a light chain variable region (VL) having an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 25, SEQ ID NO: 26 and SEQ ID NO: 27, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 28, SEQ ID NO: 29 and SEQ ID NO: 30, respectively).

[0157] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 33 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 54 have a light chain variable region (VL) having an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 25, SEQ ID NO: 26 and SEQ ID NO: 27, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 28, SEQ ID NO: 29 and SEQ ID NO: 30, respectively).

[0158] Preferably, such antibodies or antigen-binding fragments thereof of the present invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99%) identical to SEQ ID NO: 34 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99%) identical to SEQ ID NO: 54 have a light chain variable region (VL) having an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 25, SEQ ID NO: 26 and SEQ ID NO: 27, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 28, SEQ ID NO: 29 and SEQ ID NO: 30, respectively).

[0159] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 31 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 54.

[0160] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 33 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 54.

[0161] Preferably, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 34 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 54.

[0162] The present invention also provides an antibody or antigen-binding fragment thereof that specifically binds to Ara h 2 and / or Ara h 6, comprising a VH that is at least 70% identical to SEQ ID NO: 31; and a VL that is at least 70% identical to SEQ ID NO: 35 or SEQ ID NO: 36. Thus, it is preferred that the heavy chain CDR1 sequence, heavy chain CDR2 sequence, and heavy chain CDR3 sequence as shown in SEQ ID NO: 25, SEQ ID NO: 26, and SEQ ID NO: 27, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence, and light chain CDR3 sequence as shown in SEQ ID NO: 28, SEQ ID NO: 29, and SEQ ID NO: 30, respectively, be retained. In some embodiments, such an antibody or antigen-binding fragment thereof comprises a VH according to SEQ ID NO: 31; and a VL according to SEQ ID NO: 35 or SEQ ID NO: 36.

[0163] The present invention also provides an antibody or antigen-binding fragment thereof that specifically binds to Ara h 2 and / or Ara h 6, comprising a VH that is at least 70% identical to SEQ ID NO: 33 or SEQ ID NO: 34; and a VL that is at least 70% identical to SEQ ID NO: 32. Thus, it is preferred that the heavy chain CDR1 sequence, heavy chain CDR2 sequence, and heavy chain CDR3 sequence as shown in SEQ ID NO: 25, SEQ ID NO: 26, and SEQ ID NO: 27, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence, and light chain CDR3 sequence as shown in SEQ ID NO: 28, SEQ ID NO: 29, and SEQ ID NO: 30, respectively, be retained. In some embodiments, such an antibody or antigen-binding fragment thereof comprises a VH according to SEQ ID NO: 33 or SEQ ID NO: 34; and a VL according to SEQ ID NO: 32.

[0164] The present invention also provides an antibody or antigen-binding fragment thereof that specifically binds to Ara h 2 and / or Ara h 6, comprising a VH that is at least 70% identical to SEQ ID NO: 33 or SEQ ID NO: 34; and a VL that is at least 70% identical to SEQ ID NO: 35 or SEQ ID NO: 36. Therefore, it is preferred to retain the heavy chain CDR1 sequence, heavy chain CDR2 sequence, and heavy chain CDR3 sequence shown in SEQ ID NO: 25, SEQ ID NO: 26, and SEQ ID NO: 27, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence, and light chain CDR3 sequence shown in SEQ ID NO: 28, SEQ ID NO: 29, and SEQ ID NO: 30, respectively.

[0165] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 33 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 25, SEQ ID NO: 26 and SEQ ID NO: 27, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 28, SEQ ID NO: 29 and SEQ ID NO: 30, respectively).

[0166] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 33 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 76, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 25, SEQ ID NO: 26 and SEQ ID NO: 27, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 28, SEQ ID NO: 29 and SEQ ID NO: 30, respectively).

[0167] In some embodiments, such antibodies or antigen-binding fragments thereof of the invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 34 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to SEQ ID NO: 76, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 25, SEQ ID NO: 26 and SEQ ID NO: 27, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 28, SEQ ID NO: 29 and SEQ ID NO: 30, respectively).

[0168] Preferably, such antibodies or antigen-binding fragments thereof of the present invention may comprise (i) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99%) identical to SEQ ID NO: 34 and (ii) a heavy chain variable region (VH) comprising an amino acid sequence that is 70% or more (e.g., at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99%) identical to SEQ ID NO: 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. Therefore, it is preferred to retain the CDR sequences defined above (the heavy chain CDR1 sequence, heavy chain CDR2 sequence and heavy chain CDR3 sequence shown in SEQ ID NO: 25, SEQ ID NO: 26 and SEQ ID NO: 27, respectively; and the light chain CDR1 sequence, light chain CDR2 sequence and light chain CDR3 sequence shown in SEQ ID NO: 28, SEQ ID NO: 29 and SEQ ID NO: 30, respectively).

[0169] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 33 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 35.

[0170] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 33 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 36.

[0171] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 34 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 36.

[0172] Preferably, the antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 34 and a light chain variable region comprising or consisting of the amino acid sequence shown in SEQ ID NO: 35.

[0173] Generally, the antibodies or antigen-binding fragments thereof of the present invention are capable of reducing, inhibiting, or neutralizing allergen-mediated biological activities. In particular, the antibodies are capable of reducing or inhibiting the binding of IgE antibodies to peanut allergens, particularly Ara h 2, Arah 3, and / or Ara h 6 as described herein. Thus, the antibodies or binding fragments thereof according to the present invention can reduce or inhibit the activation of mast cells or basophils, and thereby reduce or prevent the release of mediators (e.g., histamine, lipid mediators, leukotrienes). Thus, the antibodies described herein can inhibit allergic symptoms that typically occur after a patient comes into contact with an allergen (e.g., contact with the eyes, nose, or mouth, or ingestion of food). Thus, the antibodies described herein are capable of reducing, inhibiting, or neutralizing allergen-mediated biological activities. In particular, the antibodies are capable of reducing or inhibiting the binding of IgE antibodies to peanut allergens, particularly Ara h 2, Ara h 3, and / or Arah 6.

[0174] In some embodiments, the CDR or variable region of an antibody or its antigen-binding fragment is a human CDR or variable region sequence or is derived from a human CDR or variable region sequence. Exemplary antibodies 2F8, 7G6, 17H9 and 15E3 (wild type) are human antibodies isolated from human patients. "Human-derived" CDR sequences or VH sequences / VL sequences include engineered human antibody sequences in which mutations are introduced into the original human CDR sequences or VH sequences / VL sequences. For example, the difference between a human-derived CDR and a fully human (wild type) CDR sequence can be that the human-derived CDR contains up to 5, i.e., 1, 2, 3, 4 or 5 mutations, preferably up to 4 mutations, and more preferably up to 3 mutations. For example, a VH sequence or VL sequence derived from a human may differ from a fully human (wild-type) VH sequence or VL sequence in that the VH sequence or VL sequence derived from a human comprises at most 10, i.e. 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 mutations, preferably at most 7 mutations, more preferably at most 5 mutations (e.g. in the framework regions).

[0175] In some embodiments, the antibody or its antigen-binding fragment is a human antibody. In some embodiments, the antibody or its antigen-binding fragment is a monoclonal antibody. For example, the antibody or its antigen-binding fragment can be a human monoclonal antibody.

[0176] Compared with the antibody of non-human origin, human antibody is advantageous because non-human antibody, including chimeric antibody and humanized antibody, can cause adverse immune response, and this can cause nausea, diarrhea and flu-like symptoms.In more serious cases, these side effects may even be fatal.Non-human antibody fragments often cause immune response (anti-drug antibodies (ADA)) in humans, thereby not only causing undesirable side effects, but also reducing the efficacy of non-human antibodies in the human body.In contrast, the antibody recovered from the human body has higher safety because antibody has been shown to have tolerance in the human body, which is combined with the typical excellent affinity maturation of the human immune system.As used herein, the term "human antibody" not only includes the antibody originally found in the class, but also includes its sequence variants, in which specific amino acid residues (rather than whole antibody fragments) are mutated. In contrast to nonhuman antibodies and humanized antibodies, which typically comprise intact antibody fragments of non-human origin (e.g., a complete set of CDR sequences), sequence variants of human antibodies are typically selective / specific mutations within selected antibody fragments (e.g., within CDR or framework regions and / or within constant regions; e.g., to modify antibody affinity, functionality, half-life, etc.).

[0177] For example, compared to the sequences shown in Table 1, the human antibodies according to the present invention may contain only a limited number of mutations per CDR (e.g., no more than 6 per CDR, preferably no more than 5, more preferably no more than 4, even more preferably no more than 3, still more preferably no more than 2, and particularly preferably only single mutations). In the case of more than two mutations, they cannot occur in a continuous manner (to avoid generating non-human sequence segments). The same applies to the framework region (or the entire VH sequence / VL sequence) and the constant region. The constant region can carry, for example, specific modifications known in the art to modify the (Fc-related) function of the antibody, as described below.

[0178] Preferably, the antibody is an IgG antibody or an IgA antibody. IgG and IgA typically compete with IgE for binding sites on allergens, thereby preventing IgE from recognizing allergens by binding to the Fes receptors on the surface of mast cells and basophils. This may include direct competition by binding to the same epitope or competition by steric hindrance. In addition, IgG antibodies bound to allergens can cause cross-linking of Fcs receptors and inhibitory FcγRIIB receptors, resulting in reduced effector cell activity. Therefore, the IgG antibodies and IgA antibodies or their binding fragments according to the present invention can be used to effectively prevent or treat allergies. In some embodiments, the variable regions or CDRs of the antibodies defined herein are derived from (human) IgE antibodies and are transplanted into the scaffold of IgG antibodies or IgA antibodies. Preferably, the scaffold is human IgG or human IgA. Therefore, the variable regions, portions thereof or CDRs can be human and transplanted into an antibody framework, which is preferably of human origin, but of a different antibody type, such as IgG or IgA instead of IgE. Typically, the portion of the variable region derived from humans transplanted into the antibody framework comprises CDRs. Among IgG, IgG1 and IgG4 are preferred.

[0179] Thus, the antibodies or antigen-binding fragments thereof according to the present invention may comprise an Fc portion.The Fc portion may be derived from human sources, for example from human IgA or human IgG, such as human IgG1, human IgG2, human IgG3 and / or human IgG4, for example human IgG1.

[0180] As used herein, the term "Fc portion" refers to a sequence derived from an immunoglobulin heavy chain portion that begins at the hinge region immediately upstream of the papain cleavage site (e.g., residue 216 in native IgG, the first residue of the heavy chain constant region is 114) and ends at the C-terminus of the immunoglobulin heavy chain. Thus, the Fc portion can be a complete Fc portion or a portion thereof (e.g., a domain). A complete Fc portion comprises at least a hinge domain, a CH2 domain, and a CH3 domain (e.g., EU amino acid positions 216 to 446). Additional lysine residues (K) sometimes appear at the terminal C-terminus of the Fc portion, but are typically cleaved from mature antibodies.

[0181] In some embodiments, in the context of the present invention, the Fc portion comprises at least one of the following: a hinge (e.g., upper, middle, and / or lower hinge region) domain, a CH2 domain, a CH3 domain, or a variant thereof, a portion thereof, or a fragment thereof. The Fc portion may comprise at least a hinge domain, a CH2 domain, or a CH3 domain. The Fc portion may be a complete Fc portion. The Fc portion may further comprise one or more amino acid insertions, deletions, or substitutions relative to a naturally occurring Fc portion. For example, at least one of the hinge domain, the CH2 domain, or the CH3 domain (or a portion thereof) may be deleted.

[0182] Those of ordinary skill in the art will appreciate that the Fc portion can be modified so that its amino acid sequence is different from the complete Fc portion of a naturally occurring immunoglobulin molecule while retaining at least one desired function conferred by the naturally occurring Fc portion. These functions include Fc receptor (FcR) binding, antibody half-life regulation, ADCC function, protein A binding, protein G binding, and complement fixation. The portions of the naturally occurring Fc portion that are responsible for and / or necessary for these functions are well known to those skilled in the art. In some embodiments, an antibody according to the present invention comprises a (complete) Fc portion / Fc region, wherein the interaction / binding with the Fc receptor is not impaired.

[0183] Generally, the binding of an antibody to an Fc receptor can be assessed by various methods known to those skilled in the art, such as ELISA (Hessell AJ, Hangartner L, Hunter M, Havenith CEG, Beurskens FJ, Bakker JM, Lanigan CMS, Landucci G, Forthal DN, Parren PWHI, et al.: Fc receptor but notcomplement binding is important in antibody protection against HIV. Nature 2007, 449: 101-104; Grevys A, Bern M, Foss S, Bratlie DB, Moen A, Gunnarsen KS, Aase A, Michaelsen TE, Sandlie I, Andersen JT: Fc Engineering of Human IgG1 for Altered Binding to the Neonatal Fc Receptor Affects Fc Effector Functions. 2015, 194: 5497-5508) or flow cytometry (Perez LG, Costa MR, Todd CA, Haynes BF, Montefiori DC: Utilization of immunoglobulin G Fc receptors by human immunodeficiency virus type 1: a specific role for antibodies against the membrane-proximal external region of gp41. J Virol 2009, 83: 7397-7410; Piccoli L, Campo I, Fregni CS, Rodriguez BMF, Minola A, Sallusto F, LuisettiM, Corti D, Lanzavecchia A: Neutralization and clearance of GM-CSF byautoantibodies in pulmonary alveolar proteinosis. Nat Commun 2015, 6: 1-9).

[0184] In some embodiments, the antibody or its antigen-binding fragment according to the present invention comprises an Fc region. As used herein, the term "Fc region" refers to a portion of an immunoglobulin formed by the Fc portion of two or more antibody heavy chains. For example, the Fc region can be a monomer or a "single-chain" Fc region (i.e., an scFc region). A single-chain Fc region is composed of Fc portions connected within a single polypeptide chain (e.g., encoded in a single continuous nucleic acid sequence). An exemplary scFc region is disclosed in WO 2008 / 143954 A2. The Fc region can be a dimer. A "dimer Fc region" or "dcFc" refers to a dimer formed by the Fc portions of two separate immunoglobulin heavy chains. A dimeric Fc region can be a homodimer of two identical Fc portions (e.g., the Fc region of a naturally occurring immunoglobulin) or a heterodimer of two different Fc portions.

[0185] In some embodiments, the Fc portion or Fc region comprises or consists of an amino acid sequence derived from a human immunoglobulin sequence (e.g., an Fc region or Fc portion from a human IgG molecule). However, the Fc portion or Fc region may comprise one or more amino acids from another mammalian species. For example, a primate Fc portion or primate binding site may be included in the antibody or antigen-binding fragment. Alternatively, one or more murine amino acids may be present in the Fc portion or Fc region.

[0186] The Fc portion of the Fc region can be of the same or different class and / or subclass. For example, the Fc portion can be derived from an immunoglobulin (eg, a human immunoglobulin) of the IgG1, IgG2, IgG3, or IgG4 subclass.

[0187] Thus, the antibodies of the present invention can be of any isotype (e.g., IgA, IgG, IgM, i.e., α heavy chain, γ heavy chain, or μ heavy chain). Preferably, the antibody can be of IgA type or IgG type. In the IgG isotype, the antibody can be of IgG1 subclass, IgG2 subclass, IgG3 subclass, or IgG4 subclass, preferably IgG1 or IgG4. Exemplary sequences of constant regions of IgG1 and IgG4 that can be used for the antibodies described herein are provided in SEQ ID NO: 59 (IgG1) and SEQ ID NO: 60 (IgG4). Thus, the antibodies of the present invention can comprise an amino acid sequence according to SEQ ID NO: 59 or SEQ ID NO: 60, or a sequence variant thereof as described herein. The human IgG4 constant region sequence of SEQ ID NO: 60 includes a stabilizing hinge mutation S228P (S. Angal, DJ King, MW Bodmer, A. Turner, ADG Lawson, G. Roberts, B. Pedley, JR Adair, A single amino acid substitution abolishes the heterogeneity of chimeric mouse / human (IgG4) antibody, Molecular Immunology, Volume 30, Issue 1, 1993, Pages 105-108, ISSN 0161-5890, https: / / doi.org / 10.1016 / 0161-5890(93)90432-B). The antibodies of the present invention may have a kappa light chain or a lambda light chain. Exemplary sequences of constant regions of kappa and lambda light chains that can be used for the antibodies described herein are provided in SEQ ID NO: 61 (Cκ) and SEQ ID NO: 62 (Cλ). Thus, an antibody of the invention may comprise an amino acid sequence according to SEQ ID NO: 61 or SEQ ID NO: 62, or a sequence variant thereof as described herein.

[0188] As described above, the present invention includes antigen binding fragments. The antigen binding fragment may or may not include an Fc portion, particularly a portion of a complete Fc region. In some embodiments, the antibody or its antigen binding fragment is selected from Fab, Fab', F(ab')2, Fv or scFv. For example, F(ab')2 (which can be obtained by pepsin cleavage or recombinant expression) and Fab' (which can be obtained by F(ab')2 or recombinant expression) generally include a hinge region. An exemplary CH1 sequence is provided in SEQ ID NO: 63, which can be used as a constant region in, for example, Fab. Therefore, the antibody or its antigen binding fragment of the present invention may include an amino acid sequence according to SEQ ID NO: 63 or a sequence variant thereof as described herein.

[0189] In some embodiments, the antibody or antigen-binding fragment can be a single-chain antibody (or fragment). The single-chain antibody (or fragment) can encode a complete set of six CDRs, i.e., including three heavy chain CDRs and three light chain CDRs. More specifically, the single-chain antibody (or fragment) can include a heavy chain variable region (VH) and a light chain variable region (VL), for example, including a VH sequence and a VL sequence as described above.

[0190] Variant antibodies are also included within the scope of the present invention. Therefore, variants of the sequences described in this application are also included within the scope of the present invention. These variants include natural variants produced by somatic mutations in vivo during the immune response process, or natural variants produced when immortalized B cell clones are cultured in vitro. Alternatively, variants may arise due to degeneracy of the genetic code, or may arise due to errors in transcription or translation.

[0191] The antibodies or antigen-binding fragments thereof of the present invention can be provided in purified form. Typically, the antibodies or antigen-binding fragments will be present in a composition that is substantially free of other polypeptides, e.g., wherein less than 90% by weight, typically less than 60% by weight, and more typically less than 50% by weight of the composition consists of other polypeptides.

[0192] The antibodies of the present invention can be immunogenic in non-human (or heterologous) hosts, such as mice. In particular, the antibodies can have a unique site that is immunogenic in non-human hosts but not in human hosts. In particular, the antibodies of the present invention for humans include antibodies that cannot be easily isolated from hosts such as mice, goats, rabbits, rats, non-primate mammals, etc., and cannot usually be obtained by humanization or from xenogeneic mice.

[0193] Antibodies of the present invention also include hybrid antibody molecules comprising six CDRs from an antibody of the present invention as defined above and one or more CDRs from another antibody of the antigen. For example, the antibody can be multispecific. In other embodiments, the antibody or its antigen-binding fragment can be monospecific.

[0194] Multispecific antibodies or multispecific antigen-binding fragments

[0195] Thus, the antibodies or antigen-binding fragments thereof described herein may be multispecific antibodies or multispecific antigen-binding fragments.

[0196] As used herein, the term "multi-specificity" refers to the ability to bind to at least two different epitopes, for example, on different antigens or the same antigen. Conventional monospecific IgG antibodies typically have two identical epitope binding sites (paratopes), so they can only bind to the same epitope (and not to different epitopes). On the contrary, multi-specific antibodies have at least two different types of paratopes (antigen binding sites), and therefore can bind to at least two different epitopes. As used herein, "paratope" refers to the antigen binding site (or epitope binding site) of an antibody. In addition, a single "specificity" can refer to one, two, three or more than three identical paratopes in a single antibody (the actual number of paratopes in a single antibody molecule is called "valence"). For example, a single natural IgG antibody is monospecific and bivalent because it has two identical paratopes. Therefore, a multi-specific antibody comprises at least two (different) paratopes. Therefore, the term "multi-specific antibody" refers to an antibody having more than one paratope and having the ability to bind to two or more than two different epitopes. The term "multispecific antibody" particularly includes bispecific antibodies, but generally also includes proteins that bind to three or more different epitopes, ie antibodies with three or more different paratopes, such as antibody scaffolds.

[0197] In particular, the multispecific antibodies or multispecific antigen-binding fragments of the present invention may comprise two or more paratopes, wherein one or more paratopes may be identical, such that all paratopes of the antibody belong to at least two different paratope types, and thus the antibody has at least two specificities. For example, a multispecific antibody or antigen-binding fragment thereof according to the present invention may comprise four paratopes, wherein each two paratopes are identical (i.e., have the same specificity), and thus the antibody or fragment thereof is bispecific and tetravalent (two identical paratopes corresponding to each of the two specificities). Thus, "one specificity" particularly refers to one or more paratopes that exhibit the same specificity (which generally means that such one or more paratopes are identical), and thus, "two specificities" can be achieved by two, three, four, five, six, or more than six paratopes, as long as they only involve two specificities. In some embodiments, the multispecific antibody comprises a single paratope for each specificity (of the at least two specificities), i.e., the multispecific antibody comprises at least two paratopes in total. For example, a bispecific antibody may comprise a single paratope for each of the two specificities, i.e., the antibody comprises two paratopes in total. In other embodiments, the antibody comprises two (identical) paratopes of one or more than one specificity.

[0198] Preferably, the multispecific antibody or multispecific antigen-binding fragment is bispecific, trispecific or tetraspecific. Thus, terms such as "bispecific," "trispecific," "tetraspecific," etc. refer to the number of different epitopes to which an antibody can bind. For example, a "bispecific" antibody has exactly two different specificities (two different antigen-binding sites, each of which can independently occur once or more than once, e.g., twice). For example, a "trispecific" antibody has exactly three different specificities (three different antigen-binding sites, each of which can independently occur once or more than once, e.g., twice). For example, a "tetraspecific" antibody has exactly four different specificities (four different antigen-binding sites, each of which can independently occur once or more than once, e.g., twice).

[0199] Various such multispecific antibody formats and methods for obtaining multispecific antibodies are known in the art. For example, the components of bispecific and trispecific antibodies are described in Xiufeng Wu, Stephen J. Demarest, Buildingblocks for bispecific and trispecific antibodies, Methods, Volume 154, 2019, Pages 3-9, ISSN 1046-2023, https: / / doi.org / 10.1016 / j.ymeth.2018.08.010, which is incorporated herein by reference. Methods for obtaining multispecific antibodies and other multispecific antibody formats are described in Amaral M, Hölper S, Lange C, Jung J, Sjuts H, Weil S, Fischer M, Radoevic K, Rao E. Engineered Technologies and Bioanalysis of multispecific antibody formats. J Appl Bioanal 6(1), 26-51 (2020), which is incorporated herein by reference.

[0200] In some embodiments, the multispecific antibody or multispecific antigen-binding fragment according to the present invention is a bispecific antibody or bispecific antigen-binding fragment. A bispecific antibody comprises (exactly) two specificities. The bispecific antibody in the context of the present invention may be any bispecific antibody format known in the art, such as described in Spiess C., Zhai Q. and Carter PJ (2015) Molecular Immunology 67: 95-106. For example, a bispecific antibody may be a complete antibody, such as a complete IgG-like molecule, or a fragment thereof that is not a complete antibody but retains antibody properties. These antibodies may be small recombinant forms, such as tandem single-chain variable fragment molecules (taFvs), diabodies (Dbs), single-chain diabodies (scDbs) and various other derivatives thereof (e.g., as described in Byrne H. et al. (2013) Trends Biotech, 31 (11): 621-632). Figure 2Various bispecific antibody formats are shown. In some embodiments, the bispecific antibody can be an IgG(H)-scFv fusion, as described in Coloma, M., Morrison, S. Design and production of novel tetravalent bispecific antibodies. Nat Biotechnol 15, 159-163 (1997), https: / / doi.org / 10.1038 / nbt0297-159. Preferred bispecific antibody formats are described in Example 6.

[0201] In some embodiments, the multispecific antibody or multispecific antigen-binding fragment according to the present invention is a trispecific antibody or trispecific antigen-binding fragment. The trispecific antibody comprises (exactly) three specificities. The trispecific antibody in the context of the present invention can be any trispecific antibody format known in the art. In some embodiments, the trispecific antibody can be a heterodimer of IgG(H)-ScFv using a knob-into-hole structure of CH3, which has the same Fab domain, as described in Ridgway JB, Presta LG, Carter P. 'Knobs-into-holes' engineering of antibody CH3 domains for heavy chain heterodimerization. Protein Eng. 1996 Jul; 9(7): 617-21, doi: 10.1093 / protein / 9.7.617. A preferred trispecific antibody format is the trispecific format described in Example 6.

[0202] In some embodiments, the multispecific antibody or multispecific antigen-binding fragment according to the present invention is a tetraspecific antibody or tetraspecific antigen-binding fragment. The tetraspecific antibody comprises (exact) four specificities. The tetraspecific antibody in the context of the present invention can be any tetraspecific antibody format known in the art. In some embodiments, the tetraspecific antibody can be a heterodimer of IgG(H)-scFv and scFv-Fc-scFv using a CH3 with a knob-into-hole structure, as described in Ridgway JB, Presta LG, Carter P. 'Knobs-into-holes' engineering of antibody CH3 domains for heavy chain heterodimerization. Protein Eng. 1996 Jul; 9(7): 617-21, doi: 10.1093 / protein / 9.7.617. In other embodiments, the tetraspecific antibody can be an IgG4 heavy chain heterodimer. Preferred tetraspecific antibody formats are as described in Example 6.

[0203] Typically, a multispecific antibody or multispecific antigen-binding fragment is at least bivalent, i.e., it has at least two paratopes. Preferably, the multispecific antibody or multispecific antigen-binding fragment is bivalent, trivalent, tetravalent, or hexavalent. More preferably, the multispecific antibody or multispecific antigen-binding fragment is tetravalent. Even more preferably, the multispecific antibody or multispecific antigen-binding fragment is tetravalent and bispecific, trispecific, or tetraspecific.

[0204] Preferably, the multispecific antibody or multispecific antigen-binding fragment binds to different, non-overlapping epitopes (specifically) of Ara h 2. Thus, the antigen-binding sites (paratopes) of the multispecific antibody or multispecific antigen-binding fragment preferably target different, non-overlapping epitopes on the same antigen (i.e., Ara h 2). To this end, the antigen-binding sites (paratopes) of the multispecific antibody or multispecific antigen-binding fragment can be selected from four different antibodies, 17H9, 15E3, 2F8, and 7G6, as described above, or variants thereof. As shown in the accompanying Examples, 17H9, 15E3, 2F8, and 7G6 bind to different, non-overlapping epitopes of Ara h 2. Methods for obtaining multispecific antibodies using the binding sites of monospecific antibodies are well known to those skilled in the art, for example as described above.

[0205] Thus, the multispecific antibody or multispecific antigen-binding fragment may comprise at least two of the following:

[0206] (i) an antigen binding site comprising the following sequences of 17H9 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence;

[0207] (ii) an antigen binding site comprising the following sequences of 15E3 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence;

[0208] (iii) an antigen binding site comprising the following sequences of 2F8 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and / or

[0209] (iv) an antigen binding site comprising the following sequences of 7G6 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence.

[0210] In some embodiments, the multispecific antibody or multispecific antigen-binding fragment may comprise (i) an antigen-binding site comprising the following sequences of 17H9, as described above, for example, as described in Tables 1 and 2, or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence, and CDRL3 sequence and / or (b) VH sequence and VL sequence; and (ii) an antigen-binding site comprising the following sequences of (wild-type) 2F8, as described above, for example, as described in Tables 1 and 2, or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence, and CDRL3 sequence and / or (b) VH sequence and VL sequence. Optionally, such an antibody may further comprise an antigen-binding site comprising the CDR sequence and / or VH sequence / VL sequence (or sequence variants thereof) of 15E3, and / or an antigen-binding site comprising the CDR sequence and / or VH sequence / VL sequence (or sequence variants thereof) of 7G6.

[0211] In some embodiments, the multispecific antibody or multispecific antigen-binding fragment may comprise (i) an antigen-binding site comprising the following sequences of 15E3, as described above, for example, as described in Tables 1 and 2, or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence, and CDRL3 sequence and / or (b) VH sequence and VL sequence; and (ii) an antigen-binding site comprising the following sequences of (wild-type) 7G6, as described above, for example, as described in Tables 1 and 2, or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence, and CDRL3 sequence and / or (b) VH sequence and VL sequence. Optionally, such an antibody may further comprise an antigen-binding site comprising the CDR sequence and / or VH sequence / VL sequence (or sequence variants thereof) of 17H9, and / or an antigen-binding site comprising the CDR sequence and / or VH sequence / VL sequence (or sequence variants thereof) of 2F8.

[0212] In some embodiments, the multispecific antibody or multispecific antigen-binding fragment may comprise (i) an antigen-binding site comprising the following sequences of 17H9, as described above, for example, as described in Tables 1 and 2, or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence, and CDRL3 sequence and / or (b) VH sequence and VL sequence; and (ii) an antigen-binding site comprising the following sequences of 15E3, as described above, for example, as described in Tables 1 and 2, or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence, and CDRL3 sequence and / or (b) VH sequence and VL sequence. Optionally, such an antibody may further comprise an antigen-binding site comprising the CDR sequence and / or VH sequence / VL sequence (or sequence variants thereof) of 2F8, and / or an antigen-binding site comprising the CDR sequence and / or VH sequence / VL sequence (or sequence variants thereof) of 7G6.

[0213] Preferably, the multispecific antibody or multispecific antigen-binding fragment may comprise (i) an antigen-binding site comprising the following sequences of 15E3, as described above, for example, as described in Tables 1 and 2, or sequence variants thereof: (a) CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3, and / or (b) VH and VL sequences; and (ii) an antigen-binding site comprising the following sequences of (wild-type) 2F8, as described above, for example, as described in Tables 1 and 2, or sequence variants thereof: (a) CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3, and / or (b) VH and VL sequences. Optionally, such an antibody may further comprise an antigen-binding site comprising the CDR sequences and / or VH / VL sequences (or sequence variants thereof) of 17H9, and / or an antigen-binding site comprising the CDR sequences and / or VH / VL sequences (or sequence variants thereof) of 7G6.

[0214] More preferably, the multispecific antibody or multispecific antigen-binding fragment may comprise (i) an antigen-binding site comprising the following sequences of 17H9, as described above, for example, as described in Tables 1 and 2, or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence, and CDRL3 sequence and / or (b) VH sequence and VL sequence; and (ii) an antigen-binding site comprising the following sequences of (wild-type) 7G6, as described above, for example, as described in Tables 1 and 2, or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence, and CDRL3 sequence and / or (b) VH sequence and VL sequence. Optionally, such an antibody may further comprise an antigen-binding site comprising the CDR sequence and / or VH sequence / VL sequence (or sequence variants thereof) of 15E3, and / or an antigen-binding site comprising the CDR sequence and / or VH sequence / VL sequence (or sequence variants thereof) of 2F8.

[0215] In some embodiments, the multispecific antibody or multispecific antigen-binding fragment may be a bispecific antibody or bispecific antigen-binding fragment comprising:

[0216] (i) an antigen binding site comprising the following sequences of 17H9 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and

[0217] (ii) an antigen binding site comprising the following sequences of 15E3 as described above or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence and CDRL3 sequence and / or (b) VH sequence and VL sequence.

[0218] In some embodiments, the multispecific antibody or multispecific antigen-binding fragment may be a bispecific antibody or bispecific antigen-binding fragment comprising:

[0219] (i) an antigen binding site comprising the following sequences of 17H9 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and

[0220] (iii) an antigen binding site comprising the following sequences of 2F8 as described above, or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence, and CDRL3 sequence and / or (b) VH sequence and VL sequence.

[0221] In some embodiments, the multispecific antibody or multispecific antigen-binding fragment may be a bispecific antibody or bispecific antigen-binding fragment comprising:

[0222] (ii) an antigen binding site comprising the following sequences of 15E3 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and

[0223] (iv) an antigen binding site comprising the following sequences of 7G6 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence.

[0224] In some embodiments, the multispecific antibody or multispecific antigen-binding fragment may be a bispecific antibody or bispecific antigen-binding fragment comprising:

[0225] (iii) an antigen binding site comprising the following sequences of 2F8 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and

[0226] (iv) an antigen binding site comprising the following sequences of 7G6 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence.

[0227] Preferably, the multispecific antibody or multispecific antigen-binding fragment may be a bispecific antibody or bispecific antigen-binding fragment comprising:

[0228] (ii) an antigen binding site comprising the following sequences of 15E3 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and

[0229] (iii) an antigen binding site comprising the following sequences of 2F8 as described above, or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence, and CDRL3 sequence and / or (b) VH sequence and VL sequence.

[0230] More preferably, the multispecific antibody or multispecific antigen-binding fragment may be a bispecific antibody or bispecific antigen-binding fragment comprising:

[0231] (i) an antigen binding site comprising the following sequences of 17H9 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and

[0232] (iv) an antigen binding site comprising the following sequences of 7G6 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence.

[0233] In some embodiments, the multispecific antibody or multispecific antigen-binding fragment may be a trispecific antibody or trispecific antigen-binding fragment comprising:

[0234] (i) an antigen binding site comprising the following sequences of 17H9 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence;

[0235] (ii) an antigen binding site comprising the following sequences of 15E3 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and

[0236] (iii) an antigen binding site comprising the following sequences of 2F8 as described above, or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence, and CDRL3 sequence and / or (b) VH sequence and VL sequence.

[0237] In some embodiments, the multispecific antibody or multispecific antigen-binding fragment may be a trispecific antibody or trispecific antigen-binding fragment comprising:

[0238] (ii) an antigen binding site comprising the following sequences of 15E3 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence;

[0239] (iii) an antigen binding site comprising the following sequences of 2F8 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and

[0240] (iv) an antigen binding site comprising the following sequences of 7G6 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence.

[0241] In some embodiments, the multispecific antibody or multispecific antigen-binding fragment may be a trispecific antibody or trispecific antigen-binding fragment comprising:

[0242] (i) an antigen binding site comprising the following sequences of 17H9 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence;

[0243] (iii) an antigen binding site comprising the following sequences of 2F8 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and

[0244] (iv) an antigen binding site comprising the following sequences of 7G6 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence.

[0245] Preferably, the multispecific antibody or multispecific antigen-binding fragment may be a trispecific antibody or trispecific antigen-binding fragment comprising:

[0246] (i) an antigen binding site comprising the following sequences of 17H9 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence;

[0247] (ii) an antigen binding site comprising the following sequences of 15E3 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and

[0248] (iv) an antigen binding site comprising the following sequences of 7G6 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence.

[0249] Also preferably, the multispecific antibody or multispecific antigen-binding fragment may be a tetraspecific antibody or tetraspecific antigen-binding fragment comprising:

[0250] (i) an antigen binding site comprising the following sequences of 17H9 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence;

[0251] (ii) an antigen binding site comprising the following sequences of 15E3 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence;

[0252] (iii) an antigen binding site comprising the following sequences of 2F8 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and

[0253] (iv) an antigen binding site comprising the following sequences of 7G6 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence.

[0254] The present invention also provides multispecific antibodies or multispecific antigen-binding fragments that bind to different non-overlapping epitopes of Ara h 2, wherein the antibody or antigen-binding fragment comprises at least two of the following:

[0255] (i) an antigen binding site comprising a CDRH1 at least 70% identical to SEQ ID NO: 1, a CDRH2 at least 70% identical to SEQ ID NO: 2, a CDRH3 at least 70% identical to SEQ ID NO: 3, a CDRL1 at least 70% identical to SEQ ID NO: 4, a CDRL2 at least 70% identical to SEQ ID NO: 5, and a CDRL3 at least 70% identical to SEQ ID NO: 6;

[0256] (ii) an antigen binding site comprising a CDRH1 at least 70% identical to SEQ ID NO: 9, a CDRH2 at least 70% identical to SEQ ID NO: 10, a CDRH3 at least 70% identical to SEQ ID NO: 11, a CDRL1 at least 70% identical to SEQ ID NO: 12, a CDRL2 at least 70% identical to SEQ ID NO: 13, and a CDRL3 at least 70% identical to SEQ ID NO: 14;

[0257] (iii) an antigen binding site comprising a CDRH1 at least 70% identical to SEQ ID NO: 17, a CDRH2 at least 70% identical to SEQ ID NO: 18, a CDRH3 at least 70% identical to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 at least 70% identical to SEQ ID NO: 20, a CDRL2 at least 70% identical to SEQ ID NO: 21, and a CDRL3 at least 70% identical to SEQ ID NO: 22; and / or

[0258] (iv) an antigen binding site comprising a CDRH1 at least 70% identical to SEQ ID NO: 25, a CDRH2 at least 70% identical to SEQ ID NO: 26, a CDRH3 at least 70% identical to SEQ ID NO: 27, a CDRL1 at least 70% identical to SEQ ID NO: 28, a CDRL2 at least 70% identical to SEQ ID NO: 29 or SEQ ID NO: 52, and a CDRL3 at least 70% identical to SEQ ID NO: 30.

[0259] Preferably, the multispecific antibody or multispecific antigen-binding fragment comprises at least two of the following:

[0260] (i) an antigen binding site comprising CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5 and CDRL3 according to SEQ ID NO: 6;

[0261] (ii) an antigen binding site comprising CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13 and CDRL3 according to SEQ ID NO: 14;

[0262] (iii) an antigen binding site comprising CDRH1 according to SEQ ID NO: 17, CDRH2 according to SEQ ID NO: 18, CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, CDRL1 according to SEQ ID NO: 20, CDRL2 according to SEQ ID NO: 21 and CDRL3 according to SEQ ID NO: 22; and / or

[0263] (iv) an antigen binding site comprising CDRH1 according to SEQ ID NO: 25, CDRH2 according to SEQ ID NO: 26, CDRH3 according to SEQ ID NO: 27, CDRL1 according to SEQ ID NO: 28, CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52 and CDRL3 according to SEQ ID NO: 30.

[0264] More preferably, the multispecific antibody or multispecific antigen-binding fragment comprises at least two of the following:

[0265] (i) an antigen binding site comprising a VH that is at least 70% identical to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL that is at least 70% identical to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49; wherein preferably CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5 and CDRL3 according to SEQ ID NO: 6 are retained;

[0266] (ii) an antigen binding site comprising a VH that is at least 70% identical to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL that is at least 70% identical to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40; wherein preferably CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13 and CDRL3 according to SEQ ID NO: 14 are retained;

[0267] (iii) an antigen binding site comprising a VH that is at least 70% identical to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL that is at least 70% identical to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43; wherein preferably CDRH1 according to SEQ ID NO: 17, CDRH2 according to SEQ ID NO: 18, CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, CDRL1 according to SEQ ID NO: 20, CDRL2 according to SEQ ID NO: 21 and CDRL3 according to SEQ ID NO: 22 are retained; and / or

[0268] (iv) an antigen binding site comprising a VH that is at least 70% identical to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL that is at least 70% identical to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 54; wherein preferably CDRH1 according to SEQ ID NO: 25, CDRH2 according to SEQ ID NO: 26, CDRH3 according to SEQ ID NO: 27, CDRL1 according to SEQ ID NO: 28, CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52 and CDRL3 according to SEQ ID NO: 30 are retained.

[0269] Even more preferably, the multispecific antibody or multispecific antigen-binding fragment comprises at least two of the following:

[0270] (i) an antigen binding site comprising a VH according to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL according to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49;

[0271] (ii) an antigen binding site comprising a VH according to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL according to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40;

[0272] (iii) an antigen binding site comprising a VH according to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL according to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43; and / or

[0273] (iv) an antigen binding site comprising a VH according to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL according to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 54.

[0274] In some embodiments, the multispecific antibody or multispecific antigen-binding fragment may be a bispecific antibody or bispecific antigen-binding fragment comprising:

[0275] (i) an antigen binding site comprising:

[0276] a CDRH1 at least 70% identical to SEQ ID NO: 1, a CDRH2 at least 70% identical to SEQ ID NO: 2, a CDRH3 at least 70% identical to SEQ ID NO: 3, a CDRL1 at least 70% identical to SEQ ID NO: 4, a CDRL2 at least 70% identical to SEQ ID NO: 5, and a CDRL3 at least 70% identical to SEQ ID NO: 6;

[0277] - in particular CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5 and CDRL3 according to SEQ ID NO: 6;

[0278] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL that is at least 70% identical to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49; wherein preferably CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5 and CDRL3 according to SEQ ID NO: 6 are retained;

[0279] - for example a VH according to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL according to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49; and

[0280] (ii) an antigen binding site comprising:

[0281] a CDRH1 at least 70% identical to SEQ ID NO: 9, a CDRH2 at least 70% identical to SEQ ID NO: 10, a CDRH3 at least 70% identical to SEQ ID NO: 11, a CDRL1 at least 70% identical to SEQ ID NO: 12, a CDRL2 at least 70% identical to SEQ ID NO: 13, and a CDRL3 at least 70% identical to SEQ ID NO: 14;

[0282] - in particular CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13 and CDRL3 according to SEQ ID NO: 14;

[0283] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL that is at least 70% identical to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40; wherein preferably CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13 and CDRL3 according to SEQ ID NO: 14 are retained;

[0284] - for example a VH according to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL according to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40.

[0285] In some embodiments, the multispecific antibody or multispecific antigen-binding fragment may be a bispecific antibody or bispecific antigen-binding fragment comprising:

[0286] (i) an antigen binding site comprising:

[0287] a CDRH1 at least 70% identical to SEQ ID NO: 1, a CDRH2 at least 70% identical to SEQ ID NO: 2, a CDRH3 at least 70% identical to SEQ ID NO: 3, a CDRL1 at least 70% identical to SEQ ID NO: 4, a CDRL2 at least 70% identical to SEQ ID NO: 5, and a CDRL3 at least 70% identical to SEQ ID NO: 6;

[0288] - in particular CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5 and CDRL3 according to SEQ ID NO: 6;

[0289] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL that is at least 70% identical to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49; wherein preferably CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5 and CDRL3 according to SEQ ID NO: 6 are retained;

[0290] - for example a VH according to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL according to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49; and

[0291] (iii) an antigen binding site comprising:

[0292] a CDRH1 at least 70% identical to SEQ ID NO: 17, a CDRH2 at least 70% identical to SEQ ID NO: 18, a CDRH3 at least 70% identical to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 at least 70% identical to SEQ ID NO: 20, a CDRL2 at least 70% identical to SEQ ID NO: 21, and a CDRL3 at least 70% identical to SEQ ID NO: 22;

[0293] - in particular a CDRH1 according to SEQ ID NO: 17, a CDRH2 according to SEQ ID NO: 18, a CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 according to SEQ ID NO: 20, a CDRL2 according to SEQ ID NO: 21 and a CDRL3 according to SEQ ID NO: 22;

[0294] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL that is at least 70% identical to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43; wherein preferably CDRH1 according to SEQ ID NO: 17, CDRH2 according to SEQ ID NO: 18, CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, CDRL1 according to SEQ ID NO: 20, CDRL2 according to SEQ ID NO: 21 and CDRL3 according to SEQ ID NO: 22 are retained;

[0295] - for example a VH according to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL according to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43.

[0296] In some embodiments, the multispecific antibody or multispecific antigen-binding fragment may be a bispecific antibody or bispecific antigen-binding fragment comprising:

[0297] (ii) an antigen binding site comprising:

[0298] a CDRH1 at least 70% identical to SEQ ID NO: 9, a CDRH2 at least 70% identical to SEQ ID NO: 10, a CDRH3 at least 70% identical to SEQ ID NO: 11, a CDRL1 at least 70% identical to SEQ ID NO: 12, a CDRL2 at least 70% identical to SEQ ID NO: 13, and a CDRL3 at least 70% identical to SEQ ID NO: 14;

[0299] - in particular CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13 and CDRL3 according to SEQ ID NO: 14;

[0300] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL that is at least 70% identical to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40; wherein preferably CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13 and CDRL3 according to SEQ ID NO: 14 are retained;

[0301] - for example a VH according to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL according to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40; and

[0302] (iv) an antigen binding site comprising:

[0303] a CDRH1 at least 70% identical to SEQ ID NO: 25, a CDRH2 at least 70% identical to SEQ ID NO: 26, a CDRH3 at least 70% identical to SEQ ID NO: 27, a CDRL1 at least 70% identical to SEQ ID NO: 28, a CDRL2 at least 70% identical to SEQ ID NO: 29 or SEQ ID NO: 52, and a CDRL3 at least 70% identical to SEQ ID NO: 30;

[0304] - in particular CDRH1 according to SEQ ID NO: 25, CDRH2 according to SEQ ID NO: 26, CDRH3 according to SEQ ID NO: 27, CDRL1 according to SEQ ID NO: 28, CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52 and CDRL3 according to SEQ ID NO: 30;

[0305] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL that is at least 70% identical to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 54; wherein preferably CDRH1 according to SEQ ID NO: 25, CDRH2 according to SEQ ID NO: 26, CDRH3 according to SEQ ID NO: 27, CDRL1 according to SEQ ID NO: 28, CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52 and CDRL3 according to SEQ ID NO: 30 are retained;

[0306] - for example a VH according to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL according to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 54.

[0307] In some embodiments, the multispecific antibody or multispecific antigen-binding fragment may be a bispecific antibody or bispecific antigen-binding fragment comprising:

[0308] (iii) an antigen binding site comprising:

[0309] a CDRH1 at least 70% identical to SEQ ID NO: 17, a CDRH2 at least 70% identical to SEQ ID NO: 18, a CDRH3 at least 70% identical to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 at least 70% identical to SEQ ID NO: 20, a CDRL2 at least 70% identical to SEQ ID NO: 21, and a CDRL3 at least 70% identical to SEQ ID NO: 22;

[0310] - in particular a CDRH1 according to SEQ ID NO: 17, a CDRH2 according to SEQ ID NO: 18, a CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 according to SEQ ID NO: 20, a CDRL2 according to SEQ ID NO: 21 and a CDRL3 according to SEQ ID NO: 22;

[0311] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL that is at least 70% identical to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43; wherein preferably CDRH1 according to SEQ ID NO: 17, CDRH2 according to SEQ ID NO: 18, CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, CDRL1 according to SEQ ID NO: 20, CDRL2 according to SEQ ID NO: 21 and CDRL3 according to SEQ ID NO: 22 are retained;

[0312] - for example a VH according to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL according to SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43; and

[0313] (iv) an antigen binding site comprising:

[0314] a CDRH1 at least 70% identical to SEQ ID NO: 25, a CDRH2 at least 70% identical to SEQ ID NO: 26, a CDRH3 at least 70% identical to SEQ ID NO: 27, a CDRL1 at least 70% identical to SEQ ID NO: 28, a CDRL2 at least 70% identical to SEQ ID NO: 29 or SEQ ID NO: 52, and a CDRL3 at least 70% identical to SEQ ID NO: 30

[0315] - in particular a CDRH1 according to SEQ ID NO: 25, a CDRH2 according to SEQ ID NO: 26, a CDRH3 according to SEQ ID NO: 27, a CDRL1 according to SEQ ID NO: 28, a CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52 and a CDRL3 according to SEQ ID NO: 30;

[0316] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL that is at least 70% identical to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 54; wherein preferably CDRH1 according to SEQ ID NO: 25, CDRH2 according to SEQ ID NO: 26, CDRH3 according to SEQ ID NO: 27, CDRL1 according to SEQ ID NO: 28, CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52 and CDRL3 according to SEQ ID NO: 30 are retained;

[0317] - for example a VH according to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL according to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 54.

[0318] Preferably, the multispecific antibody or multispecific antigen-binding fragment may be a bispecific antibody or bispecific antigen-binding fragment comprising:

[0319] (ii) an antigen binding site comprising:

[0320] a CDRH1 at least 70% identical to SEQ ID NO: 9, a CDRH2 at least 70% identical to SEQ ID NO: 10, a CDRH3 at least 70% identical to SEQ ID NO: 11, a CDRL1 at least 70% identical to SEQ ID NO: 12, a CDRL2 at least 70% identical to SEQ ID NO: 13, and a CDRL3 at least 70% identical to SEQ ID NO: 14;

[0321] - in particular CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13 and CDRL3 according to SEQ ID NO: 14;

[0322] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL that is at least 70% identical to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40; wherein preferably CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13 and CDRL3 according to SEQ ID NO: 14 are retained;

[0323] - for example a VH according to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL according to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40; and

[0324] (iii) an antigen binding site comprising:

[0325] a CDRH1 at least 70% identical to SEQ ID NO: 17, a CDRH2 at least 70% identical to SEQ ID NO: 18, a CDRH3 at least 70% identical to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 at least 70% identical to SEQ ID NO: 20, a CDRL2 at least 70% identical to SEQ ID NO: 21, and a CDRL3 at least 70% identical to SEQ ID NO: 22;

[0326] - in particular a CDRH1 according to SEQ ID NO: 17, a CDRH2 according to SEQ ID NO: 18, a CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 according to SEQ ID NO: 20, a CDRL2 according to SEQ ID NO: 21 and a CDRL3 according to SEQ ID NO: 22;

[0327] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL that is at least 70% identical to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43; wherein preferably CDRH1 according to SEQ ID NO: 17, CDRH2 according to SEQ ID NO: 18, CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, CDRL1 according to SEQ ID NO: 20, CDRL2 according to SEQ ID NO: 21 and CDRL3 according to SEQ ID NO: 22 are retained;

[0328] - for example a VH according to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL according to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43.

[0329] More preferably, the multispecific antibody or multispecific antigen-binding fragment may be a bispecific antibody or bispecific antigen-binding fragment comprising:

[0330] (i) an antigen binding site comprising:

[0331] a CDRH1 at least 70% identical to SEQ ID NO: 1, a CDRH2 at least 70% identical to SEQ ID NO: 2, a CDRH3 at least 70% identical to SEQ ID NO: 3, a CDRL1 at least 70% identical to SEQ ID NO: 4, a CDRL2 at least 70% identical to SEQ ID NO: 5, and a CDRL3 at least 70% identical to SEQ ID NO: 6;

[0332] - in particular CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5 and CDRL3 according to SEQ ID NO: 6;

[0333] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL that is at least 70% identical to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49; wherein preferably CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5 and CDRL3 according to SEQ ID NO: 6 are retained;

[0334] - for example a VH according to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL according to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49; and

[0335] (iv) an antigen binding site comprising:

[0336] a CDRH1 at least 70% identical to SEQ ID NO: 25, a CDRH2 at least 70% identical to SEQ ID NO: 26, a CDRH3 at least 70% identical to SEQ ID NO: 27, a CDRL1 at least 70% identical to SEQ ID NO: 28, a CDRL2 at least 70% identical to SEQ ID NO: 29 or SEQ ID NO: 52, and a CDRL3 at least 70% identical to SEQ ID NO: 30;

[0337] - in particular a CDRH1 according to SEQ ID NO: 25, a CDRH2 according to SEQ ID NO: 26, a CDRH3 according to SEQ ID NO: 27, a CDRL1 according to SEQ ID NO: 28, a CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52 and a CDRL3 according to SEQ ID NO: 30;

[0338] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL that is at least 70% identical to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 54; wherein preferably CDRH1 according to SEQ ID NO: 25, CDRH2 according to SEQ ID NO: 26, CDRH3 according to SEQ ID NO: 27, CDRL1 according to SEQ ID NO: 28, CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52 and CDRL3 according to SEQ ID NO: 30 are retained;

[0339] - for example a VH according to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL according to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 54.

[0340] In some embodiments, the multispecific antibody or multispecific antigen-binding fragment may be a trispecific antibody or trispecific antigen-binding fragment comprising:

[0341] (i) an antigen binding site comprising:

[0342] a CDRH1 at least 70% identical to SEQ ID NO: 1, a CDRH2 at least 70% identical to SEQ ID NO: 2, a CDRH3 at least 70% identical to SEQ ID NO: 3, a CDRL1 at least 70% identical to SEQ ID NO: 4, a CDRL2 at least 70% identical to SEQ ID NO: 5, and a CDRL3 at least 70% identical to SEQ ID NO: 6;

[0343] - in particular CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5 and CDRL3 according to SEQ ID NO: 6;

[0344] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL that is at least 70% identical to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49; wherein preferably CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5 and CDRL3 according to SEQ ID NO: 6 are retained;

[0345] - for example a VH according to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL according to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49;

[0346] (ii) an antigen binding site comprising:

[0347] a CDRH1 at least 70% identical to SEQ ID NO: 9, a CDRH2 at least 70% identical to SEQ ID NO: 10, a CDRH3 at least 70% identical to SEQ ID NO: 11, a CDRL1 at least 70% identical to SEQ ID NO: 12, a CDRL2 at least 70% identical to SEQ ID NO: 13, and a CDRL3 at least 70% identical to SEQ ID NO: 14;

[0348] - in particular CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13 and CDRL3 according to SEQ ID NO: 14;

[0349] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL that is at least 70% identical to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40; wherein preferably CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13 and CDRL3 according to SEQ ID NO: 14 are retained;

[0350] - for example a VH according to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL according to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40; and

[0351] (iii) an antigen binding site comprising:

[0352] a CDRH1 at least 70% identical to SEQ ID NO: 17, a CDRH2 at least 70% identical to SEQ ID NO: 18, a CDRH3 at least 70% identical to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 at least 70% identical to SEQ ID NO: 20, a CDRL2 at least 70% identical to SEQ ID NO: 21, and a CDRL3 at least 70% identical to SEQ ID NO: 22;

[0353] - in particular a CDRH1 according to SEQ ID NO: 17, a CDRH2 according to SEQ ID NO: 18, a CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 according to SEQ ID NO: 20, a CDRL2 according to SEQ ID NO: 21 and a CDRL3 according to SEQ ID NO: 22;

[0354] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL that is at least 70% identical to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43; wherein preferably CDRH1 according to SEQ ID NO: 17, CDRH2 according to SEQ ID NO: 18, CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, CDRL1 according to SEQ ID NO: 20, CDRL2 according to SEQ ID NO: 21 and CDRL3 according to SEQ ID NO: 22 are retained;

[0355] - for example a VH according to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL according to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43.

[0356] In some embodiments, the multispecific antibody or multispecific antigen-binding fragment may be a trispecific antibody or trispecific antigen-binding fragment comprising:

[0357] (i) an antigen binding site comprising:

[0358] a CDRH1 at least 70% identical to SEQ ID NO: 1, a CDRH2 at least 70% identical to SEQ ID NO: 2, a CDRH3 at least 70% identical to SEQ ID NO: 3, a CDRL1 at least 70% identical to SEQ ID NO: 4, a CDRL2 at least 70% identical to SEQ ID NO: 5, and a CDRL3 at least 70% identical to SEQ ID NO: 6;

[0359] - in particular CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5 and CDRL3 according to SEQ ID NO: 6;

[0360] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL that is at least 70% identical to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49; wherein preferably CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5 and CDRL3 according to SEQ ID NO: 6 are retained;

[0361] - for example a VH according to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL according to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49;

[0362] (iii) an antigen binding site comprising:

[0363] a CDRH1 at least 70% identical to SEQ ID NO: 17, a CDRH2 at least 70% identical to SEQ ID NO: 18, a CDRH3 at least 70% identical to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 at least 70% identical to SEQ ID NO: 20, a CDRL2 at least 70% identical to SEQ ID NO: 21, and a CDRL3 at least 70% identical to SEQ ID NO: 22;

[0364] - in particular a CDRH1 according to SEQ ID NO: 17, a CDRH2 according to SEQ ID NO: 18, a CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 according to SEQ ID NO: 20, a CDRL2 according to SEQ ID NO: 21 and a CDRL3 according to SEQ ID NO: 22;

[0365] In some embodiments, a VH having at least 70% identity to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50, and SEQ ID NO: 53; and a VL having at least 70% identity to any one of SEQ ID NO: 24, SEQ ID NO: 42, and SEQ ID NO: 43; wherein preferably CDRH1 according to SEQ ID NO: 17, CDRH2 according to SEQ ID NO: 18, CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, CDRL1 according to SEQ ID NO: 20, CDRL2 according to SEQ ID NO: 21, and CDRL3 according to SEQ ID NO: 22 are retained;

[0366] - for example a VH according to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL according to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43; and

[0367] (iv) an antigen binding site comprising:

[0368] a CDRH1 at least 70% identical to SEQ ID NO: 25, a CDRH2 at least 70% identical to SEQ ID NO: 26, a CDRH3 at least 70% identical to SEQ ID NO: 27, a CDRL1 at least 70% identical to SEQ ID NO: 28, a CDRL2 at least 70% identical to SEQ ID NO: 29 or SEQ ID NO: 52, and a CDRL3 at least 70% identical to SEQ ID NO: 30;

[0369] - in particular a CDRH1 according to SEQ ID NO: 25, a CDRH2 according to SEQ ID NO: 26, a CDRH3 according to SEQ ID NO: 27, a CDRL1 according to SEQ ID NO: 28, a CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52 and a CDRL3 according to SEQ ID NO: 30;

[0370] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL that is at least 70% identical to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 54; wherein preferably CDRH1 according to SEQ ID NO: 25, CDRH2 according to SEQ ID NO: 26, CDRH3 according to SEQ ID NO: 27, CDRL1 according to SEQ ID NO: 28, CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52 and CDRL3 according to SEQ ID NO: 30 are retained;

[0371] - for example a VH according to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL according to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 54.

[0372] In some embodiments, the multispecific antibody or multispecific antigen-binding fragment may be a trispecific antibody or trispecific antigen-binding fragment comprising:

[0373] (ii) an antigen binding site comprising:

[0374] a CDRH1 at least 70% identical to SEQ ID NO: 9, a CDRH2 at least 70% identical to SEQ ID NO: 10, a CDRH3 at least 70% identical to SEQ ID NO: 11, a CDRL1 at least 70% identical to SEQ ID NO: 12, a CDRL2 at least 70% identical to SEQ ID NO: 13, and a CDRL3 at least 70% identical to SEQ ID NO: 14;

[0375] - in particular CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13 and CDRL3 according to SEQ ID NO: 14;

[0376] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL that is at least 70% identical to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40; wherein preferably CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13 and CDRL3 according to SEQ ID NO: 14 are retained;

[0377] - for example a VH according to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL according to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40;

[0378] (iii) an antigen binding site comprising:

[0379] a CDRH1 at least 70% identical to SEQ ID NO: 17, a CDRH2 at least 70% identical to SEQ ID NO: 18, a CDRH3 at least 70% identical to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 at least 70% identical to SEQ ID NO: 20, a CDRL2 at least 70% identical to SEQ ID NO: 21, and a CDRL3 at least 70% identical to SEQ ID NO: 22;

[0380] - in particular a CDRH1 according to SEQ ID NO: 17, a CDRH2 according to SEQ ID NO: 18, a CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 according to SEQ ID NO: 20, a CDRL2 according to SEQ ID NO: 21 and a CDRL3 according to SEQ ID NO: 22;

[0381] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL that is at least 70% identical to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43; wherein preferably CDRH1 according to SEQ ID NO: 17, CDRH2 according to SEQ ID NO: 18, CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, CDRL1 according to SEQ ID NO: 20, CDRL2 according to SEQ ID NO: 21 and CDRL3 according to SEQ ID NO: 22 are retained;

[0382] - for example a VH according to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL according to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43; and

[0383] (iv) an antigen binding site comprising:

[0384] a CDRH1 at least 70% identical to SEQ ID NO: 25, a CDRH2 at least 70% identical to SEQ ID NO: 26, a CDRH3 at least 70% identical to SEQ ID NO: 27, a CDRL1 at least 70% identical to SEQ ID NO: 28, a CDRL2 at least 70% identical to SEQ ID NO: 29 or SEQ ID NO: 52, and a CDRL3 at least 70% identical to SEQ ID NO: 30;

[0385] - in particular a CDRH1 according to SEQ ID NO: 25, a CDRH2 according to SEQ ID NO: 26, a CDRH3 according to SEQ ID NO: 27, a CDRL1 according to SEQ ID NO: 28, a CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52 and a CDRL3 according to SEQ ID NO: 30;

[0386] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL that is at least 70% identical to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 54; wherein preferably CDRH1 according to SEQ ID NO: 25, CDRH2 according to SEQ ID NO: 26, CDRH3 according to SEQ ID NO: 27, CDRL1 according to SEQ ID NO: 28, CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52 and CDRL3 according to SEQ ID NO: 30 are retained;

[0387] - for example a VH according to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL according to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 54.

[0388] Preferably, the multispecific antibody or multispecific antigen-binding fragment may be a trispecific antibody or trispecific antigen-binding fragment comprising:

[0389] (i) an antigen binding site comprising:

[0390] a CDRH1 at least 70% identical to SEQ ID NO: 1, a CDRH2 at least 70% identical to SEQ ID NO: 2, a CDRH3 at least 70% identical to SEQ ID NO: 3, a CDRL1 at least 70% identical to SEQ ID NO: 4, a CDRL2 at least 70% identical to SEQ ID NO: 5, and a CDRL3 at least 70% identical to SEQ ID NO: 6;

[0391] - in particular CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5 and CDRL3 according to SEQ ID NO: 6;

[0392] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL that is at least 70% identical to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49; wherein preferably CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5 and CDRL3 according to SEQ ID NO: 6 are retained;

[0393] - for example a VH according to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL according to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49;

[0394] (ii) an antigen binding site comprising:

[0395] a CDRH1 at least 70% identical to SEQ ID NO: 9, a CDRH2 at least 70% identical to SEQ ID NO: 10, a CDRH3 at least 70% identical to SEQ ID NO: 11, a CDRL1 at least 70% identical to SEQ ID NO: 12, a CDRL2 at least 70% identical to SEQ ID NO: 13, and a CDRL3 at least 70% identical to SEQ ID NO: 14;

[0396] - in particular CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13 and CDRL3 according to SEQ ID NO: 14;

[0397] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL that is at least 70% identical to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40; wherein preferably CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13 and CDRL3 according to SEQ ID NO: 14 are retained;

[0398] - for example a VH according to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL according to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40; and

[0399] (iv) an antigen binding site comprising:

[0400] a CDRH1 at least 70% identical to SEQ ID NO: 25, a CDRH2 at least 70% identical to SEQ ID NO: 26, a CDRH3 at least 70% identical to SEQ ID NO: 27, a CDRL1 at least 70% identical to SEQ ID NO: 28, a CDRL2 at least 70% identical to SEQ ID NO: 29 or SEQ ID NO: 52, and a CDRL3 at least 70% identical to SEQ ID NO: 30;

[0401] - in particular a CDRH1 according to SEQ ID NO: 25, a CDRH2 according to SEQ ID NO: 26, a CDRH3 according to SEQ ID NO: 27, a CDRL1 according to SEQ ID NO: 28, a CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52 and a CDRL3 according to SEQ ID NO: 30;

[0402] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL that is at least 70% identical to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 54; wherein preferably CDRH1 according to SEQ ID NO: 25, CDRH2 according to SEQ ID NO: 26, CDRH3 according to SEQ ID NO: 27, CDRL1 according to SEQ ID NO: 28, CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52 and CDRL3 according to SEQ ID NO: 30 are retained;

[0403] - for example a VH according to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL according to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 54.

[0404] Also preferably, the multispecific antibody or multispecific antigen-binding fragment may be a tetraspecific antibody or tetraspecific antigen-binding fragment comprising:

[0405] (i) an antigen binding site comprising:

[0406] a CDRH1 at least 70% identical to SEQ ID NO: 1, a CDRH2 at least 70% identical to SEQ ID NO: 2, a CDRH3 at least 70% identical to SEQ ID NO: 3, a CDRL1 at least 70% identical to SEQ ID NO: 4, a CDRL2 at least 70% identical to SEQ ID NO: 5, and a CDRL3 at least 70% identical to SEQ ID NO: 6;

[0407] - in particular CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5 and CDRL3 according to SEQ ID NO: 6;

[0408] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL that is at least 70% identical to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49; wherein preferably CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5 and CDRL3 according to SEQ ID NO: 6 are retained;

[0409] - for example a VH according to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL according to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49;

[0410] (ii) an antigen binding site comprising:

[0411] a CDRH1 at least 70% identical to SEQ ID NO: 9, a CDRH2 at least 70% identical to SEQ ID NO: 10, a CDRH3 at least 70% identical to SEQ ID NO: 11, a CDRL1 at least 70% identical to SEQ ID NO: 12, a CDRL2 at least 70% identical to SEQ ID NO: 13, and a CDRL3 at least 70% identical to SEQ ID NO: 14;

[0412] - in particular CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13 and CDRL3 according to SEQ ID NO: 14;

[0413] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL that is at least 70% identical to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40; wherein preferably CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13 and CDRL3 according to SEQ ID NO: 14 are retained;

[0414] - for example a VH according to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL according to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40;

[0415] (iii) an antigen binding site comprising:

[0416] a CDRH1 at least 70% identical to SEQ ID NO: 17, a CDRH2 at least 70% identical to SEQ ID NO: 18, a CDRH3 at least 70% identical to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 at least 70% identical to SEQ ID NO: 20, a CDRL2 at least 70% identical to SEQ ID NO: 21, and a CDRL3 at least 70% identical to SEQ ID NO: 22;

[0417] - in particular a CDRH1 according to SEQ ID NO: 17, a CDRH2 according to SEQ ID NO: 18, a CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 according to SEQ ID NO: 20, a CDRL2 according to SEQ ID NO: 21 and a CDRL3 according to SEQ ID NO: 22;

[0418] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL that is at least 70% identical to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43; wherein preferably CDRH1 according to SEQ ID NO: 17, CDRH2 according to SEQ ID NO: 18, CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, CDRL1 according to SEQ ID NO: 20, CDRL2 according to SEQ ID NO: 21 and CDRL3 according to SEQ ID NO: 22 are retained;

[0419] - for example a VH according to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL according to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43; and

[0420] (iv) an antigen binding site comprising:

[0421] a CDRH1 at least 70% identical to SEQ ID NO: 25, a CDRH2 at least 70% identical to SEQ ID NO: 26, a CDRH3 at least 70% identical to SEQ ID NO: 27, a CDRL1 at least 70% identical to SEQ ID NO: 28, a CDRL2 at least 70% identical to SEQ ID NO: 29 or SEQ ID NO: 52, and a CDRL3 at least 70% identical to SEQ ID NO: 30;

[0422] - in particular a CDRH1 according to SEQ ID NO: 25, a CDRH2 according to SEQ ID NO: 26, a CDRH3 according to SEQ ID NO: 27, a CDRL1 according to SEQ ID NO: 28, a CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52 and a CDRL3 according to SEQ ID NO: 30;

[0423] - in some embodiments, a VH with at least 70% identity to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL with at least 70% identity to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 54; wherein preferably retained are CDRH1 according to SEQ ID NO: 25, CDRH2 according to SEQ ID NO: 26, CDRH3 according to SEQ ID NO: 27, CDRL1 according to SEQ ID NO: 28, CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52 and CDRL3 according to SEQ ID NO: 30;

[0424] - for example a VH according to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL according to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 54.

[0425] More preferably, the multispecific antibody or multispecific antigen-binding fragment may be a tetraspecific antibody or tetraspecific antigen-binding fragment comprising:

[0426] (i) an antigen binding site comprising a CDRH1 that is at least 70% identical to SEQ ID NO: 1, a CDRH2 that is at least 70% identical to SEQ ID NO: 2, a CDRH3 that is at least 70% identical to SEQ ID NO: 3, a CDRL1 that is at least 70% identical to SEQ ID NO: 4, a CDRL2 that is at least 70% identical to SEQ ID NO: 5, and a CDRL3 that is at least 70% identical to SEQ ID NO: 6; in particular a CDRH1 according to SEQ ID NO: 1, a CDRH2 according to SEQ ID NO: 2, a CDRH3 according to SEQ ID NO: 3, a CDRL1 according to SEQ ID NO: 4, a CDRL2 according to SEQ ID NO: 5, and a CDRL3 according to SEQ ID NO: 6;

[0427] (ii) an antigen binding site comprising a CDRH1 that is at least 70% identical to SEQ ID NO: 9, a CDRH2 that is at least 70% identical to SEQ ID NO: 10, a CDRH3 that is at least 70% identical to SEQ ID NO: 11, a CDRL1 that is at least 70% identical to SEQ ID NO: 12, a CDRL2 that is at least 70% identical to SEQ ID NO: 13, and a CDRL3 that is at least 70% identical to SEQ ID NO: 14; in particular a CDRH1 according to SEQ ID NO: 9, a CDRH2 according to SEQ ID NO: 10, a CDRH3 according to SEQ ID NO: 11, a CDRL1 according to SEQ ID NO: 12, a CDRL2 according to SEQ ID NO: 13, and a CDRL3 according to SEQ ID NO: 14;

[0428] (iii) an antigen binding site comprising a CDRH1 which is at least 70% identical to SEQ ID NO: 17, a CDRH2 which is at least 70% identical to SEQ ID NO: 18, a CDRH3 which is at least 70% identical to SEQ ID NO: 51, a CDRL1 which is at least 70% identical to SEQ ID NO: 20, a CDRL2 which is at least 70% identical to SEQ ID NO: 21 and a CDRL3 which is at least 70% identical to SEQ ID NO: 22, in particular a CDRH1 according to SEQ ID NO: 17, a CDRH2 according to SEQ ID NO: 18, a CDRH3 according to SEQ ID NO: 51, a CDRL1 according to SEQ ID NO: 20, a CDRL2 according to SEQ ID NO: 21 and a CDRL3 according to SEQ ID NO: 22; and

[0429] (iv) an antigen binding site comprising a CDRH1 that is at least 70% identical to SEQ ID NO: 25, a CDRH2 that is at least 70% identical to SEQ ID NO: 26, a CDRH3 that is at least 70% identical to SEQ ID NO: 27, a CDRL1 that is at least 70% identical to SEQ ID NO: 28, a CDRL2 that is at least 70% identical to SEQ ID NO: 29 or SEQ ID NO: 52, and a CDRL3 that is at least 70% identical to SEQ ID NO: 30; in particular a CDRH1 according to SEQ ID NO: 25, a CDRH2 according to SEQ ID NO: 26, a CDRH3 according to SEQ ID NO: 27, a CDRL1 according to SEQ ID NO: 28, a CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52, and a CDRL3 according to SEQ ID NO: 30.

[0430] Even more preferably, the multispecific antibody or multispecific antigen-binding fragment may be a tetraspecific antibody or tetraspecific antigen-binding fragment comprising:

[0431] (i) an antigen binding site comprising a VH that is at least 70% identical to SEQ ID NO: 45; and a VL that is at least 70% identical to SEQ ID NO: 49; wherein preferably CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5 and CDRL3 according to SEQ ID NO: 6 are retained; for example a VH according to SEQ ID NO: 45 and a VL according to SEQ ID NO: 49;

[0432] (ii) an antigen binding site comprising a VH that is at least 70% identical to SEQ ID NO: 38; and a VL that is at least 70% identical to SEQ ID NO: 39; wherein preferably CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13 and CDRL3 according to SEQ ID NO: 14 are retained; for example a VH according to SEQ ID NO: 38 and a VL according to SEQ ID NO: 39;

[0433] (iii) an antigen binding site comprising a VH that is at least 70% identical to SEQ ID NO: 53; and a VL that is at least 70% identical to SEQ ID NO: 43; wherein preferably CDRH1 according to SEQ ID NO: 17, CDRH2 according to SEQ ID NO: 18, CDRH3 according to SEQ ID NO: 51, CDRL1 according to SEQ ID NO: 20, CDRL2 according to SEQ ID NO: 21 and CDRL3 according to SEQ ID NO: 22 are retained; for example a VH according to SEQ ID NO: 53 and a VL according to SEQ ID NO: 43; and

[0434] (iv) an antigen binding site comprising a VH that is at least 70% identical to SEQ ID NO: 34; and a VL that is at least 70% identical to SEQ ID NO: 35 or SEQ ID NO: 54; wherein preferably CDRH1 according to SEQ ID NO: 25, CDRH2 according to SEQ ID NO: 26, CDRH3 according to SEQ ID NO: 27, CDRL1 according to SEQ ID NO: 28, CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52 and CDRL3 according to SEQ ID NO: 30 are retained; for example a VH according to SEQ ID NO: 34 and a VL according to SEQ ID NO: 35 or SEQ ID NO: 54.

[0435] In other words, the antigen binding site (paratope) of the multispecific antibody or multispecific antigen-binding fragment can be selected from four different antibodies 17H9, 15E3, 2F8 and 7G6 or variants thereof as described above, in particular as shown in Tables 1 and 2.

[0436] In some embodiments, the multispecific antibody or multispecific antigen-binding fragment is bispecific and comprises two different antigen-binding sites selected from (i) to (iv). In use, this bispecific antibody can be combined with a second antibody, which comprises one or two remaining antigen-binding sites selected from (i) to (iv) (i.e., combined with one or two binding antigen-binding sites selected from (i) to (iv) that are not included in the (first) bispecific antibody). For example, two bispecific antibodies can be combined, each containing two different antigen-binding sites selected from (i) to (iv), so that the combination of two bispecific antibodies comprises all four antigen-binding sites of (i) to (iv). Similarly, the bispecific antibody can be combined with one or two monospecific antibodies comprising one of the remaining antigen-binding sites. For combination, the antibodies can be included in the same composition or different compositions (but administered in the combined treatment regimen).

[0437] Preferably, the multispecific antibody or multispecific antigen-binding fragment is trispecific and comprises three different antigen-binding sites selected from (i) to (iv).

[0438] Also preferably, the multispecific antibody or multispecific antigen-binding fragment is tetraspecific and comprises four different antigen-binding sites according to (i), (ii), (iii) and (iv).

[0439] Nucleic Acids

[0440] In another aspect, the present invention also provides a nucleic acid molecule comprising a polynucleotide encoding the antibody or antigen-binding fragment thereof according to the present invention as described above.

[0441] In some embodiments, the nucleic acid molecule comprises one or more than one polynucleotide encoding an exemplary antibody of the invention as described herein (e.g., as described above, particularly as described in Tables 1 and 2), or a sequence variant thereof (e.g., having at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identity as described above).

[0442] Table 3 below shows exemplary nucleic acid sequences encoding the CDR sequences and VH sequences / VL sequences of exemplary antibodies described herein.

[0443]

[0444] Table 3: SEQ ID NOs for polynucleotide sequences encoding the CDR sequences and VH sequences / VL sequences of fully human antibodies 17H9, 15E3, 2F8, and 7G6. For 2F8, SEQ ID NO: 82 encodes the wild-type CDRH3, while SEQ ID NO: 88 encodes the variant CDRH3. The respective VHs are encoded by SEQ ID NO: 86 (wild-type VH) and SEQ ID NO: 89 (variant VH). For 7G6, SEQ ID NO: 94 encodes the wild-type CDRL2, while SEQ ID NO: 98 encodes the variant CDRL2. The respective VLs are encoded by SEQ ID NO: 97 (wild-type VL) and SEQ ID NO: 99 (variant VL).

[0445] The example of nucleic acid molecule and / or polynucleotide includes for example recombinant polynucleotide, carrier, oligonucleotide, RNA molecule such as rRNA, mRNA, miRNA, siRNA or tRNA, or DNA molecule such as cDNA. Nucleic acid can encode the light chain and / or heavy chain of antibody (or single-chain antibody). In other words, the light chain and heavy chain of antibody can be encoded by the same nucleic acid molecule (for example, for single-chain antibody or antibody with separated heavy chain and light chain in bicistronic mode, or containing expression components of more than one ribosome entry site such as IRES). Alternatively, the light chain and heavy chain of antibody can be encoded by different nucleic acid molecules. In a similar manner, for multispecific antibodies comprising two or more immunoglobulin chains, different chains can be encoded by the same nucleic acid molecule (for example, in a multicistronic mode or comprising expression components of more than one ribosome entry site such as IRES). Alternatively, the different immunoglobulin chains of multispecific antibody can be encoded by different nucleic acid molecules.

[0446] Due to the redundancy of genetic code, the present invention also includes sequence variants of the nucleotide sequence encoding the same amino acid sequence. The polynucleotides (or complete nucleic acid molecules) encoding antibodies can be optimized for the expression of antibodies. For example, the codon optimization of nucleotide sequences can be used to improve the translation efficiency of antibodies produced in expression systems. In addition, nucleic acid molecules can include heterologous elements (that is, elements that do not appear on the same nucleic acid molecule with the coding sequence of antibody (heavy chain or light chain) in nature). For example, nucleic acid molecules can include heterologous promoter elements, heterologous enhancer elements, heterologous UTR (for example, for optimal translation / expression) elements, heterologous poly (A) tail elements, heterologous DNA insulator elements etc.

[0447] A nucleic acid molecule is a molecule that contains nucleic acid components. The term nucleic acid molecule generally refers to a DNA molecule or an RNA molecule. It can be used synonymously with the term "polynucleotide," i.e., a nucleic acid molecule can be composed of a polynucleotide encoding an antibody. Alternatively, a nucleic acid molecule can contain other elements in addition to a polynucleotide encoding an antibody. Typically, a nucleic acid molecule is a polymer that contains or consists of nucleotide monomers that are covalently linked to each other via phosphodiester bonds of a sugar / phosphate backbone. The term "nucleic acid molecule" also includes modified nucleic acid molecules, such as base-modified, sugar-modified, or backbone-modified DNA or RNA molecules.

[0448] Typically, nucleic acid molecules can be manipulated to insert, delete or change certain nucleic acid sequences. Variations in such manipulations include, but are not limited to, introduction of restriction sites, modification of codon usage, addition or optimization of transcription and / or translation regulatory sequences, etc. Nucleic acids can also be changed to change the encoded amino acids. For example, it may be useful to introduce one or more than one (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) amino acid substitutions, deletions, and / or insertions into the amino acid sequence of an antibody. Such point mutations can modify effector functions, antigen binding affinity, post-translational modifications, immunogenicity, etc., and amino acids can be introduced to connect covalent groups (e.g., labels), or tags can be introduced (e.g., for purification purposes). Alternatively, mutations in nucleic acid sequences can be "silent," i.e., not reflected in the amino acid sequence due to the redundancy of the genetic code. In general, mutations can be introduced into specific sites or randomly introduced, and then selected (e.g., molecular evolution). For example, one or more than one nucleic acid encoding any light or heavy chain of an (exemplary) antibody can be randomly or directed mutated to introduce different properties into the encoded amino acids. Such changes may be the result of an iterative process in which the initial changes are retained and new changes are introduced at other nucleotide positions. Furthermore, changes achieved in separate steps may be combined.

[0449] In some embodiments, the polynucleotides encoding the antibodies or antigen-binding fragments thereof (or (complete) nucleic acid molecules) can be codon optimized. Those skilled in the art are aware of various tools for codon optimization, such as those described in: Ju Xin Chin, Bevan Kai-Sheng Chung, Dong-Yup Lee, CodonOptimization OnLine (COOL): a web-based multi-objective optimization platformfor synthetic gene design, Bioinformatics, Volume 30, Issue 15, 1 August 2014, Pages 2210-2212; or in: Grote A, Hiller K, Scheer M, Munch R, Nortemann B, Hempel DC, Jahn D, JCat: a novel tool to adapt codon usage of a target gene to its potential expression host. Nucleic Acids Res. 2005 Jul 1; 33 (Web Server issue): W526-31; or, for example, Genscript's OptimumGene TM algorithm (as described in US 2011 / 0081708 A1).

[0450] For example, the nucleic acid molecule of the present invention can comprise a nucleic acid sequence as set forth in any one of SEQ ID NO: 64 to SEQ ID NO: 99, or a sequence variant thereof having at least 70%, at least 75%, at least 80%, at least 85%, at least 88%, at least 90%, at least 92%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity. Thus, the nucleic acid molecule can encode any of the exemplary antibodies 17H9, 15E3, 2F8, and 7G6 described herein (by combining the sequences shown in Table 3), or sequence variants thereof.

[0451] The present invention also provides multiple nucleic acid molecules encoding antibodies or antigen-binding fragments thereof as described herein, wherein each nucleic acid molecule (in the multiple nucleic acid molecules) comprises a polynucleotide encoding an immunoglobulin chain of an antibody or antigen-binding fragment thereof. Thus, multiple nucleic acid molecules together encode (all immunoglobulin chains of) an antibody or antigen-binding fragment thereof as described herein. In some embodiments, multiple nucleic acid molecules encoding an antibody or antigen-binding fragment thereof as described herein can be a combination of a first nucleic acid molecule and a second nucleic acid molecule, wherein the first nucleic acid molecule comprises a polynucleotide encoding a heavy chain of an antibody or antigen-binding fragment thereof of the present invention; and the second nucleic acid molecule comprises a polynucleotide encoding the corresponding light chain of the same antibody or antigen-binding fragment thereof.

[0452] In general, the above description of the (general) features of the nucleic acid molecules of the present invention is correspondingly applicable to the nucleic acid molecules in the multiple nucleic acid molecules. Therefore, one or more polynucleotides encoding the immunoglobulin chains of an antibody or its antigen-binding fragment can be codon optimized. For example, multiple nucleic acid molecules can include a nucleotide sequence as shown in any one of SEQ ID NO: 64 to SEQ ID NO: 99; or a sequence variant thereof having at least 70%, at least 75%, at least 80%, at least 85%, at least 88%, at least 90%, at least 92%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity. Therefore, multiple nucleic acid molecules can encode any one of the exemplary antibodies 17H9, 15E3, 2F8 and 7G6 (by combining the sequences shown in Table 3) as described herein or their sequence variants.

[0453] carrier

[0454] Also included within the scope of the present invention are vectors, such as expression vectors, comprising a nucleic acid molecule according to the invention or a plurality of nucleic acid molecules according to the invention. Typically, the vector comprises a nucleic acid molecule as described above.

[0455] The present invention also provides a plurality of carriers comprising a plurality of nucleic acid molecules according to the present invention as described above. Therefore, each carrier in a plurality of carriers can comprise one or more than one nucleic acid molecule in a plurality of nucleic acid molecules according to the present invention as described above. In some embodiments, a plurality of carriers can be a combination of a first carrier and a second carrier, wherein the first carrier comprises the first nucleic acid molecule (for the combination of nucleic acid molecule) as described above, and the second carrier comprises the second nucleic acid molecule (for the combination of nucleic acid molecule) as described above.

[0456] A vector is typically a recombinant nucleic acid molecule, i.e., a nucleic acid molecule that does not exist in nature. Therefore, a vector can include heterologous elements (i.e., sequence elements from different sources in nature). For example, a vector can include a multiple cloning site element, a heterologous promoter element, a heterologous enhancer element, a heterologous selection marker (to identify cells containing the vector relative to cells that do not contain the vector) element, a heterologous replication origin element, a heterologous DNA insulator element, etc. In the context of the present invention, a vector is suitable for containing or containing a desired nucleic acid sequence. Such a vector can be a storage vector, an expression vector, a cloning vector, a transfer vector, etc. A storage vector is a vector that allows for convenient storage of nucleic acid molecules. Therefore, a vector can include a sequence corresponding to, for example, a desired antibody (heavy chain and / or light chain) according to the present invention. An expression vector can be used to produce an expression product, such as RNA, such as mRNA, or a peptide, polypeptide, or protein. For example, an expression vector can include a sequence required for transcription of a vector sequence fragment, such as a (heterologous) promoter sequence. A cloning vector is typically a vector containing a cloning site, which can be used to integrate a nucleic acid sequence into a vector. A cloning vector can be, for example, a plasmid vector or a phage vector. Transfer vectors can be vectors suitable for transferring nucleic acid molecules to cells or organisms, for example viral vectors. In the context of the present invention, vectors can be, for example, RNA vectors or DNA vectors. For example, vectors in the sense of the present application comprise cloning sites, selective markers, for example antibiotic resistance factors, and sequences suitable for vector replication, for example replication origins. The vector in the context of the present application can be a plasmid vector.

[0457] As used herein, the term "vector" may also refer to a delivery vector, such as viral delivery or non-viral delivery for nucleic acid of the present invention. Alternatively, it may refer to a viral delivery system or a non-viral delivery system. Therefore, the present invention also provides a delivery vector / system comprising a nucleic acid molecule as described above (or comprising an expression vector as described above). The delivery vector / system may be viral or non-viral. Various examples of viral and non-viral delivery vectors / delivery systems are known in the art and are described in, for example, Nayerossadat N, Maedeh T, Ali PA. Viral and nonviral delivery systems for gene delivery. Adv Biomed Res. 2012; 1: 27. doi: 10.4103 / 2277-9175.98152, which is incorporated herein by reference. Non-limiting examples of viral delivery vectors / delivery systems include retroviral vectors; adenoviral vectors; adeno-associated virus (AAV) vectors, including helper-dependent adenoviral vectors and hybrid adenoviral vectors; herpes simplex virus vectors; lentiviral vectors; poxvirus vectors and Epstein-Barr virus vectors. Among viral vectors, adenoviral vectors and adeno-associated virus (AAV) vectors are preferred. Non-limiting examples of non-viral delivery vectors / delivery systems include chemical methods and non-chemical methods. Non-chemical delivery includes physical methods, such as electroporation and other methods of instantaneous penetration of cell membranes by mechanical, electrical, ultrasonic, fluid dynamic or laser-based energy; naked DNA delivery or naked RNA delivery; gene gun; fluid dynamic delivery; ultrasonic delivery and magnetic infection. Chemical non-viral delivery systems include cationic particles, particularly cationic lipids / liposomes, cationic polymers and lipid / polymer systems. In non-viral vectors / systems, cationic liposomes are preferred.

[0458] cell

[0459] In other aspects, the present invention also provides (host) cells expressing an antibody or antigen-binding fragment thereof according to the present invention; and / or comprising a vector (or multiple vectors) according to the present invention. The (host) cell can be an isolated cell that is not part of the human or animal body, such as a cell line or an engineered cell. The cell can express one or more nucleic acids or one or more vectors of the present invention in a recombinant manner, for example, in a heterologous manner (i.e., the cell / cell type does not naturally express the antibody or antigen-binding fragment).

[0460] Examples of such cells include, but are not limited to, eukaryotic cells, such as yeast cells, animal cells, or plant cells. Other examples of such cells include, but are not limited to, prokaryotic cells, such as Escherichia coli (E. coli.). In some embodiments, the cell is a mammalian cell, such as a mammalian cell line. Examples include human cells, CHO cells, HEK293 cells, PER.C6 cells, NSO cells, human hepatocytes, myeloma cells, or hybridoma cells.

[0461] Cells can be transfected with a vector according to the present invention, for example, with an expression vector. The term "transfection" refers to the introduction of a nucleic acid molecule, such as a DNA molecule or an RNA (e.g., mRNA) molecule into a cell, for example, into a eukaryotic cell or a prokaryotic cell. In the context of the present invention, the term "transfection" includes any method known to those skilled in the art for introducing a nucleic acid molecule into a cell, for example, into a mammalian cell. These methods include, for example, electroporation, lipofection, for example, based on cationic lipids and / or cationic liposomes, calcium phosphate precipitation, nanoparticle-based transfection, virus-based transfection, or based on cationic polymers such as DEAE-dextran or polyethyleneimine. In some embodiments, the introduction is non-viral.

[0462] In addition, cells of the present invention can be stably or transiently transfected with vectors according to the present invention, for example, to express an antibody according to the present invention. In some embodiments, cells are stably transfected with vectors of the present invention encoding an antibody according to the present invention. In other embodiments, cells are transiently transfected with vectors of the present invention encoding an antibody according to the present invention.

[0463] Therefore, the present invention also provides recombinant host cells that heterologously express the antibodies of the present invention or their antigen-binding fragments. For example, the cell can be another species different from the antibody (e.g., CHO cells expressing human antibodies). In some embodiments, the cell type of the cell does not express (such) antibodies in nature. In addition, the host cell can confer post-translational modifications (PTMs; e.g., glycosylation) that are not present in the antibody in its native state. Such PTMs can lead to functional differences (e.g., reduced immunogenicity). Therefore, the antibodies of the present invention or their antigen-binding fragments may have post-translational modifications that are different from naturally occurring antibodies (e.g., antibodies of human immune responses).

[0464] Antibody preparation

[0465] Antibodies according to the present invention can be prepared by any method known in the art. For example, general methods for preparing monoclonal antibodies using hybridoma technology are well known (Kohler, G. and Milstein, C., 1975; Kozbar et al., 1983).

[0466] Standard techniques of molecular biology can be used to prepare DNA sequences encoding the antibodies or antigen-binding fragments of the present invention. The desired DNA sequence can be synthesized in whole or in part, for example, using oligonucleotide synthesis techniques. Site-directed mutagenesis techniques and polymerase chain reaction (PCR) techniques can be used as appropriate.

[0467] Any suitable host cell / vector system can be used to express the DNA sequence encoding the antibody molecule of the present invention. Eukaryotic host cell expression systems, such as mammalian host cell expression systems can be used to prepare antibody molecules, such as complete antibody molecules. Suitable mammalian host cells include, but are not limited to, CHO cells, HEK293 cells, PER.C6 cells, NSO cells, myeloma cells, or hybridoma cells. In addition, prokaryotic host cell expression systems, such as bacterial host cell expression systems can be used to prepare antibody molecules, such as complete antibody molecules. Suitable bacterial host cells include, but are not limited to, Escherichia coli cells.

[0468] Thus, the present invention provides a method for preparing an antibody or antigen-binding fragment thereof according to the present invention or one or more immunoglobulin chains thereof, said method comprising

[0469] (i) cultivating the host cell as described above; and

[0470] (ii) isolating the antibody or one or more immunoglobulin chains thereof from the culture.

[0471] In other words, the present invention also provides a method for preparing an antibody molecule according to the invention, which comprises culturing a (heterologous) host cell comprising a vector encoding a nucleic acid of the invention, in particular under conditions suitable for protein expression from a DNA encoding an antibody molecule of the invention, and isolating the antibody molecule.

[0472] In order to prepare an antibody comprising a heavy chain and a light chain, a host cell, such as a cell line, can be transfected with two vectors, wherein the first vector encodes a light chain polypeptide and the second vector encodes a heavy chain polypeptide, such as a polypeptide as described above. Alternatively, a single vector can be used that comprises sequences encoding light chain polypeptides and heavy chain polypeptides (e.g., for single-chain antibodies or in a bicistronic manner). Similarly, if a multispecific antibody having two or more immunoglobulin chains is to be expressed, multiple vectors can be used.

[0473] Therefore, the present invention also provides a method for preparing a recombinant cell, comprising the steps of: (i) providing one or more nucleic acids encoding an antibody of the present invention; (ii) inserting the nucleic acid into an expression vector, and (iii) transfecting the vector into a (heterologous) host cell to allow expression of the antibody of interest in the host cell. The nucleic acid of step (i) may, but need not, be manipulated to introduce restriction sites, to alter codon usage and / or to optimize transcription and / or translation regulatory sequences.

[0474] In addition, the present invention also provides a method for preparing a transfected host cell, comprising the step of transfecting the host cell with one or more nucleic acids encoding an antibody of interest. Thus, the process of first preparing one or more nucleic acids and then transfecting the host cell with them can be performed by different people in different places (e.g., different countries) at different times.

[0475] These recombinant cells of the present invention can then be used for expression and culture purposes. They are particularly suitable for antibody expression in large-scale pharmaceutical production. They can also be used as active ingredients in pharmaceutical compositions. Any suitable culture technique can be used, including but not limited to static culture, roller bottle culture, ascites culture, hollow fiber bioreactor cartridges, modular microfermenters, stirred tanks, microcarrier culture, ceramic core perfusion, and the like.

[0476] The transfected host cells can be eukaryotic cells, including yeast cells and animal cells, particularly mammalian cells (e.g., CHO cells, NSO cells, human cells such as PER.C6 cells, HEK293 cells or HKB-11 cells, myeloma cells or human hepatocytes), as well as plant cells. In some embodiments, the transfected host cells are mammalian cells, such as human cells. In some embodiments, the expression host can glycosylate the antibodies of the invention, particularly using carbohydrate structures that are not immunogenic in humans. In some embodiments, the transfected host cells can be grown in serum-free medium. In other embodiments, the transfected host cells can be grown in culture in the absence of animal-derived products. The transfected host cells can also be cultured to obtain cell lines.

[0477] The present invention also provides a method for preparing an antibody of interest, comprising the steps of culturing or subculturing a transfected host cell population, such as a stably transfected host cell population, under conditions that express the antibody of interest, and optionally, purifying the antibody of interest. The transfected host cell population can be prepared by the following method: (i) providing one or more nucleic acids encoding a selected antibody of interest, (ii) inserting the one or more nucleic acids into an expression vector, (iii) transfecting the vector into a host cell capable of expressing the antibody of interest, and (iv) culturing or subculturing the transfected host cells containing the inserted nucleic acids to produce the antibody of interest.

[0478] In some embodiments, antibodies according to the present invention can be prepared by (i) expressing a nucleic acid sequence according to the present invention in a host cell, for example by using a vector (or host cell) according to the present invention, and (ii) isolating the expressed antibody product. In addition, the method can include (iii) purifying the isolated antibody.

[0479] Therefore, after preparation, if desired, the antibody can be further purified using filtration, centrifugation and various chromatographic methods such as HPLC or affinity chromatography. Techniques for purifying antibodies such as monoclonal antibodies, including techniques for preparing pharmaceutical grade antibodies, are well known in the art.

[0480] Compositions and kits

[0481] The present invention also provides a composition comprising one or more of the following:

[0482] (i) an antibody or antigen-binding fragment thereof of the present invention;

[0483] (ii) a nucleic acid or nucleic acids of the invention;

[0484] (iii) a vector or vectors of the present invention; or

[0485] (iv) a cell expressing the antibody according to the present invention or a cell comprising the vector according to the present invention.

[0486] The composition can be used for therapeutic purposes or diagnostic purposes. Thus, the composition can be a pharmaceutical composition or a diagnostic composition. The composition can include a (pharmaceutically acceptable) excipient, diluent or carrier.

[0487] Therefore, the present invention also provides a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof according to the invention, a nucleic acid or nucleic acids according to the invention, a vector or vectors according to the invention, and / or a cell according to the invention.

[0488] The pharmaceutical composition may also optionally contain a pharmaceutically acceptable carrier, diluent, and / or excipient. While a carrier or excipient may facilitate administration, it should not itself induce the production of antibodies that are harmful to the individual receiving the composition. It should also not be toxic. Suitable carriers can be large, slowly metabolized macromolecules such as proteins, polypeptides, liposomes, polysaccharides, polylactic acid, polyglycolic acid, polymeric amino acids, amino acid copolymers, and inactive viral particles. In some embodiments, the pharmaceutically acceptable carrier, diluent, and / or excipient in the pharmaceutical composition is not an active ingredient with respect to peanut allergy.

[0489] Pharmaceutically acceptable salts may be used, for example, inorganic acid salts such as hydrochlorides, hydrobromides, phosphates and sulfates, or organic acid salts such as acetates, propionates, malonates and benzoates.

[0490] Pharmaceutically acceptable carriers in pharmaceutical compositions may additionally contain liquids such as water, saline, glycerol, and ethanol. In addition, auxiliary substances such as wetting agents or emulsifiers or pH buffering substances may be present in these compositions. These carriers enable pharmaceutical compositions to be formulated into tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, and suspensions for ingestion by a subject.

[0491] The pharmaceutical composition can be prepared in various forms. For example, the composition can be prepared as an injectable, or a liquid solution or suspension. It can also be prepared in a solid form suitable for solution or suspension in a liquid carrier before injection (for example, similar to Synagis TM and Herceptin ® The composition can be prepared for topical administration, for example, as an ointment, cream, or powder. The composition can be prepared for oral administration, for example, as a tablet or capsule, as a spray, or as a syrup (optionally flavored). The composition can be prepared for pulmonary administration using a powder or spray, for example, as an inhaler. The composition can be prepared as a suppository or vaginal suppository. The composition can be prepared for nasal administration, ear administration, or ophthalmic administration, for example, as drops. The composition can be in the form of a kit designed so that the combined composition is reconstituted just before administration to a subject. For example, the lyophilized antibody can be provided in the form of a kit together with sterile water or a sterile buffer.

[0492] In some embodiments, the (sole) active ingredient in the composition is an antibody as described herein. Therefore, it may be susceptible to degradation in the digestive tract. Therefore, if the composition is to be administered by a route using the digestive tract, the composition may contain an agent that protects the antibody from degradation and releases the antibody when it is absorbed by the gastrointestinal tract.

[0493] A detailed discussion of pharmaceutically acceptable carriers can be found in Gennaro (2000) Remington: The Science and Practice of Pharmacy, 20th edition, ISBN: 0683306472.

[0494] The present invention also provides a method for preparing a pharmaceutical composition comprising the steps of: (i) preparing an antibody of the present invention; and (ii) mixing the purified antibody with one or more pharmaceutically acceptable excipients, diluents or carriers.

[0495] In other embodiments, the method of preparing a pharmaceutical composition comprises the step of mixing the antibody with one or more pharmaceutically acceptable carriers, wherein the antibody is a monoclonal antibody.

[0496] The pharmaceutical composition may typically have a pH of 5.5 to 8.5, and in some embodiments, may be 6 to 8, for example, about 7. The pH may be maintained by using a buffer. The composition may be sterile and / or pyrogen-free. The composition may be isotonic to humans. In some embodiments, the pharmaceutical composition is provided in a sealed container.

[0497] The invention encompasses compositions in a variety of administration forms, including but not limited to those suitable for parenteral administration, such as by injection or infusion, such as by bolus injection or continuous infusion. When the product is intended for injection or infusion, it may be in the form of a suspension, solution, or emulsion in an oily or aqueous medium, and may contain formulations such as suspending agents, preservatives, stabilizers, and / or dispersants. Alternatively, the antibody may be in a dry form for reconstitution with a suitable sterile liquid prior to use.

[0498] A carrier is generally understood to be a material suitable for storing, transporting and / or administering a compound, such as a pharmaceutically active compound, particularly an antibody as described herein. For example, a carrier can be a physiologically acceptable liquid that is suitable for storing, transporting and / or administering a pharmaceutically active compound, particularly an antibody as described herein. Once formulated, the composition can be administered directly to a subject. In some embodiments, the composition is suitable for administration to a mammal, such as a human subject.

[0499] In particular, if packaged in a multidose form, the pharmaceutical composition may include an antimicrobial agent. It may include a detergent, such as Tween (polysorbate), such as Tween 80. Detergents are typically present at low levels, for example, less than 0.01%. The composition may also include a sodium salt (e.g., sodium chloride) to create tension. For example, a typical NaCl concentration is 10 ± 2 mg / ml.

[0500] In addition, in particular, if the pharmaceutical composition is to be lyophilized or contains material reconstituted from a lyophilized material, the pharmaceutical composition may contain, for example, about 15 mg / ml to 30 mg / ml (e.g., 25 mg / ml) of a sugar alcohol (e.g., mannitol) or a disaccharide (e.g., sucrose or trehalose). Prior to lyophilization, the pH of the composition for lyophilization may be adjusted to 5 to 8, or 5.5 to 7, or about 6.1.

[0501] The pharmaceutical composition can be administered by many routes, including but not limited to oral, intravenous, intramuscular, intraarterial, intramedullary, intraperitoneal, intrathecal, intraventricular, transdermal, percutaneous, topical, subcutaneous, intranasal, enteral, sublingual, intravaginal or rectal routes. Optionally, the pharmaceutical composition can be prepared for oral administration, for example, as a tablet, capsule, etc., prepared for topical administration, or prepared as an injection, for example, as a liquid solution or suspension. In some embodiments, the pharmaceutical composition is an injection. Also included are solid forms suitable for solutions or suspensions in liquid media before injection, for example, the pharmaceutical composition can be in a lyophilized form.

[0502] For injection, such as intravenous injection, skin injection or subcutaneous injection or injection at the affected part, the active ingredient can be in the form of an acceptable aqueous solution for parenteral administration, which does not contain pyrogens and has suitable pH, isotonicity and stability. Those skilled in the art can well use, for example, isotonic carriers such as sodium chloride injection, Ringer's injection, lactated Ringer's injection to prepare suitable solutions. If necessary, preservatives, stabilizers, buffers, antioxidants and / or other additives can be included. Whether it is an antibody, peptide, nucleic acid molecule, or another pharmaceutically useful compound for an individual, it is usually administered in an "effective amount", such as a "preventive effective amount" or a "therapeutic effective amount" (depending on the circumstances), which is enough to show the benefit to the individual. The actual amount applied, the rate of application and the time course of administration will depend on the nature and severity of the treated. For injection, a pharmaceutical composition can be provided, for example, in a pre-filled syringe.

[0503] The pharmaceutical composition can also be orally administered in any orally acceptable dosage form, including but not limited to capsules, tablets, aqueous suspensions or aqueous solutions. For oral tablets, commonly used carriers include lactose and corn starch. Lubricants, such as magnesium stearate, are also typically added. For oral administration in capsule form, useful diluents include lactose and dried corn starch. When an oral aqueous suspension is desired, the active ingredient, i.e., the antibody as defined above, is combined with an emulsifier and a suspending agent. If desired, certain sweeteners, flavorings, or coloring agents may also be added.

[0504] The pharmaceutical composition can also be applied topically, particularly when the therapeutic target includes an area or organ that is easily accessible by topical application, for example, including accessible epithelial tissue. For each of these areas and organs, suitable topical formulations are easily prepared. For topical application, the pharmaceutical composition can be formulated into a suitable ointment, which comprises a pharmaceutical composition suspended or dissolved in one or more than one carrier, particularly its components as defined above. The carrier for topical application includes but is not limited to mineral oil, liquid petrolatum, white petrolatum, propylene glycol, polyoxyethylene, polyoxypropylene compound, emulsifying wax and water. Alternatively, the pharmaceutical composition can be formulated into a suitable lotion or emulsifiable paste. Suitable carriers include but are not limited to mineral oil, sorbitan monostearate, polysorbate 60, cetyl esters wax, cetearyl alcohol, 2-octyldodecanol, benzyl alcohol and water.

[0505] The dosage regimen can be a single dose regimen or a multiple dose regimen. For a single dose, such as a daily dose, a weekly dose, or a monthly dose, the amount of the antibody in the pharmaceutical composition may not exceed 1 g or 500 mg. In some embodiments, for a single dose, the amount of the antibody in the pharmaceutical composition may not exceed 200 mg or 100 mg. For example, for a single dose, the amount of the antibody in the pharmaceutical composition may not exceed 50 mg.

[0506] In some embodiments, a composition may comprise an antibody of the invention, wherein the antibody may comprise at least 50% by weight (e.g., 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) of the total protein in the composition. In the composition, the antibody may be in purified form.

[0507] As an alternative to delivering antibodies for therapeutic purposes, nucleic acids (typically DNA) encoding the monoclonal antibodies of interest can be delivered to a subject so that the nucleic acids can be expressed in situ in the subject to provide the desired therapeutic effect. Suitable gene therapy and nucleic acid delivery vectors are known in the art.

[0508] Pharmaceutical compositions generally comprise an "effective" amount of one or more than one antibody as described herein, i.e., an amount sufficient to treat, improve, alleviate or prevent a desired disease or condition or to exhibit a detectable therapeutic effect. The therapeutic effect also includes reducing or alleviating pathogenic efficacy or physical symptoms. The precise effective amount for any particular object will depend on its size, weight and health status, the nature and extent of the condition, and the combination of the therapeutic method or therapeutic method selected for administration. The effective amount for a given situation is determined by routine experiments and is within the judgment of the clinician. The effective dose can generally be from about 0.005 mg / kg to about 100 mg / kg, for example, from about 0.0075 mg / kg to about 50 mg / kg or from about 0.01 mg / kg to about 10 mg / kg. In some embodiments, relative to the body weight (e.g., in kg) of the individual administered, the effective dose will be an antibody (e.g., the amount of the antibody in the pharmaceutical composition) of about 0.02 mg / kg to about 5 mg / kg.

[0509] In addition, the pharmaceutical composition may also include other active ingredients, which may be other antibodies or components that are not antibodies. In other embodiments, the pharmaceutical composition may not include other active ingredients (except the above-mentioned antibodies of the present invention or respective nucleic acids, vectors or cells).

[0510] Thus, a pharmaceutical composition may contain one or more than one other active ingredient. The antibodies of the present invention may be present in the same pharmaceutical composition as the other active ingredients, or the antibody may be contained in a first pharmaceutical composition and the other active ingredients may be contained in a second pharmaceutical composition different from the first pharmaceutical composition. Thus, if more than one other active ingredient is envisioned, each additional active ingredient and antibody may be contained in a different pharmaceutical composition. These different pharmaceutical compositions may be combined / administered simultaneously, or used at separate times, or administered in separate locations (e.g., separate parts of the body).

[0511] The antibody and other active ingredients can provide an additive therapeutic effect, such as a synergistic therapeutic effect. The term "synergistic" is used to describe a combined effect of two or more active agents that is greater than the sum of the individual effects of each individual active agent. Thus, where the combined effect of two or more agents results in "synergistic inhibition" of an activity or process, the inhibition of that activity or process is greater than the sum of the inhibitory effects of each individual active agent. The term "synergistic therapeutic effect" refers to a therapeutic effect observed with a combination of two or more treatment methods that (as measured by any one of a number of parameters) is greater than the sum of the individual therapeutic effects observed with each individual treatment method.

[0512] Preferably, the composition comprises at least two different antibodies or antigen-binding fragments thereof that bind to different, non-overlapping epitopes of Ara h 2. More preferably, the composition comprises (exactly) three different antibodies or antigen-binding fragments thereof that bind to different, non-overlapping epitopes of Ara h 2. Even more preferably, the composition comprises (exactly) four different antibodies or antigen-binding fragments thereof that bind to different, non-overlapping epitopes of Ara h 2. To this end, the antibodies contained in the composition can be selected from the four different antibodies 17H9, 15E3, 2F8 and 7G6 or variants thereof as described above, for example, in Tables 1 and 2. As shown in the accompanying Examples, 17H9, 15E3, 2F8 and 7G6 bind to different, non-overlapping epitopes of Ara h 2.

[0513] Thus, the composition may comprise at least two of the following:

[0514] (i) an antibody or antigen-binding fragment thereof comprising the following sequences of 17H9 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence;

[0515] (ii) an antibody or antigen-binding fragment thereof comprising the following sequences of 15E3 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence;

[0516] (iii) an antibody or antigen-binding fragment thereof comprising the following sequences of 2F8 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and / or

[0517] (iv) an antibody or antigen-binding fragment thereof comprising the following sequences of 7G6 as described above or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence and CDRL3 sequence and / or (b) VH sequence and VL sequence.

[0518] In some embodiments, the composition comprises (exactly) two different antibodies, i.e., comprises:

[0519] (i) an antibody or antigen-binding fragment thereof comprising the following sequences of 17H9 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and

[0520] (ii) an antibody or antigen-binding fragment thereof comprising the following sequences of 15E3 as described above or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence and CDRL3 sequence and / or (b) VH sequence and VL sequence.

[0521] In some embodiments, the composition comprises (exactly) two different antibodies, i.e., comprises:

[0522] (i) an antibody or antigen-binding fragment thereof comprising the following sequences of 17H9 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and

[0523] (iii) an antibody or antigen-binding fragment thereof comprising the following sequences of 2F8 as described above or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence and CDRL3 sequence and / or (b) VH sequence and VL sequence.

[0524] In some embodiments, the composition comprises (exactly) two different antibodies, i.e., comprises:

[0525] (ii) an antibody or antigen-binding fragment thereof comprising the following sequences of 15E3 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and

[0526] (iv) an antibody or antigen-binding fragment thereof comprising the following sequences of 7G6 as described above or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence and CDRL3 sequence and / or (b) VH sequence and VL sequence.

[0527] In some embodiments, the composition comprises (exactly) two different antibodies, i.e., comprises:

[0528] (iii) an antibody or antigen-binding fragment thereof comprising the following sequences of 2F8 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and

[0529] (iv) an antibody or antigen-binding fragment thereof comprising the following sequences of 7G6 as described above or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence and CDRL3 sequence and / or (b) VH sequence and VL sequence.

[0530] Preferably, the composition comprises (exactly) two different antibodies, i.e. comprises:

[0531] (ii) an antibody or antigen-binding fragment thereof comprising the following sequences of 15E3 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and

[0532] (iii) an antibody or antigen-binding fragment thereof comprising the following sequences of 2F8 as described above or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence and CDRL3 sequence and / or (b) VH sequence and VL sequence.

[0533] More preferably, the composition comprises (exactly) two different antibodies, i.e. comprises:

[0534] (i) an antibody or antigen-binding fragment thereof comprising the following sequences of 17H9 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and

[0535] (iv) an antibody or antigen-binding fragment thereof comprising the following sequences of 7G6 as described above or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence and CDRL3 sequence and / or (b) VH sequence and VL sequence.

[0536] Preferably, the composition comprises (exactly) three or four different antibodies or antigen-binding fragments that bind to different non-overlapping epitopes of Ara h2, wherein the (exactly) three or four different antibodies or antigen-binding fragments are preferably selected from (i) to (iv) above.

[0537] In some embodiments, the composition comprises (exactly) three different antibodies, i.e., comprises the following:

[0538] (i) an antibody or antigen-binding fragment thereof comprising the following sequences of 17H9 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence;

[0539] (ii) an antibody or antigen-binding fragment thereof comprising the following sequences of 15E3 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and

[0540] (iii) an antibody or antigen-binding fragment thereof comprising the following sequences of 2F8 as described above or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence and CDRL3 sequence and / or (b) VH sequence and VL sequence.

[0541] In some embodiments, the composition comprises (exactly) three different antibodies, i.e., comprises the following:

[0542] (i) an antibody or antigen-binding fragment thereof comprising the following sequences of 17H9 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence;

[0543] (iii) an antibody or antigen-binding fragment thereof comprising the following sequences of 2F8 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and

[0544] (iv) an antibody or antigen-binding fragment thereof comprising the following sequences of 7G6 as described above or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence and CDRL3 sequence and / or (b) VH sequence and VL sequence.

[0545] In some embodiments, the composition comprises (exactly) three different antibodies, i.e., comprises the following:

[0546] (ii) an antibody or antigen-binding fragment thereof comprising the following sequences of 15E3 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence;

[0547] (iii) an antibody or antigen-binding fragment thereof comprising the following sequences of 2F8 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and

[0548] (iv) an antibody or antigen-binding fragment thereof comprising the following sequences of 7G6 as described above or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence and CDRL3 sequence and / or (b) VH sequence and VL sequence.

[0549] Preferably, the composition comprises (exactly) three different antibodies, i.e. comprises:

[0550] (i) an antibody or antigen-binding fragment thereof comprising the following sequences of 17H9 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence;

[0551] (ii) an antibody or antigen-binding fragment thereof comprising the following sequences of 15E3 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and

[0552] (iv) an antibody or antigen-binding fragment thereof comprising the following sequences of 7G6 as described above or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence and CDRL3 sequence and / or (b) VH sequence and VL sequence.

[0553] Also preferably, the composition comprises (exactly) four different antibodies, i.e. comprises:

[0554] (i) an antibody or antigen-binding fragment thereof comprising the following sequences of 17H9 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence;

[0555] (ii) an antibody or antigen-binding fragment thereof comprising the following sequences of 15E3 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence;

[0556] (iii) an antibody or antigen-binding fragment thereof comprising the following sequences of 2F8 as described above, or sequence variants thereof: (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence, and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence; and

[0557] (iv) an antibody or antigen-binding fragment thereof comprising the following sequences of 7G6 as described above or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence and CDRL3 sequence and / or (b) VH sequence and VL sequence.

[0558] In some embodiments, the composition may include (i) an antibody or antigen-binding fragment thereof comprising the following sequences of 17H9 as described above, for example, as described in Tables 1 and 2, or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence, and CDRL3 sequence and / or (b) VH sequence and VL sequence; and (ii) an antibody or antigen-binding fragment thereof comprising the following sequences of (wild-type) 7G6 as described herein, for example, as described in Tables 1 and 2, or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence, and CDRL3 sequence and / or (b) VH sequence and VL sequence. Optionally, such a composition may further include: an antibody or antigen-binding fragment thereof comprising the CDR sequence and / or VH sequence / VL sequence (or sequence variants thereof) of 15E3, and / or an antibody or antigen-binding fragment thereof comprising the CDR sequence and / or VH sequence / VL sequence (or sequence variants thereof) of 2F8.

[0559] In some embodiments, the composition may include (i) an antibody or antigen-binding fragment thereof comprising the following sequences of 17H9 as described above, for example, as described in Tables 1 and 2, or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence, and CDRL3 sequence and / or (b) VH sequence and VL sequence; and (ii) an antibody or antigen-binding fragment thereof comprising the following sequences of (wild-type) 2F8 as described herein, for example, as described in Tables 1 and 2, or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence, and CDRL3 sequence and / or (b) VH sequence and VL sequence. Optionally, such a composition may further include: an antibody or antigen-binding fragment thereof comprising the CDR sequence and / or VH sequence / VL sequence (or sequence variants thereof) of 15E3, and / or an antibody or antigen-binding fragment thereof comprising the CDR sequence and / or VH sequence / VL sequence (or sequence variants thereof) of 7G6.

[0560] In some embodiments, the composition may include (i) an antibody or antigen-binding fragment thereof comprising the following sequences of 15E3 as described above, for example, as described in Tables 1 and 2, or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence, and CDRL3 sequence and / or (b) VH sequence and VL sequence; and (ii) an antibody or antigen-binding fragment thereof comprising the following sequences of (wild-type) 7G6 as described herein, for example, as described in Tables 1 and 2, or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence, and CDRL3 sequence and / or (b) VH sequence and VL sequence. Optionally, such a composition may further include: an antibody or antigen-binding fragment thereof comprising the CDR sequence and / or VH sequence / VL sequence (or sequence variants thereof) of 17H9, and / or an antibody or antigen-binding fragment thereof comprising the CDR sequence and / or VH sequence / VL sequence (or sequence variants thereof) of 2F8.

[0561] In some embodiments, the composition may include (i) an antibody or antigen-binding fragment thereof comprising the following sequences of 15E3 as described above, for example, as described in Tables 1 and 2, or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence, and CDRL3 sequence and / or (b) VH sequence and VL sequence; and (ii) an antibody or antigen-binding fragment thereof comprising the following sequences of (wild-type) 2F8 as described herein, for example, as described in Tables 1 and 2, or sequence variants thereof: (a) CDRH1 sequence, CDRH2 sequence, CDRH3 sequence, CDRL1 sequence, CDRL2 sequence, and CDRL3 sequence and / or (b) VH sequence and VL sequence. Optionally, such a composition may further include: an antibody or antigen-binding fragment thereof comprising the CDR sequence and / or VH sequence / VL sequence (or sequence variants thereof) of 17H9, and / or an antibody or antigen-binding fragment thereof comprising the CDR sequence and / or VH sequence / VL sequence (or sequence variants thereof) of 7G6.

[0562] The present invention also provides a composition comprising at least three different antibodies or antigen-binding fragments thereof, wherein the three different antibodies or antigen-binding fragments bind to different, non-overlapping epitopes of Ara h 2, wherein the composition comprises at least three of the following:

[0563] (i) an antibody or antigen-binding fragment thereof comprising a CDRH1 at least 70% identical to SEQ ID NO: 1, a CDRH2 at least 70% identical to SEQ ID NO: 2, a CDRH3 at least 70% identical to SEQ ID NO: 3, a CDRL1 at least 70% identical to SEQ ID NO: 4, a CDRL2 at least 70% identical to SEQ ID NO: 5, and a CDRL3 at least 70% identical to SEQ ID NO: 6;

[0564] (ii) an antibody or antigen-binding fragment thereof comprising a CDRH1 at least 70% identical to SEQ ID NO: 9, a CDRH2 at least 70% identical to SEQ ID NO: 10, a CDRH3 at least 70% identical to SEQ ID NO: 11, a CDRL1 at least 70% identical to SEQ ID NO: 12, a CDRL2 at least 70% identical to SEQ ID NO: 13, and a CDRL3 at least 70% identical to SEQ ID NO: 14;

[0565] (iii) an antibody or antigen-binding fragment thereof comprising a CDRH1 at least 70% identical to SEQ ID NO: 17, a CDRH2 at least 70% identical to SEQ ID NO: 18, a CDRH3 at least 70% identical to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 at least 70% identical to SEQ ID NO: 20, a CDRL2 at least 70% identical to SEQ ID NO: 21, and a CDRL3 at least 70% identical to SEQ ID NO: 22;

[0566] (iv) an antibody or antigen-binding fragment thereof comprising a CDRH1 at least 70% identical to SEQ ID NO: 25, a CDRH2 at least 70% identical to SEQ ID NO: 26, a CDRH3 at least 70% identical to SEQ ID NO: 27, a CDRL1 at least 70% identical to SEQ ID NO: 28, a CDRL2 at least 70% identical to SEQ ID NO: 29 or SEQ ID NO: 52, and a CDRL3 at least 70% identical to SEQ ID NO: 30.

[0567] Preferably, the composition comprises at least three of the following:

[0568] (i) an antibody or antigen-binding fragment thereof comprising a CDRH1 according to SEQ ID NO: 1, a CDRH2 according to SEQ ID NO: 2, a CDRH3 according to SEQ ID NO: 3, a CDRL1 according to SEQ ID NO: 4, a CDRL2 according to SEQ ID NO: 5, and a CDRL3 according to SEQ ID NO: 6;

[0569] (ii) an antibody or antigen-binding fragment thereof comprising CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13, and CDRL3 according to SEQ ID NO: 14;

[0570] (iii) an antibody or antigen-binding fragment thereof comprising a CDRH1 according to SEQ ID NO: 17, a CDRH2 according to SEQ ID NO: 18, a CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 according to SEQ ID NO: 20, a CDRL2 according to SEQ ID NO: 21, and a CDRL3 according to SEQ ID NO: 22;

[0571] (iv) an antibody or antigen-binding fragment thereof comprising CDRH1 according to SEQ ID NO: 25, CDRH2 according to SEQ ID NO: 26, CDRH3 according to SEQ ID NO: 27, CDRL1 according to SEQ ID NO: 28, CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52, and CDRL3 according to SEQ ID NO: 30.

[0572] More preferably, the composition comprises at least three of the following:

[0573] (i) an antibody or antigen-binding fragment thereof comprising a VH that is at least 70% identical to any one of SEQ ID NO: 7, SEQ ID NO: 44, and SEQ ID NO: 45; and a VL that is at least 70% identical to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, and SEQ ID NO: 49;

[0574] (ii) an antibody or antigen-binding fragment thereof comprising a VH that is at least 70% identical to any one of SEQ ID NO: 15, SEQ ID NO: 37, and SEQ ID NO: 38; and a VL that is at least 70% identical to any one of SEQ ID NO: 16, SEQ ID NO: 39, and SEQ ID NO: 40;

[0575] (iii) an antibody or antigen-binding fragment thereof comprising a VH that is at least 70% identical to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50, and SEQ ID NO: 53; and a VL that is at least 70% identical to any one of SEQ ID NO: 24, SEQ ID NO: 42, and SEQ ID NO: 43;

[0576] (iv) an antibody or antigen-binding fragment thereof comprising a VH that is at least 70% identical to any one of SEQ ID NO: 31, SEQ ID NO: 33, and SEQ ID NO: 34; and a VL that is at least 70% identical to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36, and SEQ ID NO: 54.

[0577] Even more preferably, the composition comprises at least three of the following:

[0578] (i) an antibody or antigen-binding fragment thereof comprising a VH according to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL according to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49;

[0579] (ii) an antibody or antigen-binding fragment thereof comprising a VH according to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL according to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40;

[0580] (iii) an antibody or antigen-binding fragment thereof comprising a VH according to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL according to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43;

[0581] (iv) an antibody or antigen-binding fragment thereof comprising a VH according to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL according to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 54.

[0582] In some embodiments, the composition comprises:

[0583] (i) an antibody or an antigen-binding fragment thereof, comprising:

[0584] a CDRH1 at least 70% identical to SEQ ID NO: 1, a CDRH2 at least 70% identical to SEQ ID NO: 2, a CDRH3 at least 70% identical to SEQ ID NO: 3, a CDRL1 at least 70% identical to SEQ ID NO: 4, a CDRL2 at least 70% identical to SEQ ID NO: 5, and a CDRL3 at least 70% identical to SEQ ID NO: 6;

[0585] - in particular CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5, and CDRL3 according to SEQ ID NO: 6;

[0586] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 7, SEQ ID NO: 44, and SEQ ID NO: 45; and a VL that is at least 70% identical to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, and SEQ ID NO: 49; wherein preferably CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5, and CDRL3 according to SEQ ID NO: 6 are retained;

[0587] - for example a VH according to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL according to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49;

[0588] (ii) an antibody or an antigen-binding fragment thereof comprising:

[0589] a CDRH1 at least 70% identical to SEQ ID NO: 9, a CDRH2 at least 70% identical to SEQ ID NO: 10, a CDRH3 at least 70% identical to SEQ ID NO: 11, a CDRL1 at least 70% identical to SEQ ID NO: 12, a CDRL2 at least 70% identical to SEQ ID NO: 13, and a CDRL3 at least 70% identical to SEQ ID NO: 14;

[0590] - in particular CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13, and CDRL3 according to SEQ ID NO: 14;

[0591] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL that is at least 70% identical to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40; wherein preferably CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13, and CDRL3 according to SEQ ID NO: 14 are retained;

[0592] - for example a VH according to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL according to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40; and

[0593] (iii) an antibody or an antigen-binding fragment thereof comprising:

[0594] a CDRH1 at least 70% identical to SEQ ID NO: 17, a CDRH2 at least 70% identical to SEQ ID NO: 18, a CDRH3 at least 70% identical to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 at least 70% identical to SEQ ID NO: 20, a CDRL2 at least 70% identical to SEQ ID NO: 21, and a CDRL3 at least 70% identical to SEQ ID NO: 22;

[0595] - in particular CDRH1 according to SEQ ID NO: 17, CDRH2 according to SEQ ID NO: 18, CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, CDRL1 according to SEQ ID NO: 20, CDRL2 according to SEQ ID NO: 21, and CDRL3 according to SEQ ID NO: 22;

[0596] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL that is at least 70% identical to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43; wherein preferably CDRH1 according to SEQ ID NO: 17, CDRH2 according to SEQ ID NO: 18, CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, CDRL1 according to SEQ ID NO: 20, CDRL2 according to SEQ ID NO: 21, and CDRL3 according to SEQ ID NO: 22 are retained;

[0597] - for example a VH according to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL according to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43.

[0598] In some embodiments, the composition comprises:

[0599] (i) an antibody or an antigen-binding fragment thereof, comprising:

[0600] a CDRH1 at least 70% identical to SEQ ID NO: 1, a CDRH2 at least 70% identical to SEQ ID NO: 2, a CDRH3 at least 70% identical to SEQ ID NO: 3, a CDRL1 at least 70% identical to SEQ ID NO: 4, a CDRL2 at least 70% identical to SEQ ID NO: 5, and a CDRL3 at least 70% identical to SEQ ID NO: 6;

[0601] - in particular CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5, and CDRL3 according to SEQ ID NO: 6;

[0602] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 7, SEQ ID NO: 44, and SEQ ID NO: 45; and a VL that is at least 70% identical to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, and SEQ ID NO: 49; wherein preferably CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5, and CDRL3 according to SEQ ID NO: 6 are retained;

[0603] - for example a VH according to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL according to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49;

[0604] (iii) an antibody or an antigen-binding fragment thereof comprising:

[0605] a CDRH1 at least 70% identical to SEQ ID NO: 17, a CDRH2 at least 70% identical to SEQ ID NO: 18, a CDRH3 at least 70% identical to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 at least 70% identical to SEQ ID NO: 20, a CDRL2 at least 70% identical to SEQ ID NO: 21, and a CDRL3 at least 70% identical to SEQ ID NO: 22;

[0606] - in particular CDRH1 according to SEQ ID NO: 17, CDRH2 according to SEQ ID NO: 18, CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, CDRL1 according to SEQ ID NO: 20, CDRL2 according to SEQ ID NO: 21, and CDRL3 according to SEQ ID NO: 22;

[0607] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL that is at least 70% identical to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43; wherein preferably CDRH1 according to SEQ ID NO: 17, CDRH2 according to SEQ ID NO: 18, CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, CDRL1 according to SEQ ID NO: 20, CDRL2 according to SEQ ID NO: 21, and CDRL3 according to SEQ ID NO: 22 are retained;

[0608] - for example a VH according to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL according to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43; and

[0609] (iv) an antibody or an antigen-binding fragment thereof comprising:

[0610] - a CDRH1 at least 70% identical to SEQ ID NO: 25, a CDRH2 at least 70% identical to SEQ ID NO: 26, a CDRH3 at least 70% identical to SEQ ID NO: 27, a CDRL1 at least 70% identical to SEQ ID NO: 28, a CDRL2 at least 70% identical to SEQ ID NO: 29 or SEQ ID NO: 52, and a CDRL3 at least 70% identical to SEQ ID NO: 30.

[0611] - in particular CDRH1 according to SEQ ID NO: 25, CDRH2 according to SEQ ID NO: 26, CDRH3 according to SEQ ID NO: 27, CDRL1 according to SEQ ID NO: 28, CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52, and CDRL3 according to SEQ ID NO: 30;

[0612] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL that is at least 70% identical to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 54; wherein preferably CDRH1 according to SEQ ID NO: 25, CDRH2 according to SEQ ID NO: 26, CDRH3 according to SEQ ID NO: 27, CDRL1 according to SEQ ID NO: 28, CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52, and CDRL3 according to SEQ ID NO: 30 are retained;

[0613] - for example a VH according to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL according to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 54.

[0614] In some embodiments, the composition comprises:

[0615] (ii) an antibody or an antigen-binding fragment thereof comprising:

[0616] a CDRH1 at least 70% identical to SEQ ID NO: 9, a CDRH2 at least 70% identical to SEQ ID NO: 10, a CDRH3 at least 70% identical to SEQ ID NO: 11, a CDRL1 at least 70% identical to SEQ ID NO: 12, a CDRL2 at least 70% identical to SEQ ID NO: 13, and a CDRL3 at least 70% identical to SEQ ID NO: 14;

[0617] - in particular CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13, and CDRL3 according to SEQ ID NO: 14;

[0618] - in some embodiments, a VH that is at least 70% identical to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL that is at least 70% identical to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40; wherein preferably CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13, and CDRL3 according to SEQ ID NO: 14 are retained;

[0619] - for example a VH according to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL according to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40;

[0620] (iii) an antibody or an antigen-binding fragment thereof comprising:

[0621] a CDRH1 at least 70% identical to SEQ ID NO: 17, a CDRH2 at least 70% identical to SEQ ID NO: 18, a CDRH3 at least 70% identical to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 at least 70% identical to SEQ ID NO: 20, a CDRL2 at least 70% identical to SEQ ID NO: 21, and a CDRL3 at least 70% identical to SEQ ID NO: 22;

[0622] - in particular CDRH1 according to SEQ ID NO: 17, CDRH2 according to SEQ ID NO: 18, CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51,...

Claims

1. An antibody or antigen-binding fragment thereof that specifically binds to Ara h 2 (peanut allergen 2).

2. The antibody or antigen-binding fragment thereof according to claim 1, wherein the antibody or antigen-binding fragment thereof further specifically binds to Ara h 3 or to Ara h 6.

3. The antibody or antigen-binding fragment thereof of claim 1 or 2, wherein the antibody or antigen-binding fragment thereof comprises a CDRH1 having at least 70% identity to SEQ ID NO: 1, a CDRH2 having at least 70% identity to SEQ ID NO: 2, a CDRH3 having at least 70% identity to SEQ ID NO: 3, a CDRL1 having at least 70% identity to SEQ ID NO: 4, a CDRL2 having at least 70% identity to SEQ ID NO: 5, and a CDRL3 having at least 70% identity to SEQ ID NO:

6.

4. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the antibody or antigen-binding fragment thereof comprises CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5 and CDRL3 according to SEQ ID NO:

6.

5. The antibody or antigen-binding fragment thereof of any of the preceding claims, wherein the antibody or antigen-binding fragment thereof comprises a VH that is at least 70% identical to any one of SEQ ID NO: 7, SEQ ID NO: 44, and SEQ ID NO: 45; and a VL that is at least 70% identical to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, and SEQ ID NO:

49.

6. An antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the antibody or antigen-binding fragment thereof comprises a VH according to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL according to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO:

49.

7. The antibody or antigen-binding fragment thereof of claim 1 or 2, wherein the antibody or antigen-binding fragment thereof comprises a CDRH1 having at least 70% identity to SEQ ID NO: 9, a CDRH2 having at least 70% identity to SEQ ID NO: 10, a CDRH3 having at least 70% identity to SEQ ID NO: 11, a CDRL1 having at least 70% identity to SEQ ID NO: 12, a CDRL2 having at least 70% identity to SEQ ID NO: 13, and a CDRL3 having at least 70% identity to SEQ ID NO:

14.

8. The antibody or antigen-binding fragment thereof according to any one of claims 1, 2 and 7, wherein the antibody or antigen-binding fragment thereof comprises CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13 and CDRL3 according to SEQ ID NO:

14.

9. The antibody or antigen-binding fragment thereof of any one of claims 1, 2, 7 and 8, wherein the antibody or antigen-binding fragment thereof comprises a VH at least 70% identical to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL at least 70% identical to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO:

40.

10. The antibody or antigen-binding fragment thereof according to any one of claims 1, 2 and 7 to 9, wherein the antibody or antigen-binding fragment thereof comprises a VH according to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL according to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO:

40.

11. The antibody or antigen-binding fragment thereof of claim 1 or 2, wherein the antibody or antigen-binding fragment thereof comprises a CDRH1 at least 70% identical to SEQ ID NO: 17, a CDRH2 at least 70% identical to SEQ ID NO: 18, a CDRH3 at least 70% identical to SEQ ID NO: 51, a CDRL1 at least 70% identical to SEQ ID NO: 20, a CDRL2 at least 70% identical to SEQ ID NO: 21, and a CDRL3 at least 70% identical to SEQ ID NO:

22.

12. The antibody or antigen-binding fragment thereof according to any one of claims 1, 2 and 11, wherein the antibody or antigen-binding fragment thereof comprises CDRH1 according to SEQ ID NO: 17, CDRH2 according to SEQ ID NO: 18, CDRH3 according to SEQ ID NO: 51, CDRL1 according to SEQ ID NO: 20, CDRL2 according to SEQ ID NO: 21 and CDRL3 according to SEQ ID NO:

22.

13. The antibody or antigen-binding fragment thereof of any one of claims 1, 2, 11 and 12, wherein the antibody or antigen-binding fragment thereof comprises a VH at least 70% identical to SEQ ID NO: 53; and a VL at least 70% identical to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO:

43.

14. The antibody or antigen-binding fragment thereof according to any one of claims 1, 2 and 11 to 13, wherein the antibody or antigen-binding fragment thereof comprises a VH according to SEQ ID NO: 53; and a VL according to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO:

43.

15. The antibody or antigen-binding fragment thereof of claim 1 or 2, wherein the antibody or antigen-binding fragment thereof comprises a VH that is at least 70% identical to any one of SEQ ID NO: 41, SEQ ID NO: 50, and SEQ ID NO: 53; and a VL that is at least 70% identical to SEQ ID NO: 42 or SEQ ID NO:

43.

16. The antibody or antigen-binding fragment thereof according to claim 15, wherein the antibody or antigen-binding fragment thereof comprises a VH according to any one of SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL according to SEQ ID NO: 42 or SEQ ID NO:

43.

17. The antibody or antigen-binding fragment thereof of claim 1 or 2, wherein the antibody or antigen-binding fragment thereof comprises a CDRH1 at least 70% identical to SEQ ID NO: 25, a CDRH2 at least 70% identical to SEQ ID NO: 26, a CDRH3 at least 70% identical to SEQ ID NO: 27, a CDRL1 at least 70% identical to SEQ ID NO: 28, a CDRL2 at least 70% identical to SEQ ID NO: 52, and a CDRL3 at least 70% identical to SEQ ID NO:

30.

18. The antibody or antigen-binding fragment thereof according to any one of claims 1, 2 and 17, wherein the antibody or antigen-binding fragment thereof comprises CDRH1 according to SEQ ID NO: 25, CDRH2 according to SEQ ID NO: 26, CDRH3 according to SEQ ID NO: 27, CDRL1 according to SEQ ID NO: 28, CDRL2 according to SEQ ID NO: 52 and CDRL3 according to SEQ ID NO:

30.

19. The antibody or antigen-binding fragment thereof of any one of claims 1, 2, 17 and 18, wherein the antibody or antigen-binding fragment thereof comprises a VH at least 70% identical to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL at least 70% identical to SEQ ID NO:

54.

20. The antibody or antigen-binding fragment thereof according to any one of claims 1, 2 and 17 to 19, wherein the antibody or antigen-binding fragment thereof comprises a VH according to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL according to SEQ ID NO:

54.

21. The antibody or antigen-binding fragment thereof of claim 1 or 2, wherein the antibody or antigen-binding fragment thereof comprises a VH that is at least 70% identical to SEQ ID NO: 33 or SEQ ID NO: 34; and a VL that is at least 70% identical to any one of SEQ ID NO: 35, SEQ ID NO: 36, and SEQ ID NO:

54.

22. The antibody or antigen-binding fragment thereof of claim 21, wherein the antibody or antigen-binding fragment thereof comprises a VH according to SEQ ID NO: 33 or SEQ ID NO: 34; and a VL according to any one of SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO:

54.

23. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the CDRs or variable regions of the antibody or antigen-binding fragment thereof are human CDRs or variable region sequences or are derived from human CDRs or variable region sequences.

24. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the antibody or antigen-binding fragment thereof is a human antibody.

25. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the antibody or antigen-binding fragment thereof is a monoclonal antibody.

26. The antibody of any one of the preceding claims, wherein the antibody comprises an Fc portion.

27. The antibody according to any one of the preceding claims, wherein the antibody is of the IgG type or the IgA type.

28. The antibody according to claim 27, wherein the antibody is of IgG1 type or IgG4 type.

29. An antibody according to any one of the preceding claims, wherein the variable region or CDR is derived from an IgE antibody and is grafted into a scaffold of an IgG antibody or an IgA antibody.

30. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the antibody or antigen-binding fragment thereof is purified.

31. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the antibody or antigen-binding fragment thereof is a single chain antibody.

32. The antibody or antigen-binding fragment thereof of claim 24, wherein the antibody or antigen-binding fragment thereof is a scFv.

33. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 23, wherein the antibody or antigen-binding fragment thereof is selected from Fab, Fab', F(ab')2 and Fv.

34. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the antibody or antigen-binding fragment thereof is a multispecific antibody or multispecific antigen-binding fragment.

35. The antibody or antigen binding fragment thereof of claim 34, wherein the antibody or antigen binding fragment thereof binds to different non-overlapping epitopes of Ara h 2.

36. The antibody or antigen-binding fragment thereof of claim 34, wherein the antibody or antigen-binding fragment thereof comprises at least two of the following: (i) an antigen binding site comprising (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence as defined in any one of claims 3 to 6; (ii) an antigen binding site comprising (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence as defined in any one of claims 7 to 10; (iii) an antigen binding site comprising (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence as defined in any one of claims 11 to 16; (iv) an antigen binding site comprising (a) a CDRH1 sequence, a CDRH2 sequence, a CDRH3 sequence, a CDRL1 sequence, a CDRL2 sequence and a CDRL3 sequence and / or (b) a VH sequence and a VL sequence as defined in any one of claims 17 to 22.

37. A multispecific antibody or multispecific antigen-binding fragment that binds to different non-overlapping epitopes of Ara h 2, wherein the antibody or antigen-binding fragment comprises at least two of the following: (i) an antigen binding site comprising a CDRH1 at least 70% identical to SEQ ID NO: 1, a CDRH2 at least 70% identical to SEQ ID NO: 2, a CDRH3 at least 70% identical to SEQ ID NO: 3, a CDRL1 at least 70% identical to SEQ ID NO: 4, a CDRL2 at least 70% identical to SEQ ID NO: 5, and a CDRL3 at least 70% identical to SEQ ID NO: 6; (ii) an antigen binding site comprising a CDRH1 at least 70% identical to SEQ ID NO: 9, a CDRH2 at least 70% identical to SEQ ID NO: 10, a CDRH3 at least 70% identical to SEQ ID NO: 11, a CDRL1 at least 70% identical to SEQ ID NO: 12, a CDRL2 at least 70% identical to SEQ ID NO: 13, and a CDRL3 at least 70% identical to SEQ ID NO: 14; (iii) an antigen binding site comprising a CDRH1 at least 70% identical to SEQ ID NO: 17, a CDRH2 at least 70% identical to SEQ ID NO: 18, a CDRH3 at least 70% identical to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 at least 70% identical to SEQ ID NO: 20, a CDRL2 at least 70% identical to SEQ ID NO: 21, and a CDRL3 at least 70% identical to SEQ ID NO: 22; (iv) an antigen binding site comprising a CDRH1 at least 70% identical to SEQ ID NO: 25, a CDRH2 at least 70% identical to SEQ ID NO: 26, a CDRH3 at least 70% identical to SEQ ID NO: 27, a CDRL1 at least 70% identical to SEQ ID NO: 28, a CDRL2 at least 70% identical to SEQ ID NO: 29 or SEQ ID NO: 52, and a CDRL3 at least 70% identical to SEQ ID NO:

30.

38. The antibody or antigen-binding fragment of claim 37, wherein the antibody or antigen-binding fragment comprises at least two of the following: (i) an antigen binding site comprising CDRH1 according to SEQ ID NO: 1, CDRH2 according to SEQ ID NO: 2, CDRH3 according to SEQ ID NO: 3, CDRL1 according to SEQ ID NO: 4, CDRL2 according to SEQ ID NO: 5 and CDRL3 according to SEQ ID NO: 6; (ii) an antigen binding site comprising CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13 and CDRL3 according to SEQ ID NO: 14; (iii) an antigen binding site comprising CDRH1 according to SEQ ID NO: 17, CDRH2 according to SEQ ID NO: 18, CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, CDRL1 according to SEQ ID NO: 20, CDRL2 according to SEQ ID NO: 21 and CDRL3 according to SEQ ID NO: 22; (iv) an antigen binding site comprising CDRH1 according to SEQ ID NO: 25, CDRH2 according to SEQ ID NO: 26, CDRH3 according to SEQ ID NO: 27, CDRL1 according to SEQ ID NO: 28, CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52 and CDRL3 according to SEQ ID NO:

30.

39. The antibody or antigen-binding fragment of claim 37 or 38, wherein the antibody or antigen-binding fragment comprises at least two of the following: (i) an antigen binding site comprising a VH at least 70% identical to any one of SEQ ID NO: 7, SEQ ID NO: 44, and SEQ ID NO: 45; and a VL at least 70% identical to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, and SEQ ID NO: 49; (ii) an antigen binding site comprising a VH at least 70% identical to any one of SEQ ID NO: 15, SEQ ID NO: 37, and SEQ ID NO: 38; and a VL at least 70% identical to any one of SEQ ID NO: 16, SEQ ID NO: 39, and SEQ ID NO: 40; (iii) an antigen binding site comprising a VH at least 70% identical to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50, and SEQ ID NO: 53; and a VL at least 70% identical to any one of SEQ ID NO: 24, SEQ ID NO: 42, and SEQ ID NO: 43; (iv) an antigen binding site comprising a VH at least 70% identical to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL at least 70% identical to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO:

54.

40. The antibody or antigen-binding fragment of any one of claims 37 to 39, wherein the antibody or antigen-binding fragment comprises at least two of the following: (i) an antigen binding site comprising a VH according to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL according to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49; (ii) an antigen binding site comprising a VH according to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL according to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40; (iii) an antigen binding site comprising a VH according to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL according to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43; (iv) an antigen binding site comprising a VH according to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL according to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO:

54.

41. The antibody or antigen-binding fragment of any one of claims 36 to 39, wherein the antibody or antigen-binding fragment is trispecific and comprises three different antigen-binding sites selected from (i) to (iv).

42. The antibody or antigen-binding fragment of any one of claims 36 to 39, wherein the antibody or antigen-binding fragment is tetraspecific and comprises four different antigen-binding sites according to (i), (ii), (iii) and (iv).

43. The antibody or antigen-binding fragment of claim 3 or 4, wherein the CDRH1 sequence, CDRH2 sequence and CDRH3 sequence are contained in a human variable light chain framework region VH chain, and the VH chain is selected from the amino acid sequence encoded by the following genes: IGHV1-18, IGHV1-2, IGHV1-24, IGHV1-3, IGHV1-45, IGHV1-46, IGHV1-58, IGHV1-69, IGHV1-69-2, IGHV1-69D, IGHV1-8, IGHV2-26, IGHV2-5, IGHV2-70, IGHV2-70D, IGHV3-11, IGHV3-13, IGHV3-15, IGHV3-20, IGHV3-21, IGHV3-22, IGHV3-23, IGHV3-24, IGHV3-25, IGHV3-26, IGHV3-27, IGHV3-28, IGHV3-29, IGHV4-30, IGHV4-31, IGHV4-32 V3-23, IGHV3-23D, IGHV3-30, IGHV3-30-3, IGHV3-30-5, IGHV3-33, IGHV3-35, IGHV3-43, IGHV3-43D, IGHV3-48, IGHV3-49, IGHV3-53, IGHV3-62, IGHV3-64, IGHV3-6 4D, IGHV3-66, IGHV3-7, IGHV3-72, IGHV3-73, IGHV3-74, IGHV3-9, IGHV3-NL1, IGHV4-28, IGHV4-30-1, IGHV4-30-2, IGHV4-30-4, IGHV4-31, IGHV4-34, and IGHV4-38-2.

44. according to claim 3,4 or 43 described antibody or antigen binding fragment, wherein said CDRL1 sequence, CDRL2 sequence and CDRL3 sequence are contained in the human variable light chain framework region VL chain, and described VL chain is selected from the amino acid sequence encoded by following gene: IGLV1-36, IGLV1-40, IGLV1-44, IGLV1-47, IGLV1-51, IGLV10-54, IGLV2-11, IGLV2-14, IGLV2-18, IGLV2-23, IGLV2-8, IGLV2-9, IGLV3-10, IGLV3-11, IGLV3-12, IGLV3-13, IGLV3-14, IGLV3-15, IGLV3-16, IGLV3-17, IGLV3-18, IGLV3-20, IGLV3-21, IGLV3-23, IGLV3-24, IGLV3-25, IGLV3-26, IGLV3-27, IGLV3-28, IGLV3-29, IGLV3-30, IGLV3-31, IGLV3-32, IGLV3-33, IGLV3-34, IGLV3-35, IGLV3-36, IGLV3-37, IGLV3-38, IGLV3-39, IGLV3-40, IGLV3-41, IGLV3-42, IGLV3-43, IGLV3-44, IGLV3-45, IGLV3-47, IGLV3-51, IGLV3-54, IGLV3-55, IGLV3-56, IGLV3-57, IGLV3-58, IGLV3-59, IGLV3-60, IGLV LV3-1, IGLV3-10, IGLV3-12, IGLV3-16, IGLV3-19, IGLV3-21, IGLV3-22, IGLV3-25, IGLV3-27, IGLV3-9, IGLV4-3, IG LV4-60, IGLV4-69, IGLV5-37, IGLV5-39, IGLV5-45, IGLV5-52, IGLV6-57, IGLV7-43, IGLV7-46, IGLV8-61 and IGLV9-49.

45. The antibody or antigen-binding fragment of claim 3, 4 or 43, wherein the CDRL1 sequence, CDRL2 sequence and CDRL3 sequence are contained in a human variable light chain framework region VK chain, and the VK chain is selected from the amino acid sequence encoded by the following genes: IGKV1-12, IGKV1-13, IGKV1-16, IGKV1-17, IGKV1-27, IGKV1-33, IGKV1-39, IGKV1-5, IGKV1-6, IGKV1-8, IGKV1-9, IGKV1-NL1, IGKV1D-12, IGKV1D-13, IGKV1D-16, IGKV1D-17 , IGKV1D-33, IGKV1D-39, IGKV1D-43, IGKV1D-8, IGKV2-24, IGKV2-28, IGKV2-29, IGKV2-30, IGKV2-40, IGKV2D-26, IGKV2D-28, IGKV2D-29, IGK V2D-30, IGKV2D-40, IGKV3-11, IGKV3-15, IGKV3-20, IGKV3D-11, IGKV3D-15, IGKV3D-20, IGKV3D-7, IGKV4-1, IGKV5-2, IGKV6-21 and IGKV6D-21.

46. ​​An antibody or antigen-binding fragment thereof according to any one of the preceding claims for use as a medicament.

47. The antibody or antigen-binding fragment thereof for use according to claim 46, for preventing or treating peanut allergy.

48. A nucleic acid molecule comprising a polynucleotide encoding the antibody or antigen-binding fragment thereof according to any one of claims 1 to 45.

49. A nucleic acid molecule according to claim 48, comprising a nucleic acid sequence as shown in any one of SEQ ID NO: 64 to SEQ ID NO: 99; or a sequence variant thereof having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 88%, at least 90%, at least 92%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity.

50. A plurality of nucleic acid molecules encoding the antibody or antigen-binding fragment thereof according to any one of claims 1 to 45, wherein each of the plurality of nucleic acid molecules comprises a polynucleotide encoding an immunoglobulin chain of the antibody or antigen-binding fragment thereof.

51. A combination of nucleic acid molecules according to claim 50, comprising a nucleic acid sequence as shown in any one of SEQ ID NO: 64 to SEQ ID NO: 99; or a sequence variant thereof having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 88%, at least 90%, at least 92%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity.

52. A vector comprising a nucleic acid molecule according to claim 48 or 49 or a plurality of nucleic acid molecules according to claim 50 or 51.

53. A plurality of vectors comprising a plurality of nucleic acid molecules according to claim 50 or 51.

54. A host cell expressing the antibody or antigen-binding fragment thereof according to any one of claims 1 to 45, or a combination comprising the vector according to claim 52 or the vector according to claim 53.

55. A method for preparing an antibody or antigen-binding fragment thereof or one or more than one immunoglobulin chain thereof according to any one of claims 1 to 45, the method comprising (i) culturing the host cell according to claim 54; and (ii) isolating the antibody or one or more than one immunoglobulin chains thereof from the culture.

56. A composition comprising the antibody or antigen-binding fragment thereof according to any one of claims 1 to 45, the nucleic acid or nucleic acids according to any one of claims 48 to 51, the vector or vectors according to claim 52 or 53, or the cell according to claim 54.

57. The composition of claim 56, further comprising a pharmaceutically acceptable excipient, diluent or carrier.

58. The composition of claim 56 or 57, wherein the composition comprises at least two different antibodies or antigen-binding fragments thereof that bind to different, non-overlapping epitopes of Ara h 2.

59. The composition of claim 58, wherein the composition comprises at least two of: (i) the antibody or antigen-binding fragment thereof according to any one of claims 3 to 6; (ii) the antibody or antigen-binding fragment thereof according to any one of claims 7 to 10; (iii) the antibody or antigen-binding fragment thereof according to any one of claims 11 to 16; (iv) the antibody or antigen-binding fragment thereof according to any one of claims 17 to 22.

60. The composition according to claim 58 or 59, comprising (exactly) three or four different antibodies or antigen-binding fragments binding to different non-overlapping epitopes of Ara h 2, wherein the (exactly) three or four different antibodies or antigen-binding fragments are preferably selected from (i) to (iv) of claim 59.

61. A composition comprising at least three different antibodies or antigen-binding fragments thereof, wherein the at least three different antibodies or antigen-binding fragments thereof bind to different non-overlapping epitopes of Ara h 2, wherein the composition comprises at least three of the following: (i) an antibody or antigen-binding fragment thereof comprising a CDRH1 at least 70% identical to SEQ ID NO: 1, a CDRH2 at least 70% identical to SEQ ID NO: 2, a CDRH3 at least 70% identical to SEQ ID NO: 3, a CDRL1 at least 70% identical to SEQ ID NO: 4, a CDRL2 at least 70% identical to SEQ ID NO: 5, and a CDRL3 at least 70% identical to SEQ ID NO: 6; (ii) an antibody or antigen-binding fragment thereof comprising a CDRH1 at least 70% identical to SEQ ID NO: 9, a CDRH2 at least 70% identical to SEQ ID NO: 10, a CDRH3 at least 70% identical to SEQ ID NO: 11, a CDRL1 at least 70% identical to SEQ ID NO: 12, a CDRL2 at least 70% identical to SEQ ID NO: 13, and a CDRL3 at least 70% identical to SEQ ID NO: 14; (iii) an antibody or antigen-binding fragment thereof comprising a CDRH1 at least 70% identical to SEQ ID NO: 17, a CDRH2 at least 70% identical to SEQ ID NO: 18, a CDRH3 at least 70% identical to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 at least 70% identical to SEQ ID NO: 20, a CDRL2 at least 70% identical to SEQ ID NO: 21, and a CDRL3 at least 70% identical to SEQ ID NO: 22; (iv) an antibody or antigen-binding fragment thereof comprising a CDRH1 at least 70% identical to SEQ ID NO: 25, a CDRH2 at least 70% identical to SEQ ID NO: 26, a CDRH3 at least 70% identical to SEQ ID NO: 27, a CDRL1 at least 70% identical to SEQ ID NO: 28, a CDRL2 at least 70% identical to SEQ ID NO: 29 or SEQ ID NO: 52, and a CDRL3 at least 70% identical to SEQ ID NO:

30.

62. The composition of claim 61, wherein the composition comprises at least three of the following: (i) an antibody or an antigen-binding fragment thereof comprising a CDRH1 according to SEQ ID NO: 1, a CDRH2 according to SEQ ID NO: 2, a CDRH3 according to SEQ ID NO: 3, a CDRL1 according to SEQ ID NO: 4, a CDRL2 according to SEQ ID NO: 5 and a CDRL3 according to SEQ ID NO: 6; (ii) an antibody or antigen-binding fragment thereof comprising CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13 and CDRL3 according to SEQ ID NO: 14; (iii) an antibody or antigen-binding fragment thereof comprising a CDRH1 according to SEQ ID NO: 17, a CDRH2 according to SEQ ID NO: 18, a CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 according to SEQ ID NO: 20, a CDRL2 according to SEQ ID NO: 21, and a CDRL3 according to SEQ ID NO: 22; (iv) an antibody or antigen-binding fragment thereof comprising CDRH1 according to SEQ ID NO: 25, CDRH2 according to SEQ ID NO: 26, CDRH3 according to SEQ ID NO: 27, CDRL1 according to SEQ ID NO: 28, CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52, and CDRL3 according to SEQ ID NO:

30.

63. The composition of claim 61 or 62, wherein the composition comprises at least three of the following: (i) an antibody or antigen-binding fragment thereof comprising a VH at least 70% identical to any one of SEQ ID NO: 7, SEQ ID NO: 44, and SEQ ID NO: 45; and a VL at least 70% identical to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, and SEQ ID NO: 49; (ii) an antibody or antigen-binding fragment thereof comprising a VH at least 70% identical to any one of SEQ ID NO: 15, SEQ ID NO: 37, and SEQ ID NO: 38; and a VL at least 70% identical to any one of SEQ ID NO: 16, SEQ ID NO: 39, and SEQ ID NO: 40; (iii) an antibody or antigen-binding fragment thereof comprising a VH at least 70% identical to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50, and SEQ ID NO: 53; and a VL at least 70% identical to any one of SEQ ID NO: 24, SEQ ID NO: 42, and SEQ ID NO: 43; (iv) an antibody or antigen-binding fragment thereof comprising a VH that is at least 70% identical to any one of SEQ ID NO: 31, SEQ ID NO: 33, and SEQ ID NO: 34; and a VL that is at least 70% identical to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36, and SEQ ID NO:

54.

64. A composition according to any one of claims 61 to 63, wherein the composition comprises at least three of the following: (i) an antibody or an antigen-binding fragment thereof comprising a VH according to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL according to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49; (ii) an antibody or antigen-binding fragment thereof comprising a VH according to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL according to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40; (iii) an antibody or antigen-binding fragment thereof comprising a VH according to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL according to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43; (iv) an antibody or an antigen-binding fragment thereof comprising a VH according to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL according to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO:

54.

65. A composition according to any one of claims 59 to 64, wherein the composition comprises four different antibodies or antigen-binding fragments according to (i), (ii), (iii) and (iv).

66. The composition of any one of claims 56 to 64, wherein the composition further comprises at least one additional agent for treating peanut allergy.

67. The composition of claim 66, wherein the additional agent for treating peanut allergy is selected from the group consisting of beta-adrenergic agonists, epinephrine, antihistamines, corticosteroids, anti-IgE antibodies, anti-IgE antibody binding fragments, peptide vaccines, and other antibodies capable of binding to peanut allergens.

68. The composition according to any one of claims 56 to 67, wherein the composition further comprises a peanut allergen, preferably selected from Ara h1, Ara h2, Ara h3 and Ara h6 or a mixture thereof.

69. A kit comprising one or more than one of the following: (i) the antibody or antigen-binding fragment thereof according to any one of claims 1 to 45; (ii) a nucleic acid molecule or a plurality of nucleic acid molecules according to any one of claims 48 to 51; (iii) a vector or a plurality of vectors according to claim 52 or 53; (iv) the cell according to claim 54; and / or (v) A composition according to any one of claims 56 to 68.

70. The kit of claim 69, wherein the kit comprises (i) at least two different antibodies or antigen-binding fragments thereof according to any one of claims 1 to 45 that bind to different non-overlapping epitopes of Ara h 2; (ii) one or more than one nucleic acid molecule encoding at least two different antibodies or antigen-binding fragments thereof according to any one of claims 1 to 45 that bind to different non-overlapping epitopes of Ara h 2; or (iii) one or more compositions comprising (i) or (ii).

71. A kit according to claim 70, comprising three or four different antibodies or antigen-binding fragments thereof according to any one of claims 1 to 45 that bind to different non-overlapping epitopes of Ara h 2; or one or more than one nucleic acid encoding said antibodies or a composition comprising said antibodies.

72. A kit comprising at least three different antibodies or antigen-binding fragments thereof, wherein the at least three different antibodies or antigen-binding fragments thereof bind to different non-overlapping epitopes of Ara h 2, wherein the kit comprises at least three of: (i) an antibody or antigen-binding fragment thereof comprising a CDRH1 at least 70% identical to SEQ ID NO: 1, a CDRH2 at least 70% identical to SEQ ID NO: 2, a CDRH3 at least 70% identical to SEQ ID NO: 3, a CDRL1 at least 70% identical to SEQ ID NO: 4, a CDRL2 at least 70% identical to SEQ ID NO: 5, and a CDRL3 at least 70% identical to SEQ ID NO: 6; (ii) an antibody or antigen-binding fragment thereof comprising a CDRH1 at least 70% identical to SEQ ID NO: 9, a CDRH2 at least 70% identical to SEQ ID NO: 10, a CDRH3 at least 70% identical to SEQ ID NO: 11, a CDRL1 at least 70% identical to SEQ ID NO: 12, a CDRL2 at least 70% identical to SEQ ID NO: 13, and a CDRL3 at least 70% identical to SEQ ID NO: 14; (iii) an antibody or antigen-binding fragment thereof comprising a CDRH1 at least 70% identical to SEQ ID NO: 17, a CDRH2 at least 70% identical to SEQ ID NO: 18, a CDRH3 at least 70% identical to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 at least 70% identical to SEQ ID NO: 20, a CDRL2 at least 70% identical to SEQ ID NO: 21, and a CDRL3 at least 70% identical to SEQ ID NO: 22; (iv) an antibody or antigen-binding fragment thereof comprising a CDRH1 at least 70% identical to SEQ ID NO: 25, a CDRH2 at least 70% identical to SEQ ID NO: 26, a CDRH3 at least 70% identical to SEQ ID NO: 27, a CDRL1 at least 70% identical to SEQ ID NO: 28, a CDRL2 at least 70% identical to SEQ ID NO: 29 or SEQ ID NO: 52, and a CDRL3 at least 70% identical to SEQ ID NO:

30.

73. The kit of claim 72, wherein the kit comprises at least three of the following: (i) an antibody or an antigen-binding fragment thereof comprising a CDRH1 according to SEQ ID NO: 1, a CDRH2 according to SEQ ID NO: 2, a CDRH3 according to SEQ ID NO: 3, a CDRL1 according to SEQ ID NO: 4, a CDRL2 according to SEQ ID NO: 5 and a CDRL3 according to SEQ ID NO: 6; (ii) an antibody or antigen-binding fragment thereof comprising CDRH1 according to SEQ ID NO: 9, CDRH2 according to SEQ ID NO: 10, CDRH3 according to SEQ ID NO: 11, CDRL1 according to SEQ ID NO: 12, CDRL2 according to SEQ ID NO: 13 and CDRL3 according to SEQ ID NO: 14; (iii) an antibody or antigen-binding fragment thereof comprising a CDRH1 according to SEQ ID NO: 17, a CDRH2 according to SEQ ID NO: 18, a CDRH3 according to SEQ ID NO: 19 or SEQ ID NO: 51, a CDRL1 according to SEQ ID NO: 20, a CDRL2 according to SEQ ID NO: 21, and a CDRL3 according to SEQ ID NO: 22; (iv) an antibody or antigen-binding fragment thereof comprising CDRH1 according to SEQ ID NO: 25, CDRH2 according to SEQ ID NO: 26, CDRH3 according to SEQ ID NO: 27, CDRL1 according to SEQ ID NO: 28, CDRL2 according to SEQ ID NO: 29 or SEQ ID NO: 52, and CDRL3 according to SEQ ID NO:

30.

74. The kit of claim 72 or 73, wherein the kit comprises at least three of: (i) an antibody or antigen-binding fragment thereof comprising a VH at least 70% identical to any one of SEQ ID NO: 7, SEQ ID NO: 44, and SEQ ID NO: 45; and a VL at least 70% identical to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, and SEQ ID NO: 49; (ii) an antibody or antigen-binding fragment thereof comprising a VH at least 70% identical to any one of SEQ ID NO: 15, SEQ ID NO: 37, and SEQ ID NO: 38; and a VL at least 70% identical to any one of SEQ ID NO: 16, SEQ ID NO: 39, and SEQ ID NO: 40; (iii) an antibody or antigen-binding fragment thereof comprising a VH at least 70% identical to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50, and SEQ ID NO: 53; and a VL at least 70% identical to any one of SEQ ID NO: 24, SEQ ID NO: 42, and SEQ ID NO: 43; (iv) an antibody or antigen-binding fragment thereof comprising a VH that is at least 70% identical to any one of SEQ ID NO: 31, SEQ ID NO: 33, and SEQ ID NO: 34; and a VL that is at least 70% identical to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36, and SEQ ID NO:

54.

75. The kit of any one of claims 72 to 74, wherein the kit comprises at least three of the following: (i) an antibody or an antigen-binding fragment thereof comprising a VH according to any one of SEQ ID NO: 7, SEQ ID NO: 44 and SEQ ID NO: 45; and a VL according to any one of SEQ ID NO: 8, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49; (ii) an antibody or antigen-binding fragment thereof comprising a VH according to any one of SEQ ID NO: 15, SEQ ID NO: 37 and SEQ ID NO: 38; and a VL according to any one of SEQ ID NO: 16, SEQ ID NO: 39 and SEQ ID NO: 40; (iii) an antibody or antigen-binding fragment thereof comprising a VH according to any one of SEQ ID NO: 23, SEQ ID NO: 41, SEQ ID NO: 50 and SEQ ID NO: 53; and a VL according to any one of SEQ ID NO: 24, SEQ ID NO: 42 and SEQ ID NO: 43; (iv) an antibody or an antigen-binding fragment thereof comprising a VH according to any one of SEQ ID NO: 31, SEQ ID NO: 33 and SEQ ID NO: 34; and a VL according to any one of SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO:

54.

76. A kit according to any one of claims 72 to 75, wherein the kit comprises four different antibodies or antigen-binding fragments according to (i), (ii), (iii) and (iv).

77. The kit of any one of claims 69 to 76, wherein the kit further comprises at least one additional agent for treating peanut allergy.

78. The kit of any one of claims 69 to 77, wherein the kit further comprises a peanut allergen.

79. An antibody or antigen-binding fragment thereof according to any one of claims 1 to 45, a nucleic acid or multiple nucleic acids according to any one of claims 48 to 51, a vector or multiple vectors according to claim 52 or 53, a cell according to claim 54, a composition according to any one of claims 56 to 68, or a kit according to any one of claims 69 to 78, for use as a medicament.

80. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 45, the nucleic acid or nucleic acids according to any one of claims 48 to 51, the vector or vectors according to claim 52 or 53, the cell according to claim 54, the composition according to any one of claims 56 to 68 or the kit according to any one of claims 69 to 78 for use in preventing or treating peanut allergy.

81. The antibody or antigen-binding fragment thereof, nucleic acid or nucleic acids, vector or vectors, cell or composition for use according to claim 80, wherein at least two, three or four different antibodies or antigen-binding fragments thereof that bind to different non-overlapping epitopes of Ara h 2 are administered; or one or more nucleic acids or one or more vectors encoding the different antibodies are administered; or one or more compositions comprising the different antibodies are administered.

82. The antibody or antigen-binding fragment thereof, nucleic acid or nucleic acids, vector or vectors, cell or composition for use according to claim 80 or 81, wherein administration of the antibody or antigen-binding fragment thereof, nucleic acid or nucleic acids, vector or vectors, cell or composition is combined with administration of a peanut allergen, preferably selected from Ara h1, Ara h2, Ara h3 and Ara h6 or a mixture thereof.

83. The antibody or antigen-binding fragment thereof or composition for use according to claim 82, wherein the antibody or antigen-binding fragment thereof or the composition is administered before or during a desensitization process using peanut allergen.

84. Use of the antibody or antigen-binding fragment thereof according to any one of claims 1 to 45, the composition according to any one of claims 56 to 68 or the kit according to any one of claims 69 to 78 for the (in vitro) diagnosis of peanut allergy.

85. Use of the antibody or antigen-binding fragment thereof according to any one of claims 1 to 45, the kit according to any one of claims 56 to 68, or any one of claims 69 to 78 in a method for detecting a peanut allergen.

86. Use of an antibody or antigen-binding fragment thereof according to any one of claims 1 to 45, a nucleic acid or multiple nucleic acids according to any one of claims 48 to 51, a vector or multiple vectors according to claim 52 or 53, a cell according to claim 54, a composition according to any one of claims 56 to 68, or a kit according to any one of claims 69 to 78 in the preparation of a medicament for preventing, treating or alleviating peanut allergy.

87. A method of treating, ameliorating or reducing peanut allergy or reducing the risk of peanut allergy or allergic reaction, comprising: A therapeutically effective amount of the antibody or antigen-binding fragment thereof according to any one of claims 1 to 45, the nucleic acid or nucleic acids according to any one of claims 48 to 51, the vector or vectors according to claim 52 or 53, the cell according to claim 54, the composition according to any one of claims 56 to 68, or the kit according to any one of claims 69 to 78 is administered to a subject in need thereof.

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