Anti-allergen antibodies and uses thereof

Abstract

The present invention provides antibodies binding to birch pollen allergens, in particular to Bet v 1 allergens, and also binding to Bet v 1 homologous allergens. The present invention also provides compositions and kits comprising distinct antibodies binding to distinct, non-overlapping epitopes of Bet v 1 and Bet v 1 homologous proteins. In addition, the present invention also relates to the use of such antibodies, compositions and kits, e.g. for preventing or treating tree pollen allergies as well as food-related allergies.

Description

[0001] GRAF VON STOSCH

[0002] PATENTANWALTSGESELLSCHAFT MBH

[0003] Our Ref. Date MA03P007W01 December 11, 2025

[0004] Applicant

[0005] Mabylon AG, Schlieren, Switzerland

[0006] 5 ANTI-ALLERGEN ANTIBODIES AND USES THEREOF

[0007] The present invention relates to antibodies binding to birch pollen allergens and related tree pollen and food allergens, in particular binding to Bet v 1 and Bet v 1 homologous allergens / proteins. The present invention also relates to compositions and kits comprising 10 distinct antibodies binding to distinct, non-overlapping epitopes of Bet v 1 and Bet v 1 homologous proteins. In addition, the present invention also relates to the use of such antibodies, compositions and kits, e.g. for preventing or treating tree pollen and food allergies, in particular birch pollen and related tree pollen allergies as well as food-related allergies, such as e.g. apple, hazelnut and walnut allergies.

[0008] 15

[0009] Allergies are conditions caused by hypersensitivity of the immune system. Allergen encounter results in the production of allergen-binding immunoglobulin E (IgE) antibodies, which are pre-bound on FCERI receptors on mast cells and basophils, where they trigger the release of inflammatory compounds, such as histamine, leukotriene and lipid mediators.

[0010] 20

[0011] Type I allergy or immediate hypersensitivity is the consequence of the interaction between an allergen and immunoglobulin E (IgE) antibodies, which are attached to mast cells. Allergic symptoms, including allergic asthma, rhino-conjunctivitis, and atopic dermatitis, significantly affect human health and a quality of life. It is estimated that 300–400 million people in the 25 world is affected by type 1 allergies, causing 120 billion Euros in health care costs, sick leaves, and economic losses (Calderon et al., 2012, Clin. Transl. Allergy 2: 20). These symptoms are elicited by environmental aeroallergens such as pollen or house dust mites. Birch pollen is widespread in Europe, North America, Russia, and northern Japan. More than 100 million patients suffer from allergy to birch pollen (Moverare et al., 2005, Int. Arch. Allergy Immunol.

[0012] 30 136, 33-38). The major birch pollen allergen is Bet v 1. The Bet v 1 allergen is a member of the plant pathogenesis related proteins family PR-10. Bet v 1 homologs are also included among various plant-derived food allergens such as apple Mal d 1, and hazelnut Cor a 1. The patients having birch pollen allergy usually suffer from other related tree pollen allergies, such as hazel, alder, beech, oak pollen, and also often suffer from secondary pollen food syndrome, which negatively impacts on their health-related quality of life (Popescu, 2015, World J. Methodol. 5, 31-50).

[0013] Allergen immunotherapy (AIT) is based on the repeated administration of disease-eliciting allergens to modulate the allergic immune response. During AIT, allergen-specific immunoglobulin G, particularly IgG4, is induced. IgG4 competes with IgE to bind the allergen, leading to the inhibition of the IgE-mediated hypersensitive mechanisms to alleviate allergic symptoms (Shamji et al., 2012, Allergy 67, 217-226). Bet v 1 -specific IgG4 developed by AIT competes with IgE for partly identical or largely overlapping epitopes (Groh et al., 2017, Clin. Exp. Allergy 47, 693-703).

[0014] Recently, antibodies against birch pollen allergens emerged as another promising option for treating birch pollen allergy. For example, Atanasio et al. (J. Allergy Clin. Immunol. 2020; vol. 149, 1, p. 200-211) describes that a combination of mAbs targeting Bet v 1 can prevent the birch allergic response. According to that study, Bet v 1 -specific mAbs, REGN5713, REGN5714, and REGN5715, derived from immunization of humanized mice, bind with high affinity and noncompetitively to Bet v 1. It has been shown that a cocktail of all 3 antibodies, REGN5713 / 14 / 15, blocks IgE binding to Betv 1 and inhibits Betv 1 - and birch pollen extract -induced basophil activation ex vivo and mast cell degranulation in vivo.

[0015] Due to the high cross-reactivity observed in birch allergic patients, it would be beneficial to target - in a birch pollen-targeting antibody approach - as many Betv 1 homologues proteins (PR-10 proteins) as possible.

[0016] In view of the above, it is the object of the present invention to provide an improved antibody against birch pollen allergens, in particular an antibody which targets the Bet v 1 allergen and also is cross-reactive with several Bet v 1 homologous allergens / proteins. It is also an object of the present invention to provide a composition comprising said antibody. This object is achieved by means of the subject-matter set out below and in the appended claims.

[0017] Although the present invention is described in detail below, it is to be understood that this invention is not limited to the particular methodologies, protocols and reagents described herein as these may vary. It is also to be understood that the terminology used herein is not intended to limit the scope of the present invention which will be limited only by the appended claims. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art.

[0018] In the following, the elements of the present invention will be described. These elements are listed with specific embodiments, however, it should be understood that they may be combined in any manner and in any number to create additional embodiments. The variously described examples and embodiments should not be construed to limit the present invention to only the explicitly described embodiments. This description should be understood to support and encompass embodiments which combine the explicitly described embodiments with any number of the disclosed elements. Furthermore, any permutations and combinations of all described elements in this application should be considered disclosed by the description of the present application unless the context indicates otherwise.

[0019] Throughout this specification and the claims which follow, unless the context requires otherwise, the term "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated member, integer or step but not the exclusion of any other non-stated member, integer or step. The term "consist of" is a particular embodiment of the term "comprise", wherein any other non-stated member, integer or step is excluded. In the context of the present invention, the term "comprise" encompasses the term "consist of". The term "comprising" thus encompasses "including" as well as "consisting" eg., a composition "comprising" X may consist exclusively of X or may include something additional eg., X + Y.

[0020] The terms "a" and "an" and "the" and similar reference used in the context of describing the invention (especially in the context of the claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.

[0021] The word "substantially" does not exclude "completely" e.g., a composition which is "substantially free" from Y may be completely free from Y. Where necessary, the word "substantially" may be omitted from the definition of the invention.

[0022] The term "about" in relation to a numerical value x means x ± 10%, for example, x ± 5%, or x ± 7%, or x ± 10%, or x ± 12%, or x ± 15%, or x ± 20%.

[0023] The term "disease" as used herein is intended to be generally synonymous, and is used interchangeably with, the terms "disorder" and "condition" (as in medical condition), in that all reflect an abnormal condition of the human or animal body or of one of its parts that impairs normal functioning, is typically manifested by distinguishing signs and symptoms, and causes the human or animal to have a reduced duration or quality of life.

[0024] As used herein, reference to "treatment" of a subject or patient is intended to include prevention, prophylaxis, attenuation, amelioration and therapy. The terms "subject" or "patient" are used interchangeably herein to mean 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.

[0025] Doses are often expressed in relation to the bodyweight. Thus, a dose which is expressed as [g, mg, or other unit] / kg (or g, mg etc.) usually refers to [g, mg, or other unit] "per kg (or g, mg etc.) bodyweight", even if the term "bodyweight" is not explicitly mentioned.

[0026] The term "binding" and similar reference usually means "specifically binding", which does not encompass non-specific sticking. In particular, specific binding of an antibody means that the antibody recognizes its target antigen and binds its target with greater affinity (or at lower antibody concentrations, e.g. EC50) than it does to a structurally different antigen and / or to an antigen with a modified or mutated sequence. Thereby, a "greater" affinity may be at least 2fold, 3fold, 4fold, 5fold, 10fold, 15fold, 20fold, 25fold, 50fold, 75fold, 100fold 150fold, 200fold, 500fold, 750fold, 1,000fold, 1,500fold, 2,000fold, 5,000fold, 7,500fold, 10,000fold or even higher affinity as compared to the binding to a control antigen. In some instances, antibody-binding to the control antigen may be undetectable (below detection threshold), while antibody-binding to the specific antigen may be well detected / determined.

[0027] As used herein, the term "antibody" encompasses various forms of antibodies including, without being limited to, whole antibodies, antibody fragments (such as antigen binding fragments), human antibodies, chimeric antibodies, humanized antibodies, recombinant antibodies and genetically engineered antibodies (e.g., variant or mutant antibodies) as long as the characteristic properties according to the 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 may be a human monoclonal antibody.

[0028] As described above, the term "antibody" generally also includes antibody fragments. Fragments of the antibodies may retain the antigen-binding activity of the 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. Fragments of the antibodies can be obtained from the antibodies by methods that include digestion with enzymes, such as pepsin or papain, and / or by cleavage of disulfide bonds by chemical reduction. Alternatively, fragments of the antibodies can be obtained by recombinant means, for example by cloning and expressing a part (fragment) of the sequences of the heavy and / or light chain. The invention also encompasses single-chain Fv fragments (scFv) derived from the heavy and light chains of an antibody of the invention. For example, the invention includes a scFv comprising the CDRs from an antibody of the invention. Also included are heavy or light chain monomers and dimers, single domain heavy chain antibodies, single domain light chain antibodies, as well as single chain antibodies, e.g., single chain Fv in which the heavy and light chain variable domains are joined by a peptide linker. Antibody fragments of the invention may be contained in a variety of structures known to the person skilled in the art. In addition, the sequences of the invention may be a component of multispecific molecules in which the sequences of the invention target the epitopes of the invention and other regions of the molecule bind to other targets. Although the specification, including the claims, may, in some places, refer explicitly to antigen binding fragment(s), antibody fragment(s), variant(s) and / or derivative(s) of antibodies, it is understood that the term "antibody" includes all categories of antibodies, namely, antigen binding fragment(s), antibody fragment(s), variant(s) and derivative(s) of antibodies.

[0029] Human antibodies are well-known in the state of the art (van Dijk, M. A., and van de Winkel, J. G., Curr. Opin. Chem. Biol. 5 (2001) 368-374). Human antibodies can also be produced in transgenic animals (e.g., mice or chicken) that are capable, upon immunization, of producing a full repertoire or a selection of human antibodies in the absence of endogenous immunoglobulin production. Transfer of the human germ-line immunoglobulin gene array in such germ-line 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, H. R., and Winter, G., J. Mol. Biol. 227 (1992) 381-388; Marks, J. D., et al., J. Mol. Biol. 222 (1991) 581-597). The techniques of Cole et al. and Boerner et al. are also available for the preparation of human monoclonal antibodies (Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985); and Boerner, P., etal., J. Immunol.

[0030] 147 (1991) 86-95). As used herein, the expression "human antibodies" includes non-naturally occurring sequence variants of human antibodies, which are usually obtained by introducing one or more mutations in the (naturally occurring) human antibodies. Such mutations include one or more mutations in a CDR or in a framework region, as well as Fc modifications (e.g., as known in the art for specific functionalities).

[0031] As used herein, the term "variable region" (variable region of a light chain (VL), variable region of a heavy chain (VH)) denotes each of the pair of light and heavy chains which is involved directly in binding the antibody to the antigen.

[0032] Antibodies of the invention can be of any isotype e.g., IgA, IgG, IgM i.e. an α, γ or μ heavy chain). Preferably, the antibody is of the IgG type or the IgA type. Within the IgG isotype, antibodies may be IgGI, lgG2, lgG3 or lgG4 subclass, preferably IgGI or lgG4. Antibodies of the invention may have a κ or a λ light chain. Antibodies according to the present invention may be provided in purified form. Typically, the antibody will be present in a composition that is substantially free of other polypeptides e.g., where less than 90% (by weight), usually less than 60% and more usually less than 50% of the composition is made up of other polypeptides.

[0033] Antibodies according to the present invention may be immunogenic in human and / or in non-human (or heterologous) hosts e.g., in mice. For example, the antibodies may have an idiotope that is immunogenic in non-human hosts, but not in a human host. Antibodies of the invention for human use include those 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 xeno-mice.

[0034] As used herein, the term "antigen" refers to any structural substance which serves as a target for the receptors of an adaptive immune response, in particular as a target for antibodies, T cell receptors, and / or B cell receptors. An "epitope", also known as "antigenic determinant", is the part (or fragment) of an antigen that is recognized by the immune system, in particular by antibodies, T cell receptors, and / or B cell receptors. Thus, one antigen has at least one epitope, i.e. a single antigen has one or more epitopes. An antigen may be (i) a peptide, a polypeptide, or a 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 a toxin. Thus, an antigen may be a peptide, a protein, a polysaccharide, a 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, a polypeptide, or a protein, (ii) a polysaccharide, (iii) a lipid, (iv) a lipoprotein or a lipopeptide and (v) a glycolipid; more preferably, the antigen is a peptide, a polypeptide, or a protein.

[0035] As used herein, the term "mutation" relates to a change in the nucleic acid sequence and / or in the amino acid sequence in comparison to a reference sequence, e.g. a corresponding genomic sequence. A mutation, e.g. in comparison to a genomic sequence, may be, for example, a (naturally occurring) somatic mutation, a spontaneous mutation, an induced mutation, e.g. induced by enzymes, chemicals or radiation, or a mutation obtained by site- directed mutagenesis (molecular biology methods for making specific and intentional changes in the nucleic acid sequence and / or in the amino acid sequence). Thus, the terms "mutation" or "mutating" shall be understood to also include physically making a mutation, e.g. in a nucleic acid sequence or in an amino acid sequence. A mutation includes substitution, deletion and insertion of one or more nucleotides or amino acids as well as inversion of several successive nucleotides or amino acids. To achieve a mutation in an amino acid sequence, a mutation may be introduced into the nucleotide sequence encoding said amino acid sequence in order to express a (recombinant) mutated polypeptide. A mutation may be achieved e.g., by altering, e.g., by site-directed mutagenesis, a codon of a nucleic acid molecule encoding one amino acid to result in a codon encoding a different amino acid, or by synthesizing a sequence variant, e.g., 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 a variant of the polypeptide without the need for mutating one or more nucleotides of a nucleic acid molecule.

[0036] As used herein (i.e. throughout the present specification), the term "sequence variant" refers to any alteration in comparison to a reference sequence. The term "sequence variant" includes nucleotide sequence variants and amino acid sequence variants. Preferably, a reference sequence is any of the sequences listed in the " Table of Sequences and SEQ ID Numbers" (Sequence listing), i.e. SEQ ID NO: 1 to SEQ ID NO: 804. In particular, a sequence variant shares (over the whole 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 variant shares 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. Thereby, the higher the %-identity of a sequence variant, the more it is preferred. For example, a sequence variant having at least 84% sequence identity with a reference sequence is more preferred than a sequence variant having at least 75% sequence identity, but less than 84% sequence identity, with a reference sequence. In some embodiments, the sequence variant maintains the (biological) function of the reference sequence. For example, sequence variants relating to antibodies of the invention preferably maintain the specific binding to Bet v 1 and / or a Bet v 1 homologous protein, such as e.g. Cor a 1, Ain g 1, Fag s 1, Que a 1, Cas s 1, Ost c 1, Car b1, Mal d 1, Jug r 5).

[0037] Sequence identity may be calculated as described below. Usually a sequence variant may preserve the specific function of the reference sequence. In some embodiments, an amino acid sequence variant has an altered sequence in which one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) of the amino acids in the reference sequence is deleted or substituted, or one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) amino acids are inserted into or added to the sequence of the reference amino acid sequence. As a result of the alterations, the amino acid sequence variant has an amino acid sequence which is 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% identical to the reference sequence. For example, variant sequences which are at least 90% identical have no more than 10 alterations, i.e., any combination of deletions, insertions or substitutions, per 100 amino acids of the reference sequence. The same, of course, also applies similarly to nucleic acid sequences.

[0038] The "% identity" of the sequence variant is usually determined with respect to the reference sequence. It is usually calculated with regard to the full length of the reference sequence (i.e. the sequence recited in the application). Percentage identity, as referred to herein, can be determined, for example, by methods known in the art, such as BLAST using the default parameters specified by the NCBI (the National Center for Biotechnology Information; http: / / www.ncbi.nlm.nih.gov / ) [Blosum 62 matrix; gap open penalty=11 and gap extension penalty=1 ].

[0039] In general, while it is possible to have non-conservative amino acid substitutions, the substitutions are preferably conservative amino acid substitutions, wherein the substituted amino acid has similar structural or chemical properties with the corresponding amino acid in the reference sequence. By way of example, conservative amino acid substitutions involve substitution of one aliphatic or hydrophobic amino acids, e.g. alanine, valine, leucine and isoleucine, with another; substitution of one hydoxyl-containing amino acid, e.g. serine and threonine, with another; substitution of one acidic residue, e.g. glutamic acid or aspartic acid, with another; replacement of one amide-containing residue, e.g. asparagine and glutamine, with another; replacement of one aromatic residue, e.g. phenylalanine and tyrosine, with another; replacement of one basic residue, e.g. lysine, arginine and histidine, with another; and replacement of one small amino acid, e.g., alanine, serine, threonine, cysteine, and glycine, with another.

[0040] " Bet v 1 allergens or Bet v 1 proteins", as used herein, encompasses all known isoallergens and variants of Bet v 1, including e.g. Bet v 1.0101, Bet v 1.0102, Bet v 1.0103, Bet v 1.0104, Bet v 1.0105, Bet v 1.0106, Bet v 1.0107, Bet v 1.0108, Bet v 1.0109, Bet v 1.0110, Bet v 1.0111, Bet v 1.0112, Bet v 1.0113, Bet v 1.0114, Bet v 1.0115, Bet v 1.0115, Bet v 1.0116, Bet v 1.0117, Bet v 1.0118, Bet v 1.0119, Bet v 1.0201, Bet v 1.0202, Bet v 1.0203, Bet v 1.0204, Bet v 1.0205, Bet v 1.0206, Bet v 1.0207, Bet v 1.0301, and also encompasses all known mutants of Bet v 1, such as e.g. Bet v 1 N 160A.

[0041] Allergens or proteins of the Bet v 1 family, belonging to the class 10 of the pathogenesis related protein (PR 10) family, encompass Bet v 1 {Betula verrucosa, Betula pendu / a, European white birch; "https: / / www.medu niwien.ac.at / allfam / search.php?searchtext=Betula+verrucosa+%28Betula +pendula%29" \o " List all allergens from Betula verrucosa (Betula pendula)"), and also encompass " Bet v 1 homologous allergens". Examples of " Bet v 1 homologous allergens" include e.g. Act c 8 {Actinidia chinensis, Gold kiwi fruit; "https: / / www.medu niwien.ac.at / allfam / search.php?searchtext=Actinidia+deliciosa" \o " List all allergens from Actinidia deliciosa"), Act d 8 (Actinidia deliciosa, Green Kiwi fruit), Ain g 1 {Alnus g / utinosa, European alder; "https: / / www.meduniwien.ac.at / allfam / search.php?searchtext=Alnus+glutinosa" \o " List all allergens from Alnus glutinosa"), Api g 1 {Apium graveolens, Celery; "https: / / www.meduniwien.ac.at / allfam / search.php?searchtext=Apium+graveolens" \o " List all allergens from Apium graveolens"), Ara h 8 {Arachis hypogaea, Peanut; "https: / / www.meduniwien.ac.at / allfam / search.php?searchtext=Arachis+hypogaea" \o " List all allergens from Arachis hypogaea"), Bet pl PR-10 {Betula platyphylla, Asian white birch; "https: / / www.meduniwien.ac.at / allfam / search.php?searchtext=Betula+platyphylla" \o " List all allergens from Betula platyphylla"), Can s 5 (Cannabis sativa, Indian hemp), Car b 1 {Carpinus betulus, European hornbeam; "https: / / www.meduniwien.ac.at / allfam / search.php?searchtext=Carpinus+betulus" \o " List all allergens from Carpinus betulus"), Cas s 1 {Castanea saliva, Sweet chestnut; "https: / / www.meduniwien.ac.at / allfam / search.php?searchtext=Castanea+sativa" \o " List all allergens from Castanea sativa"), Cor a 1 {Corylus avellana, European hazel; "https: / / www.meduniwien.ac.at / allfam / search.php?searchtext=Corylus+avellana" \o " List all allergens from Corylus avellana"), Dau c 1 {Caucus carota, Carrot; "https: / / www.meduniwien.ac. at / allfam / search.php?searchtext=Daucus+carota" \o " List all allergens from Daucus carota"), Lag s 1 {Fagus sy / vatica, European beech; "https: / / www.meduniwien.ac. at / allfam / search.php?searchtext=Eagus+sylvatica" \o " List all allergens from Eagus sylvatica"), Era a 1 {Fragaria ananassa, Strawberry; "https: / / www.meduniwien.ac. at / allfam / search.php?searchtext=Eragaria+ananassa" \o " List all allergens from Eragaria ananassa"), Gly m 4 {Glycine max, Soybean; "https: / / www.meduniwien.ac. at / allfam / search.php?searchtext=Glycine+max" \o " List all allergens from Glycine max"), Jug r 5 {Jug / ans regia, English walnut; "https: / / www.meduniwien.ac. at / allfam / search.php?searchtext=Juglans+regia" \o " List all allergens from Juglans regia"), Mal d 1 {Ma! us domestica, Apple; "https: / / www.meduniwien.ac.at / allfam / search.php?searchtext=Malus+domestica" \o " List all allergens from Malus domestica"), Mor a PR-10 {Morus alba, White mulberry; "https: / / www.meduniwien.ac.at / allfam / search.php?searchtext=Morus+alba" \o " List all allergens from Morus alba"), Mor b PR-10 {Morus bombycis, Chinese mulberry; "https: / / www.meduniwien.ac. at / allfam / search.php?searchtext=Morus+bombycis" \o " List all allergens from Morus bombycis"), Ost c 1 {Ostrya carpinifoHa, European hop hornbeam; "https: / / www.meduniwien.ac.at / allfam / search.php?searchtext=Ostrya+carpinifolia" \o " List all allergens from Ostrya carpinifolia"), Pru ar 1 {Prunus armeniaca, Apricot; "https: / / www.meduniwien.ac.at / allfam / search.php?searchtext=Prunus+armeniaca" \o " List all allergens from Prunus armeniaca"), Pru av 1 {Prunus avium, Sweet cherry; "https: / / www.meduniwien.ac.at / allfam / search.php?searchtext=Prunus+avium" \o " List all allergens from Prunus avium"), Pru p 1 {Prunus persica, Peach; "https: / / www.meduniwien.ac. at / allfam / search.php?searchtext=Prunus+persica" \o " List all allergens from Prunus persica"), Pyr c 1 {Pyrus communis, Pear; "https: / / www.meduniwien.ac.at / allfam / search.php?searchtext=Pyrus+communis" \o " List all allergens from Pyrus communis"), Que a 1 {Quercus alba, White oak; "https: / / www.meduniwien.ac.at / allfam / search.php?searchtext=Quercus+alba" \o " List all allergens from Quercus alba"), Que ac 1 {Quercus acutissima, Sawtooth oak), Que i 1 {Quercus Hex, holly oak), Que m 1 {Quercus mongoHca, Mongolian oak), Rub i 1 {Rubus idaeus, Red raspberry; "https: / / www.meduniwien.ac.at / allfam / search.php?searchtext=Rubus+idaeus" \o " List all allergens from Rubus idaeus"), Sola I 4 {So / anum lycopersicum, Tomato; "https: / / www.medu niwien.ac.at / allfam / search.php?searchtext=Solanum+lycopersicum" \o " List all allergens from Solanum lycopersicum"), Vig r 1 {Vigna radiata, Mung bean; "https: / / www.meduniwien.ac.at / allfam / search.php?searchtext=Vigna+radiata" \o " List all allergens from Vigna radiata"), Vig r 6 Vigna radiata, Mung bean; "https: / / www.meduniwien.ac. at / allfam / search.php?searchtext=Vigna+radiata" \o " List all allergens from Vigna radiata"). The contents of the indicated websites with respect to the allergens are incorporated herein by reference.

[0042] " Bet v 1 homologous allergens" also encompass all known isoallergens and variants of the above listed allergens, such as e.g. Ain g 1.0101, Car b 1.1 A, Car b1.2, Car b 1.0101 - Car b 1.0113, Car b 1.0201, Car b 1.301, Car b 1.302, Cas s 1.0101, Cor a 1.0101, Cor a 1.0102, Cor a 1.0103, Cor a 1.0104, Cor a 1.0201, Cor a 1.0301, Cor a 1.0401, Cor a 1.0402, Cor a 1.0403, Cor a 1.0404, Fag s 1.0101, Ost c 1.0101, Que a 1.0101, Que a 1.0201, Que a 1.0301, Que a 1.0401, Mal d 1.0101 to Mal d 1.0109, Mal d 1.0201 to Mal d 1.0208, Mal d 1.0301 to Mal d 1.0304, Mal d 1.0401 to Mal d 1.0403, Jug r 5.0101, Pru p 1.01 and Pru p 1.02 etc.

[0043] Accordingly, in the present specification, "birch pollen related allergies" encompass any allergy elicited by any of the above listed Bet v 1 homologous allergens or isoallergens.

[0044] Several documents are cited throughout the text of this specification. Each of the documents cited herein (including all patents, patent applications, scientific publications, manufacturer's specifications, instructions, etc.), whether supra or infra, are hereby incorporated by reference in their entirety. Nothing herein is to be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention. It is to be understood that this invention is not limited to the particular methodology, protocols and reagents described herein as these may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention which will be limited only by the appended claims. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art.

[0045] Antibodies and antigen-binding fragments thereof

[0046] In a first aspect the present invention provides an (isolated) antibody, or an antigen-binding fragment thereof, which (specifically) binds to Bet v 1 (Betula verrucose allergen 1 ). Bet v 1 is a major birch pollen allergen, which is recognized by serum IgE from more than 95% of patients with birch pollen hypersensitivity. Bet v 1 is a protein of approximately 17 kDa. A number of Bet v 1 isoforms are described (Bet v 1.0101, Bet v 1.0102, Bet v 1.0103 etc., supra). Accordingly, the antibody, or the antigen-binding fragment thereof, of the present invention binds in particular to a polypeptide or protein having an amino acid sequence according to SEQ ID NO: 792, and / or to a variant of a polypeptide or protein having an amino acid sequence according to SEQ ID NO: 792, as defined above.

[0047] Preferably, the (isolated) antibody, or an antigen-binding fragment thereof, which (specifically) binds to Bet v 1, further binds (specifically) to a Bet v 1 homologous allergen. The Bet v 1 homologous allergen may be another tree pollen allergen. The Bet v 1 homologous tree pollen allergen may be selected from the group consisting of Cor a 1 (Corylus avellana allergen 1), Ain g 1 (Alnus glutinosa allergen 1), Fag s 1 (Fagus sylvatica allergen 1), Que a 1 (Quercus alba allergen 1), Cas s 1 Castania sativa allergen 1), Ost c 1 Ostrya carpinifolia allergen 1), and / or Car b 1 (Carbinus betulus allergen 1). Thus, preferably, the antibody, or the antigen-binding fragment thereof, of the invention binds (specifically) (i) to Bet v 1, and also binds (specifically) (ii) to at least one Bet v 1 homologous protein, such as e.g. Cor a 1, Ain g 1, Fag s 1, Que a 1, Cas s 1, Ost c 1, Car b 1, Can s 5. Accordingly, the antibody, or the antigen-binding fragment thereof, of the present invention binds in particular to a polypeptide or protein having an amino acid sequence according to SEQ ID NO: 792, and / or to a variant of a polypeptide or protein having an amino acid sequence according to SEQ ID NO: 792, as defined above, and also preferably binds to a polypeptide or protein having an amino acid sequence according to any one of SEQ ID NOs 793-798, and / or to a variant of a polypeptide or protein having an amino acid sequence according to any one of SEQ ID NOs 793-798.

[0048] Moreover, the (isolated) antibody, or an antigen-binding fragment thereof, which (specifically) binds to Bet v 1, may further bind (specifically) to a Bet v 1 homologous food-related allergen. The food-related allergen may be selected from any of the Bet v 1 homologous allergens listed above, and is preferably selected from Mal d 1 (Mai us domestica allergen 1), Cor a 1 (Corylus avellana allergen 1), Jug r 5 (Juglans regia allergen 5), Can s 5 (Cannabis sativa allergen 5, Indian hemp) (see SEQ ID NO: 868 for amino acid sequence of Can s 5.0101) and Pru p 1 (Primus persica allergen 1; "https: / / www.meduniwien.ac. at / allfam / search.php?searchtext=Prunus+persica" \o " List all allergens from Prunus persica").

[0049] The above tree pollen allergens, in particular Bet v 1, Cor a 1, Ain g 1, Fag s 1, Que a 1, Cas s 1, Ost c 1, and / or Car b1, and the above food-related allergens (e.g. Mal d 1, Cor a 1, Jug r 5, Pru p 1) may be of natural origin, recombinantly expressed or synthetic peptides.

[0050] Standard methods to assess binding of the antibody according to the present invention, or the antigen-binding fragment thereof, are known to those skilled in the art and include, for example, ELISA (enzyme-linked immunosorbent assay). Thereby, the relative affinities of antibody binding may be determined at fixed dose of antibody by measuring the concentration of the allergen (EC5o) required to achieve 50% maximal binding at saturation. A specific example of an ELISA, which may be used to assess binding of an antibody, is described in the example section of this specification.

[0051] In general, the antibody, or an antigen-binding fragment thereof, according to the present invention, may comprise (at least) three complementarity determining regions (CDRs) on a heavy chain and (at least) three CDRs on a light chain. In general, complementarity determining regions (CDRs) are the hypervariable regions present in heavy chain variable domains and light chain variable domains, respectively. Typically, the CDRs of a heavy chain and the connected light chain of an antibody together form the antigen receptor. Usually, the three CDRs (CDR1, CDR2, and CDR3) are arranged non-consecutively in the variable domain. Since antigen receptors are typically composed of two variable domains (on two different polypeptide chains, i.e. heavy and light chain: heavy chain variable region (VH) and light chain variable region (VL)), there are typically six CDRs for each antigen receptor (heavy chain: CDRH1, CDRH2, and CDRH3; light chain: CDRL1, CDRL2, and CDRL3). For example, a classical IgG antibody molecule usually has two antigen receptors and therefore contains twelve CDRs. The CDRs on the heavy and / or light chain may be separated by framework regions, whereby a framework region (FR) is a region in the variable domain which is less "variable" than the CDR. For example, a variable region (or each variable region, respectively) may be composed of four framework regions, separated by three CDR's.

[0052] The sequences of the heavy chains and light chains of exemplary antibodies of the invention, comprising three different CDRs on the heavy chain and three different CDRs on the light chain were determined. The CDR amino acid sequences of the CDR1 of the heavy chain (CDRH1), the CDR2 of the heavy chain (CDRH2), the CDR3 of the heavy chain (CDRH3), the CDR1 of the light chain (CDRL1), the CDR2 of the light chain (CDRL2) and the CDR3 of the light chain (CDRL3) of exemplary antibodies are shown in the Table of Sequences and SEQ ID Numbers (Sequence Listing) below.

[0053] The CDRs, in particular the three different CDRs (CDR1, CDR2 and CDR3) on the heavy chain and three different CDRs (CDR1, CDR2 and CDR3) on the light chain, as identified by the present invention may be grafted on any variable framework region, in particular any variable human framework region, without abrogating their specificity.

[0054] The human variable framework regions of the heavy chain (VH) may be retrieved from the website:

[0055] "https: / / www. imgt.org / genedb / resu ltPage.action;jsessionid=49EB34C22C79EAC51862C761 08963216?gene.id.species=Homo+sapiens&molComponent=IG&geneTypeLike=variable&a llele.fcode=functional&cloneName=&locusLike=IGH&mainLocusLike=IGH+locus&cosLoc usLike=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 group consisting of the amino acid sequences encoded by the genes IGHV1-2, IGHV1-3, IGHV1-8, IGHV1-18, IGHV1-24, IGHV1-45, IGHV1-46, IGHV1-58, IGHV1-69, IGHV1-69- 2, IGHV1-69D, IGHV2-5, IGHV2-26, IGHV2-70, IGHV2-70D, IGHV3-7, IGHV3-9, IGHV3-11, IGHV3-13, IGHV3-15, IGHV3-20, IGHV3-21, IGHV3-23, IGHV3-23D, IGHV3-3O, IGHV3-3O-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, IGHV3-72, IGHV3-73, IGHV3-74, IGHV3OR16-10, IGHV3-NL1, IGHV4-4, IGHV4-28, IGHV4-30-1, IGHV4-30-2, IGHV4-30-4, IGHV4-31, IGHV4-34, IGHV4-38-2, IGHV4-39, IGHV5-10-1, IGHV5-5 and IGHV5-51.

[0056] The human variable framework regions of the light chain (VK, kappa) may be retrieved from the website:

[0057] "https: / / www. imgt.org / genedb / resu ltPage.action;jsessionid=49EB34C22C79EAC51862C761 08963216?gene.id.species=Homo+sapiens&molComponent=IG&geneTypeLike=variable&a llele.fcode=functional&cloneName=&locusLike=IGK&mainLocusLike=IGK+locus&cosLocu sLike=any&groupLike=any&subgroup=-1 &geneLike=&selection=any", the content of which is incorporated herein by reference. Thus, the VK (kappa) chain may be selected from the group consisting of the amino acid sequences encoded by the genes IGKV1-5, IGKV1-6, IGKV1-8, IGKV1 D-8, IGKV1-9, IGKV1-12, IGKV1 D-12, IGKV1-13, IGKV1 D-13, IGKV1-16, IGKV1 D-16, IGKV1-17, IGKV1 D-17, IGKV1-27, IGKV1-33, IGKV1 D-33, IGKV1-39, IGKV1 D-39, IGKV1 D-43, IGKV1-NL1, IGKV1 D-8, IGKV2-24, IGKV2D-26, IGKV2-28, IGKV2D-28, IGKV2-29, IGKV2D-29, IGKV2-30, IGKV2D-30, IGKV2-40, IGKV2D-40, IGKV3D-7, IGKV3-11, IGKV3D-11, IGKV3-15, IGKV3D-15, IGKV3-20, IGKV3D-20, IGKV4-1, IGKV5-2, IGKV6-21, and IGKV6D-21.

[0058] The human variable framework regions of the light chain (VL, lambda) may be retrieved from the website:

[0059] „ https: / / www. imgt.org / genedb / resu ItPage. action;jsessionid=49EB34C22C79EAC51862C761 08963216?gene.id.species=Homo+sapiens&molComponent=IG&geneTypeLike=variable&a llele.fcode=functional&cloneName=&locusLike=IGL&mainLocusLike=IGL+locus&cosLocus Like=any&groupLike=any&subgroup=-1 &geneLike=&selection=any", the content of which is incorporated herein by reference. Thus, the VL (lambda) chain may be selected from the group consisting of the amino acid sequences encoded by the genes IGLV1-36, IGLV1-40, IGLV1-44, IGLV1-47, IGLV1-51, IGLV10-54, IGLV2-8, IGLV2-11, IGLV2-14, IGLV2-18, IGLV2-23, IGLV3-1, IGLV3-9, IGLV3-10, IGLV3-12, IGLV3-16, IGLV3-19, IGLV3-21, IGLV3- 22, IGLV3-25, IGLV3-27, 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.

[0060] The human variable framework region of the heavy and the light chain may also contain the respective human HJ (heavy chain), and light chain KJ (kappa) or LJ (lambda) sequences.

[0061] The HJ sequences may be retrieved from the website:

[0062] "https: / / www. imgt.org / genedb / resultPage. action?gene. id. species=Homo+sapiens&molComp onent=IG&geneTypeLike=any&allele.fcode=functional&cloneName=&locusLike=IGH&mai nLocusLike=IGH+locus&cosLocusLike=any&groupLike=IGHJ&subgroup=- 1 &geneLike=&selection=any", the content of which is incorporated herein by reference. In particular, the HJ sequence may be selected from amino acid sequences encoded by the genes consisting of the group: IGHJ1, IGHJ2, IGHJ3, IGHJ4, IGHJ5, and IGHJ6.

[0063] The KJ sequences may be retrieved from the website:

[0064] "https: / / www. imgt.org / genedb / resultPage. action?gene. id. species=Homo+sapiens&molComp onent=IG&geneTypeLike=any&allele.fcode=functional&cloneName=&locusLike=IGK&mai nLocusLike=IGK+locus&cosLocusLike=any&groupLike=IGKJ&subgroup=- 1 &geneLike=&selection=any", the content of which is incorporated herein by reference. In particular, the KJ sequence may be selected from amino acid sequences encoded by the genes consisting of the group IGKJ1, IGKJ2, IGKJ3, IGKJ4, and IGKJ5.

[0065] The LJ sequences may be retrieved from the website:

[0066] "https: / / www. imgt.org / genedb / resultPage. action?gene. id. species=Homo+sapiens&molComp onent=IG&geneTypeLike=any&allele.fcode=functional&cloneName=&locusLike=IGL&mai nLocusLike=IGL+locus&cosLocusLike=any&groupLike=IGLJ&subgroup=- 1 &geneLike=&selection=any", the content of which is incorporated herein by reference. In particular, the LJ sequence may be selected from amino acid sequences encoded by the genes consisting of the group: IGLJ1, IGLJ2, IGLJ3, IGLJ6, and IGLJ7.

[0067] The heavy chain CDR sequences of the invention (CDRH1, CDRH2 and CDRH3) may be comprised by a human heavy chain variable framework sequence as defined by a human VH sequence as described herein in combination with a human HJ sequence as described herein. Analogously, the light chain CDR sequences of the invention (CDRL1, CDRL2 and CDRL3) may be comprised by a human light chain variable framework sequence as defined by a human VL or VK sequence as described herein in combination with a human LJ or KJ sequence as described.

[0068] The combination of (i) a human VH sequence (comprising an CDRH1, an CDRH2 and an CDRH3 sequence, respectively, according to the invention) and of a human VL sequence (comprising an CDRL1, an CDRL2 and an CDRL3 sequence, respectively, of the invention) or of (ii) a human VH sequence (comprising an CDRH1, an CDRH2 and an CDRH3 sequence, respectively, of the invention) and of a human VK sequence (comprising an CDRL1, an CDRL2 and an CDRL3 sequence, respectively, of the invention) may thus characterize the variable framework region of an antibody according to the invention and its binding region. Also, the variable framework region may be characterized (i) by a human VH sequence and a human HJ sequence in combination with a human VL and a human LJ sequence or (ii) by a human VH sequence and a human HJ sequence in combination with a human VK and a human KJ sequence, thereby forming the variable framework region of an antibody according to the invention and its binding region.

[0069] The CDR sequences of the invention are inserted at the sites of the variable framework sequences which present the CDR sequences.

[0070] The numbering of the residues in the variable regions was done according to the IMGT numbering system (IMGT: http: / / www.imgt.org / ; cf. Lefranc, M.-P. etal. (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 the sequences of the variable regions of Bence Jones proteins and myeloma light chains 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).

[0071] Preferably, the antibody of the invention, or the antigen-binding fragment thereof, comprises a combination of six CDR sequences, in particular three CDR sequences of the heavy chain (CDRH1, CDRH2, CDRH3), and three CDR sequences of the light chain (CDRL1, CDRL2, CDRL3), or sequence variants thereof, as defined herein. In some embodiments, the antibody, or the antigen-binding fragment thereof, according to the present invention 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. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0072] a heavy chain CDR1 sequence according to SEQ ID NO: 1;

[0073] a heavy chain CDR2 sequence according to SEQ ID NO: 2;

[0074] a heavy chain CDR3 sequence according to SEQ ID NO: 3;

[0075] a light chain CDR1 sequence according to SEQ ID NO: 4;

[0076] a light chain CDR2 sequence according to SEQ ID NO: 5; and

[0077] a light chain CDR3 sequence according to SEQ ID NO: 6.

[0078] As shown in the appended examples, such an antibody (e.g., MY010-P023, P023-HgLg, P023_HgLg-lgG4) binds specifically to Bet v 1, and also binds specifically or has affinity to several Bet v 1 homologous proteins, including tree pollen allergens, such as Fag s 1, Que a 1, Cor a 1, Ain g 1, Ost c 1 and Cas s 1, and to a number of natural PR-10 allergen extracts (birch, black alder, white alder, red alder, English oak, beech) as well as to several food allergens including Mal d 1, Pru p 1, Fra a 1, Act d 8, Jug r 5, and Can s 1. Moreover, it was shown that multispecific, in particular trispecific, antibodies including P023 HgLg-Fab as a "building block" (MY010-Tri5, MY010-Tri9) show superior cross-reactivity to PR-10 allergens and food allergens compared to prior art Regeneron antibodies, and are effective in mast cell activation test (MAT) and leukotriene release assay (LTRA) as well as in IgE competition ELISA.

[0079] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region VH comprising an amino acid sequence having 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%) identity to SEQ ID NO: 7, and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 8. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences as set forth in SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively; and light chain CDR1, CDR2, and CDR3 sequences as set forth in SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively) are preferably maintained.

[0080] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 7 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 8.

[0081] In some embodiments, the antibody, or the 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. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0082] a heavy chain CDR1 sequence according to SEQ ID NO: 9;

[0083] a heavy chain CDR2 sequence according to SEQ ID NO: 10;

[0084] a heavy chain CDR3 sequence according to SEQ ID NO: 11;

[0085] a light chain CDR1 sequence according to SEQ ID NO: 12;

[0086] a light chain CDR2 sequence according to SEQ ID NO: 13; and

[0087] a light chain CDR3 sequence according to SEQ ID NO: 14.

[0088] As shown in the appended examples, such an antibody (e.g., MY010-P031, P031-HgLg, P031_HgLg_LH) binds specifically to Bet v 1, and also binds specifically or has affinity to several Bet v 1 homologous proteins, including Que a 1, Cor a 1, Fag s 1, Cas s 1, Ost c 1, Ain g 1 and Car b 1 and to a number of natural PR-10 allergen extracts (birch, white alder, hazel pollen, beech) as well as to a number of food allergens including Act d 8. Moreover, it was shown that multispecific, in particular trispecific, antibodies including P031 HgLg Fab as a "building block" (MY010-TH5, MY010-TH19) show superior cross-reactivity to PR-10 allergens and food allergens compared to prior art Regeneron antibodies, and are effective in mast cell activation test (MAT) and leukotriene release assay (LTRA) as well as in IgE competition ELISA.

[0089] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 15 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 16. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences as set forth in SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11, respectively; and light chain CDR1, CDR2, and CDR3 sequences as set forth in SEQ ID NO: 12, SEQ ID NO: 13, and SEQ ID NO: 14, respectively) are preferably maintained.

[0090] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 15 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 16.

[0091] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 17, a CDRH2 having at least 70% identity to SEQ ID NO: 18, a CDRH3 having at least 70% identity to SEQ ID NO: 19, a CDRL1 having at least 70% identity to SEQ ID NO: 20, a CDRL2 having at least 70% identity to SEQ ID NO: 21, and a CDRL3 having at least 70% identity to SEQ ID NO: 22. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0092] a heavy chain CDR1 sequence according to SEQ ID NO: 17;

[0093] a heavy chain CDR2 sequence according to SEQ ID NO: 18;

[0094] a heavy chain CDR3 sequence according to SEQ ID NO: 19;

[0095] a light chain CDR1 sequence according to SEQ ID NO: 20;

[0096] a light chain CDR2 sequence according to SEQ ID NO: 21; and

[0097] a light chain CDR3 sequence according to SEQ ID NO: 22.

[0098] As shown in the appended examples, such an antibody (e.g. MY010-P069, P069-Hf5Lf1, P069_Hf5Lf1 -lgG4) binds specifically to Bet v 1, and also binds specifically or has affinity to several Bet v 1 homologous proteins, including Que a 1, Cor a 1, Fag s 1, Cas s 1, Ost c 1, and Car b 1 and to a number of natural PR-10 allergen extracts (birch, white alder, hazel pollen, beech) as well as to several food allergens including Mal d 1, Pru p 1, Fra a 1, Act d 8, Jur r 5. Moreover, it was shown that multispecific, in particular bispecific and trispecific, antibodies including P069 Hf5Lf1 as a "building block" (MY010-Bisp48, MY010-Bisp173, MY010-Tri10) show superior cross-reactivity to PR-10 allergens and food allergens compared to prior art Regeneron antibodies, and are effective in mast cell activation test (MAT) and leukotriene release assay (LTRA) as well as in IgE competition ELISA.

[0099] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 23 or 799, and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 24. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences as set forth in SEQ ID NO: 17, SEQ ID NO: 18, and SEQ ID NO: 19, respectively; and light chain CDR1, CDR2, and CDR3 sequences as set forth in SEQ ID NO: 20, SEQ ID NO: 21, and SEQ ID NO: 22, respectively) are preferably maintained.

[0100] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 23 or 799, and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 24. In this respect, it is noted that the heavy chain variable region according to SEQ ID NO: 799 is a variant of the heavy chain variable region according to SEQ ID NO: 23 that features an amino acid substitution (P103W) at position 103 (Kabat numbering). This variant of a heavy chain variable region (according to SEQ ID NO: 799) may advantageously be used in multispecific antibodies (e.g. trispecific antibody Tri10v2) as described herein.

[0101] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 25, a CDRH2 having at least 70% identity to SEQ ID NO: 26, a CDRH3 having at least 70% identity to SEQ ID NO: 27, a CDRL1 having at least 70% identity to SEQ ID NO: 28, a CDRL2 having at least 70% identity to SEQ ID NO: 29, and a CDRL3 having at least 70% identity to SEQ ID NO: 30. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0102] a heavy chain CDR1 sequence according to SEQ ID NO: 25;

[0103] a heavy chain CDR2 sequence according to SEQ ID NO: 26;

[0104] a heavy chain CDR3 sequence according to SEQ ID NO: 27;

[0105] a light chain CDR1 sequence according to SEQ ID NO: 28;

[0106] a light chain CDR2 sequence according to SEQ ID NO: 29; and

[0107] a light chain CDR3 sequence according to SEQ ID NO: 30.

[0108] As shown in the appended examples, such an antibody (e.g. MY010-P071 ) binds specifically to Bet v 1, and also binds specifically or has affinity to several Bet v 1 homologous proteins, including e.g. Que a 1, Cor a 1, Fag s 1, Cas s 1, Ost c 1, and Carb b 1. In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 31 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 32. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences as set forth in SEQ ID NO: 25, SEQ ID NO: 26, and SEQ ID NO: 27, respectively; and light chain CDR1, CDR2, and CDR3 sequences as set forth in SEQ ID NO: 28, SEQ ID NO: 29, and SEQ ID NO: 30, respectively) are preferably maintained.

[0109] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 31 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 32.

[0110] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 33, a CDRH2 having at least 70% identity to SEQ ID NO: 34, a CDRH3 having at least 70% identity to SEQ ID NO: 35, a CDRL1 having at least 70% identity to SEQ ID NO: 36, a CDRL2 having at least 70% identity to SEQ ID NO: 37, and a CDRL3 having at least 70% identity to SEQ ID NO: 38. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0111] a heavy chain CDR1 sequence according to SEQ ID NO: 33;

[0112] a heavy chain CDR2 sequence according to SEQ ID NO: 34;

[0113] a heavy chain CDR3 sequence according to SEQ ID NO: 35;

[0114] a light chain CDR1 sequence according to SEQ ID NO: 36; a light chain CDR2 sequence according to SEQ ID NO: 37; and

[0115] a light chain CDR3 sequence according to SEQ ID NO: 38.

[0116] As shown in the appended examples, such an antibody (e.g. MY010-P117) binds specifically to Bet v 1, and also binds specifically or has affinity to several Bet v 1 homologous proteins, including e.g. Que a 1, Cor a 1, Fag s 1, Cas s1, and Ost d.

[0117] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 39 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 40. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences as set forth in SEQ ID NO: 33, SEQ ID NO: 34, and SEQ ID NO: 35, respectively; and light chain CDR1, CDR2, and CDR3 sequences as set forth in SEQ ID NO: 36, SEQ ID NO: 37, and SEQ ID NO: 38, respectively) are preferably maintained.

[0118] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 39 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 40.

[0119] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 41, a CDRH2 having at least 70% identity to SEQ ID NO: 42, a CDRH3 having at least 70% identity to SEQ ID NO: 43, a CDRL1 having at least 70% identity to SEQ ID NO: 44, a CDRL2 having at least 70% identity to SEQ ID NO: 45, and a CDRL3 having at least 70% identity to SEQ ID NO: 46. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0120] a heavy chain CDR1 sequence according to SEQ ID NO: 41;

[0121] a heavy chain CDR2 sequence according to SEQ ID NO: 42;

[0122] a heavy chain CDR3 sequence according to SEQ ID NO: 43;

[0123] a light chain CDR1 sequence according to SEQ ID NO: 44;

[0124] a light chain CDR2 sequence according to SEQ ID NO: 45; and

[0125] a light chain CDR3 sequence according to SEQ ID NO: 46.

[0126] As shown in the appended examples, such an antibody (e.g. MY010-P123) binds specifically to Bet v 1, and also binds specifically or has affinity to several Bet v 1 homologous proteins, including Que a 1, Cor a 1, Fag s 1, and Cas s 1, Ost c 1 and Car b 1 for example.

[0127] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 47 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 48. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences as set forth in SEQ ID NO: 41, SEQ ID NO: 42, and SEQ ID NO: 43, respectively; and light chain CDR1, CDR2, and CDR3 sequences as set forth in SEQ ID NO: 44, SEQ ID NO: 45, and SEQ ID NO: 46, respectively) are preferably maintained. In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 47 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 48.

[0128] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 49, a CDRH2 having at least 70% identity to SEQ ID NO: 50, a CDRH3 having at least 70% identity to SEQ ID NO: 51, a CDRL1 having at least 70% identity to SEQ ID NO: 52, a CDRL2 having at least 70% identity to SEQ ID NO: 53, and a CDRL3 having at least 70% identity to SEQ ID NO: 54. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0129] a heavy chain CDR1 sequence according to SEQ ID NO: 49;

[0130] a heavy chain CDR2 sequence according to SEQ ID NO: 50;

[0131] a heavy chain CDR3 sequence according to SEQ ID NO: 51;

[0132] a light chain CDR1 sequence according to SEQ ID NO: 52;

[0133] a light chain CDR2 sequence according to SEQ ID NO: 53; and

[0134] a light chain CDR3 sequence according to SEQ ID NO: 54.

[0135] As shown in the appended examples, such an antibody (e.g. MY010-P126) binds specifically to Bet v 1, and also binds specifically or has affinity to several Bet v 1 homologous proteins, including Que a 1, Cor a 1, Fag s 1, and Cas s1, Ost c 1 and Car b 1, for example.

[0136] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 55 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 56. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences as set forth in SEQ ID NO: 49, SEQ ID NO: 50, and SEQ ID NO: 51, respectively; and light chain CDR1, CDR2, and CDR3 sequences as set forth in SEQ ID NO: 52, SEQ ID NO: 53, and SEQ ID NO: 54, respectively) are preferably maintained.

[0137] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 55 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 56.

[0138] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 57, a CDRH2 having at least 70% identity to SEQ ID NO: 58, a CDRH3 having at least 70% identity to SEQ ID NO: 59, a CDRL1 having at least 70% identity to SEQ ID NO: 60, a CDRL2 having at least 70% identity to SEQ ID NO: 61, and a CDRL3 having at least 70% identity to SEQ ID NO: 62. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0139] a heavy chain CDR1 sequence according to SEQ ID NO: 57;

[0140] a heavy chain CDR2 sequence according to SEQ ID NO: 58;

[0141] a heavy chain CDR3 sequence according to SEQ ID NO: 59;

[0142] a light chain CDR1 sequence according to SEQ ID NO: 60;

[0143] a light chain CDR2 sequence according to SEQ ID NO: 61; and

[0144] a light chain CDR3 sequence according to SEQ ID NO: 62.

[0145] As shown in the appended examples, such an antibody (e.g. MY010-P116) binds specifically to Bet v 1, and also binds specifically or has affinity to several Bet v 1 homologous proteins, including Que a 1, Cor a 1, Fag s 1, and Cas s1, Ost c 1 and Car b 1 for example.

[0146] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 63 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 64. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences as set forth in SEQ ID NO: 57, SEQ ID NO: 58, and SEQ ID NO: 59, respectively; and light chain CDR1, CDR2, and CDR3 sequences as set forth in SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively) are preferably maintained.

[0147] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 63 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 64.

[0148] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 65, a CDRH2 having at least 70% identity to SEQ ID NO: 66, a CDRH3 having at least 70% identity to SEQ ID NO: 67, a CDRL1 having at least 70% identity to SEQ ID NO: 68, a CDRL2 having at least 70% identity to SEQ ID NO: 69, and a CDRL3 having at least 70% identity to SEQ ID NO: 70. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0149] a heavy chain CDR1 sequence according to SEQ ID NO: 65;

[0150] a heavy chain CDR2 sequence according to SEQ ID NO: 66;

[0151] a heavy chain CDR3 sequence according to SEQ ID NO: 67;

[0152] a light chain CDR1 sequence according to SEQ ID NO: 68;

[0153] a light chain CDR2 sequence according to SEQ ID NO: 69; and

[0154] a light chain CDR3 sequence according to SEQ ID NO: 70. As shown in the appended examples, such an antibody (e.g. MY010-P130) binds specifically to Bet v 1, and also binds specifically or has affinity to several Bet v 1 homologous proteins, including Que a 1, Cor a 1, Fag s 1, and Cas s 1, for example.

[0155] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 71 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 72. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences as set forth in SEQ ID NO: 65, SEQ ID NO: 66, and SEQ ID NO: 67, respectively; and light chain CDR1, CDR2, and CDR3 sequences as set forth in SEQ ID NO: 68, SEQ ID NO: 69, and SEQ ID NO: 70, respectively) are preferably maintained.

[0156] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 71 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 72.

[0157] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 73, a CDRH2 having at least 70% identity to SEQ ID NO: 74, a CDRH3 having at least 70% identity to SEQ ID NO: 75, a CDRL1 having at least 70% identity to SEQ ID NO: 76, a CDRL2 having at least 70% identity to SEQ ID NO: 77, and a CDRL3 having at least 70% identity to SEQ ID NO: 78 or 800. Preferably, the antibody or the antigen-binding fragment thereof comprises: a heavy chain CDR1 sequence according to SEQ ID NO: 73;

[0158] a heavy chain CDR2 sequence according to SEQ ID NO: 74;

[0159] a heavy chain CDR3 sequence according to SEQ ID NO: 75;

[0160] a light chain CDR1 sequence according to SEQ ID NO: 76;

[0161] a light chain CDR2 sequence according to SEQ ID NO: 77; and

[0162] a light chain CDR3 sequence according to SEQ ID NO: 78 or 800.

[0163] As shown in the appended examples, such an antibody (e.g. MY010-P187, P187-Hg1 Lf2, P187_Hg1 Lf2-lgG4) binds specifically to Bet v 1, and also binds specifically or has affinity to several Bet v 1 homologous proteins, including Que a 1, Cor a 1, Fag s 1, Cas s1, Ost c 1, Ain g 1, and Car b 1, for example, and to a number of natural PR-10 allergen extracts (birch, black alder, white alder, red alder, hazel pollen, English oak, beech) as well as to several food allergens including Pru p 1, Fra a 1, Act d 8. Moreover, it was shown that a multispecific, in particular bispecific, antibody including P187-Hg1 Lf2 as a "building block" (MY010-Bisp94) shows superior cross-reactivity to PR-10 allergens and food allergens compared to prior art Regeneron antibodies, and are effective in mast cell activation test (MAT) and leukotriene release assay (LTRA) as well as in IgE competition ELISA.

[0164] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 79 or 801, and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 80 or 802. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences as set forth in SEQ ID NO: 73, SEQ ID NO: 74, and SEQ ID NO: 75, respectively; and light chain CDR1, CDR2, and CDR3 sequences as set forth in SEQ ID NO: 76, SEQ ID NO: 77, and SEQ ID NO: 78 or 800, respectively) are preferably maintained.

[0165] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 79 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 80.

[0166] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 81, a CDRH2 having at least 70% identity to SEQ ID NO: 82, a CDRH3 having at least 70% identity to SEQ ID NO: 83, a CDRL1 having at least 70% identity to SEQ ID NO: 84, a CDRL2 having at least 70% identity to SEQ ID NO: 85, and a CDRL3 having at least 70% identity to SEQ ID NO: 86. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0167] a heavy chain CDR1 sequence according to SEQ ID NO: 81;

[0168] a heavy chain CDR2 sequence according to SEQ ID NO: 82;

[0169] a heavy chain CDR3 sequence according to SEQ ID NO: 83;

[0170] a light chain CDR1 sequence according to SEQ ID NO: 84;

[0171] a light chain CDR2 sequence according to SEQ ID NO: 85; and

[0172] a light chain CDR3 sequence according to SEQ ID NO: 86.

[0173] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 87 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 88. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0174] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 87 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 88.

[0175] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 89, a CDRH2 having at least 70% identity to SEQ ID NO: 90, a CDRH3 having at least 70% identity to SEQ ID NO: 91, a CDRL1 having at least 70% identity to SEQ ID NO: 92, a CDRL2 having at least 70% identity to SEQ ID NO: 93, and a CDRL3 having at least 70% identity to SEQ ID NO: 94. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0176] a heavy chain CDR1 sequence according to SEQ ID NO: 89;

[0177] a heavy chain CDR2 sequence according to SEQ ID NO: 90;

[0178] a heavy chain CDR3 sequence according to SEQ ID NO: 91;

[0179] a light chain CDR1 sequence according to SEQ ID NO: 92;

[0180] a light chain CDR2 sequence according to SEQ ID NO: 93; and

[0181] a light chain CDR3 sequence according to SEQ ID NO: 94.

[0182] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 95 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 96. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0183] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 95 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 96.

[0184] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 97, a CDRH2 having at least 70% identity to SEQ ID NO: 98, a CDRH3 having at least 70% identity to SEQ ID NO: 999, a CDRL1 having at least 70% identity to SEQ ID NO: 100, a CDRL2 having at least 70% identity to SEQ ID NO: 101, and a CDRL3 having at least 70% identity to SEQ ID NO: 102. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0185] a heavy chain CDR1 sequence according to SEQ ID NO: 97;

[0186] a heavy chain CDR2 sequence according to SEQ ID NO: 98;

[0187] a heavy chain CDR3 sequence according to SEQ ID NO: 99;

[0188] a light chain CDR1 sequence according to SEQ ID NO: 100;

[0189] a light chain CDR2 sequence according to SEQ ID NO: 101; and

[0190] a light chain CDR3 sequence according to SEQ ID NO: 102.

[0191] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 103 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 104. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0192] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 103 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 104.

[0193] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 105, a CDRH2 having at least 70% identity to SEQ ID NO: 106, a CDRH3 having at least 70% identity to SEQ ID NO: 107, a CDRL1 having at least 70% identity to SEQ ID NO: 108, a CDRL2 having at least 70% identity to SEQ ID NO: 109, and a CDRL3 having at least 70% identity to SEQ ID NO: 110. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0194] a heavy chain CDR1 sequence according to SEQ ID NO: 105;

[0195] a heavy chain CDR2 sequence according to SEQ ID NO: 106;

[0196] a heavy chain CDR3 sequence according to SEQ ID NO: 107;

[0197] a light chain CDR1 sequence according to SEQ ID NO: 108;

[0198] a light chain CDR2 sequence according to SEQ ID NO: 109; and

[0199] a light chain CDR3 sequence according to SEQ ID NO: 110.

[0200] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 111 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 112. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0201] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 111 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 112.

[0202] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 113, a CDRH2 having at least 70% identity to SEQ ID NO: 114, a CDRH3 having at least 70% identity to SEQ ID NO: 115, a CDRL1 having at least 70% identity to SEQ ID NO: 116, a CDRL2 having at least 70% identity to SEQ ID NO: 117, and a CDRL3 having at least 70% identity to SEQ ID NO: 118. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0203] a heavy chain CDR1 sequence according to SEQ ID NO: 113;

[0204] a heavy chain CDR2 sequence according to SEQ ID NO: 114;

[0205] a heavy chain CDR3 sequence according to SEQ ID NO: 115;

[0206] a light chain CDR1 sequence according to SEQ ID NO: 116;

[0207] a light chain CDR2 sequence according to SEQ ID NO: 117; and

[0208] a light chain CDR3 sequence according to SEQ ID NO: 118.

[0209] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 119 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 120. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0210] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 119 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 120.

[0211] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 121, a CDRH2 having at least 70% identity to SEQ ID NO: 122, a CDRH3 having at least 70% identity to SEQ ID NO: 123, a CDRL1 having at least 70% identity to SEQ ID NO: 124, a CDRL2 having at least 70% identity to SEQ ID NO: 125, and a CDRL3 having at least 70% identity to SEQ ID NO: 126. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0212] a heavy chain CDR1 sequence according to SEQ ID NO: 121;

[0213] a heavy chain CDR2 sequence according to SEQ ID NO: 122;

[0214] a heavy chain CDR3 sequence according to SEQ ID NO: 123;

[0215] a light chain CDR1 sequence according to SEQ ID NO: 124;

[0216] a light chain CDR2 sequence according to SEQ ID NO: 125; and

[0217] a light chain CDR3 sequence according to SEQ ID NO: 126.

[0218] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 127 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 128. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0219] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 127 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 128.

[0220] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 129, a CDRH2 having at least 70% identity to SEQ ID NO: 130, a CDRH3 having at least 70% identity to SEQ ID NO: 131, a CDRL1 having at least 70% identity to SEQ ID NO: 132, a CDRL2 having at least 70% identity to SEQ ID NO: 133, and a CDRL3 having at least 70% identity to SEQ ID NO: 134. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0221] a heavy chain CDR1 sequence according to SEQ ID NO: 129;

[0222] a heavy chain CDR2 sequence according to SEQ ID NO: 130;

[0223] a heavy chain CDR3 sequence according to SEQ ID NO: 131;

[0224] a light chain CDR1 sequence according to SEQ ID NO: 132;

[0225] a light chain CDR2 sequence according to SEQ ID NO: 133; and

[0226] a light chain CDR3 sequence according to SEQ ID NO: 134.

[0227] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 135 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 136. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0228] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 135 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 136.

[0229] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 137, a CDRH2 having at least 70% identity to SEQ ID NO: 138, a CDRH3 having at least 70% identity to SEQ ID NO: 139, a CDRL1 having at least 70% identity to SEQ ID NO: 140, a CDRL2 having at least 70% identity to SEQ ID NO: 141, and a CDRL3 having at least 70% identity to SEQ ID NO: 142. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0230] a heavy chain CDR1 sequence according to SEQ ID NO: 137;

[0231] a heavy chain CDR2 sequence according to SEQ ID NO: 138;

[0232] a heavy chain CDR3 sequence according to SEQ ID NO: 139;

[0233] a light chain CDR1 sequence according to SEQ ID NO: 140;

[0234] a light chain CDR2 sequence according to SEQ ID NO: 141; and

[0235] a light chain CDR3 sequence according to SEQ ID NO: 142.

[0236] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 143 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 144. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0237] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 143 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 144.

[0238] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 145, a CDRH2 having at least 70% identity to SEQ ID NO: 146, a CDRH3 having at least 70% identity to SEQ ID NO: 147, a CDRL1 having at least 70% identity to SEQ ID NO: 148, a CDRL2 having at least 70% identity to SEQ ID NO: 149, and a CDRL3 having at least 70% identity to SEQ ID NO: 150. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0239] a heavy chain CDR1 sequence according to SEQ ID NO: 145;

[0240] a heavy chain CDR2 sequence according to SEQ ID NO: 146;

[0241] a heavy chain CDR3 sequence according to SEQ ID NO: 147;

[0242] a light chain CDR1 sequence according to SEQ ID NO: 148;

[0243] a light chain CDR2 sequence according to SEQ ID NO: 149; and

[0244] a light chain CDR3 sequence according to SEQ ID NO: 150.

[0245] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 151 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 152. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0246] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 151 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 152.

[0247] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 153, a CDRH2 having at least 70% identity to SEQ ID NO: 154, a CDRH3 having at least 70% identity to SEQ ID NO: 155, a CDRL1 having at least 70% identity to SEQ ID NO: 156, a CDRL2 having at least 70% identity to SEQ ID NO: 157, and a CDRL3 having at least 70% identity to SEQ ID NO: 158. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0248] a heavy chain CDR1 sequence according to SEQ ID NO: 153;

[0249] a heavy chain CDR2 sequence according to SEQ ID NO: 154;

[0250] a heavy chain CDR3 sequence according to SEQ ID NO: 155;

[0251] a light chain CDR1 sequence according to SEQ ID NO: 156;

[0252] a light chain CDR2 sequence according to SEQ ID NO: 157; and

[0253] a light chain CDR3 sequence according to SEQ ID NO: 158.

[0254] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 159 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 160. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0255] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 159 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 160.

[0256] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 161, a CDRH2 having at least 70% identity to SEQ ID NO: 162, a CDRH3 having at least 70% identity to SEQ ID NO: 163, a CDRL1 having at least 70% identity to SEQ ID NO: 164, a CDRL2 having at least 70% identity to SEQ ID NO: 165, and a CDRL3 having at least 70% identity to SEQ ID NO: 166. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0257] a heavy chain CDR1 sequence according to SEQ ID NO: 161;

[0258] a heavy chain CDR2 sequence according to SEQ ID NO: 162;

[0259] a heavy chain CDR3 sequence according to SEQ ID NO: 163;

[0260] a light chain CDR1 sequence according to SEQ ID NO: 164;

[0261] a light chain CDR2 sequence according to SEQ ID NO: 165; and

[0262] a light chain CDR3 sequence according to SEQ ID NO: 166. In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 167 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 168. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0263] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 167 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 168.

[0264] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 169, a CDRH2 having at least 70% identity to SEQ ID NO: 170, a CDRH3 having at least 70% identity to SEQ ID NO: 171, a CDRL1 having at least 70% identity to SEQ ID NO: 172, a CDRL2 having at least 70% identity to SEQ ID NO: 173, and a CDRL3 having at least 70% identity to SEQ ID NO: 174. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0265] a heavy chain CDR1 sequence according to SEQ ID NO: 169;

[0266] a heavy chain CDR2 sequence according to SEQ ID NO: 170;

[0267] a heavy chain CDR3 sequence according to SEQ ID NO: 171;

[0268] a light chain CDR1 sequence according to SEQ ID NO: 172;

[0269] a light chain CDR2 sequence according to SEQ ID NO: 173; and

[0270] a light chain CDR3 sequence according to SEQ ID NO: 174. In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 175 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 176. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0271] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 175 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 176.

[0272] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 177, a CDRH2 having at least 70% identity to SEQ ID NO: 178, a CDRH3 having at least 70% identity to SEQ ID NO: 179, a CDRL1 having at least 70% identity to SEQ ID NO: 180, a CDRL2 having at least 70% identity to SEQ ID NO: 181, and a CDRL3 having at least 70% identity to SEQ ID NO: 182. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0273] a heavy chain CDR1 sequence according to SEQ ID NO: 177;

[0274] a heavy chain CDR2 sequence according to SEQ ID NO: 178;

[0275] a heavy chain CDR3 sequence according to SEQ ID NO: 179;

[0276] a light chain CDR1 sequence according to SEQ ID NO: 180;

[0277] a light chain CDR2 sequence according to SEQ ID NO: 181; and a light chain CDR3 sequence according to SEQ ID NO: 182.

[0278] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 183 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 184. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0279] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 183 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 184.

[0280] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 185, a CDRH2 having at least 70% identity to SEQ ID NO: 186, a CDRH3 having at least 70% identity to SEQ ID NO: 187, a CDRL1 having at least 70% identity to SEQ ID NO: 188, a CDRL2 having at least 70% identity to SEQ ID NO: 189, and a CDRL3 having at least 70% identity to SEQ ID NO: 190. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0281] a heavy chain CDR1 sequence according to SEQ ID NO: 185;

[0282] a heavy chain CDR2 sequence according to SEQ ID NO: 186;

[0283] a heavy chain CDR3 sequence according to SEQ ID NO: 187;

[0284] a light chain CDR1 sequence according to SEQ ID NO: 188;

[0285] a light chain CDR2 sequence according to SEQ ID NO: 189; and a light chain CDR3 sequence according to SEQ ID NO: 190.

[0286] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 191 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 192. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0287] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 191 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 192.

[0288] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 193, a CDRH2 having at least 70% identity to SEQ ID NO: 194, a CDRH3 having at least 70% identity to SEQ ID NO: 195, a CDRL1 having at least 70% identity to SEQ ID NO: 196, a CDRL2 having at least 70% identity to SEQ ID NO: 197, and a CDRL3 having at least 70% identity to SEQ ID NO: 198. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0289] a heavy chain CDR1 sequence according to SEQ ID NO: 193;

[0290] a heavy chain CDR2 sequence according to SEQ ID NO: 194;

[0291] a heavy chain CDR3 sequence according to SEQ ID NO: 195;

[0292] a light chain CDR1 sequence according to SEQ ID NO: 196;

[0293] a light chain CDR2 sequence according to SEQ ID NO: 197; and a light chain CDR3 sequence according to SEQ ID NO: 198.

[0294] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 199 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 200. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0295] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 199 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 200.

[0296] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 201, a CDRH2 having at least 70% identity to SEQ ID NO: 202, a CDRH3 having at least 70% identity to SEQ ID NO: 203, a CDRL1 having at least 70% identity to SEQ ID NO: 204, a CDRL2 having at least 70% identity to SEQ ID NO: 205, and a CDRL3 having at least 70% identity to SEQ ID NO: 206. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0297] a heavy chain CDR1 sequence according to SEQ ID NO: 201;

[0298] a heavy chain CDR2 sequence according to SEQ ID NO: 202;

[0299] a heavy chain CDR3 sequence according to SEQ ID NO: 203;

[0300] a light chain CDR1 sequence according to SEQ ID NO: 204;

[0301] a light chain CDR2 sequence according to SEQ ID NO: 205; and a light chain CDR3 sequence according to SEQ ID NO: 206.

[0302] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 207 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 208. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0303] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 207 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 208.

[0304] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 209, a CDRH2 having at least 70% identity to SEQ ID NO: 210, a CDRH3 having at least 70% identity to SEQ ID NO: 211, a CDRL1 having at least 70% identity to SEQ ID NO: 212, a CDRL2 having at least 70% identity to SEQ ID NO: 213, and a CDRL3 having at least 70% identity to SEQ ID NO: 214. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0305] a heavy chain CDR1 sequence according to SEQ ID NO: 209;

[0306] a heavy chain CDR2 sequence according to SEQ ID NO: 210;

[0307] a heavy chain CDR3 sequence according to SEQ ID NO: 211;

[0308] a light chain CDR1 sequence according to SEQ ID NO: 212;

[0309] a light chain CDR2 sequence according to SEQ ID NO: 213; and a light chain CDR3 sequence according to SEQ ID NO: 214.

[0310] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 215 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 216. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0311] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 215 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 216.

[0312] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 217, a CDRH2 having at least 70% identity to SEQ ID NO: 218, a CDRH3 having at least 70% identity to SEQ ID NO: 219, a CDRL1 having at least 70% identity to SEQ ID NO: 220, a CDRL2 having at least 70% identity to SEQ ID NO: 221, and a CDRL3 having at least 70% identity to SEQ ID NO: 222. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0313] a heavy chain CDR1 sequence according to SEQ ID NO: 217;

[0314] a heavy chain CDR2 sequence according to SEQ ID NO: 218;

[0315] a heavy chain CDR3 sequence according to SEQ ID NO: 219;

[0316] a light chain CDR1 sequence according to SEQ ID NO: 220;

[0317] a light chain CDR2 sequence according to SEQ ID NO: 221; and a light chain CDR3 sequence according to SEQ ID NO: 222.

[0318] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 223 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 224. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0319] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 223 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 224.

[0320] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 225, a CDRH2 having at least 70% identity to SEQ ID NO: 226, a CDRH3 having at least 70% identity to SEQ ID NO: 227, a CDRL1 having at least 70% identity to SEQ ID NO: 228, a CDRL2 having at least 70% identity to SEQ ID NO: 229, and a CDRL3 having at least 70% identity to SEQ ID NO: 230. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0321] a heavy chain CDR1 sequence according to SEQ ID NO: 225;

[0322] a heavy chain CDR2 sequence according to SEQ ID NO: 226;

[0323] a heavy chain CDR3 sequence according to SEQ ID NO: 227;

[0324] a light chain CDR1 sequence according to SEQ ID NO: 228;

[0325] a light chain CDR2 sequence according to SEQ ID NO: 229; and a light chain CDR3 sequence according to SEQ ID NO: 230.

[0326] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 231 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 232. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0327] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 231 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 232.

[0328] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 233, a CDRH2 having at least 70% identity to SEQ ID NO: 234, a CDRH3 having at least 70% identity to SEQ ID NO: 235, a CDRL1 having at least 70% identity to SEQ ID NO: 236, a CDRL2 having at least 70% identity to SEQ ID NO: 237, and a CDRL3 having at least 70% identity to SEQ ID NO: 238. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0329] a heavy chain CDR1 sequence according to SEQ ID NO: 233;

[0330] a heavy chain CDR2 sequence according to SEQ ID NO: 234;

[0331] a heavy chain CDR3 sequence according to SEQ ID NO: 235;

[0332] a light chain CDR1 sequence according to SEQ ID NO: 236;

[0333] a light chain CDR2 sequence according to SEQ ID NO: 237; and a light chain CDR3 sequence according to SEQ ID NO: 238.

[0334] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 239 or 803 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 240 or 804. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0335] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 239 or 803, and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 240 or 804. In preferred embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 803, and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 804. This variant, which has been obtained by germline reversion of framework regions, has proven to be particularly suitable when used as a building block in multi-specific antibodies.

[0336] As shown in the appended examples, such an antibody (e.g. MY010-P236, P236-Hg1Lf1, P236_Hg1Lf1_STT_LH, P236_Hg1Lf1_LH) binds specifically to Bet v 1, and also binds specifically or has affinity to several Bet v 1 homologous proteins, including Que a 1, Cor a 1, Cas s 1, Ost c 1, and Car b 1, for example, and to a number of natural PR-10 allergen extracts (birch, black alder, white alder, red alder, hazel pollen, English oak, beech) as well as to several food allergens including Mal d 1, Pru p 1. Moreover, it was shown that multispecific, in particular trispecific, antibodies including P236 Hg1 Lf1 as a "building block" (MY010-Tri19, MY010-Tri20) show superior cross-reactivity to PR-10 allergens and food allergens compared to prior art Regeneron antibodies, and are effective in mast cell activation test (MAT) and leukotriene release assay (LTRA) as well as in IgE competition ELISA.

[0337] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 241, a CDRH2 having at least 70% identity to SEQ ID NO: 242, a CDRH3 having at least 70% identity to SEQ ID NO: 243, a CDRL1 having at least 70% identity to SEQ ID NO: 244, a CDRL2 having at least 70% identity to SEQ ID NO: 245, and a CDRL3 having at least 70% identity to SEQ ID NO: 246. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0338] a heavy chain CDR1 sequence according to SEQ ID NO: 241;

[0339] a heavy chain CDR2 sequence according to SEQ ID NO: 242;

[0340] a heavy chain CDR3 sequence according to SEQ ID NO: 243;

[0341] a light chain CDR1 sequence according to SEQ ID NO: 244;

[0342] a light chain CDR2 sequence according to SEQ ID NO: 245; and

[0343] a light chain CDR3 sequence according to SEQ ID NO: 246.

[0344] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 247 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 248. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0345] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 247 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 248.

[0346] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 249, a CDRH2 having at least 70% identity to SEQ ID NO: 250, a CDRH3 having at least 70% identity to SEQ ID NO: 251, a CDRL1 having at least 70% identity to SEQ ID NO: 252, a CDRL2 having at least 70% identity to SEQ ID NO: 253, and a CDRL3 having at least 70% identity to SEQ ID NO: 254. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0347] a heavy chain CDR1 sequence according to SEQ ID NO: 249;

[0348] a heavy chain CDR2 sequence according to SEQ ID NO: 250;

[0349] a heavy chain CDR3 sequence according to SEQ ID NO: 251;

[0350] a light chain CDR1 sequence according to SEQ ID NO: 252;

[0351] a light chain CDR2 sequence according to SEQ ID NO: 253; and

[0352] a light chain CDR3 sequence according to SEQ ID NO: 254.

[0353] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 255 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 256. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0354] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 255 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 256.

[0355] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 257, a CDRH2 having at least 70% identity to SEQ ID NO: 258, a CDRH3 having at least 70% identity to SEQ ID NO: 259, a CDRL1 having at least 70% identity to SEQ ID NO: 260, a CDRL2 having at least 70% identity to SEQ ID NO: 261, and a CDRL3 having at least 70% identity to SEQ ID NO: 262. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0356] a heavy chain CDR1 sequence according to SEQ ID NO: 257;

[0357] a heavy chain CDR2 sequence according to SEQ ID NO: 258;

[0358] a heavy chain CDR3 sequence according to SEQ ID NO: 259;

[0359] a light chain CDR1 sequence according to SEQ ID NO: 260;

[0360] a light chain CDR2 sequence according to SEQ ID NO: 261; and

[0361] a light chain CDR3 sequence according to SEQ ID NO: 262.

[0362] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 263 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 264. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0363] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 263 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 264.

[0364] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 265, a CDRH2 having at least 70% identity to SEQ ID NO: 266, a CDRH3 having at least 70% identity to SEQ ID NO: 267, a CDRL1 having at least 70% identity to SEQ ID NO: 268, a CDRL2 having at least 70% identity to SEQ ID NO: 269, and a CDRL3 having at least 70% identity to SEQ ID NO: 270. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0365] a heavy chain CDR1 sequence according to SEQ ID NO: 265;

[0366] a heavy chain CDR2 sequence according to SEQ ID NO: 266;

[0367] a heavy chain CDR3 sequence according to SEQ ID NO: 267;

[0368] a light chain CDR1 sequence according to SEQ ID NO: 268;

[0369] a light chain CDR2 sequence according to SEQ ID NO: 269; and

[0370] a light chain CDR3 sequence according to SEQ ID NO: 270.

[0371] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 271or 805, and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 272 or 806. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0372] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 271or 805, and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 272 or 806. In preferred embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 805, and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 806. This variant, which has been obtained by germline reversion of framework regions, has proven to be particularly suitable when used as a building block in multi-specific antibodies.

[0373] As shown in the appended examples, such an antibody (e.g., P252-Hg1Lf1, P252_Hg1Lf1_HL, P252_Hg1Lf1_LH, P252_Hg1Lf1-IgG4) binds specifically to Bet v 1, and also binds specifically or has affinity to several Bet v 1 homologous proteins, including Cor a 1, Que a 1, Ain g 1, Cas s 1, Fag s 1, and Ost c 1, for example, and to a number of natural PR-10 allergen extracts (birch, black alder, white alder, red alder, hazel pollen, English oak, beech), as well as to several food allergens including Mal d 1, Pru p 1, Fra a 1, Act d 8, and Jug r 5. Moreover, it was shown that multispecific, in particular bispecific and trispecific antibodies including P252 Hg1Lf2 as a "building block" (MY010-Bisp94, MY010-Tri12, MY010-Tri 16, MY010-Tri 19, MY010-Tri20) show superior cross-reactivity to PR-10 allergens and food allergens compared to prior art Regeneron antibodies, and are effective in mast cell activation test (MAT) and leukotriene release assay (LTRA) as well as in IgE competition ELISA.

[0374] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 273, a CDRH2 having at least 70% identity to SEQ ID NO: 274, a CDRH3 having at least 70% identity to SEQ ID NO: 275, a CDRL1 having at least 70% identity to SEQ ID NO: 276, a CDRL2 having at least 70% identity to SEQ ID NO: 277, and a CDRL3 having at least 70% identity to SEQ ID NO: 278. Preferably, the antibody or the antigen-binding fragment thereof comprises: a heavy chain CDR1 sequence according to SEQ ID NO: 273;

[0375] a heavy chain CDR2 sequence according to SEQ ID NO: 274;

[0376] a heavy chain CDR3 sequence according to SEQ ID NO: 275;

[0377] a light chain CDR1 sequence according to SEQ ID NO: 276;

[0378] a light chain CDR2 sequence according to SEQ ID NO: 277; and

[0379] a light chain CDR3 sequence according to SEQ ID NO: 278.

[0380] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 279 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 280. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0381] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 279 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 280.

[0382] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 281, a CDRH2 having at least 70% identity to SEQ ID NO: 282, a CDRH3 having at least 70% identity to SEQ ID NO: 283, a CDRL1 having at least 70% identity to SEQ ID NO: 284, a CDRL2 having at least 70% identity to SEQ ID NO: 285, and a CDRL3 having at least 70% identity to SEQ ID NO: 286. Preferably, the antibody or the antigen-binding fragment thereof comprises: a heavy chain CDR1 sequence according to SEQ ID NO: 281;

[0383] a heavy chain CDR2 sequence according to SEQ ID NO: 282;

[0384] a heavy chain CDR3 sequence according to SEQ ID NO: 283;

[0385] a light chain CDR1 sequence according to SEQ ID NO: 284;

[0386] a light chain CDR2 sequence according to SEQ ID NO: 285; and

[0387] a light chain CDR3 sequence according to SEQ ID NO: 286.

[0388] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 287 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 288. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0389] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 287 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 288.

[0390] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 289, a CDRH2 having at least 70% identity to SEQ ID NO: 290, a CDRH3 having at least 70% identity to SEQ ID NO: 291, a CDRL1 having at least 70% identity to SEQ ID NO: 292, a CDRL2 having at least 70% identity to SEQ ID NO: 293, and a CDRL3 having at least 70% identity to SEQ ID NO: 294. Preferably, the antibody or the antigen-binding fragment thereof comprises: a heavy chain CDR1 sequence according to SEQ ID NO: 289;

[0391] a heavy chain CDR2 sequence according to SEQ ID NO: 290;

[0392] a heavy chain CDR3 sequence according to SEQ ID NO: 291;

[0393] a light chain CDR1 sequence according to SEQ ID NO: 292;

[0394] a light chain CDR2 sequence according to SEQ ID NO: 293; and

[0395] a light chain CDR3 sequence according to SEQ ID NO: 294.

[0396] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 295 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 296. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0397] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 295 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 296.

[0398] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 297, a CDRH2 having at least 70% identity to SEQ ID NO: 298, a CDRH3 having at least 70% identity to SEQ ID NO: 299, a CDRL1 having at least 70% identity to SEQ ID NO: 300, a CDRL2 having at least 70% identity to SEQ ID NO: 301, and a CDRL3 having at least 70% identity to SEQ ID NO: 302. Preferably, the antibody or the antigen-binding fragment thereof comprises: a heavy chain CDR1 sequence according to SEQ ID NO: 297;

[0399] a heavy chain CDR2 sequence according to SEQ ID NO: 298;

[0400] a heavy chain CDR3 sequence according to SEQ ID NO: 299;

[0401] a light chain CDR1 sequence according to SEQ ID NO: 300;

[0402] a light chain CDR2 sequence according to SEQ ID NO: 301; and

[0403] a light chain CDR3 sequence according to SEQ ID NO: 302.

[0404] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 303 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 304. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0405] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 303 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 304.

[0406] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 305, a CDRH2 having at least 70% identity to SEQ ID NO: 306, a CDRH3 having at least 70% identity to SEQ ID NO: 307, a CDRL1 having at least 70% identity to SEQ ID NO: 308, a CDRL2 having at least 70% identity to SEQ ID NO: 309, and a CDRL3 having at least 70% identity to SEQ ID NO: 310. Preferably, the antibody or the antigen-binding fragment thereof comprises: a heavy chain CDR1 sequence according to SEQ ID NO: 305;

[0407] a heavy chain CDR2 sequence according to SEQ ID NO: 306;

[0408] a heavy chain CDR3 sequence according to SEQ ID NO: 307;

[0409] a light chain CDR1 sequence according to SEQ ID NO: 308;

[0410] a light chain CDR2 sequence according to SEQ ID NO: 309; and

[0411] a light chain CDR3 sequence according to SEQ ID NO: 310.

[0412] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 311 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 312. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0413] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 311 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 312.

[0414] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 313, a CDRH2 having at least 70% identity to SEQ ID NO: 314, a CDRH3 having at least 70% identity to SEQ ID NO: 315, a CDRL1 having at least 70% identity to SEQ ID NO: 316, a CDRL2 having at least 70% identity to SEQ ID NO: 317, and a CDRL3 having at least 70% identity to SEQ ID NO: 318. Preferably, the antibody or the antigen-binding fragment thereof comprises: a heavy chain CDR1 sequence according to SEQ ID NO: 313;

[0415] a heavy chain CDR2 sequence according to SEQ ID NO: 314;

[0416] a heavy chain CDR3 sequence according to SEQ ID NO: 315;

[0417] a light chain CDR1 sequence according to SEQ ID NO: 316;

[0418] a light chain CDR2 sequence according to SEQ ID NO: 317; and

[0419] a light chain CDR3 sequence according to SEQ ID NO: 318.

[0420] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 319 or 807, and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 320 or 808. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0421] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 319 or 807, and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 320 or 808. In preferred embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 807, and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 808. This variant, which has been obtained by germline reversion of framework regions, has proven to be particularly suitable when used as a building block in multi-specific antibodies.

[0422] As shown in the appended examples, such an antibody (e.g. P268-Hg1Lf1, P268_Hg1Lf1-IgG4) binds specifically to Bet v 1, and also binds specifically or has affinity to several Bet v 1 homologous proteins, including Cor a 1, Que a 1, Ain g 1, Fag s 1, Ost c 1 and Car b 1, for example, and to a number of natural PR-10 allergen extracts (birch, black alder, white alder, red alder, hazel pollen, English oak, beech), as well as to a number of food allergens including Mal d 1, Pru p 1, Fra a 1, Act d 8, and Jug r 5. Moreover, it was shown that a multispecific, in particular trispecific antibody including P268-Hg1 Lf2 as a "building block" (MY010-Tri 16) shows superior cross-reactivity to PR-10 allergens and food allergens compared to prior art Regeneron antibodies, and is effective in mast cell activation test (MAT) and leukotriene release assay (LTRA) as well as in IgE competition ELISA.

[0423] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 321, a CDRH2 having at least 70% identity to SEQ ID NO: 322, a CDRH3 having at least 70% identity to SEQ ID NO: 323, a CDRL1 having at least 70% identity to SEQ ID NO: 324, a CDRL2 having at least 70% identity to SEQ ID NO: 325, and a CDRL3 having at least 70% identity to SEQ ID NO: 326. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0424] a heavy chain CDR1 sequence according to SEQ ID NO: 321;

[0425] a heavy chain CDR2 sequence according to SEQ ID NO: 322;

[0426] a heavy chain CDR3 sequence according to SEQ ID NO: 323;

[0427] a light chain CDR1 sequence according to SEQ ID NO: 324;

[0428] a light chain CDR2 sequence according to SEQ ID NO: 325; and

[0429] a light chain CDR3 sequence according to SEQ ID NO: 326.

[0430] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 327 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 328. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0431] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 327 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 328.

[0432] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 329, a CDRH2 having at least 70% identity to SEQ ID NO: 330, a CDRH3 having at least 70% identity to SEQ ID NO: 331, a CDRL1 having at least 70% identity to SEQ ID NO: 332, a CDRL2 having at least 70% identity to SEQ ID NO: 333, and a CDRL3 having at least 70% identity to SEQ ID NO: 334. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0433] a heavy chain CDR1 sequence according to SEQ ID NO: 329;

[0434] a heavy chain CDR2 sequence according to SEQ ID NO: 330;

[0435] a heavy chain CDR3 sequence according to SEQ ID NO: 331;

[0436] a light chain CDR1 sequence according to SEQ ID NO: 332;

[0437] a light chain CDR2 sequence according to SEQ ID NO: 333; and

[0438] a light chain CDR3 sequence according to SEQ ID NO: 334.

[0439] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 335 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 336. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0440] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 335 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 336.

[0441] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 337, a CDRH2 having at least 70% identity to SEQ ID NO: 338, a CDRH3 having at least 70% identity to SEQ ID NO: 339, a CDRL1 having at least 70% identity to SEQ ID NO: 340, a CDRL2 having at least 70% identity to SEQ ID NO: 341, and a CDRL3 having at least 70% identity to SEQ ID NO: 342. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0442] a heavy chain CDR1 sequence according to SEQ ID NO: 337;

[0443] a heavy chain CDR2 sequence according to SEQ ID NO: 338;

[0444] a heavy chain CDR3 sequence according to SEQ ID NO: 339;

[0445] a light chain CDR1 sequence according to SEQ ID NO: 340;

[0446] a light chain CDR2 sequence according to SEQ ID NO: 341; and

[0447] a light chain CDR3 sequence according to SEQ ID NO: 342.

[0448] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 343 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 344. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0449] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 343 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 344.

[0450] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 345, a CDRH2 having at least 70% identity to SEQ ID NO: 346, a CDRH3 having at least 70% identity to SEQ ID NO: 347, a CDRL1 having at least 70% identity to SEQ ID NO: 348, a CDRL2 having at least 70% identity to SEQ ID NO: 349, and a CDRL3 having at least 70% identity to SEQ ID NO: 350. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0451] a heavy chain CDR1 sequence according to SEQ ID NO: 345;

[0452] a heavy chain CDR2 sequence according to SEQ ID NO: 346;

[0453] a heavy chain CDR3 sequence according to SEQ ID NO: 347;

[0454] a light chain CDR1 sequence according to SEQ ID NO: 348;

[0455] a light chain CDR2 sequence according to SEQ ID NO: 349; and

[0456] a light chain CDR3 sequence according to SEQ ID NO: 350.

[0457] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 351 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 352. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0458] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 351 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 352.

[0459] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 353, a CDRH2 having at least 70% identity to SEQ ID NO: 354, a CDRH3 having at least 70% identity to SEQ ID NO: 355, a CDRL1 having at least 70% identity to SEQ ID NO: 356, a CDRL2 having at least 70% identity to SEQ ID NO: 357, and a CDRL3 having at least 70% identity to SEQ ID NO: 358. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0460] a heavy chain CDR1 sequence according to SEQ ID NO: 353;

[0461] a heavy chain CDR2 sequence according to SEQ ID NO: 354;

[0462] a heavy chain CDR3 sequence according to SEQ ID NO: 355;

[0463] a light chain CDR1 sequence according to SEQ ID NO: 356;

[0464] a light chain CDR2 sequence according to SEQ ID NO: 357; and

[0465] a light chain CDR3 sequence according to SEQ ID NO: 358.

[0466] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 359 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 360. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0467] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 359 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 360.

[0468] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 361, a CDRH2 having at least 70% identity to SEQ ID NO: 362, a CDRH3 having at least 70% identity to SEQ ID NO: 363, a CDRL1 having at least 70% identity to SEQ ID NO: 364, a CDRL2 having at least 70% identity to SEQ ID NO: 365, and a CDRL3 having at least 70% identity to SEQ ID NO: 366. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0469] a heavy chain CDR1 sequence according to SEQ ID NO: 361;

[0470] a heavy chain CDR2 sequence according to SEQ ID NO: 362;

[0471] a heavy chain CDR3 sequence according to SEQ ID NO: 363;

[0472] a light chain CDR1 sequence according to SEQ ID NO: 364;

[0473] a light chain CDR2 sequence according to SEQ ID NO: 365; and

[0474] a light chain CDR3 sequence according to SEQ ID NO: 366.

[0475] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 367 and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 368. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0476] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 367 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 368.

[0477] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 809, a CDRH2 having at least 70% identity to SEQ ID NO: 810, a CDRH3 having at least 70% identity to SEQ ID NO: 754, a CDRL1 having at least 70% identity to SEQ ID NO: 755, a CDRL2 having at least 70% identity to SEQ ID NO: 811, and a CDRL3 having at least 70% identity to SEQ ID NO: 757. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0478] a heavy chain CDR1 sequence according to SEQ ID NO: 809;

[0479] a heavy chain CDR2 sequence according to SEQ ID NO: 810;

[0480] a heavy chain CDR3 sequence according to SEQ ID NO: 754;

[0481] a light chain CDR1 sequence according to SEQ ID NO: 755;

[0482] a light chain CDR2 sequence according to SEQ ID NO: 811; and

[0483] a light chain CDR3 sequence according to SEQ ID NO: 757.

[0484] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 812, and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 813. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0485] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 812 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 813.

[0486] As shown in the appended examples, such an antibody (e.g. 25-3D3_Hf2Lg3, 25-3D3_Hf2Lg3_STT_LH) binds specifically to Betv 1, and also binds specifically or has affinity to several Bet v 1 homologous proteins, including Cor a 1, Fag s 1, Aln g 1, Fag s 1, Ost c 1, and Car b 1, and to a number of natural PR-10 allergen extracts (birch, black alder, white alder, red alder, hazel pollen, beech) as well as to several food allergens including Pru p 1, Fra a 1, Api g 1 and Dau c 1. Moreover, it was shown that multispecific, in particular trispecific, antibodies including 25-3D3 Hf2Lg3 as a "building block" (MY010-Tri5, MY010-Tri9, MY010-Tri10, MY010-Tri12, MY010-Tri16) show superior cross-reactivity to PR-10 allergens and food allergens compared to prior art Regeneron antibodies, and are effective in mast cell activation test (MAT) and leukotriene release assay (LTRA) as well as in IgE competition ELISA.

[0487] In some embodiments, the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 768, a CDRH2 having at least 70% identity to SEQ ID NO: 814, a CDRH3 having at least 70% identity to SEQ ID NO: 770, a CDRL1 having at least 70% identity to SEQ ID NO: 815, a CDRL2 having at least 70% identity to SEQ ID NO: 816, and a CDRL3 having at least 70% identity to SEQ ID NO: 817. Preferably, the antibody or the antigen-binding fragment thereof comprises:

[0488] a heavy chain CDR1 sequence according to SEQ ID NO: 768;

[0489] a heavy chain CDR2 sequence according to SEQ ID NO: 814;

[0490] a heavy chain CDR3 sequence according to SEQ ID NO: 770;

[0491] a light chain CDR1 sequence according to SEQ ID NO: 815;

[0492] a light chain CDR2 sequence according to SEQ ID NO: 816; and

[0493] a light chain CDR3 sequence according to SEQ ID NO: 817.

[0494] In some embodiments, such an antibody of the invention, or the antigen-binding fragment thereof, may comprise a heavy chain variable region (VH) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 818, and a light chain variable region (VL) comprising an amino acid sequence having 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%) identity to SEQ ID NO: 819. Thereby, the CDR sequences as defined above (heavy chain CDR1, CDR2, and CDR3 sequences; and light chain CDR1, CDR2, and CDR3 sequences) are preferably maintained.

[0495] In some embodiments, the antibody, or an antigen-binding fragment thereof, comprises a heavy chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 818 and a light chain variable region comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 819.

[0496] As shown in the appended examples, such an antibody (e.g. 6C9 Hg21 Lf2, 6C9_Hg21Lf2_LH, 6C9_Hg21Lf2_HL, or 6C9_Hg21 Lf2_STT_LH) binds specifically to Bet v 1, and also binds specifically or has affinity to several Bet v 1 homologous proteins, including Cor a 1, Que a 1, Fag s 1, Ain g 1, Cas s 1, Fag s 1 and Ost c 1, and to a number of natural PR-10 allergen extracts (birch, black alder, white alder, hazel pollen English oak, beech) as well as to several food allergens including Act d 8 (Kiwi) and Jug r 5 (Walnut). Moreover, it was shown that multispecific, in particular bispecific and trispecific, antibodies including 6C9 Hg21 Lf2 as a "building block" (My010-Bisp48, MY010-Tri9, MY010-Tri10, MY010-Tri12, MY010-Tri20) show superior cross-reactivity to PR-10 allergens and food allergens compared to prior art Regeneron antibodies, and are effective in mast cell activation test (MAT) and leukotriene release assay (LTRA) as well as in IgE competition ELISA.

[0497] In general, the antibody, or the antigen-binding fragment thereof, of the invention may be capable of reducing, inhibiting or neutralizing allergen-mediated biological activity. In particular, the antibodies may be capable of reducing or inhibiting the binding of an IgE antibody to a birch pollen allergen, in particular Bet v 1, and, optionally to a bet v 1 homologous allergen, such as another tree pollen allergen, as described herein. Thus, the antibodies or binding fragments thereof according to the invention may decrease or inhibit the activation of the mast cells or basophils and therefore decrease or prevent the release of mediators (e.g. histamine, lipid mediators, leukotriene). Thereby, the antibodies described herein may inhibit allergy symptoms that would usually occur in the patient after contact with the allergen (e.g. contact with the eyes, nose or mouth or food uptake). Accordingly, the antibodies described herein may be capable of reducing, inhibiting or neutralizing allergen-mediated biological activity.

[0498] In some embodiments, the CDRs or the variable regions of the antibody, or the antigenbinding fragment thereof, are human or are derived from human CDR or variable region sequences. The exemplary antibodies described herein (wild-type) are human antibodies, isolated from human patients. A "human-derived" CDR or VHA / L sequence includes engineered human antibody sequences, wherein mutations were introduced in the originally human CDR or VHA / L sequences. For example, a human-derived CDR may differ from the fully human (wild-type) CDR sequence in that it contains up to 5, i.e. 1, 2, 3, 4 or 5 mutations, preferably up to 4 mutations, more preferably up to 3 mutations. For example, a human-derived VH or VL sequence may differ from the fully human (wild-type) VH or VL sequence in that it contains up to 10, i.e. 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 mutations, preferably up to 7 mutations, more preferably up to 5 mutations (e.g., in the framework regions).

[0499] In some embodiments, the antibody, or the antigen-binding fragment thereof, is a human antibody. In some embodiments, the antibody, or the antigen-binding fragment thereof, is a monoclonal antibody. For example, the antibody, or the antigen-binding fragment thereof, may be a human monoclonal antibody.

[0500] Human antibodies are advantageous as compared to antibodies of non-human origin, because non-human antibodies, including chimeric and humanized antibodies, can trigger an adverse immune response, which can lead to nausea, diarrhoea and flu-like symptoms. In more severe cases, these side-effects can even be lethal. Non-human antibody segments often trigger immune responses in humans (anti-drug antibodies (ADA)), thereby not only eliciting undesired side effects, but also reducing the efficacy of the non-human antibody in humans. In contrast thereto, antibodies retrieved from humans have a higher safety profile, as the antibodies have proven tolerability in the human body, which is combined with the outstanding affinity maturation typical of the human immune system. As used herein, the term "human antibodies" not only includes antibodies originally found in humans, but also sequence variants thereof, wherein specific amino acid residues (but not entire antibody segments) are mutated. In contrast to non-human and humanized antibodies, which usually contain entire antibody segments (such as entire sets of CDR sequences) of non-human origin, sequence variants of human antibodies typically contain only selective / specific mutations within select antibody segments (e.g., within a CDR or framework region and / or within a constant region; e.g. to modify the antibodies' affinity, functionality, half-life, etc.).

[0501] For example, a human antibody according to the present invention may comprise only a limited number of mutations per CDR (e.g. no more than 6, 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 a single mutation per CDR), as compared to the sequences shown in the Table of Sequences and SEQ ID numbers below. In case of more than two mutations they may not occur in a consecutive manner (to avoid creating a non-human sequence segment). The same applies to the framework regions (or the entire VH / VL sequences) as well to the constant regions. The latter may carry, for example, specific modifications known in the art to modify the antibody's (Fc-related) functionality, as described herein below.

[0502] Preferably, the antibody is an IgG or IgA antibody. IgG and IgA usually compete with IgE for binding sites on the allergen and thereby prevent recognition of allergens by IgE bound to Fes receptors on the surface of mast cells and basophils. This may include direct competition by binding to the same epitope or competition through steric hindrance. Furthermore, IgG antibodies bound to the allergen can lead to cross-linking of Fes and inhibitory FcyRIIB receptors, resulting in the decrease of effector cell activity. Thereby the IgG and IgA antibodies or binding fragments thereof according to the invention can be used for the effective prevention or treatment of allergies. In some embodiments, the variable regions or the CDRs of the antibody as defined herein are derived from a (human) IgE antibody and grafted in a scaffold of an IgG or IgA antibody. Preferably, the scaffold is of a human IgG or IgA. Accordingly, the variable regions, portions thereof or the CDRs may be human and grafted in an antibody framework, which is preferably of human origin, but a distinct antibody type, such as IgG or IgA instead of IgE. Typically, the human-derived portions of the variable regions that are grafted into the antibody framework comprise the CDRs. Among IgG, IgG1 and IgG4 are preferred.

[0503] Accordingly, the antibody according to the present invention, or an antigen binding fragment thereof, may comprise an Fc moiety. The Fc moiety may be derived from human origin, e.g. from human IgA or IgG, such as IgG1, IgG2, IgG3, and / or IgG4, e.g. human IgG4.

[0504] As used herein, the term " Fc moiety" refers to a sequence derived from the portion of an immunoglobulin heavy chain beginning in the hinge region just upstream of the papain cleavage site (e.g., residue 216 in native IgG, taking the first residue of heavy chain constant region to be 114) and ending at the C-terminus of the immunoglobulin heavy chain. Accordingly, an Fc moiety may be a complete Fc moiety or a portion (e.g., a domain) thereof. A complete Fc moiety comprises at least a hinge domain, a CH2 domain, and a CH3 domain (e.g., EU amino acid positions 216-446). An additional lysine residue (K) is sometimes present at the extreme C-terminus of the Fc moiety, but is often cleaved from a mature antibody. In some embodiments, in the context of the present invention an Fc moiety comprises at least one of: a hinge (e.g., upper, middle, and / or lower hinge region) domain, a CH2 domain, a CH3 domain, or a variant, portion, or fragment thereof. An Fc moiety may comprise at least a hinge domain, a CH2 domain or a CH3 domain. The Fc moiety may be a complete Fc moiety. The Fc moiety may also comprise one or more amino acid insertions, deletions, or substitutions relative to a naturally-occurring Fc moiety. For example, at least one of a hinge domain, CH2 domain or CH3 domain (or portion thereof) may be deleted.

[0505] It will be understood by one of ordinary skill in the art that the Fc moiety may be modified such that it varies in amino acid sequence from the complete Fc moiety of a naturally occurring immunoglobulin molecule, while retaining at least one desirable function conferred by the naturally-occurring Fc moiety. Such functions include Fc receptor (FcR) binding, antibody half-life modulation, ADCC function, protein A binding, protein G binding, and complement binding. The portions of naturally occurring Fc moieties, which are responsible and / or essential for such functions are well known by those skilled in the art. In some embodiments, the antibody according to the present invention comprises a (complete) Fc moiety / Fc region, wherein the interaction / binding with the Fc receptor is not compromised.

[0506] In general, binding of the antibody to an Fc receptor may be assessed by various methods known to the skilled person, such as ELISA (Hessell AJ, Hangartner L, Hunter M, Havenith CFG, Beurskens FJ, Bakker JM, Lanigan CMS, Landucci G, Forthal DN, Parren PWHI, et al.: Fc receptor but not complement 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 IgGI 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, Luisetti M, Corti D, Lanzavecchia A: Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis. Nat Commun 2015, 6:1-9). In some embodiments, the antibody, or antigen binding fragment thereof, according to the present invention comprises an Fc region. As used herein, the term " Fc region" refers to the portion of an immunoglobulin formed by two or more Fc moieties of antibody heavy chains. For example, the Fc region may be monomeric or "single-chain" Fc region (i.e., a scFc region). Single chain Fc regions are comprised of Fc moieties linked within a single polypeptide chain (e.g., encoded in a single contiguous nucleic acid sequence). Exemplary scFc regions are disclosed in WO 2008 / 143954 A2. The Fc region may be dimeric. A "dimeric Fc region" or "dcFc" refers to the dimer formed by the Fc moieties of two separate immunoglobulin heavy chains. The dimeric Fc region may be a homodimer of two identical Fc moieties (e.g., an Fc region of a naturally occurring immunoglobulin) or a heterodimer of two non-identical Fc moieties.

[0507] In some embodiments, the Fc moiety, or the Fc region, comprises or consists of an amino acid sequence derived from a human immunoglobulin sequence (e.g., from an Fc region or Fc moiety from a human IgG molecule). However, the Fc moiety, or the Fc region, may comprise one or more amino acids from another mammalian species. For example, a primate Fc moiety or a 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 moiety or in the Fc region.

[0508] The Fc moieties of the Fc region may be of the same or different class and / or subclass. For example, the Fc moieties may be derived from an immunoglobulin (e.g., a human immunoglobulin) of an IgG1, IgG2, IgG3 or IgG4 subclass.

[0509] Accordingly, antibodies of the invention can be of any isotype e.g., IgA, IgG, IgM i.e. an α, γ or μ heavy chain). Preferably, the antibody may be of the IgA or IgG type. Within the IgG isotype, antibodies may be IgG1, IgG2, IgG3 or IgG4 subclass, preferably IgG1 or IgG4, more preferably IgG4. An exemplary sequence for an IgG4 constant region, which may be useful in the antibody as described herein, is provided in SEQ ID NO: 737 or 830. Accordingly, the antibody of the invention may comprise an amino acid sequence according to SEQ ID NO: 737 or 830, or a sequence variant thereof as described herein. The human IgG4 constant region sequence of SEQ ID NO: 737 comprises the stable hinge mutation S228P (S. Angal, DJ. King, M. W. Bodmer, A. Turner, A. D. G. Lawson, G. Roberts, B. Pedley, J. R. Adair, A single amino acid substitution abolishes the heterogeneity of chimeric mouse / human (lgG4) antibody, Molecular Immunology, Volume 30, Issue 1, 1993, Pages 105-108, ISSN 0161 -5890, https: / / doi.org / 10.1016 / 0161-5890(93)90432-B). Antibodies of the invention may have a κ or a λ light chain. Exemplary sequences for κ and λ light chain constant regions, which may be useful in the antibody as described herein, are provided in SEQ ID NO: 738 (kappa LC) and SEQ ID NO: 739 (lambda LC). Accordingly, the antibody of the invention may comprise an amino acid sequence according to SEQ ID NO: 738 or 739, or a sequence variant thereof as described herein.

[0510] As outlined above, the present invention encompasses antigen-binding fragments. An antigen-binding fragment may or may not comprise an Fc moiety, in particular a portion of a complete Fc region. In some embodiments, the antibody, or antigen-binding fragment thereof, is selected from Fab, Fab', F(ab')2, Fv or scFv. For example, F(ab')2 (which may be obtained by pepsin cleavage or recombinant expression) as well as Fab' (which can be obtained from F(ab')2 or by recombinant expression) usually includes the hinge region.

[0511] In some embodiments, the antibody, or antigen-binding fragment, may be a single-chain antibody (or fragment). The single-chain antibody (or fragment) may encode the complete set of six CDRs, i.e. include the three heavy chain CDRs as well as the three light chain CDRs. More specifically, the single-chain antibody (or fragment) may include a heavy chain variable region (VH) as well as a light chain variable region (VL), for example including the VH and VL sequences as described above.

[0512] In a particular embodiment, the antibody or the antigen-binding fragment thereof, according to the present invention is a scFv.

[0513] In a particular embodiment, the scFv antibody or antigen-binding fragment thereof, according to the present invention comprises a CDRH1 having at least 70% identity to SEQ ID NO: 233, a CDRH2 having at least 70% identity to SEQ ID NO: 234, a CDRH3 having at least 70% identity to SEQ ID NO: 235, a CDRL1 having at least 70% identity to SEQ ID NO: 236, a CDRL2 having at least 70% identity to SEQ ID NO: 237, and a CDRL3 having at least 70% identity to SEQ ID NO: 238, and preferably comprises a CDRH1 according to SEQ ID NO: 233, a CDRH2 according to SEQ ID NO: 234, a CDRH3 according to SEQ ID NO: 235, a CDRL1 according to SEQ ID NO: 236, a CDRL2 according to SEQ ID NO: 237, and a CDRL3 according to SEQ ID NO: 238. In a specific embodiment, the scFv antibody or antigenbinding fragment thereof comprises a scFv having an amino acid sequence having at least 70% (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%) identity to SEQ ID NO: 857 or 858. In another specific embodiment, the scFv antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 70% (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%) identity to SEQ ID NO: 820 or SEQ ID NO: 822, and preferably comprises an amino acid sequence according to SEQ ID NO: 820, or SEQ ID NO: 822. As shown in the Examples below, such scFv antibodies (P236_Hg1Lf1_STT_LH, P236_Hg1Lf1_LH) show cross-reactivity to a number of Bet v1 related antigens and several food antigens.

[0514] In a particular embodiment the scFv antibody, or the antigen-binding fragment thereof, according to the present invention comprises a CDRH1 having at least 70% identity to SEQ ID NO: 265, a CDRH2 having at least 70% identity to SEQ ID NO: 266, a CDRH3 having at least 70% identity to SEQ ID NO: 267, a CDRL1 having at least 70% identity to SEQ ID NO: 268, a CDRL2 having at least 70% identity to SEQ ID NO: 269, and a CDRL3 having at least 70% identity to SEQ ID NO: 270, and preferably comprises a CDRH1 according to SEQ ID NO: 265, a CDRH2 according to SEQ ID NO: 266, a CDRH3 according to SEQ ID NO: 267, a CDRL1 according to SEQ ID NO: 268, a CDRL2 according to SEQ ID NO: 269, and a CDRL3 according to SEQ ID NO: 270. In a specific embodiment, the scFv antibody or antigen-binding fragment thereof comprises a scFv having an amino acid sequence having at least 70% (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%) identity to SEQ ID NO: 859 or 861. In another specific embodiment, the scFv antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 70% (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%) identity to SEQ ID NO: 823 or SEQ ID NO: 825, and preferably comprises an amino acid sequence according to SEQ ID NO: 823, or SEQ ID NO: 825. As shown in the Examples below, such scFv antibodies (P252–Hg1Lf1_HL, P252_Hg1Lf1_LH) show cross-reactivity to a number of Bet v1 related antigens and several food antigens.

[0515] In a particular embodiment the scFv antibody, or the antigen-binding fragment thereof, according to the present invention comprises a CDRH1 having at least 70% identity to SEQ ID NO: 809, a CDRH2 having at least 70% identity to SEQ ID NO: 810, a CDRH3 having at least 70% identity to SEQ ID NO: 754, a CDRL1 having at least 70% identity to SEQ ID NO: 755, a CDRL2 having at least 70% identity to SEQ ID NO: 811, and a CDRL3 having at least 70% identity to SEQ ID NO: 757, and preferably comprises a CDRH1 according to SEQ ID NO: 809, a CDRH2 according to SEQ ID NO: 810, a CDRH3 according to SEQ ID NO: 754, a CDRL1 according to SEQ ID NO: 755, a CDRL2 according to SEQ ID NO: 811, and a CDRL3 according to SEQ ID NO: 757. In a specific embodiment, the scFv antibody or antigen-binding fragment thereof comprises a scFv having an amino acid sequence having at least 70% (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%) identity to SEQ ID NO: 860. In another specific embodiment, the scFv antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 70% (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%) identity to SEQ ID NO: 824, and preferably comprises an amino acid sequence according to SEQ ID NO: 824. As shown in the Examples below, such a scFv antibody (253D3_Hf2Lg3_STT_LH) shows cross-reactivity to a number of Bet v! related antigens and several food antigens.

[0516] In a particular embodiment the scFv antibody, or the 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, and preferably comprises 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. In a specific embodiment, the scFv antibody or antigen-binding fragment thereof comprises a scFv having an amino acid sequence having at least 70% (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%) identity to SEQ ID NO: 862. In another specific embodiment, the scFv antibody or antigen-binding fragment thereof comprises an amino acid sequence having at least 70% (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%) identity to SEQ ID NO: 826, and preferably comprises an amino acid sequence according to SEQ ID NO: 826. As shown in the Examples below, such a scFv antibody (P031_HgLg_LH) shows cross-reactivity to a number of Bet v1 related antigens and several food antigens.

[0517] In a particular embodiment the scFv antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 768, a CDRH2 having at least 70% identity to SEQ ID NO: 814, a CDRH3 having at least 70% identity to SEQ ID NO: 770, a CDRL1 having at least 70% identity to SEQ ID NO: 815, a CDRL2 having at least 70% identity to SEQ ID NO: 816, and a CDRL3 having at least 70% identity to SEQ ID NO: 817, and preferably comprises a CDRH1 according to SEQ ID NO: 768, a CDRH2 according to SEQ ID NO: 814, a CDRH3 according to SEQ ID NO: 770, a CDRL1 according to SEQ ID NO: 815, a CDRL2 according to SEQ ID NO: 816, and a CDRL3 according to SEQ ID NO: 817. In a specific embodiment, the scFv antibody or antigen-binding fragment thereof comprises a scFv having an amino acid sequence having at least 70% (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%) identity to SEQ ID NO: 864, 865 or 866. In another specific embodiment, the scFv antibody, or an antigen-binding fragment thereof, comprises an amino acid sequence having at least 70% (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%) identity to SEQ ID NO: 827, 828 or 829, and preferably comprises an amino acid sequence according to SEQ ID NO: 826, 828 or 829. As shown in the Examples below, such a scFv antibody (6C9_Hg21Lf2_LH, 6C9_Hg21Lf2_HL, 6C9_Hg21 Lf2_STT_LH) shows crossreactivity to a number of Bet v1 related antigens and several food antigens.

[0518] The scFv antibodies or antigen-binding fragments thereof, may be paired with a heavy chain having at least 70% (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%) identity to SEQ ID NO: 821, preferably with a heavy chain according to SEQ ID NO: 821.

[0519] Thus, as shown in the Examples below, the antibodies according to the present invention perform their function, e.g. show cross-reactivity to a number of Bet v 1 related PR-10 allergens and several food allergens, in the form of Fabs as well as in the form of scFvs and as IgG formats.

[0520] Variant antibodies are also included within the scope of the invention. Thus, variants of the sequences recited in the application are also included within the scope of the invention. Such variants include natural variants generated by somatic mutation in vivo during the immune response or in vitro upon culture of immortalized B cell clones. Alternatively, variants may arise due to the degeneracy of the genetic code or may be produced due to errors in transcription or translation.

[0521] Antibodies of the invention, or antigen-binding fragments thereof, may be provided in purified form. Typically, the antibody, or antigen-binding fragment, will be present in a composition that is substantially free of other polypeptides e.g., where less than 90% (by weight), usually less than 60% and more usually less than 50% of the composition is made up of other polypeptides.

[0522] Antibodies of the invention may be immunogenic in non-human (or heterologous) hosts e.g., in mice. In particular, the antibodies may have an idiotope that is immunogenic in non-human hosts, but not in a human host. In particular, antibodies of the invention for human use include those 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 xeno-mice.

[0523] Antibodies of the invention also include hybrid antibody molecules that comprise the six CDRs from an antibody of the invention as defined above and one or more CDRs from another antibody to an antigen. For example, the antibody may be multispecific. In other embodiments, the antibody, or the antigen-binding fragment thereof, may be monospecific.

[0524] Accordingly, the antibody as described herein, or the antigen-binding fragment thereof, may be a multispecific antibody or a multispecific antigen-binding fragment.

[0525] As used herein, the term "multispecific" refers to the ability to bind to at least two different epitopes, e.g. on different antigens or on the same antigen. While a conventional monospecific IgG-type antibodies usually have two identical epitope binding sites (paratopes) and can, thus, only bind to identical epitopes (but not to different epitopes). A multispecific antibody, in contrast, has at least two different types of paratopes (antigen-binding sites) and can, thus, bind to at least two different epitopes. As used herein, "paratope" refers to an antigen-binding site (or epitope-binding site) of the antibody. Moreover, a single "specificity" may refer to one, two, three or more identical paratopes in a single antibody (the actual number of paratopes in one single antibody molecule is referred to as "valency"). For example, a single native IgG antibody is monospecific and bivalent, since it has two identical paratopes. Accordingly, a multispecific antibody comprises at least two (different) paratopes. Thus, the term "multispecific antibodies" refers to antibodies having more than one paratope and the ability to bind to two or more different epitopes. The term "multispecific antibodies" comprises in particular bispecific antibodies, but typically also protein, e.g. antibody scaffolds, which bind in particular to three or more different epitopes, i.e. antibodies with three or more different paratopes.

[0526] In particular, the multispecific antibody, or the multispecific antigen binding fragment, of the invention may comprise two or more paratopes, wherein one or more paratopes may be identical so that all paratopes of the antibody belong to at least two different types of paratopes and, hence, the antibody has at least two specificities. For example, the 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 for each of the two specificities). Thus, "one specificity" refers in particular to one or more paratopes exhibiting the same specificity (which typically means that such one or more paratopes are identical) and, thus, "two specificities" may be realized by two, three, four five, six or more paratopes as long as they refer to only two specificities. In some embodiments, the multispecific antibody comprises one single paratope for each (of the at least two) specificity, i.e. the multispecific antibody comprises in total at least two paratopes. For example, a bispecific antibody may comprise one single paratope for each of the two specificities, i.e. the antibody comprises in total two paratopes. In other embodiments, the antibody comprises two (identical) paratopes for one or more of the specificities. Preferably, the multispecific antibody or the multispecific antigen-binding fragment is bispecific or trispecific. As used herein, terms like "bispecific", trispecific", etc. refer to the number of different epitopes to which the antibody can bind to. For example, a "bispecific" antibody has exactly two different specificities (two different antigen-binding sites, wherein each of the two different antigen-binding sites may 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, wherein each of the three different antigen-binding sites may independently occur once or more than once, e.g. twice).

[0527] Various such multispecific antibody formats and methods for obtaining multispecific antibodies are known in the art. For example, building blocks for bispecific and trispecific antibodies are described in Xiufeng Wu, Stephen J. Demarest, Building blocks 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 further 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.

[0528] In some embodiments, the multispecific antibody, or the multispecific antigen binding fragment, according to the present invention is a bispecific antibody or a bispecific antigen binding fragment. Bispecific antibodies comprise (exactly) two specificities. A bispecific antibody in the context of the present invention may be of any bispecifc antibody format known in the art, e.g., as described in Spiess C., Zhai Q. and Carter PJ. (2015) Molecular Immunology 67: 95-106. For example, bispecific antibodies may be whole antibodies, such as whole IgG-like molecules, or fragments thereof which are not whole antibodies but retain antibody properties. These may be small recombinant formats, e.g. as tandem single chain variable fragment molecules (taFvs), diabodies (Dbs), single chain diabodies (scDbs), and various other derivatives of these (e.g., as described in Byrne H. et al. (2013) Trends Biotech, 31 (11): 621-632 with Figure 2 showing various bispecific antibody formats). In some embodiments, the bispecific antibody may be an lgG(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. In some embodiments, the multispecific antibody, or the multispecific antigen binding fragment, according to the present invention is a trispecific antibody or a trispecific antigen binding fragment. Trispecific antibodies comprise (exactly) three specificities. A trispecific antibody in the context of the present invention may be of any trispecifc antibody format known in the art. In some embodiments, the trispecific antibody may be a heterodimer of lgG(H)-scFvs with same Fab domains using knob-into-hole CH3 as described in Ridgway J B, 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.

[0529] With respect to the design and preparation of multispecific, in particular bispecific and trispecific, antibody formats, it is also referred to the International Patent Application PCT / 2023 / 082918, which is incorporated herein by reference.

[0530] In some embodiments, the multispecific antibody, or the multispecific antigen binding fragment, is at least bivalent, i.e. it has at least two paratopes. Preferably, the multispecific antibody, or the multispecific antigen binding fragment, is bivalent, trivalent, tetravalent, or hexavalent. More preferably, the multispecific antibody, or the multispecific antigen binding fragment, is tetravalent. Even more preferably, the multispecific antibody, or the multispecific antigen binding fragment, is tetravalent and bispecific, or trispecific.

[0531] Preferably, the multispecific antibody, or the multispecific antigen binding fragment, binds (specifically) to distinct, non-overlapping epitopes of Bet v 1, and optionally binds (specifically) to distinct, non-overlapping epitopes of at least one Bet v 1 homologous protein. Accordingly, the antigen-binding sites (paratopes) of the multispecific antibody, or the multispecific antigen binding fragment, preferably target different, non-overlapping epitopes on the same antigen, namely Bet v1, and optionally a Bet v 1 homologous protein. To this end, the antigen-binding sites (paratopes) of the multispecific antibody, or the multispecific antigen binding fragment, may be derived from the antibodies as disclosed herein, which preferably bind to distinct, non-overlapping epitopes of Bet v 1. The skilled artisan is well aware of methods for obtaining a multispecific antibody using the binding sites of monospecific antibodies, e.g. as described above. Accordingly, the multispecific antibody, or the multispecific antigen binding fragment, may comprise at least two of the following:

[0532] (i) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 1 -8, or sequences having at least 70% identity to SEQ ID NOs: 1 -8, respectively;

[0533] (ii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 9-16, or sequences having at least 70% identity to SEQ ID NOs: 9-16, respectively;

[0534] (iii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 17-24, or sequences having at least 70% identity to SEQ ID NOs: 17-24, respectively;

[0535] (iv) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 25-32, or sequences having at least 70% identity to SEQ ID NOs: 25-32, respectively;

[0536] (v) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 33-40, or sequences having at least 70% identity to SEQ ID NOs: 33-40, respectively;

[0537] (vi) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 41-48, or sequences having at least 70% identity to SEQ ID NOs: 41-48, respectively;

[0538] (vii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 49-56, or sequences having at least 70% identity to SEQ ID NOs: 49-56, respectively;

[0539] (viii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 57-64, or sequences having at least 70% identity to SEQ ID NOs: 57-64, respectively;

[0540] (ix) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 65-72, or sequences having at least 70% identity to SEQ ID NOs: 65-72, respectively;

[0541] (x) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 73-80, or sequences having at least 70% identity to SEQ ID NOs: 73-80, respectively;

[0542] (xi) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 81-88, or sequences having at least 70% identity to SEQ ID NOs: 81-88, respectively;

[0543] (xii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 89-96, or sequences having at least 70% identity to SEQ ID NOs: 89-96, respectively;

[0544] (xiii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 97-104, or sequences having at least 70% identity to SEQ ID NOs: 97-104, respectively;

[0545] (xiv) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 105-112, or sequences having at least 70% identity to SEQ ID NOs: 105-112, respectively;

[0546] (xv) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 113-120, or sequences having at least 70% identity to SEQ ID NOs: 113-120, respectively;

[0547] (xvi) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 121-128, or sequences having at least 70% identity to SEQ ID NOs: 121-128, respectively;

[0548] (xvii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 129-136, or sequences having at least 70% identity to SEQ ID NOs: 129-136, respectively;

[0549] (xviii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 137-144, or sequences having at least 70% identity to SEQ ID NOs: 137-144, respectively;

[0550] (xix) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 145-152, or sequences having at least 70% identity to SEQ ID NOs: 145-152, respectively;

[0551] (xx) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 153-160, or sequences having at least 70% identity to SEQ ID NOs: 153-160, respectively;

[0552] (xxi) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 161-168, or sequences having at least 70% identity to SEQ ID NOs: 161-168, respectively;

[0553] (xxii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 169-176, or sequences having at least 70% identity to SEQ ID NOs: 169-176, respectively;

[0554] (xxiii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 177-184, or sequences having at least 70% identity to SEQ ID NOs: 177-184, respectively;

[0555] (xxiv) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 185-192, or sequences having at least 70% identity to SEQ ID NOs: 185-192, respectively;

[0556] (xxv) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 193-200, or sequences having at least 70% identity to SEQ ID NOs: 193-200, respectively;

[0557] (xxvi) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 201-208, or sequences having at least 70% identity to SEQ ID NOs: 201-208, respectively;

[0558] (xxvii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 209-216, or sequences having at least 70% identity to SEQ ID NOs: 209-216, respectively;

[0559] (xxviii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 217-224, or sequences having at least 70% identity to SEQ ID NOs: 217-224, respectively;

[0560] (xxix) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 225-232, or sequences having at least 70% identity to SEQ ID NOs: 225-232, respectively;

[0561] (xxx) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 233-240, or sequences having at least 70% identity to SEQ ID NOs: 233-240, respectively;

[0562] (xxxi) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 241-248, or sequences having at least 70% identity to SEQ ID NOs: 241-248, respectively;

[0563] (xxxii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 249-256, or sequences having at least 70% identity to SEQ ID NOs: 249-256, respectively;

[0564] (xxxiii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 257-264, or sequences having at least 70% identity to SEQ ID NOs: 257-264, respectively;

[0565] (xxxiv) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 265-272, or sequences having at least 70% identity to SEQ ID NOs: 265-272, respectively;

[0566] (xxxv) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 273-280, or sequences having at least 70% identity to SEQ ID NOs: 273-280, respectively;

[0567] (xxxvi) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 281-288, or sequences having at least 70% identity to SEQ ID NOs: 281-288, respectively;

[0568] (xxxvii)an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 289-296, or sequences having at least 70% identity to SEQ ID NOs: 289-296, respectively;

[0569] (xxxviii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 297-304, or sequences having at least 70% identity to SEQ ID NOs: 297-304, respectively;

[0570] (xxxix) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 305-312, or sequences having at least 70% identity to SEQ ID NOs: 305-312, respectively;

[0571] (xl) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 313-320, or sequences having at least 70% identity to SEQ ID NOs: 313-320, respectively;

[0572] (xli) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 321-328, or sequences having at least 70% identity to SEQ ID NOs: 321-328, respectively;

[0573] (xlii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 329-336, or sequences having at least 70% identity to SEQ ID NOs: 329-336, respectively;

[0574] (xliii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 337-344, or sequences having at least 70% identity to SEQ ID NOs: 337-344, respectively;

[0575] (xliv) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 345-352, or sequences having at least 70% identity to SEQ ID NOs: 345-352, respectively;

[0576] (xlv) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 353-360, or sequences having at least 70% identity to SEQ ID NOs: 353-360, respectively;

[0577] (xlvi) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences according to SEQ ID NOs: 361-368, or sequences having at least 70% identity to SEQ ID NOs: 361-368, respectively;

[0578] (xlvii) an antigen-binding site comprising (a) a CDRH1 sequence according to SEQ ID NO: 809, a CDRH2 sequence according to SEQ ID NO: 810, a CDRH3 sequence according to SEQ ID NO: 754, a CDRL1 sequence according to SEQ ID NO: 755, a CDRL2 sequence according to SEQ ID NO: 811, and a CDRL3 sequence according to SEQ ID NO: 757, and / or (b) the VH and VL sequences according to SEQ ID NOs: 812 and 813, respectively, or sequences having at least 70% identity to said sequences; (xlviii) an antigen-binding site comprising (a) a CDRH1 sequence according to SEQ ID NO: 768, a CDRH2 sequence according to SEQ ID NO: 814, a CDRH3 sequence according to SEQ ID NO: 770, a CDRL1 sequence according to SEQ ID NO: 815, a CDRL2 sequence according to SEQ ID NO: 816, and a CDRL3 sequence according to SEQ ID NO: 817, and / or (b) the VH and VL sequences according to SEQ ID NOs: 818 and 819, respectively, or sequences having at least 70% identity to said sequences.

[0579] In a particular embodiment, the multispecific antibody, or an antigen-binding fragment thereof, comprises at least one of the above antigen-binding sites defined in (i) to (xlviii) and additionally comprises at least one antigen-binding site comprised by antibodies disclosed in the International Patent Application PCT / EP2024 / 065665, which is incorporated herein by reference. The antibodies disclosed in PCT / EP2024 / 065665 are herein referred to as "group A" antibodies. Thus, the multispecific antibody of the present invention may comprise, in addition to at least one antigen-binding site defined in (i) to (xlviii), at least one of the following antigen-binding sites (xlix) to (liv) (derived from "group A" antibodies):

[0580] (xlix) an antigen-binding site comprising a CDRH1 having at least 70% identity to SEQ ID NO: 744, a CDRH2 having at least 70% identity to SEQ ID NO: 745, a CDRH3 having at least 70% identity to SEQ ID NO: 746, a CDRL1 having at least 70% identity to SEQ ID NO: 747, a CDRL2 having at least 70% identity to SEQ ID NO: 748, and a CDRL3 having at least 70% identity to SEQ ID NO: 749, and preferably comprising a CDRH1 according to SEQ ID NO: 744, a CDRH2 according to SEQ ID NO: 745, a CDRH3 according to SEQ ID NO: 746, a CDRL1 according to SEQ ID NO: 747, a CDRL2 according to SEQ ID NO: 748, and a CDRL3 according to SEQ ID NO: 749; or comprising a VH having at least 70% identity to SEQ ID NO: 750, and a VL having at least 70% identity to SEQ ID NO: 751, and preferably comprising a VH according to SEQ ID NO: 750; and a VL according to SEQ ID NO: 751;

[0581] (I) an antigen-binding site comprising a CDRH1 having at least 70% identity to SEQ ID NO: 752, a CDRH2 having at least 70% identity to SEQ ID NO: 753, a CDRH3 having at least 70% identity to SEQ ID NO: 754, a CDRL1 having at least 70% identity to SEQ ID NO: 755, a CDRL2 having at least 70% identity to SEQ ID NO: 756, and a CDRL3 having at least 70% identity to SEQ ID NO: 757, and preferably comprising a CDRH1 according to SEQ ID NO: 752, a CDRH2 according to SEQ ID NO: 753, a CDRH3 according to SEQ ID NO: 754, a CDRL1 according to SEQ ID NO: 755, a CDRL2 according to SEQ ID NO: 756, and a CDRL3 according to SEQ ID NO: 757; or comprising a VH having at least 70% identity to SEQ ID NO: 758, and a VL having at least 70% identity to SEQ ID NO: 759, and preferably comprising a VH according to SEQ ID NO: 758; and a VL according to SEQ ID NO: 759;

[0582] (li) an antigen-binding site comprising a CDRH1 having at least 70% identity to SEQ ID NO: 760, a CDRH2 having at least 70% identity to SEQ ID NO: 761, a CDRH3 having at least 70% identity to SEQ ID NO: 762, a CDRL1 having at least 70% identity to SEQ ID NO: 763, a CDRL2 having at least 70% identity to SEQ ID NO: 764, and a CDRL3 having at least 70% identity to SEQ ID NO: 765, and preferably comprising a CDRH1 according to SEQ ID NO: 760, a CDRH2 according to SEQ ID NO: 761, a CDRH3 according to SEQ ID NO: 762, a CDRL1 according to SEQ ID NO: 763, a CDRL2 according to SEQ ID NO: 764, and a CDRL3 according to SEQ ID NO: 765; or comprising a VH having at least 70% identity to SEQ ID NO: 766, and a VL having at least 70% identity to SEQ ID NO: 767, and preferably comprising a VH according to SEQ ID NO: 766; and a VL according to SEQ ID NO: 767;

[0583] (lii) an antigen-binding site comprising a CDRH1 having at least 70% identity to SEQ ID NO: 768, a CDRH2 having at least 70% identity to SEQ ID NO: 769, a CDRH3 having at least 70% identity to SEQ ID NO: 770, a CDRL1 having at least 70% identity to SEQ ID NO: 771, a CDRL2 having at least 70% identity to SEQ ID NO: 772, and a CDRL3 having at least 70% identity to SEQ ID NO: 773, and preferably comprising a CDRH1 according to SEQ ID NO: 768, a CDRH2 according to SEQ ID NO: 769, a CDRH3 according to SEQ ID NO: 770, a CDRL1 according to SEQ ID NO: 771, a CDRL2 according to SEQ ID NO: 772, and a CDRL3 according to SEQ ID NO: 773; or comprising a VH having at least 70% identity to SEQ ID NO: 774, and a VL having at least 70% identity to SEQ ID NO: 775, and preferably comprising a VH according to SEQ ID NO: 774; and a VL according to SEQ ID NO: 775;

[0584] (liii) an antigen-binding site comprising a CDRH1 having at least 70% identity to SEQ ID NO: 776, a CDRH2 having at least 70% identity to SEQ ID NO: 777, a CDRH3 having at least 70% identity to SEQ ID NO: 778, a CDRL1 having at least 70% identity to SEQ ID NO: 779, a CDRL2 having at least 70% identity to SEQ ID NO: 780, and a CDRL3 having at least 70% identity to SEQ ID NO: 781, and preferably comprising a CDRH1 according to SEQ ID NO: 776, a CDRH2 according to SEQ ID NO: 777, a CDRH3 according to SEQ ID NO: 778, a CDRL1 according to SEQ ID NO: 779, a CDRL2 according to SEQ ID NO: 780, and a CDRL3 according to SEQ ID NO: 781; or comprising a VH having at least 70% identity to SEQ ID NO: 782, and a VL having at least 70% identity to SEQ ID NO: 783, and preferably comprising a VH according to SEQ ID NO: 782; and a VL according to SEQ ID NO: 783;

[0585] (liv) an antigen-binding site comprising a CDRH1 having at least 70% identity to SEQ ID NO: 784, a CDRH2 having at least 70% identity to SEQ ID NO: 785, a CDRH3 having at least 70% identity to SEQ ID NO: 786, a CDRL1 having at least 70% identity to SEQ ID NO: 787, a CDRL2 having at least 70% identity to SEQ ID NO: 788, and a CDRL3 having at least 70% identity to SEQ ID NO: 789, and preferably comprising a CDRH1 according to SEQ ID NO: 784, a CDRH2 according to SEQ ID NO: 785, a CDRH3 according to SEQ ID NO: 786, a CDRL1 according to SEQ ID NO: 787, a CDRL2 according to SEQ ID NO: 788, and a CDRL3 according to SEQ ID NO: 789; or comprising a VH having at least 70% identity to SEQ ID NO: 790, and a VL having at least 70% identity to SEQ ID NO: 791, and preferably comprising a VH according to SEQ ID NO: 790; and a VL according to SEQ ID NO: 791.

[0586] In some embodiments, the multispecific antibody, or the multispecific antigen binding fragment, is bispecific and comprises two distinct antigen-binding sites selected from (i) to (xlviii). In some embodiments, the multispecific antibody, or the multispecific antigen binding fragment, is bispecific and comprises two distinct antigen-binding sites, wherein one antigenbinding site is selected from (i) to (xlviii), and one antigen-binding site is selected from (xlix) to (liv).

[0587] In some embodiments, the multispecific antibody, or the multispecific antigen binding fragment, is trispecific and comprises three distinct antigen-binding sites selected from (i) to (xlviii). In some embodiments, the multispecific antibody, or the multispecific antigen binding fragment, is trispecific and comprises three distinct antigen-binding sites, wherein two antigen-binding sites are selected from (i) to (xlviii), and one antigen-binding site is selected from (xlvix) to (liv)). In some embodiments, the multispecific antibody, or the multispecific antigen binding fragment, is trispecific and comprises three distinct antigen-binding sites, wherein one antigen-binding sites is selected from (i) to (xlviii), and two antigen-binding sites are selected from (xlix) to (liv).

[0588] In some embodiments, the multispecific antibody, or the multispecific antigen binding fragment, is tetraspecific and comprises four distinct antigen-binding sites selected from (i) to (xlviii). In some embodiments, the multispecific antibody, or the multispecific antigen binding fragment, is tetraspecific and comprises four distinct antigen-binding sites, wherein three antigen-binding sites are selected from (i) to (xlviii), and one antigen-binding site is selected from (xlix) to (liv). In some embodiments, the multispecific antibody, or the multispecific antigen binding fragment, is tetraspecific and comprises four distinct antigen-binding sites, wherein two antigen-binding sites are selected from (i) to (xlviii), and two antigen-binding site is selected from (xlix) to (liv). In some embodiments, the multispecific antibody, or the multispecific antigen binding fragment, is tetraspecific and comprises four distinct antigenbinding sites, wherein one antigen-binding sites are selected from (i) to (xlviii), and three antigen-binding site is selected from (xlix) to (liv).

[0589] In a particular embodiment, the multispecific antibody comprises two heavy chains and two light chains each comprising at least one constant domain and at least one variable domain (VH / VL), wherein the multispecific antibody comprises at least three antigen-binding sites each comprising three heavy chain CDRs (CDRH1 -3) and three light chain CDRs (CDRL1 -3), wherein

[0590] at least one antigen-binding site (a) is formed by the VH1 of a first heavy chain and by the VL1 of a first light chain,

[0591] at least one antigen-binding site (b) is formed by the VH2 of a second heavy chain and by the VL2 of a second light chain, and

[0592] at least one antigen-binding site (c) is formed by a single chain variable fragment (scFv), the scFv being covalently linked to the constant domain of the at least one heavy chain, and / or at least one antigen-binding site (d) is formed by variable domains VHx and / or VLx, the variable domains VHx and / or VLx being covalently linked to at least one of variable domains VH1 / VL1 and / or VH2 / VL2, thereby forming at least one dual variable domain (DVD).

[0593] In a particular embodiment of the above multispecific antibody, the antigen-binding site (a) and the antigen-binding site (b) may have different specificities. In another embodiment, antigen-binding site (a) and antigen-binding site (b) may have the same specificity.

[0594] In a particular embodiment, the multispecific antibody described above comprises at least two antigen-binding sites (cl, c2), wherein a first scFv1 forming the antigen-binding site (c1) is covalently linked to the at least one constant domain of the first heavy chain, and a second scFv1 forming the antigen-binding site (c2) is covalently linked to the at least one constant domain of the second heavy chain. In a particular embodiment of the above multispecific antibody, the first antigen-binding site (c1), and the second antigen-binding site (c2) may have the same specificity. In another embodiment, the first antigen-binding site (c1), and the second antigen-binding site (c2) may have different specificities.

[0595] In another particular embodiment, the multispecific antibody described above comprises at least two antigen-binding sites (d1, d2), wherein the variable domains VHx1 and VLx1 forming a first antigen-binding site (d1) is covalently linked to the variable domain formed by VH1 and VL1, and a variable domain VHx2 and VLx2 forming a second antigen-binding site (d2) is covalently linked to the variable domain formed by VH2 and VL2. In a particular embodiment of the multispecific antibody, the first antigen-binding site (d1), and the second antigen-binding site (d2) may have the same specificity. In another embodiment, the first antigen-binding site (d1), and the second antigen-binding site (d2) may have different specificities.

[0596] In a particular embodiment of the multispecific antibody described above, a variable domain VHx1 and VLx1 forming the first antigen-binding site (d1) is covalently linked to the variable domain formed by VH1 and VL1, or a variable domain VHx2 and VLx2 forming a second antigen-binding site (d2) is covalently linked to the variable domain formed by VH2 and VL2. In the multispecific antibody described above, the at least three antigen-binding sites may be formed by at least two of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i) to (xlviii). Alternatively, the at least three antigen-binding sites may be formed by at least one of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i) to (xlviii) and at least one of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlix) to (liv).

[0597] In the multispecific antibody described above, the at least three antigen-binding sites may be formed by at least three of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i) to (xlviii). Alternatively, the at least three antigen-binding sites may be formed by at least two of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i) to (xlviii) and at least one of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according (xlix) to (liv). According to a further alternative, the at least three antigen-binding sites may be formed by at least one of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i) to (xlviii) and at least two of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlix) to (liv).

[0598] In a particular embodiment, the multispecific antibody described above comprises at least four antigen-binding sites which are formed by at least two of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i) to (xlviii). Alternatively, the at least four antigen-binding sites may be formed by at least one of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i) to (xlviii) and at least one of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlix) to (liv).

[0599] In another particular embodiment, the multispecific antibody described above comprises at least four antigen-binding sites which are formed by at least three of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i) to (xlviii). Alternatively, the at least four antigen-binding sites may be formed by at least two of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i) to (xlviii) and at least one of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlix) to (liv). In a further alternative embodiment, the at least four antigen-binding sites may be formed by at least one of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i) to (xlviii) and at least two of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlix) to (liv).

[0600] In preferred embodiments, the antigen-binding sites of the multispecific antibodies according to the present invention are selected from at least two of

[0601] CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i); CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (ii); CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (iii); CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (x); CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxx); CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxxiv);

[0602] CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xl); CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlvii);

[0603] CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlviii).

[0604] In a particular embodiment of the multispecific antibody described above, two antigenbinding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i) (e.g. CDRH1 -3 / CDRL1 -3 sequences according to SEQ ID Nos: 1-6 and / or VH and VL sequences according to SEQ ID NOs 7-8, respectively), and two antigenbinding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (ii) (e.g. CDRH1 -3 / CDRL1 -3 sequences according to SEQ ID Nos: 9-14 and / or VH and VL sequences according to SEQ ID NOs 15-16, respectively).

[0605] In a specific embodiment of the multispecific antibody described above, antigen-binding sites (a) and (b) are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i) (e.g. CDRH1 -3 / CDRL1 -3 sequences according to SEQ ID Nos: 1 -6 and / or VH and VL sequences according to SEQ ID NOs 7-8, respectively), and antigen-binding sites (c1) and (c2) are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (ii) (e.g. CDRH1 -3 / CDRL1 -3 sequences according to SEQ ID Nos: 9-14 and / or VH and VL sequences according to SEQ ID NOs 15-16, respectively).

[0606] In a particular embodiment, the multispecific antibody comprises a heavy chain having at least 70% identity to SEQ ID NO: 740, and a light chain having at least 70% identity to SEQ ID NO: 741. In a specific embodiment, the multispecific antibody comprises a heavy chain according to SEQ ID NO: 740, and a light chain according to SEQ ID NO: 741.

[0607] In another particular embodiment, the multispecific antibody comprises a heavy chain having at least 70% identity to SEQ ID NO: 742, and a light chain having at least 70% identity to SEQ ID NO: 743. In a specific embodiment, the multispecific antibody comprises a heavy chain according to SEQ ID NO: 742, and a light chain according to SEQ ID NO: 743.

[0608] In another particular embodiment two antigen-binding sites of the multispecific antibody are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (iii), and two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlviii). In a specific embodiment of this multispecific antibody, the antigen-binding sites (a) and (b) are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (iii), and antigen-binding sites (c1) and (c2) are formed by the CDRH1-3 / CDRL1-3 sequences and / or the VH and VL sequences according to (xlviii). Thus, in a preferred embodiment, the multispecific antibody comprises a heavy chain having at least 70% (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%) identity to SEQ ID NO: 831 or 835, and a light chain having at least 70% (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%) identity to SEQ ID NO: 832. In a specific embodiment, the multispecific antibody according to the present invention comprises a heavy chain according to SEQ ID NO: 831, and a light chain according to SEQ ID NO: 832. As shown in the Examples below, such a bispecific antibody (MY010-Bisp 48) shows superior cross-reactivity to PR-10 allergens and food allergens compared to prior art Regeneron antibodies, and is effective in mast cell activation test (MAT) and leukotriene release assay (LTRA) as well as in IgE competition ELISA.

[0609] In another particular embodiment two antigen-binding sites of the multispecific antibody are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (x), and two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxxiv). In a specific embodiment of this multispecific antibody, the antigen-binding sites (a) and (b) are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (x), and antigen-binding sites (c1) and (c2) are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxxiv). In a preferred embodiment, the multispecific antibody comprises a heavy chain having at least 70% (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%) identity to SEQ ID NO: 833, and a light chain having at least 70% (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%) identity to SEQ ID NO: 833. In a specific embodiment, the multispecific antibody according to the present invention comprises a heavy chain according to SEQ ID NO: 832, and a light chain according to SEQ ID NO: 834. As shown in the Examples below, such a bispecific antibody (MY010-Bisp 94) shows superior cross-reactivity to PR-10 allergens and food allergens compared to prior art Regeneron antibodies, and is effective in mast cell activation test (MAT) and leukotriene release assay (LTRA) as well as in IgE competition ELISA.

[0610] In another particular embodiment two antigen-binding sites of the multispecific antibody are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i), and two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlvii) and (i i), respectively. In a specific embodiment of this multispecific antibody, the antigen-binding sites (a) and (b) are formed by the CDRH1-3 / CDRL1-3 sequences and / or the VH and VL sequences according to (i), an antigen-binding site (c1) is formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlvii) and another antigen-binding site (c2) is formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (ii). Thus, in a preferred embodiment, the multispecific antibody comprises a heavy chain having at least 70% (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%) identity to SEQ ID NO: 836, a second heavy chain having at least 70% (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%) identity to SEQ ID NO: 837, and a light chain having at least 70% (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%) identity to SEQ ID NO: 838. In a specific embodiment, the multispecific antibody comprises a first heavy chain according to SEQ ID NO: 836, a second heavy chain according to SEQ ID NO: 837, and a light chain according to SEQ ID NO: 838. As shown in the Examples below, such a bispecific antibody (MY010-Tri5) shows superior cross-reactivity to PR-10 allergens and food allergens compared to prior art Regeneron antibodies, and is effective in mast cell activation test (MAT) and leukotriene release assay (LTRA) as well as in IgE competition ELISA.

[0611] In another particular embodiment two antigen-binding sites of the multispecific antibody are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i), and two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlvii) and (xlviii), respectively. In a specific embodiment of this multispecific antibody, the antigen-binding sites (a) and (b) are formed by the CDRH1 -3 / CDRL1-3 sequences and / or the VH and VL sequences according to (i), an antigen-binding site (c1) is formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlvii) and another antigen-binding site (c2) is formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlviii). Thus, in a preferred embodiment, the multispecific antibody comprises a first heavy chain having at least 70% (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%) identity to SEQ ID NO: 839, a second heavy chain having at least 70% (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%) identity to SEQ ID NO: 840, and a light chain having at least 70% (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%) identity to SEQ ID NO: 838. In a specific embodiment, the multispecific antibody comprises a first heavy chain according to SEQ ID NO: 839, a second heavy chain according to SEQ ID NO: 840, and a light chain according to SEQ ID NO: 838. As shown in the Examples below, such a bispecific antibody (MY010-Tri9) shows superior cross-reactivity to PR-10 allergens and food allergens compared to prior art Regeneron antibodies, and is effective in mast cell activation test (MAT) and leukotriene release assay (LTRA) as well as in IgE competition ELISA.

[0612] In another particular embodiment two antigen-binding sites of the multispecific antibody are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i), and two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (iii), and two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlvii) and (xlviii), respectively. In a specific embodiment of this multispecific antibody the antigenbinding sites (a) and (b) are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (iii), an antigen-binding site (c1) is formed by the CDRH1-3 / CDRL1-3 sequences and / or the VH and VL sequences according to (xlvii) and another antigen-binding site (c2) is formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlviii). Thus, in a preferred embodiment, the multispecific antibody comprises a first heavy chain having at least 70% (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%) identity to SEQ ID NO: 841, a second heavy chain having at least 70% (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%) identity to SEQ ID NO: 842, and a light chain having at least 70% (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%) identity to SEQ ID NO: 832. In a specific embodiment, the multispecific antibody comprises a first heavy chain according to SEQ ID NO: 841, a second heavy chain according to SEQ ID NO: 842, and a light chain according to SEQ ID NO: 832. As shown in the Examples below, such a bispecific antibody (MY010-Tri10) shows superior cross-reactivity to PR-10 allergens and food allergens compared to prior art Regeneron antibodies, and is effective in mast cell activation test (MAT) and leukotriene release assay (LTRA) as well as in IgE competition ELISA. In another particular embodiment two antigen-binding sites of the multispecific antibody are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxxiv), and two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlvii) and (xlviii), respectively. In a specific embodiment of this multispecific antibody, the antigen-binding sites (a) and (b) are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxxiv), an antigen-binding site (c1) is formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlvii) and another antigen-binding site (c2) is formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlviii). Thus, in a preferred embodiment, the multispecific antibody comprises a first heavy chain having at least 70% (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%) identity to SEQ ID NO: 843 or 853, a second heavy chain having at least 70% (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%) identity to SEQ ID NO: 844 or 854, and a light chain having at least 70% identity to SEQ ID NO: 845. In a specific embodiment, the multispecific antibody comprises a first heavy chain according to SEQ ID NO: 843, a second heavy chain according to SEQ ID NO: 844, and a light chain according to SEQ ID NO: 845. As shown in the Examples below, such a bispecific antibody (MY010-Tri12) shows superior cross-reactivity to PR-10 allergens and food allergens compared to prior art Regeneron antibodies, and is effective in mast cell activation test (MAT) and leukotriene release assay (LTRA) as well as in IgE competition ELISA.

[0613] In another particular embodiment two antigen-binding sites of the multispecific antibody are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xl), and two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlvii) and (xxxiv), respectively. In a specific embodiment of this multispecific antibody the antigen-binding sites (a) and (b) are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xl), an antigen-binding site (c1) is formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlvii) and another antigen-binding site (c2) is formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxxiv). Thus, in a preferred embodiment, the multispecific antibody comprises a first heavy chain having at least 70% (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%) identity to SEQ ID NO: 846, a second heavy chain having at least 70% (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%) identity to SEQ ID NO: 847, and a light chain having at least 70% (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%) identity to SEQ ID NO: 848. In a specific embodiment, the multispecific antibody comprises a first heavy chain according to SEQ ID NO: 846, a second heavy chain according to SEQ ID NO: 847, and a light chain according to SEQ ID NO: 848. As shown in the Examples below, such a bispecific antibody (MY010-Tri16) shows superior cross-reactivity to PR-10 allergens and food allergens compared to prior art Regeneron antibodies, and is effective in mast cell activation test (MAT) and leukotriene release assay (LTRA) as well as in IgE competition ELISA.

[0614] In another particular embodiment two antigen-binding sites of the multispecific antibody are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxxiv), and two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxx) and (ii), respectively. In a specific embodiment of the multispecific antibody the antigen-binding sites (a) and (b) are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxxiv), an antigen-binding site (c1) is formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxx) and another antigen-binding site (c2) is formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (ii). Thus, in a preferred embodiment, the multispecific antibody comprises a first heavy chain having at least 70% (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%) identity to SEQ ID NO: 849, a second heavy chain having at least 70% (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%) identity to SEQ ID NO: 850, and a light chain having at least 70% (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%) identity to SEQ ID NO: 845. In a specific embodiment, the multispecific antibody comprises a first heavy chain according to SEQ ID NO: 849, a second heavy chain according to SEQ ID NO: 850, and a light chain according to SEQ ID NO: 845. As shown in the Examples below, such a bispecific antibody (MY010-Tri19) shows superior cross-reactivity to PR-10 allergens and food allergens compared to prior art Regeneron antibodies, and is effective in mast cell activation test (MAT) and leukotriene release assay (LTRA) as well as in IgE competition ELISA.

[0615] In another particular embodiment two antigen-binding sites of the multispecific antibody are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxxiv), and two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxx) and (xlviii), respectively. In a specific embodiment of this multispecific antibody the antigen-binding sites (a) and (b) are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxxiv), an antigen-binding site (c1) is formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxx) and another antigen-binding site (c2) is formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlviii). Thus, in a preferred embodiment, the multispecific antibody comprises a first heavy chain having at least 70% (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%) identity to SEQ ID NO: 851 or 855, a second heavy chain having at least 70% (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%) identity to SEQ ID NO: 852 or 856, and a light chain having at least 70% (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%) identity to SEQ ID NO: 845. In a specific embodiment, the multispecific antibody comprises a first heavy chain according to SEQ ID NO: 851, a second heavy chain according to SEQ ID NO: 852, and a light chain according to SEQ ID NO: 845. As shown in the Examples below, such a bispecific antibody (MY010-Tri20) shows superior cross-reactivity to PR-10 allergens and food allergens compared to prior art Regeneron antibodies, and is effective in mast cell activation test (MAT) and leukotriene release assay (LTRA) as well as in IgE competition ELISA.

[0616] The bispecific or trispecific antibody as described herein may be combined, in use, with a second (monospecific) antibody. For combination, the antibodies may be comprised in the same composition or in different compositions (but administered in a combined treatment schedule). Nucleic Acids

[0617] In another aspect, the invention also provides a nucleic acid molecule comprising a polynucleotide encoding the antibody according to the present invention, or an antigenbinding fragment thereof, as described above.

[0618] In some embodiments, the nucleic acid molecule comprises one or more polynucleotide(s) encoding the exemplified antibodies of the invention as described above, 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 sequence identity as described above).

[0619] Examples of nucleic acid molecules and / or polynucleotides include, e.g., a recombinant polynucleotide, a vector, an oligonucleotide, an RNA molecule such as an rRNA, an mRNA, an miRNA, an siRNA, or a tRNA, or a DNA molecule such as a cDNA. Nucleic acids may encode the light chain and / or the heavy chain of an antibody (or a single chain antibody). In other words, the light chain and the heavy chain of the antibody may be encoded by the same nucleic acid molecule (e.g., for single chain antibodies or for antibodies with separate heavy and light chains in bicistronic manner or an expression cassette containing more than one ribosome entry site such as IRES). Alternatively, the light chain and the heavy chain of the antibody may be encoded by distinct nucleic acid molecules. In a similar manner, for multispecific antibodies comprising two or more immunoglobulin chains, the different chains may be encoded by the same nucleic acid molecule (e.g., in a multicistronic manner or an expression cassette containing more than one ribosome entry site such as IRES). Alternatively, the different immunoglobulin chains of the multispecific antibody may be encoded by distinct nucleic acid molecules.

[0620] Due to the redundancy of the genetic code, the present invention also comprises sequence variants of nucleic acid sequences, which encode the same amino acid sequences. The polynucleotide encoding the antibody (or the complete nucleic acid molecule) may be optimized for expression of the antibody. For example, codon optimization of the nucleotide sequence may be used to improve the efficiency of translation in expression systems for the production of the antibody. Moreover, the nucleic acid molecule may comprise heterologous elements (i.e., elements, which in nature do not occur on the same nucleic acid molecule as the coding sequence for the (heavy or light chain of) an antibody. For example, a nucleic acid molecule may comprise a heterologous promotor, a heterologous enhancer, heterologous UTR (e.g., for optimal translation / expression), a heterologous poly-A-tail, heterologous DNA insulator elements and the like.

[0621] A nucleic acid molecule is a molecule comprising nucleic acid components. The term nucleic acid molecule usually refers to DNA or RNA molecules. It may be used synonymous with the term "polynucleotide", i.e. the nucleic acid molecule may consist of a polynucleotide encoding the antibody. Alternatively, the nucleic acid molecule may also comprise further elements in addition to the polynucleotide encoding the antibody. Typically, a nucleic acid molecule is a polymer comprising or consisting of nucleotide monomers which are covalently linked to each other by phosphodiester-bonds of a sugar / phosphate-backbone. The term "nucleic acid molecule" also encompasses modified nucleic acid molecules, such as basemodified, sugar-modified or backbone-modified etc. DNA or RNA molecules.

[0622] In general, the nucleic acid molecule may be manipulated to insert, delete or alter certain nucleic acid sequences. Changes from such manipulation include, but are not limited to, changes to introduce restriction sites, to amend codon usage, to add or optimize transcription and / or translation regulatory sequences, etc. It is also possible to change the nucleic acid to alter the encoded amino acids. For example, it may be useful to introduce one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) amino acid substitutions, deletions and / or insertions into the antibody's amino acid sequence. Such point mutations can modify effector functions, antigen-binding affinity, post-translational modifications, immunogenicity, etc., can introduce amino acids for the attachment of covalent groups (e.g., labels) or can introduce tags (e.g., for purification purposes). Alternatively, a mutation in a nucleic acid sequence may 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 in specific sites or can be introduced at random, followed by selection (e.g., molecular evolution). For instance, one or more nucleic acids encoding any of the light or heavy chains of an (exemplary) antibody can be randomly or directionally mutated to introduce different properties in the encoded amino acids. Such changes can be the result of an iterative process wherein initial changes are retained and new Ill

[0623] changes at other nucleotide positions are introduced. Further, changes achieved in independent steps may be combined.

[0624] In some embodiments, the polynucleotide encoding the antibody, or an antigen-binding fragment thereof, (or the (complete) nucleic acid molecule) may be codon-optimized. The skilled artisan is aware of various tools for codon optimization, such as those described in: Ju Xin Chin, Bevan Kai-Sheng Chung, Dong-Yup Lee, Codon Optimization Online (COOL): a web-based multi-objective optimization platform for 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™ algorithm (as described in US 2011 / 0081708 A1).

[0625] For example, the nucleic acid molecule of the invention may comprise a nucleic acid sequence as set forth in any one of SEQ ID NOs 369 to 736 and SEQ ID NOs 869-895; 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. Thereby, the nucleic acid molecule may encode any one of the exemplified antibodies (by combining the sequences as shown in the Table of Sequences and SEQ ID numbers below), or a sequence variant thereof as described herein.

[0626] The present invention also provides a plurality of nucleic acid molecules encoding the antibody, or an antigen-binding fragment thereof, as described herein, wherein each of the nucleic acid molecules (of the plurality of nucleic acid molecules) comprises a polynucleotide encoding an immunoglobulin chain of the antibody, or an antigen-binding fragment thereof. Thereby, the plurality of nucleic acid molecules, taken together, encodes (all of the immunoglobulin chains of) the antibody, or an antigen-binding fragment thereof, as described herein. In some embodiments, the plurality of nucleic acid molecules encoding the antibody, or an antigen-binding fragment thereof, as described herein, may be a combination of a first and a second nucleic acid molecule, wherein the first nucleic acid molecule comprises a polynucleotide encoding the heavy chain of the antibody, or an 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 the same antigen-binding fragment thereof.

[0627] In general, the above description regarding the (general) features of the nucleic acid molecule of the invention applies accordingly to the nucleic acid molecules of the plurality of nucleic acid molecules. Accordingly, one or more of the polynucleotides encoding the immunoglobulin chains of the antibody, or an antigen-binding fragment thereof, may be codon-optimized. For example, the plurality may comprise a nucleic acid sequence as set forth in any one of SEQ ID NOs 369 to 736 and SEQ ID NOs 869 to 895; 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. Thereby, the plurality of nucleic acid molecules may encode any one of the exemplified antibodies (by combining the sequences as shown in the Table of Sequences and SEQ ID numbers below), or a sequence variant thereof as described herein.

[0628] Vectors

[0629] Further included within the scope of the invention are vectors, for example, expression vectors, comprising a nucleic acid molecule according to the present invention or the plurality of nucleic acid molecules according to the present invention. Usually, a vector comprises a nucleic acid molecule as described above.

[0630] The present invention also provides a plurality of vectors comprising the plurality of nucleic acid molecules according to invention as described above. Thereby, each vector of the plurality of vectors may contain one or more nucleic acid molecules of the plurality of nucleic acid molecules according to invention as described above. In some embodiments, the plurality of vectors may be a combination of a first and a second vector, wherein the first vector comprises a first nucleic acid molecule as described above (for the combination of nucleic acid molecules) and the second vector comprises a second nucleic acid molecule as described above (for the combination of nucleic acid molecules). A vector is usually a recombinant nucleic acid molecule, i.e. a nucleic acid molecule which does not occur in nature. Accordingly, the vector may comprise heterologous elements (i.e., sequence elements of different origin in nature). For example, the vector may comprise a multiple cloning site, a heterologous promotor, a heterologous enhancer, a heterologous selection marker (to identify cells comprising said vector in comparison to cells not comprising said vector), heterologous origin of replications, heterologous DNA insulator elements and the like. A vector in the context of the present invention is suitable for incorporating or harboring a desired nucleic acid sequence. Such vectors may be storage vectors, expression vectors, cloning vectors, transfer vectors etc. A storage vector is a vector which allows the convenient storage of a nucleic acid molecule. Thus, the vector may comprise a sequence corresponding, e.g., to a (heavy and / or light chain of a) desired antibody according to the present invention. An expression vector may be used for production of expression products such as RNA, e.g. mRNA, or peptides, polypeptides or proteins. For example, an expression vector may comprise sequences needed for transcription of a sequence stretch of the vector, such as a (heterologous) promoter sequence. A cloning vector is typically a vector that contains a cloning site, which may be used to incorporate nucleic acid sequences into the vector. A cloning vector may be, e.g., a plasmid vector or a bacteriophage vector. A transfer vector may be a vector which is suitable for transferring nucleic acid molecules into cells or organisms, for example, viral vectors. A vector in the context of the present invention may be, e.g., an RNA vector or a DNA vector. For example, a vector in the sense of the present application comprises a cloning site, a selection marker, such as an antibiotic resistance factor, and a sequence suitable for multiplication of the vector, such as an origin of replication. A vector in the context of the present application may be a plasmid vector.

[0631] As used herein, the term "vector" may also refer to a delivery vector, e.g. for viral or non-viral delivery of a nucleic acid of the invention. Alternatively, it may be referred to viral or non-viral delivery systems. Accordingly, the present invention also provides a delivery vector / system comprising the 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 / systems are known in the art and described, for example, in 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 / systems include retroviral vectors; adenoviral vectors; adeno-associated viral (AAV) vectors, including helper-dependent adenoviral vectors and hybrid adenoviral vectors; herpes simplex virus vectors; lentivirus vectors; poxvirus vectors and Epstein-Barr virus vectors. Among the viral vectors, adenoviral vectors and adeno-associated viral (AAV) vectors are preferred. Non-limiting examples of non-viral delivery vectors / systems include chemical and non-chemical methods. Non-chemical delivery includes physical methods, such as electroporation and other methods for transient penetration of the cell membrane by mechanical, electrical, ultrasonic, hydrodynamic, or laser-based energy; naked DNA or RNA delivery; gene gun; hydrodynamic delivery; ultrasound delivery and magnetofection. Chemical non-viral delivery systems include cationic particles, in particular cationic lipids / liposomes, cationic polymers and lipid / polymer systems. Among non-viral vectors / systems, cationic liposomes are preferred.

[0632] Cells

[0633] In a further aspect, the present invention also provides a (host) cell expressing the antibody according to the present invention, or an antigen-binding fragment thereof; and / or comprising the vector (or the plurality of vectors) according the present invention. The (host) cell may be an isolated cell, which is not part of a human or animal body, e.g. a cell line or an engineered cell. The cell may express the nucleic acid(s) or vector(s) of the invention in a recombinant manner, e.g. in a heterologous manner (i.e., the cell / cell type does not express the antibody or the antigen-binding fragment in nature).

[0634] Examples of such cells include, but are not limited to, eukaryotic cells, e.g., yeast cells, animal cells or plant cells. Other examples of such cells include, but are not limited to, prokaryotic cells, e.g. E. coli. In some embodiments, the cells are mammalian cells, such as a mammalian cell line. Examples include human cells, CHO cells, HEK293 cells, PER. C6 cells, NSO cells, human liver cells, myeloma cells or hybridoma cells.

[0635] The cell may be transfected with a vector according to the present invention, for example with an expression vector. The term "transfection" refers to the introduction of nucleic acid molecules, such as DNA or RNA (e.g. mRNA) molecules, into cells, e.g. into eukaryotic or prokaryotic cells. In the context of the present invention, the term "transfection" encompasses any method known to the skilled person for introducing nucleic acid molecules into cells, such as into mammalian cells. Such methods encompass, for example, electroporation, lipofection, e.g. based on cationic lipids and / or liposomes, calcium phosphate precipitation, nanoparticle based transfection, virus based transfection, or transfection based on cationic polymers, such as DEAE-dextran or polyethylenimine etc. In some embodiments, the introduction is non-viral.

[0636] Moreover, the cells of the present invention may be transfected stably or transiently with the vector according to the present invention, e.g. for expressing the antibody according to the present invention. In some embodiments, the cells are stably transfected with the vector according to the present invention encoding the antibody according to the present invention. In other embodiments, the cells are transiently transfected with the vector according to the present invention encoding the antibody according to the present invention.

[0637] Accordingly, the present invention also provides a recombinant host cell, which heterologously expresses the antibody of the invention or the antigen-binding fragment thereof. For example, the cell may be of another species than 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. Moreover, the host cell may impart a post-translational modification (PTM; e.g., glycosylation) on the antibody that is not present in their native state. Such a PTM may result in a functional difference (e.g., decreased immunogenicity). Accordingly, the antibody of the invention, or the antigen-binding fragment thereof, may have a post-translational modification, which is distinct from the naturally produced antibody (e.g., an antibody of an immune response in a human).

[0638] Production of Antibodies

[0639] Antibodies according to the invention can be made by any method known in the art. For example, the general methodology for making monoclonal antibodies using hybridoma technology is well known (Kohler, G. and Milstein, C., 1975; Kozbar et al. 1983). Standard techniques of molecular biology may be used to prepare DNA sequences encoding the antibodies or antigen-binding fragments of the present invention. Desired DNA sequences may be synthesized completely or in part, e.g., using oligonucleotide synthesis techniques. Site-directed mutagenesis and polymerase chain reaction (PCR) techniques may be used as appropriate.

[0640] Any suitable host cell / vector system may be used for expression of the DNA sequences encoding the antibody molecules of the present invention. Eukaryotic, e.g., mammalian, host cell expression systems may be used for production of antibody molecules, such as complete antibody molecules. Suitable mammalian host cells include, but are not limited to, CHO, HEK293, PER. C6, NSO, myeloma or hybridoma cells. Also, prokaryotic, e.g. bacterial host cell expression systems may be used for the production of antibody molecules, such as complete antibody molecules. Suitable bacterial host cells include, but are not limited to, E. coli cells.

[0641] Accordingly, the present invention provides a method for preparing the antibody, or an antigen-binding fragment or an immunoglobulin chain(s) thereof, according to the present invention, said method comprising

[0642] (i) culturing the host cell as described above; and

[0643] (ii) isolating the antibody or immunoglobulin chain(s) thereof from the culture.

[0644] In other words, the present invention also provides a process for the production of an antibody molecule according to the present invention comprising culturing a (heterologous) host cell comprising a vector encoding a nucleic acid of the present invention, in particular under conditions suitable for expression of protein from DNA encoding the antibody molecule of the present invention, and isolating the antibody molecule.

[0645] For production of the antibody comprising both heavy and light chains, a host cell, such as a cell line, may be transfected with two vectors, a first vector encoding a light chain polypeptide and a second vector encoding a heavy chain polypeptide, e.g. as described above. Alternatively, a single vector may be used, the vector including sequences encoding light chain and heavy chain polypeptides (e.g. for single chain antibodies or in a bicistronic manner). Likewise, a plurality of vectors may be used, if multispecific antibodies with two or more immunoglobulin chains shall be expressed. Thus, the invention also provides a method for preparing a recombinant cell, comprising the steps of: (i) providing one or more nucleic acids that encode(s) the antibody of the invention; (ii) inserting the nucleic acid into an expression vector and (iii) transfecting the vector into a (heterologous) host cell in order to permit expression of the antibody of interest in that host cell. The nucleic acid of step (i) may, but need not, be manipulated to introduce restriction sites, to change codon usage, and / or to optimize transcription and / or translation regulatory sequences.

[0646] Furthermore, the invention also provides a method of preparing a transfected host cell, comprising the step of transfecting a host cell with one or more nucleic acids that encode an antibody of interest. Thus the procedures for first preparing the nucleic acid(s) and then using it to transfect a host cell can be performed at different times by different people in different places (e.g., in different countries).

[0647] These recombinant cells of the invention can then be used for expression and culture purposes. They are particularly useful for expression of antibodies for large-scale pharmaceutical production. They can also be used as the active ingredient of a pharmaceutical composition. Any suitable culture technique can be used, including but not limited to static culture, roller bottle culture, ascites fluid, hollow-fiber type bioreactor cartridge, modular minifermenter, stirred tank, microcarrier culture, ceramic core perfusion, etc.

[0648] The transfected host cell may be a eukaryotic cell, including yeast and animal cells, particularly mammalian cells (e.g., CHO cells, NSO cells, human cells such as PER. C6, HEK293 or HKB-11 cells, myeloma cells, or a human liver cell), as well as plant cells. In some embodiments, the transfected host cell is a mammalian cell, such as a human cell. In some embodiments, expression hosts can glycosylate the antibody of the invention, particularly with carbohydrate structures that are not themselves immunogenic in humans. In some embodiments the transfected host cell may be able to grow in serum-free media. In further embodiments the transfected host cell may be able to grow in culture without the presence of animal-derived products. The transfected host cell may also be cultured to give a cell line. The invention also provides a method of preparing the antibody of interest comprising the steps of: culturing or sub-culturing a transfected host cell population, e.g. a stably transfected host cell population, under conditions where the antibody of interest is expressed and, optionally, purifying the antibody of interest. The transfected host cell population may be prepared by (i) providing nucleic acid(s) encoding a selected antibody of interest, (ii) inserting the nucleic acid(s) into an expression vector, (iii) transfecting the vector in a host cell that can express the antibody of interest, and (iv) culturing or sub-culturing the transfected host cell comprising the inserted nucleic acids to produce the antibody of interest.

[0649] In some embodiments, antibodies according to the invention may be produced by (i) expressing a nucleic acid sequence according to the invention in a host cell, e.g. by use of a vector (or host cell) according to the present invention, and (ii) isolating the expressed antibody product. Additionally, the method may include (iii) purifying the isolated antibody.

[0650] Accordingly, after production, the antibodies may be further purified, if desired, using filtration, centrifugation and various chromatographic methods such as HPLC or affinity chromatography. Techniques for purification of antibodies, e.g., monoclonal antibodies, including techniques for producing pharmaceutical-grade antibodies, are well known in the art.

[0651] Compositions

[0652] The present invention also provides a composition comprising one or more of:

[0653] (i) the antibody of the present invention, or an antigen-binding fragment thereof;

[0654] (ii) the nucleic acid or the plurality of nucleic acids of the present invention;

[0655] (iii) the vector or the plurality of vectors of the present invention; or

[0656] (iv) the cell expressing the antibody according to the present invention or comprising the vector according to the present invention.

[0657] The composition may be used for treatment or diagnostic purposes. Accordingly, the composition may be a pharmaceutical composition or a diagnostic composition. The composition may comprise a (pharmaceutically acceptable) excipient, diluent or carrier. Accordingly, the present invention also provides a pharmaceutical composition comprising the antibody according to the present invention, or an antigen-binding fragment thereof, the nucleic acid or the plurality of nucleic acids of the present invention, the vector or the plurality of vectors of the present invention, and / or the cell according to the present invention.

[0658] The pharmaceutical composition may optionally also contain a pharmaceutically acceptable carrier, diluent and / or excipient. Although the carrier or excipient may facilitate administration, it should not itself induce the production of antibodies harmful to the individual receiving the composition. Nor should it be toxic. Suitable carriers may be large, slowly metabolized macromolecules such as proteins, polypeptides, liposomes, polysaccharides, polylactic acids, polyglycolic acids, polymeric amino acids, amino acid copolymers and inactive virus particles. In some embodiments, the pharmaceutically acceptable carrier, diluent and / or excipient in the pharmaceutical composition is not an active component in respect to birch pollen allergy or related allergy.

[0659] Pharmaceutically acceptable salts can be used, for example mineral acid salts, such as hydrochlorides, hydrobromides, phosphates and sulphates, or salts of organic acids, such as acetates, propionates, malonates and benzoates.

[0660] Pharmaceutically acceptable carriers in a pharmaceutical composition may additionally contain liquids such as water, saline, glycerol and ethanol. Additionally, auxiliary substances, such as wetting or emulsifying agents or pH buffering substances, may be present in such compositions. Such carriers enable the pharmaceutical compositions to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries and suspensions, for ingestion by the subject.

[0661] Pharmaceutical compositions may be prepared in various forms. For example, the compositions may be prepared as injectables, either as liquid solutions or suspensions. Solid forms suitable for solution in, or suspension in, liquid vehicles prior to injection can also be prepared (e.g., a lyophilized composition, similar to Synagis™ and Herceptin®, for reconstitution with sterile water containing a preservative). The composition may be prepared for topical administration e.g., as an ointment, cream or powder. The composition may be prepared for oral administration e.g., as a tablet or capsule, as a spray, or as a syrup (optionally flavored). The composition may be prepared for pulmonary administration e.g., as an inhaler, using a fine powder or a spray. The composition may be prepared as a suppository or pessary. The composition may be prepared for nasal, aural or ocular administration e.g., as drops. The composition may be in kit form, designed such that a combined composition is reconstituted just prior to administration to a subject. For example, a lyophilized antibody may be provided in kit form with sterile water or a sterile buffer.

[0662] In some embodiments, the (only) active ingredient in the composition is the antibody as described herein. As such, it may be susceptible to degradation in the gastrointestinal tract. Thus, if the composition is to be administered by a route using the gastrointestinal tract, the composition may contain agents which protect the antibody from degradation but which release the antibody once it has been absorbed from the gastrointestinal tract.

[0663] A thorough discussion of pharmaceutically acceptable carriers is available in Gennaro (2000) Remington: The Science and Practice of Pharmacy, 20th edition, ISBN: 0683306472.

[0664] The present invention also provides a method of preparing a pharmaceutical composition comprising the steps of: (i) preparing an antibody of the invention; and (ii) admixing the purified antibody with one or more pharmaceutically acceptable excipients, diluents or carriers.

[0665] In other embodiments, a method of preparing a pharmaceutical composition comprises the step of: admixing an antibody with one or more pharmaceutically-acceptable carriers, wh...

Claims

CLAIMS1. An antibody, or an antigen-binding fragment thereof, which specifically binds to Bet v 1 (Betula verrucosa allergen 1).

2. The antibody, or an antigen-binding fragment thereof, according to claim 1, wherein the antibody, or the antigen-binding fragment thereof, further binds specifically to a Bet v 1 homologous allergen.

3. The antibody, or an antigen-binding fragment thereof, according to claim 2, wherein the Bet v 1 homologous allergen is a tree pollen allergen.

4. The antibody, or an antigen-binding fragment thereof, according to claim 3, wherein the Bet v 1 homologous tree pollen allergen is selected from the group consisting of Cor a 1, Al n g 1, Fag s 1, Que a 1, Cas s 1, Ost c 1 and Car b 1.

5. The antibody, or an antigen-binding fragment thereof, according to any one of the previous claims, wherein the antibody or the antigen-binding fragment thereof, further binds specifically to a Bet v 1 homologous food allergen.

6. The antibody, or an antigen-binding fragment thereof, according to claim 5, wherein the Bet v 1 homologous food allergen is selected from the group consisting of Mal d 1, Cor a 1 and Jug r 5.

7. The antibody, or an antigen-binding fragment thereof, according to any one of the previous claims, wherein the antibody, or the 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.

8. The antibody, or an antigen-binding fragment thereof, according to any one of the previous claims, wherein the antibody, or the antigen-binding fragment thereof, comprises 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.

9. The antibody, or an antigen-binding fragment thereof, according to any one of the previous claims, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 7, and a VL having at least 70% identity to SEQ ID NO: 8.

10. The antibody, or an antigen-binding fragment thereof, according to any one of the previous claims, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH according to SEQ ID NO: 7, and a VL according to SEQ ID NO: 8.

11. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the 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.

12. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6 and 11, wherein the antibody, or the antigen-binding fragment thereof, comprises 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.

13. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, 11 and 12, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 15, and a VL having at least 70% identity to SEQ ID NO: 16.

14. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6 and 11 to 13, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH according to SEQ ID NO: 15; and a VL according to SEQ ID NO: 16.

15. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 17, a CDRH2 having at least 70% identity to SEQ ID NO: 18, a CDRH3 having at least 70% identity to SEQ ID NO: 19, a CDRL1 having at least 70% identity to SEQ ID NO: 20, a CDRL2 having at least 70% identity to SEQ ID NO: 21, and a CDRL3 having at least 70% identity to SEQ ID NO: 22.

16. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6 and 15, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 according to SEQ ID NO: 17, a CDRH2 according to SEQ ID NO: 18, a CDRH3 according to SEQ ID NO: 19, 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.

17. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, 15 and 16, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 23 or 799; and a VL having at least 70% identity to SEQ ID NO: 24.

18. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6 and 15 to 17, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH according to SEQ ID NO: 23 or 799; and a VL according to SEQ ID NO: 24.

19. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 25, a CDRH2 having at least 70% identity to SEQ ID NO: 26, a CDRH3 having at least 70% identity to SEQ ID NO: 27, a CDRL1 having at least 70% identity to SEQ ID NO: 28, a CDRL2 having at least 70%identity to SEQ ID NO: 29, and a CDRL3 having at least 70% identity to SEQ ID NO: 30.

20. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6 and 19, wherein the antibody, or the antigen-binding fragment thereof, comprises 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, and a CDRL3 according to SEQ ID NO: 30.

21. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, 19 and 20, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 31; and a VL having at least 70% identity to SEQ ID NO: 32.

22. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6 and 19 to 21, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH according to SEQ ID NO: 31; and a VL according to SEQ ID NO: 32.

23. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 33, a CDRH2 having at least 70% identity to SEQ ID NO: 34, a CDRH3 having at least 70% identity to SEQ ID NO: 35, a CDRL1 having at least 70% identity to SEQ ID NO: 36, a CDRL2 having at least 70% identity to SEQ ID NO: 37, and a CDRL3 having at least 70% identity to SEQ ID NO: 38.

24. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6 and 23, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 according to SEQ ID NO: 33, a CDRH2 according to SEQ ID NO: 34, a CDRH3 according to SEQ ID NO: 35, a CDRL1 according to SEQ ID NO: 36, a CDRL2 according to SEQ ID NO: 37, and a CDRL3 according to SEQ ID NO: 38.

25. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, 23 and 24, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 39; and a VL having at least 70% identity to SEQ ID NO: 40.

26. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6 and 23 to 25, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH according to SEQ ID NO: 39; and a VL according to SEQ ID NO: 40.

27. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 41, a CDRH2 having at least 70% identity to SEQ ID NO: 42, a CDRH3 having at least 70% identity to SEQ ID NO: 43, a CDRL1 having at least 70% identity to SEQ ID NO: 44, a CDRL2 having at least 70% identity to SEQ ID NO: 45, and a CDRL3 having at least 70% identity to SEQ ID NO: 46.

28. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6 and 27, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 according to SEQ ID NO: 41, a CDRH2 according to SEQ ID NO: 42, a CDRH3 according to SEQ ID NO: 43, a CDRL1 according to SEQ ID NO: 44, a CDRL2 according to SEQ ID NO: 45, and a CDRL3 according to SEQ ID NO: 46.

29. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, 27 and 28, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 47; and a VL having at least 70% identity to SEQ ID NO: 48.

30. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6 and 27 to 29, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH according to SEQ ID NO: 47; and a VL according to SEQ ID NO: 48.

31. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 49, a CDRH2 having at least 70% identity to SEQ ID NO: 50, a CDRH3 having at least 70% identity to SEQ ID NO: 51, a CDRL1 having at least 70% identity to SEQ ID NO: 52, a CDRL2 having at least 70% identity to SEQ ID NO: 53, and a CDRL3 having at least 70% identity to SEQ ID NO: 54.

32. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6 and 31, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 according to SEQ ID NO: 49, a CDRH2 according to SEQ ID NO: 50, a CDRH3 according to SEQ ID NO: 51, a CDRL1 according to SEQ ID NO: 52, a CDRL2 according to SEQ ID NO: 53, and a CDRL3 according to SEQ ID NO: 54.

33. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, 31 and 32, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 55; and a VL having at least 70% identity to SEQ ID NO: 56.

34. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6 and 31 to 33, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH according to SEQ ID NO: 55; and a VL according to SEQ ID NO: 56.

35. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 57, a CDRH2 having at least 70% identity to SEQ ID NO: 58, a CDRH3 having at least 70% identity to SEQ ID NO: 59, a CDRL1 having at least 70% identity to SEQ ID NO: 60, a CDRL2 having at least 70% identity to SEQ ID NO: 61, and a CDRL3 having at least 70% identity to SEQ ID NO: 62.

36. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6 and 35, wherein the antibody, or the antigen-binding fragment thereof, comprisesa CDRH1 according to SEQ ID NO: 57, a CDRH2 according to SEQ ID NO: 58, a CDRH3 according to SEQ ID NO: 59, a CDRL1 according to SEQ ID NO: 60, a CDRL2 according to SEQ ID NO: 61, and a CDRL3 according to SEQ ID NO: 62.

37. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, 35 and 36, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 63; and a VL having at least 70% identity to SEQ ID NO: 64.

38. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6 and 35 to 37, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH according to SEQ ID NO: 63; and a VL according to SEQ ID NO: 64.

39. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 65, a CDRH2 having at least 70% identity to SEQ ID NO: 66, a CDRH3 having at least 70% identity to SEQ ID NO: 67, a CDRL1 having at least 70% identity to SEQ ID NO: 68, a CDRL2 having at least 70% identity to SEQ ID NO: 69, and a CDRL3 having at least 70% identity to SEQ ID NO: 70.

40. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6 and 39, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 according to SEQ ID NO: 65, a CDRH2 according to SEQ ID NO: 66, a CDRH3 according to SEQ ID NO: 67, a CDRL1 according to SEQ ID NO: 68, a CDRL2 according to SEQ ID NO: 69, and a CDRL3 according to SEQ ID NO: 70.

41. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, 39 and 40, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 71; and a VL having at least 70% identity to SEQ ID NO: 72.

42. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6 and 39 to 41, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH according to SEQ ID NO: 71; and a VL according to SEQ ID NO: 72.

43. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 73, a CDRH2 having at least 70% identity to SEQ ID NO: 74, a CDRH3 having at least 70% identity to SEQ ID NO: 75, a CDRL1 having at least 70% identity to SEQ ID NO: 76, a CDRL2 having at least 70% identity to SEQ ID NO: 77, and a CDRL3 having at least 70% identity to SEQ ID NO: 78 or 800.

44. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6 and 43, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 according to SEQ ID NO: 73, a CDRH2 according to SEQ ID NO: 74, a CDRH3 according to SEQ ID NO: 75, a CDRL1 according to SEQ ID NO: 76, a CDRL2 according to SEQ ID NO: 77, and a CDRL3 according to SEQ ID NO: 78 or 800.

45. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, 43 and 44, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 79 or 801; and a VL having at least 70% identity to SEQ ID NO: 80 or 802.

46. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6 and 43 to 45, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH according to SEQ ID NO: 79 or 801; and a VL according to SEQ ID NO: 80 or 802.

47. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 81, a CDRH2 having at least 70% identity to SEQ ID NO: 82, a CDRH3 having at least 70% identity to SEQ ID NO: 83, a CDRL1 having at least 70% identity to SEQ ID NO: 84, a CDRL2 having at least 70%identity to SEQ ID NO: 85, and a CDRL3 having at least 70% identity to SEQ ID NO: 86, and preferably comprises a CDRH1 according to SEQ ID NO: 81, a CDRH2 according to SEQ ID NO: 82, a CDRH3 according to SEQ ID NO: 83, a CDRL1 according to SEQ ID NO: 84, a CDRL2 according to SEQ ID NO: 85, and a CDRL3 according to SEQ ID NO: 86.

48. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 47, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 87; and a VL having at least 70% identity to SEQ ID NO: 88, and preferably comprises a VH according to SEQ ID NO: 87; and a VL according to SEQ ID NO: 88.

49. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 89, a CDRH2 having at least 70% identity to SEQ ID NO: 90, a CDRH3 having at least 70% identity to SEQ ID NO: 91, a CDRL1 having at least 70% identity to SEQ ID NO: 92, a CDRL2 having at least 70% identity to SEQ ID NO: 93, and a CDRL3 having at least 70% identity to SEQ ID NO: 94, and preferably comprises a CDRH1 according to SEQ ID NO: 89, a CDRH2 according to SEQ ID NO: 90, a CDRH3 according to SEQ ID NO: 91, a CDRL1 according to SEQ ID NO: 92, a CDRL2 according to SEQ ID NO: 93, and a CDRL3 according to SEQ ID NO: 94.

50. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 49, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 95; and a VL having at least 70% identity to SEQ ID NO: 96, and preferably comprises a VH according to SEQ ID NO: 95; and a VL according to SEQ ID NO: 96.

51. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 97, a CDRH2 having at least 70% identity to SEQ ID NO: 98, a CDRH3 having at least 70% identity to SEQ ID NO: 99,a CDRL1 having at least 70% identity to SEQ ID NO: 100, a CDRL2 having at least 70% identity to SEQ ID NO: 101, and a CDRL3 having at least 70% identity to SEQ ID NO: 102, and preferably comprises a CDRH1 according to SEQ ID NO: 97, a CDRH2 according to SEQ ID NO: 98, a CDRH3 according to SEQ ID NO: 99, a CDRL1 according to SEQ ID NO: 100, a CDRL2 according to SEQ ID NO: 101, and a CDRL3 according to SEQ ID NO: 102.

52. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 51, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 103; and a VL having at least 70% identity to SEQ ID NO: 104, and preferably comprises a VH according to SEQ ID NO: 103; and a VL according to SEQ ID NO: 104.

53. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 105, a CDRH2 having at least 70% identity to SEQ ID NO: 106, a CDRH3 having at least 70% identity to SEQ ID NO: 107, a CDRL1 having at least 70% identity to SEQ ID NO: 108, a CDRL2 having at least 70% identity to SEQ ID NO: 109, and a CDRL3 having at least 70% identity to SEQ ID NO: 110, and preferably comprises a CDRH1 according to SEQ ID NO: 105, a CDRH2 according to SEQ ID NO: 106, a CDRH3 according to SEQ ID NO: 107, a CDRL1 according to SEQ ID NO: 108, a CDRL2 according to SEQ ID NO: 109, and a CDRL3 according to SEQ ID NO: 110.

54. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 53, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 111; and a VL having at least 70% identity to SEQ ID NO: 112, and preferably comprises a VH according to SEQ ID NO: 111; and a VL according to SEQ ID NO: 112.

55. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 113, a CDRH2 having at least 70%identity to SEQ ID NO: 114, a CDRH3 having at least 70% identity to SEQ ID NO: 115, a CDRL1 having at least 70% identity to SEQ ID NO: 116, a CDRL2 having at least 70% identity to SEQ ID NO: 117, and a CDRL3 having at least 70% identity to SEQ ID NO: 118, and preferably comprises a CDRH1 according to SEQ ID NO: 113, a CDRH2 according to SEQ ID NO: 114, a CDRH3 according to SEQ ID NO: 115, a CDRL1 according to SEQ ID NO: 116, a CDRL2 according to SEQ ID NO: 117, and a CDRL3 according to SEQ ID NO: 118.

56. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 55, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 119; and a VL having at least 70% identity to SEQ ID NO: 120, and preferably comprises a VH according to SEQ ID NO: 119; and a VL according to SEQ ID NO: 120.

57. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 121, a CDRH2 having at least 70% identity to SEQ ID NO: 122, a CDRH3 having at least 70% identity to SEQ ID NO: 123, a CDRL1 having at least 70% identity to SEQ ID NO: 124, a CDRL2 having at least 70% identity to SEQ ID NO: 125, and a CDRL3 having at least 70% identity to SEQ ID NO: 126, and preferably comprises a CDRH1 according to SEQ ID NO: 121, a CDRH2 according to SEQ ID NO: 122, a CDRH3 according to SEQ ID NO: 123, a CDRL1 according to SEQ ID NO: 124, a CDRL2 according to SEQ ID NO: 125, and a CDRL3 according to SEQ ID NO: 126.

58. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 57, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 127; and a VL having at least 70% identity to SEQ ID NO: 128, and preferably comprises a VH according to SEQ ID NO: 127; and a VL according to SEQ ID NO: 128.

59. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises aCDRH1 having at least 70% identity to SEQ ID NO: 129, a CDRH2 having at least 70% identity to SEQ ID NO: 130, a CDRH3 having at least 70% identity to SEQ ID NO: 131, a CDRL1 having at least 70% identity to SEQ ID NO: 132, a CDRL2 having at least 70% identity to SEQ ID NO: 133, and a CDRL3 having at least 70% identity to SEQ ID NO: 134, and preferably comprises a CDRH1 according to SEQ ID NO: 129, a CDRH2 according to SEQ ID NO: 130, a CDRH3 according to SEQ ID NO: 131, a CDRL1 according to SEQ ID NO: 132, a CDRL2 according to SEQ ID NO: 133, and a CDRL3 according to SEQ ID NO: 134.

60. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 59, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 135; and a VL having at least 70% identity to SEQ ID NO: 136, and preferably comprises a VH according to SEQ ID NO: 135; and a VL according to SEQ ID NO: 136.

61. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 137, a CDRH2 having at least 70% identity to SEQ ID NO: 138, a CDRH3 having at least 70% identity to SEQ ID NO: 139, a CDRL1 having at least 70% identity to SEQ ID NO: 140, a CDRL2 having at least 70% identity to SEQ ID NO: 141, and a CDRL3 having at least 70% identity to SEQ ID NO: 142, and preferably comprises a CDRH1 according to SEQ ID NO: 137, a CDRH2 according to SEQ ID NO: 138, a CDRH3 according to SEQ ID NO: 139, a CDRL1 according to SEQ ID NO: 140, a CDRL2 according to SEQ ID NO: 141, and a CDRL3 according to SEQ ID NO: 142.

62. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 61, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 143; and a VL having at least 70% identity to SEQ ID NO: 144, and preferably comprises a VH according to SEQ ID NO: 143; and a VL according to SEQ ID NO: 144.

63. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 145, a CDRH2 having at least 70% identity to SEQ ID NO: 146, a CDRH3 having at least 70% identity to SEQ ID NO: 147, a CDRL1 having at least 70% identity to SEQ ID NO: 148, a CDRL2 having at least 70% identity to SEQ ID NO: 149, and a CDRL3 having at least 70% identity to SEQ ID NO: 150, and preferably comprises a CDRH1 according to SEQ ID NO: 145, a CDRH2 according to SEQ ID NO: 146, a CDRH3 according to SEQ ID NO: 147, a CDRL1 according to SEQ ID NO: 148, a CDRL2 according to SEQ ID NO: 149, and a CDRL3 according to SEQ ID NO: 150.

64. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 63, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 151; and a VL having at least 70% identity to SEQ ID NO: 152, and preferably comprises a VH according to SEQ ID NO: 51; and a VL according to SEQ ID NO: 152.

65. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 153, a CDRH2 having at least 70% identity to SEQ ID NO: 154, a CDRH3 having at least 70% identity to SEQ ID NO: 155, a CDRL1 having at least 70% identity to SEQ ID NO: 156, a CDRL2 having at least 70% identity to SEQ ID NO: 157, and a CDRL3 having at least 70% identity to SEQ ID NO: 158, and preferably comprises a CDRH1 according to SEQ ID NO: 153, a CDRH2 according to SEQ ID NO: 154, a CDRH3 according to SEQ ID NO: 155, a CDRL1 according to SEQ ID NO: 156, a CDRL2 according to SEQ ID NO: 157, and a CDRL3 according to SEQ ID NO: 158.

66. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 65, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 159; and a VL having at least 70% identity to SEQ ID NO: 160, and preferably comprises a VH according to SEQ ID NO: 159; and a VL according to SEQ ID NO: 160.

67. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 161, a CDRH2 having at least 70% identity to SEQ ID NO: 162, a CDRH3 having at least 70% identity to SEQ ID NO: 163, a CDRL1 having at least 70% identity to SEQ ID NO: 164, a CDRL2 having at least 70% identity to SEQ ID NO: 165, and a CDRL3 having at least 70% identity to SEQ ID NO: 166, and preferably comprises a CDRH1 according to SEQ ID NO: 161, a CDRH2 according to SEQ ID NO: 162, a CDRH3 according to SEQ ID NO: 163, a CDRL1 according to SEQ ID NO: 164, a CDRL2 according to SEQ ID NO: 165, and a CDRL3 according to SEQ ID NO: 166.

68. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 67, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 167; and a VL having at least 70% identity to SEQ ID NO: 168, and preferably comprises a VH according to SEQ ID NO: 167; and a VL according to SEQ ID NO: 168.

69. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 169, a CDRH2 having at least 70% identity to SEQ ID NO: 170, a CDRH3 having at least 70% identity to SEQ ID NO: 171, a CDRL1 having at least 70% identity to SEQ ID NO: 172, a CDRL2 having at least 70% identity to SEQ ID NO: 173, and a CDRL3 having at least 70% identity to SEQ ID NO: 174, and preferably comprises a CDRH1 according to SEQ ID NO: 169, a CDRH2 according to SEQ ID NO: 170, a CDRH3 according to SEQ ID NO: 171, a CDRL1 according to SEQ ID NO: 172, a CDRL2 according to SEQ ID NO: 173, and a CDRL3 according to SEQ ID NO: 174.

70. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 69, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 175; and a VL having atleast 70% identity to SEQ ID NO: 176, and preferably comprises a VH according to SEQ ID NO: 175; and a VL according to SEQ ID NO: 176.

71. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 177, a CDRH2 having at least 70% identity to SEQ ID NO: 178, a CDRH3 having at least 70% identity to SEQ ID NO: 179, a CDRL1 having at least 70% identity to SEQ ID NO: 180, a CDRL2 having at least 70% identity to SEQ ID NO: 181, and a CDRL3 having at least 70% identity to SEQ ID NO: 182, and preferably comprises a CDRH1 according to SEQ ID NO: 177, a CDRH2 according to SEQ ID NO: 178, a CDRH3 according to SEQ ID NO: 179, a CDRL1 according to SEQ ID NO: 180, a CDRL2 according to SEQ ID NO: 181, and a CDRL3 according to SEQ ID NO: 182.

72. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 71, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 183; and a VL having at least 70% identity to SEQ ID NO: 184, and preferably comprises a VH according to SEQ ID NO: 183; and a VL according to SEQ ID NO: 184.

73. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 185, a CDRH2 having at least 70% identity to SEQ ID NO: 186, a CDRH3 having at least 70% identity to SEQ ID NO: 187, a CDRL1 having at least 70% identity to SEQ ID NO: 188, a CDRL2 having at least 70% identity to SEQ ID NO: 189, and a CDRL3 having at least 70% identity to SEQ ID NO: 190, and preferably comprises a CDRH1 according to SEQ ID NO: 185, a CDRH2 according to SEQ ID NO: 186, a CDRH3 according to SEQ ID NO: 187, a CDRL1 according to SEQ ID NO: 188, a CDRL2 according to SEQ ID NO: 189, and a CDRL3 according to SEQ ID NO: 190.

74. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 73, wherein the antibody, or the antigen-binding fragment thereof,comprises a VH having at least 70% identity to SEQ ID NO: 191; and a VL having at least 70% identity to SEQ ID NO: 192, and preferably comprises a VH according to SEQ ID NO: 191; and a VL according to SEQ ID NO: 192.

75. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 193, a CDRH2 having at least 70% identity to SEQ ID NO: 194, a CDRH3 having at least 70% identity to SEQ ID NO: 195, a CDRL1 having at least 70% identity to SEQ ID NO: 196, a CDRL2 having at least 70% identity to SEQ ID NO: 197, and a CDRL3 having at least 70% identity to SEQ ID NO: 198, and preferably comprises a CDRH1 according to SEQ ID NO: 193, a CDRH2 according to SEQ ID NO: 194, a CDRH3 according to SEQ ID NO: 195, a CDRL1 according to SEQ ID NO: 196, a CDRL2 according to SEQ ID NO: 197, and a CDRL3 according to SEQ ID NO: 198.

76. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 75, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 199; and a VL having at least 70% identity to SEQ ID NO: 200, and preferably comprises a VH according to SEQ ID NO: 199; and a VL according to SEQ ID NO: 200.

77. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 201, a CDRH2 having at least 70% identity to SEQ ID NO: 202, a CDRH3 having at least 70% identity to SEQ ID NO: 203, a CDRL1 having at least 70% identity to SEQ ID NO: 204, a CDRL2 having at least 70% identity to SEQ ID NO: 205, and a CDRL3 having at least 70% identity to SEQ ID NO: 206, and preferably comprises a CDRH1 according to SEQ ID NO: 201, a CDRH2 according to SEQ ID NO: 202, a CDRH3 according to SEQ ID NO: 203, a CDRL1 according to SEQ ID NO: 204, a CDRL2 according to SEQ ID NO: 205, and a CDRL3 according to SEQ ID NO: 206.

78. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 77, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 207; and a VL having at least 70% identity to SEQ ID NO: 208, and preferably comprises a VH according to SEQ ID NO: 207; and a VL according to SEQ ID NO: 208.

79. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 209, a CDRH2 having at least 70% identity to SEQ ID NO: 210, a CDRH3 having at least 70% identity to SEQ ID NO: 211, a CDRL1 having at least 70% identity to SEQ ID NO: 212, a CDRL2 having at least 70% identity to SEQ ID NO: 213, and a CDRL3 having at least 70% identity to SEQ ID NO: 214, and preferably comprises a CDRH1 according to SEQ ID NO: 209, a CDRH2 according to SEQ ID NO: 210, a CDRH3 according to SEQ ID NO: 211, a CDRL1 according to SEQ ID NO: 212, a CDRL2 according to SEQ ID NO: 213, and a CDRL3 according to SEQ ID NO: 214.

80. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 79, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 215; and a VL having at least 70% identity to SEQ ID NO: 216, and preferably comprises a VH according to SEQ ID NO: 215; and a VL according to SEQ ID NO: 216.

81. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 217, a CDRH2 having at least 70% identity to SEQ ID NO: 218, a CDRH3 having at least 70% identity to SEQ ID NO: 219, a CDRL1 having at least 70% identity to SEQ ID NO: 220, a CDRL2 having at least 70% identity to SEQ ID NO: 221, and a CDRL3 having at least 70% identity to SEQ ID NO: 222, and preferably comprises a CDRH1 according to SEQ ID NO: 217, a CDRH2 according to SEQ ID NO: 218, a CDRH3 according to SEQ ID NO: 219, a CDRL1 according to SEQ ID NO: 220, a CDRL2 according to SEQ ID NO: 221, and a CDRL3 according to SEQ ID NO: 222.

82. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 81, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 223; and a VL having at least 70% identity to SEQ ID NO: 224, and preferably comprises a VH according to SEQ ID NO: 223; and a VL according to SEQ ID NO: 224.

83. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 225, a CDRH2 having at least 70% identity to SEQ ID NO: 226, a CDRH3 having at least 70% identity to SEQ ID NO: 227, a CDRL1 having at least 70% identity to SEQ ID NO: 228, a CDRL2 having at least 70% identity to SEQ ID NO: 229, and a CDRL3 having at least 70% identity to SEQ ID NO: 230, and preferably comprises a CDRH1 according to SEQ ID NO: 225, a CDRH2 according to SEQ ID NO: 226, a CDRH3 according to SEQ ID NO: 227, a CDRL1 according to SEQ ID NO: 228, a CDRL2 according to SEQ ID NO: 229, and a CDRL3 according to SEQ ID NO: 230.

84. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 83, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 231; and a VL having at least 70% identity to SEQ ID NO: 232, and preferably comprises a VH according to SEQ ID NO: 231; and a VL according to SEQ ID NO: 232.

85. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 233, a CDRH2 having at least 70% identity to SEQ ID NO: 234, a CDRH3 having at least 70% identity to SEQ ID NO: 235, a CDRL1 having at least 70% identity to SEQ ID NO: 236, a CDRL2 having at least 70% identity to SEQ ID NO: 237, and a CDRL3 having at least 70% identity to SEQ ID NO: 238, and preferably comprises a CDRH1 according to SEQ ID NO: 233, a CDRH2 according to SEQ ID NO: 234, a CDRH3 according to SEQ ID NO: 235, a CDRL1according to SEQ ID NO: 236, a CDRL2 according to SEQ ID NO: 237, and a CDRL3 according to SEQ ID NO: 238.

86. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 85, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 239 or having at least 70% identity to SEQ ID NO: 803; and a VL having at least 70% identity to SEQ ID NO: 240 or having at least 70% identity to SEQ ID NO: 804, and preferably comprises a VH according to SEQ ID NO: 239 or a VH according to SEQ ID NO 803; and a VL according to SEQ ID NO: 240 or a VL according to SEQ ID NO: 804.

87. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 241, a CDRH2 having at least 70% identity to SEQ ID NO: 242, a CDRH3 having at least 70% identity to SEQ ID NO: 243, a CDRL1 having at least 70% identity to SEQ ID NO: 244, a CDRL2 having at least 70% identity to SEQ ID NO: 245, and a CDRL3 having at least 70% identity to SEQ ID NO: 246, and preferably comprises a CDRH1 according to SEQ ID NO: 241, a CDRH2 according to SEQ ID NO: 242, a CDRH3 according to SEQ ID NO: 243, a CDRL1 according to SEQ ID NO: 244, a CDRL2 according to SEQ ID NO: 245, and a CDRL3 according to SEQ ID NO: 246.

88. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 87, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 247; and a VL having at least 70% identity to SEQ ID NO: 248, and preferably comprises a VH according to SEQ ID NO: 247; and a VL according to SEQ ID NO: 248.

89. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 249, a CDRH2 having at least 70% identity to SEQ ID NO: 250, a CDRH3 having at least 70% identity to SEQ ID NO: 251, a CDRL1 having at least 70% identity to SEQ ID NO: 252, a CDRL2 having at least70% identity to SEQ ID NO: 253, and a CDRL3 having at least 70% identity to SEQ ID NO: 254, and preferably comprises a CDRH1 according to SEQ ID NO: 249, a CDRH2 according to SEQ ID NO: 250, a CDRH3 according to SEQ ID NO: 251, a CDRL1 according to SEQ ID NO: 252, a CDRL2 according to SEQ ID NO: 253, and a CDRL3 according to SEQ ID NO: 254.

90. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 89, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 255; and a VL having at least 70% identity to SEQ ID NO: 256, and preferably comprises a VH according to SEQ ID NO: 255; and a VL according to SEQ ID NO: 256.

91. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 257, a CDRH2 having at least 70% identity to SEQ ID NO: 258, a CDRH3 having at least 70% identity to SEQ ID NO: 259, a CDRL1 having at least 70% identity to SEQ ID NO: 260, a CDRL2 having at least 70% identity to SEQ ID NO: 261, and a CDRL3 having at least 70% identity to SEQ ID NO: 262, and preferably comprises a CDRH1 according to SEQ ID NO: 257, a CDRH2 according to SEQ ID NO: 258, a CDRH3 according to SEQ ID NO: 259, a CDRL1 according to SEQ ID NO: 260, a CDRL2 according to SEQ ID NO: 261, and a CDRL3 according to SEQ ID NO: 262.

92. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 91, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 263; and a VL having at least 70% identity to SEQ ID NO: 264, and preferably comprises a VH according to SEQ ID NO: 263; and a VL according to SEQ ID NO: 264.

93. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 265, a CDRH2 having at least 70% identity to SEQ ID NO: 266, a CDRH3 having at least 70% identity to SEQ ID NO: 267,a CDRL1 having at least 70% identity to SEQ ID NO: 268, a CDRL2 having at least 70% identity to SEQ ID NO: 269, and a CDRL3 having at least 70% identity to SEQ ID NO: 270, and preferably comprises a CDRH1 according to SEQ ID NO: 265, a CDRH2 according to SEQ ID NO: 266, a CDRH3 according to SEQ ID NO: 267, a CDRL1 according to SEQ ID NO: 268, a CDRL2 according to SEQ ID NO: 269, and a CDRL3 according to SEQ ID NO: 270.

94. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 93, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 271 or having at least 70% identity to SEQ ID NO: 805; and a VL having at least 70% identity to SEQ ID NO: 272 or having at least 70% identity to SEQ ID NO: 806, and preferably comprises a VH according to SEQ ID NO: 271 or a VH according to SEQ ID NO: 805; and a VL according to SEQ ID NO: 272 or a VL according to SEQ ID NO: 806.

95. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 273, a CDRH2 having at least 70% identity to SEQ ID NO: 274, a CDRH3 having at least 70% identity to SEQ ID NO: 275, a CDRL1 having at least 70% identity to SEQ ID NO: 276, a CDRL2 having at least 70% identity to SEQ ID NO: 277, and a CDRL3 having at least 70% identity to SEQ ID NO: 278, and preferably comprises a CDRH1 according to SEQ ID NO: 273, a CDRH2 according to SEQ ID NO: 274, a CDRH3 according to SEQ ID NO: 275, a CDRL1 according to SEQ ID NO: 276, a CDRL2 according to SEQ ID NO: 277, and a CDRL3 according to SEQ ID NO: 278.

96. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 95, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 279; and a VL having at least 70% identity to SEQ ID NO: 280, and preferably comprises a VH according to SEQ ID NO: 279; and a VL according to SEQ ID NO: 280.

97. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 281, a CDRH2 having at least 70% identity to SEQ ID NO: 282, a CDRH3 having at least 70% identity to SEQ ID NO: 283, a CDRL1 having at least 70% identity to SEQ ID NO: 284, a CDRL2 having at least 70% identity to SEQ ID NO: 285, and a CDRL3 having at least 70% identity to SEQ ID NO: 286, and preferably comprises a CDRH1 according to SEQ ID NO: 281, a CDRH2 according to SEQ ID NO: 282, a CDRH3 according to SEQ ID NO: 283, a CDRL1 according to SEQ ID NO: 284, a CDRL2 according to SEQ ID NO: 285, and a CDRL3 according to SEQ ID NO: 286.

98. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 97, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 287; and a VL having at least 70% identity to SEQ ID NO: 288, and preferably comprises a VH according to SEQ ID NO: 287; and a VL according to SEQ ID NO: 288.

99. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 289, a CDRH2 having at least 70% identity to SEQ ID NO: 290, a CDRH3 having at least 70% identity to SEQ ID NO: 291, a CDRL1 having at least 70% identity to SEQ ID NO: 292, a CDRL2 having at least 70% identity to SEQ ID NO: 293, and a CDRL3 having at least 70% identity to SEQ ID NO: 294, and preferably comprises a CDRH1 according to SEQ ID NO: 289, a CDRH2 according to SEQ ID NO: 290, a CDRH3 according to SEQ ID NO: 291, a CDRL1 according to SEQ ID NO: 292, a CDRL2 according to SEQ ID NO: 293, and a CDRL3 according to SEQ ID NO: 294.

100. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 99, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 295; and a VL having at least 70% identity to SEQ ID NO: 296, and preferably comprises a VH according to SEQ ID NO: 295; and a VL according to SEQ ID NO: 296.

101. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 297, a CDRH2 having at least 70% identity to SEQ ID NO: 298, a CDRH3 having at least 70% identity to SEQ ID NO: 299, a CDRL1 having at least 70% identity to SEQ ID NO: 300, a CDRL2 having at least 70% identity to SEQ ID NO: 301, and a CDRL3 having at least 70% identity to SEQ ID NO: 302, and preferably comprises a CDRH1 according to SEQ ID NO: 297, a CDRH2 according to SEQ ID NO: 298, a CDRH3 according to SEQ ID NO: 299, a CDRL1 according to SEQ ID NO: 300, a CDRL2 according to SEQ ID NO: 301, and a CDRL3 according to SEQ ID NO: 302.

102. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 101, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 303; and a VL having at least 70% identity to SEQ ID NO: 304, and preferably comprises a VH according to SEQ ID NO: 303; and a VL according to SEQ ID NO: 304.

103. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 305, a CDRH2 having at least 70% identity to SEQ ID NO: 306, a CDRH3 having at least 70% identity to SEQ ID NO: 307, a CDRL1 having at least 70% identity to SEQ ID NO: 308, a CDRL2 having at least 70% identity to SEQ ID NO: 309, and a CDRL3 having at least 70% identity to SEQ ID NO: 310, and preferably comprises a CDRH1 according to SEQ ID NO: 305, a CDRH2 according to SEQ ID NO: 306, a CDRH3 according to SEQ ID NO: 307, a CDRL1 according to SEQ ID NO: 308, a CDRL2 according to SEQ ID NO: 309, and a CDRL3 according to SEQ ID NO: 310.

104. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 103, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 311; and a VL having atleast 70% identity to SEQ ID NO: 312, and preferably comprises a VH according to SEQ ID NO: 311; and a VL according to SEQ ID NO: 312.

105. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 313, a CDRH2 having at least 70% identity to SEQ ID NO: 314, a CDRH3 having at least 70% identity to SEQ ID NO: 315, a CDRL1 having at least 70% identity to SEQ ID NO: 316, a CDRL2 having at least 70% identity to SEQ ID NO: 317, and a CDRL3 having at least 70% identity to SEQ ID NO: 318, and preferably comprises a CDRH1 according to SEQ ID NO: 313, a CDRH2 according to SEQ ID NO: 314, a CDRH3 according to SEQ ID NO: 315, a CDRL1 according to SEQ ID NO: 316, a CDRL2 according to SEQ ID NO: 317, and a CDRL3 according to SEQ ID NO: 318.

106. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 105, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 319 or having at least 70% identity to SEQ ID NO: 807; and a VL having at least 70% identity to SEQ ID NO: 320 or having at least 70% identity to SEQ ID NO: 808, and preferably comprises a VH according to SEQ ID NO: 319 or a VH according to SEQ ID NO: 807; and a VL according to SEQ ID NO: 320 or a VL according to SEQ ID NO: 808.

107. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 321, a CDRH2 having at least 70% identity to SEQ ID NO: 322, a CDRH3 having at least 70% identity to SEQ ID NO: 323, a CDRL1 having at least 70% identity to SEQ ID NO: 324, a CDRL2 having at least 70% identity to SEQ ID NO: 325, and a CDRL3 having at least 70% identity to SEQ ID NO: 326, and preferably comprises a CDRH1 according to SEQ ID NO: 321, a CDRH2 according to SEQ ID NO: 322, a CDRH3 according to SEQ ID NO: 323, a CDRL1 according to SEQ ID NO: 324, a CDRL2 according to SEQ ID NO: 325, and a CDRL3 according to SEQ ID NO: 326.

108. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 107, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 327; and a VL having at least 70% identity to SEQ ID NO: 328, and preferably comprises a VH according to SEQ ID NO: 327; and a VL according to SEQ ID NO: 328.

109. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 329, a CDRH2 having at least 70% identity to SEQ ID NO: 330, a CDRH3 having at least 70% identity to SEQ ID NO: 331, a CDRL1 having at least 70% identity to SEQ ID NO: 332, a CDRL2 having at least 70% identity to SEQ ID NO: 333, and a CDRL3 having at least 70% identity to SEQ ID NO: 334, and preferably comprises a CDRH1 according to SEQ ID NO: 329, a CDRH2 according to SEQ ID NO: 330, a CDRH3 according to SEQ ID NO: 331, a CDRL1 according to SEQ ID NO: 332, a CDRL2 according to SEQ ID NO: 333, and a CDRL3 according to SEQ ID NO: 334.

110. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 109, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 335; and a VL having at least 70% identity to SEQ ID NO: 336, and preferably comprises a VH according to SEQ ID NO: 335; and a VL according to SEQ ID NO: 336.

111. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 337, a CDRH2 having at least 70% identity to SEQ ID NO: 338, a CDRH3 having at least 70% identity to SEQ ID NO: 339, a CDRL1 having at least 70% identity to SEQ ID NO: 340, a CDRL2 having at least 70% identity to SEQ ID NO: 341, and a CDRL3 having at least 70% identity to SEQ ID NO: 342, and preferably comprises a CDRH1 according to SEQ ID NO: 337, a CDRH2 according to SEQ ID NO: 338, a CDRH3 according to SEQ ID NO: 339, a CDRL1 according to SEQ ID NO: 340, a CDRL2 according to SEQ ID NO: 341, and a CDRL3 according to SEQ ID NO: 342.

112. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 111, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 343; and a VL having at least 70% identity to SEQ ID NO: 344, and preferably comprises a VH according to SEQ ID NO: 343; and a VL according to SEQ ID NO: 344.

113. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 345, a CDRH2 having at least 70% identity to SEQ ID NO: 346, a CDRH3 having at least 70% identity to SEQ ID NO: 347, a CDRL1 having at least 70% identity to SEQ ID NO: 348, a CDRL2 having at least 70% identity to SEQ ID NO: 349, and a CDRL3 having at least 70% identity to SEQ ID NO: 350, and preferably comprises a CDRH1 according to SEQ ID NO: 345, a CDRH2 according to SEQ ID NO: 346, a CDRH3 according to SEQ ID NO: 347, a CDRL1 according to SEQ ID NO: 348, a CDRL2 according to SEQ ID NO: 349, and a CDRL3 according to SEQ ID NO: 350.

114. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 113, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 351; and a VL having at least 70% identity to SEQ ID NO: 352, and preferably comprises a VH according to SEQ ID NO: 351; and a VL according to SEQ ID NO: 352.

115. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 353, a CDRH2 having at least 70% identity to SEQ ID NO: 354, a CDRH3 having at least 70% identity to SEQ ID NO: 355, a CDRL1 having at least 70% identity to SEQ ID NO: 356, a CDRL2 having at least 70% identity to SEQ ID NO: 357, and a CDRL3 having at least 70% identity to SEQ ID NO: 358, and preferably comprises a CDRH1 according to SEQ ID NO: 353, a CDRH2 according to SEQ ID NO: 354, a CDRH3 according to SEQ ID NO: 355, a CDRL1according to SEQ ID NO: 356, a CDRL2 according to SEQ ID NO: 357, and a CDRL3 according to SEQ ID NO: 358.

116. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 115, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 359; and a VL having at least 70% identity to SEQ ID NO: 360, and preferably comprises a VH according to SEQ ID NO: 359; and a VL according to SEQ ID NO: 360.

117. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 361, a CDRH2 having at least 70% identity to SEQ ID NO: 362, a CDRH3 having at least 70% identity to SEQ ID NO: 363, a CDRL1 having at least 70% identity to SEQ ID NO: 364, a CDRL2 having at least 70% identity to SEQ ID NO: 365, and a CDRL3 having at least 70% identity to SEQ ID NO: 366, and preferably comprises a CDRH1 according to SEQ ID NO: 361, a CDRH2 according to SEQ ID NO: 362, a CDRH3 according to SEQ ID NO: 363, a CDRL1 according to SEQ ID NO: 364, a CDRL2 according to SEQ ID NO: 365, and a CDRL3 according to SEQ ID NO: 366.

118. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 117, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 367; and a VL having at least 70% identity to SEQ ID NO: 368, and preferably comprises a VH according to SEQ ID NO: 367; and a VL according to SEQ ID NO: 368.

119. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 809, a CDRH2 having at least 70% identity to SEQ ID NO: 810, a CDRH3 having at least 70% identity to SEQ ID NO: 754, a CDRL1 having at least 70% identity to SEQ ID NO: 755, a CDRL2 having at least 70% identity to SEQ ID NO: 811, and a CDRL3 having at least 70% identity to SEQ ID NO: 757, and preferably comprises a CDRH1 according to SEQ ID NO: 809, a CDRH2according to SEQ ID NO: 8010, a CDRH3 according to SEQ ID NO: 754, a CDRL1 according to SEQ ID NO: 755, a CDRL2 according to SEQ ID NO: 811, and a CDRL3 according to SEQ ID NO: 757.

120. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 119, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 812; and a VL having at least 70% identity to SEQ ID NO: 813, and preferably comprises a VH according to SEQ ID NO: 812; and a VL according to SEQ ID NO: 813.

121. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 768, a CDRH2 having at least 70% identity to SEQ ID NO: 814, a CDRH3 having at least 70% identity to SEQ ID NO: 770, a CDRL1 having at least 70% identity to SEQ ID NO: 815, a CDRL2 having at least 70% identity to SEQ ID NO: 816, and a CDRL3 having at least 70% identity to SEQ ID NO: 817, and preferably comprises a CDRH1 according to SEQ ID NO: 768, a CDRH2 according to SEQ ID NO: 814, a CDRH3 according to SEQ ID NO: 770, a CDRL1 according to SEQ ID NO: 815, a CDRL2 according to SEQ ID NO: 816, and a CDRL3 according to SEQ ID NO: 817.

122. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 6, and 121, wherein the antibody, or the antigen-binding fragment thereof, comprises a VH having at least 70% identity to SEQ ID NO: 818; and a VL having at least 70% identity to SEQ ID NO: 819, and preferably comprises a VH according to SEQ ID NO: 818; and a VL according to SEQ ID NO: 819.

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

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

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

126. The antibody according to any one of the previous claims, wherein the antibody comprises an Fc moiety.

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

128. The antibody according to claim 23, wherein the antibody is of the IgG1 or IgG4 type, preferably of the IgG4 type.

129. The antibody according to any one according to the previous claims, wherein the variable regions or the CDRs are derived from an IgE antibody and grafted in a scaffold of an IgG or IgA antibody.

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

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

132. The antibody, or an antigen-binding fragment thereof, according to any one of the previous claims, wherein the antibody, or the antigen-binding fragment thereof, is a scFv.

133. The antibody, or an antigen-binding fragment thereof, according to claim 132, wherein the scFv comprises a CDRH1 having at least 70% identity to SEQ ID NO: 233, a CDRH2 having at least 70% identity to SEQ ID NO: 234, a CDRH3 having at least 70% identity to SEQ ID NO: 235, a CDRL1 having at least 70% identity to SEQ ID NO: 236, a CDRL2 having at least 70% identity to SEQ ID NO: 237, and a CDRL3 having at least 70% identity to SEQ ID NO: 238, and preferably comprises a CDRH1 according to SEQ ID NO: 233, a CDRH2 according to SEQ ID NO: 234, a CDRH3 according to SEQ ID NO: 235, a CDRL1 according to SEQ ID NO: 236, a CDRL2 according to SEQ ID NO: 237, and a CDRL3 according to SEQ ID NO: 238.

134. The antibody, or an antigen-binding fragment thereof, according to claim 133, wherein the scFv comprises an amino acid sequence having at least 70% identity to SEQ ID NO: 857 or SEQ ID NO: 858, and preferably comprises an amino acid sequence according to SEQ ID NO: 857, or SEQ ID NO: 858.

135. The antibody, or an antigen-binding fragment thereof, according to claim 132, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 265, a CDRH2 having at least 70% identity to SEQ ID NO: 266, a CDRH3 having at least 70% identity to SEQ ID NO: 267, a CDRL1 having at least 70% identity to SEQ ID NO: 268, a CDRL2 having at least 70% identity to SEQ ID NO: 2619, and a CDRL3 having at least 70% identity to SEQ ID NO: 270, and preferably comprises a CDRH1 according to SEQ ID NO: 265, a CDRH2 according to SEQ ID NO: 266, a CDRH3 according to SEQ ID NO: 267, a CDRL1 according to SEQ ID NO: 268, a CDRL2 according to SEQ ID NO: 269, and a CDRL3 according to SEQ ID NO: 270.

136. The antibody, or an antigen-binding fragment thereof, according to claim 135, wherein the scFv comprises an amino acid sequence having at least 70% identity to SEQ ID NO: 859 or SEQ ID NO: 861, and preferably comprises an amino acid sequence according to SEQ ID NO: 859, or SEQ ID NO: 861.

137. The antibody, or an antigen-binding fragment thereof, according to claim 132, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 809, a CDRH2 having at least 70% identity to SEQ ID NO: 810, a CDRH3 having at least 70% identity to SEQ ID NO: 754, a CDRL1 having at least 70% identity to SEQ ID NO: 755, a CDRL2 having at least 70% identity to SEQ ID NO: 811, and a CDRL3 having at least 70% identity to SEQ ID NO: 757, and preferably comprises a CDRH1 according to SEQ ID NO: 809, a CDRH2 according to SEQ ID NO: 8010, a CDRH3 according to SEQ ID NO: 754, a CDRL1 according to SEQ ID NO: 755, a CDRL2 according to SEQ ID NO: 811, and a CDRL3 according to SEQ ID NO: 757.

138. The antibody, or an antigen-binding fragment thereof, according to claim 137, wherein the scFv comprises an amino acid sequence having at least 70% identity to SEQ ID NO: 860, and preferably comprises an amino acid sequence according to SEQ ID NO: 860.

139. The antibody, or an antigen-binding fragment thereof, according to claim 132, wherein the antibody, or the 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, and preferably comprises 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.

140. The antibody, or an antigen-binding fragment thereof, according to claim 139, wherein the scFv comprises an amino acid sequence having at least 70% identity to SEQ ID NO: 862, and preferably comprises an amino acid sequence according to SEQ ID NO: 862.

141. The antibody, or an antigen-binding fragment thereof, according to claim 132, wherein the antibody, or the antigen-binding fragment thereof, comprises a CDRH1 having at least 70% identity to SEQ ID NO: 768, a CDRH2 having at least 70% identity to SEQ ID NO: 814, a CDRH3 having at least 70% identity to SEQ ID NO: 770, a CDRL1 having at least 70% identity to SEQ ID NO: 815, a CDRL2 having at least 70% identityto SEQ ID NO: 816, and a CDRL3 having at least 70% identity to SEQ ID NO: 817, and preferably comprises a CDRH1 according to SEQ ID NO: 768, a CDRH2 according to SEQ ID NO: 814, a CDRH3 according to SEQ ID NO: 770, a CDRL1 according to SEQ ID NO: 815, a CDRL2 according to SEQ ID NO: 816, and a CDRL3 according to SEQ ID NO: 817.

142. The antibody, or an antigen-binding fragment thereof, according to claim 141, wherein the scFv comprises an amino acid sequence having at least 70% identity to SEQ ID NO: 863, 864 or 865, and preferably comprises an amino acid sequence according to SEQ ID NO: 863, 864 or 865.

143. The antibody, or an antigen-binding fragment thereof, according to any one of claims 132 to 142, wherein the scFv is paired with a heavy chain having at least 70% identity to SEQ ID NO: 821, preferably with a heavy chain according to SEQ ID NO: 821.

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

145. The antibody or the antigen-binding fragment according to any one of the previous claims, wherein the CDRH1, CDRH2 and CDRH3 sequences are contained by a human variable heavy chain framework region VH chain selected from the group consisting of the amino acid sequences encoded by the genes IGHV1-2, IGHV1-3, IGHV1-8, IGHV1-18, IGHV1-24, IGHV1-45, IGHV1-46, IGHV1-58, IGHV1-69, IGHV1-69-2, IGHV1-69D, IGHV2-5, IGHV2-26, IGHV2-70, IGHV2-70D, IGHV3-7, IGHV3-9, IGHV3-11, IGHV3-13, IGHV3-15, IGHV3-20, IGHV3-21, IGHV3-23, IGHV3-23D, IGHV3-3O, IGHV3-3O-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, IGHV3-72, IGHV3-73, IGHV3-74, IGHV3OR16-10, IGHV3-NL1, IGHV4-4, IGHV4-28, IGHV4-30-1, IGHV4-30-2, IGHV4-30-4, IGHV4-31, IGHV4-34, IGHV4- 38-2, IGHV4-39, IGHV5-10-1, IGHV5-5 and IGHV5-51.

146. The antibody or the antigen-binding fragment according to any one of the previous claims, wherein the CDRL1, CDRL2 and CDRL3 sequences are contained by a human variable light chain framework region VL chain selected from the group consisting of the amino acid sequences encoded by the genes IGLV1-36, IGLV1-40, IGLV1-44, IGLV1-47, IGLV1-51, IGLV10-54, IGLV2-8, IGLV2-11, IGLV2-14, IGLV2-18, IGLV2- 23, IGLV3-1, IGLV3-9, IGLV3-10, IGLV3-12, IGLV3-16, IGLV3-19, IGLV3-21, IGLV3- 22, IGLV3-25, IGLV3-27, 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, or a contained by a human variable light chain framework region VK chain selected from the group consisting of the amino acid sequences encoded by the genes IGKV1-5, IGKV1-6, IGKV1-8, IGKV1 D-8, IGKV1-9, IGKV1-12, IGKV1 D-12, IGKV1-13, IGKV1 D- 13, IGKV1-16, IGKV1D-16, IGKV1-17, IGKV1D-17, IGKV1-27, IGKV1-33, IGKV1 D- 33, IGKV1-39, IGKV1 D-39, IGKV1 D-43, IGKV1-NL1, IGKV1 D-8, IGKV2-24, IGKV2D- 26, IGKV2-28, IGKV2D-28, IGKV2-29, IGKV2D-29, IGKV2-30, IGKV2D-30, IGKV2- 40, IGKV2D-40, IGKV3D-7, IGKV3-11, IGKV3D-11, IGKV3-15, IGKV3D-15, IGKV3- 20, IGKV3D-20, IGKV4-1, IGKV5-2, IGKV6-21, and IGKV6D-21.

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

148. The multispecific antibody, or the multispecific antigen-binding fragment thereof, according to claim 147, wherein the multispecific antibody, or the multispecific antigen-binding fragment thereof, binds to distinct, non-overlapping epitopes of Bet v 1, and optionally binds to distinct, non-overlapping epitopes of at least one bet v 1 homologous allergen.

149. The antibody, or an antigen-binding fragment thereof, according to claim 147 or 148, wherein the multispecific antibody, or the multispecific antigen-binding fragment thereof, comprises at least two of the following:(i) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 7 to 10;(ii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 11 to 14;(iii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 15 to 18;(iv) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 19 to 22;(v) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 23 to 26;(vi) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 27 to 30;(vii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 31 to 34;(viii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 35 to 38;(ix) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 39 to 42;(x) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 43 to 46;(xi) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 47 to 48;(xii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 49 to 50;(xiii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 51 to 52;(xiv) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 53 to 54;(xv) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 55 to 56;(xvi) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 57 to 58;(xvii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 59 to 60;(xviii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 61 to 62;(xix) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 63 to 64;(xx) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 65 to 66;(xxi) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 67 to 68;(xxii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 69 to 70;(xxiii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 71 to 72;(xxiv) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 73 to 74;(xxv) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 75 to 76;(xxvi) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 77 to 78;(xxvii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 79 to 80;(xxviii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 81 to 82;(xxix) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 83 to 84;(xxx) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 85 to 86;(xxxi) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 87 to 88;(xxxii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 89 to 90;(xxxiii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 91 to 92;(xxxiv) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 93 to 94;(xxxv) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 95 to 96;(xxxvi) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 97 to 98;(xxxvii)an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 99 to 100;(xxxviii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 101 to 102;(xxxix) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 103 to 104;(xl) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 105 to 106;(xli) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 107 to 108;(xlii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 109 to 110;(xliii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 111 to 112;(xliv) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 113 to 114;(xlv) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 115 to 116;(xlvi) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 117 to 118;(xlvii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 119 to 120;(xlviii) an antigen-binding site comprising (a) the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 sequences and / or (b) the VH and VL sequences as defined in any one of claims 121 to 122;or comprises at least one of the above (i) to (xlviii) and additionally comprises at least one of (xlix) to (liv):(xlix) an antigen-binding site comprising a CDRH1 having at least 70% identity to SEQ ID NO: 744, a CDRH2 having at least 70% identity to SEQ ID NO: 745, a CDRH3 having at least 70% identity to SEQ ID NO: 746, a CDRL1 having at least 70% identity to SEQ ID NO: 747, a CDRL2 having at least 70% identity to SEQ ID NO: 748, and a CDRL3 having at least 70% identity to SEQ ID NO: 749, and preferably comprising a CDRH1 according to SEQ ID NO: 744, a CDRH2 according to SEQ ID NO: 745, a CDRH3 according to SEQ ID NO: 746, a CDRL1 according to SEQ ID NO: 747, a CDRL2 according to SEQ ID NO: 748, and a CDRL3 according to SEQ ID NO: 749; or comprising a VH having at least 70% identity to SEQ ID NO: 750, and a VL having at least 70% identity to SEQ ID NO: 751, and preferably comprising a VH according to SEQ ID NO: 750; and a VL according to SEQ ID NO: 751;(I) an antigen-binding site comprising a CDRH1 having at least 70% identity to SEQ ID NO: 752, a CDRH2 having at least 70% identity to SEQ ID NO: 753, a CDRH3 having at least 70% identity to SEQ ID NO: 754, a CDRL1 having at least 70% identity to SEQ ID NO: 755, a CDRL2 having at least 70% identity to SEQ ID NO: 756, and a CDRL3 having at least 70% identity to SEQ ID NO: 757, and preferably comprising a CDRH1 according to SEQ ID NO: 752, a CDRH2 according to SEQ ID NO: 753, a CDRH3 according to SEQ ID NO: 754, a CDRL1 according to SEQ ID NO: 755, a CDRL2 according to SEQ ID NO: 756, and a CDRL3 according to SEQ ID NO: 757; or comprising a VH having at least 70% identity to SEQ ID NO: 758, and a VL having at least 70%identity to SEQ ID NO: 759, and preferably comprising a VH according to SEQ ID NO: 758; and a VL according to SEQ ID NO: 759;(li) an antigen-binding site comprising a CDRH1 having at least 70% identity to SEQ ID NO: 760, a CDRH2 having at least 70% identity to SEQ ID NO: 761, a CDRH3 having at least 70% identity to SEQ ID NO: 762, a CDRL1 having at least 70% identity to SEQ ID NO: 763, a CDRL2 having at least 70% identity to SEQ ID NO: 764, and a CDRL3 having at least 70% identity to SEQ ID NO: 765, and preferably comprising a CDRH1 according to SEQ ID NO: 760, a CDRH2 according to SEQ ID NO: 761, a CDRH3 according to SEQ ID NO: 762, a CDRL1 according to SEQ ID NO: 763, a CDRL2 according to SEQ ID NO: 764, and a CDRL3 according to SEQ ID NO: 765; or comprising a VH having at least 70% identity to SEQ ID NO: 766, and a VL having at least 70% identity to SEQ ID NO: 767, and preferably comprising a VH according to SEQ ID NO: 766; and a VL according to SEQ ID NO: 767;(lii) an antigen-binding site comprising a CDRH1 having at least 70% identity to SEQ ID NO: 768, a CDRH2 having at least 70% identity to SEQ ID NO: 769, a CDRH3 having at least 70% identity to SEQ ID NO: 770, a CDRL1 having at least 70% identity to SEQ ID NO: 771, a CDRL2 having at least 70% identity to SEQ ID NO: 772, and a CDRL3 having at least 70% identity to SEQ ID NO: 773, and preferably comprising a CDRH1 according to SEQ ID NO: 768, a CDRH2 according to SEQ ID NO: 769, a CDRH3 according to SEQ ID NO: 770, a CDRL1 according to SEQ ID NO: 771, a CDRL2 according to SEQ ID NO: 772, and a CDRL3 according to SEQ ID NO: 773; or comprising a VH having at least 70% identity to SEQ ID NO: 774, and a VL having at least 70% identity to SEQ ID NO: 775, and preferably comprising a VH according to SEQ ID NO: 774; and a VL according to SEQ ID NO: 775;(liii) an antigen-binding site comprising a CDRH1 having at least 70% identity to SEQ ID NO: 776, a CDRH2 having at least 70% identity to SEQ ID NO: 777, a CDRH3 having at least 70% identity to SEQ ID NO: 778, a CDRL1 having at least 70% identity to SEQ ID NO: 779, a CDRL2 having at least 70% identity to SEQ ID NO: 780, and a CDRL3 having at least 70% identity to SEQ ID NO: 781, and preferably comprising a CDRH1 according to SEQ ID NO: 776, a CDRH2 according to SEQ ID NO: 777, a CDRH3 according to SEQ ID NO:778, a CDRL1 according to SEQ ID NO: 779, a CDRL2 according to SEQ ID NO: 780, and a CDRL3 according to SEQ ID NO: 781; or comprising a VH having at least 70% identity to SEQ ID NO: 782, and a VL having at least 70% identity to SEQ ID NO: 783, and preferably comprising a VH according to SEQ ID NO: 782; and a VL according to SEQ ID NO: 783;(liv) an antigen-binding site comprising a CDRH1 having at least 70% identity to SEQ ID NO: 784, a CDRH2 having at least 70% identity to SEQ ID NO: 785, a CDRH3 having at least 70% identity to SEQ ID NO: 786, a CDRL1 having at least 70% identity to SEQ ID NO: 787, a CDRL2 having at least 70% identity to SEQ ID NO: 788, and a CDRL3 having at least 70% identity to SEQ ID NO: 789, and preferably comprising a CDRH1 according to SEQ ID NO: 784, a CDRH2 according to SEQ ID NO: 785, a CDRH3 according to SEQ ID NO: 786, a CDRL1 according to SEQ ID NO: 787, a CDRL2 according to SEQ ID NO: 788, and a CDRL3 according to SEQ ID NO: 789; or comprising a VH having at least 70% identity to SEQ ID NO: 790, and a VL having at least 70% identity to SEQ ID NO: 791, and preferably comprising a VH according to SEQ ID NO: 790; and a VL according to SEQ ID NO: 791.

150. The multispecific antibody, or the multispecific antigen-binding fragment thereof, according to claim 149, wherein the antibody comprises two heavy chains and two light chains each comprising at least one constant domain and at least one variable domain (VH / VL),wherein the multispecific antibody comprises at least three antigen-binding sites each comprising three heavy chain CDRs (CDRH1-3) and three light chain CDRs (CDRL1- 3),whereinat least one antigen-binding site (a) is formed by the VH1 of a first heavy chain and by the VL1 of a first light chain,at least one antigen-binding site (b) is formed by the VH2 of a second heavy chain and by the VL2 of a second light chain, andat least one antigen-binding site (c) is formed by a single chain variable fragment (scFv), the scFv being covalently linked to the constant domain of the at least one heavy chain, and / orat least one antigen-binding site (d) is formed by variable domains VHx and / or VLx, the variable domains VHx and / or VLx being covalently linked to at least one of variable domains VH1 / VL1 and / or VH2 / VL2, thereby forming at least one dual variable domain (DVD).

151. The multispecific antibody according to claim 150, wherein antigen-binding site (a) and antigen-binding site (b) have different specificities.

152. The multispecific antibody according to claim 150, wherein antigen-binding site (a) and antigen-binding site (b) have the same specificity.

153. The multispecific antibody according to any one of claims 150 to 152, wherein the multispecific antibody comprises at least two antigen-binding sites (cl, c2), wherein a first scFv1 forming the antigen-binding site (c1) is covalently linked to the at least one constant domain of the first heavy chain, and a second scFv1 forming the antigen-binding site (c2) is covalently linked to the at least one constant domain of the second heavy chain.

154. The multispecific antibody according to claim 153, wherein the first antigen-binding site (c1), and the second antigen-binding site (c2) have the same specificity.

155. The multispecific antibody according to claim 153, wherein the first antigen-binding site (c1), and the second antigen-binding site (c2) have different specificities.

156. The multispecific antibody according to any one of claims 150 to 155, wherein the multispecific antibody comprises at least two antigen-binding sites (d1, d2), wherein the variable domains VHx1 and VLx1 forming a first antigen-binding site (d1) is covalently linked to the variable domain formed by VH1 and VL1, and a variable domain VHx2 and VLx2 forming a second antigen-binding site (d2) is covalently linked to the variable domain formed by VH2 and VL2.

157. The multispecific antibody according to claim 156, wherein the first antigen-binding site (d1), and the second antigen-binding site (d2) have the same specificity.

158. The multispecific antibody according to claim 156, wherein the first antigen-binding site (d1), and the second antigen-binding site (d2) have different specificities.

159. The multispecific antibody according to any one of claims 156 to 158, wherein a variable domain VHx1 and VLx1 forming the first antigen-binding site (d1) is covalently linked to the variable domain formed by VH1 and VL1, or a variable domain VHx2 and VLx2 forming a second antigen-binding site (d2) is covalently linked to the variable domain formed by VH2 and VL2.

160. The multispecific antibody according to any one of claims 150 to 159, wherein the at least three antigen-binding sites are formed by at least two of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i) to (xlviii), or are formed by at least one of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i) to (xlviii) and at least one of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlix) to (liv).

161. The multispecific antibody according to any one of claims 150 to 159, wherein the at least three antigen-binding sites are formed by at least three of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i) to (xlviii), or are formed by at least two of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i) to (xlviii) and at least one of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according (xlix) to (liv), or are formed by at least one of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i) to (xlviii) and at least two of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlix) to (liv).

162. The multispecific antibody according to any one of claims 150 to 159, comprising at least four antigen-binding sites which are formed by at least two of the CDRH1- 3 / CDRL1-3 sequences and / or the VH and VL sequences according to (i) to (xlviii), or are formed by at least one of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i) to (xlviii) and at least one of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlix) to (liv).

163. The multispecific antibody according to claim 162, wherein the at least four antigenbinding sites are formed by at least three of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i) to (xlviii), or are formed by at least two of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i) to (xlviii) and at least one of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlix) to (liv), or are formed by at least one of the CDRH1- 3 / CDRL1-3 sequences and / or the VH and VL sequences according to (i) to (xlviii) and at least two of the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlix) to (liv).

164. The multispecific antibody according to any one of claims 140 to 154, wherein the antigen-binding sites are selected from at least two of:CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i); CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (ii); CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (iii); CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (x); CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxx); CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxxiv);CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xl); CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlvii);CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlviii).

165. The multispecific antibody according to claim 164, wherein two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i), and two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (ii).

166. The multispecific antibody according to claim 164 or 165, wherein antigen-binding sites (a) and (b) are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i), and antigen-binding sites (c1) and (c2) are formed by the CDRH1-3 / CDRL1-3 sequences and / or the VH and VL sequences according to (ii).

167. The multispecific antibody according to claim 166 which comprises a heavy chain having at least 70% identity to SEQ ID NO: 740, and a light chain having at least 70% identity to SEQ ID NO: 741.

168. The multispecific antibody according to claim 167 which comprises a heavy chain according to SEQ ID NO: 740, and a light chain according to SEQ ID NO: 741.

169. The multispecific antibody according to claim 166, which comprises a heavy chain having at least 70% identity to SEQ ID NO: 742, and a light chain having at least 70% identity to SEQ ID NO: 743.

170. The multispecific antibody according to claim 169, which comprises a heavy chain according to SEQ ID NO: 742, and a light chain according to SEQ ID NO: 743.

171. The multispecific antibody according to claim 166, wherein two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (iii), and two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlviii).

172. The multispecific antibody according to claim 171, wherein antigen-binding sites (a) and (b) are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (iii), and antigen-binding sites (c1) and (c2) are formed by the CDRH1-3 / CDRL1-3 sequences and / or the VH and VL sequences according to (xlviii).

173. The multispecific antibody according to claim 172 which comprises a heavy chain having at least 70% identity to SEQ ID NO: 831 or 835, and a light chain having at least 70% identity to SEQ ID NO: 832.

174. The multispecific antibody according to claim 173 which comprises a heavy chain according to SEQ ID NO: 831 or 835, and a light chain according to SEQ ID NO: 832.

175. The multispecific antibody according to claim 166, wherein two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (x), and two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxxiv).

176. The multispecific antibody according to claim 175, wherein antigen-binding sites (a) and (b) are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (x), and antigen-binding sites (c1) and (c2) are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxxiv).

177. The multispecific antibody according to claim 176 which comprises a heavy chain having at least 70% identity to SEQ ID NO: 833, and a light chain having at least 70% identity to SEQ ID NO: 834.

178. The multispecific antibody according to claim 177 which comprises a heavy chain according to SEQ ID NO: 833, and a light chain according to SEQ ID NO: 834.

179. The multispecific antibody according to claim 166, wherein two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i), and two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlvii) and (ii).

180. The multispecific antibody according to claim 179, wherein antigen-binding sites (a) and (b) are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i), an antigen-binding site (c1) is formed by the CDRH1-3 / CDRL1-3 sequences and / or the VH and VL sequences according to (xlvii) and another antigen-binding site (c2) is formed by the CDRH1-3 / CDRL1-3 sequences and / or the VH and VL sequences according to (ii).

181. The multispecific antibody according to claim 180 which comprises a first heavy chain having at least 70% identity to SEQ ID NO: 836, a second heavy chain having at least 70% identity to SEQ ID NO: 837, and a light chain having at least 70% identity to SEQ ID NO: 838.

182. The multispecific antibody according to claim 181 which comprises a first heavy chain according to SEQ ID NO: 836, a second heavy chain according to SEQ ID NO: 837, and a light chain according to SEQ ID NO: 838.

183. The multispecific antibody according to claim 166, wherein two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i), and two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlvii) and (xlviii).

184. The multispecific antibody according to claim 183, wherein antigen-binding sites (a) and (b) are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (i), an antigen-binding site (c1) is formed by the CDRH1-3 / CDRL1-3 sequences and / or the VH and VL sequences according to (xlvii) and another antigen-binding site (c2) is formed by the CDRH1-3 / CDRL1-3 sequences and / or the VH and VL sequences according to (xlviii).

185. The multispecific antibody according to claim 184 which comprises a first heavy chain having at least 70% identity to SEQ ID NO: 839, a second heavy chain having at least 70% identity to SEQ ID NO: 840, and a light chain having at least 70% identity to SEQ ID NO: 838.

186. The multispecific antibody according to claim 185 which comprises a first heavy chain according to SEQ ID NO: 839, a second heavy chain according to SEQ ID NO: 840, and a light chain according to SEQ ID NO: 838.

187. The multispecific antibody according to claim 166, wherein two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequencesaccording to (iii), and two antigen-binding sites are formed by the CDRH1-3 / CDRL1-3 sequences and / or the VH and VL sequences according to (xlvii) and (xlviii).

188. The multispecific antibody according to claim 187, wherein antigen-binding sites (a) and (b) are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (iii), an antigen-binding site (c1) is formed by the CDRH1-3 / CDRL1-3 sequences and / or the VH and VL sequences according to (xlvii) and another antigen-binding site (c2) is formed by the CDRH1-3 / CDRL1-3 sequences and / or the VH and VL sequences according to (xlviii).

189. The multispecific antibody according to claim 188 which comprises a first heavy chain having at least 70% identity to SEQ ID NO: 841, a second heavy chain having at least 70% identity to SEQ ID NO: 842, and a light chain having at least 70% identity to SEQ ID NO: 832.

190. The multispecific antibody according to claim 189 which comprises a first heavy chain according to SEQ ID NO: 841, a second heavy chain according to SEQ ID NO: 842, and a light chain according to SEQ ID NO: 832.

191. The multispecific antibody according to claim 166, wherein two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxxiv), and two antigen-binding sites are formed by the CDRH1- 3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlvii) and (xlviii).

192. The multispecific antibody according to claim 191, wherein antigen-binding sites (a) and (b) are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxxiv), an antigen-binding site (c1) is formed by the CDRH1-3 / CDRL1-3 sequences and / or the VH and VL sequences according to (xlvii) and another antigen-binding site (c2) is formed by the CDRH1-3 / CDRL1-3 sequences and / or the VH and VL sequences according to (xlviii).

193. The multispecific antibody according to claim 192 which comprises a first heavy chain having at least 70% identity to SEQ ID NO: 843 or 853, a second heavy chain havingat least 70% identity to SEQ ID NO: 844 or 854, and a light chain having at least 70% identity to SEQ ID NO: 845.

194. The multispecific antibody according to claim 193 which comprises a first heavy chain according to SEQ ID NO: 843 or 853, a second heavy chain according to SEQ ID NO: 844 or 854, and a light chain according to SEQ ID NO: 845.

195. The multispecific antibody according to claim 166, wherein two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xl), and two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xlvii) and (xxxiv).

196. The multispecific antibody according to claim 195, wherein antigen-binding sites (a) and (b) are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xl), an antigen-binding site (c1) is formed by the CDRH1-3 / CDRL1-3 sequences and / or the VH and VL sequences according to (xlvii) and another antigen-binding site (c2) is formed by the CDRH1-3 / CDRL1-3 sequences and / or the VH and VL sequences according to (xxxiv).

197. The multispecific antibody according to claim 196 which comprises a first heavy chain having at least 70% identity to SEQ ID NO: 846, a second heavy chain having at least 70% identity to SEQ ID NO: 847, and a light chain having at least 70% identity to SEQ ID NO: 848.

198. The multispecific antibody according to claim 197 which comprises a first heavy chain according to SEQ ID NO: 846, a second heavy chain according to SEQ ID NO: 847, and a light chain according to SEQ ID NO: 848.

199. The multispecific antibody according to claim 166, wherein two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxxiv), and two antigen-binding sites are formed by the CDRH1- 3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxx) and (ii).

200. The multispecific antibody according to claim 199, wherein antigen-binding sites (a) and (b) are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxxiv), an antigen-binding site (c1) is formed by the CDRH1-3 / CDRL1-3 sequences and / or the VH and VL sequences according to (xxx) and another antigen-binding site (c2) is formed by the CDRH1-3 / CDRL1-3 sequences and / or the VH and VL sequences according to (ii).

201. The multispecific antibody according to claim 200 which comprises a first heavy chain having at least 70% identity to SEQ ID NO: 849, a second heavy chain having at least 70% identity to SEQ ID NO: 850, and a light chain having at least 70% identity to SEQ ID NO: 845.

202. The multispecific antibody according to claim 201 which comprises a first heavy chain according to SEQ ID NO: 849, a second heavy chain according to SEQ ID NO: 850, and a light chain according to SEQ ID NO: 845.

203. The multispecific antibody according to claim 166, wherein two antigen-binding sites are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxxiv), and two antigen-binding sites are formed by the CDRH1- 3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxx) and (xlviii).

204. The multispecific antibody according to claim 203, wherein antigen-binding sites (a) and (b) are formed by the CDRH1 -3 / CDRL1 -3 sequences and / or the VH and VL sequences according to (xxxiv), an antigen-binding site (c1) is formed by the CDRH1-3 / CDRL1-3 sequences and / or the VH and VL sequences according to (xxx) and another antigen-binding site (c2) is formed by the CDRH1-3 / CDRL1-3 sequences and / or the VH and VL sequences according to (xlviii).

205. The multispecific antibody according to claim 204 which comprises a first heavy chain having at least 70% identity to SEQ ID NO: 851 or 855, a second heavy chain having at least 70% identity to SEQ ID NO: 852 or 856, and a light chain having at least 70% identity to SEQ ID NO: 845.

206. The multispecific antibody according to claim 205 which comprises a first heavy chain according to SEQ ID NO: 851 or 855, a second heavy chain according to SEQ ID NO: 852 or 856, and a light chain according to SEQ ID NO: 845.

207. The antibody, or an antigen-binding fragment thereof, according to any one of the previous claims for use as a medicament.

208. The antibody, or an antigen-binding fragment thereof, for use according to claim 207 in prophylaxis or treatment of birch pollen allergy, and / or related tree pollen allergies, and / or related food allergies.

209. A nucleic acid molecule comprising a polynucleotide encoding the antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 206.

210. The nucleic acid molecule according to claim 209 comprising a nucleic acid sequence as set forth in any one of SEQ ID NOs 369 to 736 or 869 to 895; 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.

211. A plurality of nucleic acid molecules encoding the antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 206, wherein each of the nucleic acid molecules comprises a polynucleotide encoding an immunoglobulin chain of the antibody, or an antigen-binding fragment thereof.

212. The combination of nucleic acid molecules according to claim 211 comprising a nucleic acid sequence as set forth in any one of SEQ ID NOs 369 to 736 or 869 to 895, 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.

213. A vector comprising the nucleic acid molecule according to claim 209 or 210 or the plurality of nucleic acid molecules according to claim 211 or 160.

214. A plurality of vectors comprising the plurality of nucleic acid molecules according to claim 211 or 212.

215. A host cell expressing the antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 206, or comprising the vector according to claim 213 or the plurality of vectors of claim 214.

216. A method for preparing the antibody, or an antigen-binding fragment thereof, according any one of claims 1 to 206, or immunoglobulin chain(s) thereof, said method comprising(i) culturing the host cell according to claim 215; and(ii) isolating the antibody or immunoglobulin chain(s) thereof from the culture.

217. A composition comprising the antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 206, the nucleic acid or the plurality of nucleic acids according to any one of claims 157 to 160, the vector or the plurality of vectors according to claim 213 or 162, or the cell according to claim 215.

218. The composition according to claim 217, wherein the composition comprises at least one of:an antibody or antigen-binding fragment thereof, as defined in any one of claims 7 to 10;an antibody or antigen-binding fragment thereof, as defined in any one of claims 11 to 14;an antibody or antigen-binding fragment thereof, as defined in any one of claims 15 to 18;an antibody or antigen-binding fragment thereof, as defined in any one of claims; 19 to 22;an antibody or antigen-binding fragment thereof, as defined in any one of claims 23 to 26;an antibody or antigen-binding fragment thereof, as defined in any one of claims 27 to 30;an antibody or antigen-binding fragment thereof, as defined in any one of claims; 31 to 34;an antibody or antigen-binding fragment thereof, as defined in any one of claims 35 to 38;an antibody or antigen-binding fragment thereof, as defined in any one of claims 39 to 42;an antibody or antigen-binding fragment thereof, as defined in any one of claims 43 to 46;an antibody or antigen-binding fragment thereof, as defined in any one of claims 85 to 86;an antibody or antigen-binding fragment thereof, as defined in any one of claims 93 to 94;an antibody or antigen-binding fragment thereof, as defined in any one of claims 105 to 106;an antibody or antigen-binding fragment thereof, as defined in any one of claims 119 or 120;an antibody or antigen-binding fragment thereof, as defined in any one of claims 121 or 122;a multispecific antibody or antigen-binding fragment thereof, as defined in any one of claims 147 to 206.

219. The composition according to claim 217 or 218, wherein the composition comprises at least two antibodies or antigen-binding fragments thereof, as defined in any one of claims 1 to 206.

220. The composition according to claim 219, wherein the composition comprises at least two of:an antibody or antigen-binding fragment thereof, as defined in any one of claims 7 to 10;an antibody or antigen-binding fragment thereof, as defined in any one of claims 11 to 14;an antibody or antigen-binding fragment thereof, as defined in any one of claims 15 to 18;an antibody or antigen-binding fragment thereof, as defined in any one of claims; 19 to 22;an antibody or antigen-binding fragment thereof, as defined in any one of claims 23 to 26;an antibody or antigen-binding fragment thereof, as defined in any one of claims 27 to 30;an antibody or antigen-binding fragment thereof, as defined in any one of claims; 31 to 34;an antibody or antigen-binding fragment thereof, as defined in any one of claims 35 to 38;an antibody or antigen-binding fragment thereof, as defined in any one of claims 39 to 42;an antibody or antigen-binding fragment thereof, as defined in any one of claims 43 to 46;an antibody or antigen-binding fragment thereof, as defined in any one of claims 85 to 86;an antibody or antigen-binding fragment thereof, as defined in any one of claims 93 to 94;an antibody or antigen-binding fragment thereof, as defined in any one of claims 105 to 106;an antibody or antigen-binding fragment thereof, as defined in any one of claims 119 or 120;an antibody or antigen-binding fragment thereof, as defined in any one of claims 121 or 122;a multispecific antibody or antigen-binding fragment thereof, as defined in any one of claims 147 to 206.

221. The composition according to any one of claims 217 to 220, wherein the composition additionally comprises at least one of:an antibody or antigen-binding fragments thereof, comprising the CDRH1- 3 / CDRL1-3 sequences according to SEQ ID NOs 744-751 and / or the VL and VH sequences according to SEQ ID NOs 750-751;an antibody or antigen-binding fragments thereof, comprising the CDRH1- 3 / CDRL1-3 sequences according to SEQ ID NOs 752-757 and / or the VL and VH sequences according to SEQ ID NOs 758-759;an antibody or antigen-binding fragments thereof, comprising the CDRH1- 3 / CDRL1-3 sequences according to SEQ ID NOs 760-765 and / or the VL and VH sequences according to SEQ ID NOs 766-767;an antibody or antigen-binding fragments thereof, comprising the CDRH1- 3 / CDRL1-3 sequences according to SEQ ID NOs 768-773 and / or the VL and VH sequences according to SEQ ID NOs 774-775;an antibody or antigen-binding fragments thereof, comprising the CDRH1- 3 / CDRL1-3 sequences according to SEQ ID NOs 776-781 and / or the VL and VH sequences according to SEQ ID NOs 782-783;an antibody or antigen-binding fragments thereof, comprising the CDRH1- 3 / CDRL1-3 sequences according to SEQ ID NOs 784-789 and / or the VL and VH sequences according to SEQ ID NOs 790-791.

222. The composition according to any one of claims 217 to 221, wherein the composition comprises at least one of:an antibody or antigen-binding fragment thereof, as defined in any one of claims 7 to 10;an antibody or antigen-binding fragment thereof, as defined in any one of claims 11 to 14;an antibody or antigen-binding fragment thereof, as defined in any one of claims 15 to 18; and additionally comprises at least one of:an antibody or antigen-binding fragments thereof, comprising the CDRH1- 3 / CDRL1-3 sequences according to SEQ ID NOs 744-751 and / or the VL and VH sequences according to SEQ ID NOs 750-751;an antibody or antigen-binding fragments thereof, comprising the CDRH1- 3 / CDRL1-3 sequences according to SEQ ID NOs 752-757 and / or the VL and VH sequences according to SEQ ID NOs 758-759;an antibody or antigen-binding fragments thereof, comprising the CDRH1- 3 / CDRL1-3 sequences according to SEQ ID NOs 768-773 and / or the VL and VH sequences according to SEQ ID NOs 774-775.

223. The composition according to any one of claims 217 to 222, wherein the composition further comprises at least one additional agent useful for treating birch pollen allergy and / or a related tree pollen allergy, and / or a related food allergy.

224. The composition according to claim 223, wherein the additional agent useful for treating birch pollen allergy and / or a related allergy is selected from the group consisting of: p-adrenergic agonists, epinephrine, antihistamine, corticosteroid, anti-lgE antibody, anti-lgE antibody binding fragment, peptide vaccine and further antibodies capable of binding to a birch pollen allergen.

225. The composition according to any one of claims 217 to 224, wherein the composition further comprises a birch pollen allergen and / or a Bet v 1 homologous allergen, preferably selected from the group consisting of Cor a 1, Ain g 1, Fag s 1, Que a 1, Cas s 1, Ost c 1, Car b1, Mal d 1 Jug r 5 and Pru p 1, and / or comprises an extract comprising a birch pollen allergen and / or a Bet v 1 homologous allergen, preferably selected from the group consisting of Cor a 1, Ain g 1, Fag s 1, Que a 1, Cas s 1, Ost c 1, Car b1, Mal d 1, Jug r 5 and Pru p 1.

226. The composition according to any one of claims 217 to 225 further comprising a pharmaceutically acceptable excipient, diluent or carrier.

227. A kit comprising one or more of(i) the antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 206;(ii) the nucleic acid molecule(s) according to any one of claims 157 to 160;(iii) the vector(s) according to claim 213 or 162;(iv) the cell according to claim 215; and / or(v) the composition according to any one of claims 217 to 226.

228. The Kit according to claim 227, wherein the composition comprises at least two antibodies or antigen-binding fragments thereof, as defined in any one of claims 1 to 206.

229. The kit according to any one of claims 227 or 228, wherein the kit further comprises at least one additional agent useful for treating birch pollen allergy, and / or a related tree pollen allergy, which is preferably selected from at least one of hazel pollen allergy, black alder pollen allergy, beech pollen allergy, oak tree pollen allergy, chestnut pollen allergy, hop-hornbeam pollen allergy, and hornbeam pollen allergy, and / or a related food allergy, which is preferably selected from at least one of apple allergy, hazelnut allergy and walnut allergy.

230. The kit according to any one of claims 227 to 229, wherein the kit further comprises a birch pollen allergen, and / or a related tree pollen allergen, which is preferably selected from at least one of hazel pollen allergen, black alder pollen allergen, beech pollen allergen, oak tree pollen allergen, chestnut pollen allergen, hop-hornbeam pollen allergen, hornbeam pollen allergen, preferably selected from the group consisting of Cor a 1, Ain g 1, Fag s 1, Que a 1, Cas s 1, Ost c 1, Car b1, and / or a related food allergen, which is preferably selected from at least one of apple allergen, hazelnut allergen and walnut allergen, preferably selected from Mal d 1, Cor a 1 and Jug r 5.

231. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 206, the nucleic acid or the plurality of nucleic acids according to any one of claims 157 to 160, the vector or the plurality of vectors according to claim 213 or 162, the cell according to claim 215, the composition according to any one of claims 217 to 226, or the kit according to any one of claims 227 to 230 for use as a medicament.

232. The antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 206, the nucleic acid or the plurality of nucleic acids according to any one of claims 157 to 160, the vector or the plurality of vectors according to claim 213 or 162,the cell according to claim 215, the composition according to any one of claims 217 to 226, or the kit according to any one of claims 227 to 230 for use in the prophylaxis ortreatmentof a birch pollen allergy and / or related tree pollen allergy, which preferably selected from at least one of hazel pollen allergy, black alder pollen allergy, beech pollen allergy, oak tree pollen allergy, chestnut pollen allergy, hop-hornbeam pollen allergy and hornbeam pollen allergy, and / or a related food allergy, preferably selected from at least one of apple allergy, hazelnut allergy and walnut allergy.

233. The antibody, or the antigen-binding fragment thereof, the nucleic acid or the plurality of nucleic acids, the vector or the plurality of vectors, the cell, or the composition for use according to claim 179 or 180, wherein the administration of the antibody, or the antigen-binding fragment thereof, the nucleic acid or the plurality of nucleic acids, the vector or the plurality of vectors, the cell, or the composition is combined with the administration of a Bet v 1 birch pollen allergen, and / or a related tree pollen allergen, preferably selected from at least one of Cor a 1 hazel pollen allergen, Ain g 1 black alder pollen allergen, Fag s 1 beech pollen allergen, Que a 1 oak tree pollen allergen, Cas s 1 chestnut pollen allergen, Ost c 1 hop-hornbeam pollen allergen and Car b1 hornbeam pollen allergen, and / or a related food allergen, preferably selected from at least one of Mal d 1 apple allergen, Cor a 1 hazelnut allergen and Jug r 5 walnut allergen.

234. The antibody, or the antigen-binding fragment thereof, or the composition for use according to claim 181, wherein the antibody, or the antigen-binding fragment thereof, or the composition is administered before or during a desensitization procedure with a birch pollen allergen, and / or a related tree pollen allergen, and / or a related food allergen.

235. Use of the antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 206, the composition according to any one of claims 217 to 226, or the kit according to any one of claims 227 to 230 in {in-vitro) diagnosis of a birch pollen allergy, and / or a related tree pollen allergy, preferably selected from at least one of hazel pollen allergy, black alder pollen allergy, beech pollen allergy, oak tree pollen allergy, chestnut pollen allergy, hop-hornbeam pollen allergy and hornbeam pollenallergy, and / or a related food allergy, preferably selected from at least one of apple allergy, hazelnut allergy and walnut allergy.

236. Use of the antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 206, the composition according to any one of claims 217 to 226, or the kit according to any one of claims 227 to 230 in a method for detecting a birch pollen allergen, and / or a related tree pollen allergen, preferably selected from at least one of Cor a 1 hazel pollen allergen, Ain g 1 black alder pollen allergen, Fag s 1 beech pollen allergen, Que a 1 oak tree pollen allergen, Cas s 1 chestnut pollen allergen, Ost c 1 hop-hornbeam pollen allergen and Car b1 hornbeam pollen allergen, and / or a related food allergen, preferably selected from at least one of Mal d 1 apple allergen, Cor a 1 hazelnut allergen and Jug r 5 walnut allergen.

237. Use of the antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to 206, the nucleic acid or the plurality of nucleic acids according to any one of claims 157 to 160, the vector or the plurality of vectors according to claim 213 or 162, the cell according to claim 215, the composition according to any one of claims 217 to 226, or the kit according to any one of claims 227 to 230 in the manufacture of a medicament for prophylaxis, treatment or attenuation of a birch pollen allergy, and / or a related tree pollen allergy, preferably selected from at least one of hazel pollen allergy, black alder pollen allergy, beech pollen allergy, oak tree pollen allergy, chestnut pollen allergy, hop-hornbeam pollen allergy and hornbeam pollen allergy, and / or a related food allergy, preferably selected from at least one of apple allergy, hazelnut allergy and walnut allergy.

238. A method of treating, ameliorating or reducing a birch pollen allergy and / or a related tree pollen allergy, preferably selected from at least one of hazel pollen allergy, black alder pollen allergy, beech pollen allergy, oak tree pollen allergy, chestnut pollen allergy, hop-hornbeam pollen allergy and hornbeam pollen allergy, and / or a related food allergy, preferably selected from at least one of apple allergy, hazelnut allergy and walnut allergy, or lowering the risk of a allergic or anaphylactic reaction, comprising: administering to a subject in need thereof, a therapeutically effective amount of the antibody, or an antigen-binding fragment thereof, according to any one of claims 1 to206, the nucleic acid or the plurality of nucleic acids according to any one of claims 157 to 160, the vector or the plurality of vectors according to claim 213 or 162, the cell according to claim 215, the composition according to any one of claims 217 to 226, or the kit according to any one of claims 227 to 230.

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