VHH antibodies which bind to canine il-31

Abstract

The present invention relates generally to the field of antibodies, in particular VHHs that bind to canine interleukin-31 (IL-31). The invention also relates to constructs comprising such VHHs. The invention also relates to compositions comprising such VHHs or constructs. The invention also relates to therapeutic uses of such VHHs or constructs, such as in the treatment of pruritus and atopic dermatitis.

Description

[0001]15.168105 / 01 VHH antibodies which bind to canine IL-31This invention relates generally to the field of antibodies, in particular VHHantibodies that bind to canine interleukin-31 (IL-31). The invention also relates toconstructs comprising such VHH antibodies. The invention also relates tocompositions comprising such VHH antibodies or constructs. The invention alsorelates to therapeutic uses of such VHH antibodies or constructs, such as in thetreatment of pruritus and atopic dermatitis.Interleukin-31 (IL-31) is an inflammatory cytokine. IL-31 is mainly produced by Th2 (type 2 helper) cells, and has been identified as being an important mediator in a number of chronic inflammatory diseases, for example inflammatory skin diseases. Of particular note, IL-31 has been identified as an important mediator inpruritic conditions, e.g. pruritus (itch). Pruritus the most prominent symptom ofatopic dermatitis (AD). IL-31 signals via a receptor complex composed of IL-31receptor A (IL-31RA) and the Oncostatin M receptor (OSMR), with this signalling leading to an itch sensation. IL-31 is implicated as a critical cytokine that causes pruritus associated withatopic dermatitis in a number of different species, including in companion animals,such as dogs (canines). Indeed, atopic dermatitis is prevalent in dogs, with it beingestimated to affect about 10% to 15% of the total canine population. Commonly used treatments for atopic dermatitis in dogs include, for example, corticosteroids, ciclosporin and oclacitinib. However, adverse effects of such treatments have been reported. For example, side effects may include diarrhoea and vomiting, e.g. with ciclosporin treatment. The monoclonal antibodylokivetmab (Cytopoint®) may also be used to treat canine atopic dermatitis.Lokivetmab is a monoclonal antibody (an IgG antibody) which binds to and inhibitscanine IL-31. However, a significant proportion of dogs do not respond tolokivetmab treatment. For example in this regard, although it has been reported that around 75% of dogs show a significant clinical improvement within the first two months of therapy, this equates to there being around 25% of non-responders(Pinto et al., Rev. Port. Imunoalergologia (2022); 30(1):21-30). Also, anti-drugantibodies (i.e. anti-lokivetmab antibodies) have been reported in some patients(Moyaert et al., Vet Dermatol (2017); 28: 593–e145). Such anti-drug antibodiescould reduce clinical efficacy of lokivetmab over time. There clearly remains a need for alternative, and preferably advantageous or improved, agents for the treatment for pruritic conditions such as atopic dermatitis in dogs. The present inventors have addressed this need by generating VHHantibodies that bind to canine IL-31, and inhibit, canine IL-31 signalling. VHHantibodies are single domain antibodies that have only heavy chain variable domainantibody sequences. More specifically, VHH antibodies have a VHH domain thatcontains three heavy chain complementarity determining regions (CDRs). Unlikeconventional antibodies (e.g. lokivetmab, which is an IgG antibody), VHH antibodiesare devoid of light chain antibody sequences. VHH antibodies may alternatively bereferred to as, for example, nanobodies or single domain antibodies (sdAbs).VHH antibodies have some advantages over conventional (e.g. IgG)antibodies. For example in this regard, due to their small size and structuraldifferences as compared to conventional antibodies, VHH antibodies can haveimproved tissue penetration, and they may exhibit lower immunogenicity in vivo. As indicated above, in patients, anti-drug antibodies may be generated against conventional antibodies (e.g. lokivetmab), which could reduce their efficacy over time. Without wishing to be bound by theory, it is believed that an anti-drug response is less likely to be raised against VHH antibodies, for example as VHHantibodies are smaller and they lack structures such as a Fc domain which may beresponsible for the anti-drug response.Although VHH antibodies have only a single antigen binding domain (unlikefor example IgG antibodies, which have two), the present inventors have generated VHH antibodies which bind to canine IL-31 with excellent affinity, and that are able to inhibit IL-31 signalling. Furthermore, due to their small size (e.g. as compared to conventional IgG antibodies), anti-canine IL-31 VHH antibodies of the invention are well suited to being included in more complex constructs (e.g. that comprise multiple different VHH antibodies). Indeed, the present inventors have generated such constructs and shown that these have excellent activity (e.g. in the inhibition of IL-31 signalling). Thus, in one aspect, the present invention provides a VHH antibody which binds to canine IL-31. In some embodiments, a VHH antibody of the present invention comprises aVHH domain comprising three CDRs, wherein said VHH domain comprises(i) a CDR1 that has the amino acid sequence of SEQ ID NO:4 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:5 or a sequence substantially homologous thereto and aCDR3 that has the amino acid sequence of SEQ ID NO:6 or a sequencesubstantially homologous thereto; (ii) a CDR1 that has the amino acid sequence of SEQ ID NO:12 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:13 or a sequence substantially homologous thereto and aCDR3 that has the amino acid sequence of SEQ ID NO:14 or a sequencesubstantially homologous thereto; (iii) a CDR1 that has the amino acid sequence of SEQ ID NO:20 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:21 or a sequence substantially homologous thereto and aCDR3 that has the amino acid sequence of SEQ ID NO:22 or a sequencesubstantially homologous thereto; or(iv) a CDR1 that has the amino acid sequence of SEQ ID NO:28 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:29 or a sequence substantially homologous thereto and aCDR3 that has the amino acid sequence of SEQ ID NO:30 or a sequencesubstantially homologous thereto. Substantially homologous sequences are described elsewhere herein. Preferably, said substantially homologous sequence is a sequence containing 1, 2 or 3 amino acid substitutions compared to the given CDR sequence. In some embodiments, a VHH antibody of the present invention comprises a VHH domain comprising three CDRs, wherein said VHH domain comprises (i) a CDR1 that has the amino acid sequence of SEQ ID NO:4 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:5 or a sequence substantially homologous thereto and aCDR3 that has the amino acid sequence of SEQ ID NO:6 or a sequencesubstantially homologous thereto; (ii) a CDR1 that has the amino acid sequence of SEQ ID NO:12 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:13 or a sequence substantially homologous thereto and aCDR3 that has the amino acid sequence of SEQ ID NO:14 or a sequencesubstantially homologous thereto; (iii) a CDR1 that has the amino acid sequence of SEQ ID NO:20 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:21 or a sequence substantially homologous thereto and aCDR3 that has the amino acid sequence of SEQ ID NO:22 or a sequencesubstantially homologous thereto; or(iv) a CDR1 that has the amino acid sequence of SEQ ID NO:28 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:29 or a sequence substantially homologous thereto and aCDR3 that has the amino acid sequence of SEQ ID NO:30 or a sequencesubstantially homologous thereto, wherein said substantially homologous sequence is a sequence containing 1, 2 or 3 amino acid substitutions compared to the given CDR sequence. In some embodiments, a VHH antibody of the present invention comprises a VHH domain comprising three CDRs, wherein said VHH domain comprises a CDR1that has the amino acid sequence of SEQ ID NO:4 or a sequence substantiallyhomologous thereto, a CDR2 that has the amino acid sequence of SEQ ID NO:5 ora sequence substantially homologous thereto and a CDR3 that has the amino acidsequence of SEQ ID NO:6 or a sequence substantially homologous thereto.Substantially homologous sequences are described elsewhere herein. Preferably, said substantially homologous sequence is a sequence containing 1, 2 or 3 amino acid substitutions compared to the given CDR sequence. In some embodiments, a VHH antibody of the present invention comprises a VHH domain comprising three CDRs, wherein said VHH domain comprises a CDR1that has the amino acid sequence of SEQ ID NO:12 or a sequence substantiallyhomologous thereto, a CDR2 that has the amino acid sequence of SEQ ID NO:13or a sequence substantially homologous thereto and a CDR3 that has the aminoacid sequence of SEQ ID NO:14 or a sequence substantially homologous thereto.Substantially homologous sequences are described elsewhere herein. Preferably, said substantially homologous sequence is a sequence containing 1, 2 or 3 amino acid substitutions compared to the given CDR sequence. In some embodiments, a VHH antibody of the present invention comprises a VHH domain comprising three CDRs, wherein said VHH domain comprises a CDR1that has the amino acid sequence of SEQ ID NO:20 or a sequence substantiallyhomologous thereto, a CDR2 that has the amino acid sequence of SEQ ID NO:21or a sequence substantially homologous thereto and a CDR3 that has the aminoacid sequence of SEQ ID NO:22 or a sequence substantially homologous thereto.Substantially homologous sequences are described elsewhere herein. Preferably, said substantially homologous sequence is a sequence containing 1, 2 or 3 amino acid substitutions compared to the given CDR sequence. In some embodiments, a VHH antibody of the present invention comprises a VHH domain comprising three CDRs, wherein said VHH domain comprises a CDR1that has the amino acid sequence of SEQ ID NO:28 or a sequence substantiallyhomologous thereto, a CDR2 that has the amino acid sequence of SEQ ID NO:29or a sequence substantially homologous thereto and a CDR3 that has the aminoacid sequence of SEQ ID NO:30 or a sequence substantially homologous thereto.Substantially homologous sequences are described elsewhere herein. Preferably, said substantially homologous sequence is a sequence containing 1, 2 or 3 amino acid substitutions compared to the given CDR sequence. In some embodiments, a VHH antibody of the present invention comprises aVHH domain comprising three CDRs, wherein said VHH domain comprises (i) a CDR1 that has the amino acid sequence of SEQ ID NO:4 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:5 or a sequence substantially homologous thereto and aCDR3 that has the amino acid sequence of SEQ ID NO:6 or a sequencesubstantially homologous thereto; (ii) a CDR1 that has the amino acid sequence of SEQ ID NO:12 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:13 or a sequence substantially homologous thereto and aCDR3 that has the amino acid sequence of SEQ ID NO:14 or a sequencesubstantially homologous thereto; (iii) a CDR1 that has the amino acid sequence of SEQ ID NO:20 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:21 or a sequence substantially homologous thereto and aCDR3 that has the amino acid sequence of SEQ ID NO:22 or a sequencesubstantially homologous thereto; or(iv) a CDR1 that has the amino acid sequence of SEQ ID NO:28 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:29 or a sequence substantially homologous thereto and aCDR3 that has the amino acid sequence of SEQ ID NO:30 or a sequencesubstantially homologous thereto, wherein said substantially homologous sequence is a sequence that iscaninized (or that has been caninized) compared to the given CDR sequence. Insome such embodiments, such a caninized CDR sequence may be a sequence containing 1, 2 or 3 amino acid substitutions compared to the given CDR sequence. In some embodiments, a VHH antibody of the present invention comprises a VHH domain comprising three CDRs, wherein said VHH domain comprises (i) a CDR1 that has the amino acid sequence of SEQ ID NO:4, a CDR2that has the amino acid sequence of SEQ ID NO:5 and a CDR3 that has the aminoacid sequence of SEQ ID NO:6; (ii) a CDR1 that has the amino acid sequence of SEQ ID NO:12, aCDR2 that has the amino acid sequence of SEQ ID NO:13 and a CDR3 that has theamino acid sequence of SEQ ID NO:14; (iii) a CDR1 that has the amino acid sequence of SEQ ID NO:20, aCDR2 that has the amino acid sequence of SEQ ID NO:21 and a CDR3 that has theamino acid sequence of SEQ ID NO:22; or(iv) a CDR1 that has the amino acid sequence of SEQ ID NO:28, aCDR2 that has the amino acid sequence of SEQ ID NO:29 and a CDR3 that has theamino acid sequence of SEQ ID NO:30. In some embodiments, a VHH antibody of the present invention comprises a VHH domain comprising three CDRs, wherein said VHH domain comprises a CDR1that has the amino acid sequence of SEQ ID NO:4, a CDR2 that has the amino acidsequence of SEQ ID NO:5 and a CDR3 that has the amino acid sequence of SEQID NO:6. In some embodiments, a VHH antibody of the present invention comprises a VHH domain comprising three CDRs, wherein said VHH domain comprises a CDR1that has the amino acid sequence of SEQ ID NO:12, a CDR2 that has the aminoacid sequence of SEQ ID NO:13 and a CDR3 that has the amino acid sequence ofSEQ ID NO:14. In some embodiments, a VHH antibody of the present invention comprises a VHH domain comprising three CDRs, wherein said VHH domain comprises a CDR1that has the amino acid sequence of SEQ ID NO:20, a CDR2 that has the aminoacid sequence of SEQ ID NO:21 and a CDR3 that has the amino acid sequence ofSEQ ID NO:22. In some embodiments, a VHH antibody of the present invention comprises a VHH domain comprising three CDRs, wherein said VHH domain comprises a CDR1that has the amino acid sequence of SEQ ID NO:28, a CDR2 that has the aminoacid sequence of SEQ ID NO:29 and a CDR3 that has the amino acid sequence ofSEQ ID NO:30. In some embodiments, the invention provides a VHH antibody which bindsto canine IL-31, wherein said VHH antibody comprises a VHH domain that has anamino acid sequence of SEQ ID NO:3 or a sequence substantially homologousthereto (e.g. a sequence having at least 80% sequence identity thereto, for exampleat least 85%, 90%, 95% or 98% sequence identity thereto), or that has an aminoacid sequence of SEQ ID NO:11 or a sequence substantially homologous thereto (e.g. a sequence having at least 80% sequence identity thereto, for example at least 85%, 90%, 95% or 98% sequence identity thereto), or that has an amino acid sequence of SEQ ID NO:19 or a sequence substantially homologous thereto (e.g. a sequence having at least 80% sequence identity thereto, for example at least 85%, 90%, 95% or 98% sequence identity thereto), or that has an amino acid sequence of SEQ ID NO:27 or a sequence substantially homologous thereto (e.g. a sequence having at least 80% sequence identity thereto, for example at least 85%, 90%, 95% or 98% sequence identity thereto), or that has an amino acid sequence of SEQ IDNO:57 or a sequence substantially homologous thereto (e.g. a sequence having atleast 80% sequence identity thereto, for example at least 85%, 90%, 95% or 98%sequence identity thereto), or that has an amino acid sequence of SEQ ID NO:58 ora sequence substantially homologous thereto (e.g. a sequence having at least 80% sequence identity thereto, for example at least 85%, 90%, 95% or 98% sequenceidentity thereto) or that has an amino acid sequence of SEQ ID NO:74 or asequence substantially homologous thereto (e.g. a sequence having at least 80% sequence identity thereto, for example at least 85%, 90%, 95% or 98% sequenceidentity thereto), or that has an amino acid sequence of SEQ ID NO:82 or asequence substantially homologous thereto (e.g. a sequence having at least 80% sequence identity thereto, for example at least 85%, 90%, 95% or 98% sequenceidentity thereto), or that has an amino acid sequence of SEQ ID NO:100 or asequence substantially homologous thereto (e.g. a sequence having at least 80% sequence identity thereto, for example at least 85%, 90%, 95% or 98% sequence identity thereto). Substantially homologous sequences are also described elsewhere herein. In some embodiments, the invention provides a VHH antibody which binds to canine IL-31, wherein said VHH antibody comprises a VHH domain that has anamino acid sequence of SEQ ID NO:3 or a sequence substantially homologousthereto. In some embodiments, the invention provides a VHH antibody which bindsto canine IL-31, wherein said VHH antibody comprises a VHH domain that has anamino acid sequence of SEQ ID NO:11 or a sequence substantially homologousthereto. In some embodiments, the invention provides a VHH antibody which binds to canine IL-31, wherein said VHH antibody comprises a VHH domain that has anamino acid sequence of SEQ ID NO:19 or a sequence substantially homologousthereto. In some embodiments, the invention provides a VHH antibody which binds to canine IL-31, wherein said VHH antibody comprises a VHH domain that has anamino acid sequence of SEQ ID NO:27 or a sequence substantially homologousthereto. In some embodiments, the invention provides a VHH antibody which binds to canine IL-31, wherein said VHH antibody comprises a VHH domain that has anamino acid sequence of SEQ ID NO:57 or a sequence substantially homologousthereto. In some embodiments, the invention provides a VHH antibody which binds to canine IL-31, wherein said VHH antibody comprises a VHH domain that has anamino acid sequence of SEQ ID NO:58 or a sequence substantially homologousthereto. In some embodiments, the invention provides a VHH antibody which binds to canine IL-31, wherein said VHH antibody comprises a VHH domain that has anamino acid sequence of SEQ ID NO:74 or a sequence substantially homologousthereto. In some embodiments, the invention provides a VHH antibody which binds to canine IL-31, wherein said VHH antibody comprises a VHH domain that has anamino acid sequence of SEQ ID NO:82 or a sequence substantially homologousthereto. In some embodiments, the invention provides a VHH antibody which binds to canine IL-31, wherein said VHH antibody comprises a VHH domain that has anamino acid sequence of SEQ ID NO:100 or a sequence substantially homologousthereto. In some embodiments, a VHH antibody of the present invention comprises a VHH domain having an amino acid sequence selected from the group consisting of(i) SEQ ID NO:3 or or a sequence having at least 80% sequence identity thereto, (ii)SEQ ID NO:11 or a sequence having at least 80% sequence identity thereto, (iii)SEQ ID NO:19 or a sequence having at least 80% sequence identity thereto, (iv)SEQ ID NO:27 or a sequence having at least 80% sequence identity thereto, (v) SEQ ID NO:57 or a sequence having at least 80% sequence identity thereto, (vi)SEQ ID NO:58 or a sequence having at least 80% sequence identity thereto, (vii)SEQ ID NO:74 or a sequence having at least 80% sequence identity thereto (viii)SEQ ID NO:82 or a sequence having at least 80% sequence identity thereto and (ix)SEQ ID NO:100 or a sequence having at least 80% sequence identity thereto.In some embodiments, a VHH antibody of the present invention comprises aVHH domain having an amino acid sequence of SEQ ID NO:3 or or a sequencehaving at least 80% sequence identity thereto. In some embodiments, a VHH antibody of the present invention comprises aVHH domain having an amino acid sequence of SEQ ID NO:11 or a sequencehaving at least 80% sequence identity thereto. In some embodiments, a VHH antibody of the present invention comprises aVHH domain having an amino acid sequence of SEQ ID NO:19 or a sequencehaving at least 80% sequence identity thereto. In some embodiments, a VHH antibody of the present invention comprises aVHH domain having an amino acid sequence of SEQ ID NO:27 or a sequencehaving at least 80% sequence identity thereto. In some embodiments, a VHH antibody of the present invention comprises aVHH domain having an amino acid sequence of SEQ ID NO:57 or a sequencehaving at least 80% sequence identity thereto. In some embodiments, a VHH antibody of the present invention comprises aVHH domain having an amino acid sequence of SEQ ID NO:58 or a sequencehaving at least 80% sequence identity thereto. In some embodiments, a VHH antibody of the present invention comprises aVHH domain having an amino acid sequence of SEQ ID NO:74 or a sequencehaving at least 80% sequence identity thereto. In some embodiments, a VHH antibody of the present invention comprises aVHH domain having an amino acid sequence of SEQ ID NO:82 or a sequencehaving at least 80% sequence identity thereto. In some embodiments, a VHH antibody of the present invention comprises aVHH domain having an amino acid sequence of SEQ ID NO:100 or a sequencehaving at least 80% sequence identity thereto. In some embodiments, the invention provides a VHH antibody which bindsto canine IL-31, wherein said VHH antibody comprises (i) a VHH domain that has an amino acid sequence of SEQ ID NO:3 or a sequence substantially homologous thereto; (ii) a VHH domain that has an amino acid sequence of SEQ ID NO:11 or a sequence substantially homologous thereto; (iii) a VHH domain that has an amino acid sequence of SEQ ID NO:19 or a sequence substantially homologous thereto; (iv) a VHH domain that has an amino acid sequence of SEQ ID NO:27 or a sequence substantially homologous thereto; (v) a VHH domain that has an amino acid sequence of SEQ ID NO:57 or asequence substantially homologous thereto; or (vi) a VHH domain that has an amino acid sequence of SEQ ID NO:58 or a sequence substantially homologous thereto, wherein said substantially homologous sequence is a sequence that is caninized (or that has been caninized) compared to the given VHH domain sequence. In some such embodiments, such a caninized VHH domain sequence may be a sequence having at least 70% sequence identity, or preferably at least 80% sequence identity, thereto. In some embodiments, a caninized VHH domain has an amino acid sequence of SEQ ID NO:74, SEQ ID NO:82 or SEQ ID NO:100, preferably SEQ ID NO:74 or SEQ ID NO:82. In some embodiments, a VHH antibody of the present invention comprises a VHH domain having an amino acid sequence selected from the group consisting of(i) SEQ ID NO:3, (ii) SEQ ID NO:11, (iii) SEQ ID NO:19, (iv) SEQ ID NO:27, (v) SEQ ID NO:57, (vi) SEQ ID NO:58, (vii) SEQ ID NO:74, (viii) SEQ ID NO:82, and (ix) SEQ ID NO:100. In some embodiments, a VHH antibody of the present invention comprises a VHH domain having an amino acid sequence of SEQ ID NO:3. In some embodiments, a VHH antibody of the present invention comprises a VHH domain having an amino acid sequence of SEQ ID NO:11. In some embodiments, a VHH antibody of the present invention comprises a VHH domain having an amino acid sequence of SEQ ID NO:19. In some embodiments, a VHH antibody of the present invention comprises a VHH domain having an amino acid sequence of SEQ ID NO:27. In some embodiments, a VHH antibody of the present invention comprises a VHH domain having an amino acid sequence of SEQ ID NO:57. In some embodiments, a VHH antibody of the present invention comprises a VHH domain having an amino acid sequence of SEQ ID NO:58. In some embodiments, a VHH antibody of the present invention comprises aVHH domain having an amino acid sequence of SEQ ID NO:74.In some embodiments, a VHH antibody of the present invention comprises a VHH domain having an amino acid sequence of SEQ ID NO:82. In some embodiments, a VHH antibody of the present invention comprises a VHH domain having an amino acid sequence of SEQ ID NO:100. The CDRs of VHH antibodies of the invention are preferably separated by appropriate framework regions such as those found in naturally occurring antibodies and / or effective engineered antibodies. Thus, the CDR sequences of the invention are preferably provided within or incorporated into an appropriate framework or scaffold to enable antigen binding. Such framework sequences or regions may correspond to naturally occurring framework regions, FR1, FR2, FR3 and / or FR4, as appropriate to form an appropriate scaffold, or may correspond to consensus framework regions, for example identified by comparing various naturally occurring framework regions, or may be caninized framework regions. Appropriate sequences that can be used for framework regions are well known and documented in the art and any of these may be used. Preferred sequences for framework regions are one or more of the framework regions making up the VHH domains of the invention, i.e. one or more of the framework regions ofthe VHH33, VHH40, VHH94 or VHH108 VHH antibodies, as disclosed in Tables A-D herein (or framework regions of the VHH94’ or VHH108’ VHH antibodies), orframework regions substantially homologous thereto, and in particular framework regions that allow the maintenance of antigen specificity, for example framework regions that result in substantially the same or the same 3D structure of the VHH antibody. Other preferred sequences for framework regions are one or more of the framework regions making up the caninized VHH domains of the invention, for example framework regions of the caninized versions VHH94 and VHH108, as disclosed in Tables G and H herein. In some embodiments, all four of the framework regions (FR) of SEQ IDNOs:7, 8, 9 and 10, or FR regions substantially homologous thereto, are found inthe VHH antibodies of the invention. In some embodiments, all four of the framework regions (FR) of SEQ IDNOs:15, 16, 17 and 18, or FR regions substantially homologous thereto, are foundin the VHH antibodies of the invention. In some embodiments, all four of the framework regions (FR) of SEQ ID NOs:23, 24, 25 and 26, or FR regions substantially homologous thereto, are found in the VHH antibodies of the invention. In some embodiments, all four of the framework regions (FR) of SEQ IDNOs:31, 32, 33 and 34, or FR regions substantially homologous thereto, are found in the VHH antibodies of the invention. In some embodiments, all four of the framework regions (FR) of SEQ IDNOs:78, 79, 80 and 81, or FR regions substantially homologous thereto, are foundin the VHH antibodies of the invention. In some embodiments, all four of the framework regions (FR) of SEQ IDNOs:86, 87, 88 and 89, or FR regions substantially homologous thereto, are foundin the VHH antibodies of the invention. In one aspect, the present invention provides an antibody, for example anisolated VHH antibody, that binds to (or specifically binds to) canine IL-31 and thatcomprises a VHH domain that comprises three CDRs, wherein said VHH domaincomprises a CDR1 that has the amino acid sequence of SEQ ID NO:4 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:5 or a sequence substantially homologous thereto, and aCDR3 that has the amino acid sequence of SEQ ID NO:6 or a sequence substantially homologous thereto, preferably said substantially homologous sequence is a sequence containing 1, 2 or 3 amino acid substitutions compared to the given CDR sequence. Preferred embodiments of this aspect of the invention include antibodies comprising one or more of the antibody sequences (e.g. CDRsequences and / or VHH domain sequences) that are described elsewhere herein inconnection with other aspects of the present invention. Thus, discussion of various features of the antibodies of other aspects of the invention and preferredembodiments apply mutatis mutandis to this aspect of the invention. In somepreferred embodiments of this aspect of the invention, the invention provides anantibody comprising a VHH domain that has the amino acid sequence of SEQ IDNO:3 or a sequence substantially homologous thereto (e.g. a sequence having atleast 80% sequence identity to SEQ ID NO:3). In one aspect, the present invention provides an antibody, for example an isolated VHH antibody, that binds to (or specifically binds to) canine IL-31 and that comprises a VHH domain that comprises three CDRs, wherein said VHH domaincomprises a CDR1 that has the amino acid sequence of SEQ ID NO:12 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:13 or a sequence substantially homologous thereto, and aCDR3 that has the amino acid sequence of SEQ ID NO:14 or a sequencesubstantially homologous thereto, preferably said substantially homologous sequence is a sequence containing 1, 2 or 3 amino acid substitutions compared to the given CDR sequence. Preferred embodiments of this aspect of the invention include antibodies comprising one or more of the antibody sequences (e.g. CDRsequences and / or VHH domain sequences) that are described elsewhere herein inconnection with other aspects of the present invention. Thus, discussion of various features of the antibodies of other aspects of the invention and preferredembodiments apply mutatis mutandis to this aspect of the invention. In somepreferred embodiments of this aspect of the invention, the invention provides an antibody comprising a VHH domain that has the amino acid sequence of SEQ IDNO:11 or a sequence substantially homologous thereto (e.g. a sequence having atleast 80% sequence identity to SEQ ID NO:11). In one aspect, the present invention provides an antibody, for example an isolated VHH antibody, that binds to (or specifically binds to) canine IL-31 and that comprises a VHH domain that comprises three CDRs, wherein said VHH domaincomprises a CDR1 that has the amino acid sequence of SEQ ID NO:20 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:21 or a sequence substantially homologous thereto, and aCDR3 that has the amino acid sequence of SEQ ID NO:22 or a sequencesubstantially homologous thereto, preferably said substantially homologous sequence is a sequence containing 1, 2 or 3 amino acid substitutions compared to the given CDR sequence. Preferred embodiments of this aspect of the invention include antibodies comprising one or more of the antibody sequences (e.g. CDRsequences and / or VHH domain sequences) that are described elsewhere herein inconnection with other aspects of the present invention. Thus, discussion of various features of the antibodies of other aspects of the invention and preferredembodiments apply mutatis mutandis to this aspect of the invention. In somepreferred embodiments of this aspect of the invention, the invention provides an antibody comprising a VHH domain that has the amino acid sequence of SEQ IDNO:19 or SEQ ID NO:57 or SEQ ID NO:74 or a sequence substantially homologousthereto (e.g. a sequence having at least 80% sequence identity to SEQ ID NO:19 orSEQ ID NO:57 or SEQ ID NO:74).In one aspect, the present invention provides an antibody, for example an isolated VHH antibody, that binds to (or specifically binds to) canine IL-31 and that comprises a VHH domain that comprises three CDRs, wherein said VHH domaincomprises a CDR1 that has the amino acid sequence of SEQ ID NO:28 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:29 or a sequence substantially homologous thereto, and aCDR3 that has the amino acid sequence of SEQ ID NO:30 or a sequencesubstantially homologous thereto, preferably said substantially homologous sequence is a sequence containing 1, 2 or 3 amino acid substitutions compared to the given CDR sequence. Preferred embodiments of this aspect of the invention include antibodies comprising one or more of the antibody sequences (e.g. CDRsequences and / or VHH domain sequences) that are described elsewhere herein inconnection with other aspects of the present invention. Thus, discussion of variousfeatures of the antibodies of other aspects of the invention and preferredembodiments apply mutatis mutandis to this aspect of the invention. In somepreferred embodiments of this aspect of the invention, the invention provides an antibody comprising a VHH domain that has the amino acid sequence of SEQ IDNO:27 or SEQ ID NO:58 or SEQ ID NO:82 or SEQ ID NO:100 or a sequencesubstantially homologous thereto (e.g. a sequence having at least 80% sequenceidentity to SEQ ID NO:27 or SEQ ID NO:58 or SEQ ID NO:82 or SEQ ID NO:100).In another aspect, the present invention provides a VHH antibody that bindsto (or specifically binds to) canine IL-31, said VHH antibody comprising a VHHdomain that comprises three CDRs, wherein said VHH domain comprises a variableheavy (VH) CDR1, a VH CDR2 and a VH CDR3 of (or from or from within) the VHHdomain that has the sequence of SEQ ID NO:3 (or VH CDR1, VH CDR2 and VHCDR3 sequences substantially homologous thereto). Discussion of various features of the antibodies of other aspects of the invention and preferred embodiments maybe applied mutatis mutandis to this aspect of the invention.In another aspect, the present invention provides a VHH antibody that bindsto (or specifically binds to) canine IL-31, said VHH antibody comprising a VHHdomain that comprises three CDRs, wherein said VHH domain comprises a variable heavy (VH) CDR1, a VH CDR2 and a VH CDR3 of (or from or from within) the VHHdomain that has the sequence of SEQ ID NO:11 (or VH CDR1, VH CDR2 and VHCDR3 sequences substantially homologous thereto). Discussion of various features of the antibodies of other aspects of the invention and preferred embodiments maybe applied mutatis mutandis to this aspect of the invention.In another aspect, the present invention provides a VHH antibody that bindsto (or specifically binds to) canine IL-31, said VHH antibody comprising a VHHdomain that comprises three CDRs, wherein said VHH domain comprises a variable heavy (VH) CDR1, a VH CDR2 and a VH CDR3 of (or from or from within) the VHHdomain that has the sequence of SEQ ID NO:19 or SEQ ID NO:57 or SEQ IDNO:74 (or VH CDR1, VH CDR2 and VH CDR3 sequences substantially homologousthereto). Discussion of various features of the antibodies of other aspects of theinvention and preferred embodiments may be applied mutatis mutandis to thisaspect of the invention. In another aspect, the present invention provides a VHH antibody that bindsto (or specifically binds to) canine IL-31, said VHH antibody comprising a VHHdomain that comprises three CDRs, wherein said VHH domain comprises a variable heavy (VH) CDR1, a VH CDR2 and a VH CDR3 of (or from or from within) the VHHdomain that has the sequence of SEQ ID NO:27 or SEQ ID NO:58 or SEQ IDNO:82 or SEQ ID NO:100 (or VH CDR1, VH CDR2 and VH CDR3 sequences substantially homologous thereto). Discussion of various features of the antibodies of other aspects of the invention and preferred embodiments may be appliedmutatis mutandis to this aspect of the invention. In some embodiments, the CDR sequences of (or from or from within) aVHH domain are CDR sequences as set forth in Tables A, B, C, D, G or H herein.CDR sequences of (or from or from within) a VHH domain (or heavy chain variabledomain) may be CDR sequences as identified using the IMGT numbering scheme(e.g. Lefranc, M.-P., The Immunologist, 7, 132-136 (1999); www.imgt.org), e.g. asshown in Tables A, B, C, D, E herein, G and H. In some other embodiments, CDRsequences of (or from or from within) a VHH domain are CDR sequences asidentified using any suitable method (or tool), for example as identified according to the well-known methods of Kabat (e.g. Kabat, et al., "Sequences of Proteins of Immunological Interest", 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD, 647-669, 1991) or Chothia (e.g. Chothia C, et al. (1989) Nature,342:877–883, or Al-Lazikani et al., (1997) JMB 273,927-948).Alternatively viewed, in some embodiments the invention provides a VHH antibody that binds to canine IL-31, wherein said VHH antibody comprises a CDR1 that has the amino acid sequence of SEQ ID NO:4 or a sequence substantially homologous thereto, a CDR2 that has the amino acid sequence of SEQ ID NO:5 or a sequence substantially homologous thereto and a CDR3 that has the amino acid sequence of SEQ ID NO:6 or a sequence substantially homologous thereto. Substantially homologous sequences are described elsewhere herein. Preferably, said substantially homologous sequence is a sequence containing 1, 2 or 3 amino acid substitutions compared to the given CDR sequence. Alternatively viewed, in some embodiments the invention provides a VHH antibody that binds to canine IL-31, wherein said VHH antibody comprises a CDR1that has the amino acid sequence of SEQ ID NO:12 or a sequence substantiallyhomologous thereto, a CDR2 that has the amino acid sequence of SEQ ID NO:13 or a sequence substantially homologous thereto and a CDR3 that has the aminoacid sequence of SEQ ID NO:14 or a sequence substantially homologous thereto.Substantially homologous sequences are described elsewhere herein. Preferably, said substantially homologous sequence is a sequence containing 1, 2 or 3 amino acid substitutions compared to the given CDR sequence. Alternatively viewed, in some embodiments the invention provides a VHH antibody that binds to canine IL-31, wherein said VHH antibody comprises a CDR1that has the amino acid sequence of SEQ ID NO:20 or a sequence substantiallyhomologous thereto, a CDR2 that has the amino acid sequence of SEQ ID NO:21 or a sequence substantially homologous thereto and a CDR3 that has the aminoacid sequence of SEQ ID NO:22 or a sequence substantially homologous thereto. Substantially homologous sequences are described elsewhere herein. Preferably, said substantially homologous sequence is a sequence containing 1, 2 or 3 amino acid substitutions compared to the given CDR sequence. Alternatively viewed, in some embodiments the invention provides a VHH antibody that binds to canine IL-31, wherein said VHH antibody comprises a CDR1that has the amino acid sequence of SEQ ID NO:28 or a sequence substantiallyhomologous thereto, a CDR2 that has the amino acid sequence of SEQ ID NO:29 or a sequence substantially homologous thereto and a CDR3 that has the aminoacid sequence of SEQ ID NO:30 or a sequence substantially homologous thereto.Substantially homologous sequences are described elsewhere herein. Preferably, said substantially homologous sequence is a sequence containing 1, 2 or 3 amino acid substitutions compared to the given CDR sequence. In some embodiments, the invention provides a VHH antibody which binds to canine IL-31, wherein said VHH antibody comprises (or consists of) an aminoacid sequence of SEQ ID NO:3 or a sequence substantially homologous thereto(e.g. a sequence having at least 80% sequence identity thereto). In some embodiments, the invention provides a VHH antibody which binds to canine IL-31, wherein said VHH antibody comprises (or consists of) an aminoacid sequence of SEQ ID NO:11 or a sequence substantially homologous thereto(e.g. a sequence having at least 80% sequence identity thereto). In some embodiments, the invention provides a VHH antibody which binds to canine IL-31, wherein said VHH antibody comprises (or consists of) an aminoacid sequence of SEQ ID NO:19 or SEQ ID NO:57 or SEQ ID NO:74 a sequencesubstantially homologous thereto (e.g. a sequence having at least 80% sequenceidentity thereto). In some embodiments, the invention provides a VHH antibody which binds to canine IL-31, wherein said VHH antibody comprises (or consists of) an aminoacid sequence of SEQ ID NO:27 or SEQ ID NO:58 or SEQ ID NO:82 or SEQ IDNO:100 or a sequence substantially homologous thereto (e.g. a sequence having atleast 80% sequence identity thereto). The term "substantially homologous" as used herein in connection with an amino acid or nucleic acid sequence includes sequences having at least 65%, 70% or 75%, preferably at least 80%, and even more preferably at least 85%, 90%, 95%, 96%, 97%, 98% or 99%, sequence identity to the amino acid or nucleic acid sequence disclosed. Substantially homologous sequences of the invention thus include single or multiple base or amino acid alterations (additions, substitutions, insertions or deletions) to the sequences of the invention. At the amino acid level preferred substantially homologous sequences contain up to 5, e.g. only 1, 2, 3, 4 or 5, preferably 1, 2 or 3, more preferably 1 or 2, altered amino acids, in one or more of the framework regions and / or one or more of the CDRs making up the sequences of the invention. Certain examples of substantially homologous sequences are sequences that have at least 65% identity to the amino acid sequences disclosed. In certain embodiments, the VHH antibodies of the invention comprise a VHH domain havingan amino acid sequence of at least about 65%, 70% or 75%, more preferably atleast about 80%, more preferably at least about 85%, more preferably at least about 90% or 95% and most preferably at least about 97%, 98% or 99% amino acidsequence identity to the amino acid sequence of SEQ ID NO:3 or SEQ ID NO:11 orSEQ ID NO:19 or SEQ ID NO:27 or SEQ ID NO:57 or SEQ ID NO:58 or SEQ IDNO:74 or SEQ ID NO:82 or SEQ ID NO:100. Alterations in amino acid sequences can be with conservative or non- conservative amino acids. Preferably, said alterations are conservative amino acid substitutions. Other preferred examples of substantially homologous sequences are sequences containing conservative amino acid substitutions of the amino acid sequences disclosed. Other preferred examples of substantially homologous sequences are sequences containing 1, 2 or 3, preferably 1 or 2 (more preferably 1), altered amino acids in one or more of the CDR regions disclosed. Alterations may be additions, substitutions, insertions or deletions. Such alterations might be conserved or non- conserved amino acid substitutions, or a mixture thereof. In some such embodiments, preferred alterations are conservative amino acid substitutions. Other preferred examples of substantially homologous sequences are sequences 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 90% or at least 95% sequence identity to one or more of the CDR sequences disclosed. Thus, in someembodiments, a “substantially homologous” CDR sequence may be a sequencehaving 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 90% or at least 95% sequence identity to a given CDR sequence described herein. Altered residues might be conserved or non-conserved amino acid substitutions, or a mixture thereof. In some embodiments, preferred alterations are conservative amino acid substitutions. In some embodiments, in VHH antibodies having a “substantially homologous” sequence as compared to a given sequence, or having a certain degree of sequence identity as compared to a given sequence, the altered amino acid residues(s) are not in a CDR region. For example, in antibodies having a VHH domain sequence that has a certain degree of sequence identity to a given VHH domain sequence of a particular antibody of the invention (e.g. VHH33, VHH40,VHH94, VHH108, VHH94’, VHH108’, or caninized versions of said VHHs), thealtered (or variant) residue(s) are not in a CDR region. Thus, in some embodiments, in VHH antibodies having a “substantially homologous” sequence as compared to a given sequence, or having a certain degree of sequence identity as compared to a given sequence, the altered amino acid residues(s) are in one or more framework regions. As is evident from elsewhere herein, in other embodiments, in VHH antibodies having a “substantially homologous” sequence as compared to a given sequence, or having a certain degree of sequence identity as compared to a given sequence, the altered amino acid residues(s) may be in a CDR region. In some embodiments, in a VHH antibody having a “substantiallyhomologous” sequence as compared to a given sequence, or having a certain degree of sequence identity as compared to a given sequence, the three CDRamino acid sequences (i.e. all three CDR sequences taken together) are consideredtogether to be the whole (or entire) CDR complement of the VHH antibody, and the amino acid sequence of said whole CDR complement of said antibody is at least 70%, preferably at least 80%, or at least 90%, or at least 95% identical to the corresponding whole (or entire) CDR complement of a given starting (or reference) VHH antibody. The starting (or reference) antibody may have the CDR sequences of a particular VHH antibody of the invention. Thus, the starting (or reference) VHH antibody may have the CDR sequences of the VHH33, VHH40, VHH94 or VHH108VHH antibodies of the present invention (or of a caninized version thereof).In some embodiments, a VHH antibody which binds to canine IL-31 of the present invention (or other VHH antibody as described herein, e.g. a VHH antibodywhich binds to canine albumin) has a D (Asp) residue as the first (i.e. N-terminal-most) amino acid in the framework 1 (FR1) region. A VHH antibody defined hereinas having an amino acid other than D (e.g. a Q (Gln) or an E (Glu)) residue as the first (i.e. N-terminal-most) amino acid in the FR1 region may, in some alternative embodiments, have a D residue as the first (i.e. N-terminal-most) amino acidresidue in the framework 1 (FR1) region instead of said amino acid other than D (i.e.in some embodiments the non-D residue that is the first (i.e. N-terminal-most) aminoacid residue in the FR1 region is replaced by a D residue). In some embodimentsof constructs of the invention, a VHH antibody which binds to canine IL-31 of the present invention (or other VHH antibody as described herein, e.g. a VHH antibody which binds to canine albumin) that has a D (Asp) residue as the first (i.e. N- terminal-most) amino acid in the FR1 region may be positioned as the N-terminal- most element or agent (e.g. N-terminal-most VHH antibody) in the construct. In some embodiments of constructs of the invention, the construct has a D (Asp) residue as the first (i.e. N-terminal-most) amino acid residue in the construct. In some embodiments, a VHH antibody which binds to canine IL-31 of the present invention (or other VHH antibody as described herein, e.g. a VHH antibodywhich binds to canine albumin) has an A (Ala) residue as the final (i.e. C-terminal-most) amino acid in the framework 4 (FR4) region. A VHH antibody defined hereinas having an S (Ser) residue as the final (i.e. C-terminal-most) amino acid in theFR4 region may, in some alternative embodiments, have an additional amino acidresidue, preferably an A (Ala) residue, positioned immediately C-terminal to (i.e. asthe next residue to) the S residue (that would otherwise be the C-terminal residue,e.g. such that said additional residue, preferably an A residue, is the final (C-terminal-most) amino acid in the FR4 region). In some embodiments of constructs of the invention, a VHH antibody which binds to canine IL-31 of the present invention (or other VHH antibody as described herein, e.g. a VHH antibody which binds to canine albumin) that has such an additional residue, preferably anadditional A (Ala) residue, may be positioned as the C-terminal-most element oragent (e.g. C-terminal-most VHH antibody) in the construct. In some embodiments of constructs of the invention, the construct has such an additional residue,preferably an additional A residue, as the final (i.e. C-terminal-most) amino acidresidue in the construct. In some embodiments, a VHH antibody defined herein as having an A (Ala) residue as the final (i.e. C-terminal-most) amino acid residue in the FR4 region may, in some alternative embodiments, have said A residue omitted (or alternatively viewed in some alternative embodiments said A residue may be absent). In some embodiments, a “substantially homologous” sequence may be a caninized sequence, i.e. a sequence that has been caninized compared to the given sequence (or a caninized version or caninized variant of the given sequence).Thus, in some embodiments, a “substantially homologous” CDR sequence may bea caninized CDR sequence, i.e. a CDR sequence that has been caninized compared to the given sequence (or a caninized version or caninized variant of the given sequence). In some embodiments, a “substantially homologous” VHH domain sequence may be a caninized VHH domain sequence, i.e. a VHH domain sequence that has been caninized compared to the given sequence (or a caninized version or caninized variant of the given sequence). In caninized VHH domains, the caninizedsequences (or caninized residues) may be in one or more of the CDRs and / or inone or more of the framework regions. Preferably, the caninized sequences (orcaninized residues) are in one or more (or all) of the framework regions. In some embodiments, the caninized sequences (or caninized residues) are not in the CDRs. In all embodiments, VHH antibodies containing substantially homologous sequences retain the ability to bind to canine IL-31. Preferably, antibodies containing substantially homologous sequences retain one or more (preferably all)of the properties of (e.g. described in relation to) the VHH33, VHH40, VHH94 (orcaninized VHH94), VHH108 (or caninized VHH108), VHH94’ or VHH108’ VHHantibodies (e.g. ability to inhibit canine IL-31 signalling).A "conservative amino acid substitution", as used herein, is one in which the amino acid residue is replaced with another amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art, including basic side chains (e.g. lysine, arginine, histidine), acidic side chains (e.g. aspartic acid, glutamic acid), uncharged polar side chains (e.g. asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g. glycine, cysteine, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g. threonine, valine, isoleucine) and aromatic side chains (e.g. tyrosine, phenylalanine, tryptophan, histidine). Methods of carrying out the above described manipulation of amino acids (e.g. to generate “substantially homologous” sequences) are well known to a person skilled in the art. Homology (e.g. sequence identity) may be assessed by any convenient method. However, for determining the degree of homology (e.g. identity) between sequences, computer programs that make multiple alignments of sequences are useful, for instance Clustal W (Thompson, Higgins, Gibson, Nucleic Acids Res., 22:4673-4680, 1994). If desired, the Clustal W algorithm can be used together with BLOSUM 62 scoring matrix (Henikoff and Henikoff, Proc. Natl. Acad. Sci. USA,89:10915–10919, 1992) and a gap opening penalty of 10 and gap extension penaltyof 0.1, so that the highest order match is obtained between two sequences wherein at least 50% of the total length of one of the sequences is involved in the alignment.Other methods that may be used to align sequences are the alignment method ofNeedleman and Wunsch (Needleman and Wunsch, J. Mol. Biol., 48:443, 1970) asrevised by Smith and Waterman (Smith and Waterman, Adv. Appl. Math., 2:482,1981) so that the highest order match is obtained between the two sequences andthe number of identical amino acids is determined between the two sequences. Other methods to calculate the percentage identity between two amino acidsequences are generally art recognized and include, for example, those describedby Carillo and Lipton (Carillo and Lipton, SIAM J. Applied Math., 48:1073, 1988) andthose described in Computational Molecular Biology, Lesk, e.d. Oxford University Press, New York, 1988, Biocomputing: Informatics and Genomics Projects. Generally, computer programs will be employed for such calculations. Programs that compare and align pairs of sequences, like ALIGN (Myers and Miller, CABIOS, 4:11-17, 1988), FASTA (Pearson and Lipman, Proc. Natl. Acad. Sci. USA, 85:2444-2448, 1988; Pearson, Methods in Enzymology, 183:63-98, 1990) and gapped BLAST (Altschul et al., Nucleic Acids Res., 25:3389-3402, 1997), BLASTP, BLASTN, or GCG (Devereux, Haeberli, Smithies, Nucleic Acids Res., 12:387,1984) are also useful for this purpose. Furthermore, the Dali server at the EuropeanBioinformatics institute offers structure-based alignments of protein sequences (Holm, Trends in Biochemical Sciences, 20:478-480, 1995; Holm, J. Mol. Biol., 233:123-38, 1993; Holm, Nucleic Acid Res., 26:316-9, 1998). By way of providing a reference point, sequences according to the present invention having 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%homology, sequence identity etc. may be determined using the ALIGN program withdefault parameters (for instance available on Internet at the GENESTREAM network server, IGH, Montpellier, France). In certain embodiments, if a given starting sequence is relatively short (e.g. five amino acids in length), then fewer amino acid substitutions may be present in sequences substantially homologous thereto as compared with the number of amino acid substitutions that might optionally be made in a sequence substantially homologous to a longer starting sequence. For example, in certain embodiments, a sequence substantially homologous to a starting CDR1 sequence in accordance with the present invention, e.g. a starting CDR1 sequence of five amino acid residues in length, preferably has 1 or 2 (more preferably 1) altered amino acids in comparison with the starting sequence. Accordingly, in some embodiments the number of altered amino acids in substantially homologous sequences (e.g. in substantially homologous CDR sequences) can be tailored to the length of a given starting CDR sequence. For example, different numbers of altered amino acids canbe present depending on the length of a given starting CDR sequence such as toachieve a particular % sequence identity in the CDRs, for example a sequence identity of at least 50%, 60%, 75%, 80%, 85%, 90% or 95%. Routine methods in the art such as alanine scanning mutagenesis and / or analysis of crystal structure of the antigen-antibody complex can be used in order to determine which amino acid residues of the CDRs do not contribute or do not contribute significantly to antigen binding and therefore are good candidates for alteration or substitution in the embodiments of the invention involving substantially homologous sequences. The term "substantially homologous" also includes modifications or chemical equivalents of the amino acid and nucleotide sequences of the present invention that perform substantially the same function as the proteins or nucleic acid molecules of the invention in substantially the same way. Substantially homologous sequences of VHH antibodies of the invention also include, without limitation, for example alterations that do not affect the VHH or CDR domains of the VHH antibodies, e.g. VHH antibodies where tag sequences or other components are added that do not contribute to the binding of antigen. Preferably, any substantially homologous antibody should retain the ability to bind (or specifically bind) to the same (or substantially the same) epitope asrecognized by the VHH antibody in question (e.g. a reference VHH antibody inquestion). Thus, preferably, any substantially homologous antibody should retain the ability to compete with one or more of the various VHH antibodies of theinvention (e.g. one of the described VHH antibodies VHH33, VHH40, VHH94,VHH108, VHH94’ or VHH108’) for binding to canine IL-31. Binding to the same epitope / antigen can be readily tested by methods well known and described in the art, e.g. using binding assays, e.g. a competition assay. Retention of other functional properties can also readily be tested by methods well known and described in the art or herein. Thus, a person skilled in the art will appreciate that binding assays can be used to test whether "substantially homologous" antibodies have the same binding specificities as the VHH antibodies of the invention, for example, binding assays such as competition assays or ELISA assays as described elsewhere herein.Surface Plasmon Resonance (e.g. BIAcore) assays could also be used to establishwhether "substantially homologous" antibodies bind to canine IL-31. The skilled person will be aware of other suitable methods and variations. As outlined below, a competition binding assay can be used to test whether "substantially homologous" VHH antibodies retain the ability to bind (or specificallybind) to substantially the same epitope (or the same epitope) of canine IL-31 asrecognized by a VHH antibody of the invention (e.g. antibody VHH33, VHH40,VHH94 or VHH108, or antibodies based on these antibodies, e.g. caninizedversions), or have the ability to compete with a VHH antibody of the invention (e.g.VHH33, VHH40, VHH94, VHH108, VHH94’ or VHH108’, or antibodies based onthese antibodies, e.g. caninized versions). The method described below is only one example of a suitable competition assay. The skilled person will be aware of other suitable methods and variations. An exemplary competition assay involves assessing the binding of variouseffective concentrations of a VHH antibody of the invention to canine IL-31 in thepresence of varying concentrations of a test VHH antibody (e.g. a substantially homologous VHH antibody). The amount of inhibition of binding induced by the test VHH antibody can then be assessed. A test VHH antibody that shows increasedcompetition with a VHH antibody of the invention at increasing concentrations (i.e.increasing concentrations of the test VHH antibody result in a corresponding reduction in the amount of VHH antibody of the invention binding to canine IL-31) is evidence of binding to substantially the same epitope. Preferably, the test VHH antibody significantly reduces the amount of VHH antibody of the invention that binds to canine IL-31. Preferably, the test antibody reduces the amount of VHHantibody of the invention that binds to canine IL-31 by at least about 60%, 65%,70%, 75%, 80%, 85%, 90% or 95%. ELISA assays may be used for assessing inhibition of binding in such a competition assay but other suitable techniques would be well known to a person skilled in the art. In some embodiments, “substantially homologous” antibodies which retain the ability to bind (or specifically bind) to substantially the same (or the same)epitope of canine IL-31 as recognized by an antibody of the invention (e.g. VHH33,VHH40, VHH94, VHH108, VHH94’ or VHH108’ or antibodies based on theseantibodies, e.g. caninized versions) or which have the ability to compete with one or more of the various antibodies of the invention (e.g. VHH33, VHH40, VHH94,VHH108, VHH94’ or VHH108’, or antibodies based on these antibodies, e.g.caninized versions) are preferred. The term "competing antibodies", as used herein, refers to VHH antibodies that bind to about, substantially or essentially the same, or even the same, epitope as a "reference antibody". "Competing antibodies" include VHH antibodies with overlapping epitope specificities. Competing antibodies are thus able to effectively compete with a reference VHH antibody for binding to canine IL-31. Preferably, thecompeting antibody can bind to the same epitope as the reference antibody.Alternatively viewed, a competing antibody preferably has the same epitopespecificity as the reference antibody. "Reference antibodies" as used herein include VHH antibodies of the present invention. “Reference antibodies” include antibodies which have a VHHdomain as defined herein, for example a VHH domain of SEQ ID NO:3, SEQ IDNO:11, SEQ ID NO:19, SEQ ID NO:27, SEQ ID NO:57, SEQ ID NO:58, 74, 82 or100. Certain preferred reference antibodies are selected from antibodies VHH33,VHH40, VHH94, VHH108, VHH94’ and VHH108’, or caninized versions thereof.As the identification of competing VHH antibodies is determined in comparison to a reference antibody, it will be understood that actually determining the epitope to which either or both VHH antibodies bind is not in any way required in order to identify a competing antibody. However, epitope mapping can be performed using standard techniques, if desired. In one aspect, and in some embodiments, the present invention provides aVHH antibody which binds to canine IL-31, wherein said VHH antibody binds to thesame (or substantially the same) epitope on canine IL-31 as a VHH antibody asdefined elsewhere herein (e.g. a reference antibody described herein). Otherfeatures and properties of other aspects and embodiments of the invention apply, mutatis mutandis, to this aspect of the invention. In some embodiments, the present invention provides a VHH antibody whichbinds to canine IL-31, wherein said VHH antibody binds to the same (orsubstantially the same) epitope on canine IL-31 as a VHH antibody that has a VHHdomain of SEQ ID NO:3. In some embodiments, the present invention provides a VHH antibody whichbinds to canine IL-31, wherein said VHH antibody binds to the same (orsubstantially the same) epitope on canine IL-31 as a VHH antibody that has a VHHdomain of SEQ ID NO:11. In some embodiments, the present invention provides a VHH antibody whichbinds to canine IL-31, wherein said VHH antibody binds to the same (orsubstantially the same) epitope on canine IL-31 as a VHH antibody that has a VHHdomain of SEQ ID NO:19. In some embodiments, the present invention provides a VHH antibody whichbinds to canine IL-31, wherein said VHH antibody binds to the same (orsubstantially the same) epitope on canine IL-31 as a VHH antibody that has a VHHdomain of SEQ ID NO:27. In some embodiments, the present invention provides a VHH antibody whichbinds to canine IL-31, wherein said VHH antibody binds to the same (orsubstantially the same) epitope on canine IL-31 as a VHH antibody that has a VHHdomain of SEQ ID NO:57. In some embodiments, the present invention provides a VHH antibody whichbinds to canine IL-31, wherein said VHH antibody binds to the same (orsubstantially the same) epitope on canine IL-31 as a VHH antibody that has a VHHdomain of SEQ ID NO:58. In some embodiments, the present invention provides a VHH antibody whichbinds to canine IL-31, wherein said VHH antibody binds to the same (orsubstantially the same) epitope on canine IL-31 as a VHH antibody that has a VHHdomain of SEQ ID NO:74. In some embodiments, the present invention provides a VHH antibody whichbinds to canine IL-31, wherein said VHH antibody binds to the same (orsubstantially the same) epitope on canine IL-31 as a VHH antibody that has a VHHdomain of SEQ ID NO:82. Ayet further aspect of the invention provides a VHH antibody, e.g. anisolated antibody, which binds to canine IL-31 and which has the ability to competewith (i.e. bind to the same or substantially the same epitope as) an antibody of the invention for binding to canine IL-31. For example, antibodies that can compete with antibodies (e.g. antibodies such as those described in the Example section herein) represent a further aspect of the invention. Other features and properties of other aspects and embodiments of the invention apply, mutatis mutandis, to this aspect of the invention. Binding to the same (or substantially the same) epitope / antigen can be readily tested by methods well known and described in the art, e.g. using bindingassays such as a competition assay, e.g. as described elsewhere herein (e.g. inrelation to “test” or “substantially homologous” antibodies). In the following descriptions of the VHH antibodies, constructs, polypeptides, compositions, pharmaceuticals, combinations, kits, first and second medical uses and all methods in accordance with this invention, the terms "VHH antibody", unless otherwise specifically stated or made clear from the context or scientific terminology,refer to a range of VHH antibodies that bind to canine IL-31 in accordance with theinvention as well as to the specific VHH antibodies described in the Example section herein. Antibodies in accordance with the present invention are VHH antibodies. “VHH” is an acronym for Variable Heavy domain of Heavy chain. VHH antibodies are also known as VHH antibodies, nanobodies, single domain antibodies, sdAbs, DABs or dAbs. A VHH antibody may also be referred to simply as a VHH. VHH antibodies comprise (or consist of) a single (or only a single, or one, oronly one) antigen binding domain, which may be referred to as a VHH domain (or aheavy chain variable region). Thus, VHH antibodies comprise (or consist of) asingle (or only a single, or one, or only one) monomeric variable antibody domain, which may be referred to as a VHH domain (or a heavy chain variable region) which can bind to antigen. Put another way, VHH antibodies are characterized by having a single (only a single) monomeric variable antibody domain (a single VHH domain or a single heavy chain variable region or single heavy chain variable domain). Thus, VHH antibodies have only three CDRs (typically together with four FR regions in the standard or usual order). Alternatively viewed, VHH antibodies have only three heavy chain CDRs (typically together with four heavy chain FR (framework) regions in the standard or usual order). VHH antibodies do not contain light chain antibody sequences. Thus, VHH antibodies do not contain a light chain variable region (or VL domain) and do not contain light chain CDRs. Put another way, in VHH antibodies no VL regions or domains are present. Furthermore, in VHH antibodies, no antibody constantregions or hinge regions are present. Thus, in VHH antibodies, the VHH domain isthe only part of the antibody that is antibody-derived. Thus, in some embodiments a VHH antibody in accordance with the presentinvention may consist of a VHH domain. However, in some embodiments, a VHH antibody of the invention may contain one or more additional (non-antibody derived) sequences or (non-antibody derived) moieties. For example, in some embodiments a VHH antibody may additionally comprise (i.e. in addition to the VHH domain), one or more affinity tags (e.g. a His-tag and / or a myc-tag) that may facilitate detection and / or purification. The monomeric variable antibody domain (VHH domain) of VHH antibodiesin accordance with the present invention typically corresponds to (or correspondsessentially to or is derived from or is based on or is substantially homologous to) aheavy chain variable domain (or variable heavy domain) of a heavy chain (or heavychain only) antibody (e.g. a camelid heavy chain antibody such as llama antibody).However, as is evident from discussion elsewhere herein, VHH antibodies in accordance with the present invention include antibodies having sequences (e.g.CDR sequences) that may have a VHH domain that does not correspond exactly toa VHH domain of a given heavy chain antibody, e.g. the VHH domain may have a sequence substantially homologous to a VHH domain of a heavy chain antibody (e.g. it may have substantially homologous CDR sequences and / or be a caninized version of a VHH domain). Although VHH antibodies are characterized by having a single (only a single) monomeric variable antibody domain (a single VHH domain), as described elsewhere herein, in some aspects of the present invention (e.g. constructs of the invention) more than one VHH antibody of the present invention with the same or different sequences can be present together in the same construct or molecule. VHH antibodies can be obtained or prepared using standard techniques which are well known and described in the art. For example, such VHH antibodies can be obtained by immunizing appropriate animals, e.g. camelids such llamas, with the desired antigen and then cloning the VHH domains of the antibodies generatedinto appropriate expression vectors and selecting for binders. Libraries of VHHdomains are also available or can be generated and can then be screened. In some embodiments, monoclonal VHH antibodies are preferred (e.g. llamamonoclonal VHH antibodies or caninized versions thereof).As will be understood by those in the art, the term “VHH antibody” includes or extends to recombinant and engineered forms of these antibodies. The techniques for preparing and using the VHH antibodies and constructs are well known in the art. In some embodiments, the VHH antibodies of the present invention are camelid VHH antibodies (i.e. derived from or based on the VHH domain of a camelid heavy chain (heavy chain only) antibody). In some embodiments, the VHH antibodies of the present invention are llama VHH antibodies (i.e. derived from or based on the VHH domain of a llama heavy chain (heavy chain only) antibody).The term "camelid" (e.g. llama) as used herein in connection with VHHantibodies first refers to VHH antibodies having a VHH domain or CDRs isolated orderived from a camelid (e.g. llama) repertoire or derived from or corresponding tosequences found in a camelid (e.g. llama) or a camelid (e.g. llama) repertoire, e.g.,in the camelid (e.g. llama) germline or somatic cells."Camelid" VHH antibodies further include amino acid residues not encodedby camelid sequences, e.g., mutations introduced by random or site directedmutations in vitro, for example mutations introduced by in vitro cloning or PCR.Particular examples of such mutations are mutations that involve conservative substitutions or other mutations in a small number of residues of the VHH antibody,e.g., in up to 5, 4, 3, 2 or 1 of the residues of the VHH antibody, preferably e.g., inup to 5, 4, 3, 2 or 1 of the residues making up one or more of the CDRs of the antibody. Certain examples of such "camelid" antibodies include VHH antibodiesthat have been subjected to standard modification techniques to reduce the amountof potentially immunogenic sites.Thus, "camelid" VHH antibodies include sequences derived from and related to sequences found in camelids, but which may not naturally exist within the camelid antibody germline repertoire in vivo. In addition, camelid VHH antibodies are not limited to combinations of CDRor FR regions that are themselves found in combination in camelid antibodymolecules. Thus, camelid antibodies can include or correspond to combinations ofsuch regions that do not necessarily exist naturally in camelids (e.g. are notnaturally occurring antibodies). In some embodiments, VHH antibodies of the invention are caninized VHHantibodies. “Caninized" VHH antibodies, which are based on a (or a substantially)non-canine variable region domain, are VHH antibodies in which certain aminoacids have been changed to better correspond with the amino acids typicallypresent in canine antibodies. Methods for generating caninized antibodies are wellknown in the art. In some cases, one or more CDR residues may be changed tobetter correspond with the amino acids typically present in canine antibodies. Insome cases, one or more framework residues may be changed to better correspondwith the amino acids typically present in canine antibodies. The amino acidsequences of certain exemplary caninized VHH antibodies of the present invention are set forth in Tables G and H herein. In the caninized VHH antibodies set forth inTables G and H herein, certain framework residues have been changed to bettercorrespond with the amino acids typically present in canine antibodies. In some embodiments, a caninized anti-canine IL-31 VHH antibody of the invention may be characterized in that it comprises: (i) a framework 1 (FR1) region in which amino acid residue 1 thereof is (orhas been changed to) a Q (Gln) or a D (Asp), and / or amino acid residue 12 thereofis (or has been changed to) a V (Val), and / or residue 13 thereof is (or has beenchanged to) a K (Lys), and / or residue 14 thereof is (or has been changed to) a P(Pro), and / or residue 23 thereof is (or has been changed to) a V (Val); and / or(ii) a framework 2 (FR2) region in which amino acid residue 11 thereof is (orhas been changed to) a G (Gly), and / or amino acid residue 12 thereof is (or hasbeen changed to) a L (Leu), and / or residue 13 thereof is (or has been changed to) aQ (Gln) or E (Glu); and / or(iii) a framework 3 (FR3) region in which amino acid residue 5 thereof is (orhas been changed to) an A (Ala), and / or amino acid residue 8 thereof is (or hasbeen changed to) a G (Gly), and / or residue 22 thereof is (or has been changed to) aY (Tyr), and / or residue 29 thereof is (or has been changed to) a R (Arg), and / orresidue 36 thereof is (or has been changed to) a Y (Tyr); and / or(iv) a framework 4 (FR4) region in which amino acid residue 3 thereof is (or hasbeen changed to) a Q (Gln), and / or amino acid residue 6 thereof is (or has beenchanged to) a L (Leu), and / or residue 9 thereof is (or has been changed to) a V(Val). In some cases there may be an A (Ala) residue as the final residue in FR4(e.g. at position 12), but in other cases this (additional) A may be not be present(e.g. in some cases the FR4 may be 11 amino acids in length). In one aspect, the present invention provides a caninized version of an VHH antibody of the present invention. The term "complementarity determining region" ("CDR") as used hereinrefers to a region of hypervariability within an antibody chain variable region (orvariable domain) of an antibody molecule. The term "heavy chain complementarity determining region" ("heavy chainCDR" or “VH CDR”) as used herein refers to regions of hypervariability within theheavy chain variable region of an antibody molecule or within a VHH antibodymolecule or VHH domain. The heavy chain variable region has three CDRs termedheavy chain CDR1, heavy chain CDR2 and heavy chain CDR3 from the amino terminus to carboxy terminus. The heavy chain variable region also has four framework regions (FR1, FR2, FR3 and FR4 from the amino terminus to carboxy terminus). These framework regions separate the CDRs. The term "heavy chain variable region" as used herein refers to the variable region of a heavy chain of an antibody molecule. VHH antibodies comprise a VHH domain. A VHH domain may be a considered a heavy chain variable region. As VHH antibodies comprise a VHHdomain, a CDR of a VHH antibody (i.e. of a VHH domain) may be considered orreferred to as a "heavy chain complementarity determining region" ("heavy chainCDR"). In VHH antibodies, this refers to a region of hypervariability within the VHHdomain. The VHH domain has three CDRs termed heavy chain CDR1, heavy chain CDR2 and heavy chain CDR3 from the amino terminus to carboxy terminus. Such CDRs may also be referred to herein simply as CDR1, CDR2 and CDR3. The VHHdomain also has four framework regions (FR1, FR2, FR3 and FR4 from the aminoterminus to carboxy terminus). These framework regions separate the CDRs. The term "light chain complementarity determining region" ("light chain CDR") as used herein refers to regions of hypervariability within the light chain variable region (VLdomain) of an antibody molecule. Light chain variable regions have three CDRs termed light chain CDR1, light chain CDR2 and light chain CDR3 from the amino terminus to the carboxy terminus. The light chain variable region also has four framework regions (FR1, FR2, FR3 and FR4 from the amino terminus to carboxy terminus). These framework regions separate the CDRs. The term "light chain variable region" (VL domain) as used herein refers to the variable region of a light chain of an antibody molecule. The CDRs of the VHH antibodies of the invention are preferably separatedby appropriate framework regions such as those found in naturally occurring antibodies and / or effective engineered antibodies. Thus, individual CDR sequences are preferably provided within or incorporated into an appropriate framework or scaffold to enable antigen binding. Such framework sequences or regions may correspond to naturally occurring framework regions, FR1, FR2, FR3 and / or FR4, as appropriate to form an appropriate scaffold, or may correspond to consensus framework regions, for example identified by comparing various naturally occurring framework regions. Alternatively, non-antibody scaffolds or frameworks, e.g. T cellreceptor frameworks can be used. Appropriate sequences that can be used forframework regions are well known and documented in the art and any of these may be used. In particular, framework regions that allow the maintenance of antigen specificity, for example framework regions that result in substantially the same or the same 3D structure of the antibody. CDR sequences of certain VHH antibodies of the invention are set forth herein in Tables A to D, G and H. These CDR sequences are identified using the IMGT numbering scheme (e.g. Lefranc, M.-P., The Immunologist, 7, 132-136(1999); www.imgt.org)). In some other embodiments, CDR sequences of (or fromor from within) a VHH domain may be CDR sequences as identified using anysuitable method (or tool), for example as identified according to the well-known methods of Kabat (e.g. Kabat, et al., "Sequences of Proteins of Immunological Interest", 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD, 647-669, 1991) or Chothia (e.g. Chothia C, et al. (1989) Nature, 342:877–883, or Al-Lazikani et al., (1997) JMB 273,927-948).The VHH antibodies of the invention can be produced naturally or can bewholly or partially synthetically produced. Thus, the VHH antibody may be from anyappropriate source, for example recombinant sources and / or produced in transgenic animals or transgenic plants, or using a microbial (e.g. bacterial) expression system or a mammalian cell expression system. Thus, the VHH antibody molecules (orconstructs or polypeptides) can be produced in vitro or in vivo.In some aspects of the present invention, one or more VHH antibody of thepresent invention may be present in a construct. Such a construct may compriseone or more additional components (or one or more additional elements), i.e. inaddition to one or more VHH antibody of the present invention. Thus, in one aspect, the present invention provides a construct comprising at least one VHH antibody of the present invention. In some embodiments, the present invention provides a construct comprising at least two VHH antibodies of the present invention (e.g. at least 2, at least 3, at least 4 or at least 5). In some embodiments, the present invention provides a construct in whichthere is one (only one), or two (only two), or three (only 3), or four (only 4), or five(only 5) VHH antibodies of the present invention.Typically and preferably, constructs of the invention are polypeptides (polypeptide constructs). Thus, typically and preferably, all of the components ofthe construct are on (or present on) the same (single) polypeptide chain. Thus, theconstruct may be a single polypeptide chain construct. In embodiments in which the construct comprises more than one VHH antibody (e.g.2, 3, 4, 5 or more VHH antibodies), preferably all of the VHH antibodies are on the same (single)polypeptide chain. Such polypeptides may be referred to as fusion polypeptides (or fusion proteins or single polypeptide chain constructs). This may be considered a“beads on a string” type arrangement.In embodiments of constructs of the invention in which the construct comprises more than one component, for example more than one VHH antibody,the individual components (e.g. individual VHH antibodies) are typically linked (orlinked together or connected) by appropriate linkers. Such linkers are typicallyamino acid (or peptide) linkers (i.e. comprise or consist of amino acids), e.g. non-native peptide or artificial linkers. In some embodiments, an amino acid (or peptide)linker may be 1-50, 1-25, 1-20, 1-15, 1-10, 1-5, 5-50, 5-25, 5-20, 5-15, 5-10, 10-50,10-25, 10-20, 10-15, 20-50 or 20-25 amino acids in length. In some embodiments,an amino acid (or peptide) linker may be at least 5, or at least 10, or at least 15, orat least 20, or at least 25 amino acids in length. In some embodiments, an aminoacid (or peptide) linker may be up to 10, up to 15, up to 20, up to 25 amino acids, orup to 50 amino acids in length. In some embodiments, an amino acid (or peptide)linker may be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20amino acids in length. In some embodiments, the linker may comprise (or consistof) the amino acid sequence GGGGS (SEQ ID NO:51). Thus, the linker may be a(GGGGS)n linker, wherein “n” is, for example, 1 to 5 (e.g. 1, 2, 3, 4 or 5, preferably 2or 3). In some embodiments, the linker may comprise (or consist of) the amino acidsequence GGGS (SEQ ID NO:55). Thus, the linker may be a (GGGS)n linker, wherein “n” is, for example, 1 to 5 (e.g.1, 2, 3, 4 or 5, preferably 3). Typically and preferably of course, the various (individual) components of the construct (e.g. thevarious (individual) VHH antibodies present in the construct) are linked (orconnected) together using appropriate techniques, e.g. spacing, such that eachcomponent can exert its respective effect.In some embodiments, the construct (e.g. polypeptide construct or singlepolypeptide chain construct) comprises one (only one) VHH antibody in accordance with the present invention. Thus, in some constructs of the present invention there is only one VHH antibody of the present invention. However, as described elsewhere herein, such constructs may comprise one more additional components, for example one or more additional therapeutic agents (which may be a VHHantibody that binds to a protein (or antigen) other than IL-31) and / or one or moreserum half-life extending moieties. Thus, in some embodiments, the present invention provides a construct comprising a single (only a single or only one) VHH antibody of the present invention and one or more additional components (e.g. oneor more VHH antibodies that bind to a protein (or antigen) other than IL-31). Typically and preferably, all of the components of the construct are on (or present on) the same (single) polypeptide chain, preferably with an appropriate linker(s)linking (or connecting) the various components of the construction. The linkers maybe as described elsewhere herein. In some embodiments, the construct (e.g. polypeptide construct or singlepolypeptide chain construct) comprises more than one VHH antibody in accordance with the present invention (e.g.2, 3, 4 or 5, preferably 2). Thus, in some constructs of the present invention there is more than one VHH antibody of the present invention. As described elsewhere herein, such constructs may comprise one moreadditional components (other than a VHH of the present invention), for example oneor more additional therapeutic agents (which may be a VHH antibody that binds to a protein (or antigen) other than IL-31) and / or one or more serum half-life extending moieties. Thus, in some embodiments, the present invention provides a constructcomprising more than one VHH antibody of the present invention and one or moreadditional components (e.g. one or more VHH antibodies that bind to a protein (orantigen) other than IL-31). Typically and preferably, all of the components of theconstruct are on (or present on) the same (single) polypeptide chain, preferably withan appropriate linker(s) linking (or connecting) the various components of theconstruction. The linkers may be as described elsewhere herein. In some embodiments in which a construct of the invention (e.g. polypeptideconstruct or single polypeptide chain construct) comprises more than one (e.g. 2, 3,4 or 5, preferably 2) VHH antibody in accordance with the present invention, the VHH antibodies of the present invention in the construct may be the same (i.e. havethe same sequence), or may be different (i.e. have different sequences), i.e. may bedifferent from each other. In some embodiments in which a construct (e.g. polypeptide construct orsingle polypeptide chain construct) of the invention comprises more than one (e.g. 2, 3, 4 or 5, preferably 2) VHH antibody in accordance with the present invention, each of the VHH antibodies of the present invention in the construct may be the same (i.e. have the same VHH antibody sequence). Typically and preferably, all of the components of the construct are on (or present on) the same (single) polypeptide chain, preferably with an appropriate linker(s) linking (or connecting) the various components of the construct. The linkers may be as described elsewhere herein.In some embodiments in which a construct (e.g. polypeptide construct orsingle polypeptide chain construct) of the invention comprises more than one (e.g.2, 3, 4 or 5, preferably 2) VHH antibody in accordance with the present invention,each of the VHH antibodies of the present invention in the construct may bedifferent (i.e. have different VHH antibody sequences), i.e. may be different fromeach other. In some embodiments in which a construct (e.g. polypeptide construct or single polypeptide chain construct) of the invention comprises more than one(e.g. 2, 3, 4 or 5, preferably 2) VHH antibody in accordance with the presentinvention, at least two of the VHH antibodies of the present invention in theconstruct may be different (i.e. have different VHH antibody sequences), i.e. may bedifferent from each other. Typically and preferably, all of the components of the construct are on (or present on) the same (single) polypeptide chain, preferably with an appropriate linker(s) linking (or connecting) the various components of the construct. The linkers may be as described elsewhere herein. In some embodiments in which a construct (e.g. polypeptide construct orsingle polypeptide chain construct) of the invention comprises more than one (e.g.2, 3, 4 or 5, preferably 2) VHH antibody in accordance with the present invention,each of the VHH antibodies of the present invention in the construct binds to adifferent epitope on canine IL-31 (i.e. each individual VHH antibody of the present invention in the construct binds to a different epitope on canine IL-31). In someembodiments in which a construct (e.g. polypeptide construct or single polypeptidechain construct) of the invention comprises more than one (e.g.2, 3, 4 or 5,preferably 2) VHH antibody in accordance with the present invention, at least two ofthe VHH antibodies of the present invention in the construct bind to differentepitopes on canine IL-31 (i.e. at least two individual VHH antibodies in the constructbind to different epitopes on canine IL-31).In some embodiments in which there are two (only two) VHH antibodies ofthe present invention in the construct, preferably each of said VHH antibodies of theinvention in the construct binds to a different epitope on canine IL-31 (i.e. eachindividual VHH antibody in the construct binds to a different epitope on canine IL-31). In some embodiments in which there are more than two VHH antibodies ofthe present invention in the construct, preferably two or more of said VHHantibodies of the invention in the construct bind to a different epitope on canine IL-31 (i.e. two or more of the individual VHH antibodies in the construct bind todifferent epitopes on canine IL-31). Methods of determining (or assessing whether or not different VHHs bind todifferent epitopes on canine IL-31 may be determined by any suitable means, andthe skilled person is familiar with appropriate means of determining this (e.g. by epitope mapping, by epitope binning (e.g. SPR-based epitope binning for example as described in the Example section herein), or by a competition assay (e.g. a competition ELISA). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody comprising a VHHdomain comprising three CDRs, wherein said VHH domain comprises a CDR1 thathas the amino acid sequence of SEQ ID NO:4 or a sequence substantially homologous thereto, a CDR2 that has the amino acid sequence of SEQ ID NO:5 or a sequence substantially homologous thereto and a CDR3 that has the amino acidsequence of SEQ ID NO:6 or a sequence substantially homologous thereto and (ii)at least one (e.g.1 or only 1) VHH antibody comprising a VHH domain comprisingthree CDRs, wherein said VHH domain comprises a CDR1 that has the amino acidsequence of SEQ ID NO:12 or a sequence substantially homologous thereto, aCDR2 that has the amino acid sequence of SEQ ID NO:13 or a sequencesubstantially homologous thereto and a CDR3 that has the amino acid sequence ofSEQ ID NO:14 or a sequence substantially homologous thereto. Substantiallyhomologous sequences are discussed elsewhere herein (e.g. a substantiallyhomologous sequence may be a sequence containing 1, 2 or 3 amino acid substitutions compared to the given CDR sequence). Typically, there is a linker between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii).Linkers may be as discussed elsewhere herein (e.g. the linker may have thesequence of SEQ ID NO:56). A (or the) VHH antibody of (i) and a (or the) VHHantibody of (ii) may be positioned in the construct in any order with respect to eachother, e.g. a (or the) VHH antibody of (i) may be positioned N-terminally with respectto a (or the) VHH antibody of (ii), or vice versa. However, in some preferredembodiments, a (or the) VHH antibody of (i) is positioned in the construct N-terminally with respect to a (or the) VHH antibody of (ii). The construct described inthis paragraph is based on the construct (or bivalent construct) that is referred toherein as “33-40” (that has the amino acid sequence of SEQ ID NO:47). The “33-40”construct (also referred to herein as VHH33-40) is a bivalent construct that has one VHH33 antibody of the invention linked (via a (GGGS)3 linker) to one VHH40 antibody of the invention. In the “33-40” construct, the VHH33 antibody is positioned N-terminally with respect to the VHH40 antibody. The VHH33 and VHH40 antibodies each bind to different epitopes on canine IL-31. In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody comprising a VHHdomain, wherein said VHH domain has the amino acid sequence of SEQ ID NO:3 ora sequence substantially homologous thereto and (ii) at least one (e.g. 1 or only 1)VHH antibody comprising a VHH domain, wherein said VHH domain has the amino acid sequence of SEQ ID NO:11 or a sequence substantially homologous thereto. Substantially homologous sequences are discussed elsewhere herein (e.g. a substantially homologous sequence may be a sequence having at least 80% sequence identity to the given VHH domain sequence). Typically, there is a linker between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii).Linkers may be as discussed elsewhere herein (e.g. the linker may have thesequence of SEQ ID NO:56). A (or the) VHH antibody of (i) and a VHH antibody of (ii) may be positioned in the construct in any order with respect to each other, e.g. a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the)VHH antibody of (ii), or vice versa. However, in some preferred embodiments, a (orthe) VHH antibody of (i) is positioned in the construct N-terminally with respect to a(or the) VHH antibody of (ii). The construct described in this paragraph is based onthe construct (or bivalent construct) that is referred to herein as “33-40”. In some embodiments, the present invention provides a construct (e.g. apolypeptide construct or a single chain polypeptide construct or a fusion protein) comprising the amino acid sequence of SEQ ID NO:47, or a sequence substantiallyhomologous thereto (e.g. a sequence having at least 80% sequence identitythereto). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprising the amino acid sequence of SEQ ID NO:47. Certain aspects and embodiments of (e.g. constructs of) the present invention herein refer to SEQ ID NO:3 or VHH33. In some alternativeembodiments, a caninized version (or caninized derivative) of SEQ ID NO:3 or ofVHH33 is used (or is present) or is referred to instead of SEQ ID NO:3 or VHH33 itself (i.e. instead of the (original) non-caninized version). Thus, the present invention also provides aspects and embodiments that are equivalent to aspects and embodiments of (e.g. constructs of) the present invention herein that refer to SEQ ID NO:3 or VHH33, with the exception that a caninized version (or caninized derivative) of SEQ ID NO:3 or of VHH33, or a sequence substantially homologous thereto, is used (or is present) or referred to instead of SEQ ID NO:3 or VHH33 itself. Certain aspects and embodiments of (e.g. constructs of) the present invention herein refer to SEQ ID NO:11 or VHH40. In some alternative embodiments, a caninized version (or caninized derivative) of SEQ ID NO:11 or of VHH40 is used (or is present) or referred to instead of SEQ ID NO:11 or VHH40 itself (i.e. instead of the (original) non-caninized version). Thus, the present invention also provides aspects and embodiments that are equivalent to aspects and embodiments of (e.g. constructs of) the present invention herein that refer to SEQ ID NO:11 or VHH40, with the exception that a caninized version (or caninized derivative) of SEQ ID NO:11 or of VHH40, or a sequence substantially homologous thereto, is used (or is present) or referred to instead of SEQ ID NO:11 or VHH40 itself. Certain aspects and embodiments of (e.g. constructs of) the present invention herein refer to SEQ ID NO:3 (or VHH33) and also refer to SEQ ID NO:11 (or VHH40). In some alternative embodiments, a caninized version (or caninized derivative) of SEQ ID NO:3 (or of VHH33) and a caninized version of SEQ ID NO:11 (or of SEQ ID NO:19) is used (or is present) or referred to instead of SEQ ID NO:3(or VHH33) and SEQ ID NO:11 (or VHH40) themselves (i.e. instead of the (original)non-caninized versions). Thus, the present invention also provides aspects and embodiments that are equivalent to aspects and embodiments of (e.g. constructs of) the present invention herein that refer to SEQ ID NO:3 (or VHH33) and SEQ IDNO:11 (or VHH40), with the exception that caninized versions (or caninizedderivatives) of SEQ ID NO:3 (or of VHH40) and SEQ ID NO:11 (or of VHH40), orsequences substantially homologous thereto, are used (or are present) or referredto instead of SEQ ID NO:3 (or VHH33) and SEQ ID NO:11 (VHH40) themselves.In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody that binds to the sameepitope (or substantially the same epitope) on canine IL-31 as is bound by a VHHantibody comprising a VHH domain that has the amino acid sequence of SEQ IDNO:3 and (ii) at least one (e.g.1 or only 1) VHH antibody that binds to the sameepitope (or substantially the same epitope) on canine IL-31 as is bound by a VHHantibody comprising a VHH domain that has the amino acid sequence of SEQ IDNO:11. Typically, there is a linker between (positioned between) the VHH antibodyof (i) and the VHH antibody of (ii). Linkers may be as discussed elsewhere herein. A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) may be positioned in the construct in any order with respect to each other, e.g. a (or the) VHH antibodyof (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii),or vice versa. However, in some preferred embodiments, a (or the) VHH antibody of (i) is positioned in the construct N-terminally with respect to a (or the) VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody comprising a VHHdomain comprising three CDRs, wherein said VHH domain comprises a CDR1 thathas the amino acid sequence of SEQ ID NO:28 or a sequence substantiallyhomologous thereto, a CDR2 that has the amino acid sequence of SEQ ID NO:29 or a sequence substantially homologous thereto and a CDR3 that has the aminoacid sequence of SEQ ID NO:30 or a sequence substantially homologous theretoand (ii) at least one (e.g.1 or only 1) VHH antibody comprising a VHH domaincomprising three CDRs, wherein said VHH domain comprises a CDR1 that has theamino acid sequence of SEQ ID NO:20 or a sequence substantially homologousthereto, a CDR2 that has the amino acid sequence of SEQ ID NO:21 or a sequencesubstantially homologous thereto and a CDR3 that has the amino acid sequence ofSEQ ID NO:22 or a sequence substantially homologous thereto. Substantiallyhomologous sequences are discussed elsewhere herein (e.g. a substantially homologous sequence may be a sequence containing 1, 2 or 3 amino acid substitutions compared to the given CDR sequence). Typically, there is a linker between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii).Linkers may be as discussed elsewhere herein (e.g. the linker may have thesequence of SEQ ID NO:54). A (or the) VHH antibody of (i) and a VHH antibody of (ii) may be positioned in the construct in any order with respect to each other, e.g. a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), or vice versa. However, in some preferred embodiments, a (or the) VHH antibody of (i) is positioned in the construct N-terminally with respect to a(or the) VHH antibody of (ii). The construct described in this paragraph is based onthe construct (or bivalent construct) that is referred to herein as “108-94” (that hasthe amino acid sequence of SEQ ID NO:48). The “108-94” construct (also referredto herein as VHH108-94) is a bivalent construct that has one VHH108’ antibody ofthe invention linked (via a (GGGGS)3 linker) to one VHH94’ antibody of theinvention. In the “108-94” construct, the VHH108’ antibody is positioned N-terminally with respect to the VHH94’ antibody. The VHH108 and VHH94antibodies each bind to different epitopes on canine IL-31. In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody comprising a VHHdomain, wherein said VHH domain has the amino acid sequence of SEQ ID NO:58 or a sequence substantially homologous thereto and (ii) at least one (e.g.1) VHH antibody comprising a VHH domain, wherein said VHH domain has the amino acid sequence of SEQ ID NO:57 or a sequence substantially homologous thereto.Substantially homologous sequences are discussed elsewhere herein (e.g. asubstantially homologous sequence may be a sequence having at least 80% sequence identity to the given VHH domain sequence). Typically, there is a linker between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii). Linkers may be as discussed elsewhere herein (e.g. the linker may have the sequence of SEQ ID NO:54). A (or the) VHH antibody of (i) and a VHH antibody of (ii) may be positioned in the construct in any order with respect to each other, e.g. a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), or vice versa. However, in some preferred embodiments, a (or the) VHH antibody of (i) is positioned in the construct N-terminally with respect to a (or the) VHH antibody of (ii). The construct described in this paragraph is based on the construct (or bivalent construct) that is referred to herein as “108-94”. Certain aspects and embodiments of (e.g. constructs of) the present invention herein refer to SEQ ID NO:58 or VHH108’. In some alternative embodiments, a caninized version (or caninized derivative) of SEQ ID NO:58 or of VHH108’ is used (or is present) or referred to instead of SEQ ID NO:58 or VHH108’ itself (i.e. instead of the (original) non-caninized version). Thus, the present invention also provides aspects and embodiments that are equivalent to aspects and embodiments of (e.g. constructs of) the present invention herein that refer to SEQ ID NO:58 or VHH108’, with the exception that a caninized version (or caninized derivative) of SEQ ID NO:58 or of VHH108’, or a sequence substantially homologous thereto, is used (or is present) or referred to instead of SEQ ID NO:58 or VHH108’ itself. A caninized version of SEQ ID NO:58 (or of VHH108’) may have the amino acid sequence of SEQ ID NO:100 (or a sequence substantially homologous thereto). Certain aspects and embodiments of (e.g. constructs of) the presentinvention herein refer to SEQ ID NO:57 or VHH94’. In some alternativeembodiments, a caninized version (or caninized derivative) of SEQ ID NO:57 or ofVHH94’ is used (or is present) or referred to instead of SEQ ID NO:57 or VHH94’itself (i.e. instead of the (original) non-caninized version). Thus, the present invention also provides aspects and embodiments that are equivalent to aspects and embodiments of (e.g. constructs of) the present invention herein that refer toSEQ ID NO:57 or VHH94’, with the exception that a caninized version (or caninizedderivative) of SEQ ID NO:57 or of VHH94’, or a sequence substantially homologousthereto, is used (or is present) or referred to instead of SEQ ID NO:57 or VHH94’itself. A caninized version of SEQ ID NO:57 (or of VHH94’) may have the amino acid sequence of SEQ ID NO:99 (or a sequence substantially homologous thereto). Certain aspects and embodiments of (e.g. constructs of) the present invention herein refer to SEQ ID NO:58 (or VHH108’) and also refer to SEQ ID NO:57 (or VHH94’). In some alternative embodiments, a caninized version (or caninized derivative) of SEQ ID NO:58 (or of VHH108’) and a caninized version of SEQ ID NO:57 (or of SEQ ID NO:94’) is used (or is present) or referred to instead of SEQ ID NO:58 (or VHH108’) and SEQ ID NO:57 (or VHH94’) themselves (i.e. instead of the non-caninized versions). Thus, the present invention also provides aspects and embodiments that are equivalent to aspects and embodiments of (e.g. constructs of) the present invention herein that refer to SEQ ID NO:58 (or VHH108’) and SEQ ID NO:57 (or VHH94’), with the exception that caninized versions (or caninized derivatives) of SEQ ID NO:58 (or of VHH108’) and SEQ ID NO:57 (or of VHH94’), or sequences substantially homologous thereto, are used (or are present) or referred to instead of SEQ ID NO:58 (or VHH108’) and SEQ ID NO:57 (VHH94’) themselves. In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody comprising a VHHdomain, wherein said VHH domain has the amino acid sequence of SEQ ID NO:27 or a sequence substantially homologous thereto and (ii) at least one (e.g.1) VHH antibody comprising a VHH domain, wherein said VHH domain has the amino acidsequence of SEQ ID NO:19 or a sequence substantially homologous thereto.Substantially homologous sequences are discussed elsewhere herein (e.g. a substantially homologous sequence may be a sequence having at least 80% sequence identity to the given VHH domain sequence). Typically, there is a linker between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii).Linkers may be as discussed elsewhere herein (e.g. the linker may have thesequence of SEQ ID NO:54). A (or the) VHH antibody of (i) and a VHH antibody of (ii) may be positioned in the construct in any order with respect to each other, e.g. a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), or vice versa. However, in some preferred embodiments, a (or the) VHH antibody of (i) is positioned in the construct N-terminally with respect to a (or the) VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprising the amino acid sequence of SEQ ID NO:48, or a sequence substantiallyhomologous thereto (e.g. a sequence having at least 80% sequence identitythereto). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprising the amino acid sequence of SEQ ID NO:48. Certain aspects and embodiments of (e.g. constructs of) the present invention herein refer to SEQ ID NO:27 or VHH108. In some alternative embodiments, a caninized version (or caninized derivative) of SEQ ID NO:27 or of VHH108 is used (or is present) or referred to instead of SEQ ID NO:27 or VHH108itself (i.e. instead of the (original) non-caninized version). Thus, the presentinvention also provides aspects and embodiments that are equivalent to aspects and embodiments of (e.g. constructs of) the present invention herein that refer to SEQ ID NO:27 or VHH108, with the exception that a caninized version (or caninized derivative) of SEQ ID NO:27 or of VHH108, or a sequence substantially homologous thereto, is used (or is present) or referred to instead of SEQ ID NO:27 or VHH108 itself. A caninized version of SEQ ID NO:27 (or of VHH108) may havethe amino acid sequence of SEQ ID NO:82 (or a sequence substantiallyhomologous thereto). Certain aspects and embodiments of (e.g. constructs of) the present invention herein refer to SEQ ID NO:19 or VHH94. In some alternative embodiments, a caninized version (or caninized derivative) of SEQ ID NO:19 or of VHH94 is used (or is present) or referred to instead of SEQ ID NO:19 or VHH94 itself (i.e. instead of the (original) non-caninized version). Thus, the present invention also provides aspects and embodiments that are equivalent to aspects and embodiments of (e.g. constructs of) the present invention herein that refer to SEQ ID NO:19 or VHH94, with the exception that a caninized version (or caninized derivative) of SEQ ID NO:19 or of VHH94, or a sequence substantially homologous thereto, is used (or is present) or referred to instead of SEQ ID NO:19 or VHH94 itself. A caninized version of SEQ ID NO:19 (or of VHH94) may have the aminoacid sequence of SEQ ID NO:74 (or a sequence substantially homologous thereto).Certain aspects and embodiments of (e.g. constructs of) the presentinvention herein refer to SEQ ID NO:27 (or VHH108) and also refer to SEQ IDNO:19 (or VHH94). In some alternative embodiments, a caninized version (orcaninized derivative) of SEQ ID NO:27 (or of VHH108) and a caninized version ofSEQ ID NO:19 (or VHH94) is used (or is present) or referred to instead of SEQ IDNO:27 (or VHH108) and SEQ ID NO:19 (or VHH94) themselves (i.e. instead of thenon-caninized versions). Thus, the present invention also provides aspects and embodiments that are equivalent to aspects and embodiments of (e.g. constructs of)the present invention herein that refer to SEQ ID NO:27 (or VHH108) and SEQ IDNO:19 (or VHH94), with the exception that caninized versions (or caninizedderivatives) of SEQ ID NO:27 (or of VHH108) and SEQ ID NO:19 (or of VHH94), orsequences substantially homologous thereto, are used (or are present) or referredto instead of SEQ ID NO:27 (or VHH108) and SEQ ID NO:19 (VHH94) themselves.A caninized version of SEQ ID NO:27 (or of VHH108) may have the amino acidsequence of SEQ ID NO:82 (or a sequence substantially homologous thereto), and a caninized version of SEQ ID NO:19 (or of VHH94) may have the amino acid sequence of SEQ ID NO:74 (or a sequence substantially homologous thereto). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody comprising a VHHdomain, wherein said VHH domain has the amino acid sequence of SEQ ID NO:82 or a sequence substantially homologous thereto and (ii) at least one (e.g.1) VHH antibody comprising a VHH domain, wherein said VHH domain has the amino acid sequence of SEQ ID NO:74 or a sequence substantially homologous thereto. Substantially homologous sequences are discussed elsewhere herein (e.g. a substantially homologous sequence may be a sequence having at least 80%sequence identity to the given VHH domain sequence). A (or the) VHH antibody of(i) and a VHH antibody of (ii) may be positioned in the construct in any order with respect to each other, e.g. a (or the) VHH antibody of (i) may be positioned N- terminally with respect to a (or the) VHH antibody of (ii), or vice versa. However, in some preferred embodiments, a (or the) VHH antibody of (i) is positioned in the construct N-terminally with respect to a (or the) VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody that binds to the sameepitope (or substantially the same epitope) on canine IL-31 as is bound by a VHHantibody comprising a VHH domain that has the amino acid sequence of SEQ IDNO:27 and (ii) at least one (e.g. 1 or only 1) VHH antibody that binds to the sameepitope (or substantially the same epitope) on canine IL-31 as is bound by a VHHantibody comprising a VHH domain that has the amino acid sequence of SEQ IDNO:19. Typically, there is a linker between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii). Linkers may be as discussed elsewhere herein. A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) may be positioned in the construct in any order with respect to each other, e.g. a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), or vice versa. However, in some preferred embodiments, a (or the) VHH antibody of (i) is positioned in the construct N-terminally with respect to a (or the) VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody that binds to the sameepitope (or substantially the same epitope) on canine IL-31 as is bound by a VHHantibody comprising a VHH domain that has the amino acid sequence of SEQ IDNO:58 and (ii) at least one (e.g. 1 or only 1) VHH antibody that binds to the sameepitope (or substantially the same epitope) on canine IL-31 as is bound by a VHHantibody comprising a VHH domain that has the amino acid sequence of SEQ IDNO:57. Typically, there is a linker between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii). Linkers may be as discussed elsewhere herein. A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) may be positioned in the construct in any order with respect to each other, e.g. a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), or vice versa. However, in some preferred embodiments, a (or the) VHH antibody of (i) is positioned in the construct N-terminally with respect to a (or the) VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody that binds to the sameepitope (or substantially the same epitope) on canine IL-31 as is bound by a VHHantibody comprising a VHH domain that has the amino acid sequence of SEQ IDNO:82 and (ii) at least one (e.g. 1 or only 1) VHH antibody that binds to the sameepitope (or substantially the same epitope) on canine IL-31 as is bound by a VHHantibody comprising a VHH domain that has the amino acid sequence of SEQ IDNO:74. A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) may be positioned in the construct in any order with respect to each other, e.g. a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), or vice versa. However, in some preferred embodiments, a (or the) VHH antibody of (i) is positioned in the construct N-terminally with respect to a (or the) VHH antibody of (ii). In some embodiments, constructs (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) of the present invention comprise at least one (e.g.1, 2, 3, 4 or 5, preferably 2) VHH antibody in accordance with the present invention and at least one additional component (or additional agent (e.g. additional therapeutic agent) or additional moiety) that is not a VHH antibody in accordance with the present invention. Thus, in some embodiments, a construct of the present invention further comprises at least one additional component (or additional agent (e.g. additional therapeutic agent) or additional moiety) that is not aVHH antibody in accordance with the present invention. The additional componentis typically composed of amino acids (i.e. is itself a protein or polypeptide) and,typically and preferably, is in the same (single) polypeptide chain as the at least oneVHH antibody of the invention. Thus, in some embodiments, the construct is a single polypeptide chain that comprises at least one VHH antibody (or VHH antibody sequence) of the present invention and at least one additional component.Typically, in constructs of the invention, the at least one additional component isconnected to (or linked to) at least one VHH antibody of the present invention by a linker (e.g. a linker as described elsewhere herein). In constructs of the invention that further comprise one or more additional components (e.g. one or more VHH antibody that binds to a protein (or antigen) other than IL-31, e.g. as described elsewhere herein), the additional component(s) may be positioned anywhere within construct. Of course, the positioning of the additional component in the construct should preferably be such that activity (e.g. binding ability) of the at least one VHH antibody of the invention and activity of the at least one additional component are maintained (or substantially maintained). Insome embodiments, a (or the) additional component may be positioned N-terminallywith respect to a (or the) VHH antibody of the invention in the construct, or may bepositioned N-terminally with respect the N-terminal-most VHH antibody of the invention in the construct. In some embodiments, a (or the) additional component may be positioned C-terminally with respect to a (or the) VHH antibody of the invention in the construct, or may be positioned C-terminally with respect the C- terminal-most VHH antibody of the invention in the construct. In some embodiments, in constructs comprising more than one (e.g.2, 3, 4 or 5) VHH antibody of the invention, a (or the) additional component may be positioned in theconstruct between two VHH antibodies of the invention.In some embodiments, an (or the) additional component is a VHH antibody that binds to a protein (or antigen) other than IL-31. Thus, in some preferred embodiments, constructs (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) of the present invention comprise at least one (e.g.1, 2, 3, 4 or 5, preferably 2) VHH antibody in accordance with the present inventionand at least one (e.g.1, 2 or 3) VHH antibody that binds to a protein (or antigen)other than IL-31. Thus, in some embodiments, the construct is a single polypeptide chain that comprises at least one VHH antibody (or VHH antibody sequence) of the present invention and at least one VHH antibody that binds to a protein (or antigen) other than IL-31. Typically, in constructs of the invention, the at least one VHHantibody that binds to a protein (or antigen) other than IL-31 is connected to (orlinked to) at least one VHH antibody of the present invention by a linker (e.g. a linkeras described elsewhere herein). Positioning of the at least one VHH antibody thatbinds to a protein (or antigen) other than IL-31 within the construct may be asdescribed elsewhere herein in connection with other embodiments. In someembodiments, the protein (or antigen) other than IL-31 is albumin, preferably caninealbumin (or canine serum albumin). An exemplary amino acid sequence of caninealbumin is set forth herein as SEQ ID NO:59. Canine albumin may also be referred to herein as caAlbumin. In some embodiments, an (or the) additional component is a serum half-life extending moiety (or agent). Thus, in some preferred embodiments, constructs (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) of the present invention comprise at least one (e.g.1, 2, 3, 4 or 5, preferably 2) VHH antibody in accordance with the present invention and at leastone (e.g.1, 2 or 3, preferably 1) serum half-life extending moiety (or agent). Thus,in some embodiments, the construct is a single polypeptide chain that comprises at least one VHH antibody (or VHH antibody sequence) of the present invention and at least one serum half-life extending moiety (or agent). Typically, in constructs of the invention, the at least one serum half-life extending moiety (or agent) is connected to (or linked to) at least one VHH antibody of the present invention by a linker (e.g. a linker as described elsewhere herein). Positioning of the serum half-life extending moiety (or agent) within the construct may be as described elsewhere herein in connection with other embodiments. A serum half-life extending moiety is a moiety (or agent or component) thatconfers upon the construct an extended (or longer) half-life in the circulation of asubject (e.g. in blood). More specifically, a serum half-life extending moiety is amoiety (or agent or component) that confers upon the construct a half-life in the circulation (e.g. in blood) that is longer than (i.e. extended in comparison to) an equivalent (or corresponding) construct that does not contain the serum half-life extending moiety. In accordance with the present invention, a serum half-life extending moiety is preferably a moiety (or agent or component) that confers upon the construct an extended (or longer) half-life in the circulation (e.g. in blood) of canines (or dogs). Using a half-life serum half-life extending moiety may mean that fewer and / or lower doses of a construct to a subject are required. In some embodiments, the serum half-life extending moiety is a moiety (oragent or component) that binds to albumin (preferably canine albumin). In preferredembodiments, the serum half-life extending moiety is a moiety (or agent or component) that binds to canine albumin. Preferably, the serum half-life extending moiety is a moiety (or agent or component) that binds to albumin (preferably canine albumin) at neutral pH (e.g. pH7.4; plasma / circulatory pH) and also at endosomalpH (e.g. pH5.5 or pH6.0).Preferably, the serum half-life extending moiety is a VHH antibody that bindsto albumin (preferably canine albumin). Preferably, the serum half-life extendingmoiety is VHH antibody that binds to albumin (preferably canine albumin) at neutralpH (e.g. pH7.4; plasma / circulatory pH) and also at endosomal pH (e.g. pH5.5 orpH6.0). An exemplary, and preferred, VHH antibody has amino acid sequences as set forth in Table E or in Table I herein, or has amino acid sequences substantiallyhomologous thereto. The VHH antibody that binds to albumin with sequences setforth in Table E may be referred to as “A8” or “VHHA8”. The VHH antibody thatbinds to albumin with sequences set forth in Table I is a caninized version of A8. The VHH antibody A8 binds to canine albumin at pH7.4 and at pH5.5 and at pH6.0 (e.g. as determined by Surface Plasmon Resonance (e.g. as described elsewhere herein), e.g. at 25oC). Pharmacokinetic studies in dogs have shown that the VHH antibody A8 has a significantly longer half-life in dogs than an irrelevant VHH antibody (a non-albumin binding VHH antibody). Thus, in some embodiments, the VHH antibody which binds to canine albumin comprises a VHH domain comprising three CDRs, wherein said VHHdomain comprises a CDR1 that has the amino acid sequence of SEQ ID NO:40 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:41 or a sequence substantially homologous thereto and aCDR3 that has the amino acid sequence of SEQ ID NO:42 or a sequencesubstantially homologous thereto. Substantially homologous sequences are described herein (e.g. a substantially homologous sequence may be a sequence containing 1, 2 or 3 amino acid substitutions compared to the given CDR sequence). In some embodiments, the VHH antibody which binds to canine albumin comprises a VHH domain comprising three CDRs, wherein said VHH domaincomprises a CDR1 that has the amino acid sequence of SEQ ID NO:40, a CDR2that has the amino acid sequence of SEQ ID NO:41 and a CDR3 that has the amino acid sequence of SEQ ID NO:42. In some embodiments, the VHH antibody which binds to canine albumin comprises (or consists of) a VHH domain having an amino acid sequence of SEQID NO:39 or a sequence substantially homologous thereto. Substantiallyhomologous sequences are described herein (e.g. a substantially homologous sequence may be a sequence having at least 80% sequence identity thereto). In some embodiments, the VHH antibody which binds to canine albumin comprises (or consists of) a VHH domain having an amino acid sequence of SEQ ID NO:39. In some embodiments, the VHH antibody which binds to canine albumin is acaninized version of the VHH antibody A8 described herein (e.g. having one ormore caninized CDR sequences and / or one or more caninized FR regions). In some embodiments, a caninized anti-canine albumin VHH antibody of the invention may be characterized in that it comprises: (i) a framework 1 (FR1) region in which amino acid residue 13 thereof is (orhas been changed to) a K (Lys), and / or residue 23 thereof is (or has been changedto) a V (Val); and / or(ii) a framework 2 (FR2) region in which amino acid residue 11 thereof is (orhas been changed to) a G (Gly); and / or(iii) a framework 3 (FR3) region in which amino acid residue 5 thereof is (orhas been changed to) an A (Ala), and / or residue 21 thereof is (or has been changedto) a L (Leu). In some embodiments, the VHH antibody which binds to canine albumin comprises (or consists of) a VHH domain having an amino acid sequence of SEQID NO:90 or a sequence substantially homologous thereto. Substantiallyhomologous sequences are described herein (e.g. a substantially homologous sequence may be a sequence having at least 80% sequence identity thereto). In some embodiments, the VHH antibody which binds to canine albumin comprises (or consists of) a VHH domain having an amino acid sequence of SEQ ID NO:90. Certain aspects and embodiments of (e.g. constructs of) the presentinvention herein refer to SEQ ID NO:39 or VHHA8. In some alternativeembodiments, a caninized version (or caninized derivative) of SEQ ID NO:39 or ofVHHA8 is used (or is present) or referred to instead of SEQ ID NO:39 or VHHA8itself (i.e. instead of the (original) non-caninized version). Thus, the present invention also provides aspects and embodiments that are equivalent to aspects and embodiments of (e.g. constructs of) the present invention herein that refer toSEQ ID NO:39 or VHHA8, with the exception that a caninized version (or caninizedderivative) of SEQ ID NO:39 or of VHHA8, or a sequence substantially homologousthereto, is used (or is present) or referred to instead of SEQ ID NO:39 or VHHA8itself. A caninized version of SEQ ID NO:39 (or of VHHA8) may have the aminoacid sequence of SEQ ID NO:90 (or a sequence substantially homologous thereto).Although the VHH antibody A8 (and substantially homologous VHHantibodies and caninized versions) may be a preferred VHH antibody that binds tocanine albumin, other (alternative) VHH antibodies that bind to albumin (preferablycanine albumin) may be used. A skilled person could generate alternative albumin(preferably canine albumin) binding VHH antibodies, e.g. by immunizing a camelid(e.g. a llama) with albumin (preferably canine albumin) and subsequently derivingan albumin binding (preferably a canine albumin binding) VHH antibody therefrom. Positioning of a VHH antibody which binds to canine albumin within constructs of the may be as described elsewhere herein in connection with other embodiments. Without wishing to be bound by theory, the inclusion of a VHH antibody (orother agent) that binds to albumin in constructs of the invention is advantageous, asdescribed here. An anti-albumin VHH antibody for inclusion in a construct of the present invention typically binds to albumin at a neutral pH (e.g. pH7.4; plasma / circulatory pH) and also at endosomal pH (e.g. pH5.5 or pH6.0). The ability of anti-albumin VHH antibodies to bind to albumin at a neutral pH (e.g. pH7.4; plasma / circulatory pH) and also at endosomal pH (e.g. pH5.5 or pH6.0) is advantageous, asthis property can endow the anti-albumin VHH antibodies with an extended half-life. This makes the anti-albumin VHH antibodies particularly useful as half-life extending moieties, to extend the half-life of an agent linked (e.g. fused) to such an anti- albumin VHH antibody. In the context of the present invention, an agent linked (e.g. fused) to such an anti-albumin VHH antibody is a VHH antibody that binds to canine IL-31. Serum albumin is maintained at a high concentration in plasma due to the neonatal Fc receptor (FcRn) recycling pathway. Recycling is facilitated by pH- dependent binding of albumin to FcRn. In this regard, albumin binds to FcRn in acidified intracellular compartments such as endosomes, and protects (or rescues)the albumin from lysosomal degradation following endocytosis (lysosomaldegradation that would occur for other, non-FcRn binding, proteins). In this regard, albumin binds to FcRn in acidified intracellular compartments such as endosomes, and the albumin is then recycled back to the cell surface, where it dissociates from the FcRn at neutral pH and is released, thus extending the lifetime of the albumin inthe circulation. Again without wishing to be bound be theory, an anti-albumin VHHantibody that can bind to albumin at a neutral pH (e.g. pH7.4; plasma / circulatorypH) and also at endosomal pH (e.g. pH5.5 or pH6.0) can also be protected fromdegradation and recycled back to the cell surface (and thus be endowed with anextended half-life). In this regard, such a VHH antibody can bind to albumin atneutral pH and bind (or remain bound) to albumin in acidified intracellularcompartments such as endosomes (the albumin in turn being bound to FcRn), thusprotecting the anti-albumin VHH antibody from degradation. It follows that an agentlinked (e.g. fused) to the anti-albumin VHH antibody would also be protected from lysosomal degradation (and thus can be endowed with an extended half-life). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody of the inventioncomprising a VHH domain comprising three CDRs, wherein said VHH domain comprises a CDR1 that has the amino acid sequence of SEQ ID NO:4 or a sequence substantially homologous thereto, a CDR2 that has the amino acid sequence of SEQ ID NO:5 or a sequence substantially homologous thereto and aCDR3 that has the amino acid sequence of SEQ ID NO:6 or a sequencesubstantially homologous thereto, and (ii) at least one (e.g.1 or only 1) VHHantibody which binds to canine albumin (for example comprising a VHH domain comprising three CDRs, wherein said VHH domain comprises a CDR1 that has theamino acid sequence of SEQ ID NO:40 or a sequence substantially homologousthereto, a CDR2 that has the amino acid sequence of SEQ ID NO:41 or a sequencesubstantially homologous thereto and a CDR3 that has the amino acid sequence ofSEQ ID NO:42 or a sequence substantially homologous thereto), and (iii) at leastone (e.g.1 or only one) VHH antibody of the invention comprising a VHH domaincomprising three CDRs, wherein said VHH domain comprises a CDR1 that has the amino acid sequence of SEQ ID NO:12 or a sequence substantially homologous thereto, a CDR2 that has the amino acid sequence of SEQ ID NO:13 or a sequence substantially homologous thereto and a CDR3 that has the amino acid sequence of SEQ ID NO:14 or a sequence substantially homologous thereto. Substantially homologous sequences are discussed elsewhere herein (e.g. a substantially homologous sequence may be a sequence containing 1, 2 or 3 amino acidsubstitutions compared to the given CDR sequence). Typically, there are linkersbetween (positioned between) the VHH antibody of (i) and the VHH antibody of (ii)and the VHH antibody of (iii). Linkers may be as discussed elsewhere herein (e.g.the linker may have the sequence of SEQ ID NO:53). A (or the) VHH antibody of (i)and a (or the) VHH antibody of (ii) and a (or the) antibody of (iii) may be positionedin the construct in any order with respect to each other. For example, in some embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), which in turn may be positioned N- terminally with respect to the VHH antibody of (iii). Thus, in some embodiments,such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (i), a VHH antibody of (ii) and a VHH antibody of (iii). Such a construct is based on the construct that is referred to herein as “33-A8-40” (that has the sequence of SEQ ID NO:49). The “33-A8-40” construct (alsoreferred to herein as VHH33-A8-40) is a trivalent construct that has one VHH33 antibody of the invention linked (via a (GGGGS)2linker) to one VHHA8 antibody (which binds to canine albumin), which in turn is linked (via a (GGGGS)2linker) toone VHH40 antibody of the invention of the invention. In the “33-A8-40” construct,the VHH33 antibody is positioned N-terminally with respect to the VHHA8 antibody,which in turn is positioned N-terminally with respect to the VHH40 antibody. In some other embodiments, a (or the) VHH antibody of (ii) may be positioned N- terminally with respect to a (or the) VHH antibody of (i), which in turn may be positioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N- terminal to C-terminal direction, a VHH antibody of (ii), a VHH antibody of (i) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (iii), which in turn may be positioned N-terminally with respect to the VHH antibody of (ii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (i), a VHH antibody of (iii) and a VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. apolypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody of the present inventioncomprising a VHH domain, wherein said VHH domain has the amino acid sequenceof SEQ ID NO:3 or a sequence substantially homologous thereto, and (ii) at leastone (e.g.1 or only 1) VHH antibody which binds to canine albumin (for examplecomprising a VHH domain, wherein said VHH domain has the amino acid sequenceof SEQ ID NO:39 or a sequence substantially homologous thereto) and (iii) at leastone (e.g.1 or only 1) VHH antibody of the present invention comprising a VHHdomain, wherein said VHH domain has the amino acid sequence of SEQ ID NO:11 or a sequence substantially homologous thereto. Substantially homologous sequences are discussed elsewhere herein (e.g. a substantially homologous sequence may be a sequence having at least 80% sequence identity to the given VHH domain sequence). Typically, there are linkers between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii) and the VHH antibody of (iii).Linkers may be as discussed elsewhere herein (e.g. the linker may have thesequence of SEQ ID NO:53). A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) and a (or the) antibody of (iii) may be positioned in the construct in any order with respect to each other. For example, in some embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), which in turn may be positioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (i), a VHH antibody of (ii) and a VHH antibody of (iii). Such a construct is based on the construct that is referred to herein as “33-A8-40”. In some other embodiments, a (or the) VHH antibody of (ii) may be positioned N-terminally with respect to a (or the) VHH antibody of (i), which in turn may be positioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (ii), a VHH antibody of (i) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (iii), which in turn may be positioned N- terminally with respect to the VHH antibody of (ii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C- terminal direction, a VHH antibody of (i), a VHH antibody of (iii) and a VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprising the amino acid sequence of SEQ ID NO:49, or a sequence substantiallyhomologous thereto (e.g. a sequence having at least 80% sequence identitythereto). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprising the amino acid sequence of SEQ ID NO:49. Certain aspects and embodiments of (e.g. constructs of) the present invention herein refer to SEQ ID NO:3 (or VHH33) and also refer to SEQ ID NO:39 (or VHHA8) and also refer to SEQ ID NO:11 (or VHH40). In some alternativeembodiments, a caninized version (or caninized derivative) of SEQ ID NO:3 (or ofVHH33) and a caninized version of SEQ ID NO:39 (or of VHHA8) and a caninizedversion of SEQ ID NO:11 (or of VHH40) are used (or are present) or referred toinstead of SEQ ID NO:3 (or VHH33) and SEQ ID NO:39 (or VHHA8) and SEQ IDNO:11 (or VHH40) themselves (i.e. instead of the non-caninized versions). Thus,the present invention also provides aspects and embodiments that are equivalent to aspects and embodiments of (e.g. constructs of) the present invention herein thatrefer to SEQ ID NO:3 (or VHH33) and SEQ ID NO:39 (or VHHA8) and SEQ IDNO:11 (VHH40), with the exception that caninized versions (or caninizedderivatives) of SEQ ID NO:3 (or of VHH33) and SEQ ID NO:39 (or of VHHA8) andSEQ ID NO:11 (or of VHH40), or sequences substantially homologous thereto, areused (or are present) or referred to instead of SEQ ID NO:3 (or VHH33) and SEQ IDNO:39 (VHHA8) and SEQ ID NO:11 (VHH40) themselves. A caninized version ofSEQ ID NO:39 (or of VHHA8) may have the amino acid sequence of SEQ ID NO:90(or a sequence substantially homologous thereto). In some embodiments, the present invention provides a construct (e.g. apolypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody of the inventioncomprising a VHH domain comprising three CDRs, wherein said VHH domaincomprises a CDR1 that has the amino acid sequence of SEQ ID NO:28 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:29 or a sequence substantially homologous thereto and aCDR3 that has the amino acid sequence of SEQ ID NO:30 or a sequencesubstantially homologous thereto, and (ii) at least one (e.g.1 or only 1) VHHantibody which binds to canine albumin (for example comprising a VHH domain comprising three CDRs, wherein said VHH domain comprises a CDR1 that has theamino acid sequence of SEQ ID NO:40 or a sequence substantially homologousthereto, a CDR2 that has the amino acid sequence of SEQ ID NO:41 or a sequence substantially homologous thereto and a CDR3 that has the amino acid sequence of SEQ ID NO:42 or a sequence substantially homologous thereto), and (iii) at leastone (e.g.1 or only 1) VHH antibody of the invention comprising a VHH domaincomprising three CDRs, wherein said VHH domain comprises a CDR1 that has theamino acid sequence of SEQ ID NO:20 or a sequence substantially homologousthereto, a CDR2 that has the amino acid sequence of SEQ ID NO:21 or a sequencesubstantially homologous thereto and a CDR3 that has the amino acid sequence ofSEQ ID NO:22 or a sequence substantially homologous thereto. Substantiallyhomologous sequences are discussed elsewhere herein (e.g. a substantiallyhomologous sequence may be a sequence containing 1, 2 or 3 amino acid substitutions compared to the given CDR sequence). Typically, there are linkers between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii)and the VHH antibody of (iii). Linkers may be as discussed elsewhere herein (e.g.the linker may have the sequence of SEQ ID NO:53). A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) and a (or the) antibody of (iii) may be positioned in the construct in any order with respect to each other. For example, in some embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), which in turn may be positioned N- terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C- terminal direction, a VHH antibody of (i), a VHH antibody of (ii) and a VHH antibody of (iii). Such a construct is based on the construct that is referred to herein as “108- A8-94”. The “108-A8-94” construct (also referred to herein as VHH108-A8-94) is atrivalent construct that has one VHH108’ antibody of the invention linked (via a(GGGGS)2linker) to one VHHA8 antibody (which binds to canine albumin), which inturn is linked (via a (GGGGS)2 linker) to one VHH94’ antibody of the invention of theinvention. In the “108-A8-94” construct, the VHH108’ antibody is positioned N-terminally with respect to the VHHA8 antibody, which in turn is positioned N-terminally with respect to the VHH94’ antibody. In some other embodiments, a (orthe) VHH antibody of (ii) may be positioned N-terminally with respect to a (or the) VHH antibody of (i), which in turn may be positioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (ii), a VHH antibody of (i) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (iii), which in turn may be positioned N-terminally with respect tothe VHH antibody of (ii). Thus, in some embodiments, such a construct maycomprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (i), a VHH antibody of (iii) and a VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody of the present inventioncomprising a VHH domain, wherein said VHH domain has the amino acid sequenceof SEQ ID NO:58 or a sequence substantially homologous thereto, and (ii) at leastone (e.g.1 or only 1) VHH antibody which binds to canine albumin (for examplecomprising a VHH domain, wherein said VHH domain has the amino acid sequenceof SEQ ID NO:39 or a sequence substantially homologous thereto) and (iii) at leastone (e.g.1 or only 1) VHH antibody of the present invention comprising a VHHdomain, wherein said VHH domain has the amino acid sequence of SEQ ID NO:57 or a sequence substantially homologous thereto. Substantially homologous sequences are discussed elsewhere herein (e.g. a substantially homologous sequence may be a sequence having at least 80% sequence identity to the given VHH domain sequence). Typically, there are linkers between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii) and the VHH antibody of (iii). Linkers may be as discussed elsewhere herein. A (or the) VHH antibody of (i) and a(or the) VHH antibody of (ii) and a (or the) antibody of (iii) may be positioned in theconstruct in any order with respect to each other. For example, in some embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), which in turn may be positioned N- terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C- terminal direction, a VHH antibody of (i), a VHH antibody of (ii) and a VHH antibody of (iii). Such a construct is based on the construct that is referred to herein as “108- A8-94”. In some other embodiments, a (or the) VHH antibody of (ii) may be positioned N-terminally with respect to a (or the) VHH antibody of (i), which in turn may be positioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (ii), a VHH antibody of (i) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (iii), which in turn may be positioned N-terminally with respect to the VHH antibody of (ii). Thus, in some embodiments, such a construct may comprise, in sequence (ororder), in the N-terminal to C-terminal direction, a VHH antibody of (i), a VHHantibody of (iii) and a VHH antibody of (ii). Certain aspects and embodiments of (e.g. constructs of) the present invention herein refer to SEQ ID NO:58 (or VHH108’) and also refer to SEQ ID NO:39 (or VHHA8) and also refer to SEQ ID NO:57 (or VHH94’). In some alternative embodiments, a caninized version (or caninized derivative) of SEQ ID NO:58 (or of VHH108’) and a caninized version of SEQ ID NO:39 (or of VHHA8)and a caninized version of SEQ ID NO:57 (or of VHH94’) are used (or are present)or referred to instead of SEQ ID NO:58 (or VHH108’) and SEQ ID NO:39 (orVHHA8) and SEQ ID NO:57 (or VHH94’) themselves (i.e. instead of the non-caninized versions). Thus, the present invention also provides aspects and embodiments that are equivalent to aspects and embodiments of (e.g. constructs of)the present invention herein that refer to SEQ ID NO:58 (or VHH108’) and SEQ IDNO:39 (or VHHA8) and SEQ ID NO:57 (VHH94’), with the exception that caninizedversions (or caninized derivatives) of SEQ ID NO:58 (or of VHH108’) and SEQ IDNO:39 (or of VHHA8) and SEQ ID NO:57 (or of VHH94’), or sequences substantiallyhomologous thereto, are used (or are present) or referred to instead of SEQ IDNO:58 (or VHH108’) and SEQ ID NO:39 (VHHA8) and SEQ ID NO:57 (VHH94’)themselves. A caninized version of SEQ ID NO:58 (or of VHH108’) may have the amino acid sequence of SEQ ID NO:100 (or a sequence substantially homologous thereto). A caninized version of SEQ ID NO:39 (or of VHHA8) may have the amino acid sequence of SEQ ID NO:90 (or a sequence substantially homologous thereto). A caninized version of SEQ ID NO:57 (or of VHH94’) may have the amino acid sequence of SEQ ID NO:99 (or a sequence substantially homologous thereto). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody of the present inventioncomprising a VHH domain, wherein said VHH domain has the amino acid sequenceof SEQ ID NO:27 or a sequence substantially homologous thereto, and (ii) at leastone (e.g.1 or only 1) VHH antibody which binds to canine albumin (for examplecomprising a VHH domain, wherein said VHH domain has the amino acid sequenceof SEQ ID NO:39 or a sequence substantially homologous thereto) and (iii) at leastone (e.g.1 or only 1) VHH antibody of the present invention comprising a VHHdomain, wherein said VHH domain has the amino acid sequence of SEQ ID NO:19 or a sequence substantially homologous thereto. Substantially homologous sequences are discussed elsewhere herein (e.g. a substantially homologous sequence may be a sequence having at least 80% sequence identity to the given VHH domain sequence). Typically, there are linkers between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii) and the VHH antibody of (iii). Linkers may be as discussed elsewhere herein. A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) and a (or the) antibody of (iii) may be positioned in the construct in any order with respect to each other. For example, in some embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), which in turn may be positioned N- terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C- terminal direction, a VHH antibody of (i), a VHH antibody of (ii) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (ii) may be positioned N-terminally with respect to a (or the) VHH antibody of (i), which in turn may be positioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (ii), a VHH antibody of (i) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (iii), which in turn may be positioned N-terminally with respect to the VHH antibody of (ii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (i), a VHH antibody of (iii) and a VHH antibody of (ii). Certain aspects and embodiments of (e.g. constructs of) the present invention herein refer to SEQ ID NO:27 (or VHH108) and also refer to SEQ ID NO:39 (or VHHA8) and also refer to SEQ ID NO:19 (or VHH94). In some alternative embodiments, a caninized version (or caninized derivative) of SEQ IDNO:27 (or of VHH108) and a caninized version of SEQ ID NO:39 (or of VHHA8) anda caninized version of SEQ ID NO:19 (or of VHH94) are used (or are present) or referred to instead of SEQ ID NO:27 (or VHH108) and SEQ ID NO:39 (or VHHA8) and SEQ ID NO:19 (or VHH94) themselves (i.e. instead of the non-caninized versions). Thus, the present invention also provides aspects and embodiments that are equivalent to aspects and embodiments of (e.g. constructs of) the present invention herein that refer to SEQ ID NO:27 (or VHH108) and SEQ ID NO:39 (orVHHA8) and SEQ ID NO:19 (VHH94), with the exception that caninized versions (orcaninized derivatives) of SEQ ID NO:27 (or of VHH108) and SEQ ID NO:39 (or of VHHA8) and SEQ ID NO:19 (or of VHH94), or sequences substantially homologous thereto, are used (or are present) or referred to instead of SEQ ID NO:27 (orVHH108) and SEQ ID NO:39 (VHHA8) and SEQ ID NO:19 (VHH94) themselves. Acaninized version of SEQ ID NO:27 (or of VHH108) may have the amino acidsequence of SEQ ID NO:82 (or a sequence substantially homologous thereto). Acaninized version of SEQ ID NO:39 (or of VHHA8) may have the amino acid sequence of SEQ ID NO:90 (or a sequence substantially homologous thereto). Acaninized version of SEQ ID NO:19 (or of VHH94) may have the amino acidsequence of SEQ ID NO:74 (or a sequence substantially homologous thereto).In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprising the amino acid sequence of SEQ ID NO:50, or a sequence substantiallyhomologous thereto (e.g. a sequence having at least 80% sequence identitythereto). In some embodiments, the present invention provides a construct (e.g. apolypeptide construct or a single chain polypeptide construct or a fusion protein)comprising the amino acid sequence of SEQ ID NO:50. In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody of the present inventioncomprising a VHH domain, wherein said VHH domain has the amino acid sequenceof SEQ ID NO:82 or a sequence substantially homologous thereto, and (ii) at leastone (e.g.1 or only 1) VHH antibody which binds to canine albumin (for examplecomprising a VHH domain, wherein said VHH domain has the amino acid sequenceof SEQ ID NO:90 or a sequence substantially homologous thereto) and (iii) at leastone (e.g.1 or only 1) VHH antibody of the present invention comprising a VHHdomain, wherein said VHH domain has the amino acid sequence of SEQ ID NO:74 or a sequence substantially homologous thereto. Substantially homologous sequences are discussed elsewhere herein (e.g. a substantially homologous sequence may be a sequence having at least 80% sequence identity to the given VHH domain sequence). Typically, there are linkers between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii) and the VHH antibody of (iii). Linkers may be as discussed elsewhere herein. A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) and a (or the) antibody of (iii) may be positioned in the construct in any order with respect to each other. For example, in some embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), which in turn may be positioned N- terminally with respect to the VHH antibody of (iii). Thus, in some preferred embodiments, such a construct may comprise, in sequence (or order), in the N- terminal to C-terminal direction, a VHH antibody of (i), a VHH antibody of (ii) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (ii)may be positioned N-terminally with respect to a (or the) VHH antibody of (i), whichin turn may be positioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (ii), a VHH antibody of (i) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (iii), which in turn may be positioned N-terminally with respect to the VHH antibody of (ii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (i), a VHH antibody of (iii) and a VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprising the amino acid sequence of SEQ ID NO:98, or a sequence substantiallyhomologous thereto (e.g. a sequence having at least 80% sequence identitythereto). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprising the amino acid sequence of SEQ ID NO:98. References herein to a VHH antibody “based on VHH33” may mean (i) a VHH antibody comprising a VHH domain comprising three CDRs, wherein said VHH domain comprises a CDR1 that has the amino acid sequence of SEQ ID NO:4 or a sequence substantially homologous thereto, a CDR2 that has the amino acid sequence of SEQ ID NO:5 or a sequence substantially homologous thereto and a CDR3 that has the amino acid sequence of SEQ ID NO:6 or a sequence substantially homologous thereto, (ii) a VHH antibody comprising a VHH domain that has the amino acid sequence of SEQ ID NO:3 or a sequence homologous thereto, or (iii) a VHH antibody comprising a caninized VHH domain, wherein said caninized VHH domain is caninized version of the (non-caninized) VHH domain that has the amino acid sequence of SEQ ID NO:3 (or a sequence homologous thereto). References herein to a VHH antibody “based on VHH40” may mean (i) a VHH antibody comprising a VHH domain comprising three CDRs, wherein said VHHdomain comprises a CDR1 that has the amino acid sequence of SEQ ID NO:12 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:13 or a sequence substantially homologous thereto and aCDR3 that has the amino acid sequence of SEQ ID NO:14 or a sequencesubstantially homologous thereto, (ii) a VHH antibody comprising a VHH domainthat has the amino acid sequence of SEQ ID NO:11 or a sequence homologousthereto, or (iii) a VHH antibody comprising a caninized VHH domain, wherein said caninized VHH domain is caninized version of the (non-caninized) VHH domain thathas the amino acid sequence of SEQ ID NO:11 (or a sequence homologousthereto). References herein to a VHH antibody “based on VHH94” may mean (i) a VHH antibody comprising a VHH domain comprising three CDRs, wherein said VHHdomain comprises a CDR1 that has the amino acid sequence of SEQ ID NO:20 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:21 or a sequence substantially homologous thereto and aCDR3 that has the amino acid sequence of SEQ ID NO:22 or a sequencesubstantially homologous thereto, (ii) a VHH antibody comprising a VHH domainthat has the amino acid sequence of SEQ ID NO:19 or a sequence homologousthereto, or (iii) a VHH antibody comprising a caninized VHH domain, wherein said caninized VHH domain is caninized version of the (non-caninized) VHH domain thathas the amino acid sequence of SEQ ID NO:19 (or a sequence homologousthereto), for example a VHH antibody comprising a VHH domain that has the aminoacid sequence of SEQ ID NO:74 or a sequence homologous thereto.References herein to a VHH antibody “based on VHH108” may mean (i) a VHH antibody comprising a VHH domain comprising three CDRs, wherein said VHHdomain comprises a CDR1 that has the amino acid sequence of SEQ ID NO:28 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:29 or a sequence substantially homologous thereto and aCDR3 that has the amino acid sequence of SEQ ID NO:30 or a sequencesubstantially homologous thereto, (ii) a VHH antibody comprising a VHH domainthat has the amino acid sequence of SEQ ID NO:27 or a sequence homologousthereto, or (iii) a VHH antibody comprising a caninized VHH domain, wherein said caninized VHH domain is caninized version of the (non-caninized) VHH domain thathas the amino acid sequence of SEQ ID NO:27 (or a sequence homologousthereto), for example a VHH antibody comprising a VHH domain that has the aminoacid sequence of SEQ ID NO:82 or a sequence homologous thereto.References herein to a VHH antibody “based on VHH94’ ” may mean (i) a VHH antibody comprising a VHH domain comprising three CDRs, wherein said VHHdomain comprises a CDR1 that has the amino acid sequence of SEQ ID NO:20 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:21 or a sequence substantially homologous thereto and aCDR3 that has the amino acid sequence of SEQ ID NO:22 or a sequencesubstantially homologous thereto, (ii) a VHH antibody comprising a VHH domainthat has the amino acid sequence of SEQ ID NO:57 or a sequence homologousthereto, or (iii) a VHH antibody comprising a caninized VHH domain, wherein said caninized VHH domain is caninized version of the (non-caninized) VHH domain thathas the amino acid sequence of SEQ ID NO:58 (or a sequence homologousthereto), for example a VHH antibody comprising a VHH domain that has the aminoacid sequence of SEQ ID NO:99 or a sequence homologous thereto.References herein to a VHH antibody “based on VHH108’ ” may mean (i) a VHH antibody comprising a VHH domain comprising three CDRs, wherein said VHHdomain comprises a CDR1 that has the amino acid sequence of SEQ ID NO:28 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:29 or a sequence substantially homologous thereto and aCDR3 that has the amino acid sequence of SEQ ID NO:30 or a sequencesubstantially homologous thereto, (ii) a VHH antibody comprising a VHH domainthat has the amino acid sequence of SEQ ID NO:58 or a sequence homologousthereto, or (iii) a VHH antibody comprising a caninized VHH domain, wherein said caninized VHH domain is caninized version of the (non-caninized) VHH domain thathas the amino acid sequence of SEQ ID NO:58 (or a sequence homologousthereto), for example a VHH antibody comprising a VHH domain that has the aminoacid sequence of SEQ ID NO:100 or a sequence homologous thereto.References herein to a VHH antibody “based on VHHA8” may mean (i) a VHH antibody comprising a VHH domain comprising three CDRs, wherein said VHHdomain comprises a CDR1 that has the amino acid sequence of SEQ ID NO:40 or asequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:41 or a sequence substantially homologous thereto and aCDR3 that has the amino acid sequence of SEQ ID NO:42 or a sequencesubstantially homologous thereto, (ii) a VHH antibody comprising a VHH domainthat has the amino acid sequence of SEQ ID NO:39 or a sequence homologousthereto or (iii) a VHH antibody comprising a caninized VHH domain, wherein saidcaninized VHH domain is caninized version of the (non-caninized) VHH domain thathas the amino acid sequence of SEQ ID NO:39 (or a sequence homologousthereto), for example a VHH antibody comprising a VHH domain that has the aminoacid sequence of SEQ ID NO:90 or a sequence homologous thereto.In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody based on VHH33, and (ii)at least one (e.g.1 or only 1) VHH antibody that binds to the same epitope (orsubstantially the same epitope) on canine IL-31 as is bound by a VHH antibodycomprising a VHH domain that has the amino acid sequence of SEQ ID NO:11. Insome embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprising (i)at least one (e.g.1 or only 1) VHH antibody that binds to the same epitope (orsubstantially the same epitope) on canine IL-31 as is bound by a VHH antibodycomprising a VHH domain that has the amino acid sequence of SEQ ID NO:3, and(ii) at least one (e.g. 1 or only 1) VHH antibody based on VHH40. Typically, thereis a linker between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii). Linkers may be as discussed elsewhere herein. A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) may be positioned in the construct in any order with respect to each other, e.g. a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), or vice versa. However, in some preferred embodiments, a (or the) VHH antibody of (i) is positioned in the construct N-terminally with respect to a (or the) VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody based on VHH108’, and(ii) at least one (e.g. 1 or only 1) VHH antibody that binds to the same epitope (orsubstantially the same epitope) on canine IL-31 as is bound by a VHH antibodycomprising a VHH domain that has the amino acid sequence of SEQ ID NO:57. Insome embodiments, the present invention provides a construct (e.g. a polypeptideconstruct or a single chain polypeptide construct or a fusion protein) comprising (i)at least one (e.g.1 or only 1) VHH antibody that binds to the same epitope (orsubstantially the same epitope) on canine IL-31 as is bound by a VHH antibodycomprising a VHH domain that has the amino acid sequence of SEQ ID NO:58, and(ii) at least one (e.g. 1 or only 1) VHH antibody based on VHH94’. Typically, there isa linker between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii). Linkers may be as discussed elsewhere herein. A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) may be positioned in the construct in any order with respect to each other, e.g. a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), or vice versa. However, in some preferred embodiments, a (or the) VHH antibody of (i) is positioned in the construct N-terminally with respect to a (or the) VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody based on VHH108, and(ii) at least one (e.g. 1 or only 1) VHH antibody that binds to the same epitope (orsubstantially the same epitope) on canine IL-31 as is bound by a VHH antibodycomprising a VHH domain that has the amino acid sequence of SEQ ID NO:19. Insome embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprising (i)at least one (e.g.1 or only 1) VHH antibody that binds to the same epitope (orsubstantially the same epitope) on canine IL-31 as is bound by a VHH antibodycomprising a VHH domain that has the amino acid sequence of SEQ ID NO:27, and(ii) at least one (e.g. 1 or only 1) VHH antibody based on VHH94. Typically, thereis a linker between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii). Linkers may be as discussed elsewhere herein. A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) may be positioned in the construct in any order with respect to each other, e.g. a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), or vice versa. However, in some preferred embodiments, a (or the) VHH antibody of (i) is positioned in the construct N-terminally with respect to a (or the) VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody based on VHH108, and(ii) at least one (e.g. 1 or only 1) VHH antibody that binds to the same epitope (orsubstantially the same epitope) on canine IL-31 as is bound by a VHH antibodycomprising a VHH domain that has the amino acid sequence of SEQ ID NO:74. Insome embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprising (i)at least one (e.g. 1 or only 1) VHH antibody that binds to the same epitope (orsubstantially the same epitope) on canine IL-31 as is bound by a VHH antibodycomprising a VHH domain that has the amino acid sequence of SEQ ID NO:82, and(ii) at least one (e.g. 1 or only 1) VHH antibody based on VHH94. Typically, thereis a linker between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii). Linkers may be as discussed elsewhere herein. A (or the) VHHantibody of (i) and a (or the) VHH antibody of (ii) may be positioned in the constructin any order with respect to each other, e.g. a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), or vice versa.However, in some preferred embodiments, a (or the) VHH antibody of (i) ispositioned in the construct N-terminally with respect to a (or the) VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprising (i) at least one (e.g.1 or only 1) VHH based on VHH33, and (ii) at least one (e.g.1 or only 1) VHH antibody which binds to canine albumin (e.g. as described elsewhere herein, for example an antibody based on VHHA8), and (iii) at least one (e.g.1 or only one) VHH that binds to the same epitope (or substantially the same epitope) on canine IL-31 as is bound by a VHH antibody comprising a VHH domain that has the amino acid sequence of SEQ ID NO:11. In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprising (i) at least one (e.g.1 or only one) VHH that binds to the same epitope (or substantiallythe same epitope) on canine IL-31 as is bound by a VHH antibody comprising aVHH domain that has the amino acid sequence of SEQ ID NO:3, and (ii) at least one (e.g.1 or only 1) VHH antibody which binds to canine albumin (e.g. as described elsewhere herein, for example an antibody based on VHHA8), and (iii) at least one (e.g.1 or only 1) VHH based on VHH40. Typically, there are linkers between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii) and the VHH antibody of (iii). Linkers may be as discussed elsewhere herein. A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) and a (or the) antibody of (iii) may be positioned in the construct in any order with respect to each other. For example, in some embodiments, a (or the) VHH antibody of (i) may be positioned N- terminally with respect to a (or the) VHH antibody of (ii), which in turn may be positioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N- terminal to C-terminal direction, a VHH antibody of (i), a VHH antibody of (ii) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (ii) may be positioned N-terminally with respect to a (or the) VHH antibody of (i), which in turn may be positioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (ii), a VHH antibody of (i) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (iii), which in turn may be positioned N-terminally with respect to theVHH antibody of (ii). Thus, in some embodiments, such a construct may comprise,in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (i), a VHH antibody of (iii) and a VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprising (i) at least one (e.g.1 or only 1) VHH based on VHH108’, and (ii) at least one (e.g.1 or only 1) VHH antibody which binds to canine albumin (e.g. as described elsewhere herein, for example an antibody based on VHHA8), and (iii) at least one (e.g.1 or only one) VHH that binds to the same epitope (or substantially the same epitope) on canine IL-31 as is bound by a VHH antibody comprising a VHH domain that has the amino acid sequence of SEQ ID NO:57. In some embodiments, the present invention provides a construct (e.g. a polypeptideconstruct or a single chain polypeptide construct or a fusion protein) comprising (i)at least one (e.g.1 or only one) VHH that binds to the same epitope (or substantially the same epitope) on canine IL-31 as is bound by a VHH antibody comprising a VHH domain that has the amino acid sequence of SEQ ID NO:58, and (ii) at least one (e.g.1 or only 1) VHH antibody which binds to canine albumin (e.g. as described elsewhere herein, for example an antibody based on VHHA8), and (iii) at least one (e.g.1 or only 1) VHH based on VHH94’. Typically, there are linkers between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii) and the VHH antibody of (iii). Linkers may be as discussed elsewhere herein. A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) and a (or the) antibody of (iii) may be positioned in the construct in any order with respect to each other. For example, in some embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), which in turn may bepositioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N- terminal to C-terminal direction, a VHH antibody of (i), a VHH antibody of (ii) and aVHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (ii)may be positioned N-terminally with respect to a (or the) VHH antibody of (i), which in turn may be positioned N-terminally with respect to the VHH antibody of (iii).Thus, in some embodiments, such a construct may comprise, in sequence (ororder), in the N-terminal to C-terminal direction, a VHH antibody of (ii), a VHH antibody of (i) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (iii), which in turn may be positioned N-terminally with respect to the VHH antibody of (ii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (i), a VHH antibody of (iii) and a VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprising (i) at least one (e.g.1 or only 1) VHH based on VHH108, and (ii) at least one (e.g.1 or only 1) VHH antibody which binds to canine albumin (e.g. asdescribed elsewhere herein, for example a VHH antibody based on VHHA8), and(iii) at least one (e.g.1 or only one) VHH that binds to the same epitope (or substantially the same epitope) on canine IL-31 as is bound by a VHH antibody comprising a VHH domain that has the amino acid sequence of SEQ ID NO:19. In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprising (i) at least one (e.g.1 or only one) VHH that binds to the same epitope (or substantially the same epitope) on canine IL-31 as is bound by a VHH antibody comprising a VHH domain that has the amino acid sequence of SEQ ID NO:27, and (ii) at least one (e.g.1 or only 1) VHH antibody which binds to canine albumin (e.g. as described elsewhere herein, for example an antibody based on VHHA8), and (iii) at least one (e.g.1 or only 1) VHH based on VHH94. Typically, there are linkers between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii) and the VHH antibody of (iii). Linkers may be as discussed elsewhere herein. A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) and a (or the) antibody of (iii) may be positioned in the construct in any order with respect to each other. Forexample, in some embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), which in turn may be positioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N- terminal to C-terminal direction, a VHH antibody of (i), a VHH antibody of (ii) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (ii) may be positioned N-terminally with respect to a (or the) VHH antibody of (i), which in turn may be positioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (ii), a VHH antibody of (i) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (iii), which in turn may be positioned N-terminally with respect to theVHH antibody of (ii). Thus, in some embodiments, such a construct may comprise,in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (i), a VHH antibody of (iii) and a VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprising (i) at least one (e.g.1 or only 1) VHH based on VHH108, and (ii) at least one (e.g.1 or only 1) VHH antibody which binds to canine albumin (e.g. asdescribed elsewhere herein, for example a VHH antibody based on VHHA8), and(iii) at least one (e.g.1 or only one) VHH that binds to the same epitope (or substantially the same epitope) on canine IL-31 as is bound by a VHH antibodycomprising a VHH domain that has the amino acid sequence of SEQ ID NO:74. Insome embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprising (i) at least one (e.g.1 or only one) VHH that binds to the same epitope (or substantially the same epitope) on canine IL-31 as is bound by a VHH antibody comprising a VHH domain that has the amino acid sequence of SEQ ID NO:82, and (ii) at leastone (e.g. 1 or only 1) VHH antibody which binds to canine albumin (e.g. asdescribed elsewhere herein, for example a VHH antibody based on VHHA8), and(iii) at least one (e.g.1 or only 1) VHH based on VHH94. Typically, there are linkers between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii) and the VHH antibody of (iii). Linkers may be as discussed elsewhere herein. A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) and a (or the) antibody of (iii) may be positioned in the construct in any order with respect to each other. For example, in some embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), which in turn may be positioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (i), a VHH antibody of (ii) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (ii) may be positioned N-terminally with respect to a (or the) VHH antibody of (i), which in turn may be positioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (ii), a VHH antibody of (i) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (iii), which in turn may be positioned N-terminally with respect to the VHH antibody of (ii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of(i), a VHH antibody of (iii) and a VHH antibody of (ii).In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody based on VHH33, and (ii)at least one (e.g.1 or only 1) VHH antibody that binds to an epitope on canine IL-31that is different from the epitope on canine IL-31 that is bound by a VHH antibodybased on VHH33. Typically, there is a linker between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii). A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) may be positioned in the construct in any order with respect to each other, e.g. a (or the) VHH antibody of (i) may be positioned N- terminally with respect to a (or the) VHH antibody of (ii), or vice versa. However, in some embodiments, a (or the) VHH antibody of (i) is positioned in the construct N- terminally with respect to a (or the) VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. apolypeptide construct or a single chain polypeptide construct or a fusion protein) comprising (i) at least one (e.g.1 or only 1) VHH based on VHH33, and (ii) at least one (e.g.1 or only 1) VHH antibody which binds to canine albumin (e.g. as described elsewhere herein, for example an antibody based on VHHA8), and (iii) atleast one (e.g. 1 or only 1) VHH antibody that binds to an epitope on canine IL-31that is different from the epitope on canine IL-31 that is bound by a VHH antibodybased on VHH33. Typically, there are linkers between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii) and the VHH antibody of (iii). A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) and a (or the) antibody of (iii) may be positioned in the construct in any order with respect to each other. For example, in some embodiments, a (or the) VHH antibody of (i) may be positioned N- terminally with respect to a (or the) VHH antibody of (ii), which in turn may be positioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N- terminal to C-terminal direction, a VHH antibody of (i), a VHH antibody of (ii) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (ii) may be positioned N-terminally with respect to a (or the) VHH antibody of (i), which in turn may be positioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (ii), a VHH antibody of (i) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (iii), which in turn may be positioned N-terminally with respect to theVHH antibody of (ii). Thus, in some embodiments, such a construct may comprise,in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (i), a VHH antibody of (iii) and a VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody based on VHH40, and (ii)at least one (e.g.1 or only 1) VHH antibody that binds to an epitope on canine IL-31that is different from the epitope on canine IL-31 that is bound by a VHH antibody based on VHH40. Typically, there is a linker between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii). A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) may be positioned in the construct in any order with respect to each other, e.g. a (or the) VHH antibody of (i) may be positioned N- terminally with respect to a (or the) VHH antibody of (ii), or vice versa. However, in some embodiments, a (or the) VHH antibody of (i) is positioned in the construct C- terminally with respect to a (or the) VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprising (i) at least one (e.g.1 or only 1) VHH based on VHH40, and (ii) at least one (e.g.1 or only 1) VHH antibody which binds to canine albumin (e.g. as described elsewhere herein, for example an antibody based on VHHA8), and (iii) atleast one (e.g. 1 or only 1) VHH antibody that binds to an epitope on canine IL-31that is different from the epitope on canine IL-31 that is bound by a VHH antibody based on VHH40. Typically, there are linkers between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii) and the VHH antibody of (iii). Linkers may be as discussed elsewhere herein. A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) and a (or the) antibody of (iii) may be positioned in the construct in any order with respect to each other. For example, in some embodiments, a (or the) VHH antibody of (i) may be positioned C-terminally with respect to a (or the) VHH antibody of (ii), which in turn may be positioned C- terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C- terminal direction, a VHH antibody of (iii), a VHH antibody of (ii) and a VHH antibody of (i). In some other embodiments, a (or the) VHH antibody of (ii) may be positioned N-terminally with respect to a (or the) VHH antibody of (iii), which in turn may be positioned N-terminally with respect to the VHH antibody of (i). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N- terminal to C-terminal direction, a VHH antibody of (ii), a VHH antibody of (iii) and a VHH antibody of (i). In some other embodiments, a (or the) VHH antibody of (iii) may be positioned N-terminally with respect to a (or the) VHH antibody of (i), which in turn may be positioned N-terminally with respect to the VHH antibody of (ii). Thus, in some embodiments, such a construct may comprise, in sequence (ororder), in the N-terminal to C-terminal direction, a VHH antibody of (iii), a VHHantibody of (i) and a VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody based on VHH94’, and (ii)at least one (e.g.1 or only 1) VHH antibody that binds to an epitope on canine IL-31that is different from the epitope on canine IL-31 that is bound by a VHH antibody based on VHH94’. Typically, there is a linker between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii). A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) may be positioned in the construct in any order with respect to each other, e.g. a (or the) VHH antibody of (i) may be positioned N- terminally with respect to a (or the) VHH antibody of (ii), or vice versa. However, in some embodiments, a (or the) VHH antibody of (i) is positioned in the construct C- terminally with respect to a (or the) VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. apolypeptide construct or a single chain polypeptide construct or a fusion protein) comprising (i) at least one (e.g.1 or only 1) VHH based on VHH94’, and (ii) at least one (e.g.1 or only 1) VHH antibody which binds to canine albumin (e.g. as described elsewhere herein, for example an antibody based on VHHA8), and (iii) atleast one (e.g. 1 or only 1) VHH antibody that binds to an epitope on canine IL-31that is different from the epitope on canine IL-31 that is bound by a VHH antibody based on VHH94’. Typically, there are linkers between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii) and the VHH antibody of (iii). A (orthe) VHH antibody of (i) and a (or the) VHH antibody of (ii) and a (or the) antibody of(iii) may be positioned in the construct in any order with respect to each other. For example, in some embodiments, a (or the) VHH antibody of (i) may be positioned C- terminally with respect to a (or the) VHH antibody of (ii), which in turn may be positioned C-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N- terminal to C-terminal direction, a VHH antibody of (iii), a VHH antibody of (ii) and a VHH antibody of (i). In some other embodiments, a (or the) VHH antibody of (ii) may be positioned N-terminally with respect to a (or the) VHH antibody of (iii), which in turn may be positioned N-terminally with respect to the VHH antibody of (i). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (ii), a VHH antibody of (iii) and a VHH antibody of (i). In some other embodiments, a (or the) VHH antibody of (iii) may be positioned N-terminally with respect to a (or the) VHH antibody of (i), which in turn may be positioned N-terminally with respect to the VHH antibody of (ii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (iii), a VHH antibody of (i) and a VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody based on VHH108’, and(ii) at least one (e.g. 1 or only 1) VHH antibody that binds to an epitope on canineIL-31 that is different from the epitope on canine IL-31 that is bound by a VHH antibody based on VHH108’. Typically, there is a linker between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii). A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) may be positioned in the construct in any order with respect to each other, e.g. a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), or vice versa. However, in some embodiments, a (or the) VHH antibody of (i) is positioned in the construct N-terminally with respect to a (or the) VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprising (i) at least one (e.g.1 or only 1) VHH based on VHH108’, and (ii) at least one (e.g.1 or only 1) VHH antibody which binds to canine albumin (e.g. as described elsewhere herein, for example an antibody based on VHHA8), and (iii) atleast one (e.g. 1 or only 1) VHH antibody that binds to an epitope on canine IL-31that is different from the epitope on canine IL-31 that is bound by a VHH antibody based on VHH108’. Typically, there are linkers between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii) and the VHH antibody of (iii). A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) and a (or the) antibody of (iii) may be positioned in the construct in any order with respect to each other. For example, in some embodiments, a (or the) VHH antibody of (i) may be positioned N- terminally with respect to a (or the) VHH antibody of (ii), which in turn may be positioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N- terminal to C-terminal direction, a VHH antibody of (i), a VHH antibody of (ii) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (ii) may be positioned N-terminally with respect to a (or the) VHH antibody of (i), which in turn may be positioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (ii), a VHH antibody of (i) and a VHH antibody of (iii). In some other embodiments, a (or the)VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHHantibody of (iii), which in turn may be positioned N-terminally with respect to the VHH antibody of (ii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (i), a VHH antibody of (iii) and a VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody based on VHH94, and (ii)at least one (e.g.1 or only 1) VHH antibody that binds to an epitope on canine IL-31that is different from the epitope on canine IL-31 that is bound by a VHH antibody based on VHH94. Typically, there is a linker between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii). A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) may be positioned in the construct in any order with respect to each other, e.g. a (or the) VHH antibody of (i) may be positioned N- terminally with respect to a (or the) VHH antibody of (ii), or vice versa. However, in some embodiments, a (or the) VHH antibody of (i) is positioned in the construct C-terminally with respect to a (or the) VHH antibody of (ii).In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprising (i) at least one (e.g.1 or only 1) VHH based on VHH94, and (ii) at least one (e.g.1 or only 1) VHH antibody which binds to canine albumin (e.g. as described elsewhere herein, for example an antibody based on VHHA8), and (iii) atleast one (e.g. 1 or only 1) VHH antibody that binds to an epitope on canine IL-31that is different from the epitope on canine IL-31 that is bound by a VHH antibodybased on VHH94. Typically, there are linkers between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii) and the VHH antibody of (iii). A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) and a (or the) antibody of (iii) may be positioned in the construct in any order with respect to each other. For example, in some embodiments, a (or the) VHH antibody of (i) may be positioned C- terminally with respect to a (or the) VHH antibody of (ii), which in turn may be positioned C-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N- terminal to C-terminal direction, a VHH antibody of (iii), a VHH antibody of (ii) and a VHH antibody of (i). In some other embodiments, a (or the) VHH antibody of (ii) may be positioned N-terminally with respect to a (or the) VHH antibody of (iii), which in turn may be positioned N-terminally with respect to the VHH antibody of (i). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (ii), a VHH antibody of (iii) and a VHH antibody of (i). In some other embodiments, a (or the) VHH antibody of (iii) may be positioned N-terminally with respect to a (or the) VHH antibody of (i), which in turn may be positioned N-terminally with respect to the VHH antibody of (ii).Thus, in some embodiments, such a construct may comprise, in sequence (ororder), in the N-terminal to C-terminal direction, a VHH antibody of (iii), a VHH antibody of (i) and a VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody based on VHH108, and(ii) at least one (e.g. 1 or only 1) VHH antibody that binds to an epitope on canineIL-31 that is different from the epitope on canine IL-31 that is bound by a VHHantibody based on VHH108. Typically, there is a linker between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii). A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) may be positioned in the construct in any order with respect to each other, e.g. a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), or vice versa.However, in some embodiments, a (or the) VHH antibody of (i) is positioned in theconstruct N-terminally with respect to a (or the) VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprising (i) at least one (e.g.1 or only 1) VHH based on VHH108, and (ii) at least one (e.g.1 or only 1) VHH antibody which binds to canine albumin (e.g. as described elsewhere herein, for example an antibody based on VHHA8), and (iii) atleast one (e.g. 1 or only 1) VHH antibody that binds to an epitope on canine IL-31that is different from the epitope on canine IL-31 that is bound by a VHH antibody based on VHH108. Typically, there are linkers between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii) and the VHH antibody of (iii). A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) and a (or the) antibody of (iii) may be positioned in the construct in any order with respect to each other. For example, in some embodiments, a (or the) VHH antibody of (i) may be positioned N- terminally with respect to a (or the) VHH antibody of (ii), which in turn may be positioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N- terminal to C-terminal direction, a VHH antibody of (i), a VHH antibody of (ii) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (ii) may be positioned N-terminally with respect to a (or the) VHH antibody of (i), which in turn may be positioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (ii), a VHH antibody of (i) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (iii), which in turn may be positioned N-terminally with respect to the VHH antibody of (ii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (i), a VHH antibody of (iii) and a VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody that inhibits the ability ofcanine IL-31 to bind to canine OSMR, but does not significantly inhibit the ability ofcanine IL-31 to bind to canine IL-31RA (e.g. a VHH antibody based on VHH108 orVHH108’), and (ii) at least one (e.g.1 or only 1) VHH antibody that inhibits the abilityof canine IL-31 to bind to canine IL-31RA, but does not significantly inhibit the abilityof canine IL-31 to bind to canine OSMR (e.g. a VHH antibody based on VHH94 orVHH94’). Typically, there is a linker between (positioned between) the VHHantibody of (i) and the VHH antibody of (ii). A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) may be positioned in the construct in any order with respect to each other, e.g. a (or the) VHH antibody of (i) may be positioned N- terminally with respect to a (or the) VHH antibody of (ii), or vice versa. However, in some embodiments, a (or the) VHH antibody of (i) is positioned in the construct N- terminally with respect to a (or the) VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody that inhibits the ability ofcanine IL-31 to bind to canine OSMR, but does not significantly inhibit the ability ofcanine IL-31 to bind to canine IL-31RA (e.g. a VHH antibody based on VHH108 orVHH108’), and (ii) at least one (e.g.1 or only 1) VHH antibody which binds to canine albumin (e.g. as described elsewhere herein, for example an antibody based onVHHA8), and (iii) at least one (e.g.1 or only 1) VHH antibody that inhibits the abilityof canine IL-31 to bind to canine IL-31RA, but does not significantly inhibit the abilityof canine IL-31 to bind to canine OSMR (e.g. a VHH antibody based on VHH94 orVHH94’). Typically, there are linkers between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii) and the VHH antibody of (iii). A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) and a (or the) antibody of (iii) may be positioned in the construct in any order with respect to each other. For example, in some embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), which in turn may bepositioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N- terminal to C-terminal direction, a VHH antibody of (i), a VHH antibody of (ii) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (ii) may be positioned N-terminally with respect to a (or the) VHH antibody of (i), which in turn may be positioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (ii), a VHH antibody of (i) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (iii), which in turn may be positioned N-terminally with respect to the VHH antibody of (ii). Thus, in some embodiments, such a construct may comprise,in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of(i), a VHH antibody of (iii) and a VHH antibody of (ii). In some embodiments, the present invention provides a construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody that inhibits the ability ofcanine IL-31 to bind to canine OSMR and inhibits the ability of canine IL-31 to bind to canine IL-31RA (e.g. an antibody based on VHH33 or VHH40), and (ii) at leastone (e.g.1 or only 1) VHH antibody that has a VHH domain amino acid sequencethat is different from the VHH antibody of (i) (and preferably that binds to an epitope on canine IL-31 that is different from the epitope on canine IL-31 that is bound bythe VHH antibody of (i)) and that inhibits the ability of canine IL-31 to bind to canineIL-31RA and inhibits the ability of canine IL-31 to bind to canine IL-31RA. Typically,there is a linker between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii). A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) may be positioned in the construct in any order with respect to each other, e.g. a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), or vice versa. In some embodiments, the present invention provides a construct (e.g. apolypeptide construct or a single chain polypeptide construct or a fusion protein)comprising (i) at least one (e.g.1 or only 1) VHH antibody that inhibits the ability ofcanine IL-31 to bind to canine OSMR and inhibits the ability of canine IL-31 to bind to canine IL-31RA (e.g. an antibody based on VHH33 or VHH40), and (ii) at least one (e.g.1 or only 1) VHH antibody which binds to canine albumin (e.g. as described elsewhere herein, for example an antibody based on VHHA8), and (iii) atleast one (e.g. 1 or only 1) VHH antibody that has a VHH domain amino acidsequence that is different from the VHH antibody of (i) (and preferably that binds to an epitope on canine IL-31 that is different from the epitope on canine IL-31 that is bound by the VHH antibody of (i)) and that inhibits the ability of canine IL-31 to bindto canine IL-31RA and inhibits the ability of canine IL-31 to bind to canine IL-31RA.Typically, there are linkers between (positioned between) the VHH antibody of (i) and the VHH antibody of (ii) and the VHH antibody of (iii). A (or the) VHH antibody of (i) and a (or the) VHH antibody of (ii) and a (or the) antibody of (iii) may be positioned in the construct in any order with respect to each other. For example, in some embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (ii), which in turn may be positioned N- terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C- terminal direction, a VHH antibody of (i), a VHH antibody of (ii) and a VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (ii) may be positioned N-terminally with respect to a (or the) VHH antibody of (i), which in turn may be positioned N-terminally with respect to the VHH antibody of (iii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in theN-terminal to C-terminal direction, a VHH antibody of (ii), a VHH antibody of (i) anda VHH antibody of (iii). In some other embodiments, a (or the) VHH antibody of (i) may be positioned N-terminally with respect to a (or the) VHH antibody of (iii), which in turn may be positioned N-terminally with respect to the VHH antibody of (ii). Thus, in some embodiments, such a construct may comprise, in sequence (or order), in the N-terminal to C-terminal direction, a VHH antibody of (i), a VHH antibody of (iii) and a VHH antibody of (ii). In some embodiments, a construct of the invention does not comprise aVHH antibody which binds to canine albumin. In some embodiments, a construct ofthe invention does not comprise a VHH antibody which binds to canine albumincomprising a VHH domain having an amino acid sequence of SEQ ID NO:39. In some embodiments of constructs of the invention in which the construct(e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprises more than one (e.g.2, 3, 4 or 5, preferably 2) VHH antibody in accordance with the present invention, said construct comprises (i) a first VHH antibody which binds to canine IL-31 and (ii) a second VHH antibody which binds tocanine IL-31, wherein there is an amino acid sequence (or chain of amino acids)between the C-terminal end of said first VHH antibody of (i) and the N-terminal endof said second VHH antibody of (ii). In some embodiments, said amino acidsequence (or said amino acid chain) is at least 5, at least 10, at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 110, at least 120, at least 130, at least 140, at least 150, at least 200, atleast 250, at least 300, at least 350, at least 400, at least 450 or at least 500 aminoacids in length. In some embodiments, said amino acid sequence (or said aminoacid chain) is at least 100, at least 110, preferably at least 120 or at least 130 amino acids in length. In some embodiments, said amino acid sequence (or said amino acid chain) is 5 to 500, 50 to 500, 100 to 500, 120 to 500, 130 to 500, 200 to 500, 300 to 500, 5 to 300, 50 to 300, 100 to 300, 120 to 300, 130 to 300, 200 to 300, 5 to 200, 50 to 200, 100 to 200, 120 to 200, 130 to 200, 5 to 150, 50 to 150, 100 to 150,120 to 150, 130 to 150, 5 to 120, 50 to 120, 5 to 130 or 50 to 130. In someembodiments, said amino acid sequence (or said amino acid chain) is up to 100, up to 110, up to 120, up to 130, up to 140, up to 150, up to 200, up to 300, up to 400 orup to 500 amino acids in length. In some embodiments, the amino acid sequence(or amino acid chain) comprises a VHH antibody that binds to canine albumin (e.g.a VHH antibody that binds to canine albumin as described elsewhere herein). Insome embodiments, the amino acid sequence (or amino acid chain) does notcomprise a VHH antibody that binds to canine albumin. In some embodiments, theamino acid sequence (or amino acid chain) does not comprise a VHH antibody thatbinds to canine albumin comprising a VHH domain having an amino acid sequenceof SEQ ID NO:39. In some embodiments, said amino acid sequence (or said amino acid chain)may comprise one or more functional moiety (e.g. one or more therapeuticallyuseful moiety). However, in some other embodiments, said amino acid sequence (or said amino acid chain) may simply act as a spacer (and e.g. have no otherfunction). In some embodiments, the amino acid sequence (or amino acid chain) may comprise at least one (e.g.1, 2 or 3, e.g. only 1 or only 2 or only 3, preferably1) VHH antibody which binds to a protein other than canine IL-31 (e.g. the proteincanine albumin). In some embodiments, the amino acid sequence (or amino acidchain) does not comprise a VHH antibody that binds to canine albumin. In someembodiments, the amino acid sequence (or amino acid chain) does not comprise aVHH antibody that binds to canine albumin comprising a VHH domain having anamino acid sequence of SEQ ID NO:39. In some embodiments, the amino acidsequence may comprise at least one (e.g.1, 2 or 3, e.g. only 1 or only 2 or only 3, preferably 1) moiety which, when folded, is substantially the same size (e.g. hassubstantially the same length and / or dimensions) as a VHH antibody (e.g. asdetermined by in silico modelling). In some embodiments in which said amino acid sequence comprises one or more moiety (e.g. one or more functional or therapeutically useful moiety or one or more VHH antibody that binds to a protein other than canine IL-31), said amino acid sequence may include one or more linkers (e.g. as described elsewhere herein). Linkers may connect the amino acid sequence (or chain) to the C-terminal end of said first VHH antibody of (i) and the N- terminal end of said first VHH antibody of (i). In some embodiments of constructs of the invention in which the construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprises more than one (e.g.2, 3, 4 or 5, preferably 2) VHH antibody in accordance with the present invention, said construct comprises (i) a first VHH antibody which binds to canine IL-31 and (ii) a second VHH antibody which binds tocanine IL-31, wherein, when said construct is folded, there is a distance of at least10 angstroms (Å), at least 20Å, at least 30Å, at least 40Å (e.g. at least 41Å, at least42Å, at least 43Å, at least 44Å or at least 45Å), at least 50Å, at least 60Å, at least70Å, at least 80Å, at least 90Å or at least 100Å between the C-terminal end of saidfirst VHH antibody of (i) and the N-terminal end of said second VHH antibody of (ii).In some embodiments of constructs of the invention in which the construct (e.g. apolypeptide construct or a single chain polypeptide construct or a fusion protein) comprises more than one (e.g.2, 3, 4 or 5, preferably 2) VHH antibody in accordance with the present invention, said construct comprises (i) a first VHH antibody which binds to canine IL-31 and (ii) a second VHH antibody which binds tocanine IL-31, wherein, when said construct is folded, there is a distance of 10Å to45Å, 10Å to 50Å, 10Å to 60Å, 10Å to 70Å, 10Å to 80Å, 10Å to 90Å, 10Å to 100Å, 20Å to 45Å, 20Å to 50Å, 20Å to 60Å, 20Å to 70Å, 20Å to 80Å, 20Å to 90Å, 20Å to 100Å, 40Å to 45Å, 40Å to 50Å, 40Å to 60Å, 40Å to 70Å, 40Å to 80Å, 40Å to 90Å,40Å to 100Å between the C-terminal end of said first VHH antibody of (i) and the N-terminal end of said second VHH antibody of (ii). In some embodiments of constructs of the invention in which the construct (e.g. a polypeptide construct or a single chain polypeptide construct or a fusion protein) comprises more than one (e.g.2, 3, 4 or 5, preferably 2) VHH antibody in accordance with the present invention, said construct comprises (i) a first VHH antibody which binds to canine IL- 31 and (ii) a second VHH antibody which binds to canine IL-31, wherein, when saidconstruct is folded, there is a distance of up to 45Å, up to 50Å, up to 60Å, up to 70Å,up to 80Å, up to 90Å, up to 100Å or up to 200Å between the C-terminal end of saidfirst VHH antibody of (i) and the N-terminal end of said second VHH antibody of (ii). Methods of measuring (or determining) the distance between the C-terminal end of a said first VHH antibody of (i) and the N-terminal end of a said second VHHantibody of (ii) are well-known to a person skilled in the art, and any appropriatemethod can be used (e.g. in silico modelling methods). In some embodiments, thedistance between the C-terminal end of a said first VHH antibody of (i) and the N-terminal end of a said second VHH antibody of (ii) is determined by in silicomodelling. Suitable in silico modelling programs and software are well-known to aperson skilled in the art (e.g. YASARA software may be used). In someembodiments, there is an amino acid sequence comprising a VHH antibody thatbinds to canine albumin between the C-terminal end of said first VHH antibody of (i)and the N-terminal end of said second VHH antibody of (ii) (e.g. a VHH antibodythat binds to canine albumin as described elsewhere herein). In someembodiments, there is not an amino acid sequence comprising a VHH antibody thatbinds to canine albumin between the C-terminal end of said first VHH antibody of (i) and the N-terminal end of said second VHH antibody of (ii). In some embodiments, between the C-terminal end of said first VHH antibody of (i) and the N-terminal endof said second VHH antibody of (ii) there is not an amino acid sequence comprisinga VHH antibody that binds to canine albumin comprising a VHH domain having an amino acid sequence of SEQ ID NO:39. In some preferred embodiments that comprise (i) a first VHH antibody which binds to canine IL-31 and (ii) a second VHH antibody which binds to canine IL-31, said first VHH antibody of (i) and said second VHH antibody of (ii) have different amino acid sequences from each other. In some preferred embodiments that comprise (i) a first VHH antibody whichbinds to canine IL-31 and (ii) a second VHH antibody which binds to canine IL-31, said first VHH antibody of (i) and said second VHH antibody of (ii) bind to different epitopes on canine IL-31. In some embodiments that comprise (i) a first VHH antibody which binds to canine IL-31 and (ii) a second VHH antibody which binds to canine IL-31, said first VHH antibody of (i) may be based on VHH33 and said second VHH antibody of (ii) may be based on VHH40. In some embodiments that comprise (i) a first VHH antibody which binds to canine IL-31 and (ii) a second VHH antibody which binds to canine IL-31, said first VHH antibody of (i) may be based on VHH108’ and said second VHH antibody of (ii) may be based on VHH94’. In some embodiments that comprise (i) a first VHH antibody which binds to canine IL-31 and (ii) a second VHH antibody which binds to canine IL-31, said first VHH antibody of (i) may be based on VHH108 and said second VHH antibody of (ii) may be based on VHH94. In some such embodiments, said first VHH antibody of (i) is positioned in the construct N- terminally with respect to said second VHH antibody of (ii), although other configurations are also possible (e.g. as discussed elsewhere herein). Of course, in constructs of the present invention, activity (e.g. ability to bindto canine IL-31 or inhibit canine IL-31 signalling) of the VHH antibody of theinvention should be maintained (or substantially maintained). In constructs of thepresent invention that contain one or more additional components, activity of such additional components should be maintained (or substantially maintained). For example, in constructs of the present invention that contain one or more VHH antibody which binds to canine albumin, activity (e.g. ability to bind to caninealbumin, for example at neutral pH (e.g. pH7.4) and endosomal pH (e.g. pH5.5 orpH6.0)) should be maintained (or substantially maintained).Typically and preferably, constructs in accordance with the present invention do not comprise any antibody light chain sequences (e.g. light chain CDRs) and do not comprise any antibody constant domain (or antibody constant region) sequences and do not comprise any antibody hinge region sequences. As described herein, in one aspect the present invention provides a construct comprising at least one VHH antibody of the present invention. In another aspect, and in some embodiments, the present invention provides a constructcomprising at least one VHH domain sequence in accordance with the presentinvention. Embodiments of other aspects of the invention described herein apply,mutatis mutandis, to this aspect of the invention. As described elsewhere herein, constructs of the invention are preferably single chain polypeptides (or single chain polypeptide constructs or fusionpolypeptides or fusion polypeptide constructs). Thus, in multi-component constructsthe various (individual) components of the constructs are preferably on a singlepolypeptide chain (or present in a single fusion polypeptide or single fusion protein).However, in some other embodiments, various (individual) components of amulti-component construct may be linked (or conjugated) together by chemicalmeans. For example, various (individual) components could be linked (or conjugated or coupled) using heterobifunctional thiol-containing linkers, N-succinimidyl-3-(2-pyridyldithio-proprionate) or N-succinimidyl- 5 thioacetate.In another aspect, the present invention provides a polypeptide comprising(or consisting of) at least one VHH antibody in accordance with the presentinvention, or at least one VHH domain sequence in accordance with the presentinvention or at least one construct in accordance with the present invention. Embodiments of other aspects of the invention described herein apply, mutatis mutandis, to this aspect of the invention. As indicated above, VHH antibodies in accordance with the present invention bind to canine IL-31 (or are capable of binding or specifically binding to canine IL-31). Constructs and polypeptides of the present invention also bind to canine IL-31. Canine IL-31 may also be referred to herein as “caIL-31” or “caIL31”.Exemplary forms of canine IL-31 include native canine IL-31 andrecombinant canine IL-31. Exemplary forms of canine IL-31 (e.g. recombinant canine IL-31 and nativecanine IL-31) include full length canine IL-31 (with or without its signal peptide,preferably without its signal peptide). Canine IL-31 without its signal peptide may beconsidered full-length mature (or full-length processed) canine Il-31. Thus, full-length mature (or full-length processed) canine IL-31 is canine IL-31 lacking itssignal peptide. Sequences of canine IL-31 are well known and described in the art and canbe obtained for example from various sequence databases, e.g. Uniprot. Canine IL-31 (e.g. full-length mature (or full-length processed) canine IL-31) is commerciallyavailable. Apreferred and exemplary canine IL-31 molecule has the amino acidsequence of SEQ ID NO:2. The amino acid sequence of SEQ ID NO:2 is a canineIL-31 amino acid sequence that does not include the signal peptide sequence.Thus, the amino acid sequence of SEQ ID NO:2 is a full-length mature (or full-lengthprocessed) canine IL-31 amino acid sequence Thus, preferred VHH antibodies,constructs and polypeptides of the invention bind to or are capable of binding (or specifically binding) to SEQ ID NO:2. The amino acid sequence of SEQ ID NO:1 is an exemplary canine IL-31 molecule that includes additionally the signal peptide. In some embodiments, the canine IL-31 may be a His-tagged version (or form) of canine IL-31. Thus, in some embodiments, the canine IL-31 has the amino acid sequence of SEQ ID NO:2 and further includes a His-tag. Methods of assessing binding to (or ability to bind to) appropriate forms ofcanine IL-31 would be well-known to a person skilled in the art and any appropriatemethod can be used. A convenient and appropriate method for assessing binding would include invitro binding assays such as ELISA assays to assess binding of VHH antibodies,constructs and polypeptides to immobilised antigen, such as immobilised forms of canine IL-31 as described above, e.g. canine IL-31 of SEQ ID NO:2. Thus, in certain embodiments, VHH antibodies, constructs and polypeptides of the present invention bind to canine IL-31 (e.g. recombinant canine IL-31, e.g. with SEQ ID NO:2) in (as determined in) an ELISA assay. In some embodiments, the canine IL- 31 may be a His-tagged form of canine IL-31 (e.g. SEQ ID NO:2 with a His-tag). The skilled person will be familiar with ELISA assays and readily able to establish suitable conditions to assess the ability of VHH antibodies, constructs andpolypeptides to bind to canine IL-31 in such an assay. For example, in certainembodiments, VHH antibodies (or constructs or polypeptides) of the presentinvention bind to canine IL-31 (e.g. of SEQ ID NO:2) in (as determined in) an ELISAassay when a VHH antibody (or construct or polypeptide) is used at a concentrationof at least 10nM, at least 50nM, at least 100nM, at least 300nM or at least 500nM,or a concentration (or concentrations) in the range of 10nM to 10µM, 50nM to 10µM,100nM to 10µM, 300nM to 10µM, 500nM to 10µM, 10nM to 1µM, 50nM to 1µM,100nM to 1µM, 300nM to 1µM, or 500nM to 1µM. In some embodiments, VHHantibodies (or constructs or polypeptides) of the present invention bind to canine IL-31 (e.g. of SEQ ID NO:2) in (as determined in) an ELISA assay with a VHH antibody(or construct or polypeptide) EC50 concentration of <1µM, <500nM, <250nM,<100nM, <50nM, or <10nM. In some embodiments, the ability of a VHH antibody of the present invention to bind to canine IL-31 may be determined in (or be as determined in) an ELISA assay that comprises: (a) coating wells of an ELISA (e.g. MaxiSorp) plate (e.g.96 well plate) with (e.g.50µl of 3µg / ml in PBS of) a canine IL-31 polypeptide (e.g. SEQ ID NO:2, orcanine IL-31 of SEQ ID NO:2 with a His-tag) (e.g. overnight at 4oC), (b) blocking the coated wells with (e.g.200µl / well of a 96 well plate), e.g. for 1 hour and / or e.g. with milk (e.g. 4% skimmed milk / PBS);(c) washing blocked wells (e.g. with PBS-Tween 0.05% (pH7.4), e.g.200µl / well of a 96 well plate); (d) adding a c-myc tagged (preferably C-terminally c-myc tagged) form of the VHH antibody (test VHH antibody) (e.g. at a (or a range of) finalconcentration(s), or serial dilutions, of between 0.06nM to 10µM) to thecoated and blocked wells and incubating (e.g. for 1 hour, e.g. at roomtemperature); (e) washing wells (e.g. with PBS-Tween 0.05%, e.g.3 times (e.g.3x 200µl / well of a 96 well plate); (f) adding a mouse-anti-c-myc tag-HRP antibody, e.g. in PBS-Tween 0.05%(e.g.60µl of mouse-anti-c-myc tag-HRP, Roche Cat No.: 11667203001), and incubating (e.g. for 1 hour, e.g. at room temperature);(g) washing wells (e.g. with PBS-Tween 0.05%, e.g.3 times (e.g.3x 200µl / well of a 96 well plate); (h) adding a chromogenic substrate (e.g.3,3´,5,5´-tetramentylbenzidine, TMB) for HRP (horseradish peroxidase) to the wells, and preferably then stopping the reaction (e.g. with 0.5M H2SO4, e.g.75µl thereof / well of a 96 well plate); (i) detecting (or measuring or quantifying) the signal produced from the chromogenic substrate / HRP reaction (e.g. with a spectrophotometer, e.g. measuring absorbance at 450nm), wherein detected signal is indicative of binding of the VHH antibody to canine IL- 31. Particularly preferred ELISA assays are described elsewhere herein, e.g. in theExamples section (e.g. in Example 2 herein).In some embodiments, the ability of a VHH antibody or construct orpolypeptide of the present invention to bind to canine IL-31 may be determined in(or be as determined in) an ELISA assay in which a VHH antibody or construct orpolypeptide of the invention is immobilised (e.g. coated on an ELISA plate) and the ability of canine IL-31 (e.g. of SEQ ID NO:2) to bind to the immobilised VHH antibody or construct or polypeptide is determined. In some embodiments, the ability of a VHH antibody or construct orpolypeptide of the present invention to bind to canine IL-31 may be determined in(or be as determined in) an ELISA assay that comprises: (a) coating wells of an ELISA (e.g. MaxiSorp) plate (e.g.96 well plate) with aVHH antibody or construct or polypeptide of the invention (e.g.100nM of aVHH antibody or 200nM of a construct or polypeptide), for example in PBS, for example overnight at 4oC, (b) blocking the coated wells with (e.g.200µl / well of a 96 well plate), e.g. for 1 hour and / or e.g. with 1% casein, e.g.1% casein / PBS); (c) washing blocked wells (e.g. with PBS-Tween 0.05% (pH7.4), e.g.200µl / well of a 96 well plate); (d) adding biotinylated canine IL-31 (e.g. biotinylated form of IL-31 of SEQ ID NO:2) (e.g. at a (or a range of) final concentration(s), or serial dilutions (e.g.3-fold serial dilution), of between 1µM or 3µM down to 0.006nM or 0.017nM)to the coated and blocked wells and incubating (e.g. for 1 hour, e.g. at roomtemperature); (e) washing wells (e.g. with PBS-Tween 0.05%, e.g.3 times (e.g.3x 200µl / well of a 96 well plate);(f) adding streptavidin-HRP (e.g.60µl of streptavidin-HRP of JIR Cat No.: 0.16-030-084), e.g. in 0.25% casein, and incubating (e.g. for 1 hour, e.g. at room temperature); (g) washing wells (e.g. with PBS-Tween 0.05%, e.g.3 times (e.g.3x 200µl / well of a 96 well plate); (h) adding a chromogenic substrate (e.g.3,3´,5,5´-tetramentylbenzidine, TMB) for HRP (horseradish peroxidase) to the wells, and preferably then stopping the reaction (e.g. with 0.5M H2SO4, e.g.75µl thereof / well of a 96 well plate); (i) detecting (or measuring or quantifying) the signal produced from the chromogenic substrate / HRP reaction (e.g. with a spectrophotometer, e.g. measuring absorbance at 450nm), wherein detected signal is indicative of binding of the VHH antibody to canine IL- 31. In some such embodiments, VHH antibodies or constructs or polypeptides of the present invention bind to canine IL-31 (e.g. of SEQ ID NO:2) in (as determinedin) such an ELISA assay when canine IL-31 (e.g. biotinylated canine IL-31) is usedat a concentration of at least 10nM, at least 50nM, at least 100nM, at least 300nMor at least 500nM, or a concentration (or concentrations) in the range of 10nM to1µM, 50nM to 1µM, 100nM to 1µM, 300nM to 1µM, or 500nM to 1µM. In someembodiments, VHH antibodies (or constructs or polypeptides) of the present invention bind to canine IL-31 (e.g. of SEQ ID NO:2) in (as determined in) an ELISAassay, wherein the canine IL-31 EC50 concentration is <1µM, <500nM, <250nM,<100nM, preferably <50nM, <10nM, or <5nM . Particularly preferred ELISA assaysare described elsewhere herein, e.g. in the Examples section (e.g. in Example 3and 4 herein).In certain embodiments, VHH antibodies (or constructs or polypeptides) ofthe present invention bind to canine IL-31 (e.g. of SEQ ID NO:2) in (as determinedin) a Surface Plasmon Resonance (SPR) assay (or, alternatively viewed, by SPR).A SPR assay may, for example, be a Biacore assay (e.g. performed on a T200Biacore (Cytiva) or a Biacore 8K+). Suitable SPR assays are known in the art. Insome embodiments, the SPR assay is a single cycle kinetics (SCK) SPR assay. In some embodiments, the SPR assay is a multi-cycle kinetics (MCK) SPR assay. Insome embodiments, a Surface Plasmon Resonance (SPR) assay may beperformed (or as performed), for example, at 25oC (e.g. at pH7.4). In someembodiments, a Surface Plasmon Resonance (SPR) assay may be performed (or as performed), for example, at room (or ambient) temperature (e.g. approximately22oC) (e.g. at pH7.4). In some embodiments, the SPR assay is a single cyclekinetics (SCK) SPR assay performed at room (or ambient) temperature (e.g.approximately 22oC) (e.g. at pH7.4). In some embodiments, the SPR assay is amulti-cycle kinetics (MCK) SPR assay performed at 25oC (e.g. at pH7.4). Inpreferred embodiments, SPR assays are performed at pH7.4. In certain preferred SPR assays, canine IL-31, is captured (or immobilised) on a solid support (e.g. a sensor chip), for example via amine coupling (e.g. with EDC / NHS and / or e.g. approximately 500 or approximately 1000 or approximately 5000 Resonance Units(RU) canine IL-31 is immobilized) and various concentrations (e.g. a dilution series,e.g. a doubling or five-fold dilution series, e.g.2-fold serial dilutions from 10nM to 0.6nM) of the VHH antibody (or construct or polypeptide) to be tested is then injected. VHH antibody (or construct or polypeptide) concentrations may be selected at a range such that the chip is not saturated and which allow robust fitting by the SPR / Biacore software. Preferred concentrations and flow-rates for injection are described in the Examples section. Particularly preferred SPR assays are described elsewhere herein, e.g. in the Examples section (e.g. in Examples 2, 3, 4,5 and 6 herein).In some embodiments, VHH antibodies (or constructs or polypeptides) of thepresent invention have an affinity (KD(equilibrium dissociation constant)) for canine IL-31 (e.g. of SEQ ID NO:2) in the nanomolar (nM) or picomolar range (pM), for example when determined in a SPR assay (e.g. a SPR assay as described herein). In some embodiments, VHH antibodies (or constructs or polypeptides) of the present invention have an affinity (KD(equilibrium dissociation constant)) for canineIL-31 (e.g. of SEQ ID NO:2) in the range of 1pM to 100nM or 10pM to 100nM, orlower (better / stronger), for example when determined in a SPR assay (e.g. a SPR assay as described herein), for example an SPR assay performed at pH7.4. In some embodiments, VHH antibodies (or constructs or polypeptides) of the present invention have an affinity (KD (equilibrium dissociation constant)) for canineIL-31 (e.g. of SEQ ID NO:2), for example as determined in a SPR assay (e.g. a SPRassay as described herein, e.g. a SPR assay performed at pH7.4), in the range of 10pM to 75nM, 10pM to 50nM, 10pM to 25nM, 10pM to 10nM, 10pM to 5nM, 10pM to 1nM, 10pM to 500pM, 50pM to 100nM, 50pM to 75nM, 50pM to 50nM, 50pM to25nM, 50pM to 10nM, 50pM to 5nM, 50pM to 1nM, 50pM to 500pM, 100pM to100nM, 100pM to 75nM, 100pM to 50nM, 100pM to 25nM, 100pM to 10nM, 100pM to 5nM, 100pM to 1nM, 100pM to 500pM, 500pM to 100nM, 500pM to 75nM, 500pM to 50nM, 500pM to 25nM, 500pM to 10nM, 500pM to 5nM, 500pM to 1nM, 1nM to100nM, 1nM to 75nM, 1nM to 50nM, 1nM to 25nM, 1nM to 10nM, or 1nM to 5nM.In some embodiments, VHH antibodies (or constructs or polypeptides) of the present invention have an affinity (KD (equilibrium dissociation constant)) for canineIL-31 (e.g. e.g. of SEQ ID NO:2), for example as determined in a SPR assay (e.g. aSPR assay as described herein, e.g. a SPR assay performed at pH7.4), in the range of 10pM to 50nM, 10pM to 40nM, 10pM to 30nM, 10pM to 20nM, 50pM to 50nM, 50pM to 40nM, 50pM to 30nM, 100pM to 50nM, 100pM to 40nM, 100pM to 30nM, 500pM to 50nM, 500pM to 40nM, or 500pM to 30nM. In some embodiments, VHH antibodies (or constructs or polypeptides) of thepresent invention have a binding affinity for canine IL-31 (e.g. of SEQ ID NO:2) thatcorresponds to a KD of less than 200nM, preferably less than 100 nM, less than 50nM, less than 25nM, less than 20nM, less than 10nM, less than 5nM, less than 1nM (or less than 1000pM), less than 900pM, less than 800pM, less than 700pM, less than 600pM, less than 500pM, less than 400pM, less than 300pM, less than 200pM, less than 100pM or less than 50pM, for example when determined in an SPR assay (e.g. at pH7.4). Particular exemplary binding affinities are disclosed in the Examples. Some preferred VHH antibodies (or constructs or polypeptides) of theinvention bind to canine IL-31 (e.g. of SEQ ID NO:2) with a KD of 50nM or less (orless than 50nM), for example when determined in an SPR assay (e.g. at pH7.4). Some preferred VHH antibodies (or constructs or polypeptides) of theinvention bind to canine IL-31 (e.g. of SEQ ID NO:2) with a KDof 20nM or less (or less than 20nM), for example when determined in an SPR assay (e.g. at pH7.4). Some preferred constructs of the invention bind to canine IL-31 (e.g. of SEQ ID NO:2) with a KDof 10nM or less (or less than 10nM), for example when determined in an SPR assay (e.g. at pH7.4). Some preferred constructs of the invention bind to canine IL-31 (e.g. of SEQ ID NO:2) with a KD of 1nM or less (or less than 1nM), for example when determined in an SPR assay (e.g. at pH7.4). Some preferred constructs of the invention bind to canine IL-31 (e.g. of SEQ ID NO:2) with a KD of 500pM or less (or less than 500pM), for example when determined in an SPR assay (e.g. at pH7.4). Some preferred constructs of the invention bind to canine IL-31 (e.g. of SEQ ID NO:2) with a KD of 200pM or less (or less than 200pM), for example when determined in an SPR assay (e.g. at pH7.4). Some preferred constructs of the invention bind to canine IL-31 (e.g. of SEQ ID NO:2) with a KD of 100pM or less (or less than 100pM), for example when determined in an SPR assay (e.g. at pH7.4). Binding affinity (or binding affinity values, e.g. KD) and / or other kinetic parameters (e.g. Ka (or “on-rate” or “association rate constant” or Kon) and Kd (or “off-rate” or “dissociation rate constant” or Koff)) may be determined by SPR, for example as described elsewhere herein. In some embodiments, binding affinity (or binding affinity values, e.g. KD)and / or other kinetic parameters of VHH antibodies in accordance with the presentinvention is determined (or is as determined) in a single cycle kinetics SPR assay (e.g. at pH7.4 and / or e.g. at room (or ambient) temperature). Suitable SPR assays are described elsewhere herein. In some embodiments, binding affinity (or binding affinity values, e.g. KD) and / or other kinetic parameters of constructs (or polypeptides) in accordance with the present invention is determined (or is as determined) in a single cycle kinetics SPR assay (e.g. at pH7.4 and / or e.g. at room (or ambient) temperature). Suitable SPR assays are described elsewhere herein. In some embodiments, binding affinity (or binding affinity values, e.g. KD) and / or other kinetic parameters of constructs (or polypeptides) in accordance with the present invention is determined (or is as determined) in a multi cycle kinetics SPR assay (e.g. at pH7.4 and / or e.g. at 25oC). Suitable SPR assays are described elsewhere herein. In some embodiments, VHH antibodies (or constructs or polypeptides) of the present invention bind to (or are capable of binding to) canine IL-31 (e.g. of SEQ ID NO:2), e.g. with an affinity or affinity value (e.g. KD) described elsewhere herein, in (or as determined in) a (single cycle kinetics) SPR assay (e.g. a BIACore assay, e.g. Biacore 8K+ assay) in which (a) EDC (1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide) and NHS (N-hydroxysuccinimide) are used to activate the sensor chip (matrix) surface (e.g. a CM5 sensor chip surface (matrix surface)); (b) Canine IL-31 (e.g. of SEQ ID NO:2) (or a His tagged versionof canine IL-31), preferably diluted in pH5.0 acetate buffer (preferably in 10mM Sodium Acetate buffer, pH5.0), is flowed over the activated chip surface to immobilise canine IL-31 (e.g. with the aim to reach 5,000 RU or 500RU, or e.g. achieving about 5000 RU or 500RU);(c) Remaining activated surface groups are blocked (ordeactivated) (preferably with ethanolamine, e.g. with 1M ethanolamine-HCl, pH8.5); (d) Serial dilutions (e.g. a concentration series, e.g. doublingdilutions, e.g. from 10nM down to 0.6nM) of VHH antibody (or construct or polypeptide) in running buffer (e.g. HBS-EP+), e.g. a pH7.4 running buffer (e.g. HBS-EP+, pH7.4), are injected at a flowrate of 30µl / minute (e.g. for 2 minutes), preferably with an off-ratewash (of e.g.1 minute) between VHH antibody (or construct or polypeptide) injections (between injections of different concentrations / dilutions of VHH antibody (or construct or polypeptide)). In such a (single cycle kinetics) SPR assay, there is a final off-rate wash after the final injection of VHH antibody (or construct or polypeptide), i.e. after theinjection of the final concentration / dilution of VHH antibody (or construct orpolypeptide). The final off-rate wash may be for 5 minutes. In single cycle kinetics SPR assays, at the end of the cycle (i.e. at the end of the assay, i.e. after all injections in the cycle) chip regeneration may be performed (e.g. by one injection of 1M NaCl followed by an injection of a Glycine pH1.5 buffer (e.g.1mM Glycine pH1.5 buffer). Preferably, single cycle kinetics SPR assays are performed at room (or ambient) temperature (e.g. approximately 22oC). Particularly preferred single cycle kinetics SPR assays are described in the Example section herein (e.g. Example 2, Example 3 and Example 5). In some embodiments, VHH antibodies (or constructs or polypeptides) of thepresent invention bind to (or are capable of binding to) canine IL-31 (e.g. of SEQ IDNO:2), e.g. with an affinity or affinity value (e.g. KD) described elsewhere herein, in(or as determined in) a (multi-cycle kinetics) SPR assay (e.g. a BIACore assay, e.g. Biacore T200 assay) in which (a) EDC (1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide) and NHS (N-hydroxysuccinimide) are used to activate the sensor chip (matrix) surface (e.g. a CM5 sensor chip surface (matrix surface)); (b) Canine IL-31 (e.g. of SEQ ID NO:2) (or a His tagged versionof canine IL-31), preferably diluted in pH5.0 acetate buffer (preferably in 10mM Sodium Acetate buffer, pH5.0), is flowed over the activated chip surface to immobilise canine IL-31 (e.g. with the aim to reach1,000 RU, or e.g. achieving about 1000 RU);(c) Remaining activated surface groups are blocked (ordeactivated) (preferably with ethanolamine, e.g. with 1Methanolamine-HCl, pH8.5); (d) Serial dilutions (e.g. a concentration series, e.g. five-foldserial dilutions, e.g. from 40nM down to 0.32nM) of VHH antibody (orconstruct or polypeptide) in running buffer (e.g. HBS-P+), e.g. apH7.4 running buffer (e.g. HBS-P+, pH7.4), are injected at a flow rateof 10µl / minute;(e) Association is measured, e.g. over 5 minutes (i.e. five minuteassociation) and dissociation is measured over 5 minutes (i.e. 5minute dissociation phase), and preferably all measurements areperformed at 25oC (preferably at pH7.4) (e.g. HBS-P+, pH7.4), andchip regeneration (preferably 1 minute regeneration) is preferablyperformed with Glycine pH1.5 buffer (e.g.10mM Glycine pH1.5 buffer, e.g. from Cytvia); and (f) Kinetic parameters are determined by fitting curves using a1:1 binding model (e.g. using Biacore T200 evaluation software). In some embodiments, VHH antibodies (or constructs or polypeptides) of the present invention bind to (or are capable of binding to) canine IL-31 (e.g. of SEQ ID NO:2), e.g. with an affinity or affinity value (e.g. KD) described elsewhere herein, in (or as determined in) a (multi-cycle kinetics) SPR assay (e.g. a BIACore assay, e.g. Biacore T200 assay) having a step (e) in which association is measured, e.g. over 5 minutes (i.e. five minute association) and dissociation is measured over 60 minutes (i.e.5 minute dissociation phase), and preferably all measurements are performed at 25oC (preferably at pH7.4) (e.g. in buffer HBS-P+, pH7.4), and chip regeneration (preferably 1 minute regeneration) is preferably performed with Glycine pH1.5 buffer (e.g.10mM Glycine pH1.5 buffer, e.g. from Cytvia). In some embodiments, VHH antibodies (or constructs or polypeptides) of the present invention bind to (or are capable of binding to) canine IL-31 (e.g. of SEQ ID NO:2), e.g. with an affinity or affinity value (e.g. KD) described elsewhere herein, in (or as determined in) a (multi-cycle kinetics) SPR assay (e.g. a BIACore assay, e.g. Biacore 1K+ assay) in which (a) EDC (1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide) and NHS (N-hydroxysuccinimide) are used to activate the sensor chip (matrix) surface (e.g. a CM5 sensor chip surface (matrix surface)); (b) Canine IL-31 (e.g. of SEQ ID NO:2) (or a His tagged versionof canine IL-31), preferably diluted in pH4.5 acetate buffer (preferablyin 10mM Sodium Acetate buffer, pH4.5), is flowed over the activated chip surface to immobilise canine IL-31 (e.g. with the aim to reach e.g.600 RU or 3,200 RU, or e.g. achieving about 600 RU or about3,200 RU); (c) Remaining activated surface groups are blocked (ordeactivated) (preferably with ethanolamine, e.g. with 1M ethanolamine-HCl, pH8.5);(d) Dilutions (e.g. serial dilutions or a concentration series, e.g.concentrations of 250nM and 25nM or e.g. five-fold serial dilutions, e.g. from 250nM down to 0.4nM or down to 0.2nM) of VHH antibody(or construct or polypeptide) in running buffer (e.g. HBS-EP+), e.g. a pH7.4 running buffer (e.g. HBS-EP+, pH7.4), are injected at a flowrate of 30µl / minute; (e) Association is measured, e.g. over 2 minutes or over 5minutes (i.e. two minute or five minute association) and dissociation is measured over 10 minutes (i.e. 10 minute dissociation phase), andpreferably all measurements are performed at 25oC (preferably at pH7.4) (e.g. HBS-EP+, pH7.4), and chip regeneration (preferably 30 second regeneration) is preferably performed with Glycine pH1.5buffer (e.g.10mM Glycine pH1.5 buffer, e.g. from Cytvia); and (f) Kinetic parameters are determined by fitting curves using a1:1 binding model (e.g. using Biacore 1K+ evaluation software).Preferably, multi-cycle kinetics SPR assays are performed at 25oC. Particularly preferred multi cycle kinetics SPR assays are described in theExample section herein (e.g. Example 4 and Example 6 and Example 8 andExample 9). In addition to being useful to determine KD (equilibrium dissociationconstant), SPR assays described herein may also be used to determine otherkinetic parameters (e.g. Ka (or “on-rate” or “association rate constant” or Kon) and Kd (or “off-rate” or “dissociation rate constant” or Koff)). In some embodiments, VHH antibodies (or constructs or polypeptides) of the present invention have an off-rate (Kd, “dissociation rate constant” or Koff) for canineIL-31 (e.g. e.g. of SEQ ID NO:2) that corresponds to a Kd in the range of 1x10-61 / sto 1x10-11 / s, or in the range of 1x10-61 / s to 5x10-21 / s, or in the range of 1x10-61 / s to 1.5x10-21 / s, or in the range of 5x10-61 / s to 1x10-11 / s, or in the range of 5x10-61 / s to 5x10-21 / s, or in the range of 5x10-61 / s to 1.5x10-21 / s, or in the range of 1x10-51 / s to 1x10-11 / s, or in the range of 1x10-51 / s to 5x10-21 / s, or in the range of 1x10-51 / s to 1.5x10-21 / s (1 / s is the unit of off-rate), for example when determined in a SPR assay (e.g. a SPR assay as described herein). Such a SPR assay may be performed (or as performed) at pH7.4. Such a SPR assay may, for example, beperformed (or as performed) at 25oC or at room (or ambient) temperature (e.g.approximately 22oC). In some embodiments, VHH antibodies (or constructs or polypeptides) of thepresent invention have an off-rate (Kd, “dissociation rate constant” or Koff) for canineIL-31 (e.g. of SEQ ID NO:2) that corresponds to a Kd of less than 5x10-1, less than1x10-1, less than 5x10-2, less than 1x10-21 / s, less than 5x10-3, less than 1x10-31 / s,less than 5x10-4, less than 1x10-41 / s, or less than 5x10-51 / s, for example when determined in a SPR assay (e.g. a SPR assay as described herein). Such a SPR assay may be performed (or as performed) at pH7.4. Such a SPR assay may, forexample, be performed (or as performed) at 25oC or at room (or ambient)temperature (e.g. approximately 22oC). In some embodiments, VHH antibodies (or constructs or polypeptides) of thepresent invention have an off-rate (Kd, “dissociation rate constant” or Koff) for canineIL-31 (e.g. of SEQ ID NO:2) that corresponds to a Kd of at least 1x10-61 / s, at least5x10-6, or 1x10-5, for example when determined in a SPR assay (e.g. a SPR assayas described herein). Such a SPR assay may be performed (or as performed) at pH7.4. Such a SPR assay may, for example, be performed (or as performed) at 25oC or at room (or ambient) temperature (e.g. approximately 22oC). IL-31 signals via a receptor complex that is composed of IL-31 receptor A (IL-31RA) and oncostatin M receptor (OSMR). In some embodiments, a VHH antibody (or construct or polypeptide) of thepresent invention binds to (or is capable of binding to) canine IL-31 and (i) inhibits(or impairs, or is capable of inhibiting or impairing) canine IL-31 binding to canine IL-31RA (e.g. extracellular domain of canine IL-31RA) and / or (ii) inhibits (or impairs, oris capable of inhibiting or impairing) canine IL-31 binding to canine OSMR (e.g.extracellular domain of canine OSMR). In some embodiments, a VHH antibody (or construct or polypeptide) of thepresent invention binds to (or is capable of binding to) canine IL-31 and (i) inhibits(or impairs, or is capable of inhibiting or impairing) canine IL-31 binding to canine IL-31RA (e.g. extracellular domain of canine IL-31RA) and (ii) inhibits (or impairs, or iscapable of inhibiting or impairing) canine IL-31 binding to canine OSMR (e.g.extracellular domain of canine OSMR). Such a VHH antibody may be, for example, an antibody based on the VHH33 or VHH40 antibody of the present invention. In some embodiments, a VHH antibody (or construct or polypeptide) of thepresent invention binds to (or is capable of binding to) canine IL-31 and inhibits (orimpairs, or is capable of inhibiting or impairing) canine IL-31 binding to canine IL-31RA (e.g. extracellular domain of canine IL-31RA), but does not inhibit (or impair), or does not significantly inhibit (or significantly impair) canine IL-31 binding to canineOSMR (e.g. extracellular domain of canine OSMR). Such a VHH antibody may be,for example, an antibody based on the VHH94 or VHH94’ antibody of the presentinvention. In some embodiments, a VHH antibody (or construct or polypeptide) of thepresent invention binds to (or is capable of binding to) canine IL-31 and inhibits (orimpairs, or is capable of inhibiting or impairing) canine IL-31 binding to canineOSMR (e.g. extracellular domain of canine OSMR), but does not inhibit (or impair),or does not significantly inhibit (or significantly impair) canine IL-31 binding to canineIL-31RA (e.g. extracellular domain of canine IL-31RA). Such a VHH antibody maybe, for example, an antibody based on the VHH108 or VHH108’ antibody of thepresent invention. Negligible inhibition of binding of canine IL-31 (or de minimis inhibition ofbinding) to canine OSMR (or extracellular domain of canine OSMR) and / or tocanine IL-31RA (or extracellular domain of canine IL-31RA) is not consideredinhibition of binding, or significant inhibition of binding. By way of example, anynegligible / de minimis amount (or level) of inhibition of binding that may beobserved (or measured or detected) for a VHH antibody (or construct or polypeptide) of the invention that is equivalent to (or that is essentially equivalent to), or that corresponds to (or that essentially corresponds to), or that is less than or equal to, or that is not greater than (or not significantly greater than) inhibition of binding observed (or measured) with an appropriate negative control (e.g. with anegative control VHH antibody that does not bind to canine IL-31), is not consideredinhibition of binding, or significant inhibition of binding. Thus, for example, in embodiments in which VHH antibodies (or constructs or polypeptides) of the presentinvention do not inhibit, or do not significantly inhibit, binding of canine IL-31 tocanine OSMR (or extracellular domain of canine OSMR), the amount (or level) of inhibition of binding (if any) observed (or measured) may be equivalent to (or may be essentially equivalent to), or may correspond to (or may essentially correspond to), or may be less than or equal to, or may be not greater than (or not significantly greater than) binding observed (or measured) with an appropriate negative control (e.g. with a negative control VHH antibody that does not bind to canine IL-31). Thus, for example, in embodiments in which VHH antibodies (or constructs or polypeptides) of the present invention do not inhibit, or do not significantly inhibit, binding of canine IL-31 to canine IL-31RA (or extracellular domain of canine IL- 31RA), the amount (or level) of inhibition of binding (if any) observed (or measured) may be equivalent to (or may be essentially equivalent to), or may correspond to (or may essentially correspond to), or may be less than or equal to, or may be not greater than (or not significantly greater than) binding observed (or measured) with an appropriate negative control (e.g. with a negative control VHH antibody that does not bind to canine IL-31). In some embodiments, the level of inhibition (or amount of inhibition) of binding of canine IL-31 to canine OSMR (or extracellular domain of canine OSMR)or to canine IL-31RA (or extracellular domain of canine IL-31RA) observed with (orcaused by or elicited by) a negative control (e.g. a control VHH antibody that does not bind to canine IL-31) represents (or is set as) the zero inhibition level (or zero inhibition value or 0% inhibition level or value). Thus, in some embodiments, the % inhibitions of binding of canine IL-31 to canine OSMR (or extracellular domain of canine OSMR) or to canine IL-31RA (or extracellular domain of canine IL-31RA) discussed elsewhere herein are as compared to (or relative to) the inhibition observed with (or caused by or elicited by) a negative control (e.g. a control VHHantibody that does not bind to canine IL-31).In some embodiments, inhibition of binding of canine IL-31 to canine OSMR (or extracellular domain of canine OSMR) and / or to canine IL-31RA (or extracellular domain of canine IL-31RA), as appropriate, is an inhibition of at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, preferably at least 35%, preferably at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, atleast 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or100%. In some embodiments, inhibition of binding of canine IL-31 to canine OSMR (or extracellular domain of canine OSMR) and / or to canine IL-31RA (or extracellulardomain of canine IL-31RA), as appropriate, is an inhibition of up to 50%, up to 55%,up to 60%, up to 65%, up to 70%, up to 75%, up to 80%, up to 85%, up to 90%, up to 95% or up to 100%. In some embodiments, inhibition of binding of canine IL-31 to canine OSMR (or extracellular domain of canine OSMR) and / or to canine IL-31RA (or extracellular domain of canine IL-31RA), as appropriate, is an inhibition of 10%-100%, 15%- 100%, 20%-100%, 25%-100%, 30%-100%, 35%-100%, 40%-100%, 45%-100%, 50%-100%, 55%-100%, 60%-100%, 65%-100%, 70%-100%, 75%-100%, 80%- 100%, 85%-100%, 90%-100% or 95%-100%. In some embodiments, inhibition of binding of canine IL-31 to canine OSMR (or extracellular domain of canine OSMR) and / or to canine IL-31RA (or extracellular domain of canine IL-31RA), as appropriate, is an inhibition of 10%-75%, 15%-75%, 20%-75%, 25%-75%, 30%-75%, 35%-75%, 40%-75%, 45%-75%, 50%-75%, 55%- 75%, 60%-75%, 65%-75% or 70%-75%. In some embodiments, inhibition of binding of canine IL-31 to canine OSMR(or extracellular domain of canine OSMR) and / or to canine IL-31RA (or extracellular domain of canine IL-31RA), as appropriate, is an inhibition of 10%-50%, 15%-50%, 20%-50%, 25%-50%, 30%-50%, 35%-50%, 40%-50% or 45%-50%. In some embodiments, a VHH antibody (or construct or polypeptide) of thepresent invention binds to (or is capable of binding to) canine IL-31 and (i) inhibits(or impairs, or is capable of inhibiting or impairing) canine IL-31 binding to canine IL-31RA (e.g. extracellular domain of canine IL-31RA) and (ii) inhibits (or impairs, or iscapable of inhibiting or impairing) canine IL-31 binding to canine OSMR (e.g. extracellular domain of canine OSMR), wherein the inhibition of binding of canine IL- 31 to canine OSMR (or extracellular domain of canine OSMR) and the inhibition of binding of canine IL-31 to canine IL-31RA (or extracellular domain of canine IL- 31RA) is an inhibition of at least 30%, preferably at least 35%, preferably at least 40%, at least 45%, 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 90%, at least 95% or 100%. Such a VHH antibody may be, for example, an antibody based on the VHH33 or VHH40 antibody of the present invention. In some embodiments, a VHH antibody (or construct or polypeptide) of thepresent invention binds to (or is capable of binding to) canine IL-31 and inhibits (orimpairs, or is capable of inhibiting or impairing) canine IL-31 binding to canine IL- 31RA (e.g. extracellular domain of canine IL-31RA), but does not inhibit (or impair), or does not significantly inhibit (or significantly impair) canine IL-31 binding to canine OSMR (e.g. extracellular domain of canine OSMR), wherein the inhibition of binding of canine IL-31 to canine IL-31RA (or extracellular domain of canine IL-31RA) is an inhibition of at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, preferably at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or 100%. In some such embodiments, the inhibition of binding of canine IL-31 to canine OSMR (or extracellular domain of canine OSMR) may be 0%. A VHH antibody described in this paragraph may be, for example, VHH antibody based on the VHH94 antibody or VHH94’ of the present invention.In some embodiments, a VHH antibody (or construct or polypeptide) of thepresent invention binds to (or is capable of binding to) canine IL-31 and inhibits (orimpairs, or is capable of inhibiting or impairing) canine IL-31 binding to canineOSMR (e.g. extracellular domain of canine OSMR), but does not inhibit (or impair),or does not significantly inhibit (or significantly impair), canine IL-31 binding tocanine IL-31RA (e.g. extracellular domain of canine IL-31RA), wherein the inhibition of binding of canine IL-31 to canine OSMR (or extracellular domain of canine OSMR) is an inhibition of at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, preferably at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or 100%. In some such embodiments, the inhibition of binding of canine IL-31 to canine IL-31RA (or extracellular domain of canine IL-31RA) may be 0%. A VHH antibody described inthis paragraph may be, for example, VHH antibody based on the VHH108 orVHH108’ antibody of the present invention. In some embodiments, a VHH antibody that does not inhibit (or impair), or does not significantly inhibit (or significantly impair) canine IL-31 binding to canine IL-31RA (e.g. extracellular domain of canine IL-31RA) shows 0% inhibition of canine IL-31 binding to canine IL-31RA (e.g. extracellular domain of canine IL-31RA). In some embodiments, a VHH antibody that does not inhibit (or impair), or does not significantly inhibit (or significantly impair) canine IL-31 binding to canine OSMR (e.g. extracellular domain of canine OSMR) shows 0% inhibition of canine IL-31 binding to canine OSMR (e.g. extracellular domain of canine OSMR). IL-31 binds to the extracellular domains of IL-31RA and OSMR. Thus, if a VHH antibody (or construct or polypeptide) of the invention inhibits binding of canine IL-31 to extracellular domain of canine IL-31RA, then that is indicative of inhibition of binding to canine IL-31RA. Likewise, if a VHH antibody (or construct or polypeptide) of the invention inhibits binding of canine IL-31 to extracellular domain of canine OSMR, then that is indicative of inhibition of binding to canine OSMR. Sequences of canine IL-31RA and canine OSMR (and extracellular domains thereof) are well known and described in the art and can be obtained for examplefrom various sequence databases, e.g. Uniprot. A preferred and exemplary canineIL-31RA extracellular domain has the amino acid sequence of SEQ ID NO:62. Apreferred and exemplary canine OSMR extracellular domain has the amino acid sequence of SEQ ID NO:63. Methods of assessing (or determining) ability of a VHH antibody (orconstruct or polypeptide) of the present invention to inhibit (or impair) binding ofcanine IL-31 to canine IL-31RA (or extracellular domain of canine IL-31RA) and / orcanine OSMR (or extracellular domain of canine OSMR) are well-known to a personskilled in the art, and any appropriate method can be used. For example, an ELISA (e.g. a blocking ELISA) may be used. Thus, in certain embodiments, the ability of a VHH antibody (or construct or polypeptide) of the present invention to inhibit binding of canine IL-31 to canine IL- 31RA (or extracellular domain of canine IL-31RA) and / or canine OSMR (orextracellular domain of canine OSMR) may be determined in (or as determined in)an ELISA assay. In some embodiments, the canine IL-31 may be a His-tagged form of canine IL-31 (e.g. SEQ ID NO:2 with a His-tag). The skilled person will be familiar with ELISA assays and readily able to establish suitable conditions to assess the ability of VHH antibodies, constructs and polypeptides to inhibit binding of canine IL- 31 to canine IL-31RA (or extracellular domain of canine IL-31RA) and / or to canine OSMR (or extracellular domain of canine OSMR) in such an assay. For example, in certain embodiments, the ability of a VHH antibody (or construct or polypeptide) of the present invention to inhibit binding of canine IL-31 to canine IL-31RA (or extracellular domain of canine IL-31RA) and / or to canine OSMR (or extracellular domain of canine OSMR) may be determined in (or as determined in) an ELISA assay in which (i) canine IL-31RA (or extracellular domain of canine IL-31RA) or canine OSMR (or extracellular domain of canine OSMR) is immobilised (orcoated) in wells of an ELISA plate, (ii) a VHH antibody (or construct or polypeptide)of the invention is pre-incubated with canine IL-31 to form VHH antibody (orconstruct or polypeptide):canine IL-31 complexes, (iii) the (pre-incubated) VHH (or construct or polypeptide):canine IL-31 complexes are added to the coated (andpreferably blocked) wells and then incubated and (iv) binding of canine IL-31 to theimmobilised canine IL-31RA (or extracellular domain of canine IL-31RA) or canineOSMR (or extracellular domain of canine OSMR) is determined (or measured ordetected). Typically, if the determined binding (or measured amount or level of binding) of canine IL-31 to canine IL-31RA (or extracellular domain of canine IL- 31RA) or canine OSMR (or extracellular domain of canine OSMR) is lower than the determined binding (or measure amount or level of binding) for a negative control (e.g. with a negative control VHH antibody that does not bind to canine IL-31), then that is indicative that the VHH antibody (or construct or polypeptide) of the invention) inhibits binding of canine IL-31 to canine IL-31RA (or extracellular domain of canine IL-31RA) or canine OSMR (or extracellular domain of canine OSMR), as appropriate. In some embodiments, the ability of a VHH antibody (or construct or polypeptide) of the present invention to inhibit binding of canine IL-31 to canine IL- 31RA (or extracellular domain of canine IL-31RA) and / or to canine OSMR (or extracellular domain of canine OSMR) may be determined in (or as determined in) an ELISA assay that comprises: (a) coating wells of an ELISA (e.g. MaxiSorp) plate (e.g.96 well plate) with (e.g.5µg / ml of) a canine IL-31RA extracellular domain-humanFc fusion protein (e.g. SEQ ID NO:60) (e.g. overnight at 4oC), or with (e.g.5µg / ml of) a canine OSMR extracellular domain-humanFc fusion protein (e.g. SEQ ID NO:61) (e.g. overnight at 4oC); (b) blocking the coated wells (e.g. with 4% skimmed milk, e.g. for two hours atroom (or ambient) temperature); (c) pre-incubating a VHH antibody (or construct or polypeptide) of the invention with a His-tagged form of canine IL-31 (e.g. SEQ ID NO:2 with a His-tag;caIL31-His), for example at a 10-fold molar excess (VHH (or construct or polypeptide):caIL-31), in order to form VHH (or construct or polypeptide):canine IL-31 complexes; (d) adding complexes formed in step (c) to the coated and blocked wells andincubating (e.g. for 1 hour, e.g. at room (or ambient) temperature);(e) adding an anti-His-HRP antibody (and incubating, e.g. for 1 hour, e.g. atroom (or ambient) temperature);(f) adding a chromogenic substrate (e.g.3,3´,5,5´-tetramentylbenzidine, TMB) for HRP (horseradish peroxidase) to the wells, and preferably then stopping the reaction (e.g. with H2SO4); and (g) detecting (or measuring or quantifying) the signal produced from the chromogenic substrate / HRP reaction (e.g. with a spectrophotometer, e.g.measuring absorbance at 450nm), wherein detected signal is indicative of binding of canine IL-31 to canine IL- 31RA (or extracellular domain of canine IL-31RA) or to canine OSMR (or extracellular domain of canine OSMR), as appropriate. Typically, if the determined binding (or measured or quantified amount or level of binding) of canine IL-31 to canine IL-31RA (or extracellular domain of canine IL-31RA) or canine OSMR (or extracellular domain of canine OSMR) is lower than the determined binding (ormeasured amount or level of binding) for a negative control (e.g. with a negativecontrol VHH antibody that does not bind to canine IL-31), then that is indicative that the VHH antibody (or construct or polypeptide) of the invention) inhibits binding of canine IL-31 to canine IL-31RA (or extracellular domain of canine IL-31RA) or canine OSMR (or extracellular domain of canine OSMR), as appropriate. Typically,washing steps (e.g. with a buffer) may be performed between one or more (or all)steps of ELISA assays, e.g. one or more (or all) steps (a) to (g) in the ELISA assaydescribed above. A particularly preferred ELISA assay is described in Example 2herein. The % inhibitions of binding of canine IL-31 to canine OSMR (or extracellular domain of canine OSMR) and / or to canine IL-31RA (or extracellular domain of canine IL-31RA) may be as determined in an ELISA assay described herein (e.g. in an ELISA assay comprising steps (a) to (g) as set out above). As discussed elsewhere herein, the % inhibitions of binding of canine IL-31 to canine OSMR (or extracellular domain of canine OSMR) or to canine IL-31RA (or extracellular domain of canine IL-31RA) discussed elsewhere herein may be as compared to (or relative to) the inhibition observed with (or caused by or elicited by) a negative control (e.g.a control VHH antibody that does not bind to canine IL-31), with the negative controlrepresenting the zero inhibition level (or zero inhibition value or 0% inhibition level or value). In some embodiments, a VHH antibody (or construct or polypeptide) of thepresent invention binds to an epitope on canine IL-31 that is different from theepitope on canine IL-31 that is bound by the antibody lokivetmab. Thus, in some embodiments, lokivetmab does not interfere with (or does not impair or does not inhibit), or does not significantly interfere with (or does not significantly impair or does not significantly inhibit) the ability of a VHH antibody of the present invention (or construct or polypeptide of the invention) to bind to canine IL-31. Thus, in some embodiments, when lokivetmab is bound to canine IL-31 it(i.e. the bound lokivetmab) does not interfere (or does not impair or does not inhibit), or does not significantly interfere (or does not significantly impair or does notsignificantly inhibit) the ability of a VHH antibody of the invention (or construct orpolypeptide of the invention) to bind to canine IL-31.Thus, in some embodiments of the present invention, when lokivetmab isbound to canine IL-31, said canine IL-31 maintains (or substantially maintains) theability to bind to a VHH antibody of the invention (or construct or polypeptide of the invention). Thus, in some embodiments, a VHH antibody (or construct orpolypeptide) of the invention and lokivetmab may simultaneously bind to canine IL-31. Thus, in some embodiments, lokivetmab does not prevent a VHH antibody (orconstruct or polypeptide) of the present invention binding to canine IL-31.Thus, in some embodiments, a VHH antibody (or construct or polypeptide) ofthe present invention does not compete with lokivetmab for binding to canine IL-31.Lokivetmab is a monoclonal IgG antibody that binds to and inhibits canineIL-31. Lokivetmab may also be referred to herein as Cytopoint® (Cytopoint® is a tradename of lokivetmab). The light chain variable region amino acid sequence of lokivetmab is set out herein as SEQ ID NO:37. The heavy chain variable region amino acid sequence of lokivetmab is set out herein as SEQ ID NO:35. The light chain amino acid sequence of lokivetmab is set out herein as SEQ ID NO:38. The heavy chain amino acid sequence of lokivetmab is set out herein as SEQ ID NO:36. Methods of assessing (or determining) whether or not two or more antibodies bind to the same or different epitopes on a target protein (in this case IL- 31) are well-known to a person skilled in the art, and any appropriate method can beused. For example, an ELISA (e.g. a competition ELISA) may be used, or anepitope binning experiment (e.g. SPR-based epitope binning) may be used). In some embodiments, the ability of a VHH antibody (or construct or polypeptide) of the present invention to bind to an epitope on canine IL-31 that is different from the epitope on canine IL-31 that is bound by the antibody lokivetmabmay be determined in (or be as determined in) an assay in which a VHH antibody(or construct or polypeptide) of the present invention is tested (or assayed) for itsability to bind to canine IL-31 that is (already) in complex with (or that is already bound to) lokivetmab. In such an assay, binding to (or the ability to bind to) canine IL-31 that is (already) in complex with (or that is already bound to) lokivetmab is indicative that the VHH antibody (or construct or polypeptide) binds to an epitope on canine IL-31 that is different from the epitope on canine IL-31 that is bound by the antibody lokivetmab. In some embodiments, the ability of a VHH antibody (or construct or polypeptide) of the present invention to bind to an epitope on canine IL-31 that is different from the epitope on canine IL-31 that is bound by the antibody lokivetmab may be determined in (or be as determined in) a SPR epitope binning experiment. In some embodiments, the ability of a VHH antibody (or construct or polypeptide) of the present invention to bind to an epitope on canine IL-31 that is different from the epitope on canine IL-31 that is bound by the antibody lokivetmabmay be determined in (or be as determined in) a SPR experiment (or SPR binningexperiment) in which (i) canine IL-31 is immobilized on a SPR sensor chip;(ii) Lokivetmab is injected over (or flowed over) the immobilized canineIL-31, thereby forming canine IL-31:lokivetmab complexes; (iii) a VHH antibody (or construct or polypeptide) of the present invention(e.g. a VHH antibody (or construct or polypeptide) of the presentinvention mixed with lokivetmab) is injected over (or flowed over) thecanine IL-31:lokivetmab complexes; (iv) binding of the VHH antibody (or construct or polypeptide) to canineIL-31 is determined (or measured).In such an experiment, binding (or the ability to bind to) to canine IL-31 is indicative that the VHH antibody (or construct or polypeptide) binds to an epitope on canine IL-31 that is different from the epitope on canine IL-31 that is bound by the antibody lokivetmab. Preferred SPR epitope binning experiments are described herein in Example2, Example 3 and Example 4. If a VHH antibody of the present invention has a different (e.g. qualitativelydifferent) functional property as compared to lokivetmab, that may also be indicativethat a VHH antibody binds to an epitope on canine IL-31 that is different from theepitope on canine IL-31 that is bound by the antibody lokivetmab. For example, if aVHH antibody of the present invention (i) binds to canine IL-31 and inhibits canineIL-31 binding to canine IL-31RA, but does not inhibit (or does not significantlyinhibit) canine IL-31 binding to canine OSMR, or (ii) binds to canine IL-31 and inhibits canine IL-31 binding to canine OSMR, but does not inhibit (or does not significantly inhibit) canine IL-31 binding to canine IL-31RA, then that may be indicative that said VHH antibody binds to an epitope on canine IL-31 that is different from the epitope on canine IL-31 that is bound by the antibody lokivetmab (as lokivetmab binds to canine IL-31 and inhibits canine IL-31 binding to canine IL- 31RA and inhibits canine IL-31 binding to canine OSMR). Of course, in some embodiments, and as is evident from elsewhere herein, VHH antibodies of thepresent invention that bind to canine IL-31 and inhibit canine IL-31 binding to canineIL-31RA and inhibit canine IL-31 binding to canine OSMR may bind to an epitope on canine IL-31 that is different from the epitope on canine IL-31 that is bound by the antibody lokivetmab. In preferred embodiments, a VHH antibody (or construct or polypeptide) ofthe present invention inhibits (or is capable of inhibiting) canine IL-31 signalling.Canine IL-31 signalling may be canine IL-31 mediated STAT3 signalling (or canineIL-31 mediated phospho-STAT3 signalling). Thus, in some embodiments, a VHHantibody (or construct or polypeptide) of the present invention inhibits (or is capableof inhibiting) canine IL-31 mediated STAT3 signalling (or canine IL-31 mediatedphospho-STAT3 signalling). Thus, in aspects and embodiments of the presentinvention that refer to canine IL-31 signalling, or inhibition of (or inhibiting) canine IL-31 signalling, the canine IL-31 signalling may be canine IL-31 mediated STAT3signalling (or canine IL-31 mediated phospho-STAT3 signalling).IL-31 signals through a heterodimeric receptor complex composed on IL-31 receptor A (IL-31RA) and oncostatin M receptor (OSMR). Thus, alternativelyviewed, in preferred embodiments, a VHH antibody (or construct or polypeptide) ofthe present invention inhibits (or is capable of inhibiting) canine IL-31 signallingthrough the IL-31RA / OSMR receptor complex. Thus, in preferred embodiments, a VHH antibody (or construct orpolypeptide) of the present invention binds to (or is capable of binding to) canine IL-31 and inhibits (or is capable of inhibiting) canine IL-31 signalling. Alternativelyviewed, in preferred embodiments, a VHH antibody (or construct or polypeptide) ofthe present invention binds to (or is capable of binding to) canine IL-31 and inhibits(or is capable of inhibiting) canine IL-31 signalling through the IL-31RA / OSMR receptor complex. Methods of assessing (or determining) ability of a VHH antibody (orconstruct or polypeptide) of the present invention to inhibit (or impair) canine IL-31signalling are well-known to a person skilled in the art, and any appropriate method can be used. For example, typically a cell-based assay is used. Suitable cell-based assays are described elsewhere herein. Thus, in preferred embodiments, a VHH antibody (or construct orpolypeptide) of the present invention binds to (or is capable of binding to) canine IL- 31 and inhibits (or is capable of inhibiting) canine IL-31 signalling in cells, or asdetermined in a cell-based assay (e.g. a cell-based reporter assay).Negligible inhibition of canine IL-31 signalling (or de minimis inhibition ofcanine IL-31 signalling) is not considered inhibition of signalling, or significantinhibition of signalling. By way of example, any negligible / de minimis amount (orlevel) of inhibition of canine IL-31 signalling that may be observed (or measured ordetected) for a VHH antibody (or construct or polypeptide) of the invention that is equivalent to (or that is essentially equivalent to), or that corresponds to (or that essentially corresponds to), or that is less than or equal to, or that is not greaterthan (or not significantly greater than) inhibition of signalling observed (ormeasured) with an appropriate negative control (e.g. with a negative control VHH antibody that does not bind to canine IL-31), is not considered inhibition of signalling, or significant inhibition of signalling. In some embodiments, a VHH antibody (or construct or polypeptide) of thepresent invention inhibits (or is capable of inhibiting) canine IL-31 signalling to agreater extent (or greater degree) than lokivetmab. Put another way, in someembodiments, a VHH antibody (or construct or polypeptide) of the present inventionis more effective than lokivetmab in inhibiting canine IL-31 signalling. Alternativelyviewed, in some embodiments, the amount or level of inhibition of canine IL-31signalling by a VHH antibody (or construct or polypeptide) of the present invention isgreater than (or higher than) than the amount or level of inhibition of canine IL-31 signalling by lokivetmab. In some embodiments, a VHH antibody (or construct or polypeptide) of thepresent invention has an IC50 with respect to inhibition of canine IL-31 signalling(e.g. as determined in cell-based assay, e.g. as described elsewhere herein) of≤5µM, ≤1µM, ≤900nM, ≤800nM, ≤700nM, ≤600nM, ≤500nM, ≤400nM, ≤300nM, ≤200nM, ≤150nM, ≤100nM, ≤75nM, ≤50nM, ≤40nM, ≤35nM, ≤30nM, ≤25nM, ≤20nM, ≤15nM, ≤10nM, ≤5nM, ≤2nM, or ≤1nM. Preferably, the IC50 is ≤200nM, ≤150nM, ≤100nM, ≤75nM, ≤50nM, ≤40nM, ≤35nM, ≤30nM, ≤25nM, ≤20nM, ≤15nM, ≤10nM, ≤5nM, ≤4nM, ≤3nM, ≤2nM, or ≤1nM. In some embodiments, a construct of the present invention has an IC50 withrespect to inhibition of canine IL-31 signalling (e.g. as determined in cell-based assay, e.g. as described elsewhere herein) of ≤100nM, ≤75nM, preferably ≤50nM, ≤40nM, ≤35nM, ≤30nM, ≤25nM, ≤20nM, ≤15nM, ≤10nM, ≤5nM, ≤4nM, ≤3nM, ≤2nM, or ≤1nM.In some embodiments, a construct of the present invention has an IC50 withrespect to inhibition of canine IL-31 signalling (e.g. as determined in cell-based assay, e.g. as described elsewhere herein) of ≤100nM. In some embodiments, a construct of the present invention has an IC50 withrespect to inhibition of canine IL-31 signalling (e.g. as determined in cell-based assay, e.g. as described elsewhere herein) of ≤50nM. In some embodiments, a construct of the present invention has an IC50 withrespect to inhibition of canine IL-31 signalling (e.g. as determined in cell-basedassay, e.g. as described elsewhere herein) of ≤10nM. In some embodiments, a construct of the present invention has an IC50 withrespect to inhibition of canine IL-31 signalling (e.g. as determined in cell-basedassay, e.g. as described elsewhere herein) of ≤5nM.In some embodiments, the IC50 value for a VHH antibody (or construct orpolypeptide) of the present invention may be in the range of 100pM-5µM, 100pM-1µM, 100pM-500nM, 100pM-200nM, 100pM-100nM, 100pM-50nM, 100pM-40nM,100pM-30nM, 100pM-20nM, 100pM-10nM, 100pM-5nM, 500pM-5µM, 500pM-1µM,500pM-500nM, 500pM-500nM, 500pM-100nM, 500pM-50nM, 500pM-40nM,500pM-30nM, 500pM-20nM, 500pM-10nM, 500pM-5nM, 750pM-5µM, 750pM-1µM,750pM-500nM, 750pM-500nM, 750pM-100nM, 750pM-50nM, 750pM-40nM,750pM-30nM, 750pM-20nM, 750pM-10nM, 750pM-5nM, In some embodiments, the IC50 for a VHH antibody (or construct orpolypeptide) of the present invention value may be up to 5µM, or up to 1µM, or up to900nM, or up to 800nM, or up to 700nM, or up to 600nM, or up to 500nM, or up to 400nM, or up to 300nM, or up to 200nM, or up to 100nM, or up to 50nM, or up to40nM, or up to 30nM, or up to 20nM, or up to 10nM, or up to 5nM.An IC50 (or IC50) value represents the half maximal inhibitory concentrationof a substance for a biological process under study, in the context of the presentinvention the half maximal inhibitory concentration of a VHH antibody (or constructor polypeptide) of the present invention for the inhibition canine IL-31 signalling (e.g.in a cell-based assay, such as a cell-based assay described herein). IC50 values may be calculated by any suitable means (and be based on any suitable tests, methods or assays, for example methods as described herein). In some embodiments, a VHH antibody (or construct or polypeptide) of thepresent invention has an IC50 (or IC50 value or concentration, e.g. in nM) with respect to inhibition of canine IL-31 signalling that is lower than (preferably significantly lower than) than the IC50 (or IC50 value or concentration, e.g. in nM) oflokivetmab. Alternatively viewed, in some embodiments, a VHH antibody (orconstruct or polypeptide) of the present invention has an IC50 (or IC50 value orconcentration, e.g. in nM) with respect to inhibition of canine IL-31 signalling that is lower than (preferably significantly lower than) than the IC50 (or IC50 value or concentration, e.g. in nM) with respect to inhibition of canine IL-31 signalling of lokivetmab. In some embodiments, a construct of the present invention has an IC50 (orIC50 value or concentration, e.g. in nM) with respect to inhibition of canine IL-31 signalling that is lower than (preferably significantly lower than) than the IC50 (or IC50 value or concentration, e.g. in nM) of lokivetmab. In some embodiments, a VHH antibody (or construct or polypeptide) of thepresent invention has an IC50 (or IC50 value or concentration, e.g. in nM) withrespect to inhibition of canine IL-31 signalling that is at least 5% lower, at least 10%lower, at least 20% lower, at least 30% lower, at least 40% lower, at least 50%lower, at least 60% lower, at least 70% lower, at least 80% lower, at least 90%lower or at least 95% lower than the IC50 (or IC50 value or concentration, e.g. innM) of lokivetmab. In some embodiments, a VHH antibody (or construct or polypeptide) of thepresent invention has an IC50 (or IC50 value or concentration, e.g. in nM) withrespect to inhibition of canine IL-31 signalling that is at least 50% lower than theIC50 (or IC50 value or concentration, e.g. in nM) of lokivetmab. In some embodiments, a construct of the present invention has an IC50 (orIC50 value or concentration, e.g. in nM) with respect to inhibition of canine IL-31signalling that is at least 5% lower, at least 10% lower, at least 20% lower, at least30% lower, at least 40% lower, at least 50% lower, at least 60% lower, at least 70%lower, at least 80% lower, at least 90% lower or at least 95% lower than the IC50 (orIC50 value or concentration, e.g. in nM) of lokivetmab. In some embodiments, a construct of the present invention has an IC50 (orIC50 value or concentration, e.g. in nM) with respect to inhibition of canine IL-31signalling that is at least 50% lower at least 60% lower, at least 70% lower, at least80% lower, at least 90% lower or at least 95% lower than the IC50 (or IC50 value orconcentration, e.g. in nM) of lokivetmab. The IC50 values with respect to inhibition of canine IL-31 signalling may beas determined in cell-based assay (e.g. as described herein). In embodiments inwhich an IC50 value of a VHH antibody (or construct or polypeptide) of the presentinvention is described as being lower than the IC50 value of lokivetmab, the IC50value for a VHH antibody (or construct or polypeptide) of the present invention andthe IC50 value for lokivetmab may be as determined in a cell-based assay (e.g. asdescribed herein), e.g. determination of the IC50 value of lokivetmab may be donein parallel with determination of the IC50 value a VHH antibody (or construct orpolypeptide) of the present invention.Various embodiments of the invention set out herein refer to an IC50 (or IC50 value or IC50 concentration). In some alternative embodiments, IC90 (or IC90 value) may be referred to, mutatis mutandis, instead of IC50. An IC90 (or IC90)value represents 90% of the maximal inhibitory concentration of a substance for abiological process under study, in the context of the present invention 90% of themaximal inhibitory concentration of a VHH antibody (or construct or polypeptide) ofthe present invention for the inhibition canine IL-31 signalling (e.g. in a cell-basedassay, such as a cell-based assay described herein). IC90 values may be calculated by any suitable means (and be based on any suitable tests, methods or assays, for example methods as described herein). In some embodiments, when used at a molar excess of 1000:1 (VHH antibody (or construct or polypeptide) of the invention:canine IL-31), for example ina cell-based assay (e.g. as described herein), a VHH antibody (or construct orpolypeptide) of the present invention inhibits (or is capable of inhibiting) canine IL-31signalling by at least 5%, at least 10%, preferably at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 95% or 100%. In some embodiments, when used at a molar excess of 333:1 (VHH antibody (or construct or polypeptide) of the invention:canine IL-31), for example ina cell-based assay (e.g. as described herein), a VHH antibody (or construct orpolypeptide) of the present invention inhibits (or is capable of inhibiting) canine IL-31signalling by at least 5%, at least 10%, preferably at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 95% or 100%. In some embodiments, when used at a molar excess of about 10:1 (e.g.12:1 or 12.34:1) (VHH antibody (or construct or polypeptide) of the invention:canine IL- 31), for example in a cell-based assay (e.g. as described herein), a VHH antibody(or construct or polypeptide) of the present invention inhibits (or is capable ofinhibiting) canine IL-31 signalling by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 95% or 100%. In some embodiments, when used at a molar excess of about 10:1 (e.g.12:1 or 12.34:1) (construct of the invention:canine IL-31), for example in a cell-basedassay (e.g. as described herein), a construct of the present invention inhibits (or iscapable of inhibiting) canine IL-31 signalling by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, preferably at least 50%, at least 60%, at least 70%, at least 80%, at least 95% or 100%. In some embodiments, when used at a molar excess of about 10:1 (e.g.12:1 or 12.34:1) (construct of the invention:canine IL-31), for example in a cell-basedassay (e.g. as described herein), a construct of the present invention inhibits (or iscapable of inhibiting) canine IL-31 signalling by at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 95% or 100%. In some embodiments, when used at a molar excess of about 10:1 (e.g.12:1 or 12.34:1) (VHH antibody (or construct or polypeptide) of the invention:canine IL- 31), for example in a cell-based assay (e.g. as described herein), a VHH antibody(or construct or polypeptide) of the present invention inhibits (or is capable ofinhibiting) canine IL-31 signalling to a greater extent than lokivetmab (whenlokivetmab is used at the same molar excess). In some embodiments, when used at a molar excess of about 10:1 (e.g.12:1 or 12.34:1) (VHH antibody (or construct or polypeptide) of the invention:canine IL-31), for example in a cell-based assay(e.g. as described herein), the amount (or level) of inhibition of canine IL-31signalling by a VHH antibody (or construct or polypeptide) of the present invention isgreater than (or higher than) than the amount or level of inhibition of canine IL-31signalling by lokivetmab (when lokivetmab is used at the same molar excess). Insome such embodiments, the % inhibition value determined (or measured) for aVHH antibody (or construct or polypeptide) of the present invention for inhibition ofcanine IL-31 signalling is at least 5%, at least 10%, at least 20%, at least 30%, atleast 40%, at least 50%, at least 60%, at least 70% or at least 80% higher than the% inhibition value determined (or measured) for lokivetmab (when lokivetmab isused at the same molar excess). In some embodiments, when used at a molar excess of about 10:1 (e.g.12:1 or 12.34:1) (construct of the invention:canine IL-31), for example in a cell-basedassay (e.g. as described herein), a construct of the present invention inhibits (or iscapable of inhibiting) canine IL-31 signalling to a greater extent than lokivetmab (when lokivetmab is used at the same molar excess). In some embodiments, when used at a molar excess of about 10:1 (e.g.12:1 or 12.34:1) (construct of the invention:canine IL-31), for example in a cell-based assay (e.g. as described herein), the amount (or level) of inhibition of canine IL-31 signalling by a construct ofthe present invention is greater than (or higher than) than the amount or level ofinhibition of canine IL-31 signalling by lokivetmab (when lokivetmab is used at the same molar excess). In some such embodiments, the % inhibition value determined (or measured) for a construct of the present invention for inhibition ofcanine IL-31 signalling is at least 5%, at least 10%, at least 20%, at least 30%, atleast 40%, at least 50%, at least 60%, at least 70% or at least 80% higher than the % inhibition value determined (or measured) for lokivetmab (when lokivetmab is used at the same molar excess). In some embodiments, the level of inhibition (or amount of inhibition) of canine IL-31 signalling observed with (or caused by or elicited by) a negative control (e.g. a control VHH antibody that does not bind to canine IL-31) represents (or is set as) the zero inhibition level (or zero inhibition value or 0% inhibition level or value). Thus, in some embodiments, the % inhibitions of canine IL-31 signalling discussed elsewhere herein are as compared to (or relative to) the inhibition observed with (or caused by or elicited by) a negative control (e.g. a control VHH antibody that does not bind to canine IL-31). As discussed elsewhere herein, in preferred embodiments, a VHH antibody(or construct or polypeptide) of the present invention inhibits (or is capable ofinhibiting) canine IL-31 signalling in cells. Thus, inhibition of canine IL-31 signallingmay be determined in (or be as determined in) a cell-based assay (e.g. a cell-basedreporter assay). As is evident from discussion elsewhere wherein, such cells (e.g. cells for use in a cell-based assay) express IL-31RA and OSMR. The IL-31-RA and OSMR may be canine IL-31RA and canine OSMR. Alternatively, the IL-31RA may be a chimeric IL-31RA protein comprising a canine IL-31RA extracellular domain(e.g. of SEQ ID NO:67) and a non-canine IL-31RA transmembrane signallingdomain, and the OSMR may be a chimeric OSMR protein comprising a canine OSMR extracellular domain (e.g. of SEQ ID NO:72) and a non-canine OSMR transmembrane signalling domain. Preferably, the IL-31RA may be a chimeric IL-31RA protein comprising a canine IL-31RA extracellular domain (e.g. of SEQ IDNO:67) and a human IL-31RA transmembrane signalling domain (e.g. of SEQ IDNO:68), and the OSMR may be a chimeric OSMR protein comprising a canineOSMR extracellular domain (e.g. of SEQ ID NO:72) and a human OSMRtransmembrane signalling domain (e.g. of SEQ ID NO:73). A “transmembranesignalling domain” as referred to herein is a domain which comprises both atransmembrane portion (or domain) and an intracellular signalling portion (ordomain). Sequences of canine IL-31RA and canine OSMR (and extracellular domains thereof) are well known and described in the art and can be obtained for example from various sequence databases, e.g. Uniprot. A preferred and exemplary canine IL-31RA extracellular domain (e.g. for use in a cell-based assay) has the amino acid sequence of SEQ ID NO:67. A preferred and exemplary canine OSMR extracellular domain (e.g. for use in a cell-based assay) has the amino acidsequence of SEQ ID NO:72.In some embodiments, inhibition of canine IL-31 signalling (or the ability ofan antibody (or construct or polypeptide) to inhibit canine IL-31 signalling) may bedetermined in (or be as determined in) a cell-based assay (e.g. a cell-based reporter assay), in which (a) Canine IL-31 (e.g. of SEQ ID NO:2, or e.g. a His tagged-canine IL-31) is incubated (or pre-incubated) with an antibody (or construct orpolypeptide) (e.g. for 30 minutes at room (or ambient) temperature)in order to form antibody (or construct or polypeptide):canine IL-31complexes; (b) Complexes formed in (a) are added to cells (or a cell culture of cells),preferably mammalian (e.g. human) cells, that (i) express IL-31RAthat has a canine IL-31RA extracellular domain and express OSMR that has a canine OSMR extracellular domain (and thus are able totransmit signal upon canine IL-31 binding to a heterodimeric IL- 31RA / OSMR receptor), and (ii) express a reporter gene (or reporter gene system) that is responsive to canine IL-31 signalling; (c) Cells to which the complexes have been added are incubated orcultured in culture medium (e.g. for 24 hours, e.g. at 37oC, e.g. at 5% CO2); and(d) The activity of the reporter gene (or reporter gene system) isdetermined (or measured or quantified or detected),wherein reporter gene (or reporter gene system) activity is indicative of canine IL-31 signalling. Typically, if the determined (or measured or quantifiedamount or level of) reporter gene activity is lower than the determined reporter geneactivity (or measured amount or level of reporter gene activity) for a negative control(e.g. with a negative control VHH antibody that does not bind to canine IL-31), then that is indicative that the antibody (or construct or polypeptide) (being tested)inhibits canine IL-31 signalling.In some embodiments, inhibition of canine IL-31 signalling (or the ability of an antibody (or construct or polypeptide) to inhibit canine IL-31 signalling) may be determined in (or be as determined in) a cell-based assay (e.g. a cell-based reporter assay), in which (a) A dilution series (e.g. a three-fold dilution series) of antibody (orconstruct or polypeptide):canine IL-31 complexes is prepared, for example a dilution series (e.g. a three-fold dilution series) ranging from 1000:1 to 0.45:1 molar excess (antibody (or construct orpolypeptide):canine IL-31), the complexes being formed by incubating (or pre-incubating) canine IL-31 (e.g. of SEQ ID NO:2, or e.g. a His tagged-canine IL-31) with an antibody (or construct orpolypeptide) (e.g. for 30 minutes at room (or ambient) temperature);(b) Complexes formed in (a) are added to cells (or a cell culture of cells), preferably mammalian (e.g. human) cells, that (i) express IL-31RA that has a canine IL-31RA extracellular domain and express OSMR that has a canine OSMR extracellular domain (and thus are able to transmit signal upon canine IL-31 binding to a heterodimeric IL- 31RA / OSMR receptor), and (ii) express a reporter gene (or reporter gene system) that is responsive to canine IL-31 signalling;(c) Cells to which the complexes have been added are incubated orcultured in culture medium (e.g. for 24 hours, e.g. at 37oC, e.g. at 5% CO2); and (d) The activity of the reporter gene (or reporter gene system) isdetermined (or measured or quantified or detected), wherein reporter gene (or reporter gene system) activity is indicative of canine IL-31 signalling. Typically, if the determined (or measured or quantified amount or level of) reporter gene activity is lower (e.g. if there is a dose dependent lowering of (or reduction in) reporter gene activity as molar excess increases) ascompared to (or relative to) the determined reporter gene activity (or measuredamount or level of reporter gene activity) for a negative control (e.g. with a negative control VHH antibody that does not bind to canine IL-31), then that is indicative thatthe antibody (or construct or polypeptide) (being tested) inhibits canine IL-31signalling. In some embodiments, inhibition of canine IL-31 signalling (or the ability ofan antibody (or construct or polypeptide) to inhibit canine IL-31 signalling) may bedetermined in (or be as determined in) a cell-based assay (e.g. a cell-based reporter assay), in which (a) Canine IL-31 (e.g. of SEQ ID NO:2, or e.g. a His tagged-canine IL-31) is incubated (or pre-incubated) with an antibody (or construct orpolypeptide) (e.g. for 30 minutes at room (or ambient) temperature)in order to form antibody (or construct or polypeptide):canine IL-31complexes; (b) Complexes formed in (a) are added to human cells (or a cell culture of human cells), preferably HEK (human embryonic kidney) cells(e.g. HEK293), that (i) have been transfected (preferably transientlytransfected) with a plasmid, and that express from said plasmid, afusion protein that has an amino acid sequence of SEQ ID NO:65,and (ii) express human STAT3, and (iii) comprise a STAT3 inducible reporter gene that, upon induction by human STAT3, expressesalkaline phosphatase that is then secreted from (or secretable from)the cells (also referred to as secreted alkaline phosphatase (SEAP));(c) Human cells to which the complexes have been added are incubatedor cultured in culture medium (e.g. DMEM containing 10% fetalbovine serum (FBS)), (e.g. for 24 hours, e.g. at 37oC, e.g. at 5% CO2); and (d) The activity of the reporter gene (or reporter gene system) isdetermined (or measured or quantified or detected) by determining(or measuring or quantifying or detecting) the level or amount of alkaline phosphatase activity in the (or in a sample of the) cell culture medium (alkaline phosphatase that has been secreted into the cell culture medium) or cell culture medium supernatant,wherein reporter gene (or reporter gene system) activity is indicative of canine IL-31 signalling. Typically, if the determined (or measured or quantified amount or level of) reporter gene activity is lower than the determined reporter gene activity (or measured amount or level of reporter gene activity) for a negative control (e.g. with a negative control VHH antibody that does not bind to canine IL-31), then that is indicative that the antibody (or construct or polypeptide) (being tested) inhibits canine IL-31 signalling. In some embodiments, inhibition of canine IL-31 signalling (or the ability of an antibody (or construct or polypeptide) to inhibit canine IL-31 signalling) may be determined in (or be as determined in) a cell-based assay (e.g. a cell-based reporter assay), in which (a) Canine IL-31 (e.g. of SEQ ID NO:2, or e.g. a His tagged-canine IL-31) is incubated (or pre-incubated) with an antibody (or construct orpolypeptide) (e.g. for 30 minutes at room (or ambient) temperature)in order to form antibody (or construct or polypeptide):canine IL-31complexes; (b) Transfection (e.g. transiently transfection) of human cells (or a cellculture of human cells), preferably HEK (human embryonic kidney) cells (e.g. HEK293), with a plasmid that expresses a fusion protein that has an amino acid sequence of SEQ ID NO:65 is performed,wherein said cells also (i) express human STAT3, and (ii) comprise a STAT3 inducible reporter gene that, upon induction by human STAT3, expresses alkaline phosphatase that is then secreted from (or secretable from) the cells (also referred to as secreted alkaline phosphatase (SEAP)), and complexes formed in (a) are added to transfected cells; (c) Human cells to which the complexes have been added are incubatedor cultured in culture medium (e.g. DMEM containing 10% fetal bovine serum (FBS)), (e.g. for 24 hours, e.g. at 37oC, e.g. at 5% CO2); and (d) The activity of the reporter gene (or reporter gene system) isdetermined (or measured or quantified or detected) by determining (or measuring or quantifying or detecting) the level or amount of alkaline phosphatase activity in the (or in a sample of the) cell culture medium (alkaline phosphatase that has been secreted into the cell culture medium) or cell culture medium supernatant, wherein reporter gene (or reporter gene system) activity is indicative of canine IL-31 signalling. Typically, if the determined (or measured or quantified amount or level of) reporter gene activity is lower than the determined reporter gene activity (or measured amount or level of reporter gene activity) for a negative control (e.g. with a negative control VHH antibody that does not bind to canine IL-31), then that is indicative that the antibody (or construct or polypeptide) (being tested) inhibits canine IL-31 signalling. In some embodiments, inhibition of canine IL-31 signalling (or the ability of a an antibody (or construct or polypeptide) of the present invention to inhibit canine IL- 31 signalling) may be determined in (or be as determined in) a cell-based assay (e.g. a cell-based reporter assay), in which (a) A dilution series (e.g. a three-fold dilution series) of antibody (orconstruct or polypeptide):canine IL-31 complexes is prepared, for example a dilution series (e.g. a three-fold dilution series) ranging from 1000:1 to 0.45:1 molar excess (antibody (or construct or polypeptide):canine IL-31), the complexes being formed by incubating (or pre-incubating) canine IL-31 (e.g. of SEQ ID NO:2, or e.g. a His tagged-canine IL-31) with an antibody (or construct orpolypeptide) (e.g. for 30 minutes at room (or ambient) temperature);(b) Complexes formed in (a) are added to human cells (or a cell culture of human cells), preferably HEK (human embryonic kidney) cells (e.g. HEK293), that (i) have been transfected (preferably transiently transfected) with a plasmid, and that express from said plasmid, a fusion protein that has an amino acid sequence of SEQ ID NO:65, and (ii) express human STAT3, and (iii) comprise a STAT3 inducible reporter gene that, upon induction by human STAT3, expresses alkaline phosphatase that is then secreted from (or secretable from) the cells (also referred to as secreted alkaline phosphatase (SEAP)); (c) Human cells to which the complexes have been added are incubatedor cultured in culture medium (e.g. DMEM containing 10% fetal bovine serum (FBS)), (e.g. for 24 hours, e.g. at 37oC, e.g. at 5% CO2); and(d) The activity of the reporter gene (or reporter gene system) isdetermined (or measured or quantified or detected) by determining (or measuring or quantifying or detecting) the level or amount of alkaline phosphatase activity in the (or in a sample of the) cell culture medium (alkaline phosphatase that has been secreted into the cell culture medium) or cell culture medium supernatant, wherein reporter gene (or reporter gene system) activity is indicative of canine IL-31 signalling. Typically, if the determined (or measured or quantified amount or level of) reporter gene activity is lower (e.g. if there is a dose dependent lowering of (or reduction in) reporter gene activity as molar excess increases) as compared to (or relative to) the determined reporter gene activity (or measured amount or level of reporter gene activity) for a negative control (e.g. with a negative control VHH antibody that does not bind to canine IL-31), then that is indicative thatthe antibody (or construct or polypeptide) (being tested) inhibits canine IL-31signalling. In some embodiments, inhibition of canine IL-31 signalling (or the ability of a VHH antibody (or construct or polypeptide) of the present invention to inhibit canine IL-31 signalling) may be determined in (or be as determined in) a cell-based assay (e.g. a cell-based reporter assay), in which (a) A dilution series (e.g. a three-fold dilution series) of antibody (orconstruct or polypeptide):canine IL-31 complexes is prepared, for example a dilution series (e.g. a three-fold dilution series) ranging from 1000:1 to 0.45:1 molar excess (antibody (or construct or polypeptide):canine IL-31), the complexes being formed by incubating (or pre-incubating) canine IL-31 (e.g. of SEQ ID NO:2, or e.g. a His tagged-canine IL-31) with an antibody (or construct orpolypeptide) (e.g. for 30 minutes at room (or ambient) temperature);(b) Transfection (e.g. transient transfection) of human cells (or a cellculture of human cells), preferably HEK (human embryonic kidney) cells (e.g. HEK293), with a plasmid that expresses a fusion protein that has an amino acid sequence of SEQ ID NO:65 is performed,wherein said cells also (i) express human STAT3, and (ii) comprise a STAT3 inducible reporter gene that, upon induction by human STAT3, expresses alkaline phosphatase that is then secreted from (or secretable from) the cells (also referred to as secreted alkaline phosphatase (SEAP)), and complexes formed in (a) are added to transfected cells; (c) Human cells to which the complexes have been added are incubatedor cultured in culture medium (e.g. DMEM containing 10% fetal bovine serum (FBS)), (e.g. for 24 hours, e.g. at 37oC, e.g. at 5% CO2); and (d) The activity of the reporter gene (or reporter gene system) isdetermined (or measured or quantified or detected) by determining (or measuring or quantifying or detecting) the level or amount of alkaline phosphatase activity in the (or in a sample of the) cell culturemedium (alkaline phosphatase that has been secreted into the cell culture medium) or cell culture medium supernatant, wherein reporter gene (or reporter gene system) activity is indicative of canine IL-31 signalling. Typically, if the determined (or measured or quantified amount or level of) reporter gene activity is lower (e.g. if there is a dose dependent lowering of (or reduction in) reporter gene activity as molar excess increases) as compared to (or relative to) the determined reporter gene activity (or measured amount or level of reporter gene activity) for a negative control (e.g. with a negative control VHH antibody that does not bind to canine IL-31), then that is indicative thatthe antibody (or construct or polypeptide) (being tested) inhibits canine IL-31signalling. In some embodiments, inhibition of canine IL-31 signalling (or the ability ofan antibody (or construct or polypeptide) to inhibit canine IL-31 signalling) may bedetermined in (or be as determined in) a cell-based assay (e.g. a cell-based reporter assay), in which (a) A three-fold dilution series of antibody (or construct orpolypeptide):canine IL-31 complexes is prepared ranging from1000:1 to 0.45:1 molar excess (antibody (or ...

Claims

CLAIMS1. A construct comprising more than one VHH antibody which binds to canineIL-31, wherein at least two of said VHH antibodies have different VHH antibodysequences.

2. The construct of claim 1, wherein at least two of said VHH antibodies in theconstruct bind to different epitopes on canine IL-31.

3. The construct of claim 1 or claim 2, wherein said construct(i) comprises (a) at least one VHH antibody comprising a VHH domain comprising three CDRs, wherein said VHH domain comprises a CDR1 that has the amino acid sequence of SEQ ID NO:28 or a sequence substantially homologous thereto, a CDR2 that has the amino acid sequence of SEQ ID NO:29 or a sequence substantially homologous thereto and a CDR3 that has the amino acid sequence of SEQ ID NO:30 or a sequence substantially homologous thereto, and (b) at least one VHH antibody comprising aVHH domain comprising three CDRs, wherein said VHH domain comprises a CDR1 that has the amino acid sequence of SEQ ID NO:20 or a sequence substantially homologous thereto, a CDR2 that has the amino acid sequence of SEQ ID NO:21 or a sequence substantially homologous thereto and a CDR3 that has the aminoacid sequence of SEQ ID NO:22 or a sequence substantially homologous thereto; or (ii) comprises (a) at least one VHH antibody comprising a VHH domaincomprising three CDRs, wherein said VHH domain comprises a CDR1 that has the amino acid sequence of SEQ ID NO:4 or a sequence substantially homologous thereto, a CDR2 that has the amino acid sequence of SEQ ID NO:5 or a sequence substantially homologous thereto and a CDR3 that has the amino acid sequence of SEQ ID NO:6 or a sequence substantially homologous thereto,and (b) at least one VHH antibody comprising a VHH domain comprising three CDRs, wherein said VHH domain comprises aCDR1 that has the amino acid sequence of SEQ ID NO:12 or a sequence substantially homologous thereto, a CDR2 that has the amino acid sequence of SEQ ID NO:13 or a sequence substantially homologous thereto and a CDR3 that has the amino acid sequence of SEQ ID NO:14 or a sequence substantially homologous thereto, wherein said substantially homologous sequence is a sequence containing 1, 2 or 3 amino acid substitutions compared to the given CDR sequence.

4. The construct of any one of claims 1 to 3, wherein said construct (i) comprises (a) at least one VHH antibody comprising a VHH domain comprising three CDRs, wherein said VHH domain comprises a CDR1 that has the amino acid sequence of SEQ ID NO:28, a CDR2 that has the amino acid sequence of SEQ ID NO:29 and a CDR3 that has the amino acid sequence of SEQ ID NO:30, and (b) at least one VHH antibody comprising a VHH domain comprising three CDRs, wherein said VHH domain comprises a CDR1 that has the amino acid sequence of SEQ ID NO:20, a CDR2 that has the amino acid sequence of SEQ ID NO:21 and a CDR3 that has the amino acid sequence of SEQ ID NO:22; or (ii) comprises (a) at least one VHH antibody comprising a VHH domaincomprising three CDRs, wherein said VHH domain comprises aCDR1 that has the amino acid sequence of SEQ ID NO:4, a CDR2 that has the amino acid sequence of SEQ ID NO:5 and a CDR3 that has the amino acid sequence of SEQ ID NO:6, and (b) at least one VHH antibody comprising a VHH domain comprising three CDRs, wherein said VHH domain comprises a CDR1 that has the amino acid sequence of SEQ ID NO:12, a CDR2 that has the amino acid sequence of SEQ ID NO:13 and a CDR3 that has the amino acid sequence of SEQ ID NO:14.

5. The construct of any one of claims 1 to 4, wherein said construct(i) comprises (a) at least one VHH antibody comprising a VHH domainthat has an amino acid sequence of SEQ ID NO:82 or a sequence having at least 80% sequence identity thereto, and (b) at least one VHH antibodycomprising a VHH domain that has an amino acid sequence of SEQ ID NO:74 or a sequence having at least 80% sequence identity thereto; or(ii) comprises (a) at least one VHH antibody comprising a VHH domainthat has an amino acid sequence of SEQ ID NO:58 or a sequence having at least 80% sequence identity thereto, and (b) at least one VHH antibodycomprising a VHH domain that has an amino acid sequence of SEQ ID NO:57 or a sequence having at least 80% sequence identity thereto; or (iii) comprises (a) at least one VHH antibody comprising a VHH domainthat has an amino acid sequence of SEQ ID NO:27 or a sequence having at least 80% sequence identity thereto, and (b) at least one VHH antibodycomprising a VHH domain that has an amino acid sequence of SEQ ID NO:19 or a sequence having at least 80% sequence identity thereto; or (iv) comprises (a) at least one VHH antibody comprising a VHH domainthat has an amino acid sequence of SEQ ID NO:3 or a sequence having at least 80% sequence identity thereto, and (b) at least one VHH antibodycomprising a VHH domain that has an amino acid sequence of SEQ ID NO:11 or a sequence having at least 80% sequence identity thereto.

6. The construct of any one of claims 1 to 5, wherein said construct comprises(a) at least one VHH antibody comprising a VHH domain that has an amino acidsequence of SEQ ID NO:82 and (b) at least one VHH antibody comprising a VHHdomain that has an amino acid sequence of SEQ ID NO:74.

7. The construct of any one of claims 1 to 6, wherein said construct furthercomprises a serum half-life extending moiety.

8. The construct of claim 7, wherein said serum half-life extending moiety is aVHH antibody which binds to canine albumin.

9. The construct of claim 8, wherein said VHH antibody which binds to caninealbumin comprises a VHH domain comprising three CDRs, wherein said VHH domain comprises a CDR1 that has the amino acid sequence of SEQ ID NO:40 or a sequence substantially homologous thereto, a CDR2 that has the amino acidsequence of SEQ ID NO:41 or a sequence substantially homologous thereto and a CDR3 that has the amino acid sequence of SEQ ID NO:42 or a sequence substantially homologous thereto, wherein said substantially homologous sequence is a sequence containing 1, 2 or 3 amino acid substitutions compared to the given CDR sequence.

10. The construct of claim 8 or claim 9, wherein said VHH antibody which bindsto canine albumin comprises a VHH domain having an amino acid sequence of SEQ ID NO:90 or a sequence having at least 80% sequence identity thereto, or ofSEQ ID NO:39 or a sequence or a sequence having at least 80% sequence identitythereto.

11. The construct of any one of claims 7 to 10, wherein said serum half-lifeextending moiety is positioned in the construct between two VHH antibodies whichbind to canine IL-31.

12. The construct of any one of claims 3 to 11, wherein said construct isselected from the group consisting of: (i) a construct that comprises, in sequence, in the N-terminal to C-terminaldirection, a VHH antibody as defined in part (i)(a) of claim 3 or claim 4, a VHHantibody as defined in any one of claims 8 to 10, and a VHH antibody as defined inpart (i)(b) of claim 3 or claim 4;(ii) a construct that comprises, in sequence, in the N-terminal to C-terminaldirection, a VHH antibody as defined in part (i)(a) of claim 5, a VHH antibody asdefined in any one of claims 8 to 10, and a VHH antibody as defined in part (i)(b) ofclaim 5; (iii) a construct that comprises, in sequence, in the N-terminal to C-terminaldirection, a VHH antibody as defined in part (a) of claim 6, a VHH antibody asdefined in any one of claims 8 to 10, and a VHH antibody as defined in part (b) ofclaim 6; (iv) a construct that comprises, in sequence, in the N-terminal to C-terminaldirection, a VHH antibody as defined in part (ii)(a) of claim 5, a VHH antibody asdefined in any one of claims 8 to 10, and a VHH antibody as defined in part (ii)(b) ofclaim 5; (v) a construct that comprises, in sequence, in the N-terminal to C-terminaldirection, a VHH antibody as defined in part (iii)(a) of claim 5, a VHH antibody asdefined in any one of claims 8 to 10, and a VHH antibody as defined in part (iii)(b) ofclaim 5; (vi) a construct that comprises, in sequence, in the N-terminal to C-terminaldirection, a VHH antibody as defined in part (ii)(a) of claim 3 or claim 4, a VHHantibody as defined in any one of claims 8 to 10, and a VHH antibody as defined in part (ii)(b) of claim 3; and (vii) a construct that comprises, in sequence, in the N-terminal to C-terminaldirection, a VHH antibody as defined in part (iv)(a) of claim 5, a VHH antibody asdefined in any one of claims 8 to 10, and a VHH antibody as defined in part (iv)(b) ofclaim 5.

13. The construct of any one of claims 1 to 12, wherein said construct comprisesan amino acid sequence of SEQ ID NO:98, SEQ ID NO:50 or SEQ ID NO:49, or a sequence having at least 80% sequence identity to SEQ ID NO:98, SEQ ID NO:50 or SEQ ID NO:49.

14. The construct of any one of claims 1 to 13, wherein said construct comprisesan amino acid sequence of SEQ ID NO:98, SEQ ID NO:50 or SEQ ID NO:49.

15. The construct of any one of claims 1 to 11, wherein said construct comprisesan amino acid sequence of SEQ ID NO:47 or SEQ ID NO:48, or a sequence havingat least 80% sequence identity to SEQ ID NO:47 or SEQ ID NO:48.

16. A VHH antibody which binds to canine IL-31, wherein said VHH antibodycomprises a VHH domain comprising three CDRs, wherein said VHH domain comprises (i) a CDR1 that has the amino acid sequence of SEQ ID NO:28 or a sequence substantially homologous thereto, a CDR2 that has the amino acid sequence of SEQ ID NO:29 or a sequence substantially homologous thereto and aCDR3 that has the amino acid sequence of SEQ ID NO:30 or a sequence substantially homologous thereto; (ii) a CDR1 that has the amino acid sequence of SEQ ID NO:20 or a sequence substantially homologous thereto, a CDR2 that has the amino acid sequence of SEQ ID NO:21 or a sequence substantially homologous thereto and a CDR3 that has the amino acid sequence of SEQ ID NO:22 or a sequence substantially homologous thereto; (iii) a CDR1 that has the amino acid sequence of SEQ ID NO:4 or a sequence substantially homologous thereto, a CDR2 that has the amino acid sequence of SEQ ID NO:5 or a sequence substantially homologous thereto and a CDR3 that has the amino acid sequence of SEQ ID NO:6 or a sequencesubstantially homologous thereto; or(iv) a CDR1 that has the amino acid sequence of SEQ ID NO:12 or a sequence substantially homologous thereto, a CDR2 that has the amino acid sequence of SEQ ID NO:13 or a sequence substantially homologous thereto and a CDR3 that has the amino acid sequence of SEQ ID NO:14 or a sequence substantially homologous thereto, wherein said substantially homologous sequence is a sequence containing 1, 2 or 3 amino acid substitutions compared to the given CDR sequence.

17. The VHH antibody claim 16, wherein said VHH antibody comprises a VHHdomain comprising three CDRs, wherein said VHH domain comprises (i) a CDR1 that has the amino acid sequence of SEQ ID NO:28, a CDR2 that has the amino acid sequence of SEQ ID NO:29 and a CDR3 that has the amino acid sequence of SEQ ID NO:30; (ii) a CDR1 that has the amino acid sequence of SEQ ID NO:20, a CDR2 that has the amino acid sequence of SEQ ID NO:21 and a CDR3 that has the amino acid sequence of SEQ ID NO:22; (iii) a CDR1 that has the amino acid sequence of SEQ ID NO:4, a CDR2that has the amino acid sequence of SEQ ID NO:5 and a CDR3 that has the aminoacid sequence of SEQ ID NO:6; or(iv) a CDR1 that has the amino acid sequence of SEQ ID NO:12, a CDR2 that has the amino acid sequence of SEQ ID NO:13 and a CDR3 that has the amino acid sequence of SEQ ID NO:14.

18. The VHH antibody of claim 16 or claim 17, wherein said VHH antibodycomprises a VHH domain having an amino acid sequence selected from the group consisting of (i) SEQ ID NO:82 or or a sequence having at least 80% sequence identity thereto, (ii) SEQ ID NO:74 or a sequence having at least 80% sequence identity thereto, (iii) SEQ ID NO:27 or a sequence having at least 80% sequenceidentity thereto, (iv) SEQ ID NO:19 or a sequence having at least 80% sequenceidentity thereto, (v) SEQ ID NO:58 or a sequence having at least 80% sequence identity thereto, (vi) SEQ ID NO:57 or a sequence having at least 80% sequenceidentity thereto, (vii) SEQ ID NO:3 or a sequence having at least 80% sequenceidentity thereto, and (viii) SEQ ID NO:4 or a sequence having at least 80%sequence identity thereto.

19. The VHH antibody of any one of claims 16 to 18, wherein said VHH antibodycomprises a VHH domain having an amino acid selected from the group consistingof (i) SEQ ID NO:82, (ii) SEQ ID NO:74, (iii) SEQ ID NO:19, (iv) SEQ ID NO:27, (v)SEQ ID NO:57, (vi) SEQ ID NO:58, (vii) SEQ ID NO:3 and (viii) SEQ ID NO:11.

20. A VHH antibody which binds to the same epitope on canine IL-31 as a VHHantibody as defined in any one of claims 16 to 19.

21. A construct comprising at least one VHH antibody as defined in any one ofclaims 16 to 20.

22. A composition comprising a construct of any one of claims 1 to 15 or 21 or aVHH antibody of any one of claims 16 to 20, wherein said composition comprises a diluent, carrier or excipient, preferably a pharmaceutically acceptable diluent, carrier or excipient.

23. A nucleic acid molecule comprising a nucleotide sequence that encodes aconstruct of any one of claims 1 to 15 or 21 or a VHH antibody of any one of claims16 to 20.

24. An expression vector comprising a nucleic acid molecule of claim 23.

25. A host cell comprising the nucleic acid molecule of claim 23, or theexpression vector of claim 24, or expressing the VHH antibody of any one of claims 16 to 20, or expressing the construct of any one of claims 1 to 15 or 21.

26. A method of producing a construct of any one of claims 1 to 15 or 21 or aVHH antibody of any one of claims 16 to 20, comprising the steps of: (i) culturing a host cell comprising (a) one or more nucleic acid molecules encoding a construct of any one of claims 1 to 15 or 21 or a VHH antibody of anyone of claims 16 to 20 or (b) one or more expression vectors comprising one ormore of said nucleic acid molecules, under conditions suitable for the expression of the encoded construct or VHH antibody; and (ii) isolating or obtaining the construct or the VHH antibody from the host cell or from the growth medium / supernatant.

27. A construct as defined in any one of claims 1 to 15 or 21 or a VHH antibodyas defined in any one of claims 16 to 20 for use in therapy of a subject.

28. A construct as defined in any one of claims 1 to 15 or 21 or a VHH antibodyas defined in any one of claims 16 to 20 for use in the treatment or prevention of pruritus in a subject.

29. A construct as defined in any one of claims 1 to 15 or 21 or a VHH antibodyas defined in any one of claims 16 to 20 for use in the treatment or prevention of atopic dermatitis in a subject.

30. A method of treating or preventing pruritus or atopic dermatitis, said methodcomprising administering to a subject in need thereof a therapeutically effectiveamount of a construct as defined in any one of claims 1 to 15 or claim 21 or a VHH antibody as defined in any one of claims 16 to 20.

31. Use of a construct as defined in any one of claims 1 to 15 or 21 or a VHHantibody as defined in any one of claims 16 to 20 in the manufacture of amedicament for the treatment or prevention of pruritus or atopic dermatitis in asubject.

32. The construct for use or VHH antibody for use according to any one ofclaims 27 to 29 or the method of claim 30 or the use of claim 31, wherein saidsubject is a canine.

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