Modified antibodies and their uses

Description

1 / 69 “MODIFIED ANTIBODIES AND THEIR USES”

[0001] The present invention relates to the field of biomedicine. The invention relates specifically to a new class of antibodies and their fragments which are fused for stabilizing purposes, their uses in medicine and the process for their production. BACKGROUND

[0002] Monoclonal antibodies, antibody fragments, and derived fusion proteins are widely used in diagnostics and therapies to detect and treat numerous diseases, such as cancer, inflammatory or autoimmune diseases, neurodegenerative disorders, immunological diseases, or rare blood diseases, as well as for the prevention and treatment of solid organ transplant rejection.

[0003] The antibody revolution in medicine is evidenced by the increasing number of antibody-based products. Antibodies are generally highly specific to a particular target and therefore tend to have less off-target toxicity than that observed with small molecule therapies.

[0004] Despite the importance of biological drugs in medicine, including antibodies and their derivatives, the biopharmaceutical industry faces significant challenges in their production (high costs and long processing times associated with the production of mammalian cells) and routes of administration. For example, due to their instability and high production cost, antibodies are administered as intravenous infusion or subcutaneous injection dosage forms, which are associated with side effects. Petition 870250104642, dated 11 / 14 / 2025, page 5 / 87 2 / 69 adverse events, such as systemic inflammatory response, infusion reactions, and poor adherence to therapy due to pain. These factors currently restrict the use of these agents to patients with more severe disease.

[0005] In order to overcome these factors, several efforts have been made, including engineered antibody derivatives, alternative production hosts or complex formulations, all aimed at increasing stability and efficiency in the specific target tissue / organ / cell.

[0006] New formulations that significantly stabilize mAbs under unfavorable conditions, such as low concentration or body temperature, have shown positive results with the antiVEGF antibodies Bevacizumab, Ranibizumab, and Aflibercept, all of which are prone to decreased function after being removed from the manufacturer's vial and diluted. (Giannos et al., Pharm Res. 2018; 35(4): 78).

[0007] Recombinant antibodies against tumor necrosis factor alpha (TNFα) and anti-IL23 are being developed for the oral treatment of inflammatory bowel disease. A modified anti-TNF antibody has demonstrated improved permeation into diseased tissue within the gastrointestinal (GI) tract (Nurbhai, Suhail, et al., Scientific Reports, 2019, 9, Article number: 14042, Roberts et al., Sci Rep. 2021, 11: 19422).

[0008] Antibodies that combat infectious gastrointestinal diseases are of interest for oral administration in both animals and humans. The fusion of antibodies or antibody fragments with fractions Petition 870250104642, dated 11 / 14 / 2025, page 6 / 87 3 / 69 recombinants demonstrated improved tolerance to intestinal proteases and resistance to degradation.

[0009] Oral administration of fusion antibody derivatives to mucosal IgA Fc regions has proven effective in protecting piglets against infection by enterotoxigenic E. coli (F4-ETEC) bearing F4 fimbriae (Virdi V. et al., Nat Biotechnol. 2019 May; 37(5):527-530). Another example is Patent document LIS20150252100A1, which describes a fusion protein comprising an anti-enterotoxigenic Escherichia coli (anti-ETEC) VHH fused to an IgA Fc domain.

[00010] Engineered antibodies similar to bovine colostrum antibody sequences have demonstrated efficacy as an oral therapy (Kailash C. Bhol et al., Inflamm Bowel Dis. 2013 Oct; 19(11): 2273-2281).

[00011] Pegylation to increase half-life (Certolizumab PEGOL) (Pasut G. et al., BioDrugs. 2014 Apr; 28 Suppl 1:S15-23), PASILATION (Somayeh Mazaheri et al., Scientific Reports volume 10, Article number: 18464, 2020) or anti-albumin antibodies (Ralph Adams et al., MAbs. 2016 Oct; 8(7): 1336-1346) are also alternatives to increase antibody stability in serum.

[00012] Topical, non-invasive routes of administration for biopharmaceuticals offer potential advantages over injections due to their ease of administration, high patient acceptability, low manufacturing cost, and potential local effect. Petition 870250104642, dated 11 / 14 / 2025, p. 7 / 87 4 / 69

[00013] New formulations of biological products that are easy and safe to administer are highly needed to meet the growing demand for affordable and stable biological products for non-injectable routes of administration. This is especially true for those conditions that require a localized effect without systemic exposure (e.g., dermal, intestinal, or respiratory diseases). Non-injectable biological products would reduce systemic adverse effects, avoid drug metabolism and dilution, and therefore reduce the required doses. New antibody derivatives are continuously being generated to interact with a variety of therapeutic targets. The economical and efficient production of these and other antibody derivatives is crucial for their future success.

[00014] Although research on the oral administration of biological products has been conducted for almost a century, its current therapeutic administration remains unchanged and limited to injection. The main barrier to oral administration is the stability of these biologics across adverse gastrointestinal (GI) conditions. The challenges to be overcome in order to make the oral administration of biological products a reality are improving biological stability in the gastrointestinal tract and achieving greater penetration and targeted administration. SUMMARY OF THE INVENTION

[00015] The authors of the present invention have discovered that novel modified antibodies fused to glycomodule motifs are superior to unmodified antibodies in terms of potency, stability and Petition 870250104642, dated 11 / 14 / 2025, page 8 / 87 5 / 69 resistance to aggregation. The inventors demonstrated that the addition of glycomodule motifs confers greater neutralizing activity compared to the unmodified antibody and makes antibodies fused to glycomodule motifs more stable with respect to temperature and proteases.

[00016] In view of the foregoing, a first aspect of the present invention relates to a modified antibody (hereinafter the “modified antibody of the invention”) comprising a first antibody chain consisting of a VH region and a CH1 region and a second antibody chain comprising a VL region and a CL region, wherein at least one of the antibody chains is fused to at least one glycomodule (GM) motif.

[00017] In a second aspect, the present invention relates to a polynucleotide (hereinafter “the first polynucleotide of the invention”) encoding the antibody chains of the modified antibody of the invention or a polynucleotide composition (hereinafter “the polynucleotide composition of the invention”) comprising a first polynucleotide encoding the first antibody chain of the modified antibody of the invention and a second polynucleotide encoding the second antibody chain of the modified antibody of the invention.

[00018] In a third aspect, the present invention relates to a vector (hereinafter “the first vector of the invention”) comprising the polynucleotide of the invention or a vector composition (hereinafter “the vector composition of the invention”) wherein each vector comprises one of the polynucleotides of the polynucleotide composition of the invention. Petition 870250104642, dated 11 / 14 / 2025, page 9 / 87 6 / 69

[00019] In another aspect, the present invention relates to a host cell (hereinafter “the host cell of the invention”) comprising the first vector of the invention or the vector composition of the invention.

[00020] In another aspect, the present invention relates to a pharmaceutical composition (hereinafter “the pharmaceutical composition of the invention”) comprising the modified antibody of the invention, the first polynucleotide of the invention or the polynucleotide composition of the invention, the first vector or the vector composition of the invention, or the host cell of the invention, and at least one pharmaceutically acceptable excipient.

[00021] In another aspect, the present invention relates to the modified antibody of the invention, to the first polynucleotide or polynucleotide composition of the invention, to the first vector or vector composition of the invention, to the host cell of the invention or to the pharmaceutical composition of the invention for use in medicine.

[00022] In another aspect, the present invention relates to the modified antibody of the invention, to the first polynucleotide or polynucleotide composition of the invention, to the first vector or vector composition of the invention, to the host cell of the invention or to the pharmaceutical composition of the invention, wherein the modified antibody is a TNFα-neutralizing modified antibody for use in the treatment of inflammatory diseases.

[00023] In another aspect, the present invention relates to the modified antibody of the invention, to the first polynucleotide or polynucleotide composition of the invention, to the first vector or vector composition of the invention, to Petition 870250104642, dated 11 / 14 / 2025, page 10 / 87 7 / 69 host cell of the invention or to the pharmaceutical composition of the invention for use in the treatment of gastrointestinal diseases.

[00024] In another aspect, the present invention relates to the modified antibody of the invention, to the first polynucleotide or polynucleotide composition of the invention, to the first vector or vector composition of the invention, to the host cell of the invention or to the pharmaceutical composition of the invention, wherein the modified antibody is against VEGF for use in the treatment of diseases associated with unwanted vascularization.

[00025] In another aspect, the present invention relates to the modified antibody of the invention, to the first polynucleotide or polynucleotide composition of the invention, to the first vector or vector composition of the invention, to the host cell of the invention or to the pharmaceutical composition of the invention, wherein the modified antibody is specific for VEGF for use in the treatment of endovascular age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema, diabetic retinopathy, or myopic choroidal neovascularization.

[00026] In another aspect, the present invention relates to a method, hereinafter referred to as "the first method of the invention", for producing the modified antibody of the invention, wherein the method comprises: (i) cultivate a cell comprising the first polynucleotide or polynucleotide composition of the invention, under conditions suitable to permit expression of the modified antibody from the polynucleotide or polynucleotides of the polynucleotide composition; and Petition 870250104642, dated 11 / 14 / 2025, page 11 / 87 8 / 69 (ii) recover the modified antibody from the culture.

[00027] In another aspect, the present invention relates to an antibody chain (hereinafter “the antibody chain of the invention”) comprising: (i) a VH region and a CH1 region; or (ii) a VL region and a CL region; in which the antibody chain is fused to a glycomodule (GM) motif.

[00028] In another aspect, the present invention relates to a polynucleotide (hereinafter “the second polynucleotide of the invention”) that encodes the antibody chain of the invention.

[00029] In another aspect, the present invention relates to a vector (hereinafter “the second vector of the invention”) comprising the second polynucleotide of the invention.

[00030] In another aspect, the present invention relates to a host cell comprising the second vector of the invention.

[00031] In another aspect, the present invention relates to an in vitro method, hereinafter "the second method of the invention for the detection of an antigen of interest present in a sample comprising: (i) placing the sample in contact with the modified antibody of the invention, wherein the modified antibody is capable of specifically binding to the antigen of interest under conditions suitable for the binding of the antigen of interest to the modified antibody; (ii) determine the presence of complexes containing the antigen of interest and the modified antibody. Petition 870250104642, dated 11 / 14 / 2025, page 12 / 87 9 / 69

[00032] In another aspect, the present invention relates to an in vitro method, hereinafter the third method of the invention, for the purification of an antigen of interest present in a sample comprising: (i) placing the sample in contact with the modified antibody of the invention, wherein the modified antibody is capable of specifically binding to the antigen of interest, under conditions suitable for the binding of the antigen of interest to the modified antibody; (ii) recover the complexes containing the antigen of interest and the modified antibody. DESCRIPTION OF THE FIGURES

[00033] Figure 1. Screening of antibody expression by direct ELISA. For the present study, the plate was coated with 0.5 μg / mL of human TNFα, incubated with culture media from independent clones and detected with an anti-human IgG antibody conjugated with HRP peroxidase (specific for Fab). The value is presented as a double increase relative to the wild-type strain signal.

[00034] Figure 2. Non-reducing ranibizumab immunoblots fused to GM at different positions. Equal amounts of culture media from independent clones (designated c1-13) were loaded. A) Detection with anti-human IgG antibody (specific for Fab) of independent clones expressing AF. B) Detection with anti-human IgG antibody (specific for Fab) of independent clones expressing GM-AF. C) Detection with anti-OLLAS antibody of independent clones expressing AFs. Full-length human monoclonal antibody (human IgG) and OLLAS-containing protein (C+OLLAS protein) were Petition 870250104642, dated 11 / 14 / 2025, p. 13 / 87 10 / 69 diluted in 0.1% BSA PBX and used as controls. AF: antibody fragment, HC: heavy chain, LC: light chain.

[00035] Figure 3. Recognition of ranibizumab and GB-AF-010 antigens (SEQ ID NO: 15 and SEQ ID NO: 16). Antigen recognition assessment was performed by Direct ELISA: A 96-well plate was coated with 0.5 μg / mL of VEGF, incubated with ranibizumab (commercial, purified) or GB-AF-010, and detected with an HRP-conjugated anti-human IgG (specific for Fab). Results are normalized by total Fab.

[00036] Figure 4. Non-reducing certolizumab immunoblots fused to GM at different positions. Equal amounts of culture media from independent clones (designated c1-c4) expressing AF were loaded. The cassettes tested were: (SP)10-certolizumab consists of (SP)10 at the N-terminus of certolizumab, in both heavy and light chains (SEQ ID NO: 19 and SEQ ID NO: 20), certolizumab-(SP)10 consists of (SP) at the C-terminus of certolizumab, in both heavy and light chains (SEQ ID NO: 21 and SEQ ID NO: 22), certolizumab-HC-(SP)10 consists of (SP)10 at the C-terminus of the certolizumab heavy chain (SEQ ID NO: 21) and the glycomodule-free light chain (SEQ ID NO: 24), certolizumab has no GM fusion (SEQ ID NO: 23 and SEQ ID NO: 24). Detection with anti-human IgG (specific for Fab). Full-length human monoclonal antibody (human IgG) prepared in 0.1% BSA PBX was used as a positive control.

[00037] Figure 5. Recognition of certolizumab and certolizumab-GM antigens. Antigen recognition was assessed by direct ELISA: Petition 870250104642, dated 11 / 14 / 2025, page 14 / 87 11 / 69 A 96-well plate was coated with 0.5 μg / mL of human TNFα (hTNFa), incubated with certolizumab (commercial, purified) or GB-AF-011 and detected with an anti-human IgG antibody conjugated with HRP peroxidase (specific for Fab). Results are normalized by total Fab.

[00038] Figure 6. Specificity of recognition of the GB-AF-011 antigen. The evaluation of antigen recognition was performed by direct ELISA: a 96-well plate was coated with 0.5 μg / mL of human TNFα (hTNα), Murine TNFα or PBS as a negative control (blank), incubated with GB-AF-011 and detected with an anti-human IgG antibody conjugated with HRP peroxidase (specific for Fab).

[00039] Figure 7. Comparison of TNFα neutralization capacity by various anti-TNFα agents. The evaluation of neutralization capacity (measured as % inhibition of hTNα binding to etanercept) was performed by competitive ELISA: the 96-well plate was coated with 1 μg / mL of etanercept, certolizumab (commercial, purified), infliximab (commercial, purified) or GB-AF-011, then biotinylated hTNα mixtures along with the anti-TNFα agent were added to the 96-well plate and detected with streptavidin-HRP conjugate.

[00040] Figure 8. Temperature stability of GB-AF-011, in comparison to commercial certolizumab, and GB-AF011 were incubated at 37°C and monitored over time. Concentrations were 8 μg / mL for GB-AF-011 (lyophilized and dialyzed to PBS) and 34 μg / mL for certolizumab (purified). Results were analyzed by A) direct ELISA (average of two replicates); B) reduction immunoblot with Petition 870250104642, dated 11 / 14 / 2025, page 15 / 87 12 / 69 anti-human IgG (specific for Fab) for detection; C) non-reducing immunoblot with anti-human IgG (specific for Fab) for detection.

[00041] Figure 9. Stability of certolizumab-GM compared to commercial anti-TNFα references under colonic conditions. Initial concentrations were 8 μg / mL for GB-AF-011, 32 μg / mL for certolizumab (purified), and 24 μg / mL for infliximab (purified). The anti-TNFα agents were diluted 1 / 5 in colonic contents, incubated at 37°C, and collected at different times. Results were analyzed by A) reduction immunoblot with anti-human IgG (specific for Fab) for detection, B) non-reduction immunoblot with anti-human IgG (specific for Fab) for detection.

[00042] Figure 10. Analysis of GB-AF011 production in a heterotrophic bioreactor. A) Monitoring the growth of strain-producing microalgae in a 1 L bioreactor. Growth was monitored by optical density (OD) at 750 nm. B) Non-reducing immunoblot with anti-human IgG (specific for Fab) for detection. The culture medium separated from the cells is loaded.

[00043] Figure 11. Novel antibody fragment structures. AF: antibody fragment. LC: light chain. HC: heavy chain. GM: glycomodule. CL: enterokinase cleavage sequence. SS-1: metalloprotease gametolysin secretion signal. SS-2: carbonic anhydrase 1 secretion sequence. DETAILED DESCRIPTION OF THE INVENTION Modified antibodies Petition 870250104642, dated 11 / 14 / 2025, page 16 / 87 13 / 69

[00044] The authors of the present invention have discovered that modified antibodies fused to glycomodular motifs confer greater efficacy through improved stability and / or activity. In particular, they have found that modified antibodies fused to glycomodular motifs are superior to unmodified antibodies in terms of potency, stability, and resistance to aggregation.

[00045] Given the properties of the modified antibodies fused to the glycomodule motifs, these new antibodies will allow applications beyond injected routes and facilitate the use of antibodies in several different areas. Due to their greater stability under physiological conditions, the AFs described herein, alone or in combination with other proteins, such as growth factors or cytokines, can be used as treatment for inflammatory diseases, infectious diseases, gastrointestinal diseases and / or for diseases associated with unwanted vascularization, specifically in a non-parenteral formulation (e.g., oral, topical or inhaled).

[00046] Thus, in a first aspect, the invention relates to a modified antibody (hereinafter the “modified antibody of the invention”) comprising a first antibody chain comprising a VH region and a CH1 region and a second antibody chain comprising a VL region and a CL region, wherein at least one of the antibody chains is fused to at least one glycomodule (GM) motif.

[00047] As used in this document, a “modified antibody” refers to an immunoglobulin of any isotype that can compete with the intact antibody. Petition 870250104642, dated 11 / 14 / 2025, p. 17 / 87 14 / 69 by specific binding to the target antigen, and includes, for example, chimeric, humanized and fully human modified antibodies.

[00048] As used in this document, isotype refers to the class of antibodies (e.g., lgG1, lgG2, lgG3, lgG-4, IgM, lgA1, lgA2, IgD, and IgE antibody) that is encoded by genes in the heavy chain constant region.

[00049] The modified antibodies of the present invention relate to: (i) antibodies comprising complete heavy chains (VH region and CH1, CH2 and CH3 regions) and complete light chains (VL regions and CL regions) and (ii) shortened versions of an antibody comprising a first antibody chain comprising a VH region and a CH1 region and a second antibody chain comprising a VL region and a CL region. The modified antibodies may be derived from only a single source or may be “chimeric”, i.e., different portions of the modified antibody may be derived from two different antibodies. In some embodiments, the modified antibody is an antibody fragment in which the heavy chain does not contain the CH2 constant domains and / or the CH3 constant domain.

[00050] The modified antibody of the invention comprises a first chain, which refers to the heavy chain. In a specific embodiment, the heavy chain consists of a variable domain, VH, and three constant domains CH1, CH2 and CH3. In another particular embodiment of the present invention, the modified antibody comprises only the variable domain (VH) and the first constant domain (CH1). In one embodiment Petition 870250104642, dated 11 / 14 / 2025, page 18 / 87 15 / 69 in particular, the CH1 region is C-terminal to the VH region. In another particular embodiment, the heavy chain of the modified antibody of the invention does not comprise the constant domains CH2 and / or CH3.

[00051] The modified antibody of the invention comprises a second chain, which refers to the light chain. In a specific embodiment, the light chain consists of a variable domain, VL, and a constant domain, CL. The modified antibody of the invention comprises the VL and CL regions. The modified antibody according to the invention may comprise a complete light chain or a fragment thereof, provided that the fragment comprises the VL and CL regions. In a specific embodiment, the CL region is C-terminal relative to the VL region.

[00052] The variable regions of the heavy and light chains (VH and VL, respectively) of the modified antibody according to the invention comprise the antigen-binding sites of immunoglobulin (Ig) molecules.

[00053] The term antigen-binding site, as used in this document, refers to the part of the modified antibody that determines the specific antigens to which it can bind. The variable region of the heavy chain and light chain of the modified antibody of the invention (VH and VL) can be specified as a hypervariable because this region can bind to a wide variety of antigens. This variable region contains a region at the top that is called the antigen-binding site. The antigen-binding site is also called a paratope. Each paratope is composed of six complementarity-determining regions (CDRs) — three from each of the light and heavy chains — that Petition 870250104642, dated 11 / 14 / 2025, page 19 / 87 16 / 69 extend from a fold of antiparallel beta sheets. As used in this document, the term CDR refers to the complementarity-determining region within variable antibody sequences and corresponds to an antibody region that has a structure that is complementary to its target antigen or epitope.

[00054] In the modified antibody of the invention, at least one of the antibody chains is fused to at least one glycomodule (GM) motif.

[00055] “A glycomodule (GM) motif”, as used herein, refers to an amino acid sequence comprising at least one residue that can be hydroxylated and glycosylated or one residue that can be glycosylated. As used herein, the term “glycosylation site” refers to an amino acid that acts as a glycosylation target site. In a preferred embodiment, the glycosylation site is an amino acid sequence that acts as a target for glycosylation in a microalga. Glycosylation is the reaction catalyzed by glycosyltransferases, which adds carbohydrates at a specific location to another molecule, preferably proteins. Protein glycosylation can occur in different ways, such as N-linked glycosylation, O-linked glycosylation, and phosphoserine glycosylation.Non-limiting examples of amino acids that can become glycosylated include: proline, serine, threonine, hydroxylysine, hydroxyproline, arginine, asparagine, and any variant of a naturally occurring amino acid with glycosylation potential. Thus, within the glycosylation sites, proline residues can be hydroxylated to form hydroxyprolines (Hyp). In one embodiment. Petition 870250104642, dated 11 / 14 / 2025, page 20 / 87 Preferred, glycosylation occurs at either serine (Ser) or hydroxyproline (Pro) of the glycomodule motif. The glycosylation sites can be located at one or both ends of the glycomodule motif and / or within the glycomodule, if desired. Preferably, glycosylation of the glycomodule motifs is O-glycosylation.

[00056] Hydroxyproline O-glycosylation is generally of two types: 1) arabinogalactan glycomodules comprise clustered non-contiguous hydroxyproline (Hyp) residues in which the Hyp residues are O-glycosylated with arabinogalactan adducts; and 2) arabinosylation glycomodules comprise contiguous Hyp residues in which some or all of the Hyp residues are arabinosylated (O-glycosylated) with arabinose chains of about 1 to 5 residues in length. O-glycosylation may occur after hydroxylation of one or more residues at the site.

[00057] In some embodiments, the modified antibody of the invention comprises only one glycomodulator motif, which may be on the first antibody chain or the second antibody chain, and these glycomodulator motifs may be in the C-terminal position or the N-terminal position of the antibody chains.

[00058] Thus, in a particular embodiment, the modified antibody of the invention comprises a glycomodule motif, which is located at the C-terminal position of the first antibody chain.

[00059] In another particular embodiment, the modified antibody of the invention comprises a motif of Petition 870250104642, dated 11 / 14 / 2025, page 21 / 87 18 / 69 glycomodule, which is located at the N-terminal position of the first antibody chain.

[00060] In another specific embodiment, the modified antibody of the invention comprises a glycomodule motif, which is located at the C-terminal position of the second antibody chain.

[00061] In another particular embodiment, the modified antibody of the invention comprises a glycomodular motif, which is located at the N-terminal position of the second antibody chain.

[00062] In some embodiments, the modified antibody of the invention comprises more than one glycomodular motif, in particular, two glycomodular motifs, one on the first antibody chain and the other on the second antibody chain. These glycomodular motifs may be in the C-terminal or N-terminal position of the antibody chains.

[00063] In one specific embodiment, the glycomodule motifs are located at the C-terminal position of the first antibody chain and at the C-terminal position of the second antibody chain.

[00064] In another specific embodiment, the glycomodule motifs are in the N-terminal position of the first antibody chain and in the N-terminal position of the second antibody chain.

[00065] In another specific embodiment, the glycomodule motif comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID: NO 4, SEQ ID NO: 5 and a functionally equivalent variant thereof, and (SP)n. Petition 870250104642, dated 11 / 14 / 2025, p. 22 / 87 19 / 69

[00066] (SP)n as disclosed in this document, refers to a nucleic acid construct encoding Serine-Proline n-repeat units, as disclosed in US9006410B2.

[00067] In one specific embodiment, the n repeat units are between 5 and 30. In a preferred embodiment, the n repeat units are 10 or 20. Thus, in a particular embodiment, the glycomodule motif comprises an amino acid sequence selected from the group consisting of (SP)io (SEQ ID NO: 6) or (SP)20 (SEQ ID NO: 7).

[00068] “Functionally equivalent variant of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4 or SEQ ID NO: 5”, as used in this document, refers to all sequences that result from the modification, insertion and / or deletion of one or more amino acids from the above sequence, provided that the function of the glycomodule motif is substantially maintained.

[00069] Suitable assays to determine whether a polypeptide can be considered a functionally equivalent variant of glycomodules would involve the expression of a fusion protein comprising the glycomodule variant and a marker protein, and detecting whether the addition of the glycomodule to the marker protein results in glycosylation of the fusion protein. The presence of glycosylation in a protein can be determined by any method known in the art, including, without limitation: glycoprotein staining (e.g., methods based on periodic acid-Schiff staining), enzymatic or chemical removal of protein-bound glycans, and detection of molecular weight change by Western blot and / or mass spectrometry. Petition 870250104642, dated 11 / 14 / 2025, page 23 / 87 20 / 69 A suitable assay to determine whether a given sequence acts as a glycomodule and can be considered a functionally equivalent variant of the glycomodules used in the invention was described by Ramos-Martinez and colleagues (Plant Biotechnol J. 2017, 15: 1214-1224).

[00070] Preferably, variants of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4 or SEQ ID NO: 5 are (i) polypeptides in which one or more amino acid residues are replaced by a preserved or non-preserved amino acid residue (preferably a preserved amino acid residue) and such substituted amino acid may or may not be encoded by the genetic code, (ii) polypeptides in which there are one or more modified amino acid residues, for example, residues modified by substituent linkage, (iii) polypeptides resulting from alternative processing of a similar mRNA, (iv) polypeptide fragments and / or (v) polypeptides resulting from the fusion of the polypeptide defined in (i) to (iii) with another polypeptide, such as a secretory leader sequence or a sequence being used for purification (e.g., His tag) or for detection (e.g., Sv5 epitope tag). Fragments include polypeptides generated by proteolytic cleavage (including multisite proteolysis) of an original sequence.Variants can be modified post-translationally or chemically. Such variants should be apparent to those skilled in the art.

[00071] One versed in the field will recognize that the identity values ​​of nucleotide sequences can be appropriately adjusted to determine the corresponding sequence identity of two sequences of Petition 870250104642, dated 11 / 14 / 2025, page 24 / 87 21 / 69 nucleotides that encode the polypeptides of the present invention, taking into account codon degeneracy, conservative amino acid substitutions, and reading frame positioning.

[00072] In the context of the present invention, conservative amino acid modifications and conservative amino acid substitutions are used synonymously in the invention. “Conservative amino acid substitutions” refers to the interchangeability of endo-residues with similar side chains and middle substitutions of one or more amino acids in a native amino acid sequence with other amino acid(s) having similar side chains, resulting in a silent change that does not alter the protein's function. Conserved substitutes for an amino acid within a native amino acid sequence may be selected from other members of the group to which the natural amino acid belongs.For example, a group of amino acids with aliphatic side chains includes glycine, alanine, valine, leucine, and isoleucine; a group of amino acids with aliphatic-hydroxyl side chains includes serine and threonine; a group of amino acids with amide-containing side chains includes asparagine and glutamine; a group of amino acids with aromatic side chains includes phenylalanine, tyrosine, and tryptophan; a group of amino acids with basic side chains includes lysine, arginine, and histidine; and a group of amino acids with sulfur-containing side chains includes cysteine ​​and methionine. In some embodiments of the invention, the preferred conservative amino acid substitutions are: valine-leucine, valine-isoleucine, phenylalanine-tyrosine, lysine-arginine, alanine-valine, aspartic acid. Petition 870250104642, dated 11 / 14 / 2025, p. 25 / 87 22 / 69 glutamic and asparagine-glutamine. Thus, the invention relates to functionally equivalent variants of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4 or SEQ ID NO: 5; and having an amino acid sequence that differs in one or more amino acids from the given sequence as a result of one or more conservative amino acid substitutions. It is well known in the art that one or more amino acids in a polypeptide sequence can be substituted by at least one other amino acid with similar charge and polarity, such that the substitution(s) result in a silent change in the modified polypeptide that does not alter its function relative to the function of the unmodified sequence. The invention relates to any polypeptide sequence that differs in one or more amino acids, whether as a result of conserved or non-conserved substitutions, and / or as a result of sequence insertions or deletions, relative to the sequence given by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4 or SEQ ID NO: 5, provided that the additionally supplied polypeptide sequence has the same glycomodule motif or a similar or equivalent motif as SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4 or SEQ ID NO: 5.

[00073] The terms identity, “identical” or “percent identity” in the context of two or more amino acid or nucleotide sequences refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acid or nucleotide residues that are the same when compared and aligned (introducing gaps, if necessary) for maximum matching, not considering any substitutions. Petition 870250104642, dated 11 / 14 / 2025, p. 26 / 87 23 / 69 conservative amino acids as part of the sequence identity. The percent identity can be measured using sequence software or comparison algorithms or by visual inspection. Several algorithms and software are known in the art that can be used to obtain alignments of amino acid or nucleotide sequences.

[00074] The percentage of sequence identity can be determined by comparing two ideally aligned sequences in a comparison window. The aligned sequences can be polynucleotide sequences or polypeptide sequences. For ideal alignment of the two sequences, the portion of the polynucleotide or amino acid sequence in the comparison window may include insertions or deletions (i.e., gaps) compared to the reference sequence (which does not include insertions or deletions). The percentage of sequence identity is calculated by determining the number of positions where identical nucleotide residues, or identical amino acid residues, occur in both compared sequences to yield the number of matching positions, then dividing the number of matching positions by the total number of positions in the comparison window and multiplying the result by 100 to yield the percentage of sequence identity.The sequence identity between two polypeptide sequences or two polynucleotide sequences can be determined, for example, using the Gap program in the WISCONSIN PACKAGE version 10.0-UNIX from Genetics Computer Group, Inc., based on the method of Needleman and Wunsch (J. Mol. Biol. 48:443-453, 1970) using the standard parameter set for pairwise comparison. Petition 870250104642, dated 11 / 14 / 2025, page 27 / 87 24 / 69 (for amino acid sequence comparison: Gap creation penalty=8, Gap extension penalty=2; for nucleotide sequence comparison: Gap creation penalty=50; Gap extension penalty=3), or using the TBLASTN program in the BLAST 2.2.1 software package (Altschul et al., Nucleic Acids Res. 25:33893402), using the BLOSUM62 matrix (Henikoff and Henikoff, Proc. National. Academic. Science. USA 89:10915-10919, 1992) and the standard parameter set for pairwise comparison (gap creation cost = 11, gap extension cost = 1).

[00075] Functionally equivalent variants of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5 also include sequences with sequence identity of at least 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% with sequences SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5, respectively.

[00076] In a preferred embodiment, the functionally equivalent variant of SEQ ID NO: 1, 2, 3, 4 or 5 has a sequence identity of at least 50% with the corresponding sequence SEQ ID NO, 1, 2, 3, 4 or 5 and the sequence identity is determined throughout the length of the sequence SEQ ID NO: 1, 2, 3, 4 or 5.

[00077] In a specific embodiment, the first antibody chain (heavy chain) and / or the second antibody chain (light chain) of the modified antibody of the invention comprises at least one glycomodule motif, at least Petition 870250104642, dated 11 / 14 / 2025, page 28 / 87 25 / 69 two glycomodule motifs, at least three glycomodule motifs, at least four glycomodule motifs, at least five glycomodule motifs, at least six glycomodule motifs, at least seven glycomodule motifs, at least eight glycomodule motifs, at least nine glycomodule motifs, at least ten glycomodule motifs or more.

[00078] In some embodiments, if the first antibody chain and / or the second antibody chain comprise more than one glycomodular motif, all of these glycomodular motifs may be in the C-terminal position or in the N-terminal position of the antibody chains. In other embodiments, some of these glycomodular motifs may be in the C-terminal position and others may be in the N-terminal position of the antibody chains.

[00079] In a specific embodiment, the glycomodule motif is connected to the first antibody chain by a linkage sequence.

[00080] In another specific embodiment, the glycomodule motif is connected to the second antibody chain by a linker sequence.

[00081] As used in this document, the term linker means a suitable peptide that allows two or more functional domains to be joined into a fusion protein. Linkers can be flexible or rigid. In a preferred embodiment, the linker is a flexible linker. Flexible linker, as used in this document, means that the joined domains require a certain degree of movement or interaction. They are usually composed of small nonpolar (e.g., Gly) or polar elements. Petition 870250104642, dated 11 / 14 / 2025, page 29 / 87 26 / 69 (e.g., Ser or Thr amino acids). The small size of these amino acids provides flexibility and allows for the mobility of functional linkage domains. The incorporation of Ser or Thr can maintain ligand stability in aqueous solutions by forming hydrogen bonds with water molecules and thus reduces unfavorable interactions between the ligand and protein fractions.

[00082] In certain embodiments, the linker is a peptide containing 1-25 amino acid residues, 1-20 amino acid residues, 2-15 amino acid residues, 3-10 amino acid residues, 3-7 amino acid residues, 4-25 amino acid residues, 4-20 amino acid residues, 4-15 amino acid residues, 4-10 amino acid residues, 5-25 amino acid residues, 5-20 amino acid residues, 5-15 amino acid residues, or 5-10 amino acid residues.

[00083] Exemplary ligands include glycine- and serine-rich ligands, for example, (GGP)n or (GGGS)n, where n is 1-5. The most commonly used flexible ligands have sequences consisting primarily of stretches of Gly and Ser residues (GS ligand). By adjusting the copy number n, the length of this GS ligand can be optimized to achieve appropriate separation of functional domains or to maintain necessary interdomain interactions. In a preferred embodiment, the linking sequence connecting the glycomodule motif to the first antibody chain comprises (GGGS)n or (GGGGS)n.

[00084] In another particular embodiment, the modified antibody of the invention further comprises a detection marker. As used in this document, the term marker means a polypeptide useful for Petition 870250104642, dated 11 / 14 / 2025, p. 30 / 87 27 / 69 facilitate the detection, isolation, and / or purification of a protein. Generally, the aforementioned labeling sequence is located in a part of the protein of interest that does not adversely affect its functionality. In a more particular embodiment, the detection marker is selected from the group consisting of the OLLAS marker (SEQ ID NO: 8), Flag marker (SEQ ID NO: 26), and His marker (SEQ ID NO: 25, SEQ ID NO: 29-34). In a still more particular embodiment, the detection marker is the OLLAS marker (SEQ ID NO: 8).

[00085] In another particular embodiment, the modified antibody of the invention comprises a processing site between the detection marker and the remainder of the chain. In a more specific embodiment, the processing site is a protease recognition site. As used herein, the term “protease recognition site” refers to an amino acid sequence that is susceptible to being cleaved by an enzyme that performs proteolysis, catabolism of proteins by hydrolysis of peptide bonds, once the protein has been translated. Suitable processing sites for use in the modified antibodies according to the present invention include amino acid sequences that are cleavable by proteases such as enterokinase, Arg-C endoprotease, Glu-C endoprotease, Lys-C endoprotease, factor Xa, SUMO proteases (Tauseef et al., 2005 Protein Expr. Purif. 43:1-9) and the like.In a more particular embodiment, the processing site is an enterokinase cleavage sequence (SEQ ID NO: 9) or a TEV protease (SEQ ID NO: 28), preferably an enterokinase cleavage sequence. The modified antibody of the invention may be... Petition 870250104642, dated 11 / 14 / 2025, p. 31 / 87 28 / 69 derived from different antibodies. In one specific embodiment, the modified antibody is derived from an anti-tumor necrosis factor (TNFα) neutralizing antibody.

[00086] Tumor necrosis factor (TNFα) is a pleiotropic cytokine with beneficial functions in immune regulation and host defense, but with deleterious pro-inflammatory and cytotoxic functions during inflammation. TNFα represents a critical mediator of the autoimmune process, playing a fundamental role in several inflammatory diseases, including rheumatoid arthritis (RA), ulcerative colitis, and Crohn's disease. Inhibition of TNFα has been achieved by the anti-TNFα biological etanercept, antibodies such as infliximab and adalimumab, or with the modified antibody certolizumab, used to treat autoimmune diseases.

[00087] In a more particular embodiment, the modified antibody of the invention is derived from a neutralizing tumor necrosis factor α (TNFα) selected from the group consisting of: adalimumab, infliximab, certolizumab or golimumab. In a still more particular embodiment, the modified antibody of the invention is derived from certolizumab.

[00088] Adalimumab is a monoclonal antibody used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativa, uveitis, and juvenile idiopathic arthritis.

[00089] Infliximab is a monoclonal antibody used to treat Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, and Behçet's disease. Petition 870250104642, dated 11 / 14 / 2025, page 32 / 87 29 / 69

[00090] Certolizumab is a Fab fragment of a recombinant humanized antibody that is used to treat Crohn's disease, rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

[00091] Golimumab is a monoclonal antibody used to treat rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

[00092] In a specific embodiment, the modified antibody of the invention is derived from certolizumab and comprises a heavy chain as defined in SEQ ID NO: 19 or SEQ ID NO: 21 and / or a light chain as defined in SEQ ID NO: 20 or SEQ ID NO: 22.

[00093] SEQ ID NO: 19, as disclosed in this document, refers to a modified antibody derived from certolizumab, comprising a glycomodule motif, comprising the amino acid sequence (SP) (SEQ ID NO: 6) and located at the N-terminal position of the first antibody chain (heavy chain).

[00094] SEQ ID NO: 20, as disclosed in this document, refers to a modified antibody derived from, comprising a glycomodule motif, comprising the amino acid sequence (SP) (SEQ ID NO: 6) and located at the N-terminal position of the second antibody chain (light chain).

[00095] SEQ ID NO: 21, as disclosed in this document, refers to a modified antibody derived from certolizumab, comprising a glycomodule motif, comprising the amino acid sequence (SP) (SEQ ID NO: 6) and located at the C-terminal position of the first antibody chain (heavy chain). Petition 870250104642, dated 11 / 14 / 2025, p. 33 / 87 30 / 69

[00096] SEQ ID NO: 22, as disclosed in this document, refers to a modified antibody derived from certolizumab, comprising a glycomodule motif, comprising the amino acid sequence (SP) (SEQ ID NO: 6) and located at the C-terminal position of the second antibody chain (light chain).

[00097] In another specific embodiment, the modified antibody of the invention is derived from a neutralizing antivascular endothelial growth factor (VEGF). In a more particular embodiment, the modified antibody of the invention is derived from bevacizumab or ranibizumab, preferably from ranibizumab.

[00098] Vascular endothelial cell growth factor (VEGF) is a potent mitogen for vascular endothelial cells that has been reported as a key regulator of normal and abnormal angiogenesis.

[00099] Bevacizumab is a modified antibody used for colon cancer, lung cancer, glioblastoma, and renal cell carcinoma. Ranibizumab is a modified antibody against VEGF indicated for the treatment of endovascular (wet) age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema, diabetic retinopathy, and myopic choroidal neovascularization. [000100] In another specific embodiment, the modified antibody of the invention is derived from ranibizumab and comprises a heavy chain as defined in SEQ ID NO: 15 or SEQ ID NO: 17 and / or a light chain as defined in SEQ ID NO: 16 or SEQ ID NO: 18. Petition 870250104642, dated 11 / 14 / 2025, p. 34 / 87 31 / 69 [000101] SEQ ID NO: 15, as disclosed in this document, refers to a modified antibody derived from ranibizumab, comprising a glycomodule motif, comprising the amino acid sequence (SP)20 (SEQ ID NO: 7) and which is at the C-terminal position of the first antibody chain (heavy chain). The sequence SEQ ID NO: 15 comprises the enterokinase cleavage sequence. [000102] SEQ ID NO: 16, as disclosed in this document, refers to a modified antibody derived from ranibizumab comprising a glycomodule motif, comprising the amino acid sequence (SP)20 (SEQ ID NO: 7) and located at the C-terminal position of the second antibody chain (light chain). The sequence SEQ ID NO: 16 comprises the enterokinase cleavage sequence. [000103] SEQ ID NO: 17, as disclosed in this document, refers to a modified antibody derived from ranibizumab comprising a glycomodule motif, comprising the amino acid sequence (SP)10 (SEQ ID NO: 6) and located at the N-terminal position of the first antibody chain (heavy chain). The sequence SEQ ID NO: 17 comprises the enterokinase cleavage sequence. [000104] SEQ ID NO: 18, as disclosed herein, refers to a modified antibody derived from ranibizumab, comprising a glycomodule motif, which comprises the amino acid sequence (SP)10 (SEQ ID NO: 6) and which is located at the N-terminal position of the second antibody chain (light chain). The sequence SEQ ID NO: 18 comprises the enterokinase cleavage sequence. [000105] In another specific embodiment, the modified antibody of the invention is derived from an antiintegrin. Petition 870250104642, dated 11 / 14 / 2025, page 35 / 87 32 / 69 neutralizing agent. In a more specific embodiment, the modified antibody of the invention is derived from natalizumab or vedolizumab. [000106] Natalizumab is used to treat multiple sclerosis and Crohn's disease, and vedolizumab is used to treat ulcerative colitis or Crohn's disease. [000107] In another specific embodiment, the modified antibody of the invention is derived from a neutralizing anti-IL23 / IL12 agent. In a more specific embodiment, the modified antibody of the invention is derived from a neutralizing anti-IL23 / IL-12 agent selected from the group consisting of ustekinumab, guselkumab, tildrakizumab, or risankizumab. [000108] Ustekinumab is used to treat Crohn's disease, ulcerative colitis, plaque psoriasis, and psoriatic arthritis; guselkumab, tildrakizumab, and risankizumab are used to treat psoriasis and have potential application for Crohn's disease and ulcerative colitis. Polynucleotides, Vectors and Host Cells [000109] In a second aspect, the present invention relates to a polynucleotide, hereinafter referred to as "the first polynucleotide of the invention," which encodes the antibody chains of the modified antibody of the invention, or a polynucleotide composition, hereinafter referred to as the polynucleotide composition of the invention, comprising a first polynucleotide which encodes the first antibody chain of the modified antibody of the invention and a second polynucleotide which encodes the second antibody chain of the modified antibody of the invention. Petition 870250104642, dated 11 / 14 / 2025, page 36 / 87 33 / 69 [000110] The terms “nucleic acid,” “polynucleotide,” and “nucleotide sequence,” as used interchangeably herein, refer to any polymeric form of nucleotides of any length and composed of ribonucleotides or deoxyribonucleotides. The terms include single-stranded and double-stranded polynucleotides, as well as modified polynucleotides (e.g., methylated, shielded). Typically, nucleic acid is a “coding sequence” which, as used herein, refers to a DNA sequence that is transcribed and translated into a polypeptide in a host cell when placed under the control of appropriate regulatory sequences. The boundaries of the coding sequence are determined by a start codon at the 5' (amino) end and a translation stop codon at the 3' (carboxy) end.A coding sequence may include, but is not limited to, prokaryotic sequences, eukaryotic mRNA cDNA, eukaryotic genomic DNA sequences (e.g., mammalian), and even synthetic DNA sequences. A transcription termination sequence will typically be located 3' relative to the coding sequence. [000111] In some embodiments, the first polynucleotide of the invention or each of the polynucleotides that are part of the composition of the invention further comprises a nucleotide sequence that encodes a secretory signal peptide, wherein the secretory signal peptide is fused into the structure to the N-terminus of the first and second antibody chains. Petition 870250104642, dated 11 / 14 / 2025, page 37 / 87 34 / 69 [000112] As used in this document, the term “signal peptide” or secretory signal peptide refers to a relatively short peptide, generally between 5 and 40 amino acid residues, directing proteins synthesized in the cell toward the secretory pathway. The signal peptide usually contains a series of hydrophobic amino acids that adopt a secondary alpha helix structure. In addition, many peptides include a series of positively charged amino acids that may contribute to the protein adopting the appropriate topology for its translocation. The signal peptide tends to have at its carboxyl terminus a motif for recognition by a peptidase, which is capable of hydrolyzing the signal peptide, giving rise to a free signal peptide and a mature protein. [000113] Any secretory signal peptide may be used in the present invention, as a non-limiting illustrative example the carbonic anhydrase (CAH1) signal peptide of Chlamydomonas reinhardtii having a nucleotide sequence shown in SEQ ID NO: 10, the periplasmic arylsulfatase 1 (ARS1) signal peptide of Chlamydomonas reinhardtii having a nucleotide sequence shown in SEQ ID NO: 11 or the gametolysin signal peptide of Chlamydomonas reinhardtii having a nucleotide sequence shown in SEQ ID NO: 12. [000114] It will be understood that, in order for the polynucleotide of the invention to be expressed in the host cell of interest, the polynucleotide can be provided in a manner operably linked to a regulatory region. Those skilled in the art will understand that suitable regulatory regions Petition 870250104642, dated 11 / 14 / 2025, page 38 / 87 35 / 69 can be used based on the host cell in which the polynucleotide can be expressed. The nature of the regulatory region is not specifically limiting in the present invention. [000115] In another aspect, the invention relates to a vector, hereinafter the first vector of the invention, comprising the first polynucleotide of the invention or a vector composition, hereinafter the vector composition of the invention, wherein each vector comprises one of the polynucleotides of the polynucleotide composition of the invention. [000116] As used in this document, the term vector or expression vector refers to a replicative DNA construct used to express the first polynucleotide or polynucleotide composition of the invention in a cell, preferably a eukaryotic cell. The choice of expression vector will depend on the choice of host. A wide variety of host / expression vector combinations can be employed. Useful expression vectors for eukaryotic hosts include, for example, vectors comprising expression control sequences of SV40, bovine papillomavirus, adenovirus, and cytomegalovirus. Useful expression vectors for bacterial hosts include known bacterial plasmids, such as Escherichia coli plasmids, including pCR1, pBR322, pMB9 and their derivatives, wider host range plasmids such as M13, and single-stranded filamentous DNA phages. [000117] In one specific embodiment, the vector is suitable for expression in microalgae. Preferred vectors Petition 870250104642, dated 11 / 14 / 2025, page 39 / 87 36 / 69 for this invention are vectors developed for algae, such as vectors commonly known to those skilled in the art, such as the pChlamy_4 vector (Invitrogen), or vectors available through the Chlamydomonas center. [000118] In another aspect, the present invention relates to a host cell, hereinafter the host cell of the invention, comprising the first vector or vector composition of the invention. [000119] The term host cell is used to refer not only to the specific target cell, but to the progeny or potential progeny of such a cell. Since certain modifications may occur in subsequent generations due to mutations or environmental influences, this progeny may not, in fact, be identical to the mother cell, but is still included within the scope of the term as employed in this document. A host cell can be any prokaryotic cell (e.g., E. coli) or eukaryotic cell (e.g., yeast or plant cells). [000120] In one particular embodiment, the host cell is a microalga. Microalga, as used herein, refers to a large and diverse group of simple, typically autotrophic organisms, ranging from unicellular to multicellular forms, microscopic algae, commonly found in freshwater and marine systems. Examples of suitable microalgae include microalgae from the phyla Cyanophyta, Chlorophyta, Rhodophyta, Heterokontophyta, and Haptophyta. Algae from the phylum Cyanophyta may include Spirulina (Arthrospira), Aphanizomenon flos-aquae, Anabaena cylindrica, or Lyngbya majuscule. Algae from the phylum Chlorophyta may include Chlorella, Scenedesmus, Dunaliella, Tetraselmis, Petition 870250104642, dated 11 / 14 / 2025, page 40 / 87 37 / 69 Haematococcus, Ulva, Codium, Botryococcus or Caulerpa spp. Algae of the Rhodophyta phylum can be Porphyridium cruentum, Gracilaria sp., Grateloupia sp, Palmaria sp. Corallina sp., Chondrus crispus, Porphyra sp. or Rhodosorus sp. Algae of the Heterokontophyta phylum can be Nannochlorropsis oculata, Odontella aurita, Phaeodactylum tricornutum. Fucus sp. Sargassum sp. Padina sp., Undaria pinnatifida or Laminaria sp. Algae of the Haptophyta phylum can be Isochrysis sp. Tisochrysis sp. or Pavlova sp. Algae can be Chrypthecodinium cohnii, Schizochytrium, Ulkenia or Euglena gracilis. Algae can be green microalgae such as Chlorella, Scenedesmus, Dunialiella, Haematococcus and Bracteacoccus, haptophyte microalgae such as Isochrysis and heterokontophyte microalgae such as Phaeodactylum, Ochromonas and Odontella. [000121] In a more specific embodiment, the microalga is a green alga. Suitable examples of green algae are Chlorella or Haematyococcus, Botryococcus or Chlamydomonas. In an even more specific embodiment, the microalga is of the genus Chlamydomonas. [000122] Chlamydomonas, as used in this document, refers to a genus of green algae consisting of about 325 species, all unicellular flagellates, found in stagnant water and moist soil, in freshwater, seawater, and even in snow as snow algae. In a preferred embodiment, the microalga is of the species Chlamydomonas reinhardtii. [000123] Chlamydomonas reinhardtii, as used in this document, is a unicellular green alga about 10 micrometers in diameter that swims with two flagella. It has a cell wall made of glycoproteins rich in Petition 870250104642, dated 11 / 14 / 2025, p. 41 / 87 38 / 69 hydroxyproline, a large cup-shaped chloroplast, a large pyrenoid, and an eyespot that detects light. [000124] In another specific embodiment, the host cell is a plant cell. The term “plant cell,” as used in this document, refers to a plant expression system that is capable of producing the glycosylation that was described in the definition of “glycomodule motif.” Pharmaceutical Compositions [000125] In another aspect, the invention relates to a pharmaceutical composition, hereinafter "the pharmaceutical composition of the invention", comprising the modified antibody of the invention, the first polynucleotide or polynucleotide composition of the invention, the first vector or vector composition of the invention or the host cell of the invention, and at least one pharmaceutically acceptable excipient. [000126] The term “pharmaceutical composition” is a form that allows the biological activity of the active ingredient contained therein to be effective and to have unacceptable toxicity for the individual to whom the composition is administered. The term pharmaceutical composition also encompasses veterinary compositions. The term “veterinary compositions,” as used in this document, refers to any substance or combination of substances presented as having properties to treat or prevent diseases in animals or that may be administered to animals for the purpose of restoring, correcting, or modifying physiological functions, exerting a pharmacological, immunological, or metabolic action, or for obtaining a veterinary diagnosis. Premixes for medicated feed prepared for Petition 870250104642, dated 11 / 14 / 2025, p. 42 / 87 39 / 69 incorporation into a feed should also be considered veterinary compositions. [000127] The term excipient refers to a substance that assists in the absorption of any of the components or compounds of the pharmaceutical composition of the invention, or stabilizes the components or compounds and / or assists in the preparation of the pharmaceutical composition in order to give it consistency or flavors to make it more palatable. Thus, excipients may have the function, by way of example but not limited to, of binding the components (e.g., starches, sugars or cellulose), sweetening, coloring, protecting the active substance (e.g., isolating it from air and / or moisture), filling a tablet, capsule or any other presentation or a disintegrating function to facilitate the dissolution of the components, without excluding other excipients not listed in the paragraph.The term excipient is therefore defined as a material that, included in pharmaceutical dosage forms, is added to the active substances or their combinations to allow their preparation and stability, to modify their organoleptic properties, or to determine the physical and chemical properties of the pharmaceutical composition and its bioavailability. [000128] The expression “pharmaceutically acceptable excipient”, as used herein, includes any and all solvents, dispersing media, coatings, antibacterial and antifungal agents, isotonic agents and absorption retardants that are physiologically compatible with the modified antibody of the invention, the first polynucleotide or polynucleotide composition of the invention, the first vector or the Petition 870250104642, dated 11 / 14 / 2025, page 43 / 87 40 / 69 vector composition of the invention, or the first host cell of the invention. [000129] A “pharmaceutical form” is the configuration to which the active ingredients and excipients are adapted to provide a pharmaceutical composition or medicinal product. It is defined by the combination of how the pharmaceutical composition is presented by the manufacturer and how it is administered. [000130] The pharmaceutical composition of the invention comprises the modified antibody of the invention in a therapeutically effective amount. The “therapeutically effective amount” is any quantity of the component or compound of the composition which, when administered to an individual, is sufficient to produce the desired effect. Said component or compound of the composition refers to the modified antibody of the invention. The therapeutically effective amount may vary depending on, for example, the age, body weight, general health status, sex and diet of the individual, as well as the mode and timing of administration, the rate of excretion or any possible co-treatment with other medications. [000131] In a specific embodiment, the modified antibody of the invention or the pharmaceutical composition of the invention must be administered orally, topically, via inhalation, or by eye drops. [000132] The term “topically,” as used in this document, refers to a form of administration that has a local effect on a body surface and, therefore, the topical route of administration may also include enteral administration of medications that are minimally invasive. Petition 870250104642, dated 11 / 14 / 2025, page 44 / 87 41 / 69 absorbable by the gastrointestinal tract or inhaled formulations for administration into the respiratory tract. [000133] The term “enteral administration,” as used in this document, refers to the administration of medications via the human gastrointestinal tract. Enteral administration involves the esophagus, stomach, and small and large intestines (i.e., the gastrointestinal tract). Methods of administration include oral, sublingual (dissolving the medication under the tongue), and rectal administration. [000134] The modified antibody of the invention, or the pharmaceutical composition of the invention, may be in a form suitable for oral use, for example, as tablets, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsions, solutions, hard or soft capsules, syrups or elixirs. Compositions intended for oral use may be prepared according to any method known in the art for the manufacture of pharmaceutical compositions and such compositions may contain one or more agents selected from the group consisting of sweetening agents, flavoring agents, coloring agents and preservative agents, in order to provide pharmaceutically elegant and palatable preparations. [000135] Formulations for oral use may also be presented as hard gelatin capsules, in which the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules, in which the active ingredient is mixed with water or an oily medium, for example, peanut oil, liquid paraffin or olive oil. Petition 870250104642, dated 11 / 14 / 2025, page 45 / 87 42 / 69 [000136] Aqueous suspensions contain the active materials mixed with excipients suitable for the manufacture of aqueous suspensions. Such excipients are suspending agents, for example, sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinylpyrrolidone, tragacanth gum and acacia gum; Dispersing or wetting agents may be a naturally occurring phosphatide, for example, lecithin, or condensation products of an alkylene oxide with fatty acids, for example, polyoxyethylene stearate, or condensation products of ethylene oxide with long-chain aliphatic alcohols, for example, heptadecaethylene oxyethanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol, such as polyoxyethylene sorbitol monoleate, or condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides, for example, polyethylene sorbitan monoleate.Aqueous suspensions may also contain one or more preservatives, for example, ethyl or n-propyl hydroxybenzoate, one or more colorants, one or more flavorings, and one or more sweeteners, such as sucrose or saccharin. [000137] Oil suspensions can be formulated by suspending the active ingredient in a vegetable oil, for example, peanut oil, olive oil, sesame oil or coconut oil, or in a mineral oil, such as liquid paraffin. Oil suspensions may contain a thickening agent, for example, beeswax, hard paraffin or cetyl alcohol. Sweetening agents, such as those described above, and agents Petition 870250104642, dated 11 / 14 / 2025, page 46 / 87 43 / 69 Flavorings may be added to provide a palatable oral preparation. These compositions may be preserved by the addition of an antioxidant, such as ascorbic acid. [000138] Furthermore, various systems are known that can be used for sustained-release administration of the pharmaceutical composition of the invention, including, without limitation, encapsulation in liposomes, microbubbles, microparticles or microcapsules and the like. Suitable sustained-release forms, as well as materials and methods for their preparation, are well known in the state of the art. Thus, the orally administrable form of the pharmaceutical composition of the invention is in a sustained-release form, further comprising at least one coating or matrix. The sustained-release coating or matrix includes, without limitation, semi-synthetic or synthetic polymers, water-insoluble or modified natural polymers, waxes, fats, fatty alcohols, fatty acids, natural, semi-synthetic or synthetic plasticizers or a combination of two or more of these. Enteric coatings can be applied by conventional processes known to those skilled in the art. [000139] For topical use, creams, ointments, gels, solutions or suspensions and the like, containing the modified antibody of the present invention, are employed. Similarly, transdermal patches can also be used for topical administration. [000140] The term “respiratory administration,” as used in this document, refers to the administration of medications via the respiratory tract. Petition 870250104642, dated 11 / 14 / 2025, page 47 / 87 44 / 69 It is an effective route of administration, especially for medications with low oral bioavailability. For respiratory use, inhalation devices, dry powder, nebulizers, aerosolized liquid solutions, metered-dose inhalers (MDIs), soft mist inhalers (SMIs), and similar devices containing the modified antibody of the present invention are employed. [000141] The term “eye drops,” as used in this document, refers to liquid drops applied directly to the surface of the eye, usually in small amounts, such as a single drop or a few drops. Eye drops containing the modified antibody of the invention are employed. The eye drops may contain saline solution to match the salinity of the eye and / or a lubricant. The eye drops may be administered using a dropper or a glass pipette with a rubber bulb. [000142] However, it should be understood that the specific dose level and dosing frequency for any particular patient may vary and will depend on a variety of factors, including the activity of the specific compound employed, the metabolic stability and duration of action of that compound, age, body weight, general health, sex, diet, mode and timing of administration, excretion rate, drug combination, severity of the specific condition, and the host on therapy. [000143] In addition to what has been described above, the present invention also encompasses the possibility that the pharmaceutical composition of the invention may be administered to an individual together with other components or compounds, Petition 870250104642, dated 11 / 14 / 2025, page 48 / 87 45 / 69 even if these are not part of the pharmaceutical composition of the invention. Therapeutic uses [000144] In another aspect, the present invention relates to the modified antibody of the invention, to the first polynucleotide or polynucleotide composition of the invention, to the first vector or vector composition of the invention, to the host cell of the invention or to the pharmaceutical composition of the invention for use in medicine. The use in medicine to which the present invention refers may be for human or veterinary use. [000145] In another aspect, the present invention relates to the modified antibody of the invention, to the first polynucleotide or polynucleotide composition of the invention, to the first vector or vector composition of the invention, to the host cell of the invention or to the pharmaceutical composition of the invention for use in medicine, wherein the antibody is administered topically. The term topically has been described or explained above, and this definition is applicable to the therapeutic uses of the invention. [000146] In another aspect, the present invention relates to the modified antibody of the invention, to the first polynucleotide or polynucleotide composition of the invention, to the first vector or vector composition of the invention, to the host cell of the invention or to the pharmaceutical composition of the invention, wherein the modified antibody is a TNFα-neutralizing modified antibody for use in the treatment of inflammatory diseases. [000147] As used in this document, the term treat (or treat or treatment) refers to Petition 870250104642, dated 11 / 14 / 2025, p. 49 / 87 46 / 69 processes that involve slowing down, interrupting, halting, controlling, stopping, reducing, or reversing the progression or severity of an existing symptom, disorder, condition, or disease, but do not necessarily involve the total elimination of all symptoms, conditions, or disorders related to the disease. Treatment of a disorder or disease may lead, for example, to an interruption in the progression of the disorder or disease (e.g., no deterioration of symptoms) or to a delay in the progression of the disorder or disease (if the interruption in progression is only of a transient nature). Treatment of a disorder or disease may also lead to a partial response (e.g., improvement of symptoms) or a complete response (e.g., disappearance of symptoms) in the individual / patient suffering from the disorder or disease.Consequently, the treatment of a disorder or disease can also refer to an improvement in the disorder or disease, which may, for example, lead to an interruption in the progression of the disorder or disease or a delay in the progression of the disorder or disease. This partial or complete response may be followed by a relapse. It is important to understand that an individual / patient may experience a wide range of responses to treatment. [000148] The term “individual,” as used herein, refers to an individual, plant, or animal, such as a human being, a non-human primate (e.g., chimpanzees and other species of monkeys and apes); farm animals, such as birds, fish, cattle, sheep, pigs, goats, and horses; domestic mammals, such as dogs and cats; laboratory animals, including rodents, such as Petition 870250104642, dated 11 / 14 / 2025, page 50 / 87 47 / 69 mice, rats, and guinea pigs. The term does not denote a specific age or sex. In a preferred embodiment of the invention, the individual is a human being. [000149] In the present invention, the condition or disorder to be treated is inflammatory diseases. Inflammatory diseases include a wide range of disorders and conditions that are characterized by inflammation. Inflammatory diseases can affect the nervous system (examples include, but are not limited to, encephalitis, myelitis, meningitis, neuritis, dacryoadenitis, scleritis, episcleritis, keratitis, retinitis, chorioretinitis, blepharitis, conjunctivitis, uveitis, otitis, labyrinthitis, and mastoiditis), the cardiovascular system (examples include, but are not limited to, endocarditis, myocarditis, pericarditis, arteritis, phlebitis, and capillaritis), the respiratory system (examples include, but are not limited to, sinusitis, rhinitis, pharyngitis, laryngitis, tracheitis, bronchitis, bronchiolitis, pneumonitis, and pleurisy), the digestive system (examples include, but are not limited to, inflammatory bowel disease, including ulcerative colitis and Crohn's disease, stomatitis, gingivitis, gingivostomatitis, glossitis,tonsillitis, sialadenitis / parotitis, cheilitis, esophagitis, gastritis, gastroenteritis, enteritis, colitis, enterocolitis, duodenitis, ileitis, cecitis, appendicitis, proctitis, hepatitis, ascending cholangitis, cholecystitis, pancreatitis, and peritonitis), the musculoskeletal system (examples include, but are not limited to, arthritis, dermatomyositis, myositis, synovitis, bursitis, tendinitis, panniculitis, osteochondritis, spondylitis, periostitis, and chondritis), the urinary system (examples include, but are not limited to, nephritis, Petition 870250104642, dated 11 / 14 / 2025, page 51 / 87 48 / 69 urethritis, cystitis and urethritis), the reproductive system (examples include, but are not limited to, oophoritis, salpingitis, endometritis, parametritis, cervicitis, vaginitis, vulvitis, mastitis, orchitis, epididymitis and prostatitis) and the endocrine system (examples include, but are not limited to, insulitis, hypophysitis, thyroiditis, parathyroiditis and adrenalitis) [000150] In another aspect, the present invention relates to the modified antibody of the invention, to the first polynucleotide or polynucleotide composition of the invention, to the first vector or vector composition of the invention, to the host cell of the invention or to the pharmaceutical composition of the invention for use in the treatment of infectious diseases. Infectious diseases are caused by the entry into the body of pathogenic agents or microorganisms (such as bacteria, viruses, protozoa, or fungi) that grow and multiply there. An infectious disease can be different from a simple infection, which is the invasion and replication in the body by any of several agents—including bacteria, viruses, fungi, protozoa, and worms—as well as the reaction of tissues to their presence or the toxins they produce. The most important barriers to the invasion of the human host by infectious agents are the skin and mucous membranes. When these tissues are broken or affected by previous diseases, invasion by infectious agents can occur. These infectious agents can cause a local infectious disease, such as boils, or they can invade the bloodstream and be carried throughout the body, causing generalized bloodstream infection (septicemia) or localized infection at a distant site, such as meningitis. Petition 870250104642, dated 11 / 14 / 2025, p. 52 / 87 49 / 69 Infectious diseases can be caused by a virus, such as the common cold, influenza, COVID-19, gastroenteritis, hepatitis, or respiratory syncytial virus (RSV); by bacteria, such as strep throat, salmonella, tuberculosis, whooping cough, chlamydia, gonorrhea, and other sexually transmitted infections (STIs), urinary tract infections (UTIs), E. coli, or Clostridioides difficile; by fungi, such as ringworm (like athlete's foot), fungal nail infections, vaginal candidiasis (vaginal yeast infection), or thrush; and by parasites, such as giardiasis, toxoplasmosis, hookworms, or pinworms. [000151] In another aspect, the present invention relates to the modified antibody of the invention, the first polynucleotide or polynucleotide composition of the invention, the first vector or vector composition of the invention, the host cell of the invention or the pharmaceutical composition of the invention for use in the treatment of gastrointestinal diseases. One skilled in the field will understand that the gastrointestinal disease to be treated will require a modified antibody according to the invention, which is specific for a molecule that needs to be targeted in the specific disease. For example, if the disease to be treated is an enterotoxigenic E. coli infection, the modified antibody to be used will be an antibody specific for E. coli fimbriae and which prevents the pathogen from adhering to the gastrointestinal tract. [000152] Gastrointestinal diseases refer to various disorders of the digestive system. These conditions can range from mild to severe. Some common problems include heartburn, cancer, irritable bowel syndrome, histamine intolerance, and lactose intolerance. Other Petition 870250104642, dated 11 / 14 / 2025, page 53 / 87 50 / 69 Digestive diseases include: gallstones, cholecystitis and cholangitis, rectal problems (anal fissure, hemorrhoids, proctitis and rectal prolapse), esophageal problems (stenosis, achalasia and esophagitis), stomach problems (gastritis, gastric ulcers usually caused by Helicobacter pylori infection and cancer), liver problems (hepatitis B, hepatitis C, cirrhosis, liver failure and alcoholic and autoimmune hepatitis), pancreatitis and pancreatic pseudocyst, intestinal problems such as polyps and cancer, infections, celiac disease, Crohn's disease, ulcerative colitis, diverticulosis, malabsorption, short bowel syndrome and intestinal ischemia, gastroesophageal reflux disease, peptic ulcer and hiatal hernia, among others. [000153] In another aspect, the present invention relates to the modified antibody of the invention, to the first polynucleotide or polynucleotide composition of the invention, to the first vector or vector composition of the invention, to the host cell of the invention or to the pharmaceutical composition of the invention, wherein the modified antibody is a modified VEGF-neutralizing antibody for use in the treatment of diseases associated with unwanted vascularization. [000154] Diseases associated with unwanted vascularization refer to any condition affecting the circulatory system. Some common problems related to unwanted vascularization include edema, venous occlusion, peripheral vascular disease (PVD), carotid artery disease, ischemia, abdominal aortic aneurysm, chronic venous insufficiency, deep vein thrombosis, among others. Petition 870250104642, dated 11 / 14 / 2025, p. 54 / 87 51 / 69 [000155] In another aspect, the present invention relates to the modified antibody of the invention, to the first polynucleotide or polynucleotide composition of the invention, to the first vector or vector composition of the invention, to the first host cell of the invention or to the pharmaceutical composition of the invention, wherein the modified antibody is a VEGF-neutralizing antibody for use in the treatment of endovascular age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema, diabetic retinopathy or myopic choroidal neovascularization. Methods for Producing Modified Antibodies [000156] In another aspect, the present invention relates to a method, hereinafter referred to as "the first method of the invention", for producing the modified antibody of the invention, wherein the method comprises: (i) cultivate a cell comprising the first polynucleotide or polynucleotide composition of the invention under suitable conditions, so as to allow expression of the modified antibody from the polynucleotide or polynucleotides of the polynucleotide composition; and (ii) recover the modified antibody from the culture. [000157] In one specific embodiment, the cell is a plant cell or a microalga. In a more specific embodiment, if the cell is a microalga, it is a green alga, more specifically of the genus Chlamydomonas, preferably of the species Chlamydomonas reinhardtii. [000158] The first method of the invention comprises a first growth step of a cell comprising the first polynucleotide or polynucleotide composition of the invention. The first polynucleotide or composition Petition 870250104642, dated 11 / 14 / 2025, page 55 / 87 52 / 69 polynucleotides of the invention that are comprised in the first vector or vector composition of the invention can be introduced into the cell by means of well-known techniques such as transfection, electroporation, particle bombardment and transformation using the first vector of the invention that has been isolated. In a preferred embodiment, the vector is introduced by transformation or electroporation. The transformed cell can be recovered in a solid nutrient medium or in a liquid medium. [000159] Furthermore, the first method of the invention comprises growing said cell under suitable conditions to permit the expression of the modified antibody from the first polynucleotide or polynucleotide composition of the invention. The suitable culture conditions for microalgae growth and for modified antibody expression may differ for each type of microalga. However, these conditions are well known in the art and are easily determined. [000160] In a specific embodiment, the microalga is cultivated in a bioreactor in a suitable medium, without illumination, under mixotrophic or heterotrophic conditions, at a suitable temperature. Virtually any medium suitable for microalgae cultivation can be used; however, illustrative and non-limiting examples of such media include TAP media. The temperature can generally vary between approximately 17°C and 37°C, specifically between 21°C and 30°C. The culture can be carried out in the absence of aeration or with aeration. Similarly, the maintenance duration can vary according to the microalga and the amount of modified antibody to be prepared. Again, Petition 870250104642, dated 11 / 14 / 2025, pp. 56 / 87 53 / 69 These conditions are well known and can be easily determined in specific situations. [000161] The second step of the first method of the invention comprises recovering the modified antibody from the culture. [000162] In a specific embodiment of the first method of the invention, the first polynucleotide or polynucleotide composition comprises a nucleotide sequence encoding secretory signal peptides. Thus, the modified antibody is recovered from the culture supernatant. [000163] In another specific embodiment of the first method of the invention, the modified antibodies are retained and accumulated within the cells. Thus, the first method of the invention comprises an additional step comprising the extraction of the modified antibodies from the cells. [000164] Techniques and conditions for extracting an active compound from cells are widely known in the prior art, and any of them can be employed in the context of the present invention. [000165] Extraction refers to the process by which the active compounds retained within the cell, specifically the modified antibody of the invention, are released into the medium. This extraction can be carried out, for example, by mechanical means such as pressure or ultrasound. Modified Antibody Chains with GMs [000166] In another aspect, the invention relates to an antibody chain, hereinafter the antibody chain of the invention, comprising: (i) a VH region and a CH1 region; the Petition 870250104642, dated 11 / 14 / 2025, page 57 / 87 54 / 69 (ii) a VL region and a CL region; in which the antibody chain is fused to a glycomodule (GM) motif. [000167] In a specific embodiment, if the antibody chain of the invention comprises a VH region and a CH1 region, then the CH1 region will be C-terminal relative to the VH region. [000168] In another specific embodiment, if the antibody chain of the invention comprises a VL region and a CL region, then the CL region will be C-terminal relative to the VL region. [000169] The term “glycomodule” has been defined or explained above, and this definition is applicable to the antibody chain of the invention. The glycomodule motif may be in the C-terminal position or in the N-terminal position of the antibody chain of the invention. [000170] In a specific embodiment, the glycomodule motif is located at the C-terminal position of the antibody chain, comprising a VH region and a CH1 region (heavy chain). [000171] In another specific embodiment, the glycomodule motif is located at the C-terminal position of the antibody chain, comprising a VL region and a CL region (light chain). [000172] In another specific embodiment, the glycomodule motif is located at the N-terminal position of the antibody chain, comprising a VH region and a CH1 region (heavy chain). [000173] In another specific embodiment, the glycomodule motif is in the N-terminal position of the chain of Petition 870250104642, dated 11 / 14 / 2025, pp. 58 / 87 55 / 69 antibody comprising a VL region and a CL (light chain) region. [000174] In another specific embodiment, the glycomodule motif comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, or a functionally equivalent variant thereof, and (SP)n, specifically (SP)io (SEQ ID NO: 6) or (SP)20 (SEQ ID NO: 7). [000175] In another specific embodiment, the glycomodule motif is connected to the antibody chain of the invention by a linker. [000176] The terms “SEQ ID NO: 1”, “SEQ ID NO: 2”, “SEQ ID NO: 3”, “SEQ ID NO: 4”, “SEQ ID NO: 5”, “(SP)ne and “ligand” have been explained or defined above and these definitions are applicable to the antibody chain of the invention. [000177] In another specific embodiment, the antibody chain of the invention further comprises a detection marker. In a more specific embodiment, the detection marker is selected from the group consisting of the OLLAS marker (SEQ ID NO: 8), Flag marker (SEQ ID NO: 26) and His marker (SEQ ID NO: 25, SEQ ID NO: 29-34). In a still more specific embodiment, the detection marker is the OLLAS marker (SEQ ID NO: 8). [000178] The term “marker” has been defined or explained above and this definition is applicable to the antibody chain of the invention. [000179] In another specific embodiment, the antibody chain of the invention comprises a processing site between the detection marker and the remainder of the Petition 870250104642, dated 11 / 14 / 2025, p. 59 / 87 56 / 69 chain. In a more specific embodiment, the processing site is a protease recognition site. In an even more specific embodiment, the processing site is preferably an enterokinase cleavage sequence (SEQ ID NO: 9) or a TEV protease (SEQ ID NO: 28), preferably an enterokinase cleavage sequence. [000180] The term “protease recognition site” has been defined or explained above and this definition is applicable to the antibody chain of the invention. [000181] In another aspect, the present invention relates to a polynucleotide, hereinafter "the second polynucleotide of the invention", which encodes the antibody chain of the invention. [000182] In a specific embodiment, the second polynucleotide of the invention further comprises a nucleotide sequence encoding a secretory signal peptide, wherein the secretory signal peptide is fused into the structure to the N-terminus of the antibody chain of the invention. [000183] In a more specific embodiment, the signal peptide is selected from the group consisting of the carbonic anhydrase 1 (CAH) signal peptide (SEQ ID NO: 10), the ARS signal peptide (SEQ ID NO: 11) or the gametolysin signal peptide (SEQ ID NO: 12). [000184] The terms “polynucleotide” and “signal peptide” have been defined or explained above, and these definitions are applicable to the second polynucleotide of the invention. Petition 870250104642, dated 11 / 14 / 2025, pp. 60 / 87 57 / 69 [000185] In another aspect, the present invention relates to a vector, hereinafter "the second vector of the invention", comprising the second polynucleotide of the invention. [000186] The term “vector” has been defined or explained above and this definition is applicable to the second vector of the invention. [000187] In another aspect, the present invention relates to a host cell comprising the second vector of the invention. [000188] In one specific embodiment, the host cell is a plant cell or a microalgal cell, preferably a microalgal cell of the species Chlamydomonas reinhardtii. [000189] The term “host cell” has been defined or explained above. Methods for Antigen Detection in a Sample [000190] In another aspect, the present invention relates to an in vitro method, hereinafter "the second method of the invention," for detecting an antigen of interest present in a sample comprising: (i) placing the sample in contact with the modified antibody of the invention, wherein the modified antibody is capable of specifically binding to the antigen of interest under conditions suitable for the binding of the antigen of interest to the modified antibody; (ii) determine the presence of complexes containing the antigen of interest and the modified antibody. [000191] In the present invention, the term in vitro means that the determination of the presence of complexes containing the antigen of interest and the modified antibody is Petition 870250104642, dated 11 / 14 / 2025, pp. 61 / 87 58 / 69 performed outside the individual's body. The term "individual" has been defined or explained above, and this definition is applicable to the second method of the invention. [000192] The term “sample” refers to a small part or quantity of something that is considered representative of the whole and that is taken or separated from it for purposes of study, analysis, or experimentation. In the present invention, said study, analysis, or experimentation refers to the detection of the presence of complexes containing the antigen of interest and the modified antibody. The term sample also includes samples that have been manipulated in some way after their collection, for example, by treatment with reagents, solubilization, or enrichment of certain components. In a preferred embodiment, the sample is a biological sample. [000193] The term biological sample includes, but is not limited to, biological tissues and / or fluids from an individual, obtained by any method known to a person skilled in the field for that purpose. Examples of such samples include, but are not limited to, blood samples and other liquid samples of biological origin, solid tissue samples such as biopsy samples or tissue cultures or cells derived therefrom and their progeny such as cells in cell culture, cell supernatants, cell lysates, serum, plasma, biological fluids and tissue samples. [000194] The term “detect” or “detection” refers to reporting or identifying the presence of complexes containing the antigen of interest and the modified antibody that are present in the sample, generating a signal. Petition 870250104642, dated 11 / 14 / 2025, pp. 62 / 87 59 / 69 [000195] In a first step, the second method of the invention comprises placing the sample in contact with the modified antibody of the invention, wherein the modified antibody is capable of specifically binding to the antigen of interest. The contact between the sample and the modified antibody of the invention must be made under conditions suitable for the binding of the antigen of interest to the modified antibody of the invention. [000196] Contacting the sample with the modified antibody of the invention under effective conditions and for a period sufficient to allow the formation of complexes is generally a matter of simply adding the antibody composition to the sample and incubating the mixture for a period long enough for the modified antibodies to form complexes with the antigen of interest. [000197] Under conditions suitable for complex formation” means that the conditions preferably include dilution of the modified antigens and / or antibodies with solutions such as BSA, bovine gamma globulin (BGG), or phosphate-buffered saline (PBS) / Tween. These added agents also tend to help reduce non-specific background. [000198] “Appropriate” or “suitable” conditions also mean that incubation takes place at a temperature or for a period sufficient to allow effective bonding. Incubation steps generally last 1 to 2 to 4 hours, preferably at temperatures in the order of 21°C to 37°C, or may last overnight at around 4°C. [000199] The second stage of the second method of the invention comprises determining the presence of the complexes. Petition 870250104642, dated 11 / 14 / 2025, pp. 63 / 87 60 / 69 containing the antigen of interest and modified antibodies. In general, the detection of these complexes is well known in the art and can be achieved through the application of numerous approaches. These methods are generally based on the detection of a marker or tracer, such as any of these radioactive, fluorescent, biological, and enzymatic markers. Of course, it is possible to find additional advantages through the use of a secondary ligand, such as a second antibody and / or a biotin / avidin ligand array, as known in the art. [000200] As those skilled in the art will understand, there is a wide range of conventional assays that can be used in the second method of the present invention, such as Western blot or immunoblot, ELISA (Enzyme-Linked Immunosorbent Assay), RIA (Radioimmunoassay), Competitive EIA (Competitive Enzyme Immunoassay), DAS-ELISA (Double Antibody Sandwich-ELISA), immunocytochemical and immunohistochemical techniques, flow cytometry, or multiplex detection techniques based on the use of protein microspheres, biochips, or microarrays that include the modified antibody of the invention. [000201] It will also be understood that modified antibodies that are not labeled need to be detected with an additional reagent, for example, a secondary antibody that is labeled, which will be labeled. This is specifically useful for increasing the sensitivity of the detection method, as it allows the signal to be amplified. Methods for Purifying Antigens of Interest [000202] In another aspect, the present invention relates to an in vitro method, hereinafter “the third method of Petition 870250104642, dated 11 / 14 / 2025, pp. 64 / 87 61 / 69 invention for the purification of an antigen of interest present in a sample comprising: (i) placing the sample in contact with the modified antibody of the invention, wherein the modified antibody is capable of specifically binding to the antigen of interest under conditions suitable for the binding of the antigen of interest to the modified antibody; (ii) recover the complexes containing the antigen of interest and the modified antibody. [000203] The terms “in vitro”, “sample” and “biological sample” have been defined or explained above, and these definitions are applicable to the third method of the invention. [000204] The phrase specific binding to refers to a binding reaction that determines the presence of a target antigen in the presence of a heterogeneous population of proteins and other biological components. Thus, under designated assay conditions, the modified antibodies preferentially bind to a specific antigen and do not bind in significant amounts to other components present in the sample. [000205] In a first step, the third method of the invention comprises placing the sample in contact with the modified antibody of the invention, wherein the modified antibody is capable of specifically binding to the antigen of interest. The contact between the sample and the modified antibody of the invention must be made under conditions suitable for the binding of the antigen of interest to the modified antibody of the invention. [000206] Contact of the sample with the modified antibody of the invention under effective conditions and, for a Petition 870250104642, dated 11 / 14 / 2025, pp. 65 / 87 62 / 69 sufficient time to allow the formation of complexes is generally a matter of simply adding the antibody composition to the sample and incubating the mixture for a long enough period for the modified antibodies to form complexes with the antigen of interest. [000207] Under conditions suitable for complex formation” means that the conditions preferably include dilution of the modified antigens and / or antibodies with solutions such as BSA, bovine gamma globulin (BGG), or phosphate-buffered saline (PBS) / Tween. These added agents also tend to help reduce non-specific background. [000208] “Appropriate” or “suitable” conditions also mean that incubation takes place at a temperature or for a period sufficient to allow effective bonding. Incubation steps generally last 1 to 2 to 4 hours, preferably at temperatures in the order of 21°C to 37°C, or may last overnight at around 4°C. [000209] The second step of the third method of the invention comprises the recovery of complexes containing the antigen of interest and the modified antibody. Techniques and conditions for recovering these complexes are widely known in the art, and any of them can be employed in the context of the present invention. Some examples of suitable techniques for recovering these complexes are affinity chromatography techniques, ligand assays, or lectin binding assays. EXAMPLES [000210] The following examples illustrate the invention and should not be considered as limiting its scope. Petition 870250104642, dated 11 / 14 / 2025, pp. 66 / 87 63 / 69 Example 1. Design, production and HTS comparison of different antibody fragments in microalgae [000211] The heavy chain (VH and CH1 regions) and light chain (VL and CL regions) of the referenced antibody fragments (AFs) were cloned into the co-expression vector (as in the vector described in Patent Document WO2019215303A1). The heavy chain (HC) and light chain (LC) sequences were adapted to Chlamydomonas nuclear codon light and heavy chains fused with glycomodule (GM) motifs of different sizes and in different positions and tested (Figure 11). Different GMs were considered, including (SP)io (SEQ ID NO: 6), (SP)20 (SEQ ID NO: 7), GP1 (SEQ ID NO: 2), PHC21A (SEQ ID NO: 4) and LCL (SEQ ID NO: 1). The secretion signal sequences were cloned 5' from the AF sequences so that the AFs are directed to the periplasmic space or secreted into culture media and therefore easily recovered with culture media. The signal sequences included were the metalloprotease gametolysin secretion signal (SEQ ID NO: 12) or the carbonic anhydrase 1 secretion sequence (SEQ ID NO: 10). The enterokinase cleavage sequence (SEQ ID NO: 9) was added to some of the expression cassettes. [000212] Co-expression vectors (such as the vector described in Patent document WO2019215303A1) carrying DNA sequences for the expression of novel AFs (as shown in Figure 11) plus an additional hygromycin or zeocin resistance cassette were transformed into Chlamydomonas reinhardtii by electroporation or glass bead transformation. After selection of transformants by growth on TAP plates containing zeocin, the microalgae Petition 870250104642, dated 11 / 14 / 2025, pp. 67 / 87 64 / 69 transgenic microalgae expressing polynucleotides encoding heavy chain (VH and CH1 regions) and light chain (VL and CL regions) fused to GM motifs and directed to the periplasmic medium or secreted were cultured in 96-well plates. Transgenic microalgae expressing the fully assembled antibody fragment are selected by a screening method which can be dot blot, ELISA or western blot. The algae-independent transformant is cultured in flasks under mixotrophic or heterotrophic conditions. [000213] In this example, expression strain screening was performed by direct ELISA from culture media (Figure 1). The screening results show how the use of GM fused to any of the antibody fragment chains results in increased yield of functional AF. Example 2. Production of fully assembled anti-VEGF (ranibizumab) with and without GM. [000214] The anti-VEGF (ranibizumab) was cloned without GM fusion (SEQ ID NO: 13 and SEQ ID NO: 14), fused with (SP)20 at the C-terminus of the heavy and light chains (SEQ ID NO: 15 and SEQ ID NO: 16), or fused with (SP)io at the N-terminus of the heavy and light chains (SEQ ID NO: 17 and SEQ ID NO: 18). Detection markers such as the OLLAS marker (SEQ ID NO: 8) and the enterokinase cleavage sequence (SEQ ID NO: 9) were included in some of the cassettes. Vectors containing DNA cassettes for the expression of these AFs, plus an additional cassette for the expression of hygromycin or zeocin resistance, were transformed into Chlamydomonas reinhardtii by electroporation or glass bead transformation. After selecting transformants by growing them on TAP plates containing zeocin, the transgenic microalgae Petition 870250104642, dated 11 / 14 / 2025, pp. 68 / 87 65 / 69 expressing polynucleotides encoding heavy chain (VH and CH1 regions) and light chain (VL and CL regions) fused to GM motifs and directed to the periplasmic or secreted medium were cultured in 96-well plates. Transgenic microalgae expressing the fully assembled antibody fragment were selected by non-reducing immunoblot of harvested culture media. Figure 2 shows the comparison of the expression of different cassettes (ranibizumab fused to GM at different positions) by non-reducing immunoblot. As can be seen in Figure 2, without GM fusion there is no detectable fully assembled Fab. Furthermore, GM fusion results in a higher proportion of Fab than free chain and a higher yield of assembled Fab. [000215] The novel GM-fused ranibizumab is designated GB-AF-010 (SEQ NO ID: 15 and SEQ NO ID: 16). As of this document, GB-AF-010 was obtained from culture media of a transgenic microalga expressing polynucleotides encoding heavy chain (VH and CH1 regions) and light chain (VL and CL regions) fused to GM motifs and directed to the periplasmic space or secreted into the media. The activity of GB-AF-010 (unpurified, in culture medium) was compared to commercially available ranibizumab (purified) by direct ELISA (Figure 3). The results show that GBAF-010, without any purification step, tested directly in culture medium, has the same affinity for VEGF as commercially available purified ranibizumab. Example 3. Production of fully assembled anti-TNFa (certolizumab) with and without GM. [000216] The heavy chain (VH and CH1 regions) and the light chain (VL and CL regions) of certolizumab were cloned Petition 870250104642, dated 11 / 14 / 2025, p. 69 / 87 66 / 69 in a co-expression vector (like the vector described in Patent Document WO2019215303A1) fused to the GM at different positions: (SP)10-certolizumab consists of (SP) at the N-terminus of certolizumab, in both the heavy and light chains (SEQ ID NO: 19 and SEQ ID NO: 20), certolizumab-(SP)10 consists of (SP)io at the C-terminus of certolizumab, in both the heavy and light chains (SEQ ID NO: 21 and SEQ ID NO: 22), certolizumab-HC-(SP)1o consists of (SP)io at the C-terminus of the certolizumab heavy chain (SEQ ID NO: 21), certolizumab has no fusion with the GM (SEQ ID NO: 23 and SEQ ID NO: 24). [000217] The heavy chain (HC) and light chain (LC) sequences were codon-matched. After affinity screening by ELISA, as in Example 1 - Figure 2, several positive clones were selected to analyze the expression of fully assembled FA. Immunoblotting under non-reducing conditions confirmed the increased expression of Fab in GM-containing constructs (Figure 5). Small amounts of GM-free FA were not sufficient to detect Fab by immunoblotting directly from the culture medium. [000218] The novel GM-fused certolizumab (SEQ ID NO: 21 and SEQ ID NO: 22) is hereby referred to as GB-AF-011. GB-AF-011 was obtained from culture media of a transgenic microalga expressing polynucleotides encoding heavy chain (VH and CH1 regions) and light chain (VL and CL regions) fused to GM motifs and directed to the periplasmic space or secreted into the medium. The activity of GB-AF-011 (unpurified) was compared by direct ELISA with purified certolizumab from a commercially available source (Figure 5). Petition 870250104642, dated 11 / 14 / 2025, pp. 70 / 87 67 / 69 [000219] The results show that GB-AF-011, without any purification step but tested directly in culture media, maintains affinity for TNFα as purified certolizumab. [000220] In addition, the specificity of GB-AF-011 was tested by direct ELISA (Figure 6). The results show that GB-AF-011 retains specificity against human TNFα and does not recognize murine TNF, being comparable to unmodified certolizumab (Figure 6). [000221] The efficacy of GB-AF-011 in neutralizing TNFα was evaluated by competitive ELISA, testing the ability of various anti-TNF agents to inhibit the binding of labeled TNFα to its receptor (using etanercept). Surprisingly, GB-AF-011 was significantly (>10X) more effective in inhibiting the binding of TNFα to its receptor than commercially available purified certolizumab (Figure 7). Example 4. Increased stability of GB-AF-011 compared to certolizumab. [000222] GB-AF-011 was obtained from culture media of a transgenic microalga expressing polynucleotides encoding heavy chain (VH and CH1 regions) and light chain (VL and CL regions) fused to GM motifs and directed to the periplasmic medium or secreted. GB-AF011 was subjected to different temperatures and monitored over time, and its stability was compared with commercially available purified certolizumab. The results were analyzed by direct ELISA and immunoblot under non-reducing and reducing conditions (Figure 8). After >72 h at room temperature or 37°C, certolizumab-GM was more Petition 870250104642, dated 11 / 14 / 2025, pp. 71 / 87 68 / 69 more stable than purified certolizumab. Furthermore, certolizumab exhibited bands of larger molecular size than the corresponding Fab, which are associated with aggregation patterns not observed in GB-AF-011. Example 5. Stability of certolizumab-GM in relation to colonic protease [000223] GB-AF-011 was obtained from culture media of a transgenic microalga expressing polynucleotides encoding heavy chain (VH and CH1 regions) and light chain (VL and CL regions) fused to GM motifs and directed to the periplasmic space or secreted into the media. GB-AF-011 and commercially available purified anti-TNFα agents (certolizumab, infliximab, and etanercept) were incubated under colonic conditions (1 / 5 dilution in colonic contents, 37°C) and monitored over time. The stability of the anti-TNF agents against colonic proteases was compared by immunoblot under reducing conditions. The results show that GB-AF-011 is significantly more resistant to intestinal proteases than current therapeutically relevant antibodies. Example 6. Method for producing GB-AF-011 by fermentation. [000224] Algae expressing fully assembled Fab (GB-AF-011) were cultivated in a bioreactor under heterotrophic conditions until high cell density was reached. A 1 L bioreactor (PSI Photobioreactor FMT150) was used for the cultivation of C. reinhardtii capable of operating under fed-batch conditions. The bioreactor was filled with 0.9 L of a modified TAP medium. The bioreactor, all connected tubes, filters, glass flasks and media Petition 870250104642, dated 11 / 14 / 2025, pp. 72 / 87 Samples of 69 / 69 were subsequently autoclaved at 121°C for 20 minutes before use. A concentrated feed mimicking the basal medium was prepared. The feed was sterilized by filtration with a 0.22 mm vacuum filter and stored at room temperature. Before each batch-fed bioreactor culture, 200 mL of feed was transferred to a 250 mL Erlenmeyer flask connected to the bioreactor. The unit was used to maintain the culture temperature (21-25°C), pH (7.30), agitation, and airflow rate (0.6 L / min) throughout the process. Antifoaming agent was added as needed. [000225] To prepare the Chlamydomonas strain inoculum, a shaker flask containing 80 mL of TAP medium was inoculated with the desired strain and cultured to the stationary phase in an orbital shaker at 150 rpm in mixotrophy for 3 days. Then, 80 mL of inoculum was sterilely added to the bioreactor pre-filled with 0.9 L of modified TAP medium. OD at 750 nm was measured to monitor culture growth and estimate cell density. Because Fab is secreted directly into the control culture medium to be used with or without prior purification, the culture medium was separated from the cells and frozen at each culture time point for later analysis of Fab production. The fed-batch culture was cultured for 8 days without illumination. [000226] Figure 10 shows the growth profiles of Chlamydomonas reinhardtii strains cultivated in a 1 L bioreactor. GB-AF-011 production analysis was performed by non-reducing immunoblot (Figure 10). Petition 870250104642, dated 11 / 14 / 2025, pp. 73 / 87

Claims

1 / 12 CLAIMS 1. Modified antibody comprising a first antibody chain consisting of a VH region and a CH1 region and a second antibody chain comprising a VL region and a CL region, characterized in that at least one of the antibody chains is fused to at least one glycomodule (GM) motif.

2. Fusion protein according to claim 1, characterized in that: (i) the modified antibody comprises a glycomodular motif and is located at the C-terminal position of the first antibody chain; (ii) the modified antibody comprises a glycomodular motif and is located at the N-terminal position of the first antibody chain; (iii) the modified antibody comprises a glycomodular motif and is located at the C-terminal position of the second antibody chain; or (iv) the modified antibody comprises a glycomodular motif and is located at the N-terminal position of the second antibody chain.

3. Fusion protein according to claim 2, characterized in that the modified antibody comprises glycomodule motifs in the first antibody chain and in the second antibody chain.

4. Fusion protein according to claim 3, characterized in that: (i) the glycomodule motifs are at the C-terminal position of the first antibody chain and at the C-terminal position of the second antibody chain; or Petition 870250104639, dated 11 / 14 / 2025, page 5 / 34 2 / 12 (ii) the glycomodule motifs are at the N-terminal position of the first antibody chain and at the N-terminal position of the second antibody chain.

5. Modified antibody according to any one of claims 1 to 4, characterized in that the glycomodule motif comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and (SP)n, specifically (SP)10 (SEQ ID NO: 6) or (SP)20 (SEQ ID NO: 7).

6. Modified antibody according to claim 5, characterized in that the glycomodule motif comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 2 or a functionally equivalent variant thereof, or is a nucleotide sequence encoding (SP)10 or (SP)20.

7. Modified antibody according to any one of claims 1 to 6, characterized in that the glycomodule motif is connected to the first antibody chain by a linkage sequence.

8. Modified antibody according to any one of claims 1 to 6, characterized in that the glycomodule motif is connected to the second antibody chain by a linkage sequence.

9. Modified antibody according to any one of claims 1 to 8, characterized in that the CL region is C-terminal relative to the VL region.

10. Modified antibody according to any one of claims 1 to 9, characterized in that the CH1 region is C-terminal relative to the VH region. Petition 870250104639, dated 11 / 14 / 2025, p. 6 / 34 3 / 12 11. Modified antibody according to any one of claims 1 to 10, characterized in that the modified antibody further comprises a detection marker.

12. Modified antibody according to claim 11, characterized in that the detection marker is the OLLAS marker (SEQ ID NO: 8).

13. Modified antibody according to any one of claims 11 or 12, characterized in that the modified antibody comprises a processing site between the detection marker and the remainder of the chain, and wherein the processing site is preferably an enterokinase cleavage sequence (SEQ ID NO: 9).

14. Modified antibody according to any one of claims 1 to 13, characterized in that the modified antibody is derived from a neutralizing antibody against tumor necrosis factor α (TNFα), preferably certolizumab.

15. Modified antibody according to claim 14, characterized in that the modified antibody has a heavy chain as defined in SEQ ID NO: 19 or SEQ ID NO: 21 and / or a light chain as defined in SEQ ID NO: 20 or SEQ ID NO:

22.

16. Modified antibody according to any one of claims 1 to 13, characterized in that the modified antibody is derived from a neutralizing antivascular endothelial growth factor (VEGF), preferably ranibizumab.

17. Modified antibody according to claim 16, characterized in that the modified antibody Petition 870250104639, dated 11 / 14 / 2025, page 7 / 34 4 / 12 has a heavy chain as defined in SEQ ID NO: 15 or SEQ ID NO: 17 and / or a light chain as defined in SEQ ID NO: 16 or SEQ ID NO:

18.

18. A polynucleotide encoding the antibody chains of the modified antibody according to any one of claims 1 to 17, or a polynucleotide composition, characterized in that it comprises a first polynucleotide encoding the first antibody chain of the modified antibody according to any one of claims 1 to 17 and a second polynucleotide encoding the second antibody chain of the modified antibody according to any one of claims 1 to 17.

19. A polynucleotide or polynucleotide composition according to claim 18, characterized in that the polynucleotide or each of the polynucleotides of the polynucleotide composition further comprises a nucleotide sequence encoding a secretory signal peptide, wherein the secretory signal peptide is fused into the structure to the N-terminus of the first and second antibody chains.

20. Polynucleotide or polynucleotide composition according to claim 19, characterized in that the signal peptide is selected from the group consisting of carbonic anhydrase 1 (CAH) signal peptide (SEQ ID NO: 10), arylsulfatase 1 signal peptide (SEQ ID NO: 11) or gametolysin signal peptide (SEQ ID NO: 12).

21. Vector comprising the polynucleotide according to any one of claims 18 to 20 or a vector composition, characterized in that each vector comprises one of the polynucleotides of the polynucleotide composition according to any one of claims 18 to 20.

22. Host cell, characterized in that it comprises the vector or vector composition according to claim 21.

23. Host cell according to claim 22, characterized in that the cell is a plant cell or a microalgal cell, preferably a microalgal cell of the species Chlamydomonas reinhardtii.

24. Pharmaceutical composition, characterized in that it comprises the modified antibody according to any one of claims 1 to 17, the polynucleotide or polynucleotide composition according to any one of claims 18 to 20, the vector or vector composition according to claim 21 or the host cell according to claims 22 or 23, and at least one pharmaceutically acceptable excipient.

25. Modified antibody according to any one of claims 1 to 17, polynucleotide or polynucleotide composition according to any one of claims 18 to 20, vector or vector composition according to claim 21, host cell according to any one of claims 22 or 23 or pharmaceutical composition according to claim 24, characterized in that it is intended for use in medicine.

26. Modified antibody according to any one of claims 1 to 17, the polynucleotide or polynucleotide composition according to any one of claims 18 to 20, the vector or vector composition according to claim 21, the host cell according to any one of claims 22 or 23 or the pharmaceutical composition according to claim 24, for use in medicine, characterized in that the antibody is administered topically.

27. Modified antibody according to any one of claims 1 to 17, the polynucleotide or polynucleotide composition according to any one of claims 18 to 20, the vector or vector composition according to claim 21, the host cell according to any one of claims 22 or 23, or the pharmaceutical composition according to claim 24, characterized in that the modified antibody is against TNFα for use in the treatment of inflammatory diseases.

28. Modified antibody according to any one of claims 1 to 17, the polynucleotide or polynucleotide composition according to any one of claims 18 to 20, the vector or vector composition according to claim 21, the host cell according to any one of claims 22 or 23, or the pharmaceutical composition according to claim 24, characterized in that the modified antibody is against a pathogen for use in the treatment of an infectious disease caused by said pathogen.

29. Modified antibody according to any one of claims 1 to 17, the polynucleotide or polynucleotide composition according to any one of claims 18 to 20, the vector or vector composition according to claim 21, the host cell according to any one of claims 22 or 23, or the pharmaceutical composition according to claim 24, characterized in that it is intended for use in the treatment of gastrointestinal diseases.

30. Modified antibody according to any one of claims 1 to 17, the polynucleotide or polynucleotide composition according to any one of claims 18 to 20, the vector or vector composition according to claim 21, the host cell according to any one of claims 22 or 23, or the pharmaceutical composition according to claim 24, characterized in that the modified antibody is against VEGF for use in the treatment of diseases associated with unwanted vascularization.

31. Modified antibody according to any one of claims 1 to 17, the polynucleotide or polynucleotide composition according to any one of claims 18 to 20, the vector or vector composition according to claim 21, the host cell according to any one of claims 22 or 23, or the pharmaceutical composition according to claim 24, characterized in that the modified antibody is against VEGF for use in the treatment of endovascular age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema, diabetic retinopathy, or myopic choroidal neovascularization.

32. Modified antibody for use according to any of claims 25 to 31, characterized by Petition 870250104639, dated 11 / 14 / 2025, page 11 / 34 8 / 12, in that the modified antibody must be administered orally or by topical application.

33. Method for producing the modified antibody according to any one of claims 1 to 12, characterized in that the method comprises: (i) culturing a cell comprising a polynucleotide or a polynucleotide composition according to any one of claims 18 to 20 under suitable conditions to permit expression of the modified antibody from the polynucleotide or polynucleotides of the polynucleotide composition; and (ii) recovering the modified antibody from the culture.

34. Method according to claim 33, characterized in that if the polynucleotide or polynucleotide composition comprises a nucleotide sequence encoding secretory signal peptides, then the modified antibody is recovered from the culture supernatant.

35. Method according to any one of claims 33 or 34, characterized in that the cell is a plant cell or a microalgae cell, preferably a transgenic microalga of the species Chlamydomonas reinhardtii.

36. Antibody chain, characterized in that it comprises: (i) a VH region and a CH1 region; or (ii) a VL region and a CL region; wherein the antibody chain is fused to a glycomodule (GM) motif. Petition 870250104639, dated 11 / 14 / 2025, page 12 / 34 9 / 12 37. Antibody chain according to claim 36, characterized in that: (i) the glycomodule motif is in the C-terminal position of the antibody chain; or (ii) the glycomodule motif is in the N-terminal position of the antibody chain.

38. Antibody chain according to any one of claims 36 or 37 characterized in that the glycomodule motif comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 or a functionally equivalent variant thereof, or is a nucleotide sequence encoding (SP)n, specifically (SP)io (SEQ ID NO: 6) or (SP)2o (SEQ ID NO: 7).

39. Antibody chain according to claim 38, characterized in that the glycomodule motif comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 2 or a functionally equivalent variant thereof, or is a nucleotide sequence encoding (SP)io (SP)2o.

40. Antibody chain according to any one of claims 36 to 39, characterized in that the glycomodule motif is connected to the antibody chain by a linker.

41. Antibody chain according to any one of claims 36 to 40, characterized in that: Petition 870250104639, 11 / 14 / 2025, page 13 / 34 10 / 12 (i) if the antibody comprises a VH region and a CH1 region, then the CH1 region will be C-terminal to the VH region; or (ii) if the antibody chain comprises a VL region and a CL region, then the CL region will be C-terminal to the VL region.

42. Antibody chain according to any one of claims 36 to 41, characterized in that the antibody chain further comprises a detection marker.

43. Antibody chain according to claim 42, characterized in that the detection marker is the OLLAS marker (SEQ ID NO: 8).

44. Antibody chain according to any one of claims 42 or 43, characterized in that the antibody chain comprises a processing site between the detection marker and the remainder of the chain, and wherein the processing site is preferably an enterokinase cleavage sequence (SEQ ID NO: 9).

45. Polynucleotide, characterized in that it encodes an antibody chain fused to a glycomodule motif, according to any one of claims 36 to 44.

46. ​​Polynucleotide according to claim 45, characterized in that the polynucleotide further comprises a nucleotide sequence encoding a secretory signal peptide, wherein the secretory signal peptide is fused into the structure to the N-terminus of the antibody chain. Petition 870250104639, dated 11 / 14 / 2025, page 14 / 34 11 / 12 47. Polynucleotide according to claim 46, characterized in that the signal peptide is selected from the group consisting of the carbonic anhydrase 1 (CAH) signal peptide (SEQ ID NO: 10), the ARS signal peptide (SEQ ID NO: 11) or the gametolysin signal peptide (SEQ ID NO: 12).

48. Vector, characterized in that it comprises the polynucleotide according to any one of claims 45 to 47.

49. Host cell, characterized in that it comprises a vector according to claim 48.

50. Host cell according to claim 49, characterized in that the cell is a plant cell or a microalgal cell, preferably a microalgal cell of the species Chlamydomonas reinhardtii.

51. In vitro method for detecting an antigen of interest present in a sample, characterized in that it comprises: (i) bringing the sample into contact with the modified antibody according to any one of claims 1 to 17, wherein the modified antibody is capable of specifically binding to the antigen of interest under suitable conditions, for the binding of the antigen of interest to the modified antibody; and (ii) determining the presence of complexes containing the antigen of interest and the modified antibody.

52. In vitro method for the purification of an antigen of interest present in a sample, characterized in that it comprises: Petition 870250104639, dated 11 / 14 / 2025, page 15 / 34 12 / 12 (i) bringing the sample into contact with the modified antibody according to any one of claims 1 to 17, wherein the modified antibody is capable of specifically binding to the antigen of interest under suitable conditions, for the binding of the antigen of interest to the modified antibody; and (ii) recovering the complexes containing the antigen of interest and the modified antibody. Petition 870250104639, dated 11 / 14 / 2025, page 16 / 34

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