TN3-derived scaffolds specific to CD40L for the treatment and prevention of Sjögren's syndrome.

Description

TN3-derived scaffolds specific to CD40L for the treatment and prevention of Sjögren's syndrome. Cross-reference to related applications.

[0001] This application claims priority of US Applications Nos. 63 / 492,715, filed March 28, 2023; 63 / 504,003, filed May 24, 2023; 63 / 584,134, filed September 20, 2023; and 63 / 624,959, filed January 25, 2024, each of which is incorporated herein by reference in its entirety for all purposes. REFERENCE TO A LISTING OF ELECTRONIC SEQUENCES

[0002] The contents of the electronic sequence listing (HOPA_067_04WO_SeqList_ST26.xml; Size: 23,046 bytes; and Creation Date: February 16, 2024) are incorporated in their entirety by reference in this document. FIELD OF TECHNIQUE

[0003] The present disclosure relates to compositions comprising a Tn3 framework and methods using the same in the treatment and prevention of Sjogren's syndrome. BACKGROUND

[0004] Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by chronic lymphocytic inflammation of the exocrine glands, primarily the salivary and lacrimal glands, leading to loss of function manifesting as excessive dryness. The subjective aspects of SS, which include the patient's perception of dryness, musculoskeletal pain, and fatigue, can be debilitating and have been shown to have a substantial negative impact on quality of life. Petition 870250087411, dated 09 / 26 / 2025, page 47 / 404 2 / 327 of life expectancy (QoL). The main contributors to decreased QoL are dryness and fatigue. QoL is also affected by psychological and emotional challenges and impaired social life with dependence on family members in daily life and difficulties at work, as well as with other tasks.

[0005] Currently, there are no approved immunomodulatory agents or evidence-based therapeutic guidelines available for the treatment of extra-glandular manifestations of SS. There is, therefore, a need for new treatments for Sjögren's syndrome. BRIEF DESCRIPTION OF THE DRAWINGS

[0006] Figure 1 shows an illustrative study flow diagram. Δ = delta; D = day(s); Dazo = dazodalibep; EoS = end of study; EP = outcome; DASPRI = Diary for Analysis of Patient-Reported Symptom Index with Sjögren's Syndrome; ESSDAI = EULAR Disease Activity Index in Sjögren's Syndrome; EULAR = European Alliance of Associations for Rheumatology; n = number of subjects in the treatment group; PBO = placebo; q4wk = once every 4 weeks; q12wk = once every 12 weeks; wk = week. Note: Randomization on Day 1 is stratified based on geographic location (North America and Europe versus Japan versus Rest of the World), the concomitant presence of rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) (yes versus no), and the ESSDAI score obtained at screening (< 10 versus h ≥ 10).

[0007] Figure 2 shows an illustrative study flow diagram. D = day(s); Dazo = dazodalibep; EP = outcome; ESSPRI = EULAR Sjögren's Syndrome Patient-Reported Symptom Index; EULAR = European Alliance of Petition 870250087411, dated 09 / 26 / 2025, page 48 / 404 3 / 327 Associations for Rheumatology; n = number of subjects in the treatment group; PBO = placebo; q4wk = once every 4 weeks; q12wk = once every 12 weeks; wk = week. Randomization on Day 1 is stratified based on geographic location (North America and Europe versus Japan versus Rest of the World) and ESSPRI score obtained at screening (< 7.5 versus ≥ 7.5).

[0008] Figure 3 shows an illustrative study flowchart. DAZ = dazodalibep; ESSDAI = EULAR Sjögren's Syndrome Disease Activity Index (EULAR); EULAR = European League Against Rheumatism. Arrows indicate dosing day for dazodalibep or placebo.

[0009] Figure 4 shows an illustrative change from baseline in the ESSDAI Total Score. Changes from baseline in the ESSDAI total score were plotted as a function of time (days). The dazodalibep and placebo administration schedule is described in Figure 3. Analyzed using a mixed repeated measures model (MMRM); *p<0.1; DAZ = dazodalibep; ESSDAI = EULAR Sjögren's Syndrome Disease Activity Index; LS = least squares; MCID = least clinically important difference; SE = standard error.

[0010] Figure 5 shows an illustrative change from baseline in the ESSPRI Total Score. Changes from baseline in the ESSPRI total score were plotted as a function of time (days). The dazodalibep and placebo administration schedule is described in Figure 3. Analyzed using a repeated measures mixed model (MMRM); DAZ = dazodalibep; ESSDAI = EULAR Sjögren's Syndrome Disease Activity Index; LS Petition 870250087411, dated 09 / 26 / 2025, pp. 49 / 404 4 / 327 = least squares; MCID = least clinically important difference; SE = standard error.

[0011] Figures 6A–6C show exemplary changes from baseline in FACITFatgue score (Figure 6A), OSDI (Figure 6B), and PGIS (Figure 6C). Changes from baseline were plotted as a function of time (days). The dazodalibep and placebo administration schedule is described in Figure 3.

[0012] Figures 7A–7G show exemplary baseline changes for blood biomarkers of B and T cell co-stimulation as a function of dazodalibep or placebo administration over time (baseline to Day 365): CXCL13 (Figure 7A); Rheumatoid Factor (RF; Figure 7B); Ki67+ post-switching memory B cells (Figure 7C); Plasblasts (Figure 7D); CD11cbr+ plus B cells (Figure 7E); Ki67+ T cells (Figure 7F); TfH cells (Figure 7G). The dazodalibep and placebo administration schedule is described in Figure 3. Data presented as mean change (MC) from baseline ± IQR. Black symbols represent the placebo group (subjects receiving placebo at Stage I and dazodalibep at Stage II). The pink symbols represent the dazodalibep group (subjects receiving dazodalibep in Stage I and placebo in Stage II).The statistical significance of differences in heart rate (HR) from baseline values ​​between treatment groups was assessed using a Mann-Whitney U test. Subjects were included in the risk factor (RF) analysis only if they were positive at baseline. *p<0.05; **p<0.01; ***p<0.001; DAZ. Petition 870250087411, dated 09 / 26 / 2025, page 50 / 404 5 / 327 = dazodalibep; FC = fold-change; IQR = interquartile range; PBO = placebo; FR = rheumatoid factor.

[0013] Figure 8 shows an illustrative heat map of biomarkers, displaying the median change (FC) from baseline to Day 365, using biomarkers from Figures 7A–7G and the total ESSDAI score. DAZ = dazodalibep; ESSDAI = EULAR Sjögren's Syndrome Disease Activity Index; PBO = placebo.

[0014] Figure 9 shows an illustrative study flow diagram. DAZ = dazodalibep; ESSPRI = EULAR Sjögren's Syndrome Patient-Reported Symptom Index; EULAR = European League Against Rheumatism. Arrows indicate dosing day for dazodalibep or placebo.

[0015] Figure 10 shows an illustrative change from baseline in the ESSPRI Total Score. Changes from baseline in the ESSPRI total score were plotted as a function of time (days). The dazodalibep and placebo administration schedule is described in Figure 9. Analyzed using a mixed repeated measures model (MMRM); DAZ = dazodalibep; ESSDAI = EULAR Sjögren's Syndrome Disease Activity Index; LS = least squares; MCID = least clinically important difference; SE = standard error.

[0016] Figures 11A–11C show exemplary changes in dryness (Figure 11A), fatigue (Figure 11B), and pain (Figure 11C) from baseline. Changes from baseline were plotted as a function of time (days). The administration schedule for dazodalibep and placebo is described in Figure 9. Plotted data Petition 870250087411, dated 09 / 26 / 2025, page 51 / 404 6 / 327 per study visit; analyzed using MMRM. **p<0.01; BSL = baseline; DAZ = dazodalibep; LS = least squares; PBO = placebo; SE = standard error.

[0017] Figure 12 shows the exemplary proportion of subjects achieving ESSPRI response for subjects treated with dazodalibep versus placebo up to Day 169. The ESSPRI response rate is plotted as a function of day. ESSPRI response is defined as a 1-point or 15% reduction from baseline in the ESSPRI score, with no early discontinuation of the study and no receipt of rescue therapy. Data were analyzed using a logistic regression model. ***p<0.001. CI = Confidence interval. DAZ = dazodalibep. ESSPRI = EULAR Sjögren's Syndrome Patient-Reported Symptom Index. EULAR = European Alliance of Associations for Rheumatology.

[0018] Figures 13A–13C show exemplary changes from baseline in FACITFatgue (Figure 13A), OSDI (Figure 13B), and PGIS (Figure 13C) scores. Changes from baseline were plotted as a function of time (days). The dazodalibep and placebo administration schedule is described in Figure 9. BRIEF SUMMARY

[0019] Methods for treating Sjögren's syndrome (SS) in a subject in need thereof are provided in this document, comprising: administering a Tn3 scaffold, wherein the Tn3 scaffold comprises a specific CD40L monomeric subunit, wherein the specific CD40L monomeric subunit comprises seven beta strands designated A, B, C, D, E, F, and G, and six regions Petition 870250087411, dated 09 / 26 / 2025, p. 52 / 404 7 / 327 of designated loops AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the Tn3 framework is administered at a dose of approximately 1500 mg once every 4 weeks, wherein the subject has moderate to severe symptom status defined by an ESSPRI score of ≥ 5, with low systemic disease activity defined by an ESSDAI score of < 5, and wherein a Diary for Analysis of Sjögren's Patient-Reported Index (DASPRI) score is reduced in the subject after administration. In aspects, prior to dosing every 4 weeks, the subject was administered at least 3 loading doses of 1500 mg each. In aspects, the at least 3 loading doses are administered in weeks 0, 2, and 4.

[0020] Methods for treating Sjögren's syndrome (SS) in a subject in need thereof are provided in this document, comprising: administering a Tn3 scaffold, wherein the Tn3 scaffold comprises a specific CD40L monomeric subunit, wherein the specific CD40L monomeric subunit comprises seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the Tn3 scaffold is administered at a dose of approximately 3,000 mg once every 12 weeks, wherein the subject has state of Petition 870250087411, dated 09 / 26 / 2025, p. 53 / 404 8 / 327 moderate to severe symptom defined by ESSPRI score ^ 5, with low systemic disease activity defined by ESSDAI score < 5, and in which a Diary for Analysis of the Sjögren's Patient-Reported Index (DASPRI) score is reduced in the subject after administration. In aspects, prior to dosing every 12 weeks, the subject was given at least 3 loading doses of 3000 mg each. In aspects, the at least 3 loading doses are administered at weeks 0, 4, and 12.

[0021] In some aspects, salivary gland function in the subject is improved after administration of the Tn3 scaffold by approximately 3 weeks, 1 month, 2 months, or 4 months after administration. In some aspects, salivary gland function is determined by total stimulated salivary flow. In some aspects, the ESSPRI score is reduced after administration. In some aspects, the ESSPRI score is reduced by at least approximately 1.5, 2, 3, 4, or 5 points. In some aspects, the DASPRI score is reduced by 2 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, or 6 months after administration. In some aspects, the DASPRI score is reduced by at least approximately 5, 10, 15, or 20 points. In some aspects, administration of the Tn3 scaffold is effective in reducing a baseline score of the subject's tender and swollen joint counts after administration.

[0022] In some respects, administration of the Tn3 framework is effective in reducing a subject's baseline score on the Short Form Health Survey 36 (SF-36) after administration. In some respects, administration of the Tn3 framework is effective in improving a subject's baseline score, wherein baseline scores are Petition 870250087411, dated 09 / 26 / 2025, page 54 / 404 9 / 327 selected from the group consisting of: Functional Fatigue Analysis in Chronic Disease Therapy (FACITFatgue), PROMIS Fatigue Short Form 10a, Ocular Surface Disease Index (OSDI), EQ-5D-5L, and Patient Global Impression of Severity (PGIS). In aspects, administration of the Tn3 framework is effective in reducing a baseline level of inflammatory markers after administration, and in which the markers are selected from the group consisting of: immunoglobulin, β2-microglobulin, C-reactive protein, and combinations thereof.In some aspects, administration of the Tn3 scaffold is effective in reducing a baseline level of a biomarker, wherein the biomarker is selected from the group consisting of: plasma soluble CD40L, Ki67+CD27+ memory B cell, CD19, CD20, CD27, CD38, CD138, bright / elevated CD11c B cell, CD3, CD4, CD8, follicular helper T cell (Tfh), serum CXCL13, rheumatoid factor, anti-SSA autoantibodies, anti-Ro autoantibodies, anti-SSB autoantibodies, anti-La autoantibodies, and combinations thereof. In others, administration of the Tn3 scaffold is effective in reducing a baseline level of a disease symptom, wherein the disease symptom is selected from the group consisting of: fatigue, dry mouth, dry eyes, vaginal dryness, pain, and combinations thereof. In some respects, gene expression levels, or levels of proteins encoded by genes, associated with SS are reduced in a blood sample from the subject at week 48 after administration.In some aspects, the levels of selected B cells from the group consisting of: CD27+ memory B cells, marginal zone B cells, plasmablasts,. Petition 870250087411, dated 09 / 26 / 2025, page 55 / 404 10 / 327 plasma cells and combinations thereof are reduced in a blood sample from the subject up to week 48 after administration. In aspects, the subject is positive for anti-Ro autoantibodies, rheumatoid factor (RF), or both anti-Ro and RF autoantibodies. In aspects, the Tn3 framework is administered intravenously.

[0023] In methods disclosed herein, a Tn3 framework comprises two CD40L-specific monomeric subunits connected in tandem. In aspects, the two CD40L-specific monomeric subunits each comprise SEQ ID NO: 3. In aspects, the CD40L-specific monomeric subunits are connected by a linker. In aspects, at least one CD40L-specific monomeric subunit is fused or conjugated directly to a polyethylene glycol (PEG). In aspects, at least one CD40L-specific monomeric subunit is fused or conjugated, via a linker, to a polyethylene glycol (PEG). In aspects, the linker comprises a peptide linker. In aspects, the ligand comprises SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10. In aspects, at least one specific CD40L monomeric subunit is fused or conjugated to an albumin. In aspects, the albumin is human serum albumin (HSA).In some respects, HSA is a variant of HSA comprising SEQ ID NO: 4. In some respects, the Tn3 framework comprises SEQ ID NO: 1.

[0024] In some respects, a subject of the disclosure has a coexisting autoimmune indication. In some respects, the coexisting autoimmune indication is rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or both RA and SLE. In some respects, the coexisting autoimmune indication is arthritis. Petition 870250087411, dated 09 / 26 / 2025, page 56 / 404 11 / 327 rheumatoid. In some aspects, the coexisting autoimmune indication is systemic lupus erythematosus. BRIEF DESCRIPTION Definitions

[0025] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by a person of ordinary skill in the art to which the subject matter pertains. All publications, patent applications, patents and other references mentioned in this document are expressly incorporated in their entirety by way of reference. In case of conflict, this application, including definitions, shall prevail. Furthermore, the materials, methods and examples described in this document are illustrative only and are not intended to be limiting.

[0026] As used in the descriptive report and attached claims, the singular forms a, an and the or “a” include plural referents, unless the context clearly indicates otherwise.

[0027] The term “about” or “approximately,” when immediately preceding a numerical value, signifies a range (e.g., plus or minus 10% of that value). For example, “about 50” might mean 45 to 55, “about 25000” might mean 22500 to 27500, etc., unless the context of the disclosure indicates otherwise or is inconsistent with such an interpretation. For example, in the context of a list of numerical values ​​such as “about 49, about 50, about 55, ...,” “about 50” signifies a range extending to less than half the range(s) between the Petition 870250087411, dated 09 / 26 / 2025, p. 57 / 404 12 / 327 preceding and subsequent values, for example, more than 49.5 to less than 52.5. Furthermore, the phrases “less than about” a value or “more than about” a value should be understood considering the definition of the term “about” provided here. Similarly, the term “about” when preceding a series of numerical values ​​or a range of values ​​(for example, “about 10, 20, 30” or “about 10-30”) refers, respectively, to all the values ​​in the series, or to the outcomes of the range.

[0028] As used in this document, the term “subject” refers to any subject, for example, human or non-human mammal, for whom diagnosis, prognosis, or therapy is desired. The term “subject” may mean a human or non-human mammal affected, likely affected, or suspected of being affected by a disease. In some respects, the subject is a mammal. A mammal includes primates, such as humans, monkeys, chimpanzees, and great apes, and non-primates, such as domestic animals.

[0029] As used in this document, the term a subject in need of treatment includes subjects who could or would benefit from the methods described in this document. Subjects in need of treatment include, without limitation, those who already have the condition or disorder, those likely to have the condition or disorder, those in whom the condition or disorder is suspected, as well as those in whom the condition or disorder should be prevented, improved, or reversed.

[0030] As used in this document, “fused” refers to at least two polypeptides joined in a recombinant fashion. As used in this document, Petition 870250087411, dated 09 / 26 / 2025, page 58 / 404 13 / 327 Conjugate refers to the formation of a bond between two components through a chemical reaction. Typically, two components that are conjugated to each other are chemically connected by a covalent bond.

[0031] As used in this document, “treating” or “treating” describes the management and care of a subject for the purpose of combating a disease, condition, or disorder and includes the administration of a Tn3 framework used in the methods described in this document to alleviate the symptoms or complications of a disease, condition, or disorder, or to eliminate the disease, condition, or disorder. Thus, the term “treating” or “treating” refers to therapy where the objective is to prevent, slow down (attenuate), or improve the progression of a disease (e.g., an autoimmune disease). Beneficial or desired clinical outcomes include, but are not limited to, symptom relief, reduction in disease extent, stabilized disease status (i.e., not worsening), slowing or deceleration of disease progression, improvement or palliation of disease status, and reversal of disease (either partial or total).

[0032] As used in this document, an effective dose describes an amount of a Tn3 framework used in the methods described in this document that reduces or eliminates one or more symptoms of a disease, condition, or disorder.

[0033] With reference to a nucleic acid sequence or protein sequence, the term “identity” is used to designate similarity between two sequences. Unless otherwise indicated, identity percentages described here are determined using the BLAST algorithm. Petition 870250087411, dated 09 / 26 / 2025, p. 59 / 404 14 / 327 available at the World Wide Web address: blast.ncbi.nlm.nih.gov / Blast.cgi using predefined parameters. Tn3 Frameworks

[0034] Compositions that bind to CD40L are provided in this document. In some aspects, the compositions provided comprise CD40L antagonists. In aspects, compositions comprising a Tn3 scaffold protein comprising a CD40L-specific monomer subunit (e.g., Tn3 scaffold) are provided in this document. In aspects, compositions comprising a Tn3 scaffold comprising two CD40L-specific monomeric subunits are provided in this document. In aspects, a CD40L-specific monomeric subunit is also known as a CD40L-specific Tn3 monomer.The term Tn3 framework used in this document refers to molecules comprising at least one Fnlll framework wherein beta strand A comprises SEQ ID NO: 5, 23 or 24, beta strand B comprises SEQ ID NO: 6, beta strand C comprises SEQ ID NO: 17, beta strand D comprises SEQ ID NO: 18, beta strand E comprises SEQ ID NO: 19, beta strand F comprises SEQ ID NO: 20 and beta strand G comprises SEQ ID NO: 21.

[0035] In aspects, the compositions provided may comprise any of the Tn3 scaffolds having the amino acid sequences as described in International Applications Nos. PCT / US2012 / 059477 and PCT / US2019 / 052997, which are incorporated herein by reference in their entirety. In aspects, the compositions provided may comprise a Tn3 scaffold having the Petition 870250087411, dated 09 / 26 / 2025, p. 60 / 404 15 / 327 amino acid sequence as shown in SEQ ID NO: 1 (referred to herein as Dazodalibep). Dazodalibep may also be referred to as VIB4920, MEDI4920, or HZN-4920.

[0036] In aspects, a CD40L monomeric subunit of a Tn3 framework comprises seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG. In aspects, the Tn3 framework comprises a single CD40L-specific monomeric subunit. In aspects, the Tn3 framework comprises two CD40L-specific monomeric subunits. In aspects, the two CD40L-specific monomeric subunits are tandemly connected. In aspects, the two CD40L-specific monomeric subunits are connected by a linker. In aspects, the linker comprises a peptide linker, which may be a flexible peptide linker. In some respects, the peptide linker comprises a sequence (GmX)n where X is Serine (S), Alanine (A), Glycine (G), Leu (L), Isoleucine (I) or Valine (V); men are integer values; m is 1, 2, 3 or 4; en is 1, 2, 3, 4, 5, 6 or 7.

[0037] In aspects, the Tn3 framework comprises a ligand comprising a functional chemical moiety. In aspects, this functional chemical moiety is an immunoglobulin or a fragment thereof. In aspects, this immunoglobulin or fragment thereof comprises an Fc domain. In aspects, this Fc domain does not induce at least one FcyR-mediated effector function (e.g., Fc-deficient). In aspects, this at least one FcyR-mediated effector function is antibody-dependent cellular cytotoxicity (ADCC). Petition 870250087411, dated 09 / 26 / 2025, page 61 / 404 16 / 327

[0038] In aspects, the Tn3 framework comprises a specific CD40L monomeric subunit comprising seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein the AB loop comprises or consists of SEQ ID NO: 11, the BC loop comprises or consists of SEQ ID NO: 12, the CD loop comprises or consists of SEQ ID NO: 13, the DE loop comprises or consists of SEQ ID NO: 14, the EF loop comprises or consists of SEQ ID NO: 15, and the FG loop comprises or consists of SEQ ID NO: 16. In aspects, the Tn3 framework comprises or consists of SEQ ID NO: 1 (also known as VIB4920).In terms of aspects, beta tape A comprises or consists of SEQ ID NO: 5, beta tape B comprises or consists of SEQ ID NO: 6, beta tape C comprises or consists of SEQ ID NO: 17, beta tape D comprises or consists of SEQ ID NO: 18, beta tape E comprises or consists of SEQ ID NO: 19, beta tape F comprises or consists of SEQ ID NO: 20, and beta tape G comprises or consists of SEQ ID NO: 21.

[0039] In aspects, one or more CD40L-specific Tn3 monomers have a beta A strand comprising or consisting of IEV (SEQ ID NO: 5), RLDAPSQIEV (SEQ ID NO: 23), or SQIEV (SEQ ID NO: 24). In aspects, a Tn3 scaffold may comprise one or more CD40L-specific Tn3 monomers having the same or different beta A strand sequences. For example, a first CD40L-specific beta A monomeric Tn3 strand may comprise or consist of IEV (SEQ ID NO: 5), and a second CD40L-specific beta A monomeric Tn3 strand may comprise or consist of RLDAPSQIEV (SEQ ID NO: 23) or SQIEV (SEQ ID NO: 24). Petition 870250087411, dated 09 / 26 / 2025, page 62 / 404 17 / 327

[0040] The Tn3 scaffold may have the amino acid sequence as shown in SEQ ID NO: 1 and described above, or it may have one or more amino acid residue changes relative to the amino acid sequence as shown in SEQ ID NO: 1. For example, if the scaffold has amino acid sequence changes relative to those shown in SEQ ID NO: 1, the changes may be to one of the linkers. The Tn3 scaffold may comprise a Gly15 linker that separates two specific CD40L monomers and a Gly10 linker that separates a specific CD40L monomer from an HSA sequence. Both or one of these linkers may be altered, and may be replaced by an amino acid sequence of (GMX)n where X is Serine (S), Alanine (A), Glycine (G), Leu (L), Isoleucine (I), or Valine (V); men are integer values; m is 1, 2, 3 or 4; en is 1, 2, 3, 4, 5, 6 or 7.For example, one or both ligands may be altered to have an amino acid sequence comprising one of GGGGSGGGGS (SEQ ID NO: 7), GGGGSGGGGSGGGGS (SEQ ID NO: 8), GGGGGGGGGG (SEQ ID NO: 9), or GGGGGGGGGGGGGGG (SEQ ID NO: 10). If the Tn3 scaffold has an amino acid sequence relative to the amino acid sequence as provided in SEQ ID NO: 1, it may be due to alterations or changes in the HSA amino acid sequence fused to the two specific CD40L monomers. The HSA fused to the two specific CD40L monomers may be altered from the HSA fused to the two specific CD40L Tn3 monomers, except for at least one amino acid substitution, numbered relative to its position in the mature full-length HSA, at a position selected from the group consisting of 407, 415, 463, 500, 506, 508, 509, 511, 512, 515, 516, 521, 523, 524. Petition 870250087411, dated 09 / 26 / 2025, p. 63 / 404 18 / 327 526, 535, 550, 557, 573, 574 and 580; wherein at least one amino acid substitution does not comprise a lysine (K) to glutamic acid (E) at position 573.

[0041] Exemplary sequences for Tn3 frameworks are shown in Table 1. In aspects, a Tn3 framework comprises at least about or at most about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or up to about 100% identity with any of the SEQ ID NO: 1 - SEQ ID NO: 25 shown in Table 1. In aspects, any of the sequences in Table 1 may be modified. In aspects, a modification comprises one or more truncations, deletions, insertions and combinations thereof. A modification can occur in any of the wastes presented in Table 1 and in any number of wastes from Table 1. In terms of aspects, a modification can comprise 1-3, 1-5, 1-10, 5-20, 1-3, 1-5, 1-10, 1-20, 38, 3-10, 3-15, 5-8, 5-10 or 5-20 wastes. In terms of aspects, a modification can occur in up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400 or 450 wastes. Table 1. Exemplary sequences for a Tn3 framework comprising a specific CD40L monomeric subunit. SEQ ID NO ID Sequence VIB4920 SQIEVKDVTDTTALITWSDDFGEYVWCELTYGIKDVPGD (Construction RTTIDLWYHHAHYSIGNLKPDTEYEVSLICRSGDMSSNP 1 or bivalent AKETFTTGGGGGGGGGGGRLDAPSQIEVKDVTDTT ALITWSDDFGEYVWCELTYGIKDVPGDRTTIDLWYHHAH 342-G15- YSIGNLKPDTEYEVSLICRSGDMSSNPAKETFTTGGGGG Petition 870250087411, dated 09 / 26 / 2025, page 64 / 404 19 / 327 SEQ ID NO Sequence ID 342-G10- HSAC34S 2all GLY ligands; HSA underlined ) GGGGGDAHKSEVAHRFCDLGEENFKALVLIAFAQYLQQS PFEDHVKLVNEVTEFACTQADESAENCDKSLHTLFGDK LCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNL PRLVRPEWDVMCTHKHKFLYFYFYFGDK PELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGK ASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFA EVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQ DSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAA KDFKKRRYKFLEKDVDVDVHDPHE YSVVL L LRLACTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQ NLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLV EVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVL HEKTPVSDRVTKCCTFETTFTEVFLEV HADICTLSEKERQIKKQTALVKHKPKATK EQLKAVMDDFAAFVEKCCADDKETCFAEEGKKLVAASQ AALGL 2 Tn3 monomer specific for CD40L with affinity-matured variant Clone 342 - variant IEVKDVTDTTALGITWDVDVPYKDWDVPGYRTG TIDLWYHHAHYSIGNLKPDTEYEVSLICRRGDMSSNPAK ETFTT Petition 870250087411, of 26 / 09 / 2025, p. 65 / 404 20 / 327 SEQ ID NO ID Affinity-matured sequence (W / WT FG loop; W / O N-terminal A, C-terminal ligand and His8 tag) 3 CD40L-specific Tn3 monomer with affinity-matured variant Clone 342 - affinity-matured variant (FR W / FG loop variant -> IEVKDVTDTTALITWSDDFGEYVWCELTYGIKDVPGDRT TIDLWYHHAHYSIGNLKPDTEYEVSLICRSGDMSSNPAK ETFTT Petition 870250087411, dated 09 / 26 / 2025, page 66 / 404 21 / 327 SEQ ID NO ID Underlined RS sequence ) 4 Human Serum Albumin Variant DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQSPFEDH VKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCCTVA TLRETYGEMADCCAKQEPERNECFLQLPHLPNLPKVR PEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLF FAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAK QRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKL VTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISS KLKKKKKKKLKELPLEDCALDCALDCALDKASSAK KDVCKNYAEAKDVF L GMFLYEYARRHP D YSVVL LLRLAK TYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQ NCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRN LGKVGSKCCKHPEAKRMCAEDQLQLVLVLV VSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETF TFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKA VMDDFAAFVEKCCKADDKETCFAEEGKKLVAASQAALGL 5 Fita beta A within a monomer specific for CD40L Fita IAL EV in BWIT Petition 870250087411, of 26 / 09 / 2025, p. 67 / 404 22 / 327 SEQ ID NO ID CD40L-specific monomer sequence 7 Linker GGGGSGGGGS 8 Linker GGGGSGGGGSGGGGS 9 Linker GGGGGGGGGG 10 Linker GGGGGGGGGGGGGGG 11 Loop AB KDVTDTT 12 Loop BC SDDFGEYVW 13 Loop CD KDVPGDR 14 Loop DE WYHHAH 15 Loop EF GNLKPDTE 16 Loop FG RSGDMSSNPA 17 Beta C strand within a CD40L-specific monomer CELTYGI 18 Beta D strand within a CD40L-specific monomer TTIDL Petition 870250087411, dated 09 / 26 / 2025, page 68 / 404 23 / 327 SEQ ID NO ID Sequence 19 Beta E strand within a CD40L-specific monomer YSI 20 Beta F strand within a CD40L-specific monomer YEVSLIC 21 Beta G strand within a CD40L-specific monomer KETFTT 22 CD40L-specific Tn3 monomer Clone 342 - mature variant SQIEVKDVTDTTALITWSDDFGEYVWCELTYGIKDVPGD RTTIDLWYHHAHYSIGNLKPDTEYEVSLICRSGDMSSNP AKETFTT Petition 870250087411, dated 09 / 26 / 2025, page 69 / 404 24 / 327 SEQ ID NO ID Affinity sequence (Loop variant W / FG FR-> RS underlined) 23 Beta A strand sequence within a CD40L-specific monomer RLDAPSQIEV 24 Beta A strand within a CD40L-specific monomer SQIEV Monomer RLDAPSQIEVKDVTDTTALITWSDDFGEYVWCELTYGIK 25 CD40L-specific Tn3 DVPGDRTTIDLWYHHAHYSIGNLKPDTEYEVSLICRSGD MSSNPAKETFTT Petition 870250087411, dated 09 / 26 / 2025, page 70 / 404 25 / 327

[0042] If the Tn3 scaffold has amino acid sequence changes relative to those shown in SEQ ID NO: 1, the changes may be in the amino acid sequence of one or both CD40L-specific Tn3 monomers, provided that it does not adversely affect the in vivo efficacy of the scaffold, for example, a change in the amino acid sequence such that one or both CD40L-specific Tn3 monomers have the amino acid sequence as shown in SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 22 and SEQ ID NO: 25. In aspects, the first one or two N-terminal (SQ) amino acid residues may be absent and / or replaced by alternative amino acid residues. In aspects, a Tn3 scaffold comprises a monomeric subunit comprising SEQ ID NO: 22, SEQ ID NO: 25, or both SEQ ID NO: 22 and SEQ ID NO: 25.

[0043] In aspects, a Tn3 scaffold comprises at least one specific CD40L monomeric subunit linked to a heterologous chemical moiety. In aspects, this heterologous chemical moiety is selected from the group consisting of: a protein, a peptide, a protein domain, a ligand, a drug, a toxin, a cytotoxic agent, an imaging agent, a radionuclide, a radioactive compound, an organic polymer, an inorganic polymer, a polyethylene glycol (PEG), biotin, an albumin, an HSA FcRn-binding moiety, an antibody or fragment thereof, a single-chain antibody, a domain antibody, an albumin-binding domain, an enzyme, a ligand, a receptor, a binding peptide, a non-FnIII scaffold, an epitope tag, a recombinant polypeptide polymer, a cytokine, and a combination of two or more Petition 870250087411, dated 09 / 26 / 2025, page 71 / 404 26 / 327 of said chemical moieties. In aspects, the heterologous chemical moiety is albumin, and albumin comprises human serum albumin. In aspects, the heterologous chemical moiety is an antibody. In aspects, the antibody is selected from the group consisting of: an Fc domain of an antibody, an antibody fragment, and a single-chain antibody.

[0044] In some respects, the heterologous chemical portion is an antibody. In some respects, the antibody is selected from the group consisting of: an Fc domain of an antibody, an antibody fragment, and a single-chain antibody.

[0045] In some respects, the heterologous chemical portion is an imaging agent; for example, a radionuclide or biotin. In other respects, the heterologous chemical portion is a drug; for example, a cytotoxic agent or a radioactive compound.

[0046] In aspects, the heterologous chemical portion comprises PEG. In aspects, the Tn3 framework comprises at least one specific CD40L monomeric subunit fused or conjugated directly or via a ligand to PEG. In aspects, both specific CD40L monomeric subunits are fused, conjugated, or connected via a ligand to PEG. In aspects, the Tn3 framework comprises at least one (e.g., two) specific CD40L monomeric subunit fused or conjugated directly or via a ligand to PEG.

[0047] In aspects, the heterologous chemical portion comprises albumin. In aspects, the Tn3 framework comprises at least one specific CD40L monomeric subunit fused or conjugated directly or via a ligand to an albumin. In exemplary aspects, albumin is Petition 870250087411, dated 09 / 26 / 2025, page 72 / 404 27 / 327 HSA. In certain respects, this HSA is a variant HSA. In certain respects, the amino acid sequence of the variant HSA is SEQ ID NO: 4. In certain respects, the variant HSA has at least one enhanced property compared to a native HSA or a native HSA fragment. In certain respects, the amino acid sequence of the variant HSA is SEQ ID NO: 4 or a sequence that has at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or even 100% identity with SEQ ID NO: 4. In certain respects, the enhanced property is an altered plasma half-life compared to the plasma half-life of a native HSA or a native HSA fragment. In certain respects, the altered plasma half-life is a longer plasma half-life compared to the plasma half-life of a native HSA or a native HSA fragment. In some respects, the altered plasma half-life is a shorter plasma half-life compared to the plasma half-life of a native HSA or a fragment of native HSA. Dosage

[0048] In some respects, any of the compositions comprising a Tn3 framework of the disclosure may be administered in any form. In some respects, a Tn3 framework is administered intravenously, subcutaneously, orally, intramuscularly, intrathecally, sublingually, rectally, vaginally, cutaneously, systemically, topically, transdermally, or by inhalation. In some respects, the Tn3 framework is administered intravenously. In some respects, the Tn3 framework is administered by intravenous infusion.

[0049] A Tn3 framework of revelation can be administered at any dose. In aspects, the Tn3 framework is administered at a dose of approximately and / or up to approximately: 800 Petition 870250087411, dated 09 / 26 / 2025, p. 73 / 404 28 / 327 mg, mg, 1500 850 mg, 900 mg, 950 mg, 1000 mg, 1650 mg, 1350 mg, 1050 mg, 1700 mg, 1400 mg, 1100 mg, 1750 mg, 1450 mg, 1150 mg, 1800 1200 mg, mg, 1550 1250 mg, mg, 1600 1300 mg, mg, 1850 mg, 1900 mg, 1950 mg, 2000 mg, 2050 mg, 2100 mg, 2150 mg, 2200 mg, 2250 mg, 2300 mg, 2350 mg, 2400 mg, 2450 mg, 2500 mg, 2550 mg, 2600 mg, 2650 mg, 2700 mg, 2750 mg, 2800 mg, 2850 mg, 2900 mg, 2950 mg, 3000 mg, 3050 mg, 3100 mg, 3150 mg, 3200 mg, 3250 mg, 3300 mg, 3350 mg, 3400 mg, 3450 mg, 3500 mg, 3550 mg, 3600 mg, 3650 mg, 3700 mg, 3750 mg, 3800 mg, 3850 mg, 3900 mg, 3950 mg, 4000 mg, 4050 mg, 4100 mg, 4150 mg, 4200 mg, 4250 mg, 4300 mg, 4350 mg, 4400 mg, 4450 mg, 4500 mg, 4550 mg, 4600 mg, 4650 mg, 4700 mg, 4750 mg, 4800 mg, 4850 mg, 4900 mg, 4950 mg or approximately 5000 mg. Any of the above-mentioned dosages may be effective dosages for a method comprising treatment, reduction or elimination.

[0050] In some respects, the Tn3 framework is administered at a dose of approximately: 800-5000 mg, 900-4900 mg, 1000-4800 mg, 1100-4700 mg, 1200-4600 mg, 1300-4500 mg, or 1500-3000 mg. In some respects, a Tn3 framework is administered at a dose selected from the group consisting of: 1300 mg, 1350 mg, 1400 mg, 1450 mg, 1500 mg, 1550 mg, 1600 mg, 1650 mg, 1700 mg, 1750 mg, 1800 mg, 1850 mg, 1900 mg, 1950 mg, 2000 mg, 2050 mg, 2100 mg, 2150 mg, 2200 mg, 2250 mg, 2300 mg, 2350 mg, 2400 mg, 2450 mg, 2500 mg, 2550 mg, 2600 mg, 2650 mg, 2700 mg, 2750 mg, 2800 mg, 2850 mg, 2900 mg, 2950 mg, 3000 mg, 3050 mg, 3100 mg, 3150 mg, 3200 mg, 3250 mg, 3300 mg, 3350 mg, 3400 mg, 3450 mg, 3500 mg, 3550 mg, 3600 mg, 3650 mg, 3700 mg, 3750 mg, 3800 mg, 3850 mg, 3900 mg, 3950 mg, 4000 mg, 4050 mg, 4100 mg, 4150 mg, 4200 mg, 4250 mg, Petition 870250087411, dated 09 / 26 / 2025, page 74 / 404 29 / 327 4300 mg, 4350 mg, 4400 mg, 4450 mg, and 4500 mg. In some respects, the Tn3 framework is administered at a dose between approximately 1500 mg and 3000 mg. In some respects, the Tn3 framework is administered at a dose of 1500 mg or 3000 mg. In some respects, a Tn3 framework is administered at a dose of approximately 1500 mg. In some respects, a Tn3 framework is administered at a dose of approximately 3000 mg. Dosage Frequency

[0051] In some respects, a Tn3 disclosure framework is administered on a schedule that provides optimal results. In some respects, a Tn3 framework is administered to a subject in need of it approximately once a week, approximately twice a week, approximately once every two weeks, approximately once a month, approximately once every four weeks, approximately once every two months, approximately once every 3 months, approximately once every 12 weeks, approximately once every fifteen weeks, approximately once every sixteen weeks, approximately once every four months, approximately once every five months, approximately once every six months, or semi-annually. Any number of administrations may be provided to a subject in need of it. In some respects, a Tn3 disclosure framework is administered as a loading dose. A loading dose may also be known as an induction dose. In some respects, a Tn3 framework is administered as a maintenance dose.

[0052] A Tn3 framework of revelation can be administered in approximately 1-10, 10-50, 50-75, 75-100, 100-200, or 200-300 total doses, or up to a subject's lifetime. In some respects, a Tn3 framework is administered Petition 870250087411, dated 09 / 26 / 2025, p. 75 / 404 30 / 327 as approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30 or more doses. In some respects, a Tn3 framework is administered with at least approximately or at most approximately 2, 3, 4 or 5 total doses. In some respects, a Tn3 framework is administered with at least approximately or at most approximately 10, 11, 12 or 13 total doses.

[0053] In aspects, an effective dose is administered to a subject approximately every 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 2 years, 3 years, 4 years or 5 years, or up to the subject's lifetime after treatment initiation. In aspects, a subject receives an effective dose on Day 1, Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225, Day 253, Day 281, and Day 309 post-treatment initiation. In aspects, a subject receives 1500 mg-3000 mg of a Tn3 framework on Day 1, Day 85, Day 29, Day 57, Day 15, Day 113, Day 141, Day 169, Day 197, Day 225, Day 253, Day 281, and Day 309 post-treatment initiation.

[0054] In aspects, a subject is administered approximately 1500 mg–3000 mg of a Tn3 scaffold every 2 weeks for approximately 3 administrations, then every 4 weeks thereafter. In aspects, a subject is administered approximately 1500 mg of a Tn3 scaffold every 2 weeks for approximately 3 administrations, then every 4 weeks thereafter. In aspects, a subject is administered approximately 3000 mg of a Tn3 scaffold at weeks 0, 4, and 12, then every 12 weeks thereafter. In Petition 870250087411, dated 09 / 26 / 2025, page 76 / 404 In aspects 31 / 327, a subject is administered approximately 1500 mg of a Tn3 scaffold every 4 weeks. In aspects 31 / 327, a subject is administered approximately 3000 mg of a Tn3 scaffold every 12 weeks. In aspects 31 / 327, a subject is administered an initial dose of a developing Tn3 scaffold of approximately 1500 mg-3000 mg every 2 weeks for at least 2, at least 3, or more administrations, and then every 4 weeks thereafter. In aspects 31 / 327, a subject is administered an initial dose of a developing Tn3 scaffold of approximately 1500 mg every 2 weeks for at least 2, at least 3, or more administrations, and then every 4 weeks thereafter. In some aspects, a subject is administered an initial dose of a Tn3 development framework of approximately 3000 mg every 2 weeks for at least 2, at least 3, or more administrations, and then every 12 weeks thereafter.In aspects, a subject is administered an initial dose of a Tn3 framework of approximately 3000 mg every 4 weeks for at least 2, at least 3, or more administrations, and then every 12 weeks thereafter. In aspects, administration treats a subject with SS with low systemic disease activity but moderate to severe symptom status. In aspects, administration treats a subject with SS with moderate systemic disease activity. In aspects, administration treats a subject with SS with severe systemic disease activity. In aspects, administration treats a subject with SS with moderate to severe systemic disease activity. In aspects, administration of a Tn3 framework treats a subject with SS with moderate or severe systemic disease activity, as defined by an ESSDAI score of 5. In aspects, a. Petition 870250087411, dated 09 / 26 / 2025, page 77 / 404 32 / 327 Administration of a Tn3 framework treats a subject with SS with moderate to severe systemic disease activity, as defined by an ESSDAI score ^ 5. In aspects, administration of a Tn3 framework treats a subject with SS with moderate to severe symptomatic activity, as defined by an ESSPRI score of ^ 5 and low systemic disease activity with an ESSDAI score < 5. In aspects, administration of a Tn3 framework treats a subject with SS with moderate or severe systemic disease activity, as defined by an ESSDAI score ^ 5. In aspects, administration of a Tn3 framework treats a subject with SS with moderate or severe systemic disease activity, as defined by an ESSDAI score ^ 5. In aspects, administration of a Tn3 framework treats a subject with SS with moderate or severe symptomatic activity, as defined by an ESSPRI score ^ of ^ 5 and low systemic disease activity with an ESSDAI score < 5.

[0055] Methods for treating or preventing disclosure comprise administering a disclosure Tn3 framework to a subject in need thereof. In aspects, a treatment method comprises administering an effective dose of a Tn3 framework to a subject in need thereof every 2 weeks for approximately 3 doses, followed by administration of a Tn3 framework every 4 weeks thereafter. In aspects, a treatment method comprises administering an effective dose of a Tn3 framework to a subject in need thereof in weeks 0, 4, and 12, followed by administration of a Tn3 framework every 12 weeks thereafter. In aspects, a treatment method comprises administering from approximately 1400 mg to approximately 1600 mg Petition 870250087411, dated 09 / 26 / 2025, p. 78 / 404 33 / 327 mg of a Tn3 scaffold to a subject requiring it every 2 weeks for approximately 3 administrations, followed by administration of a Tn3 scaffold every 4 weeks thereafter. In aspects, one treatment method comprises administering approximately 2,000 mg to approximately 4,000 mg of a Tn3 scaffold to a subject requiring it in weeks 0, 4, and 12, followed by administration of a Tn3 scaffold every 12 weeks thereafter.

[0056] In aspects, a treatment method comprises administering approximately 1500 mg of a Tn3 scaffold to a subject in need of it every 2 weeks for 7 administrations. In aspects, a treatment method comprises administering approximately 1500 mg of a Tn3 scaffold to a subject in need of it every 4 weeks for 5 administrations. In aspects, a treatment method comprises administering approximately 1500 mg of a Tn3 scaffold to a subject in need of it every 2 weeks for approximately 3 administrations, followed by administration of the Tn3 scaffold every 4 weeks thereafter. In aspects, a treatment method comprises administering approximately 3000 mg of a Tn3 scaffold to a subject in need of it in weeks 0, 4, and 12, followed by administration of the Tn3 scaffold every 12 weeks thereafter.In some respects, administrations continue every 4 weeks thereafter, up to about 1 year, 2 years, 3 years, 4 years, or 5 years, or up to the subject's lifetime. In some respects, any of the aforementioned administrations may deviate by about 1 day to about 4 days, about 3 days to about 7 days, or about 1 day to about 7 days. In some respects, any. Petition 870250087411, dated 09 / 26 / 2025, p. 79 / 404 34 / 327 one of the aforementioned administrations may deviate by approximately 1 day, 3 days, 4 days, or 7 days. In some respects, any of the aforementioned administrations may deviate by approximately 1 day. In some respects, any of the aforementioned administrations may deviate by approximately 3 days. In some respects, any of the aforementioned administrations may deviate by approximately 4 days. In some respects, any of the aforementioned administrations may deviate by approximately 7 days.

[0057] In aspects, a subject receives an effective dose of a Tn3 scaffold on Day 1, Day 15 (-3 days to +1 day), Day 29 (± 4 days), and Day 57 (± 7 days) post-treatment initiation. In aspects, a subject in need is administered 1500 mg of a Tn3 scaffold on Day 1, Day 15 (3 days to +1 day), Day 29 (± 4 days), and Day 57 (± 7 days) post-treatment initiation and then every 4 weeks thereafter as needed. In aspects, a subject in need is administered 1500 mg of a Tn3 scaffold on Day 1, Day 15 (± 1 day), and Day 29 (± 3 days) post-treatment initiation. In some aspects, a subject requiring the same is administered 1500 mg of a Tn3 scaffold on Day 1 and Day 57 (±7 days) post-treatment initiation. In some aspects, a subject requiring the same is administered 1500 mg of a Tn3 scaffold on Day 1, Day 15 (± 1 day), Day 29 (± 3 days), Day 57 (± 7 days), Day 85 (± 7 days), Day 113 (± 7 days), Day 141 (± 7 days) post-treatment initiation.In aspects, a subject requiring the same is administered 1500 mg of a Tn3 framework on Day 169 (± 7 days), Day 197 (± 7 days), Day 225 (± 7 days), Day 253 (± 7 days), and Day 281 (± 7 days) post-treatment initiation. In aspects, a subject. Petition 870250087411, dated 09 / 26 / 2025, page 80 / 404 35 / 327 requiring the same is administered 3000 mg of a Tn3 scaffold on Day 1, Day 15 (-3 days to +1 day), Day 29 (± 4 days), and Day 57 (± 7 days) post-treatment initiation, and then every 6 weeks thereafter as needed. In aspects, a subject requiring the same is administered 3000 mg of a Tn3 scaffold on Day 1, Day 15 (-3 days to +1 day), and Day 29 (± 4 days) post-treatment initiation. In aspects, a subject requiring the same is administered 3000 mg of a Tn3 scaffold on Day 1 and Day 57 (± 7 days) post-treatment initiation, and then every 12 weeks thereafter as needed.

[0058] In aspects, a subject in need receives a dose of a Tn3 framework on Day 1, Day 15 (-3 days to +1 day), Day 29 (± 4 days), Day 57 (± 7 days), Day 85 (± 7 days), Day 113 (± 7 days), and Day 141 (± 7 days). In aspects, a subject in need receives an effective dose of a Tn3 framework on Day 169 (± 7 days), Day 197 (± 7 days), Day 225 (± 7 days), Day 253 (± 7 days), Day 281 (± 7 days), and Day 309 (± 7 days).

[0059] In aspects, a subject in need receives an effective dose of a Tn3 scaffold once every 24 weeks. In aspects, a subject in need receives an effective dose of a Tn3 scaffold once every 2 weeks, 4 weeks, 6 weeks, 8 weeks, or 12 weeks. In aspects, a subject in need is administered 1500 mg of a Tn3 scaffold once every 2 weeks for at least 3 doses, once every 4 weeks for at least 12 doses, once every 4 weeks for at least 13 doses, or a combination thereof. In aspects, a subject in need is administered 3000 mg of a scaffold Petition 870250087411, dated 09 / 26 / 2025, page 81 / 404 36 / 327 Tn3 once every 2 weeks for at least 3 doses, once every 4 weeks for at least 4 doses, once every 4 weeks for at least 5 doses, or a combination thereof. In some cases, 3000 mg of a Tn3 framework is administered every 3 months. In others, 3000 mg of a Tn3 framework is administered every 12 weeks.

[0060] In some respects, a Tn3 framework is administered at a dose of approximately 1500 mg once every 2 weeks for at least 2 doses and is administered approximately once a month thereafter. In some respects, a Tn3 framework is administered at a dose of approximately 1500 mg once every 2 weeks for at least 3 doses and is administered approximately once a month thereafter. In some respects, a Tn3 framework is administered at a dose of approximately 1500 mg once every 2 weeks for at least 3 doses and is administered every 4 weeks thereafter. In some respects, a Tn3 framework is administered at a dose of approximately 1500 mg once a month, once every two months, or once every three months. In some respects, a Tn3 framework is administered at a dose of approximately 3000 mg once every 2 weeks for at least about 2 doses and is administered approximately once a month, every two months, or every three months thereafter, or combinations thereof.In some respects, a Tn3 framework is administered at a dose of approximately 3000 mg once every 4 weeks for at least approximately 2 doses and is administered approximately once a month, every two months, or every three months thereafter, or combinations thereof. In some respects, a Tn3 framework is administered at a dose of approximately 3000 mg once every 4 weeks for at least approximately 2 doses and is administered approximately every twelve weeks thereafter. In some respects, a Tn3 framework is... Petition 870250087411, dated 09 / 26 / 2025, p. 82 / 404 37 / 327 administered at a dose of approximately 3000 mg once a month, once every two months, or once every three months. In some cases, a Tn3 scaffold is administered for two or more doses. In some cases, a subject is administered 1500 mg of a Tn3 scaffold every 2 weeks. In some cases, a subject is administered 1500 mg of a Tn3 scaffold every 4 weeks. In some cases, a subject is administered 3000 mg of a Tn3 scaffold every 12 weeks.

[0061] In aspects, a method of disclosure comprises administering a Tn3 scaffold at a dose of 3000 mg of a Tn3 scaffold every 12 weeks, with a dose of 3000 mg of a Tn3 scaffold at week 0 and week 4. In aspects, a method of disclosure comprises administering a Tn3 scaffold at a dose of 1500 mg of a Tn3 scaffold every 4 weeks. In some respects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 1 at a dose of 3000 mg of a Tn3 scaffold every 12 weeks, with a dose of 3000 mg of a Tn3 scaffold at week 0 and week 4. In some respects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 1 at a dose of 1500 mg of a Tn3 scaffold every 2 weeks. In some respects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 1 at a dose of 1500 mg of a Tn3 scaffold every 4 weeks.In aspects, a method of disclosure comprises administering a Tn3 framework comprising SEQ ID NO: 1 at a dose of 1500 mg of a Tn3 framework every two weeks for 3 administrations and then every 4 weeks thereafter. In aspects, a method of disclosure. Petition 870250087411, dated 09 / 26 / 2025, p. 83 / 404 38 / 327 comprises the administration of a Tn3 framework comprising SEQ ID NO: 1 at a dose of 3,000 mg of a Tn3 framework every two weeks for 3 administrations and then every 12 weeks thereafter.

[0062] In aspects, a method of disclosure comprises administering a Tn3 scaffold at a dose of 3000 mg of a Tn3 scaffold every 12 weeks, with a dose of 3000 mg of a Tn3 scaffold at week 0 and week 4. In aspects, a method of disclosure comprises administering a Tn3 scaffold at a dose of 1500 mg of a Tn3 scaffold every 4 weeks. In some aspects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 22 or SEQ ID NO: 25 at a dose of 3000 mg of a Tn3 scaffold every 12 weeks, with a dose of 3000 mg of a Tn3 scaffold in week 0 and week 4. In some aspects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 22 or SEQ ID NO: 25 at a dose of 1500 mg of a Tn3 scaffold every 2 weeks. In some aspects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 22 or SEQ ID NO: 25 at a dose of 1500 mg of a Tn3 scaffold every 4 weeks.In some aspects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 22 or SEQ ID NO: 25 at a dose of 1500 mg of a Tn3 scaffold every two weeks for 3 administrations and then every 4 weeks thereafter. In other aspects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 22 or SEQ ID NO: 25 at a dose of 3000 mg of a Tn3 scaffold every two weeks for 3 administrations and then every 12 weeks thereafter. Petition 870250087411, dated 09 / 26 / 2025, p. 84 / 404 39 / 327

[0063] In aspects, a method of disclosure comprises administering a Tn3 scaffold to a subject in need thereof at a dose of 3000 mg of a Tn3 scaffold every 12 weeks, with a dose of 3000 mg of a Tn3 scaffold at week 0 and week 4. In aspects, a method of disclosure comprises administering a Tn3 scaffold to a subject in need thereof at a dose of 1500 mg of a Tn3 scaffold every 4 weeks. In some aspects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 1 to a subject in need thereof at a dose of 3000 mg of a Tn3 scaffold every 12 weeks, with a dose of 3000 mg of a Tn3 scaffold at week 0 and week 4. In other aspects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 1 to a subject in need thereof at a dose of 1500 mg of a Tn3 scaffold every 2 weeks.In some respects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 1 to a subject in need thereof at a dose of 1500 mg of a Tn3 scaffold every 4 weeks. In some respects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 1 to a subject in need thereof at a dose of 1500 mg of a Tn3 scaffold every two weeks for 3 administrations and then every 4 weeks thereafter. In some respects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 1 to a subject in need thereof at a dose of 1500 mg of a Tn3 scaffold every 2 weeks for 7 administrations. In some respects, a method of disclosure comprises administering a Tn3 scaffold comprising... Petition 870250087411, dated 09 / 26 / 2025, page 85 / 404 40 / 327 a SEQ ID NO: 1 to a subject in need thereof at a dose of 1500 mg of a Tn3 scaffold every 4 weeks for 5 administrations. In aspects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 1 to a subject in need thereof at a dose of 3000 mg of a Tn3 scaffold every two weeks for 3 administrations and then every 12 weeks thereafter.

[0064] In aspects, a method of disclosure comprises administering a Tn3 scaffold to a subject in need thereof at a dose of 3000 mg of a Tn3 scaffold every 12 weeks, with a dose of 3000 mg of a Tn3 scaffold at week 0 and week 4. In aspects, a method of disclosure comprises administering a Tn3 scaffold to a subject in need thereof at a dose of 1500 mg of a Tn3 scaffold every 2 weeks.In some aspects, a method of disclosure comprises administering a Tn3 scaffold to a subject in need thereof at a dose of 1500 mg of a Tn3 scaffold every 4 weeks. In some aspects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 22 or SEQ ID NO: 25 to a subject in need thereof at a dose of 3000 mg of a Tn3 scaffold every 12 weeks, with a dose of 3000 mg of a Tn3 scaffold in week 0 and week 4. In some aspects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 22 or SEQ ID NO: 25 to a subject in need thereof at a dose of 1500 mg of a Tn3 scaffold every 2 weeks. In some respects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 22 or SEQ ID NO: 25 to a subject in need thereof at a dose of 1500 mg of a Tn3 scaffold every 4 days. Petition 870250087411, dated 09 / 26 / 2025, page 86 / 40441 / 327 weeks. In aspects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 22 or SEQ ID NO: 25 to a subject in need thereof at a dose of 1500 mg of a Tn3 scaffold every 2 weeks for 7 administrations. In aspects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 22 or SEQ ID NO: 25 to a subject in need thereof at a dose of 1500 mg of a Tn3 scaffold every 4 weeks for 5 administrations. In some respects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 22 or SEQ ID NO: 25 to a subject in need thereof at a dose of 1500 mg of a Tn3 scaffold every two weeks for administrations 3 and then every 4 weeks thereafter.In some respects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 22 or SEQ ID NO: 25 to a subject in need thereof at a dose of 3000 mg of a Tn3 scaffold every two weeks for administrations 3 and then every 12 weeks thereafter.

[0065] In some respects, a Tn3 scaffold is administered at a dose of approximately 1500 mg. In some respects, a Tn3 scaffold is administered at a dose of approximately 3000 mg. In some respects, a Tn3 scaffold is administered at a dose of approximately 1500 mg every 2 weeks. In some respects, a Tn3 scaffold is administered at a dose of approximately 1500 mg every 4 weeks. In some respects, a Tn3 scaffold is administered at a dose of approximately 1500 mg once every 2 weeks for at least 2 or more doses. In some respects, a Tn3 scaffold is administered at a dose of approximately 1500 mg twice every 2 weeks for at least 2 or more doses. In some respects, a scaffold Petition 870250087411, dated 09 / 26 / 2025, p. 87 / 404 42 / 327 Tn3 is administered at a dose of approximately 1500 mg once every 4 weeks for at least 2 or more doses. In some respects, a Tn3 framework is administered at a dose of approximately 1500 mg twice every 4 weeks for at least 2 or more doses. In some respects, a Tn3 framework is administered at a dose of approximately 1500 mg twice every 4 weeks subsequently. In some respects, a Tn3 framework is administered at a dose of approximately 1500 mg every 2 weeks for 3 doses and subsequently every 4 weeks. In some respects, a Tn3 framework is administered at a dose of approximately 1500 mg every 2 weeks for 2 doses and subsequently every 4 weeks. In some aspects, a Tn3 framework is administered at a dose of approximately 3000 mg every 2 weeks. In some aspects, a Tn3 framework is administered at a dose of approximately 3000 mg every 4 weeks. In some aspects, a Tn3 framework is administered at a dose of approximately 3000 mg twice every 2 weeks for at least 2 or more doses.In some respects, a Tn3 framework is administered at a dose of approximately 3000 mg twice every 4 weeks for at least 2 or more doses. In some respects, a Tn3 framework is administered at a dose of approximately 3000 mg twice every 12 weeks for at least 2 or more doses. In some respects, a Tn3 framework is administered at a dose of approximately 3000 mg twice every 12 weeks subsequently. In some respects, a Tn3 framework is administered at a dose of approximately 3000 mg every 2 weeks for 3 doses and subsequently every 12 weeks. In some respects, a Tn3 framework is administered at a dose of approximately 3000 mg every 4 weeks for at least 2 doses and subsequently every 12 weeks. Methods Petition 870250087411, dated 09 / 26 / 2025, p. 88 / 404 43 / 327

[0066] In aspects of this document, the methods are directed to treat, reduce, or eliminate an autoimmune disease or disorder. In aspects, the method comprises administering a Tn3 framework of the disclosure. In aspects, a Tn3 framework is used to treat SS. In aspects, a Tn3 framework is administered to a subject in need thereof to treat SS using any of the dosing schedules disclosed in this document. In aspects, a Tn3 framework is administered at a dose of approximately 1500 mg once every 2 weeks for at least 2 doses and is administered approximately once a month thereafter. In aspects, a Tn3 framework is administered at a dose of approximately 1500 mg once every 2 weeks for at least 3 doses and is administered thereafter approximately once a month or once every 4 weeks. In some aspects, a Tn3 framework is administered at a dose of approximately 1500 mg once a month, once every two months, or once every three months.In some aspects, a Tn3 framework is administered at a dose of approximately 3,000 mg once a month, once every two months, or once every three months. In some aspects, a Tn3 framework is administered at a dose of approximately 3,000 mg once every 2 weeks for at least 3 doses, and is subsequently administered approximately once every 3 months. In some aspects, a Tn3 framework is administered at a dose of approximately 3,000 mg once every 4 weeks for at least 2 doses, and is subsequently administered approximately once every 3 months. In some aspects, a Tn3 framework is administered at a dose of approximately 3,000 mg once every 4 weeks for at least 2 doses and is subsequently administered approximately once every 12 weeks. In some aspects, a Tn3 framework is administered. Petition 870250087411, dated 09 / 26 / 2025, p. 89 / 404 44 / 327 at a dose of approximately 3,000 mg followed by additional administrations at 4 weeks and 12 weeks, and is administered approximately once every 3 months, or once every 12 weeks thereafter. In some cases, a Tn3 framework is administered for two or more doses.

[0067] In aspects, a method comprises treating a subject with SS. In aspects, a method comprises treating a subject with SS with a European Alliance of Associations for Rheumatology (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) of approximately 1, approximately 2, approximately 3, approximately 4, approximately 5, approximately 6, approximately 7, approximately 8, approximately 9, approximately 10, approximately 11, approximately 12, approximately 13, approximately 14, approximately 15, approximately 20, approximately 25, approximately 30, approximately 40, approximately 50, approximately 60, approximately 70, approximately 80, approximately 90, approximately 100, approximately 110 or approximately 120 or higher. In some respects, a method comprises treating a subject with SS with a score on the EULAR Sjögren's Syndrome Patient Reported Symptom Index (ESSPRI) of approximately 1, approximately 2, approximately 4, approximately 5, approximately 6, approximately 7, approximately 8, approximately 9, or approximately 10.

[0068] In some respects, a method comprises treating a subject in need of the same. In some respects, a method comprises treating a subject with SS. In some respects, a method comprises treating a subject with SS with low systemic disease activity. In some respects, a method comprises treating a subject with SS with low systemic disease activity, but with a moderate to severe symptomatic state. In some respects, a method comprises treating a subject with SS with moderate systemic disease activity. In some respects, a method comprises treating Petition 870250087411, dated 09 / 26 / 2025, page 90 / 404 45 / 327 a subject with SS with severe systemic disease activity. In aspects, a method comprises treating a subject with SS with moderate to severe systemic disease activity. In aspects, a method comprises treating a subject with SS with moderate to severe systemic disease activity by administering a Tn3 framework at any dose on any schedule disclosed herein. In aspects, a method comprises treating a subject with SS and coexisting rheumatoid arthritis (RA). In aspects, a method comprises treating a subject with SS and coexisting systemic lupus erythematosus (SLE). In aspects, moderate to severe systemic disease activity may be defined by the EULAR Sjögren's Syndrome Patient Reported Symptom Index (ESSPRI) ± 5. In aspects, moderate to severe systemic disease activity may be defined by the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) ± 5.In aspects, low systemic disease activity can be defined by ESSDAI < 5. In aspects, a method comprises treating a subject with SS with low subjective symptoms by administering a Tn3 framework. In aspects, a method comprises treating a subject with SS with moderate to severe subjective symptoms by administering a Tn3 framework. In aspects, the subject may have moderate to severe symptomatic activity, as defined by an ESSPRI score ≥ 5, but with low systemic disease activity defined by an ESSDAI score < 5. In aspects, moderate to severe systemic disease activity can be defined by an ESSDAI score ≥ 5. In aspects, a method comprises treating a subject with severe SS. In aspects, a method comprises treating a subject with SS with an ESSDAI above 14. In aspects, a method... Petition 870250087411, dated 09 / 26 / 2025, page 91 / 404 46 / 327 comprises treating an SS subject with an ESSDAI of 14. In aspects, a method comprises treating an SS subject with an ESSDAI of 14 to about 20, 14 to about 30, 14 to about 40, 14 to about 50, 14 to about 60, 15 to about 40, about 20 to about 70, about 30 to about 80, about 40 to about 90, about 50 to about 100, about 60 to about 110, about 70 to about 120, or about 80 to about 123. In aspects, the Tn3 framework is administered at a dose of 1500 mg. In other respects, a Tn3 framework is administered at a dose of 3000 mg.

[0069] In aspects, a method for treating a subject in need thereof comprises administering an effective dose of a Tn3 framework. In aspects, an administration is effective in reducing a disease or disorder compared with: a) the disease or disorder in an otherwise comparable subject lacking the administration; or b) a baseline measurement of the disease or disorder in the subject in need thereof. In aspects, an administration is effective as assessed by the Sjogren's Diary for Analysis of the Patient-Reported Index (DASPRI). In terms of aspects, a DASPRI score is reduced in a subject administered with a Tn3 framework by at least or at most about: 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 95, 96, 97, 98, 99, or 100. In terms of aspects, an administration is effective as assessed by the Sjogren Response Analysis Tool (STAR).In terms of aspects, a STAR score is increased in a subject administered a Tn3 framework by at least or more approximately: 1, 2, 3, 4, 5, 6, 7, or 8 points. In terms of aspects, an administration is effective in one. Petition 870250087411, dated 09 / 26 / 2025, page 92 / 404 47 / 327 reduction of an ESSPRI score in a subject in need of it compared to the subject's baseline level. In aspects, an ESSPRI score is reduced in a subject administered with a Tn3 framework by at least about, or at most about: 1 time, 5 times, 10 times, 25 times, 50 times, 75 times, 100 times, 150 times, or 250 times compared to the subject's baseline level. In aspects, an ESSPRI score is reduced in a subject administered a Tn3 framework by at least about or at most about 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, or 10 points or more compared to a subject's baseline level.In some respects, an ESSPRI score is reduced in a subject administered with a Tn3 framework by at least about, or at most about, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, 34%, 36%, 38%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or up to about 100% compared to a subject's baseline level. In aspects, an administration is effective in reducing an ESSDAI score in a subject in need of it compared to the subject's baseline level. In aspects, an ESSDAI score is reduced in a subject administered with a Tn3 framework by at least about, or at most about: 1 time, 5 times, 10 times, 25 times, 50 times, 75 times, 100 times, 150 times, or 250 times compared to the subject's baseline level.In some respects, an ESSDAI score is reduced in a subject administered a Tn3 framework by at least approximately, or at most approximately, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6. Petition 870250087411, dated 09 / 26 / 2025, page 93 / 404 48 / 327 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 90, or 100 points or more compared to the subject's baseline level. In some respects, an ESSDAI score is reduced in a subject administered with a Tn3 framework by at least about, or at most about, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, 34%, 36%, 38%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or up to about 100% compared to a subject's baseline level.

[0070] In aspects, a Tn3 development framework has an increased response rate in a selected domain from the group consisting of: constitutional, lymphadenopathy, glandular, articular, cutaneous, pulmonary, renal, muscular, peripheral nervous system, central nervous system, hematological, and biological, compared with subjects who received control. In aspects, the response rate is increased by at least approximately: 5%, 10%, 15%, 20%, 30%, 40%, or 50% compared with the administered control subject. In aspects, a response rate is increased in a subject administered with a Tn3 development framework in a constitutional domain compared to the response of a subject administered with control. In aspects, a response rate is increased in a subject administered with a Tn3 development framework in a lymphadenopathy domain compared to the response of a subject administered with control.In some aspects, a response rate is increased in a subject administered with a Tn3 framework of development in a glandular domain compared to the response of a subject administered with a control. In other aspects, a. Petition 870250087411, dated 09 / 26 / 2025, pp. 94 / 404 49 / 327 response rate is increased in a subject administered with a Tn3 development framework in an articular domain compared to the response of a subject administered with a control. In aspects, a response rate is increased in a subject administered with a Tn3 development framework in a cutaneous domain compared to the response of a subject administered with a control.

[0071] In some respects, a Tn3 scaffold is administered at a dose of approximately 1500 mg via intravenous administration. In some respects, a Tn3 scaffold is administered at a dose of approximately 3000 mg via intravenous administration. In some respects, a Tn3 scaffold is administered at a dose of approximately 1500 mg once every 2 weeks via intravenous administration. In some respects, a Tn3 scaffold is administered at a dose of approximately 1500 mg once every 4 weeks via intravenous administration. In some respects, a Tn3 scaffold is administered at a dose of approximately 1500 mg twice every 4 weeks thereafter via intravenous administration. In some respects, a Tn3 scaffold is administered at a dose of approximately 1500 mg every 2 weeks for 3 doses and thereafter every 4 weeks via intravenous administration. In some respects, a Tn3 framework is administered at a dose of approximately 1500 mg in weeks 0, 2, and 4, and subsequently every 4 weeks (Q4W).In some aspects, a Tn3 framework is administered at a dose of approximately 1500 mg in weeks 0, 2, and 4, and subsequently once every 4 weeks (Q4W) via intravenous administration. In others, a Tn3 framework is administered at a dose of approximately 1500 mg every 2 weeks for 7 doses. In others, a Tn3 framework is administered. Petition 870250087411, dated 09 / 26 / 2025, pp. 95 / 404 50 / 327 at a dose of approximately 1500 mg every 2 weeks for 7 doses via intravenous administration. In some cases, a Tn3 framework is administered at a dose of approximately 1500 mg every 4 weeks for 5 doses. In some cases, a Tn3 framework is administered at a dose of approximately 1500 mg every 4 weeks for 5 doses via intravenous administration. In some cases, a Tn3 framework is administered at a dose of approximately 3000 mg twice every 12 weeks subsequently, doses via intravenous administration. In some cases, a Tn3 framework is administered at a dose of approximately 3000 mg every 2 weeks for 3 doses and subsequently every 12 weeks via intravenous administration. In practice, a Tn3 framework is administered at a dose of approximately 3000 mg every 2 weeks for at least 2 weeks and subsequently every 12 weeks via intravenous administration.In practice, a Tn3 framework is administered at a dose of approximately 3000 mg every 4 weeks for at least 2 doses and subsequently every 12 weeks via intravenous administration.

[0072] In aspects, a method of disclosure comprises administering a Tn3 scaffold to a subject in need thereof at a dose of 3000 mg of a Tn3 scaffold every 12 weeks, with a dose of 3000 mg of a Tn3 scaffold in week 0 and week 4 via intravenous administration. In aspects, a method of disclosure comprises administering a Tn3 scaffold to a subject in need thereof at a dose of 1500 mg of a Tn3 scaffold every 4 weeks via intravenous administration, with a dose of 1500 mg of the Tn3 scaffold in week 0 and week 2. In aspects, a method of disclosure comprises the Petition 870250087411, dated 09 / 26 / 2025, page 96 / 404 51 / 327 administration of a Tn3 scaffold comprising SEQ ID NO: 22 or SEQ ID NO: 25 to a subject in need thereof at a dose of 3,000 mg of a Tn3 scaffold every 12 weeks, with a dose of 3,000 mg of a Tn3 scaffold in week 0 and week 4, by intravenous administration. In aspects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 22 or SEQ ID NO: 25 to a subject in need thereof at a dose of 1,500 mg of a Tn3 scaffold every 4 weeks by intravenous administration. In some respects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 22 or SEQ ID NO: 25 to a subject in need thereof at a dose of 1500 mg of a Tn3 scaffold every two weeks for administrations 3 and then every 4 weeks thereafter, by intravenous administration.In some respects, a method of disclosure comprises administering a Tn3 scaffold comprising SEQ ID NO: 22 or SEQ ID NO: 25 to a subject in need thereof at a dose of 3000 mg of a Tn3 scaffold every two weeks for administrations 3 and then every 12 weeks thereafter, by intravenous administration.

[0073] In some respects, a composition comprising a Tn3 framework is formulated for administration. In some respects, a Tn3 framework thereof is formulated at a concentration of at least about, or at most about: 1 mg / ml, 2 mg / ml, 3 mg / ml, 4 mg / ml, 5 mg / ml, 6 mg / ml, 7 mg / ml, 8 mg / ml, 9 mg / ml, 10 mg / ml, 15 mg / ml, 20 mg / ml, 25 mg / ml, 30 mg / ml, 35 mg / ml, 40 mg / ml, 45 mg / ml, 50 mg / ml, 55 mg / ml, 60 mg / ml, 65 mg / ml, 70 mg / ml, 75 mg / ml, 80 mg / ml, 85 mg / ml, 90 mg / ml, 95 mg / ml, 100 mg / ml, 105 mg / ml, 110 mg / ml, 115 mg / ml, 120 mg / ml, Petition 870250087411, dated 09 / 26 / 2025, page 97 / 404 52 / 327 125 mg / ml, 130 mg / ml, 135 mg / ml, 140 mg / ml, 145 mg / ml, 150 mg / ml, 155 mg / ml, 160 mg / ml, 165 mg / ml, 170 mg / ml, 175 mg / ml, 180 mg / ml, 185 mg / ml, 190 mg / ml, 195 mg / ml, 200 mg / ml, 205 mg / ml, 210 mg / ml, 215 mg / ml, 220 mg / ml, 225 mg / ml, 230 mg / ml, 235 mg / ml, 240 mg / ml, 245 mg / ml, 250 mg / ml, 255 mg / ml, 260 mg / ml, 265 mg / ml, 270 mg / ml, 275 mg / ml, 280 mg / ml, 285 mg / ml, 290 mg / ml, 295 mg / ml, 300 mg / ml, 305 mg / ml, 310 mg / ml, 315 mg / ml, 320 mg / ml, 325 mg / ml, 330 mg / ml, 335 mg / ml, 340 mg / ml, 345 mg / ml, 350 mg / ml, 355 mg / ml, 360 mg / ml, 365 mg / ml, 370 mg / ml, 375 mg / ml, 380 mg / ml, 385 mg / ml, 390 mg / ml, 395 mg / ml or up to about 400 mg / ml. In some respects, an effective dose of Tn3 framework can be formulated at a concentration of about 100 mg / ml.

[0074] In some respects, the administration of a Tn3 framework is effective in eliminating disease in a subject in need of it. In some respects, the administration of a Tn3 framework is effective in reducing disease in a subject in need of it. In some cases, the administration of a Tn3 framework is effective in eliminating or reducing disease in a subject in need of it for at least approximately 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 2 years, 3 years, 4 years, at least approximately 5 years, or for the lifetime of a subject. In some respects, the administration of a Tn3 framework is effective in eliminating disease in a subject who requires it for at least approximately 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, or at least approximately 12 weeks. In some respects, the administration of a Petition 870250087411, dated 09 / 26 / 2025, pp. 98 / 404 53 / 327 The Tn3 framework is effective in eliminating or reducing disease in a subject who needs it for at least about 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or at least about 12 months. In aspects, the administration of a Tn3 framework is effective in eliminating or reducing disease in a subject who needs it for at least about 1 year, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, or at least about 10 years. In aspects, the administration of a Tn3 framework is effective in eliminating or reducing disease for the lifetime of a subject who needs it.

[0075] In aspects, a subject who needs it is administered a Tn3 framework. In some respects, a subject in need of such treatment is administered a Tn3 framework as first-line therapy.In some respects, a subject has not been administered one or more prior and / or concurrent therapies for the treatment of SS prior to administration of a Tn3 framework. In some respects, a subject in need of the same has been administered one or more prior and / or concurrent therapies for the treatment of SS prior to administration of a Tn3 framework. In some respects, a prior and / or concurrent therapy comprises a medication and / or vaccine (e.g., over-the-counter [OTC] or prescription medications, recreational medications, vitamins, and / or herbal supplements). Exemplary prior and / or concurrent therapies are described below. B-cell depletion biological therapy

[0076] In some respects, a subject was previously treated with a biological therapy for B cell depletion (by Petition 870250087411, dated 09 / 26 / 2025, p. 99 / 404 54 / 327 example, rituximab, ocrelizumab, inebilizumab, ofatumumab, belimumab, or ianalumab, or combinations thereof). In aspects, a subject was previously treated with B-cell depleting biological therapy more than about 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or about 12 months prior to screening. In aspects, a subject was previously treated with B-cell depleting biological therapy more than about 3 months prior to screening. In aspects, a subject was previously treated with B-cell depleting biological therapy more than about 12 months prior to screening. In aspects, a subject was previously treated with belimumab more than about 3 months prior to screening. In some respects, a subject has been previously treated with rituximab, ocrelizumab, inebilizumab, ofatumumab, or ianalumab, or combinations thereof, more than approximately 12 months prior to screening. Corticosteroids

[0077] In aspects, the subject was previously treated with a corticosteroid. In aspects, the subject is concomitantly treated with a corticosteroid. In aspects, a corticosteroid is a glucocorticoid. In aspects, a subject was previously treated with an injectable corticosteroid (e.g., intra-articular [IA] or intramuscular [IM]) or an oral dose of prednisone (or equivalent) of >10 mg per day. In aspects, a subject was previously treated with an injectable corticosteroid (e.g., intra-articular [IA] or intramuscular [IM]) or an oral dose (e.g., prednisone or equivalent) of >10 mg per day more than 6 weeks prior to screening. In aspects, a Petition 870250087411, dated 09 / 26 / 2025, page 100 / 404 55 / 327 subjects were previously treated with a systemic corticosteroid for 2 or more weeks more than 6 months prior to screening. In aspects, a subject is concomitantly treated with an oral corticosteroid at a dose of <10 mg / day (e.g., prednisone or equivalent) where the dose is stable for at least 2 weeks or more prior to screening. In aspects, a subject is concomitantly treated with an inhaled corticosteroid, intranasal corticosteroid, or topical corticosteroid at a stable dose. In aspects, the subject is not treated with a corticosteroid.

[0078] In aspects, a subject who has an ESSDAI score of h 5 before administration, is treated or has been previously treated with a corticosteroid (e.g., dose <10 mg / day). In aspects, the subject is treated with 1500 mg or 3000 mg of a Tn3 development framework.

[0079] In aspects, a subject who has an ESSDAI score of 5 and an ESSPRI score of 5 before administration is not administered with a corticosteroid. In aspects, the subject is treated with 1500 mg or 3000 mg of a Tn3 development framework. Antimalarials

[0080] In some respects, a subject is concomitantly treated with an antimalarial (e.g., chloroquine, hydroxychloroquine, quinacrine, and similar drugs). In some respects, the subject has been previously treated with an antimalarial. In some respects, a subject is concomitantly treated with an antimalarial and initiated the antimalarial more than 8 weeks prior to screening. In some respects, a subject is concomitantly treated with an antimalarial and maintains a Petition 870250087411, dated 09 / 26 / 2025, page 101 / 404 56 / 327 stable dose of antimalarial drug more than 8 weeks before screening. Immunomodulatory agent

[0081] In some respects, the subject was previously treated with an immunomodulatory agent. In some respects, the subject is concomitantly treated with an immunomodulatory agent. In some respects, an immunomodulatory agent is also a disease-modifying antirheumatic drug (DMARD) (e.g., methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, plaquenil, cevimeline, pilocarpine, cyclosporine, etanercept, baricitinib, tofacitinib, upadacitinib, infliximab, adalimumab, certolizumab, and golimumab, and combinations thereof). In some respects, the subject was previously treated with a DMARD. In some respects, a subject was previously treated with a DMARD 4 weeks or more prior to screening. In some respects, a subject was previously treated with cevimeline, pilocarpine, and / or cyclosporine 2 weeks or more prior to screening. In some aspects, a subject is concomitantly treated with cevimeline, pilocarpine, and / or cyclosporine, and the dose is stable from 2 weeks or more before screening. NSAID

[0082] In aspects, a subject has been previously treated with a nonsteroidal anti-inflammatory drug (NSAID). In aspects, the subject is concomitantly treated with an NSAID. Exemplary NSAIDs may include, but are not limited to, aspirin, ibuprofen, naproxen, and nabumetone. In aspects, a subject is treated with an NSAID and the NSAID has been at a stable dose for at least 2 weeks or more prior to screening. In aspects, a subject is treated with an NSAID and the NSAID is not Petition 870250087411, dated 09 / 26 / 2025, page 102 / 404 57 / 327 administered for the first time at least 2 weeks or more before screening. Cholinergic agonist

[0083] In some respects, a subject has been previously treated with a cholinergic agonist. In some respects, the subject is concomitantly treated with a cholinergic agonist. Exemplary cholinergic agonists include, but are not limited to, cevimeline and pilocarpine.

[0084] In some respects, one or more prior and / or concurrent therapies are administered more than about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 20, about 25, about 30, about 35, about 40, about 45 or about 52 weeks or more before administration of a Tn3 scaffold. In some respects, one or more prior or concurrent therapies are administered more than about 1 week, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, or about 12 months or more before administration of a Tn3 scaffold.

[0085] The dosage and administration regimen of a Tn3 scaffold disclosed herein may be such that any therapeutic effect achieved from the administration of a Tn3 scaffold to treat any autoimmune disease or disorder may be considered to be of long duration. A long-term effect of a Tn3 scaffold in treatment Petition 870250087411, dated 09 / 26 / 2025, pp. 103 / 404 58 / 327 of an autoimmune disease or disorder is one in which the therapeutic effect achieved by a Tn3 scaffold is maintained (although a Tn3 scaffold is no longer administered) for at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 16 weeks, at least 20 weeks, at least 24 weeks, at least 28 weeks, at least 32 weeks, at least 36 weeks, at least 40 weeks, at least 44 weeks, at least 48 weeks, at least 1 year, at least 2 years, or up to approximately at least 5 years after administration of the last dose of a course of a Tn3 scaffold. In some respects, less frequent dosing of any of the compositions provided herein may be advantageous.Exemplary advantages of less frequent dosing include, but are not limited to, reduced frequency of side effects associated with an administered composition, reduced treatment-associated toxicity, increased quality of life for treated subjects, and the like. Analyses

[0086] In aspects, a subject is evaluated. In aspects, a subject is evaluated as part of a treatment. In aspects, a subject who has a confirmed or probable autoimmune disease or disorder (e.g., SS) is evaluated as part of a treatment. An analysis may occur at any point before, during, or after administration with a Tn3 framework. In aspects, an analysis is performed before the start of an administration. In aspects, an analysis is performed concurrently with an administration. In aspects, an analysis is performed after the end of an administration. Petition 870250087411, dated 09 / 26 / 2025, pp. 104 / 404 59 / 327

[0087] Any of the assessments mentioned below can occur at any time. In some aspects, a subject is assessed by minute, hour, day, week, month, or year. In aspects, an analysis is completed twice a day, fortnightly, bimonthly, or semiannually. In aspects, an analysis is performed starting from day -28, -27, -26, -25, -24, -23, -22, -21, -20, -19, -18, -17, -16, -15, -14, -13, -12, -11,- 10, -9, -8 , -7 , -6, -5, -4, -3 , -2, -1, 0, 1 •, 2, 3, 4, 5, 6 , 7, 8, 9, 10, 11, 12, 13, 14 , 15, 16, 17, 18, 19 , 20, 21, 22, 23, 24 , 25 , 26, 27, 28, 29 , 30, 31, 32, 33, 34 , 35, 36, 37, 38, 39 , 40 , 41, 42, 43, 44 , 45, 46, 47, 48, 49 , 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, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191,192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, Petition 870250087411, dated 09 / 26 / 2025, pp. 105 / 404 60 / 327 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380 381, 382, ​​383, 384, 385, 386, 387, 388, 389, 390, 391, 392 or up to approximately 393 days ±7 days post-treatment.

[0088] In some respects, SS treatment may be characterized by a reduction of at least about 5%, about 10%, about 15%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99%, or even about 100% of the clinical symptoms of the disease or disorder, or by a reduction in inflammation, or by a reduction in the biomarkers of the disease or disorder, relative to their levels before treatment with a Tn3 scaffold.A reduction in any of these symptoms, or inflammation, or biomarkers, may be a reduction in symptoms, or inflammation, or biomarkers of at least about 10%, 15%, 20%, 25%, about 30%, about 40%, about 50%, about 60%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99%, or even about 100% relative to their levels before the start of treatment with a Tn3 framework. A reduction may be such that SS is characterized as being in remission. Petition 870250087411, dated 09 / 26 / 2025, pp. 106 / 404 61 / 327

[0089] In some aspects, a subject is assessed, and a baseline disease measurement is determined. In some aspects, a subject is assessed, and a baseline disease measurement is determined at any time before, during, or after administration with a Tn3 scaffold. In some aspects, an analysis is performed, and a baseline disease measurement is determined before administration with a Tn3 scaffold. In some aspects, an analysis is performed, and a baseline disease measurement is determined concomitantly with administration of a Tn3 scaffold. In some aspects, an analysis is performed, and a baseline disease measurement is determined after administration of a Tn3 scaffold.

[0090] In some respects, a baseline disease measurement increases or decreases in response to a developmental administration or a lack thereof. In some respects, a baseline disease measurement may increase and indicate effective treatment of a disease or disorder. In some respects, a baseline disease measurement may decrease and indicate effective treatment of a disease or disorder. In some respects, a baseline disease measurement increases or decreases after administration with a Tn3 scaffold. In some respects, a baseline disease measurement may increase after administration with a Tn3 scaffold and indicate effective treatment of a disease or disorder. In some respects, a baseline disease measurement may decrease after administration with a Tn3 scaffold and indicate effective treatment of a disease or disorder.

[0091] In some respects, a baseline disease measurement is compared to the subject's disease measurement after administration of a Tn3 scaffold.In some respects, a disease measurement of a subject administered a Tn3 framework increases. Petition 870250087411, dated 09 / 26 / 2025, page 107 / 404 62 / 327 compared to a baseline disease measurement taken before administration with a Tn3 scaffold. In aspects, a disease measurement of a subject administered a Tn3 scaffold decreases compared to a baseline disease measurement taken before administration with a Tn3 scaffold. In aspects, a disease measurement of a subject administered a Tn3 scaffold increases compared to a baseline disease measurement taken before administration with a Tn3 scaffold and indicates effective treatment. In aspects, a disease measurement of a subject administered a Tn3 scaffold decreases compared to a baseline disease measurement taken before administration with a Tn3 scaffold and indicates effective treatment.

[0092] In aspects, an analysis comprises determining the effectiveness of the treatment. Effectiveness can be determined by any of the disclosure assessments. In aspects, effectiveness in preventing, reducing, or eliminating an autoimmune disease or disorder (e.g., SS) is determined by detecting a change in a European Alliance of Associations for Rheumatology (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) score. In aspects, the ESSDAI is reduced by approximately 1 point, approximately 2 points, approximately 3 points, approximately 4 points, approximately 5 points, approximately 6 points, approximately 7 points, approximately 8 points, approximately 9 points, approximately 10 points, or more from baseline. In some respects, the effectiveness in preventing, reducing, or eliminating an autoimmune disease or disorder (e.g., SS) is determined by detecting a change in a score on the EULAR Sjögren's Syndrome Patient-Reported Symptom Index (ESSPRI). In other respects, the Petition 870250087411, dated 09 / 26 / 2025, pp. 108 / 404 63 / 327 ESSPRI is reduced by about 1 point (ESSPRI [1]), about 1.5 points (ESSPRI [1,5]), about 2 points (ESSPRI [2]), about 3 points (ESSPRI [3]), about 4 points (ESSPRI [4]), about 5 points (ESSPRI [5]), about 6 points (ESSPRI [6]), about 7 points (ESSPRI [7]), about 8 points (ESSPRI [8]), about 9 points (ESSPRI [9]), about 10 points (ESSPRI

[10] ) or more from the baseline. In some respects, the effectiveness in preventing, reducing, or eliminating an autoimmune disease or disorder is determined by evaluating: pharmacokinetic parameters of a Tn3 framework used to treat a subject in need of it, a change from baseline in a subject's blood levels of IgM, rheumatoid factor (RF), sCD40L, CXCL13, the presence of antidrug antibodies (ADA), and combinations thereof.In some aspects, the effectiveness in preventing, reducing, or eliminating an autoimmune disease or disorder is determined by evaluating a subject's plasma immunoglobulin levels (IgM, IgG, and IgA), beta-2 microglobulin, high-sensitivity CRP, serum C3, C4, free light chains, cryoglobulins, and serum for anti-SSA (e.g., anti-Ro), anti-SSB (e.g., anti-LA), and IgG. In others, the effectiveness in preventing, reducing, or eliminating an autoimmune disease or disorder is determined by evaluating rheumatoid factor(s) (RF). RFs are antibodies with various isotypes and affinities, directed against the Fc portion of immunoglobulin G. The most common rheumatoid factor is an IgM RF, although other immunoglobulin types, including IgG and IgA, may be found.

[0093] In some respects, the effectiveness in preventing, reducing, or eliminating an autoimmune disease or disorder is determined by evaluating a subject's leukocyte population, by. Petition 870250087411, dated 09 / 26 / 2025, pp. 109 / 404 64 / 327 example, B lymphocytes. The subject's B cells may be present in the peripheral blood. In some aspects, the subject's B cells are present in the salivary glands. In some aspects, a developing subject exhibits disturbed B cell homeostasis comprising decreased frequencies and / or absolute numbers of peripheral CD27+ memory B cells, in particular a reduction in the circulating CD27+ IgM+ subpopulation. In some aspects, a developing subject comprises an increase in the number of naive non-switched peripheral memory B cells (CD19+, CD27-, IgD+) with a decrease in the number of CD19+, CD27+, IgD- peripheral memory B cells. In some aspects, a developing subject comprises an increased frequency of transitional B cells and mature naive B cells expressing polyreactive antibodies in the peripheral blood. The compositions and methods in the present document are effective in resolving any of the B cell level disorders described in the present document.For example, a subject treated with a revealing composition may exhibit increased frequencies and / or absolute numbers of peripheral CD27+ memory B cells after administration of a revealing composition (e.g., a Tn3 scaffold). In aspects, a subject who was administered with a revealing composition exhibits an increase in the CD27+ IgM+ subpopulation compared to a baseline level of the subject. In aspects, a revealing subject exhibits a decrease in the number of unswitched peripheral memory B cells (CD19+, CD27-, IgD+) with an increase in the number of peripheral memory B cells (CD19+, CD27+, IgD-) compared to baseline. Petition 870250087411, dated 09 / 26 / 2025, page 110 / 404 65 / 327

[0094] In some respects, efficacy in preventing, reducing, or eliminating an autoimmune disease or disorder is determined by evaluating a subject's population of CD27+ memory B cells, marginal zone B cells, plasmablasts, plasma cells, and combinations thereof. In some respects, efficacy in preventing, reducing, or eliminating an autoimmune disease or disorder is determined by evaluating a subject's B cell population, for example, Ki67+ post-switching memory B cells (CD27+ / IgD- / CD19+ cells), Ki67+ / CD27+ memory B cells, CD27br / CD38br / IgD- plasmablasts, CD11alta memory B cells, or CD11cbr atypical memory B cells, or combinations thereof. In some respects, efficacy in preventing, reducing, or eliminating an autoimmune disease or disorder is determined by evaluating a subject's TFH cell level. In some aspects, a subject's TFH cell level is assessed by evaluating the percentage of CXCR5+ and / or ICOS+ positive cells.In some aspects, a subject's TFH cell level is assessed by evaluating the percentage of CXCR5+ and / or ICOS+ positive cells compared to the percentage of CD4+ and / or CD3+ cells identified.

[0095] In some respects, a subject of the revelation exhibits a B-cell disturbance within an exocrine gland infiltrate. For example, a disturbance may comprise one or more of the following: a presence of germinal center-like structures, increased frequency of IgG plasma cells compared to a healthy subject, autoreactive B cells and / or plasma cells, increased levels of B-cell-associated cytokines and chemokines (e.g., IL-6, IL-21, BAFF, APRIL, CXCL12, CXCL13) compared to Petition 870250087411, dated 09 / 26 / 2025, page 111 / 404 66 / 327 A healthy subject, presence of clonal populations of B cells and / or autoantibody-producing plasma cells, and any combination thereof. In aspects, a subject administered with a development composition exhibits reduced levels of a B cell-associated cytokine or chemokine selected from the group consisting of: IL-6, IL-21, BAFF, APRIL, CXCL12, CXCL13 and any combination thereof. In aspects, a reduction is at least about or at most about: 5%, 10%, 20%, 40%, 60%, 80%, 100% or 150%. In aspects, assessing the level of one or more parameters (e.g., B cells) comprises quantifying the number of said parameter(s) in a sample from a subject. Inclusion Analysis

[0096] In some respects, a subject in need of the same is assessed before the start of treatment.

[0097] In some respects, a subject with the same need may be male or female. In some respects, a subject with the same need is an adult. In some respects, a subject with the same need may be at least about 18 years old. In some respects, a subject is between 18 and 100 years old.

[0098] In some respects, a subject with the same needs has a diagnosis of SS. In some respects, a subject with the same needs has a diagnosis of SS according to the criteria of the American College of Rheumatology (ACR). In some respects, a subject with the same needs has a diagnosis of SS according to the criteria of the American College of Rheumatology (ACR) 2016. In some respects, a subject with the same needs has an ESSPRI score of 5. In Petition 870250087411, dated 09 / 26 / 2025, page 112 / 404 67 / 327 aspects, a subject in need of the same has an ESSDAI score of < 5. In aspects, a subject in need of the same has an ESSDAI score of < 5. In aspects, a subject in need of the same is positive for anti-SSA autoantibodies (e.g., anti-Ro). In aspects, a subject in need of the same is positive for rheumatoid factor (RF). In aspects, a subject in need of the same is positive for both anti-SSA autoantibodies (e.g., anti-Ro) and RF. In aspects, a subject in need of the same has a diagnosis of rheumatoid arthritis (RA). In aspects, a subject in need of the same has a diagnosis of systemic lupus erythematosus (SLE). In aspects, a subject in need of the same has coexisting SS and RA. In aspects, a subject in need of the same has coexisting SS and SLE.An inclusion analysis of the disclosure can be evaluated at approximately -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, up to approximately 0 days post-treatment initiation. ESSPRI

[0099] In some respects, an analysis may include an ESSPRI assessment. In some respects, an ESSPRI assessment is a self-assessment (Seror et al., 2011). In some respects, an ESSPRI assessment uses a numerical analog scale from 0 to 10 (ranging from 0 [no symptoms] to 10 [maximum imaginable severity]), one for the analysis of each of the 3 domains: dryness, fatigue, and pain (joint and / or muscle). Fatigue of Petition 870250087411, dated 09 / 26 / 2025, page 113 / 404 68 / 327 ESSPRI has been shown to be one of the main predictors of poor quality of life (QoL) in a subject with SS, along with pain. In aspects, the ESSPRI dryness domain has been shown to correlate with sleep quality, presence and degree of anxiety and depression (Gandia et al., 2014) and overall QoL (Schmalz et al., 2020). In aspects, a subject with a need for it has an ESSPRI score of 5, which can be considered the cutoff point for an unsatisfactory symptom state (Seror et al., 2016).

[0100] The domain weights may be identical and the average of the 3 domain scores represents the final score. The recovery period may be stated in each question as the last 2 weeks. In aspects, a subject has an ESSPRI score of approximately 1 to approximately 100 before the administration of a disclosure composition. In aspects, a subject has an ESSPRI score of approximately 1-10, 5-15, 10-20, 15-25, 20-30, 25-35, 30-40, 35-45, 40-50, 45-55, 50-60, 55-65, 60-70, 65-75, 70-80, 75-85, 80-90, 90-100 or approximately 95-100 before the administration of a disclosure composition. In some aspects, a subject has an ESSPRI score of around 5-6, 5-7, 6-8, 6-9, or around 5-10 before the administration of a revealing composition.

[0101] ESSPRI[1.5] refers to a reduction of at least 1.5 points from baseline in an ESSPRI score.

[0102] In aspects, treatment with a developmental composition is effective in reducing an ESSPRI score. In aspects, an ESSPRI score is reduced by at least approximately: 0.6, 0.7, 0.8, 0.9 1, 1.1, 1.3, 1.4, 1.5, 1.6, Petition 870250087411, dated 09 / 26 / 2025, page 114 / 404 69 / 327 1.7, 1.8, 1.9, 2, 3, 4, 5, 6, 7, 8, 9, or 10 points. In aspects, an ESSPRI score is reduced by approximately 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 3, 4, 5, 6, 7, 8, 9, or 10 points. In aspects, the ESSPRI score is reduced by approximately 0.6-5, 0.6-10, 110, 1-5, 2-10, or 5-10 points. In some respects, an ESSPRI score is reduced compared to an otherwise comparable method where the subject of the otherwise comparable method is not administered with a Tn3 framework, for example, the reduction may be approximately: 10%, 15%, 20%, 25%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or even 100% compared to an ESSPRI score in an otherwise comparable method where the subject of the otherwise comparable method is not administered with a Tn3 framework.In some respects, an ESSPRI score is reduced compared to an otherwise comparable method where the subject of the otherwise comparable method is not administered with a Tn3 framework, for example, the reduction may be around: 10%, 15%, 20%, 25%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or even 100% compared to baseline.

[0103] In aspects, the ESSPRI score is assessed at approximately -28 days, -27 days, -26 days, -25 days, -24 days, - 23 days, -22 days, -21 days, -20 days, -19 days, -18 days, - 17 days, -16 days, -15 days, -14 days, -13 days, -12 days - 11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 Petition 870250087411, dated 09 / 26 / 2025, page 115 / 404 70 / 327 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least about 56 weeks after starting treatment. In terms of aspects, the ESSPRI score is evaluated at approximately Day -28, Day -27, Day -26, Day -25, Day -24, Day -23, Day -22, Day -21, Day -20, Day 19, Day -18, Day -17, Day -16, Day -15, Day -14, Day -13, Day -12, Day -11, Day -10, Day -9, Day -8, Day -7, Day -6, Day -5, Day -4, Day -3, Day -2, Day -1, Day 0, Day 1, Day 29 (±4 days), Day 57 (±7 days), Day 85 (±7 days), Day 113 (±7 days), Day 141 (±7 days), Day 169 (±7 days), Day 197 (±7 days), Day 225 (±7 days), Day 253 (±7 days), Day 281 (±7 days), Day 309 (±7 days), or approximately Day 337 (±7 days) post-treatment initiation. As described in this document, an ESSPRI score can be assessed at any time before, during, or after treatment with a Tn3 disclosure framework. Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form Survey 10a

[0104] In aspects, an analysis comprises a survey PROMIS Fatigue Survey 10th Anniversary. A PROMIS Fatigue Survey 10th Anniversary can assess a range of self-reported symptoms, from mild subjective feelings of tiredness to a sensation of fatigue. Petition 870250087411, dated 09 / 26 / 2025, page 116 / 404 71 / 327 overwhelming, debilitating, and sustained exhaustion. In aspects, fatigue is divided into the experience of fatigue (frequency, duration, and intensity) and the impacts of fatigue on physical, mental, and social activities. In aspects, a PROMIS fatigue survey assesses symptoms in the previous week. In aspects, a PROMIS fatigue survey may include assessing a subject in need of the same, administered with a Tn3 developmental framework compared to baseline. In aspects, a subject's self-reported symptoms are improved compared to an otherwise comparable method, where the subject in the otherwise comparable method is not administered with a Tn3 developmental framework.

[0105] In aspects, a PROMIS fatigue research for Tn3 framework of revelation can be evaluated at approximately -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks,48 weeks, 49, Petition 870250087411, dated 09 / 26 / 2025, page 117 / 404 72 / 327 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least approximately 56 weeks post-treatment initiation. In some respects, PROMIS fatigue is analyzed at any time before, during, or after treatment with a Tn3 development framework. Level 5 EQ-ED (EQ-5D-5L)

[0106] In some respects, an analysis may comprise an EQ-5D-5L survey. The EQ-5D-5L survey provided a subject with information encompassing five dimensions of their health status: mobility, self-care, usual activities, pain / discomfort, and anxiety / depression. The EQ-5D-5L survey has five response levels: no problems (1), mild problems (2), moderate problems (3), severe problems (4), unable to / extreme problems. The subject indicates their health by choosing the most appropriate response level for each of the five dimensions. In some respects, an EQ-5D-5L survey assesses symptoms in the previous week. In some respects, an EQ-5D-5L survey may comprise analyzing a subject in need of the same, administered with a Tn3 disclosure framework compared to baseline.In some aspects, a subject's self-reported symptoms are improved compared to an otherwise comparable method, where the subject of the otherwise comparable method is not administered with the Tn3 disclosure framework.

[0107] In some respects, an EQ-5D-5L search for Tn3 framework of revelation can be evaluated at approximately - 28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days Petition 870250087411, dated 09 / 26 / 2025, page 118 / 404 73 / 327 -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least about 56 weeks post-treatment initiation. In aspect, EQ-5D-5L is evaluated at any time before, during or after treatment with a Tn3 Revelation Framework. 36-item Short Form Survey (SF-36)

[0108] In some respects, an analysis may comprise an SF- 36. The SF-36 is a 36-item comprehensive health status assessment that can capture information on 8 health domains: Physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health. The SF-36 provides scores for each domain, as well as 2 summary scores based on psychometrics: Physical Component Score (PCS) and Mental Component Score (MCS). The recovery period for the acute version is one week (i.e., the last week). The SF-36 is a widely used and validated occupational quality of life score that... Petition 870250087411, dated 09 / 26 / 2025, page 119 / 404 74 / 327 encompasses multiple domains and is sensitive to change (Hemingway et al., 1997). The SF-36 PCS is derived from multiple physical domains and has been shown to be validated and responsive in related autoimmune diseases (Kosinski et al., 1999; Devilliers et al., 2015). The SF-36 PCS score can comprehensively capture improvements in physical activity and mental functioning, as these scores are based on the analysis of various symptoms relevant to subjects with SS, such as pain and mental and physical health (Sjogren Foundation 2021).

[0109] In aspects, an SF-36 study may comprise evaluating a subject in need of the same, administered with a Tn3 framework compared to baseline. In aspects, a subject's functional health and well-being is improved compared to an otherwise comparable method, where the subject of the otherwise comparable method is not administered with a Tn3 framework.

[0110] In some respects, an SF-36 for a Tn3 framework of revelation can be estimated at approximately 28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 Petition 870250087411, dated 09 / 26 / 2025, page 120 / 404 75 / 327 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least about 56 weeks after starting treatment. In terms of aspects, an SF-36 for a Tn3 development scaffold can be assessed at approximately Day 1, Day 29 (±4 days), Day 57 (±7 days), Day 85 (±7 days), Day 113 (±7 days), Day 141 (±7 days), Day 169 (±7 days), Day 197 (±7 days), Day 225 (±7 days), Day 253 (±7 days), Day 281 (±7 days), Day 309 (±7 days), or at approximately Day 337 (±7 days) post-treatment initiation. In terms of aspects, SF-36 is assessed at any time before, during, or after treatment with a Tn3 development scaffold. Location of Dryness Improvement Items

[0111] The assessments of the disclosure may include location of dryness improvement items. The Location of Dryness Improvement Items is a series of questions that assess the location of dryness. In aspects, the questions are completed during screening and have subjects rank dryness locations as most important for them to improve (1 = most important location for improvement, 4 = least important location for improvement). Subsequent questions include having subjects choose the location that has improved the most (if any) at 2 different time points: Week 24 (Question 2) and Week 48 (Question 3). Additional time points are contemplated in this document including 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 Petition 870250087411, dated 09 / 26 / 2025, page 121 / 404 76 / 327 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least about 56 weeks post-initiation of treatment. In some aspects, the location of dryness improvement is analyzed at any time before, during, or after treatment with a Tn3 development framework.

[0112] In aspects, treatment with a development composition is effective in reducing dryness as determined by the location of the dryness improvement assay. In aspects, a subject treated with a development composition experiences reduced dryness in one or more locations with dryness identified prior to treatment. Dryness may be self-identified or clinically identified by a professional. In aspects, reduced dryness is determined by self-identification and comprises a reduction in self-identification of at least about or at most about 1 event, 2 events, 3 events, 4 events, or 5 events. Functional Analysis of Chronic Disease Therapy (FACIT) Fatigue

[0113] In some respects, an analysis may include a FACIT-Fatigue assessment. The FACIT-Fatigue is a 13-item questionnaire completed by the subject used to assess the impacts of fatigue. The FACIT-Fatigue recovery period is 7 days. Responses are in the range of 0 (none) to 4. Petition 870250087411, dated 09 / 26 / 2025, p. 122 / 404 77 / 327 (very). In some aspects, a FACIT-Fatigue score for a question is approximately 0, 1, 2, 3, or even approximately 4. In others, a FACIT-Fatigue score for a question is in the range of approximately 0 to approximately 4 or approximately 1 to approximately 4. To calculate the total score, negatively stated items are reversed by subtracting the response from 4. The final scores are the sum of the responses and are in the range of 0 to 52. In some aspects, a total FACIT-Fatigue score is approximately 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, or even up to about 52. Higher scores indicate better quality of life. In some respects, a FACITFatique assessment may involve evaluating a subject in need of the same, administered with a Tn3 framework compared to baseline.In some respects, the subject's FACIT-Fatigue score is increased compared to an otherwise comparable method, where the subject of the otherwise comparable method is not administered with a Tn3 framework.

[0114] In aspects, treatment with a developmental composition is effective in reducing a FACIT-Fatigue score. In aspects, a FACIT-Fatigue score is reduced by at least approximately: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, or 52 points. In aspects, a FACIT-Fatigue score is reduced by up to approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, or 52 points. In some aspects, the FACIT-Fatigue score is reduced by approximately 15, 2-10, 5-10, 5-20, 10-20, 25-45, or 20-30 points. Petition 870250087411, dated 09 / 26 / 2025, page 123 / 404 78 / 327

[0115] In some respects, a FACIT-Fatigue assessment of a Tn3 framework of the revelation can be assessed at approximately - 28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks,or at least about 56 weeks post-treatment initiation. In aspects, a FACIT-Fatigue assessment for a Tn3 framework of development can be evaluated at approximately Day 1, Day 29 (±4 days), Day 57 (±7 days), Day 85 (±7 days), Day 113 (±7 days), Day 141 (±7 days), Day 169 (±7 days), Day 197 (±7 days), Day 225 (±7 days), Day 253 (±7 days), Day 281 (±7 days), Day 309 (±7 days) or at approximately Day 337 (±7 days) post-treatment initiation. In aspects, FACIT-Fatigue is analyzed at any time before, during, or after treatment with a Tn3 disclosure framework. Visual Analogue Scale (VAS) for Eye, Oral and / or Vaginal Dryness Petition 870250087411, dated 09 / 26 / 2025, page 124 / 404 79 / 327

[0116] In some respects, an analysis may comprise a VAS of ocular, oral, and / or vaginal dryness. The Oral / Ocular / Vaginal VAS consists of 3 instruments that use continuous 100 mm VAS scales (0 mm = best, 100 mm = worst) to assess the change in severity of oral, ocular, and vaginal dryness over the course of the study. The subject is asked to place a line perpendicular to the VAS line at the point representing the intensity of symptoms over the past 2 weeks. The oral VAS assesses the question: How dry does the mouth feel most of the time (not dry at all 0 mm; desert-dry 100 mm). The ocular VAS assesses the question: How do the eyes feel most of the time (not dry 0 mm; very dry 100 mm). The vaginal VAS asks respondents (as appropriate) to rate symptoms of vaginal dryness (no symptoms 0 mm; worst possible symptoms 100 mm).In terms of aspects, an Oral / Ocular / Vaginal Visual Analogue Scale (VAS) test is scored on a scale of approximately 0 to approximately 100, approximately 1 to approximately 100, approximately 10 to approximately 100, or approximately 0 to approximately 90. In terms of aspects, an ocular / oral / vaginal VAS survey is scored from approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 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, 99, up to approximately 100. In some aspects, an EVA assessment Oral / Ocular / Vaginal assessment can be used to evaluate a subject in need of the same administered with a Tn3 framework compared to baseline. In aspects, the VAS score Petition 870250087411, dated 09 / 26 / 2025, page 125 / 404 80 / 327 A subject's Oral / Ocular / Vaginal score is reduced compared to an otherwise comparable method, where the subject of the otherwise comparable method is not administered with a Tn3 scaffold. In aspects, a baseline Oral / Ocular / Vaginal VAS score is reduced by approximately 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or even approximately 100% compared to a subject's Oral / Ocular / Vaginal VAS score before administration of a Tn3 scaffold.

[0117] In some aspects, treatment with a developmental composition is effective in reducing an Oral / Ocular / Vaginal VAS score. In some aspects, the Oral / Ocular / Vaginal VAS score is reduced by at least approximately: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50 or 55 points. In some aspects, an Oral / Ocular / Vaginal VAS score is reduced by up to approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or even up to approximately 100 points. In some aspects, the Oral / Ocular / Vaginal VAS score is reduced by approximately 1-5, 2-10, 5-10, 5-20, 10-20, 20-30, 30-40, 40-50, 50-60, 60-70, 70-80, 80-90 or approximately 90-100 points.

[0118] In aspects, an Oral / Ocular / Vaginal VAS assessment of a Tn3 framework of the development can be evaluated at approximately -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 Petition 870250087411, dated 09 / 26 / 2025, page 126 / 404 81 / 327 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least Approximately 56 weeks post-treatment initiation. In aspects, an Oral / Ocular / Vaginal VAS assessment for a Tn3 disclosure framework can be evaluated at approximately Day 1, Day 29 (±4 days), Day 57 (±7 days), Day 85 (±7 days), Day 113 (±7 days), Day 141 (±7 days), Day 169 (±7 days), Day 197 (±7 days), Day 225 (±7 days), Day 253 (±7 days), Day 281 (±7 days), Day 309 (±7 days) or at approximately Day 337 (±7 days) post-treatment initiation. In aspects, Oral / Ocular / Vaginal dryness VAS is evaluated at any time before, during, or after treatment with a Tn3 disclosure framework. Patient Global Impression of Severity (PGIS)

[0119] In some respects, an analysis may comprise a PGIS survey. The PGIS is a single-item questionnaire designed to capture a subject's perception of the severity of their worst overall SS symptoms (e.g., pain, fatigue, and / or dryness) over the past 7 days on a 5-point categorical response scale (1=none, 2=mild, 3=moderate, 4=severe, or 5=very severe). In some respects, a PGIS score may comprise assessing a subject's need for the same, Petition 870250087411, dated 09 / 26 / 2025, page 127 / 404 82 / 327 administered with a Tn3 framework compared to baseline. In aspects, a subject's PGIS score is decreased compared to an otherwise comparable method, where the subject in the otherwise comparable method is not administered a Tn3 framework. A reduction may be of approximately 1, 2, 3, 4, or even approximately 5 points. In aspects, a subject receives 3 symptom-specific PGIS items (e.g., pain, fatigue, and / or dryness) as well as a general symptom PGIS. A global symptom PGIS may comprise additional symptoms beyond pain, fatigue, and / or dryness.

[0120] In aspects, treatment with a composition of the revelation is effective in reducing a PGIS score. In aspects, a PGIS score is reduced by at least approximately: 1, 2, 3, 4, or 5 points. In aspects, a PGIS score is reduced by up to approximately 1, 2, 3, 4, or 5 points. In aspects, a PGIS score is reduced by approximately 1-5, 25, 1-4, or 3-5 points.

[0121] In terms of aspects, the PGIS search is evaluated at approximately -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 Petition 870250087411, dated 09 / 26 / 2025, page 128 / 404 83 / 327 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least about 56 weeks after starting treatment. In terms of aspects, the PGIS research can be evaluated on approximately Day -28, Day -27, Day 26, Day -25, Day -24, Day -23, Day -22, Day -21, Day -20, Day -19, Day -18, Day -17, Day -16, Day -15, Day -14, Day 13, Day -12, Day -11, Day -10, Day -9, Day -8, Day -7, Day -6, Day -5, Day -4, Day -3, Day -2, Day -1, Day 0, Day 1, Day 29 (±4 days), Day 57 (±7 days), Day 85 (±7 days), Day 113 (±7 days), Day 141 (±7 days), Day 169 (±7 days), Day 197 (±7 days), Day 225 (±7 days), Day 253 (±7 days), Day 281 (±7 days), Day 309 (±7 days), or approximately Day 337 (±7 days) after starting treatment.In some aspects, PIGS is analyzed at any time before, during, or after treatment with a Tn3 framework of the revelation. Patient Global Impression of Change (PGIC)

[0122] In some respects, an analysis may comprise a PGIC survey. The PGIC is a single-item questionnaire designed to capture a subject's perception of change in their SS symptoms (e.g., pain, fatigue, and / or dryness) from the start of treatment. Change in severity is captured using a 5-point scale (1=much ​​better, 2=somewhat better, 3=no change, 4=somewhat worse, or 5=much ​​worse). In some respects, a PGIC score may comprise assessing a subject's need for the same, administered with a Tn3 framework compared to baseline. In some respects, a subject's PGIC score is Petition 870250087411, dated 09 / 26 / 2025, page 129 / 404 84 / 327 decreased compared to an otherwise comparable method, where the subject of the otherwise comparable method is not administered a Tn3 framework. A reduction may be of approximately 1, 2, 3, 4, or even approximately 5 points. In aspects, subjects receive 3 symptom-specific PGIC items (pain, fatigue, and / or dryness) as well as general symptom PGIC.

[0123] In aspects, treatment with a development composition is effective in reducing a PGIC score. In aspects, a PGIC score is reduced by at least approximately: 1, 2, 3, 4, or 5 points. In aspects, a PGIC score is reduced by up to approximately 1, 2, 3, 4, or 5 points. In aspects, a PGIC score is reduced by approximately 1-5, 25, 1-4, or 3-5 points.

[0124] In aspects, PGIC research is evaluated at approximately -28 days, -27 days, -26 days, -25 days, -24 days, - 23 days, -22 days, -21 days, -20 days, -19 days, -18 days, - 17 days, -16 days, -15 days, -14 days, -13 days, -12 days -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days. , -2 days _ , 1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 Petition 870250087411, dated 09 / 26 / 2025, page 130 / 404 85 / 327 weeks, 54 weeks, 55 weeks, or at least approximately 56 weeks post-treatment initiation. In aspects, PGIC research can be assessed at approximately 15 days (-3 days to +1 day), Day 29 (±4 days), Day 57 (±7 days), Day 85 (±7 days), Day 113 (±7 days), Day 141 (±7 days), Day 169 (±7 days), Day 197 (±7 days), Day 225 (±7 days), Day 253 (±7 days), Day 281 (±7 days), Day 309 (±7 days), or at approximately Day 337 (±7 days) post-treatment initiation. In aspects, PGIC is analyzed at any time before, during, or after treatment with a Tn3 development framework. Salivary Flow Not Stimulated

[0125] Disclosure assessments may include an unstimulated salivary flow assay. Unstimulated salivary flow analysis may be performed prior to stimulated salivary flow collection, but other time periods are also contemplated. Subjects receiving standard treatment for xerostomia at screening may discontinue pilocarpine and / or cevimeline use for at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 hours and / or artificial saliva for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 hours prior to saliva collection. Participants should abstain from eating or drinking for at least approximately 30, 60, 90, 120, or 175 minutes prior to saliva collection.

[0126] For unstimulated salivary flow collection, subjects refrain from swallowing or speaking throughout the collection time, except for a single swallow immediately before the start of the collection time. In terms of aspects, the total duration of the procedure is approximately 1 minute, 2 minutes, 3 minutes. Petition 870250087411, dated 09 / 26 / 2025, p. 131 / 404 86 / 327 minutes, 4 minutes, 5 minutes, 6 minutes, 7 minutes, 8 minutes, 9 minutes, or 10 minutes during which subjects allow saliva to accumulate in the oral cavity for a period of 60 seconds before emptying it into a pre-weighed container. This should be repeated a total of approximately 1, 2, 3, 4, 5, 6, 7, or 8 times during the test. The weight of the container needs to be recorded before the start and at the end of the procedure.

[0127] In aspects, a subject treated with a composition of the revelation experiences increased salivary flow as determined by unstimulated salivary flow assay. In aspects, a subject exhibits increased salivary flow in which their recipient comprises increased weight compared to the recipient's weight at baseline. In aspects, the weight is increased by at least about or at most about 5%, 10%, 20%, 30%, 40%, 50%, 75%, 100%, 120%, 150% or up to about 200%. Female Sexual Function Index (FSFI)

[0128] In some respects, an analysis may include an FSFI survey. The FSFI survey was designed to define female sexual function in clinical and non-clinical samples, establishing clear outcomes and results for female sexual function research (Rosen et al., 2000). The FSFI is a self-administered and validated 19-item questionnaire that assesses function over the past 4 weeks in the following domains: desire, arousal, lubrication, orgasm, satisfaction, and pain. Each question is scored on a scale from 0 (no sexual activity) or 1 (maximum dysfunction) to 5 (no sexual dysfunction). The final score is calculated as follows: to normalize each domain based on the item number, the Petition 870250087411, dated 09 / 26 / 2025, page 132 / 404 87 / 327 The sum of each domain score is first multiplied by a domain factor ratio (0.6 for desire; 0.3 for arousal; 0.3 for lubrication; 0.4 for orgasm; 0.4 for satisfaction; and 0.4 for pain), and then the domain scores are added together to produce a final score. In terms of aspects, an FSFI survey is scored from approximately 0 to approximately 36, approximately 1 to approximately 36, approximately 2 to approximately 36, approximately 0 to approximately 30, approximately 1 to approximately 30, or approximately 2 to approximately 30. In terms of aspects, an FSFI survey is scored from approximately 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, up to approximately 36. This questionnaire can be completed by female subjects. In some respects, an FSFI score can be used to assess a subject's need for the same, administered with a Tn3 framework compared to baseline.In some respects, a subject's FSFI score is increased compared to an otherwise comparable method, where the subject of the otherwise comparable method is not administered a Tn3 framework.

[0129] In aspects, treatment with a developmental composition is effective in increasing an FSFI research score. In aspects, an FSFI score is increased by at least approximately: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, up to approximately 36 points. In terms of aspects, a PGIC score is increased by up to approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, up to approximately 36. In terms of aspects, an FSFI score is Petition 870250087411, dated 09 / 26 / 2025, page 133 / 404 88 / 327 increased by approximately 1-36, 1-30 1-20, 1-10, 5-10, 15-25, 20-36 or 25-36 points.

[0130] In aspects, the FSFI research is evaluated at approximately -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least about 56 weeks after the start of treatment. In some respects, the research FSFI can be assessed at approximately Day 1, Day 29 (±4 days), Day 57 (±7 days), Day 85 (±7 days), Day 113 (±7 days), Day 141 (±7 days), Day 169 (±7 days), Day 197 (±7 days), Day 225 (±7 days), Day 253 (±7 days), Day 281 (±7 days), Day 309 (±7 days) or at approximately Day 337 (±7 days) post-treatment initiation. In some aspects, FSFI is analyzed at any time before, during, or after treatment with a Tn3 development framework. Petition 870250087411, dated 09 / 26 / 2025, page 134 / 404 89 / 327 ESSDAI

[0131] Disclosure assessments may include an ESSDAI assessment. In some respects, an ESSDAI assessment includes a physical examination. The ESSDAI is a systemic disease activity index that includes organ-by-organ definitions of disease activity (Seror et al., 2010). The ESSDAI classifies disease activity into 12 domains (cutaneous, respiratory, renal, articular, muscular, peripheral nervous system, central nervous system, hematologic, glandular, constitutional, lymphadenopathic, and biological). The weights for each domain were obtained through multiple regression modeling, using the Physician's Global Activity Analysis as the gold standard.

[0132] Each domain is weighted from 1 (biological domain) to 6 (muscular domain) and has 3 or 4 activity levels per domain, ranging from 0 (no activity) to 3 or 4 (severe activity).

[0133] The theoretical range of values ​​for the ESSDAI is from 0 to 123, with the final score being calculated as follows: 1) Final score = Sum of all 12 domain scores; 2) Domain score = Activity level x Domain weight.

[0134] Low activity status is defined as ESSDAI < 5, moderate activity as 5 ≤ ​​ESSDAI ≤ 13, and severe activity as ESSDAI ≤ 14 (Seror et al., 2016). ESSDAI may be an appropriate primary outcome because it is a validated and widely used measure of systemic disease activity in SS (Seror et al., 2015). It has been found to have good construct validity with reliable scoring; furthermore, systemic scores have demonstrated good sensitivity to Petition 870250087411, dated 09 / 26 / 2025, page 135 / 404 90 / 327 change in subjects whose disease activity improves. ESSDAI [3] may refer to a 3-point reduction from baseline in an ESSDAI score of a subject in need of the same, previously administered a Tn3 disclosure framework. ESSDAI [4] may refer to a 4-point reduction from baseline in an ESSDAI score of a subject in need of the same, previously administered a Tn3 disclosure framework. ESSDAI [5] may refer to a 5-point reduction from baseline in an ESSDAI score of a subject in need of the same, previously administered a Tn3 disclosure framework. ESSDAI [6] may refer to a 6-point reduction from baseline in an ESSDAI score of a subject in need of the same, previously administered a Tn3 disclosure framework.

[0135] In aspects, an ESSDAI score is in the range of approximately 0 to 123, approximately 1 to approximately 123, approximately 2 to approximately 123, approximately 10 to approximately 120, or approximately 5 to approximately 120. In aspects, an ESSDAI score is approximately 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 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, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, or even around 123. In some respects, a subject has an ESSDAI score of around 5. Petition 870250087411, dated 09 / 26 / 2025, p. 136 / 404 91 / 327 7, 5-10, 5-13 or 10-13 before treatment with a developing composition.

[0136] In aspects, treatment with a composition of the revelation is effective in reducing an ESSDAI score. In aspects, an ESSDAI score is reduced by at least approximately: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115 or 120 points. In aspects, an ESSDAI score is reduced by up to approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, or 120 points. In aspects, an ESSDAI score is reduced from approximately 1-5, 2-10, 5-10, 5-20, 10-20, 20-30, 30-40, 40-50, 50-60, 60-70, 70-80, 80-90, 90-100, 100-110, or 110-120 points.

[0137] In some respects, treatment with a developmental composition is effective in reducing an ESSDAI score. In some respects, an ESSDAI score is reduced by at least approximately of or at most about: 12%, 2s%, 3%, 42%, 52%, 6%, 72%, 8%, 92%, 10%, 11%, 122%, 132%, 142%, 152%, 162%, 172%, 18 2%, 19 2%, 20 %, 21 %, 22 2%, 23 2%, 24 2%, 25 2%, 26 2%, 27 2%, 28 2%, 29 2%, 30 %, 31 %, 32 2%, 33 2%, 34 2%, 35 2%, 36 2%, 37 2%, 38 2%, 39 2%, 40 %, 41 %, 42 2%, 43 2%, 44 2%, 45 2%, 46 2%, 47 2%, 48 2%, 49 2%, 50 %, 51 %, 52 2%, 53 2%, 54 2%, 55 2%, 56 2%, 57 2%, 58 2%, 59 2%, 60 %, 61 %, 62 2%, 63 2%, 64 2%, 65 2%, 66 2%, 67 2%, 68 2%, 69 2%, 70 %, 71 %, 72 2%, 73 2%, 74 2%, 75 2%, 76 2%, 77 2%, 78 2%, 79 2%, 80 %, 81 %, 82 2%, 83 2%, 84 2%, 85 2%, 86 2%, 87 2%, 88 2%, 89 2%, 90 %, 91 %, 92 2%, 93 2%, 94 2%, 95 2%, 96 2%, 97 2%, 98 %, 99% or 100%. In terms of aspects, an ESSDAI score is reduced by approximately 1-10%, 1-20%, 5-20%, 10-30%, 20-30%, 25-30%. Petition 870250087411, dated 09 / 26 / 2025, p. 137 / 404 92 / 327%, 25-35%, 30-40%, 35-55%, 40-60%, 50-70%, 60-80%, 70-90%, 80-100%, or approximately 90-100%.

[0138] In aspects, the ESSDAI assessment is evaluated at approximately -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, 10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days. -2 days_, 1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least approximately 56 weeks post-treatment initiation. In some respects, the assessment ESSDAI can be assessed at approximately Day -28, Day -27, Day -26, Day -25, Day -24, Day -23, Day -22, Day -21, Day -20, Day -19, Day -18, Day -17, Day -16, Day -15, Day -14, Day 13, Day -12, Day -11, Day -10, Day -9, Day -8, Day -7, Day -6, Day -5, Day -4, Day -3, Day -2, Day -1, Day 0, Day 1, Day 29 (±4 days), Day 57 (±7 days), Day 85 (±7 days), Day 113 (±7 days), Day 141 (±7 days), Day 169 (±7 days), Day 197 (±7 days), Day 225 (±7 days), Day 253 (±7 days), Day 281 (±7 days), Day 309 (±7 days), or around Day 337 (±7 days) post Petition 870250087411, dated 09 / 26 / 2025, page 138 / 404 93 / 327 start of treatment. In some aspects, ESSDAI is analyzed at any time before, during, or after treatment with a Tn3 framework of disclosure. EULAR Sjögren's Syndrome Clinical Disease Activity Index (ClinESSDAI)

[0139] In some respects, an analysis may include a ClinESSDAI assessment. The ClinESSDAI is a validated SS disease activity index based on the ESSDAI that excludes the biological domain and assigns different weights to each domain. The ClinESSDAI was developed to reduce potential associations between B-cell biomarkers measured by the ESSDAI biological domain and measures of clinical activity (Seror et al., 2016). The theoretical range of values ​​for the ClinESSDAI is 0 to 135. Similar to the ESSDAI, low activity is defined as < 5, moderate activity as 5 ≤ ​​ClinESSDAI ≤ 13, and high activity as ≥ 14 (Seror et al., 2016). ClinESSDAI has been validated and shown to correlate well with ESSDAI and is considered a useful tool for detecting changes independent of the biological effect of the drug (Seror et al., 2016; Dumusc et al., 2018; Quartuccio et al., 2017).

[0140] In aspects, a ClinESSDAI score is in the range of approximately 0 to 135, approximately 1 to approximately 135, approximately 2 to approximately 135, approximately 10 to approximately 130, or approximately 5 to approximately 130. In aspects, a ClinESSDAI score is approximately 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 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, Petition 870250087411, dated 09 / 26 / 2025, p. 139 / 404 94 / 327 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, or even around 135. In some respects, a ClinESSDAI score can be used to analyze a subject in need of the same, administered with a Tn3 framework compared to baseline. In other respects, a subject's ClinESSDAI score is lower compared to an otherwise comparable method, where the subject in the otherwise comparable method is not administered a Tn3 framework.

[0141] In aspects, treatment with a developmental composition is effective in reducing a ClinESSDAI score. In aspects, a ClinESSDAI score is reduced by at least approximately: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 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, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, or 135 points. In aspects, a ClinESSDAI score is reduced by up to approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, Petition 870250087411, dated 09 / 26 / 2025, pp. 140 / 404 95 / 327 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, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, or 135 points. In aspects, a ClinESSDAI score is reduced by approximately 1-5, 2-10, 5-10, 5-20, 10-20, 20-30, 30-40, 40-50, 50-60, 60-70, 70-80, 80-90, 90-100, 100-110, 110-120, 120-130, or 125-135 points.

[0142] In aspects, the ClinESSDAI assessment can be done in approximately -28 days, -27 days, -26 days, -25 days, 24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks,51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least about 56 weeks post-treatment initiation. In some aspects, a ClinESSDAI can be done at about Day -2 8, Day -27, Day -26, Day -25, Day -24, Day -23, Day -22, Day -21, Day Petition 870250087411, dated 09 / 26 / 2025, page 141 / 404 96 / 327 20, Day -19, Day -18, Day -17, Day -16, Day -15, Day -14, Day -13, Day -12, Day -11, Day -10, Day -9, Day -8, Day -7, Day -6, Day -5, Day -4, Day -3, Day -2, Day -1, Day 0, Day 1, Day 29 (±4 days), Day 57 (±7 days), Day 85 (±7 days), Day 113 (±7 days), Day 141 (±7 days), Day 169 (±7 days), Day 197 (±7 days), Day 225 (±7 days), Day 253 (±7 days), Day 281 (±7 days), Day 309 (±7 days), or approximately Day 337 (±7 days) after the start of treatment. In some aspects, ClinESSDAI is evaluated at any time before, during, or after treatment with a Tn3 disclosure framework. Analysis of 28 joints (TJC and SJC)

[0143] In some respects, an analysis may comprise an analysis of 28 joints. In some respects, an analysis of 28 joints comprises a count of tender joints (TJC). In some respects, a count of 28 joints comprises a count of swollen joints (SJC). In some respects, a count of 28 joints comprises both a TJC and an SJC. The 28-joint analysis will assess the following joints for tenderness and swelling: left and right shoulder, elbow, wrist, metacarpophalangeal (MCP) joints1, MCP2, MCP3, MCP4, MCP5, proximal interphalangeal (PIP) joints1, PIP2, PIP3, PIP4, PIP5 of the upper extremities, and left and right knee of the lower extremities. Each of the 28 joints may be assessed for the presence of synovitis. At the beginning of the 28-joint count (before the tenderness and swelling analysis), the subject may be asked if he or she has felt or is feeling pain in any of the 28 joints.In terms of aspects, a joint analysis score of 28 joints falls within the range of approximately 0 to approximately 28. Petition 870250087411, dated 09 / 26 / 2025, page 142 / 404 97 / 327 aspects, a 28-joint analysis score is approximately 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, up to approximately 28. In aspects, a 28-joint analysis may comprise assessing a subject in need of the same, administered with a Tn3 framework compared to baseline. In aspects, a subject's 28-joint analysis score is lower compared to an otherwise comparable method, where the subject in the otherwise comparable method is not administered a Tn3 framework.

[0144] In aspects, treatment with a revelation composition is effective in reducing a 28-joint analysis score. In aspects, a 28-joint analysis score is reduced by at least approximately: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 or 28 points. In terms of aspects, a 28-joint analysis score is reduced by approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 points. In terms of aspects, a 28-joint analysis score is reduced by approximately 1-28, 1-5, 2-10, 5-10, 1-20, 5-20, 10-15, 10-20, 15-25, or 20-28 points.

[0145] In aspects, the analysis of 28 joints can be done in approximately -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 Petition 870250087411, dated 09 / 26 / 2025, page 143 / 404 98 / 327 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least approximately 56 weeks after the start of treatment. In some aspects, an analysis of 28 joints can be done around Day 1, Day 29 (±4 days), Day 57 (±7 days), Day 85 (±7 days), Day 113 (±7 days), Day 141 (±7 days), Day 169 (±7 days), Day 197 (±7 days), Day 225 (±7 days), Day 253 (±7 days), Day 281 (±7 days), Day 309 (±7 days) or around Day 337 (±7 days) post-treatment initiation. In aspects, the 28-joint count is analyzed at any time before, during, or after treatment with a Tn3 development framework. Stimulated Salivary Flow

[0146] In some respects, an analysis may comprise a measurement of stimulated salivary flow. In some respects, total stimulated salivary flow will be measured to objectively analyze functional changes in the salivary glands during treatment with a Tn3 developmental framework. A subject receiving standard care for xerostomia at screening may discontinue the use of pilocarpine or cevimecin for at least 12 hours and artificial saliva for at least 3 hours before saliva collection. A subject may be Petition 870250087411, dated 09 / 26 / 2025, page 144 / 404 99 / 327 It is forbidden to eat or drink for at least 90 minutes before saliva collection. Saliva can be collected at the same time on all visits.

[0147] For measurements of the stimulated total salivary flow rate, a square of parafilm approximately 5 x 5 cm is rolled up and given to a subject to be chewed like chewing gum at a rate of approximately 60 strokes per minute. The subject should be seated upright with eyes open and head tilted slightly forward and begin chewing the parafilm for 60 seconds, at which point all the collected saliva should be spat into an extra (unweighed) falcon tube, keeping the parafilm in the mouth. This first collection accustoms the subject to the procedure. Three rounds of salivary collection, after 20 seconds of chewing each, follow in a pre-weighed falcon tube. These rounds are continuous, but the time should be stopped during saliva collection and restarted immediately after saliva deposition in a pre-weighed falcon tube, for a total stimulation time of 60 seconds.If collection for 60 seconds is not feasible due to the subject's incapacity, the total collection time should be recorded. The total stimulated saliva collected is analyzed by subtracting the weight of the tube before collection from the final weight of the tube. In this respect, a change from baseline in stimulated salivary flow is determined.

[0148] In some respects, a measurement of stimulated salivary flow can be analyzed in approximately -28 days, -27 days, 26 days, -25 days, -24 days, -23 days, -22 days, -21 days, 20 days, -19 days, -18 days, -17 days, -16 days, -15 days, 14 days, -13 days, -12 days, -11 days, -10 days, -9 days Petition 870250087411, dated 09 / 26 / 2025, page 145 / 404 100 / 327 -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least approximately 56 weeks post-treatment initiation. In aspects, a measurement of stimulated salivary flow can be analyzed around Day 1, Day 85 (±7 days), Day 169 (±7 days), Day 253 (±7 days), or around Day 337 (±7 days) post-treatment initiation. In aspects, salivary flow is analyzed at any time before, during, or after treatment with a Tn3 development framework. European Quality of Life - 5 Levels and 5 Dimensions Version (EQ-5D-5L)

[0149] An analysis of the revelation may be EQ-5D-5L. The 5-domain, 5-level version of the EQ (EQ-5D-5L) is a generic PRO instrument that measures health status. It consists of a descriptive system and the EQ visual analog scale (EQ VAS). The EQ-5D-5L descriptive system comprises 5 health dimensions: mobility, self-care, usual activities, pain / discomfort, and anxiety / depression. For each dimension, patients select one of the 5 levels of Petition 870250087411, dated 09 / 26 / 2025, page 146 / 404 101 / 327 severity: no problems, mild problems, moderate problems, severe problems, and extreme problems. The EQ VAS records the patient's self-assessment of health on a vertical visual analog scale from 0 to 100, where outcomes are marked as the worst and best imaginable health, respectively.

[0150] In aspects, after treatment with a developmental framework, a subject reports an increased level of health as determined by EQ-5D-5L. In aspects, health increases by at least approximately or at most: 5, 10, 20, 30, 40, 50, 60, 70, 80, or 90 points compared to a baseline level before treatment. In aspects, an EQ5D-5L test is performed at any time before, during, or after treatment with a Tn3 developmental framework. Schirmer test

[0151] One assessment of the revelation may be the Schirmer test. In some respects, a Schirmer test is performed without local anesthesia. The Schirmer test measures lacrimal gland function. It uses calibrated strips of non-toxic filter paper to measure tear flow. One end of the strip is placed inside the lower eyelid. Both eyes need to be measured simultaneously. After placement, participants are asked to keep their eyes gently closed for 5 minutes, at which point the strips are removed from the eyelids and the extent of wetting of each strip is recorded.

[0152] In aspects, after treatment with a developing composition, increased wetting is detected compared to a wetting level before treatment or a baseline level. In aspects, wetting is increased Petition 870250087411, dated 09 / 26 / 2025, page 147 / 404 102 / 327 in at least about or at most about 5%, 10%, 20%, 30%, 40%, or 50% compared to baseline. In some respects, the Schirmer test is performed at any time before, during, or after treatment with a Tn3 developmental framework. Physician Global Impression of Severity (MDGIS)

[0153] In aspects, an analysis may comprise an MDGIS survey. The MDGIS represents an analysis of the severity of SS disease and is a 5-point categorical response scale (1=none, 2=mild, 3=moderate, 4=severe, or 5=very severe). In aspects, an MDGIS score may range from about 0 to about 5 or from about 1 to about 5. In aspects, an MDGIS score may be about 1, 2, 3, 4, or even about 5. In aspects, an MDGIS score may be about 0, 1, 2, 3, or even about 4. In aspects, an MDGIS score may comprise assessing a subject in need of the same, administered with a Tn3 framework compared to baseline. In aspects, a subject's MDGIS score is decreased compared to an otherwise comparable method, where the subject of the otherwise comparable method is not administered a Tn3 framework.

[0154] In aspects, treatment with a composition of the revelation is effective in reducing an MDGIS score. In aspects, an MDGIS score is reduced by at least approximately: 1, 2, 3, 4, or 5 points. In aspects, an MDGIS score is reduced by up to approximately 1, 2, 3, 4, or 5 points. In aspects, an MDGIS score is reduced by approximately 1-5, 25, 1-4, or 3-5 points. Petition 870250087411, dated 09 / 26 / 2025, pp. 148 / 404 103 / 327

[0155] In terms of aspects, an MDGIS search can be done in approximately -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks 48 weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least around 56 weeks post-treatment initiation. In aspects, an MDGIS scan can be performed around Day 1, Day 29 (±4 days), Day 57 (±7 days), Day 85 (±7 days), Day 113 (±7 days), Day 141 (±7 days), Day 169 (±7 days), Day 197 (±7 days), Day 225 (±7 days), Day 253 (±7 days), Day 281 (±7 days), Day 309 (±7 days) or around Day 337 (±7 days) post-treatment initiation. In aspects, MDGIS is analyzed at any time before, during or after treatment with a Tn3 development framework. Electrocardiogram (ECG)

[0156] In some respects, an analysis can include a ECG. A single 12-lead ECG can be performed with the Petition 870250087411, dated 09 / 26 / 2025, page 149 / 404 104 / 327 subject in the supine position. Electrocardiogram measurement may be delayed by at least 10 minutes if performed after phlebotomy. Each ECG may include ventricular heart rate and intervals (PR, QRS, QT, RR).

[0157] In some respects, an ECG assessment can be analyzed in approximately -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks,52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least approximately 56 weeks post-treatment initiation. In some cases, an ECG assessment can be performed around Day 1, Day 169 (±7 days), or around Day 337 (±7 days) post-treatment initiation. In some cases, ECG is analyzed at any time before, during, or after treatment with a Tn3 development framework. Clinical Safety Laboratory Tests Petition 870250087411, dated 09 / 26 / 2025, page 150 / 404 105 / 327

[0158] In some respects, an analysis may comprise a clinical safety laboratory test. Blood and urine samples may be collected for laboratory safety testing using clinically acceptable methods and devices. Abnormal laboratory findings associated with the underlying disease may not be considered clinically significant.

[0159] All laboratory tests with values ​​considered clinically significantly abnormal during study participation or within the protocol follow-up period after the last dose of a Tn3 frame may be repeated until the values ​​return to normal or baseline or are no longer considered clinically significant. Additional tests may be performed at any time during the study.

[0160] In some respects, a clinical safety laboratory test may include hematology, clinical chemistry, urinalysis, pregnancy test, and other screening tests. Exemplary hematological parameters may include, but are not limited to, platelet count, red blood cell count (RBC), RBC indices (mean corpuscular volume [MCV] and mean corpuscular hemoglobin [MCH]), white blood cell count [WBC] with differential (e.g., neutrophils, lymphocytes, monocytes, eosinophils, and / or basophils), hemoglobin, hematocrit, and immunoglobulins (IgG, IgM, and IgA). Exemplary clinical chemistry parameters may include, but are not limited to, blood urea nitrogen (BUN), potassium, creatinine, sodium, calcium, chloride, bicarbonate, phosphorus, glucose, aspartate aminotransferase (AST) / glutamic transaminase. Petition 870250087411, dated 09 / 26 / 2025, page 151 / 404 106 / 327 serum oxaloacetic acid (SGOT), alanine aminotransferase (ALT) / serum glutamic-pyruvic transaminase (SPGT), alkaline phosphatase, bilirubin, gamma-glutamyltransferase, albumin, total protein, creatine kinase, estimated glomerular filtration rate (eGFR), uric acid, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides. Exemplary urine test parameters include, but are not limited to, specific gravity, pH, glucose, protein, blood, ketones, microscopic examination (e.g., crystals, casting, WBCs, RBCS), and protein:creatinine ratio. Exemplary pregnancy test parameters may include, but are not limited to, serum beta-human chorionic gonadotropin (β-hCG) pregnancy tests and urine pregnancy tests.Other screening test parameters may include, but are not limited to, follicle-stimulating hormone, serology (e.g., hepatitis B virus [HBV], HCV, human immunodeficiency virus-1 [HIV-1], HIV-2), rapid test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), tuberculosis testing (e.g., interferon gamma release assay [IGRA]), and a coagulation panel (e.g., prothrombin time, international normalized ratio [INR], partial thromboplastin time [PTT]). In some respects, a clinical safety laboratory test may comprise analyzing a subject in need of such testing, administered with a Tn3 framework compared to baseline. In some respects, the clinical safety laboratory test of the subject is diminished compared to an otherwise comparable method, where the subject of the otherwise comparable method... Petition 870250087411, dated 09 / 26 / 2025, page 152 / 404 107 / 327 is not administered with a Tn3 scaffold. In some respects, the laboratory testing of clinical safety of the subject is increased compared with an otherwise comparable method, where the subject of the otherwise comparable method is not administered with a Tn3 scaffold.

[0161] In some respects, a clinical safety laboratory test can be analyzed in approximately -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks,50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least about 56 weeks after the start of treatment. In some respects, a clinical safety laboratory test may, to be evaluated on approximately Day -28, Day -27, Day -26, Day -25, Day -24, Day -23, Day -22, Day -21, Day -20, Day -19, Day 18, Day -17, Day -16, Day -15, Day -14, Day -13, Day -12, Day -11, Day -10, Day -9, Day -8, Day -7, Day -6, Day -5, Day -4, Day -3, Day -2, Day -1, Day 0, Day 1, Day 15 (-3 Petition 870250087411, dated 09 / 26 / 2025, page 153 / 404 108 / 327 days +1 day), Day 29 (±4 days), Day 57 (±7 days), Day 85 (±7 days), Day 113 (±7 days), Day 141 (±7 days), Day 169 (±7 days), Day 197 (±7 days), Day 225 (±7 days), Day 253 (±7 days), Day 281 (±7 days), Day 309 (±7 days), Day 337 (±7 days) or around Day 393 (±7 days) post-treatment initiation. In some respects, clinical trials are conducted anytime before, during, or after treatment with a Tn3 development framework. Immunogenicity

[0162] In some respects, an analysis may comprise determining the level of immunogenicity, if any, of a developing anti-Tn3 scaffold. Immunogenicity comprises determining the presence of an anti-drug antibody (ADA) in a Tn3 scaffold. The presence of ADA can be assessed using a plasma sample from a subject administered with a Tn3 scaffold. Plasma samples for ADA to a developing Tn3 scaffold can be obtained prior to IP administration according to visits and analyzed using a validated immunoassay. In some respects, ADA is not detected post-administration of a Tn3 scaffold.In some respects, ADA levels are reduced compared to an otherwise comparable method where the subject of the otherwise comparable method is not administered with a Tn3 framework, for example, the reduction may be approximately: 10%, 15%, 20%, 25%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or even 100% compared to ADA levels in an otherwise comparable method where the subject of the otherwise comparable method is not administered with a Tn3 framework. Petition 870250087411, dated 09 / 26 / 2025, pp. 154 / 404 109 / 327

[0163] Antibodies to a Tn3 scaffold from development can be assessed in plasma samples collected from all subjects. Additionally, plasma samples should also be collected at the final visit from subjects who discontinued administration of a Tn3 scaffold or were withdrawn from the study.

[0164] Plasma samples can be screened for antibodies that bind to a Tn3 development scaffold and the titer of confirmed positive samples can be reported. Other analyses can be performed to verify antibody stability on a Tn3 development scaffold and / or further characterize the immunogenicity of a Tn3 development scaffold.

[0165] Detection and characterization of antibodies in a Tn3 detection scaffold can be performed using a validated assay method. Antibodies can be further characterized and / or evaluated for their ability to neutralize the activity of the study intervention(s). Samples can be stored for at least 15 years after the subject's last study visit to allow for further analysis of immune responses to a Tn3 detection scaffold. The number and percentage of subjects developing ADA and the ADA titer can be summarized by visit and by treatment group.

[0166] In aspects, an immunogenicity analysis can be done in approximately -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 Petition 870250087411, dated 09 / 26 / 2025, page 155 / 404 110 / 327 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least approximately 56 weeks after the start of treatment. In some respects, an immunogenicity analysis can be performed at approximately Day 1, Day 15 (-3 days to +1 day), Day 29 (±4 days), Day 57 (±7 days), Day 85 (±7 days), Day 113 (±7 days), Day 141 (±7 days), Day 169 (±7 days), Day 197 (±7 days), Day 225 (±7 days), Day 253 (±7 days), Day 281 (±7 days), Day 309 (±7 days), Day 337 (±7 days) or approximately Day 393 (±7 days) after the start of treatment. In terms of aspects, immunogenicity, or lack thereof, is analyzed at any time before, during, or after treatment with a Tn3-detection framework. Ultrasound Imaging

[0167] In some respects, an analysis may include an ultrasound imaging study. In some respects, an ultrasound imaging study may be of one or more joints. In some respects, an ultrasound imaging study may be of one or more salivary glands.

[0168] Ultrasound Imaging of the Salivary Glands Petition 870250087411, dated 09 / 26 / 2025, page 156 / 404 111 / 327

[0169] Ultrasound measurement of the parotid and submandibular glands can be performed. A subject with significant glandular disease can be selected to participate. The above glands can be analyzed in longitudinal and transverse planes with subjects in the supine position. After image capture and quality analysis, the images will be scored and the data summed. The echostructure of each gland in B-mode images can be scored on a 5-point scale (0 to 4) as previously described (Gazeau et al., 2018). The classification criteria will be as follows: Grade 0: normal homogeneous gland; Grade 1: small hypoechoic areas with hyperechoic bands; Grade 2: multiple hypoechoic areas < 2 mm; Grade 3: multiple hypoechoic areas from 2 to 6 mm; Grade 4: multiple hypoechoic areas > 6 mm.

[0170] At each time point analyzed, 4 scores can be collected, one for each parotid gland and one for each submandibular gland. The Salivary Gland Ultrasound score for each analysis will be the sum of these scores. Ultrasound Imaging of the Joints

[0171] Ultrasound assessment of small peripheral joints can be performed. Subjects with possible joint involvement can be selected. A modified German 7-joint US scoring system can be used (Backhaus et al., 2009). After image capture and quality analysis, the images will be transmitted for scoring and the data summed.

[0172] Gray-scale ultrasound (GS) can be performed on the following clinically dominant joints of the hands and feet: wrist (dorsal, palmar and ulnar planes), second and third MCP joints (MCP2 and MCP3, plane Petition 870250087411, dated 09 / 26 / 2025, page 157 / 404 112 / 327 palmar) and PIP (PIP2 and PIP3, palmar planes) and second and fifth metatarsophalangeal joints (MTP2 and MTP5, dorsal plane). In GS, each joint and each plane can be scored semi-quantitatively on the following scale from 0 to 3 for synovitis: Grade 0 = absence of synovitis; Grade 1 = mild synovitis (small hypoechoic / anechoic line below the joint capsule); Grade 2 = moderate synovitis (joint capsule elevated parallel to the joint); and Grade 3 = severe synovitis (maximum distension of the joint capsule). The total GS for synovitis scoring will be the sum of each joint or plane, for a score of 0-27. In terms of aspects, the total GS score for synovitis can range from about 0 to about 27, or from about 1 to about 27. In terms of aspects, the total GS score for synovitis will be approximately 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, or even up to about 27.

[0173] Power Doppler ultrasound will be performed on the following clinically dominant joints of the hands and feet: wrist (dorsal, palmar, and ulnar planes), second and third MCP joints (MCP2 and MCP3, palmar and dorsal planes) and PIP joints (PIP2 and PIP3, palmar and dorsal planes), and second and fifth metatarsophalangeal joints (MTP2 and MTP5, dorsal plane only). Synovitis analysis using power Doppler will be scored on a scale of 0 to 3 as follows: Grade 0 = no color IA signal; Grade 1 = mild synovitis (up to 3 color signals or 2 single signals and 1 confluent signal in the IA space); Grade 2 = moderate synovitis (greater than Grade 1, but color occupying less than 50% of the IA space); and Grade 3 = severe synovitis (greater than 50% color in the IA space). Petition 870250087411, dated 09 / 26 / 2025, pp. 158 / 404 113 / 327 IA). The total GS score for synovitis will be the sum of each joint or plane, for a score of 0-39. In some aspects, a total GS score is approximately 0 to approximately 39 or approximately 1 to approximately 39. In aspects, a total GS score is approximately 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, up to about 39.

[0174] The total synovitis score will be the sum of the GS and power Doppler scores, for a range of 0 to 66. In some aspects, a total synovitis score is approximately 0 to approximately 66 or approximately 1 to approximately 66. In aspects, a total synovitis score is approximately 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, up to about 66.

[0175] In some respects, a synovitis reveal score may involve assessing a subject in need of the same, administered with a Tn3 framework compared to baseline. In some respects, a synovitis reveal score is lowered compared to an otherwise comparable method, where the subject of the otherwise comparable method is not administered a Tn3 framework.

[0176] In aspects, treatment with a developmental composition is effective in reducing a synovitis score. In aspects, a synovitis score is reduced by at least approximately: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, Petition 870250087411, dated 09 / 26 / 2025, page 159 / 404 114 / 327 40, 45, 50, 55, 60, 65, or 66 points. In aspects, a synovitis score is reduced by up to approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, or 66 points. In aspects, a synovitis score is reduced by approximately 1-5, 2-10, 5-10, 5-20, 10-20, 20-30, 30-40, 40-50, 50-60, or 55-66 points.

[0177] ultrasound 26 days, -20 days, -14 days, -8 days, days, -1 In aspects, an imaging analysis can be done in about -28 days, -27 days, -25 days, -24 days, -23 days, -22 days, -21 days, -19 days, -18 days, -17 days, -16 days, -15 days, -13 days, -12 days, -11 days, -10 days, -9 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks,50 weeks, 51 weeks, at least 52 weeks, approximately 53 weeks, 54 weeks, 55 weeks, 56 weeks after starting treatment. or In, In some aspects, an ultrasound imaging analysis can be performed at approximately Day 1, Day 197 (±7 days), or approximately Day 337 (±7 days) post-treatment initiation. In some aspects, imaging is completed at any time before, during, or after treatment with a Tn3 development framework. Petition 870250087411, dated 09 / 26 / 2025, page 160 / 404 115 / 327 Transcriptomics

[0178] In some respects, an analysis may include transcriptomic assessment. In some respects, RNA testing is performed. In some respects, RNA testing is performed to measure the expression levels of genes associated with disease activity, specific cell types (e.g., plasma cell gene signature), follicular T cell helper gene signature, and signaling, e.g., the CD40L / CD40 pathway.

[0179] In aspects, blood RNA is used to measure the expression levels of genes associated with disease activity, specific cell types (e.g., plasma cell gene signature), follicular T cell helper gene signature, and signaling, including the CD40L / CD40 pathway. In aspects, a blood sample will be collected using the PAXgene Blood RNA System for blood collection, transport, and storage, and intracellular RNA stabilization in a closed tube, followed by isolation and purification of whole blood intracellular RNA for microarray analysis and quantitative polymerase chain reaction.

[0180] In aspects, the expression levels of genes associated with disease activity through RNA analysis can be reduced by at least about 10%, 15%, 20%, 25%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or even 100% compared with an otherwise comparable method, where the subject of the otherwise comparable method is not administered with a Tn3 scaffold.

[0181] In some respects, a transcriptomic assessment can be evaluated in approximately -28 days, -27 days, -26 days, Petition 870250087411, dated 09 / 26 / 2025, page 161 / 404 116 / 327 -25 days, -19 days, -13 days, 7 days, -0 days, 1 - 24 days, -23 days, -22 days, -21 days, -20 days, -18 days, -17 days, -16 days, -15 days, -14 days, -12 days, -11 days, -10 days, -9 days, -8 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, at least 52 weeks, around 53-56 weeks, post-54 weeks, beginning of 55 weeks,treatment. or In, In terms of aspects, a transcriptomic assessment can be evaluated around Day 1, Day 15 (-3 days to +1 day), Day 29 (±4 days), Day 85 (±7 days), Day 169 (±7 days), or around Day 337 (±7 days) post-treatment initiation. In terms of aspects, transcriptomics is performed at any time before, during, or after treatment with a Tn3-detection framework. Genetic Analyses

[0182] In some respects, an analysis provided in this document may include genetic assessment by means of DNA or RNA testing. In some respects, DNA testing is performed. In some respects, RNA testing is performed. In some respects, DNA testing may be performed to measure the pharmacogenomic profile (single nucleotide polymorphism [SNP]) of CD40 and others. Petition 870250087411, dated 09 / 26 / 2025, page 162 / 404 117 / 327 genes involved in the CD40 / CD40L geometric axis. In some aspects, DNA is collected for epigenetic analysis, such as DNA methylation, of genes related to immunity. In others, an analysis comprises determining the sequence of genes associated with disease activity through DNA analysis of whole blood.

[0183] In some respects, whole blood can be collected and used to evaluate gene sequences before, during, and after treatment with any of the compositions provided in this document. Gene sequences found to be modulated by treatment can be analyzed in whole blood using quantitative methods. Samples can be used to examine gene sequences and their changes over time, as assessed by NGS, Sanger Sequencing or PCR.

[0184] In some respects, a genetic analysis can be evaluated in about 28 days. -24 days, -23 days, -22 days, -18 days, -17 days, -16 days, -12 days, -11 days, -10 days, -27 days, -26 days, -25 days, -21 days, -20 days, -19 days, -15 days, -14 days, -13 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks 42 Petition 870250087411, dated 09 / 26 / 2025, page 163 / 404 118 / 327 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least approximately 56 weeks post-treatment initiation. In some respects, a genetic assessment is performed at any time before, during, or after treatment with a Tn3 developmental scaffold. Pharmacokinetics

[0185] In aspects, a method provided herein may comprise determining a Tn3 scaffold concentration in a subject in need thereof after administration. In aspects, a method comprises a pharmacokinetic analysis. In aspects, a sample is a blood sample or a plasma sample, or a combination of both. In aspects, a suitable assay for measuring pharmacokinetics may comprise an electrochemiluminescence (ECL) assay, a spherule-based assay, a cell-based assay, and combinations thereof. In aspects, a sample may comprise plasma, and the plasma is evaluated for Tn3 scaffold concentration by measuring: maximum observed concentration (Cmax), area under the concentration-time curve (AUC), clearance (CL), and terminal elimination half-life (t1 / 2).

[0186] Samples will be used to evaluate the PK of a Tn3 framework for development. Samples collected for Tn3 framework plasma concentration analysis may also be used to evaluate safety or efficacy aspects during or after the study.

[0187] In some respects, a pharmacokinetic analysis can be performed at approximately -28 days, -27 days, -26 days, -25 days, Petition 870250087411, dated 09 / 26 / 2025, pp. 164 / 404 119 / 327 -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least approximately 56 weeks after the start of treatment.In terms of aspects, an immunogenicity analysis can be performed at approximately Day 1, Day 85 (±7 days), Day 169 (±7 days), Day 253 (±7 days), Day 337 (±7 days), or approximately Day 393 (±7 days) after the start of treatment. In terms of aspects, pharmacokinetics is evaluated at any time before, during, or after treatment with a Tn3 development framework. Pharmacodynamics

[0188] In some respects, an analysis may comprise pharmacodynamic (PD) assessment. In some respects, an analysis may occur over a period of time. Samples of whole blood, plasma, urine, saliva, and serum may be collected to assess the PD of a Tn3 development framework. In some respects, a sample may be analyzed by Petition 870250087411, dated 09 / 26 / 2025, page 165 / 404 120 / 327 is a validated assay that includes, but is not limited to, flow cytometry.

[0189] Samples may be collected to analyze a biomarker level which includes, but is not limited to, immunoglobulins (IgM, IgG, and IgA), sCD40L, CXCL13, β-2 microglobulin, high-sensitivity CRP, serum C3, C4, free light chains, peripheral blood mononuclear cells (PBMCs), anti-SSA, anti-SSB, cryoglobulins, and serum and urine immunofixation. In some respects, immunoglobulins are plasma immunoglobulins. In some respects, a biomarker is a cellular biomarker such as one expressed by a subset of B cells or T cells.Exemplary B and T cell subsets include, but are not limited to, plasmablasts (e.g., CD27br / CD38br / IgD- subsets of CD19+ cells), memory precursor B cells (e.g., CD11cbr subsets of CD19+ cells), follicular helper T cells (Tfh) (e.g., CXCR5+ / ICOS+ subsets of CD3+ / CD4+ cells), post-switching memory B cell proliferation (e.g., Ki67+ subsets of CD27br / IgD- / CD19+ cells), and / or total T cell proliferation (e.g., Ki67+ subsets of CD3+ cells). In aspects, an analysis comprises determining a level of one or more of the following: CD19, CD20, CD27, CD38, and CD138.

[0190] In aspect, a biomarker level is increased in a subject requiring the same post-administration of a Tn3 developmental scaffold. In aspect, a biomarker level is decreased in a subject requiring the same post-administration of a Tn3 developmental scaffold. In aspects, a reduction in biomarkers can be detected. Petition 870250087411, dated 09 / 26 / 2025, page 166 / 404 121 / 327 compared to an otherwise comparable method, where the subject of the otherwise comparable method is not administered with a Tn3 scaffold. In aspects, the elimination of a biomarker can be detected compared to an otherwise comparable method, where the subject of the otherwise comparable method is not administered with a Tn3 scaffold compared to an otherwise comparable method that lacks the administration of a Tn3 scaffold.In terms of aspects, the reduction of a biomarker comprises at least approximately or at most approximately: 1 time, 2 times, 3 times, 4 times, 5 times, 10 times, 15 times, 20 times, 25 times, 30 times, 35 times, 40 times, 45 times, 50 times, 55 times, 60 times, 65 times, 70 times, 75 times, 80 times, 85 times, 90 times, 95 times, 100 times, 105 times, 110 times, 115 times, 120 times, 125 times, 130 times, 135 times, 140 times, 145 times, 150 times, 155 times, 160 times, 165 times, 170 times, 175 times, 180 times, 185 times, 19 times, 195 times, 200 times, 210 times, 220 times, 230 times, 240 times, 250 times, 260 times, 270 times, 280 times, 290 times, or even approximately 300 times reduction compared to a comparable method that lacks administration. In some respects, the effectiveness of Tn3 scaffold treatment on a biomarker can be analyzed over time using a suitable immunoassay.In some aspects, the effects of a Tn3 scaffold are analyzed over time using a qualified immunoassay.

[0191] The revelation provides compositions containing Tn3 scaffolding that alter the CD40 / CD40L pathway in a subject. The revelation provides compositions containing Tn3 scaffolding that efficiently reduce or deplete soluble CD40L (sCD40L) in a subject. Once a Tn3 scaffolding binds and depletes a Petition 870250087411, dated 09 / 26 / 2025, page 167 / 404 122 / 327 biomarker, the reduction or elimination of a biomarker can be used as a measure of treatment efficacy. In some respects, sCD40L is a measure of target engagement. In some respects, suitable assays to analyze sCD40L levels may include flow cytometry, histology, immunohistochemistry, blood analysis, microscopy, PCR, ELISA, and combinations thereof.

[0192] The discovery provides compositions containing Tn3 scaffolding that efficiently reduce, eliminate, or inhibit major leukocyte populations (e.g., B lymphocytes), anti-SSA (Ro), anti-SSB (La), antinuclear antibodies, rheumatoid factor (RF), and combinations thereof. Suitable assays for analyzing leukocyte populations, anti-SSA (Ro), anti-SSB (La), antinuclear antibodies, and rheumatoid factor (RF) may include flow cytometry, histology, immunohistochemistry, blood analysis, microscopy, PCR, ELISA, and combinations thereof.

[0193] In aspects, Tn3 scaffolds of the breakthrough can achieve at least about 10%, 15%, 20%, 25%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or even about 100% reduction in CD40L compared to an otherwise comparable method, where the subject of the otherwise comparable method is not administered with a Tn3 scaffold. The reduction in major leukocyte populations can persist for long periods of time. In some aspects, the depletion of the main populations of CD40L leukocytes, anti-SSA (Ro), anti-SSB (La), antinuclear antibodies and rheumatoid factor (RF), or a combination thereof, may persist for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days. Petition 870250087411, dated 09 / 26 / 2025, page 168 / 404 123 / 327 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 15 days, at least 20 days, at least 25 days, or at least 30 days. In aspects, depletion of CD40L, major leukocyte populations, anti-SSA (Ro), anti-SSB (La), antinuclear antibodies, and rheumatoid factor (RF), or a combination thereof, may persist for at least 1 week, at least 2 weeks, at least 3 weeks, at least 10 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, or at least 4 weeks.In some aspects, depletion of CD40L, major leukocyte populations, anti-SSA (Ro), anti-SSB (La), antinuclear antibodies and rheumatoid factor (RF), or a combination thereof, may persist for at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months or at least 12 months.

[0194] In aspects, a pharmacodynamic analysis can be analyzed in approximately -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 Petition 870250087411, dated 09 / 26 / 2025, page 169 / 404 124 / 327 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least about 56 weeks after starting treatment. In terms of aspects, a pharmacodynamic analysis can be analyzed on approximately Day -28, Day -27, Day -26, Day -25, Day -24, Day 23, Day -22, Day -21, Day -20, Day -19, Day -18, Day -17, Day -16, Day -15, Day -14, Day -13, Day -12, Day -11, Day 10, Day -9, Day -8, Day -7, Day -6, Day -5, Day -4, Day -3, Day -2, Day -1, Day 0, Day 1, Day 15 (-3 days to +1 day), Day 29 (±4 days), Day 57 (±7 days), Day 85 (±7 days), Day 113 (±7 days), Day 141 (±7 days), Day 169 (±7 days), Day 197 (±7 days). days), Day 225 (±7 days), Day 253 (±7 days), Day 281 (±7 days), Day 309 (±7 days) or around Day 337 (±7 days) post-treatment initiation. In aspects, pharmacodynamics is analyzed at any time before, during, or after treatment with a Tn3 development framework. Inflammatory Markers

[0195] In aspects, an analysis comprises determining a level of inflammatory markers. Exemplary markers of inflammation include, but are not limited to: immunoglobulins (IgM, IgG, IgA), beta-2 microglobulin, C-reactive protein (CRP), CXCL13, serum C3, C4 and free light chains, cryoglobulins, and serum and urinary immunofixation and combinations thereof. In aspects, whole blood, plasma, serum, and urine are collected to assess markers of Petition 870250087411, dated 09 / 26 / 2025, page 170 / 404 125 / 327 Inflammation. In aspects, a change is determined compared to a baseline. In aspects, a change is determined from the baseline in levels of inflammation markers (immunoglobulins, beta-2 microglobulin, CRP, CXCL13, serum C3, C4 and free light chains). In aspects, suitable assays to analyze a level of inflammation include: ELISA, high-sensitivity CRP test (HS), CRP test, Luminex and combinations thereof. In some respects, administration of a Tn3 scaffold is effective in reducing the level of an inflammation biomarker in a subject by at least about or at most about: 20%, 30%, 40%, 45%, 50%, 60%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or up to 100% compared to autoantibody levels in an otherwise comparable method, where the subject of the otherwise comparable method is not administered with a Tn3 scaffold.In some respects, administration of a Tn3 framework is effective in reducing the level of an inflammation biomarker in a subject by at least about or at most about: 3%-5%, 5%-10%, 10%-20%, or 5%-25% compared to a baseline level before administration.

[0196] In some respects, an analysis of inflammatory markers can be done in approximately -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 Petition 870250087411, dated 09 / 26 / 2025, page 171 / 404 126 / 327 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least about 56 weeks after the start of treatment. In In terms of aspects, an analysis of inflammatory markers can be performed at approximately Day 1, 15 days (-3 days to +1 day), Day 29 (±4 days), Day 57 (±7 days), Day 85 (±7 days), Day 113 (±7 days), Day 141 (±7 days), Day 169 (±7 days), Day 197 (±7 days), Day 225 (±7 days), Day 253 (±7 days), Day 281 (±7 days), Day 309 (±7 days) or at approximately Day 337 (±7 days) post-treatment initiation. In terms of aspects, markers are analyzed at any time before, during, or after treatment with a Tn3 development framework. American College of Rheumatology / European Alliance of Associations for Rheumatology (ACR / EULAR)

[0197] In aspects, an analysis comprises an ACR / EULAR classification. In aspects, an analysis comprises a 2016 ACR / EULAR classification. In aspects, an analysis comprises a 2016 ACR / EULAR classification for primary Sjögren's syndrome. In aspects, a classification comprises a score based on the following items: labial salivary gland with focal lymphocytic sialadenitis and focus score, positive anti-SSA (Ro) score, ocular staining score and / or van Bijsterveld score, score of Petition 870250087411, dated 09 / 26 / 2025, page 172 / 404 127 / 327 Schirmer is a measure of the total unstimulated salivary flow rate. In aspects, a labial salivary gland with focal lymphocytic sialadenitis and a focus score is h 1. In aspects, an ocular staining score is h 5 in at least one eye. In aspects, a van Bijsterveld score is h 4. In aspects, a Schirmer score is d 5 mm / 5 min in at least one eye. In aspects, the total unstimulated salivary flow rate is d 0.1 ml / min. In aspects, one or more scores from an ACR / EULAR classification are weighted. In aspects, a labial salivary gland with focal lymphocytic sialadenitis and focus is weighted 3. In aspects, an ocular coloration score is weighted 3. In aspects, a van Bijsterveld score is weighted 1. In aspects, a Schirmer score is weighted 1. In aspects, a total unstimulated salivary flow rate is weighted 1. In aspects, a subject with need of the same has a combined weighted score of h 4.In some respects, a person with this need may be asked at least one of the following questions: 1) Have you ever had daily, persistent, and problematic dry eyes for more than 3 months?; 2) Do you have a recurring sensation of sand or gravel in your eyes?; 3) Do you use tear substitutes 3 times a day?; 4) Have you had a daily sensation of dry mouth for more than 3 months?; 5) Do you usually drink liquids to help swallow dry foods?

[0198] In aspects, an ACR / EULAR analysis can be done in approximately -28 days, -27 days, -26 days, -25 days, 24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, Petition 870250087411, dated 09 / 26 / 2025, page 173 / 404 128 / 327 -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least approximately 56 weeks post-treatment initiation. In some respects, an ACR / EULAR analysis can be performed around Day -28. Day -27, Day -26, Day -25, Day -24, Day -23, Day -22, Day - 21, Day -20, Day -19, Day -18, Day -17, Day -16, Day -15, Day -14, Day -13, Day -12, Day -11, Day -10, Day -9, Day - 8, Day -7, Day -6, Day -5, Day -4, Day -3, Day -2, Day -1, or around Day 0 post-treatment initiation. In aspects, ACR / EULAR is analyzed at any time before, during, or after treatment with a Tn3 development framework. Ocular Surface Disease Index (OSDI)

[0199] In aspects, an analysis comprises an OSDI assessment. In aspects, an OSDI assessment comprises an OSDI questionnaire. The OSDI is effective in discriminating between normal, mild to moderate, and severe dry eye diseases. In aspects, an OSDI assessment evaluates three subsets: Petition 870250087411, dated 09 / 26 / 2025, page 174 / 404 129 / 327 function related to vision, eye symptoms or environmental triggers or combinations thereof.

[0200] In aspects, an OSDI assessment produces a score. In aspects, an OSDI score ranges from about 0 to about 100: 0 to 12 represents normal, 13-22 represents mild dry eye disease, 23-32 represents moderate dry eye disease, 33-100 represents severe dry eye disease. In aspects, an OSDI score ranges from about 0 to about 12, from about 13 to about 22, from about 23 to about 32, from about 33 to about 100, from about 20 to about 50, from about 60 to about 100, from about 40 to about 70, from about 10 to about 30, or from 5 to about 25.

[0201] In some respects, an OSDI score is decreased in a subject in need of the same after administration of a Tn3 disclosure framework. In some respects, an OSDI score may be decreased compared to an otherwise comparable method, where the subject of the otherwise comparable method is not administered with a Tn3 framework compared to an otherwise comparable method that lacks the administration of a Tn3 framework. In terms of aspects, an OSDI score is reduced by at least approximately or at most approximately: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 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, 99 or 100 Petition 870250087411, dated 09 / 26 / 2025, page 175 / 404 130 / 327 points compared to a comparable method that lacks administration.

[0202] In aspects, the OSDI assessment can be analyzed in approximately -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks 48 weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least about 56 weeks after starting treatment. In some respects, OSDI is Analyzed at any time before, during, or after treatment with a Tn3 framework of revelation. Sjogren's Tool for Response Analysis (STAR)

[0203] In some respects, an analysis can include Sjogren's Tool for Response Analysis (STAR). STAR is a composite responder index that was developed by the NECESSITY consortium, supported by an international panel of pSS experts, scientists, methodologists, and patients to analyze the effectiveness of Petition 870250087411, dated 09 / 26 / 2025, page 176 / 404 131 / 327 treatment based on improvement in disease activity (Seror et al., 2022). The STAR contains 5 domains: systemic activity, symptoms, lacrimal gland function, salivary gland function, and biomarkers of autoimmune activity. The domains are weighted differently. In some aspects, a STAR domain comprises another analysis of the development.

[0204] In aspects, a STAR survey is scored from approximately 1 to approximately 9. In aspects, a STAR survey is scored from approximately 1, 2, 3, 4, 5, 6, 7, 8 or approximately 9. In aspects, a STAR survey is scored from approximately 1 to approximately 3, from approximately 1 to approximately 5, from approximately 5 to approximately 9, from approximately 6 to approximately 9, from approximately 7 to approximately 9 or from approximately 4 to approximately 9. In aspects, a STAR survey is scored at approximately ^ 5. In aspects, a STAR survey may comprise analyzing a subject in need of the same, administered with a Tn3 disclosure framework compared to baseline. In aspects, a subject's STAR score is increased compared to an otherwise comparable method, where the subject of the otherwise comparable method is not administered a Tn3 disclosure framework. In some respects, a subject with the same needs administered with a Tn3 framework of disclosure has an increased STAR score compared to baseline.In some aspects, a STAR score is increased by approximately 1, 2, 3, 4, 5, 6, 7, or 8 points.

[0205] In some respects, a STAR survey can be analyzed in approximately -35 days, -34 days, -33 days, -32 days, 31 days, -30 days, -29 days, -28 days, -27 days, -26 days, 25 days, -24 days, -23 days, -22 days, -21 days, -20 days, 19 days, -18 days, -17 days, -16 days, -15 days, -14 days Petition 870250087411, dated 09 / 26 / 2025, page 177 / 404 132 / 327 -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, 3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least about 56 weeks after the start of treatment. In In terms of aspects, a STAR study can be analyzed at approximately 15 days (+-3 to 1 day), 29 days ± 4 days, 57 days ± 7 days, 85 days ± 7 days, 113 days ± 7 days, 141 days ± 7 days, 169 days ± 7 days, 197 days ± 7 days, 225 days ± 7 days, 253 days ± 7 days, 281 days ± 7 days, 309 days ± 7 days, 337 days ± 7 days, or 421 days ± 7 days post-treatment initiation. In terms of aspects, a STAR study is analyzed at any time before, during, or after treatment with a Tn3 development framework. Diary for Analysis of the Patient-Reported Index of Sjögren's Syndrome (DASPRI)

[0206] In some respects, an analysis can include Diary for Analysis of Sjögren's Patient-Reported Index (DASPRI). In some respects, DASPRI is also known as the SS Symptom Diary (SSSD). DASPRI is a Petition 870250087411, dated 09 / 26 / 2025, page 178 / 404 133 / 327 questionnaire completed by participants to measure the severity of main symptoms in patients with SS. There may be a recovery period of approximately 24 hours. Subjects rate the severity of each symptom at its worst in domains comprising: dryness, fatigue (e.g., feeling tired), and pain (joint or muscle pain in the arms and / or legs), using a numerical rating scale (ranging from 0 [no symptoms] to 10 [maximum imaginable severity]). The dryness domain assesses the severity of location-specific dryness (mouth, eyes, skin, and genitals). Additionally, subjects will be asked to rate their most bothersome dryness locations. In terms of aspects, outcomes based on the DASPRI are defined as average daily scores over a 7-day period.

[0207] In aspects, a DASPRI domain is scored from about 0 to about 10. In some aspects, a DASPRI question is scored from about 0 to about 2, from about 1 to about 5, from about 2 to about 7, from about 0 to about 9, from about 1 to about 10, from about 8 to about 10, or from about 6 to about 10. In aspects, a DASPRI composite score is in the range of about 0 to about 100. In aspects, a DASPRI composite score is approximately 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 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, 99 or about 100. In aspects, Petition 870250087411, dated 09 / 26 / 2025, page 179 / 404 134 / 327 A composite DASPRI score is approximately 0 to approximately 10, approximately 5 to approximately 15, approximately 20 to approximately 20, approximately 15 to approximately 25, approximately 20 to approximately 30, approximately 20 to approximately 50, approximately 30 to approximately 60, approximately 40 to approximately 70, approximately 50 to approximately 80, approximately 60 to approximately 90, or approximately 70 to approximately 100.

[0208] In some aspects, a DASPRI may involve analyzing a subject in need of the same, administered with a Tn3 disclosure framework compared to baseline. In some aspects, a subject's DASPRI score is reduced compared to an otherwise comparable method, where the subject of the otherwise comparable method is not administered a Tn3 disclosure framework. In some aspects, a subject in need of the same administered with a Tn3 disclosure framework has a reduced DASPRI score compared to baseline. In some aspects, a DASPRI score is reduced by approximately 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 95, 96, 97, 98, 99, or 100.

[0209] In aspects, a DASPRI survey can be analyzed in approximately -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 Petition 870250087411, dated 09 / 26 / 2025, pp. 180 / 404 135 / 327 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, 52 weeks, 53 weeks, 54 weeks, 55 weeks, or at least Approximately 56 weeks post-treatment initiation. In aspects, a DASPRI survey can be analyzed at approximately -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 days and approximately once a week, twice a week, three times a week, four times a week, five times a week, six times a week, or seven times a week post-treatment initiation. In aspects, a DASPRI survey is analyzed at any time before, during, or after treatment with a Tn3 disclosure framework. Pharmaceutical Compositions

[0210] In some respects, pharmaceutical compositions are provided. A pharmaceutical composition may comprise a Tn3 disclosure framework. In some respects, a pharmaceutical composition is part of a therapeutic regimen comprising a Tn3 disclosure framework and one or more additional therapeutic agents provided herein.

[0211] For a subcutaneous route, a needle is inserted into fatty tissue immediately beneath the skin. After a drug is injected, it then moves into small blood vessels. Petition 870250087411, dated 09 / 26 / 2025, page 181 / 404 136 / 327 blood vessels (capillaries) and are transported by the bloodstream. Alternatively, a drug reaches the bloodstream through the lymphatic vessels. The intramuscular route is preferred over the subcutaneous route when larger volumes of a drug product are needed. Since muscles lie beneath the skin and adipose tissue, a longer needle is used. Drugs are usually injected into the muscle of the forearm, thigh, or buttock. How quickly the drug is absorbed into the bloodstream depends, in part, on the blood supply to the muscle: the poorer the blood supply, the longer it takes for the drug to be absorbed. For the intravenous route, a needle is inserted directly into a vein. A solution containing the drug can be administered in a single dose or by continuous infusion.For infusion, the solution is moved by gravity (from a collapsible plastic bag) or, more commonly, by an infusion pump through thin flexible tubing to a tube (catheter) inserted into a vein, usually in the forearm.

[0212] In some respects, a pharmaceutical composition provided herein is administered by infusion. An infusion may occur over a period of time. For example, an infusion may be the administration of a pharmaceutical agent over a period of about 5 minutes up to about 10 hours. An infusion may occur over a period of about 5 min, 10 min, 20 min, 30 min, 40 min, 50 min, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, or up to about 10 hours. In some respects, intravenous administration is used to administer Petition 870250087411, dated 09 / 26 / 2025, page 182 / 404 137 / 327 a precise dose is delivered quickly and in a well-controlled manner throughout the body. It is also used for irritating solutions that would cause pain and tissue damage if administered by subcutaneous or intramuscular injection. When administered intravenously, a drug is delivered immediately into the bloodstream and tends to take effect more quickly than when administered by any other route. Consequently, healthcare providers closely monitor people receiving an intravenous injection for signs that the drug is working or causing unwanted side effects. Furthermore, the effect of a drug administered this way tends to last less time. As a result, some drugs need to be administered by continuous infusion to maintain their constant effect. In some cases, infusion reactions can occur and include headaches, nausea, drowsiness, dyspnea, fever, myalgia, skin rashes, or other symptoms.The potential risks associated with administering a Tn3 scaffold are infection, redness, swelling, pain, and induration at the administration site. Prior to each IV infusion, subjects may receive prophylaxis with IV methylprednisolone, oral diphenhydramine, and oral acetaminophen, or equivalent(s) to reduce the risk or severity of potential reactions.

[0213] In some respects, a treatment regimen comprising a pharmaceutical composition may be dosed according to a subject's body weight. In subjects determined to be obese (BMI > 35) it may be necessary to use a practical weight. In some respects, body surface area may be used to calculate a dosage. Petition 870250087411, dated 09 / 26 / 2025, pp. 183 / 404 138 / 327

[0214] In some respects, a pharmaceutical composition may be administered alone or in combination with a pharmaceutically acceptable carrier or excipient, by any route, and such administration may be carried out in single or multiple doses. More particularly, a pharmaceutical composition may be combined with various pharmaceutically acceptable inert carriers in the form of tablets, capsules, lozenges, lozenges, candies, powders, sprays, aqueous suspensions, injectable solutions, elixirs, syrups and the like. Such carriers include diluents or solid fillers, sterile aqueous media and various non-toxic organic solvents, etc. In addition, pharmaceutical formulations may be suitably sweetened and / or flavored by means of various agents of the type commonly used for such purposes.Exemplary carriers and excipients may include dextrose, monobasic sodium phosphate, dibasic sodium phosphate, monobasic / dibasic sodium phosphate, sodium chloride (NaCl), sucrose, lactose, cellulose, xylitol, sorbitol, maltitol, gelatin, PEG, PVP, histidine / histidine hydrochloride, trehalose dihydrate, polysorbate 80, poloxamer 188 (pH 7.4), and any combination thereof. In aspects, a pharmaceutical composition used in the methods of the invention comprises: monobasic / dibasic sodium phosphate, sucrose, and poloxamer 188 (pH 7.4). NUMBERED MODALITIES Set of Modalities 1 1. A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising: administering a Tn3 framework, wherein the Tn3 framework comprises a Petition 870250087411, dated 09 / 26 / 2025, pp. 184 / 404 139 / 327 CD40L-specific monomeric subunit, wherein the CD40L-specific monomeric subunit comprises seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the Tn3 scaffold comprising the CD40L-specific monomeric subunit is administered at a dose of approximately 1500 mg to approximately 3000 mg, and wherein the subject has moderate to severe systemic disease activity as determined by the European Alliance of Associations' Disease Activity Index SS Rheumatology (EULAR) (ESSDAI). 2. The modality 1 method, in which the subject has an ESSDAI score of 5-7, 5-10, 5-13, or 10-13 before administration of the Tn3 framework. 3. The method of modality 2, in which the subject has an ESSDAI ^5 score. 4. The method of any of the modalities 1-3, in which administration of the Tn3 framework is effective in reducing the EULAR Sjögren's Syndrome Patient-Reported Index (ESSPRI) score after administration. 5. The method of modality 4, in which the ESSPRI score is reduced by at least 2, 3, 4, or 5 points. 6. A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising: administering a Tn3 scaffold, wherein the Tn3 scaffold comprises a specific CD40L monomeric subunit, wherein the specific CD40L monomeric subunit comprises seven Petition 870250087411, dated 09 / 26 / 2025, pp. 185 / 404 140 / 327 beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the Tn3 scaffold comprising the specific monomeric subunit of CD40L is administered at a dose of approximately 1500 mg to approximately 3000 mg, and wherein the subject has an ESSPRI score ^ 5. 7. The modality 6 method, in which the subject has an ESSDAI score of < 5 before administration of the Tn3 framework. 8. The method of any of the modalities 6-7, in which the subject has residual salivary gland function, as defined by a total stimulated salivary flow greater than 0.1 ml / min. 9. The method of any of the modalities 1-8, in which a sample from the subject is positive for: anti-Ro autoantibodies, rheumatoid factor, or both anti-Ro autoantibodies and rheumatoid factor. 10. The method of any of the modalities 1-9, where the dose is 1500 mg. 11. The method of any of the modalities 1-9, where the dose is 3,000 mg. 12. The method of any of the modalities 2-11, in which the baseline change in ESSDAI is determined after administration of the Tn3 framework. Petition 870250087411, dated 09 / 26 / 2025, pp. 186 / 404 141 / 327 13. The modality 12 method, in which the change from baseline is determined every four weeks until week 48 after administration of the Tn3 framework. 14. The method of any of the modalities 2-13, in which administration of the Tn3 framework is effective in reducing the subject's ESSDAI score after administration. 15. The method of modality 14, in which the ESSDAI score is reduced by at least 1, 2, 3, 4, or 5 points. 16. The method of modality 14, in which the ESSDAI score is reduced by at least 5 points. 17. The method of any of the modalities 1-16, in which administration of the Tn3 framework is effective in reducing a baseline score of tender and swollen joint counts of the subject after administration. 18. The method of any of the modalities 1-16, in which administration of the Tn3 framework is effective in reducing a subject's baseline score on the Short Form Health Survey 36 (SF-36) after administration. 19. The method of any of the modalities 1-18, in which administration of the Tn3 framework is effective in reducing a baseline level of inflammatory markers after administration, and in which the markers are selected from the group consisting of: immunoglobulin, β2-microglobulin, C-reactive protein, and combinations thereof. 20. The method of any of the modalities 1-19, in which administration of the Tn3 framework is effective in reducing a baseline level of a biomarker, and in which the biomarker is selected from the group consisting of: plasma-soluble CD40L, B cells, serum CXCL13, Petition 870250087411, dated 09 / 26 / 2025, pp. 187 / 404 142 / 327 rheumatoid factor autoantibodies, anti-Ro autoantibodies and combinations thereof. 21. The method of any of the modalities 1-20, in which administration of the Tn3 framework is effective in reducing a baseline level of a disease symptom, and in which the disease symptom is selected from the group consisting of: fatigue, dry mouth, dry eyes, vaginal dryness, pain, and combinations thereof. 22. The method of any of the modalities 1-21, in which the expression levels of genes associated with SS are reduced in a blood sample from the subject at week 48 after administration. 23. The method of any of the modalities 1-22, in which the levels of B cells, selected from the group consisting of: CD27+ memory B cells, marginal zone B cells, plasmablasts, plasma cells and combinations thereof, are reduced in a blood sample from the subject up to week 48 after administration. 24. The method of any of the modalities 1-23, in which the Tn3 framework is administered as a loading dose and subsequently as a maintenance dose. 25. The 24-mode method, in which the loading dose comprises administering the Tn3 framework once every 2 weeks for at least 3 doses. 26. The 24-mode method, in which the maintenance dose comprises administering the Tn3 framework once every 4 weeks for at least 4 doses. 27. The 24-week modality method, in which the time between the last loading dose and the first maintenance dose is approximately 4 weeks. Petition 870250087411, dated 09 / 26 / 2025, pp. 188 / 404 143 / 327 28. The method of any of the modalities 1-27, in which the Tn3 framework is administered once every 4 weeks, once every 2 months, once every 3 months, once every 4 months, or once every 6 months. 29. The method of any of the modalities 1-28, in which the Tn3 framework is administered in at least 4 doses. 30. The method of any of the modalities 1-28, in which the Tn3 framework is administered in at least 5 doses. 31. The method of any of the modalities 1-30, in which the Tn3 scaffold is administered intravenously, subcutaneously, orally, intramuscularly, intrathecally, sublingually, rectally, vaginally, cutaneously, systemically, topically, transdermally, or by inhalation. 32. The method of modality 31, in which the Tn3 framework is administered intravenously. 33. The method of any of the embodiments 1-32, in which the Tn3 framework comprises two specific CD40L monomeric subunits connected in tandem. 34. The method of embodiment 33, in which the two specific monomeric subunits of CD40L each comprise SEQ ID NO: 3. 35. The method of any of the embodiments 33-34, in which specific monomeric subunits of CD40L are connected by a ligand. 36. The method of any of the embodiments 33-35, in which at least one specific monomeric subunit of CD40L is fused or conjugated directly to a polyethylene glycol (PEG). 37. The method of any of the embodiments 33-35, in which at least one specific monomeric subunit of CD40L is Petition 870250087411, dated 09 / 26 / 2025, pp. 189 / 404 144 / 327 fused or conjugated, by means of a binder, to a polyethylene glycol (PEG). 38. The method of embodiment 37, in which the ligand comprises a peptide ligand. 39. The method of embodiment 37, in which the ligand comprises SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 or SEQ ID NO: 10. 40. The method of any of the modalities 33-39, in which at least one specific monomeric subunit of CD40L is fused or conjugated to an albumin. 41. The method of modality 40, in which the albumin is human serum albumin (HSA). 42. The method of modality 41, wherein HSA is a variant of HSA comprising SEQ ID NO: 4. 43. The method of any of the modalities 24-42, in which the loading and maintenance doses are the same. 44. The method of any of the 24-42 modalities, in which the loading and maintenance doses are different. 45. The method of any of the modalities 1-44, in which the Tn3 framework comprises SEQ ID NO: 1. 46. ​​The method of any of the modalities 10-45, in which 1,500 mg of the Tn3 framework is administered intravenously at weeks 0, 2, and 4, and then once every 4 weeks thereafter. 47. The method of any of the modalities 11-45, in which 3000 mg of the Tn3 framework are administered intravenously at weeks 0, 4 and 12 and then once every 12 weeks thereafter. 48. A method for treating Sjögren's syndrome (SS) in a subject with the need for the same, comprising: administering a Tn3 framework comprising the SEQ ID NO: 1 Petition 870250087411, dated 09 / 26 / 2025, pp. 190 / 404 145 / 327 to the subject, in which the Tn3 framework is administered at a dose of approximately 1500 mg, in which the subject has an ESSDAI score of ^5 before administration, and in which administration is effective in reducing the ESSDAI score compared to a comparable subject who received placebo. 49. The method of modality 48, in which 1500 mg are administered intravenously in weeks 0, 2 and 4 and then once every 4 weeks thereafter. 50. A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising: administering a Tn3 scaffold comprising SEQ ID NO: 1 to the subject, wherein the Tn3 scaffold is administered at a dose of approximately 3000 mg, wherein the subject has an ESSDAI score of ^5 prior to administration, and wherein the administration is effective in reducing the ESSDAI score compared to a comparable subject who received placebo. 51. The modality 50 method, in which 3000 mg of the Tn3 framework are administered intravenously at weeks 0, 4, and 12, and then once every 12 weeks thereafter. 52. The method of any of the modalities 48-51, in which the ESSDAI score is reduced by 2 points, 3 points, 4 points, or 5 points. 53. The method of any of the modalities 48-52, in which the subject has an ESSDAI score of 5-7, 5-10, 5-13 or 10-13. 54. A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising: administering a Tn3 scaffold comprising SEQ ID NO: 1 to the subject, wherein the Tn3 scaffold is administered at a dose of approximately 1500 mg, wherein the subject has a score on Petition 870250087411, dated 09 / 26 / 2025, pp. 191 / 404 146 / 327 European Alliance of Associations for Rheumatology (EULAR) SS Disease Activity Index (ESSDAI) < 5, and in which the subject has a score on the EULAR Sjögren's Syndrome Patient-Reported Index (ESSPRI) ^ 5 prior to administration. 55. The method of modality 54, in which 1500 mg are administered intravenously in weeks 0, 2 and 4 and then once every 4 weeks thereafter. 56. A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising: administering a Tn3 scaffold comprising SEQ ID NO: 1 to the subject, wherein the Tn3 scaffold is administered at a dose of approximately 3000 mg, wherein the subject has a score on the European Alliance of Associations for Rheumatology (EULAR) SS Disease Activity Index (ESSDAI) < 5, and wherein the subject has a score on the EULAR Sjögren's Syndrome Patient-Reported Index (ESSPRI) ^ 5 prior to administration. 57. The method of modality 56, in which 3000 mg of the Tn3 framework are administered intravenously at weeks 0, 4, and 12, and then once every 12 weeks thereafter. 58. The method of any of the modalities 54-57, in which the subject's ESSPRI score is 5-6, 5-7, 6-8, 6-9, or 5-10 prior to administration. Set of Modalities 2 1. A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising: administering a Tn3 scaffold, wherein the Tn3 scaffold comprises a specific CD40L monomeric subunit, wherein the specific CD40L monomeric subunit comprises seven Petition 870250087411, dated 09 / 26 / 2025, pp. 192 / 404 147 / 327 beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the Tn3 scaffold comprising the specific monomeric subunit of CD40L is administered at a dose of approximately 1500 mg to approximately 3000 mg, and wherein the subject has moderate to severe systemic disease activity as determined by the European Alliance of Associations for Rheumatology (EULAR) Disease Activity Index (ESSDAI). 2. The modality 1 method, in which the subject has an ESSDAI score of 5-7, 5-10, 5-13, or 10-13 before administration of the Tn3 framework. 3. The method of modality 2, in which the subject has an ESSDAI ^5 score. 4. The method of any of the modalities 1-4, in which administration of the Tn3 framework is effective in reducing the EULAR Sjögren's Syndrome Patient-Reported Index (ESSPRI) score after administration. 5. The method of modality 4, in which the ESSPRI score is reduced by at least 2, 3, 4, or 5 points. 6. A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising: administering a Tn3 scaffold, wherein the Tn3 scaffold comprises a specific CD40L monomeric subunit, wherein the specific CD40L monomeric subunit comprises seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein the AB loop Petition 870250087411, dated 09 / 26 / 2025, pp. 193 / 404 Loop 148 / 327 comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the Tn3 scaffold comprising the specific monomeric subunit of CD40L is administered at a dose of approximately 1500 mg to approximately 3000 mg, and wherein the subject has an ESSPRI score of 5. 7. The modality 6 method, in which the subject has an ESSDAI score of < 5 before administration of the Tn3 framework. 8. The method of any of the modalities 6-7, in which the subject has residual salivary gland function, as defined by a total stimulated salivary flow greater than 0.1 ml / min. 9. The method of any of the modalities 1-8, in which a sample from the subject is positive for: anti-Ro autoantibodies, rheumatoid factor, or both anti-Ro autoantibodies and rheumatoid factor. 10. The method of any of the modalities 1-9, where the dose is 1500 mg. 11. The method of any of the modalities 1-9, where the dose is 3,000 mg. 12. The method of any of the modalities 2-11, in which the baseline change in ESSDAI is determined after administration of the Tn3 framework. 13. The modality 12 method, in which the change from baseline is determined every four weeks until week 48 after administration of the Tn3 framework. Petition 870250087411, dated 09 / 26 / 2025, pp. 194 / 404 149 / 327 14. The method of any of the modalities 2-13, in which administration of the Tn3 framework is effective in reducing the subject's ESSDAI score after administration. 15. The method of modality 14, in which the ESSDAI score is reduced by at least 1, 2, 3, 4, 5, 6, or 7 points. 16. The method of modality 14, in which the ESSDAI score is reduced by at least 6 points. 17. The method of any of the modalities 1-16, in which administration of the Tn3 framework is effective in reducing a baseline score of tender and swollen joint counts of the subject after administration. 18. The method, according to any of the modalities 116, in which administration of the Tn3 framework is effective in reducing a subject's baseline score on the Short Form Health Survey 36 (SF-36) at week 48 after administration. 19. The method of any of the modalities 1-16, in which the administration of the Tn3 framework is effective in improving a subject's baseline score, wherein the baseline scores are selected from the group consisting of: Functional Fatigue Analysis in Chronic Disease Therapy (FACIT-Fatigue), PROMIS Fatigue Short Form 10a, Ocular Surface Disease Index (OSDI), EQ-5D-5L and Patient Global Impression of Severity (PGIS). 20. The method of any of the modalities 1-18, in which administration of the Tn3 framework is effective in reducing a baseline level of inflammatory markers after administration, and in which the markers are selected from among Petition 870250087411, dated 09 / 26 / 2025, pp. 195 / 404 150 / 327 the group consisting of: immunoglobulin, β2 microglobulin, C-reactive protein and combinations thereof. 21. The method of any of the modalities 1-19, in which administration of the Tn3 framework is effective in reducing a baseline level of a biomarker, and in which the biomarker is selected from the group consisting of: plasma soluble CD40L, B cells, serum CXCL13, rheumatoid factor autoantibodies, anti-SSA autoantibodies (i.e., anti-Ro autoantibodies), anti-SSB autoantibodies (i.e., auto-La autoantibodies), and combinations thereof. 22. The method of any of the modalities 1-20, in which administration of the Tn3 framework is effective in reducing a baseline level of a disease symptom, and in which the disease symptom is selected from the group consisting of: fatigue, dry mouth, dry eyes, vaginal dryness, pain, and combinations thereof. 23. The method of any of the modalities 1-21, in which the expression levels of genes associated with SS are reduced in a blood sample from the subject at week 48 after administration. 24. The method of any of the modalities 1-22, in which the levels of B cells, selected from the group consisting of: CD27+ memory B cells, marginal zone B cells, plasmablasts, plasma cells and combinations thereof, are reduced in a blood sample from the subject up to week 48 after administration. 25. The method of any of the modalities 1-23, in which the Tn3 framework is administered as a loading dose and subsequently as a maintenance dose. Petition 870250087411, dated 09 / 26 / 2025, pp. 196 / 404 151 / 327 26. The 24-mode method, in which the loading dose comprises administering the Tn3 framework once every 2 weeks for at least 3 doses. 27. The 24-mode method, in which the maintenance dose comprises administering the Tn3 framework once every 4 weeks for at least 4 doses. 28. The 24-mode method, in which the time between the last loading dose and the first maintenance dose is approximately 4 weeks. 29. The method of any of the modalities 1-27, in which the Tn3 framework is administered once every 4 weeks, once every 2 months, once every 3 months, once every 4 months, or once every 6 months. 30. The method of any of the modalities 1-28, in which the Tn3 framework is administered in at least 4 doses. 31. The method of any of the modalities 1-28, in which the Tn3 framework is administered in at least 5 doses. 32. The method of any of the modalities 1-30, in which the Tn3 scaffold is administered intravenously, subcutaneously, orally, intramuscularly, intrathecally, sublingually, rectally, vaginally, cutaneously, systemically, topically, transdermally, or by inhalation. 33. The method of modality 31, in which the Tn3 framework is administered intravenously. 34. The method of any of the embodiments 1-32, in which the Tn3 framework comprises two specific CD40L monomeric subunits connected in tandem. 35. The method of embodiment 33, in which the two specific monomeric subunits of CD40L each comprise SEQ ID NO: 3. Petition 870250087411, dated 09 / 26 / 2025, pp. 197 / 404 152 / 327 36. The method of any of the embodiments 33-34, in which specific monomeric subunits of CD40L are connected by a ligand. 37. The method of any of the embodiments 33-35, in which at least one specific monomeric subunit of CD40L is fused or conjugated directly to a polyethylene glycol (PEG). 38. The method of any of the embodiments 33-35, in which at least one specific monomeric subunit of CD40L is fused or conjugated, by means of a ligand, to a polyethylene glycol (PEG). 39. The method of embodiment 37, in which the ligand comprises a peptide ligand. 40. The method of embodiment 37, in which the ligand comprises SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 or SEQ ID NO: 10. 41. The method of any of the embodiments 33-39, in which at least one specific monomeric subunit of CD40L is fused or conjugated to an albumin. 42. The method of modality 40, in which the albumin is human serum albumin (HSA). 43. The method of modality 41, wherein HSA is a variant of HSA comprising SEQ ID NO: 4. 44. The method of any of the 24-42 modalities, in which the loading and maintenance doses are the same. 45. The method of any of the 24-42 modalities, in which the loading and maintenance doses are different. 46. ​​The method of any of the modalities 1-44, in which the Tn3 framework comprises SEQ ID NO: 1. 47. The method of any of the modalities 10-45, in which 1500 mg of the Tn3 framework are administered via Petition 870250087411, dated 09 / 26 / 2025, pp. 198 / 404 153 / 327 intravenously at weeks 0, 2, and 4, and then every 4 weeks thereafter. 48. The method of any of the modalities 11-45, in which 3000 mg of the Tn3 framework are administered intravenously at weeks 0, 2 and 4 and then every 4 weeks thereafter. 49. A method for treating Sjögren's syndrome (SS) in a subject with need thereof comprising: administering a Tn3 scaffold comprising SEQ ID NO: 1 to the subject, wherein the Tn3 scaffold is administered at a dose of approximately 1500 mg, wherein the subject has an ESSDAI score of 5 prior to administration, and wherein the administration is effective in reducing the ESSDAI score compared to a comparable subject who received placebo. 50. The 48-mode method, in which 1500 mg are administered intravenously at weeks 0, 2, and 4, and then once every 4 weeks thereafter. 51. A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising: administering a Tn3 scaffold comprising SEQ ID NO: 1 to the subject, wherein the Tn3 scaffold is administered at a dose of approximately 3000 mg, wherein the subject has an ESSDAI score of 5 prior to administration, and wherein the administration is effective in reducing the ESSDAI score compared to a comparable subject who received placebo. 52. The modality 50 method, in which 3000 mg of the Tn3 framework are administered intravenously at weeks 0, 4, and 12, and then once every 12 weeks thereafter. Petition 870250087411, dated 09 / 26 / 2025, pp. 199 / 404 154 / 327 53. The method of any of the modalities 48-51, in which the ESSDAI score is reduced by 2 points, 3 points, 4 points, 5 points, 6 points, or 7 points after administration. 54. The method of any of the modalities 48-51, in which the subject has an ESSDAI score of 5-7, 5-10, 5-13, or 10-13 before administration. 55. A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising: administering a Tn3 scaffold comprising SEQ ID NO: 1 to the subject, wherein the Tn3 scaffold is administered at a dose of approximately 1500 mg, wherein the subject has a score on the European Alliance of Associations for Rheumatology (EULAR) SS Disease Activity Index (ESSDAI) < 5, and wherein the subject has a score on the EULAR Sjögren's Syndrome Patient-Reported Index (ESSPRI) < 5 prior to administration. 56. The method of modality 54, in which 1500 mg are administered intravenously in weeks 0, 2 and 4 and then once every 4 weeks thereafter. 57. A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising: administering a Tn3 scaffold comprising SEQ ID NO: 1 to the subject, wherein the Tn3 scaffold is administered at a dose of approximately 3000 mg, wherein the subject has a score on the European Alliance of Associations for Rheumatology (EULAR) SS Disease Activity Index (ESSDAI) < 5, and wherein the subject has a score on the EULAR Sjögren's Syndrome Patient-Reported Index (ESSPRI) < 5 prior to administration. Petition 870250087411, dated 09 / 26 / 2025, pages 200 / 404 155 / 327 58. The method of modality 56, in which 3000 mg of the Tn3 framework are administered intravenously at weeks 0, 4, and 12, and then once every 12 weeks thereafter. 59. The method of any of the modalities 54-57, in which the subject's ESSPRI score is 5-6, 5-7, 6-8, 6-9, or 5-10 prior to administration. 60. The method of any of the modalities 5-58, in which administration is effective in achieving at least a reduction of 0.6 points, 0.8 points, 1 point, 1.8 points, or 2 points in the ESSPRI score compared to baseline. 61. A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising: administering a Tn3 scaffold, wherein the Tn3 scaffold comprises a specific CD40L monomeric subunit, wherein the specific CD40L monomeric subunit comprises seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the subject is positive for anti-SSA / Ro antibodies. 62. A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising: administering a Tn3 scaffold, wherein the Tn3 scaffold comprises a specific CD40L monomeric subunit, wherein the specific CD40L monomeric subunit comprises seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID Petition 870250087411, dated 09 / 26 / 2025, pages 201 / 404 156 / 327 In section NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, where the subject is positive for FR antibodies. 63. The method of any of the modalities 1-60, in which administration is effective in achieving a 5%, 10%, 15%, 20%, 40%, or 60% reduction in the ESSPRI score compared to a comparable subject administered placebo or compared to a baseline level of the subject. Set of Modalities 3 1. A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising: administering a Tn3 scaffold, wherein the Tn3 scaffold comprises a specific monomeric subunit of CD40L, wherein the specific monomeric subunit of CD40L comprises seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the Tn3 scaffold comprising the specific monomeric subunit of CD40L is administered at a dose of approximately 1500 mg to approximately 3000 mg, and in which the subject has moderate to severe systemic disease activity, as determined by the European Alliance of Associations for Rheumatology (EULAR) SS Disease Activity Index (ESSDAI). 2. The modality 1 method, in which the subject has an ESSDAI score of 5-7, 5-10, 5-13, or 10-13 before administration of the Tn3 framework. Petition 870250087411, dated 09 / 26 / 2025, pages 202 / 404 157 / 327 3. The method of modality 2, in which the subject has an ESSDAI b5 score. 4. The method of any of the modalities 1-3, in which administration of the Tn3 framework is effective in reducing one EULAR Sjögren's Syndrome Patient-Reported Index (ESSPRI) score after administration. 5. The method of modality 4, in which the ESSPRI score is reduced by at least 2, 3, 4, or 5 points. 6. The method of any of the modalities 1-3, in which the administration of the Tn3 framework is effective in reducing the DASPRI score. 7. The method of modality 6, in which the DASPRI score is reduced by at least approximately 5, 10, 15, or 20 points. 8. A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising: administering a Tn3 scaffold, wherein the Tn3 scaffold comprises a specific monomeric subunit of CD40L, wherein the specific monomeric subunit of CD40L comprises seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the Tn3 scaffold comprising the specific monomeric subunit of CD40L is administered at a dose of approximately 1500 mg. approximately 3000 mg, and in which the subject has an ESSPRI b score of 5. Petition 870250087411, dated 09 / 26 / 2025, pp. 203 / 404 158 / 327 9. The modality 8 method, in which the subject has an ESSDAI score of < 5 before administration of the Tn3 framework. 10. The method of any of the modalities 8-9, in which the subject has residual salivary gland function, as defined by a total stimulated salivary flow greater than 0.1 ml / min. 11. The method of any of the modalities 1-10, in which a sample from the subject is positive for: anti-Ro autoantibodies, rheumatoid factor autoantibodies, or both anti-Ro autoantibodies and rheumatoid factor autoantibodies. 12. The method of any of the modalities 1-11, where the dose is 1500 mg. 13. The method of any of the modalities 1-11, where the dose is 3,000 mg. 14. The method of any of the modalities 2-13, in which the baseline change in ESSDAI is determined after administration of the Tn3 framework. 15. The modality 14 method, in which the change from baseline is determined every four weeks until week 48 after administration of the Tn3 framework. 16. The method of any of the modalities 2-15, in which administration of the Tn3 framework is effective in reducing the subject's ESSDAI score after administration. 17. The method of modality 16, in which the ESSDAI score is reduced by at least 1, 2, 3, 4, 5, 6, or 7 points. 18. The method of modality 16, in which the ESSDAI score is reduced by at least 6 points. Petition 870250087411, dated 09 / 26 / 2025, pages 204 / 404 159 / 327 19. The method of any of the modalities 8-18, in which the administration of the Tn3 framework is effective in reducing the DASPRI score. 20. The method of modality 19, in which the DASPRI score is reduced by at least approximately 5, 10, 15, or 20 points. 21. The method of any of the modalities 1-20, in which administration of the Tn3 framework is effective in reducing a baseline score of tender and swollen joint counts of the subject after administration. 22. The method, according to any of the modalities 121, in which administration of the Tn3 framework is effective in reducing a subject's baseline score on the Short Form Health Survey 36 (SF-36) at week 48 after administration. 23. The method of any of the modalities 1-22, in which the administration of the Tn3 framework is effective in improving a subject's baseline score, wherein the baseline scores are selected from the group consisting of: functional analysis of fatigue in chronic disease therapy (FACIT-Fatigue), PROMIS Fatigue Short Form 10a, Ocular Surface Disease Index (OSDI), EQ-5D-5L and patient's global impression of severity (PGIS). 24. The method of any of the modalities 1-23, in which administration of the Tn3 framework is effective in reducing a baseline level of inflammatory markers after administration, and in which the markers are selected from the group consisting of: immunoglobulin, β2 microglobulin, C-reactive protein and combinations thereof. Petition 870250087411, dated 09 / 26 / 2025, pp. 205 / 404 160 / 327 25. The method of any of the modalities 1-24, in which administration of the Tn3 framework is effective in reducing a baseline level of a biomarker, and in which the biomarker is selected from the group consisting of: plasma soluble CD40L, B cells, serum CXCL13, rheumatoid factor autoantibodies, anti-SSA autoantibodies (i.e., anti-Ro autoantibodies), anti-SSB autoantibodies (i.e., auto-La autoantibodies), and combinations thereof. 26. The method of any of the modalities 1-25, in which administration of the Tn3 framework is effective in reducing a baseline level of a disease symptom, and in which the disease symptom is selected from the group consisting of: fatigue, dry mouth, dry eyes, vaginal dryness, pain, and combinations thereof. 27. The method of any of the modalities 1-26, in which the expression levels of genes associated with SS are reduced in a blood sample from the subject at week 48 after administration. 28. The method of any of the modalities 1-27, in which the levels of B cells, selected from the group consisting of: CD27+ memory B cells, marginal zone B cells, plasmablasts, plasma cells and combinations thereof, are reduced in a blood sample from the subject up to week 48 after administration. 29. The method of any of the modalities 1-28, in which the Tn3 framework is administered as a loading dose and subsequently as a maintenance dose. 30. The modality 29 method, in which the loading dose comprises administering the Tn3 framework once every 2 weeks for at least 3 doses. Petition 870250087411, dated 09 / 26 / 2025, pp. 206 / 404 161 / 327 31. The modality 30 method, in which the maintenance dose comprises administering the Tn3 framework once every 4 weeks for at least 4 doses. 32. The method of modality 31, in which the time between the last loading dose and the first maintenance dose is approximately 4 weeks. 33. The method of any of the modalities 1-31, in which the Tn3 framework is administered once every 4 weeks, once every 2 months, once every 3 months, once every 4 months, or once every 6 months. 34. The method of any of the modalities 1-33, in which the Tn3 framework is administered in at least 4 doses. 35. The method of any of the modalities 1-33, in which the Tn3 framework is administered in at least 5 doses. 36. The method of any of the modalities 1-35, in which the Tn3 scaffold is administered intravenously, subcutaneously, orally, intramuscularly, intrathecally, sublingually, rectally, vaginally, cutaneously, systemically, topically, transdermally, or by inhalation. 37. The method of modality 36, in which the Tn3 framework is administered intravenously. 38. The method of any of the embodiments 1-37, in which the Tn3 framework comprises two specific CD40L monomeric subunits connected in tandem. 39. The method of embodiment 38, in which the two specific monomeric subunits of CD40L each comprise SEQ ID NO: 3. 40. The method of any of the embodiments 38-39, in which specific monomeric subunits of CD40L are connected by a ligand. Petition 870250087411, dated 09 / 26 / 2025, pp. 207 / 404 162 / 327 41. The method of any of the embodiments 38-40, in which at least one specific monomeric subunit of CD40L is fused or conjugated directly to a polyethylene glycol (PEG). 42. The method of any of the embodiments 38-40, in which at least one specific monomeric subunit of CD40L is fused or conjugated, by means of a ligand, to a polyethylene glycol (PEG). 43. The method of embodiment 42, in which the ligand comprises a peptide ligand. 44. The method of embodiment 43, in which the ligand comprises SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 or SEQ ID NO: 10. 45. The method of any of the modalities 38-40, in which at least one specific monomeric subunit of CD40L is fused or conjugated to an albumin. 46. ​​The method of modality 45, in which the albumin is human serum albumin (HSA). 47. The method of modality 46, wherein HSA is a variant of HSA comprising SEQ ID NO: 4. 48. The method of any of the modalities 29-47, in which the loading and maintenance doses are the same. 49. The method of any of the modalities 29-47, in which the loading and maintenance doses are different. 50. The method of any of the modalities 1-49, in which the Tn3 framework comprises SEQ ID NO: 1. 51. The method of any of the 12-50 modalities, in which 1,500 mg of the Tn3 framework is administered intravenously at weeks 0, 2, and 4, and then every 4 weeks thereafter. Petition 870250087411, dated 09 / 26 / 2025, pp. 208 / 404 163 / 327 52. The method of any of the modalities 13-50, in which 3000 mg of the Tn3 framework are administered intravenously at weeks 0, 2 and 4 and then every 4 weeks thereafter. 53. A method for treating Sjögren's syndrome (SS) in a subject with need thereof comprising: administering a Tn3 scaffold comprising SEQ ID NO: 1 to the subject, wherein the Tn3 scaffold is administered at a dose of approximately 1500 mg, wherein the subject has an ESSDAI score of h 5 prior to administration, and wherein the administration is effective in reducing the ESSDAI score compared to a comparable subject who received placebo. 54. The modality 49 method, in which 1500 mg are administered intravenously at weeks 0, 2, and 4, and then once every 4 weeks thereafter. 55. A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising: administering a Tn3 scaffold comprising SEQ ID NO: 1 to the subject, wherein the Tn3 scaffold is administered at a dose of approximately 3000 mg, wherein the subject has an ESSDAI score of h 5 prior to administration, and wherein the administration is effective in reducing the ESSDAI score compared to a comparable subject who received placebo. 56. The method of modality 55, in which 3000 mg of the Tn3 framework are administered intravenously at weeks 0, 4, and 12, and then once every 12 weeks thereafter. 57. The method of any of the modalities 49-56, in which the ESSDAI score is reduced by 2 points, 3 points, 4 points, 5 points, 6 points, or 7 points after administration. Petition 870250087411, dated 09 / 26 / 2025, pp. 209 / 404 164 / 327 58. The method of any of the modalities 49-57, in which the subject has an ESSDAI score of 5-7, 5-10, 5-13, or 10-13 before administration. 59. A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising: administering a Tn3 scaffold comprising SEQ ID NO: 1 to the subject, wherein the Tn3 scaffold is administered at a dose of approximately 1500 mg, wherein the subject has a score on the European Alliance of Associations for Rheumatology (EULAR) SS Disease Activity Index (ESSDAI) < 5, and wherein the subject has a score on the EULAR Sjögren's Syndrome Patient-Reported Index (ESSPRI) < 5 prior to administration. 60. The method of modality 59, in which 1500 mg are administered intravenously at weeks 0, 2, and 4, and then once every 4 weeks thereafter. 61. A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising: administering a Tn3 scaffold comprising SEQ ID NO: 1 to the subject, wherein the Tn3 scaffold is administered at a dose of approximately 3000 mg, wherein the subject has a score on the European Alliance of Associations for Rheumatology (EULAR) SS Disease Activity Index (ESSDAI) < 5, and wherein the subject has a score on the EULAR Sjögren's Syndrome Patient-Reported Index (ESSPRI) < 5 prior to administration. 62. The method of modality 61, in which 3000 mg of the Tn3 framework are administered intravenously at weeks 0, 4, and 12, and then once every 12 weeks thereafter. Petition 870250087411, dated 09 / 26 / 2025, page 210 / 404 165 / 327 63. The method of any of the modalities 59-62, in which the subject's ESSPRI score is 5-6, 5-7, 6-8, 6-9, or 5-10 before administration. 64. The method of any of the modalities 4-63, in which administration is effective in achieving at least a reduction of 0.6 points, 0.8 points, 1 point, 1.8 points, or 2 points in the ESSPRI score compared to the baseline. 65. A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising: administering a Tn3 scaffold, wherein the Tn3 scaffold comprises a specific CD40L monomeric subunit, wherein the specific CD40L monomeric subunit comprises seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the subject is positive for anti-SSA / Ro antibodies. 66. A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising: administering a Tn3 scaffold, wherein the Tn3 scaffold comprises a specific CD40L monomeric subunit, wherein the specific CD40L monomeric subunit comprises seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID Petition 870250087411, dated 09 / 26 / 2025, page 211 / 404 166 / 327 NO: 15, and the FG loop comprises SEQ ID NO: 16, where the subject is positive for FR antibodies. 67. The method of any of the modalities 1-66, in which administration is effective in achieving a reduction > 5%, 10%, 15%, 20%, 40% or 60% in the ESSPRI score compared to a comparable subject administered placebo or compared to a baseline level of the subject. 68. The method of any of the modalities 1-67, in which administration is effective in achieving a reduction > 5%, 10%, 15%, 20%, 40% or 60% in the DASPRI score compared to a comparable subject administered placebo or compared to a baseline level of the subject. Set of Modalities 4 1. A Tn3 scaffold for use in the treatment of Sjögren's syndrome (SS), wherein the Tn3 scaffold comprises a CD40L-specific monomeric subunit, wherein the CD40L-specific monomeric subunit comprises seven beta strands designated A, B, C, D, E, F, and G and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the Tn3 scaffold comprising the CD40L-specific monomeric subunit is administered at a dose of approximately 1500 mg once every 4 weeks, at which point the subject exhibits systemic activity. of moderate to severe disease, as determined by the European Alliance of Rheumatology Associations (EULAR) SS Disease Activity Index (ESSDAI) of >5. Petition 870250087411, dated 09 / 26 / 2025, page 212 / 404 167 / 327 2. The Tn3 framework for use, according to modality 1, in which at least 3 loading doses were administered to the subject prior to dosing every 4 weeks. 3. The Tn3 framework for use, according to modality 2, in which at least 3 loading doses occur in weeks 0, 2 and 4. 4. A Tn3 scaffold for use in the treatment of Sjögren's syndrome (SS), wherein the Tn3 scaffold comprises a CD40L-specific monomeric subunit, wherein the CD40L-specific monomeric subunit comprises seven beta strands designated A, B, C, D, E, F, and G and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the Tn3 scaffold comprising the CD40L-specific monomeric subunit is administered at a dose of approximately 3000 mg once every 12 weeks, in which the subject exhibits activity Systemic disease of moderate to severe degree, as determined by the European Alliance of Associations for Rheumatology (EULAR) SS Disease Activity Index (ESSDAI) of >5. 5. The Tn3 framework for use, according to modality 4, in which at least 3 loading doses were administered to the subject prior to dosing every 12 weeks. 6. The Tn3 framework for use, according to modality 5, in which at least 3 loading doses occur at weeks 0, 4, and 12. Petition 870250087411, dated 09 / 26 / 2025, pp. 213 / 404 168 / 327 7. A Tn3 scaffold for use in the treatment of Sjögren's syndrome (SS), wherein the Tn3 scaffold comprises a CD40L-specific monomeric subunit, wherein the CD40L-specific monomeric subunit comprises seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the Tn3 scaffold comprising the CD40L-specific monomeric subunit is administered at a dose of approximately 1500 mg once every 4 weeks, in which the subject presents with a state Moderate to severe symptoms defined by an ESSPRI score ^ 5, with low systemic disease activity defined by an ESSDAI score < 5. 8. The Tn3 framework for use, according to modality 7, in which at least 3 loading doses were administered to the subject prior to dosing every 4 weeks. 9. The Tn3 framework for use, according to modality 8, in which at least 3 loading doses occur in weeks 0, 2 and 4. 10. A Tn3 scaffold for use in the treatment of Sjögren's syndrome (SS), wherein the Tn3 scaffold comprises a CD40L-specific monomeric subunit, wherein the CD40L-specific monomeric subunit comprises seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE Petition 870250087411, dated 09 / 26 / 2025, pp. 214 / 404 Loop 169 / 327 comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the Tn3 scaffold comprising the specific monomeric subunit of CD40L is administered at a dose of approximately 3000 mg once every 12 weeks, in which the subject presents with a moderate to severe symptom state defined by an ESSPRI score ^ 5, with low systemic disease activity defined by an ESSDAI score < 5. 11. The Tn3 framework for use, according to modality 10, in which at least 3 loading doses were administered to the subject prior to dosing every 12 weeks. 12. The Tn3 framework for use, according to modality 11, in which at least 3 loading doses occur in weeks 0, 4 and 12. 13. The Tn3 framework for use, according to any of the modalities 1-5, in which the subject has an ESSDAI score of 5-7, 5-10, 5-13, or 10-13 before administration of the Tn3 framework. 14. The Tn3 framework for use, according to any of the modalities 1-5, in which administration is effective in reducing ESSDAI. 15. The Tn3 framework for use, according to modality 14, in which the ESSDAI score is reduced by at least 1, 2, 3, 4, 5, 6 or 7 points. 16. The Tn3 framework for use, according to modality 15, in which the ESSDAI score is reduced by at least 6 points. 17. The Tn3 framework for use, according to any of the modalities 13-16, in which the ESSDAI score is reduced by at least 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 1 Petition 870250087411, dated 09 / 26 / 2025, pp. 215 / 404 170 / 327 years after administration of the first loading dose compared to a baseline ESSDAI score. 18. The Tn3 framework for use, according to modality 17, in which the ESSDAI score is reduced 11 months after administration of the first loading dose. 19. The Tn3 framework for use, according to any of the modalities 7-12, in which the subject comprises stimulated total salivary flow > 0.1 ml / min at baseline. 20. The Tn3 framework for use, according to modality 19, in which the ESSPRI score is reduced by at least approximately 1.5, 2, 3, 4, or 5 points after administration of the week 0 loading dose. 21. The Tn3 framework for use, according to any of the modalities 7-12, in which a DASPRI score is reduced after administration. 22. The Tn3 framework for use, according to modality 21, in which the DASPRI score is reduced by at least approximately 5, 10, 15, or 20 points after administration of the week 0 loading dose. 23. The Tn3 framework for use, according to any of the embodiments 1-22, in which administration of the Tn3 framework is effective in reducing a baseline score of tender and swollen joint counts of the subject after administration. 24. The Tn3 framework for use, according to any of the modalities 1-23, in which administration of the Tn3 framework is effective in reducing a subject's baseline score on the Short Form Health Survey 36 (SF-36) after administration. Petition 870250087411, dated 09 / 26 / 2025, pp. 216 / 404 171 / 327 25. The Tn3 framework for use, according to any of the modalities 1-22, wherein administration of the Tn3 framework is effective in improving a subject's baseline score, wherein baseline scores are selected from the group consisting of: Functional Fatigue Analysis in Chronic Disease Therapy (FACITFatigue), PROMIS Fatigue Short Form 10a, Ocular Surface Disease Index (OSDI), EQ-5D-5L and Patient Global Impression of Severity (PGIS). 24. The Tn3 framework for use, according to any of the embodiments 1-23, wherein administration of the Tn3 framework is effective in reducing a baseline level of inflammatory markers after administration, and wherein the markers are selected from the group consisting of: immunoglobulin, β-2 microglobulin, C-reactive protein and combinations thereof. 25. The Tn3 scaffold for use, according to any of the embodiments 1-24, wherein administration of the Tn3 scaffold is effective in reducing a baseline level of a biomarker, and wherein the biomarker is selected from the group consisting of: plasma soluble CD40L, Ki67+CD27+ memory B cell, plasmablast, bright / elevated CD11c B cell, CD3, CD4, CD8, Tfh cell, serum CXCL13, rheumatoid factor, anti-SSA autoantibodies, anti-Ro autoantibodies, anti-SSB autoantibodies (i.e., anti-La autoantibodies) and combinations thereof. 26. The Tn3 framework for use, according to any of the embodiments 1-25, wherein administration of the Tn3 framework is effective in reducing a baseline level of a disease symptom, and wherein the disease symptom is selected from Petition 870250087411, dated 09 / 26 / 2025, p. 217 / 404 172 / 327 the group consisting of: fatigue, dry mouth, dry eyes, vaginal dryness, pain and combinations thereof. 27. The Tn3 framework for use, according to any of the embodiments 1-26, in which the expression levels of genes associated with SS are reduced in a blood sample from the subject at week 48 after administration. 28. The Tn3 framework for use, according to any of the embodiments 1-27, in which the levels of B cells, selected from the group consisting of: CD27+ memory B cells, marginal zone B cells, plasmablasts, plasma cells and combinations thereof, are reduced in a blood sample from the subject up to week 48 after administration. 29. The Tn3 framework for use, according to any of the modalities 1-28, in which the Tn3 framework is administered intravenously. 30. The Tn3 framework for use, according to any of the embodiments 1-29, wherein the Tn3 framework comprises two specific CD40L monomeric subunits connected in tandem. 31. The Tn3 framework of embodiment 30, in which the two specific monomeric subunits of CD40L each comprise SEQ ID NO: 3. 32. The Tn3 framework for use, according to any of the embodiments 30-31, in which specific monomeric CD40L subunits are connected by a linker. 33. The Tn3 framework for use, according to any of the embodiments 30-32, in which at least one specific CD40L monomeric subunit is fused or directly conjugated to a polyethylene glycol (PEG). Petition 870250087411, dated 09 / 26 / 2025, pp. 218 / 404 173 / 327 34. The Tn3 framework for use, according to any of the embodiments 30-33, in which at least one specific CD40L monomeric subunit is fused or conjugated, by means of a linker, to a polyethylene glycol (PEG). 35. The Tn3 framework for use, according to embodiment 34, wherein the ligand comprises a peptide ligand. 36. The Tn3 framework for use, according to embodiment 35, wherein the binder comprises SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 or SEQ ID NO: 10. 37. The Tn3 scaffold for use, according to any of the embodiments 30-36, in which at least one specific CD40L monomeric subunit is fused or conjugated to an albumin. 38. The Tn3 framework for use, according to embodiment 37, wherein the albumin is human serum albumin (HSA). 39. The Tn3 framework for use, according to embodiment 38, where HSA is a variant of HSA comprising SEQ ID NO: 4. 40. The Tn3 framework for use, according to any of the embodiments 1-39, wherein the Tn3 framework comprises SEQ ID NO: 1. Set of 5 Modalities 1. A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising: administering a Tn3 scaffold, wherein the Tn3 scaffold comprises a specific CD40L monomeric subunit, wherein the specific CD40L monomeric subunit comprises seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID Petition 870250087411, dated 09 / 26 / 2025, page 219 / 404 174 / 327 NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the Tn3 framework is administered at a dose of approximately 1500 mg once every 4 weeks, wherein the subject has moderate to severe systemic disease activity of ^5, as determined by the European Alliance of Associations for Rheumatology (EULAR) Disease Activity Index (ESSDAI). 2. The method of modality 1, wherein, prior to dosing every 4 weeks, the subject has been given at least 3 loading doses of 1500 mg each. 3. The modality 2 method, in which at least 3 loading doses are administered in weeks 0, 2, and 4. 4. A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising: administering a Tn3 scaffold, wherein the Tn3 scaffold comprises a specific monomeric subunit of CD40L, wherein the specific monomeric subunit of CD40L comprises seven beta strands designated A, B, C, D, E, F, and G and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the Tn3 scaffold is administered at a dose of approximately 3000 mg once every 12 weeks, wherein the subject has systemic disease activity. Moderate to severe of ^5, as determined by the European Alliance of Associations for Rheumatology (EULAR) SS Disease Activity Index (ESSDAI). Petition 870250087411, dated 09 / 26 / 2025, pp. 220 / 404 175 / 327 5. The method described in modality 4, in which, prior to dosing every 12 weeks, the subject was administered at least 3 loading doses of 3000 mg each. 6. The modality 5 method, in which at least 3 loading doses are administered in weeks 0, 4, and 12. 7. A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising: administering a Tn3 scaffold, wherein the Tn3 scaffold comprises a specific monomeric subunit of CD40L, wherein the specific monomeric subunit of CD40L comprises seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the Tn3 scaffold is administered at a dose of approximately 1500 mg once every 4 weeks, wherein the subject has a moderate symptomatic state. Severe disease defined by an ESSPRI score of 5, with low systemic disease activity defined by an ESSDAI score of < 5,and in which a Diary for Analysis of the Patient-Reported Index of Sjögren's Syndrome (DASPRI) score is reduced in the subject after administration. 8. The method described in modality 7, in which, prior to dosing every 4 weeks, the subject was given at least 3 loading doses of 1500 mg each. 9. The modality 8 method, in which at least 3 loading doses are administered in weeks 0, 2, and 4. 10. A method for treating Sjögren's syndrome (SS) in a subject in need thereof, comprising: administering Petition 870250087411, dated 09 / 26 / 2025, page 221 / 404 176 / 327 a Tn3 scaffold, wherein the Tn3 scaffold comprises a CD40L-specific monomeric subunit, wherein the CD40L-specific monomeric subunit comprises seven beta strands designated A, B, C, D, E, F, and G and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the Tn3 scaffold is administered at a dose of approximately 3000 mg once every 12 weeks, wherein the subject has a moderate to severe symptom status defined by an ESSPRI h5 score, with low systemic disease activity. defined by an ESSDAI score < 5, and in which a Diary for Analysis of the Sjogren's Patient-Reported Index (DASPRI) score is reduced in the subject after administration. 11. The method of modality 10, in which, prior to dosing every 12 weeks, the subject was administered at least 3 loading doses of 3000 mg each. 12. The method of modality 11, in which at least 3 loading doses are administered in weeks 0, 4, and 12. 13. The method of any of the modalities 1-5, in which the subject has an ESSDAI score of 5-7, 5-10, 5-13 or 10-13 before the administration of the Tn3 framework. 14. The method of any of the modalities 1-6, in which administration is effective in reducing the ESSDAI score. 15. The method of modality 14, in which the ESSDAI score is reduced by at least 1, 2, 3, 4, 5, 6, or 7 points. 16. The method of modality 15, in which the ESSDAI score is reduced by at least 6 points. Petition 870250087411, dated 09 / 26 / 2025, page 222 / 404 177 / 327 17. The method of any of the modalities 15-16, in which the ESSDAI score is reduced by at least 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 1 year after administration of the first loading dose compared to a baseline ESSDAI score. 18. The method of modality 17, in which the ESSDAI score is reduced 11 months after administration of the first loading dose. 19. The method of any of the modalities 7-18, in which salivary gland function in the subject is improved after administration of the Tn3 framework by approximately 3 weeks, 1 month, 2 months, or 4 months after administration. 20. The method of modality 19, in which the function of the salivary glands is determined by fully stimulated salivary flow. 21. The method of any of the modalities 9-20, in which the ESSPRI score is reduced by at least approximately 1.5, 2, 3, 4, or 5 points after the loading dose administrations. 22. The method of any of the modalities 7-21, in which the DASPRI score is reduced by 2 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, or 6 months after administration. 23. The method of modality 22, in which the DASPRI score is reduced by at least approximately 5, 10, 15, or 20 points after the loading dose administrations. 24. The method of any of the modalities 1-23, in which administration of the Tn3 framework is effective in reducing a baseline score of tender and swollen joint counts of the subject after administration. Petition 870250087411, dated 09 / 26 / 2025, pp. 223 / 404 178 / 327 25. The method of any of the modalities 1-24, in which administration of the Tn3 framework is effective in reducing a subject's baseline score on the Short Form Health Survey 36 (SF-36) after administration. 26. The method of any of the modalities 1-25, in which the administration of the Tn3 framework is effective in improving a subject's baseline score, wherein the baseline scores are selected from the group consisting of: Functional Fatigue Analysis in Chronic Disease Therapy (FACIT-Fatigue), PROMIS Fatigue Short Form 10a, Ocular Surface Disease Index (OSDI), EQ-5D-5L and Patient Global Impression of Severity (PGIS). 27. The method of any of the modalities 1-26, in which administration of the Tn3 framework is effective in reducing a baseline level of inflammatory markers after administration, and in which the markers are selected from the group consisting of: immunoglobulin, β2 microglobulin, C-reactive protein and combinations thereof. 28. The method of any of the modalities 1-27, in which administration of the Tn3 framework is effective in reducing a baseline level of a biomarker, and in which the biomarker is selected from the group consisting of: plasma soluble CD40L, Ki67+CD27+ memory B cell, CD19, CD20, CD27, CD38, CD138, bright / elevated CD11c B cell, CD3, CD4, CD8, Tfh cell, serum CXCL13, rheumatoid factor, anti-SSA autoantibodies, anti-Ro autoantibodies, anti-SSB autoantibodies (i.e., anti-La autoantibodies), and combinations thereof. Petition 870250087411, dated 09 / 26 / 2025, pp. 224 / 404 179 / 327 29. The method of any of the modalities 1-28, in which administration of the Tn3 framework is effective in reducing a baseline level of a disease symptom, and in which the disease symptom is selected from the group consisting of: fatigue, dry mouth, dry eyes, vaginal dryness, pain, and combinations thereof. 30. The method of any of the modalities 1-29 in which the expression levels of genes, or levels of proteins encoded by genes, associated with SS are reduced in a blood sample from the subject at week 48 after administration. 31. The method of any of the modalities 1-30, in which the levels of B cells, selected from the group consisting of: CD27+ memory B cells, marginal zone B cells, plasmablasts, plasma cells and combinations thereof, are reduced in a blood sample from the subject up to week 48 after administration. 32. The method of any of the modalities 1-31, in which the subject is positive for anti-Ro autoantibodies, rheumatoid factor (RF), or both anti-Ro autoantibodies and RF. 33. The method of any of the modalities 1-32, in which the Tn3 framework is administered intravenously. 34. The method of any of the embodiments 1-33, in which the Tn3 framework comprises two specific CD40L monomeric subunits connected in tandem. 35. The method of embodiment 34, in which the two specific monomeric subunits of CD40L each comprise SEQ ID NO: 3. Petition 870250087411, dated 09 / 26 / 2025, p. 225 / 404 180 / 327 36. The method of any of the embodiments 34-35, in which specific monomeric subunits of CD40L are connected by a ligand. 37. The method of any of the embodiments 34-36, in which at least one specific monomeric subunit of CD40L is fused or conjugated directly to a polyethylene glycol (PEG). 38. The method of any of the embodiments 34-37, in which at least one specific monomeric subunit of CD40L is fused or conjugated, by means of a ligand, to a polyethylene glycol (PEG). 39. The method of embodiment 38, in which the ligand comprises a peptide ligand. 40. The method of embodiment 39, in which the ligand comprises SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 or SEQ ID NO: 10. 41. The method of any of the modalities 34-40, in which at least one specific monomeric subunit of CD40L is fused or conjugated to an albumin. 42. The method of modality 41, in which the albumin is human serum albumin (HSA). 43. The method of modality 42, wherein HSA is a variant of HSA comprising SEQ ID NO: 4. 44. The method of any of the modalities 1-42, in which the Tn3 framework comprises SEQ ID NO: 1. Set of 6 Modalities 1. Use of a Tn3 scaffold for the preparation of a medicament to treat Sjögren's syndrome (SS) in a subject with a need for it, wherein the medicament is formulated for administration at a dose of 1500 mg once every 4 weeks, wherein the Tn3 scaffold comprises a Petition 870250087411, dated 09 / 26 / 2025, p. 226 / 404 181 / 327 CD40L-specific monomeric subunit, wherein the CD40L-specific monomeric subunit comprises seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the subject has moderate to severe systemic disease activity of ^5, as determined by the European Alliance of Associations for Rheumatology (EULAR) SS Disease Activity Index (ESSDAI). 2. The use of modality 1, in which, prior to dosing every 4 weeks, the subject was administered at least 3 loading doses of 1500 mg each. 3. The use of modality 2, in which at least 3 loading doses are administered in weeks 0, 2, and 4. 4. Use of a Tn3 scaffold for the preparation of a medicament to treat Sjögren's syndrome (SS) in a subject with need thereof, wherein the medicament is formulated for administration at a dose of 3000 mg once every 12 weeks, wherein the Tn3 scaffold comprises a specific CD40L monomeric subunit, wherein the specific CD40L monomeric subunit comprises seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the Petition 870250087411, dated 09 / 26 / 2025, p. 227 / 404 Subject 182 / 327 has moderate to severe systemic disease activity of h5, as determined by the European Alliance of Associations for Rheumatology (EULAR) Disease Activity Index (ESSDAI). 5. The use of modality 4, in which, prior to dosing every 12 weeks, the subject was administered at least 3 loading doses of 3000 mg each. 6. The use of modality 5, in which at least 3 loading doses are administered in weeks 0, 4, and 12. 7. Use of a Tn3 scaffold for the preparation of a medicament for the treatment of Sjögren's syndrome (SS) in a subject with a need for the same, wherein the medicament is formulated for administration at a dose of 1500 mg once every 4 weeks, wherein the Tn3 scaffold comprises a specific CD40L monomeric subunit, wherein the specific CD40L monomeric subunit comprises seven beta strands designated A, B, C, D, E, F and G, and six loop regions designated AB, BC, CD, DE, EF and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14.The EF loop comprises SEQ ID NO: 15, and the FG loop comprises SEQ ID NO: 16, wherein the subject has a moderate to severe symptom status defined by an ESSPRI score of 5, with low systemic disease activity defined by an ESSDAI score of < 5, and wherein a Diary for Analysis of the Sjogren Patient-Reported Index (DASPRI) score is reduced in the subject after administration. Petition 870250087411, dated 09 / 26 / 2025, pp. 228 / 404 183 / 327 8. The use of modality 7, in which, prior to dosing every 4 weeks, the subject was administered at least 3 loading doses of 1500 mg each. 9. The use of modality 8, in which at least 3 loading doses are administered in weeks 0, 2, and 4. 10. Use of a Tn3 scaffold for the preparation of a medicament for the treatment of Sjögren's syndrome (SS) in a subject with a need for the same, wherein the medicament is formulated for administration at a dose of 3000 mg once every 12 weeks, wherein the Tn3 scaffold comprises a specific CD40L monomeric subunit, wherein the specific CD40L monomeric subunit comprises seven beta strands designated A, B, C, D, E, F and G, and six loop regions designated AB, BC, CD, DE, EF and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, .Loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the subject has a moderate to severe symptom status defined by an ESSPRI score of ≥ 5, with low systemic disease activity defined by an ESSDAI score of < 5, and wherein a Diary for Analysis of the Sjögren Patient-Reported Index (DASPRI) score is reduced in the subject after administration. 11. The use of modality 10, in which, prior to dosing every 12 weeks, the subject was administered at least 3 loading doses of 3000 mg each. 12. The use of modality 11, in which at least 3 loading doses are administered in weeks 0, 4, and 12. Petition 870250087411, dated 09 / 26 / 2025, page 229 / 404 184 / 327 13. The use of any of the modalities 1-5, in which the subject has an ESSDAI score of 5-7, 5-10, 5-13 or 10-13 before administration of the Tn3 framework. 14. The use of any of the modalities 1-6, in which administration is effective in reducing the ESSDAI score. 15. The use of modality 14, in which the ESSDAI score is reduced by at least 1, 2, 3, 4, 5, 6, or 7 points. 16. The use of modality 15, in which the ESSDAI score is reduced by at least 6 points. 17. The use of any of the modalities 15-16, in which the ESSDAI score is reduced by at least 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 1 year after administration of the first loading dose compared to a baseline ESSDAI score. 18. The use of modality 17, in which the ESSDAI score is reduced 11 months after administration of the first loading dose. 19. The use of any of the modalities 7-18, in which salivary gland function in the subject is improved after administration of the Tn3 framework by approximately 3 weeks, 1 month, 2 months, or 4 months after administration. 20. The use of modality 19, in which the function of the salivary glands is determined by fully stimulated salivary flow. 21. The use of any of the modalities 9-20, in which the ESSPRI score is reduced by at least approximately 1.5, 2, 3, 4, or 5 points after loading dose administrations. 22. The use of any of the modalities 7-21, in which the DASPRI score is reduced by 2 weeks, 4 weeks, 1 month, Petition 870250087411, dated 09 / 26 / 2025, pp. 230 / 404 185 / 327 months, 3 months, 4 months, 5 months, or 6 months after administration. 23. The use of modality 22, in which the DASPRI score is reduced by at least approximately 5, 10, 15, or 20 points after the loading dose administrations. 24. The use of any of the modalities 1-23, in which administration of the Tn3 framework is effective in reducing a baseline score of the subject's tender and swollen joint counts after administration. 25. The use of any of the modalities 1-24, in which administration of the Tn3 framework is effective in reducing a subject's baseline score on the Short Form Health Survey 36 (SF-36) after administration. 26. The use of any of the modalities 1-25, in which the administration of the Tn3 framework is effective in improving a subject's baseline score, wherein the baseline scores are selected from the group consisting of: Functional Fatigue Analysis in Chronic Disease Therapy (FACIT-Fatigue), PROMIS Fatigue Short Form 10a, Ocular Surface Disease Index (OSDI), EQ-5D-5L and Patient Global Impression of Severity (PGIS). 27. The use of any of the modalities 1-26, in which administration of the Tn3 framework is effective in reducing a baseline level of inflammatory markers after administration, and in which the markers are selected from the group consisting of: immunoglobulin, β2-microglobulin, C-reactive protein, and combinations thereof. 28. The use of any of the modalities 1-27, in which administration of the Tn3 framework is effective in reducing a Petition 870250087411, dated 09 / 26 / 2025, pp. 231 / 404 186 / 327 baseline level of a biomarker, wherein the biomarker is selected from the group consisting of: plasma soluble CD40L, Ki67+CD27+ memory B cell, CD19, CD20, CD27, CD38, CD138, bright / elevated CD11c B cell, CD3, CD4, CD8, Tfh cell, serum CXCL13, rheumatoid factor, anti-SSA autoantibodies, anti-Ro autoantibodies, anti-SSB autoantibodies (i.e., anti-La autoantibodies), and combinations thereof. 29. The use of any of the modalities 1-28, in which administration of the Tn3 framework is effective in reducing a baseline level of a disease symptom, and in which the disease symptom is selected from the group consisting of: fatigue, dry mouth, dry eyes, vaginal dryness, pain, and combinations thereof. 30. The use of any of the modalities 1-29 in which gene expression levels, or levels of proteins encoded by genes, associated with SS are reduced in a blood sample from the subject at week 48 after administration. 31. The use of any of the modalities 1-30, in which the levels of B cells, selected from the group consisting of: CD27+ memory B cells, marginal zone B cells, plasmablasts, plasma cells and combinations thereof, are reduced in a blood sample from the subject up to week 48 after administration. 32. The use of any of the modalities 1-31, in which the subject is positive for anti-Ro autoantibodies, rheumatoid factor (RF), or both anti-Ro and RF autoantibodies. 33. The use of any of the modalities 1-32, in which the Tn3 framework is administered intravenously. Petition 870250087411, dated 09 / 26 / 2025, pp. 232 / 404 187 / 327 34. The use of any of the embodiments 1-33, in which the Tn3 framework comprises two specific CD40L monomeric subunits connected in tandem. 35. The use of embodiment 34, in which the two specific monomeric subunits of CD40L each comprise SEQ ID NO: 3. 36. The use of any of the embodiments 34-35, in which specific monomeric subunits of CD40L are connected by a linker. 37. The use of any of the embodiments 34-36, in which at least one specific monomeric subunit of CD40L is fused or conjugated directly to a polyethylene glycol (PEG). 38. The use of any of the embodiments 34-37, in which at least one specific monomeric subunit of CD40L is fused or conjugated, by means of a ligand, to a polyethylene glycol (PEG). 39. The use of modality 38, in which the ligand comprises a peptide ligand. 40. The use of modality 39, where the linker comprises SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 or SEQ ID NO: 10. 41. The use of any of the modalities 34-40, in which at least one specific monomeric subunit of CD40L is fused or conjugated to an albumin. 42. The use of modality 41, in which the albumin is human serum albumin (HSA). 43. The use of modality 42, where HSA is a variant of HSA comprising SEQ ID NO: 4. 44. The use of any of the modalities 1-42, in which the Tn3 framework comprises the SEQ ID NO: 1. Petition 870250087411, dated 09 / 26 / 2025, pp. 233 / 404 188 / 327 EXAMPLES Example 1 - A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Dazodalibep in Participants with Sjögren's Syndrome with Moderate to Severe Systemic Disease Activity

[0215] A double-blind, randomized, placebo-controlled phase 3 study to evaluate the efficacy and safety of Dazodalibep in participants with Sjogren's Syndrome (SS) with moderate to severe systemic disease activity is disclosed in this document. Objectives and outcomes:

[0216] The objectives and outcomes of the study are presented in Table 2. Table 2. Exemplary study objectives and outcomes Objectives Outcomes Primary To evaluate the effect of dazodalibep on systemic manifestations of SS in participants with moderate to severe systemic activity • Change from baseline in ESSDAI score at Week 48 Secondary To evaluate the effect of dazodalibep on measures of systemic activity and PROs in participants with SS • Proportion of participants achieving the ESSDAI response, defined as a decrease of at least 5 points from baseline in the ESSDAI Petition 870250087411, dated 09 / 26 / 2025, pp. 234 / 404 189 / 327 Objectives and Outcomes at Week 4: 8 without premature discontinuation of treatment and without receiving rescue or potentially confounding therapy • Change from baseline in the ESSPRI dryness domain at Week 48 • Change from baseline in tender and swollen joint scores at Week 48 • Change from baseline in the SF-3 PCS score at Week 48 Exploratory Objective(s) and Exploratory Outcome(s): To evaluate biomarkers of inflammation and autoantibodies in participants with SS following treatment with dazodalibep • Change from baseline in levels of inflammation markers (immunoglobulins, β-2 microglobulin, and C-reactive protein [CRP]) Petition 870250087411, dated 09 / 26 / 2025, pp. 235 / 404 190 / 327 Objectives Outcomes Evaluate target engagement of dazodalibep (TE) • Change from baseline in plasma soluble CD40L levels Evaluate the DP of dazodalibep • Change from baseline in rheumatoid factor (RF). • Change from baseline in biomarker levels including, but not limited to, peripheral blood flow cytometry for changes in B-cell subsets, serum CXCL13. Evaluate the effects of dazodalibep on systemic disease activity, as well as on joint and salivary and lacrimal function in participants who achieve ESSDAI[3] or ESSDAI[4] • Proportion of participants with SS. • Change in Physician Global Impression of Severity (MDGIS) • Change from baseline in imaging by Petition 870250087411, dated 09 / 26 / 2025, pp. 236 / 404 191 / 327 Objectives and Outcomes: Salivary gland ultrasound (subset of participants) • Change from baseline in joint ultrasound imaging (subset of participants) To assess changes in the main subjective complaints associated with SS. • Change from baseline in the total ESSPRI score • Change from baseline in the ESSPRI pain domain score • Change from baseline in the ESSPRI fatigue domain score • Proportion of participants achieving the ESSPRI response, defined as a decrease of at least 1.5 points from baseline in the ESSPRI, without premature discontinuation Petition 870250087411, dated 09 / 26 / 2025, pp. 237 / 404 192 / 327 Objectives: Treatment outcomes without receiving rescue or potentially confounding therapy. • Change from baseline in FACIT-Fatigue score • Change from baseline in Oral Dryness VAS • Change from baseline in Ocular Dryness VAS • Change from baseline in Vaginal Dryness VAS • Change from baseline in Total Stimulated Salivary Flow • Change from baseline in Patient Global Impression of Severity (PGIS) • Patient Global Impression of Change (PGIC) • Change from baseline in Female Sexual Function Index Petition 870250087411, dated 09 / 26 / 2025, pp. 238 / 404 193 / 327 Objectives and Outcomes (FSFI) (when appropriate) • Change from baseline in the EULAR Sjögren's Syndrome Clinical Disease Activity Index (ClinESSDAI) To assess the effects of dazodalibep on blood gene expression • Change from baseline in global gene expression by PAXgene RNA assay To characterize exploratory biomarkers of disease and treatment response • C...

Claims

1. Method for treating Sjögren's syndrome (SS) in a subject in need thereof, characterized by comprising: administering a Tn3 scaffold, wherein the Tn3 scaffold comprises a specific monomeric subunit of CD40L, wherein the specific monomeric subunit of CD40L comprises seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the Tn3 scaffold is administered at a dose of approximately 1500 mg once every 4 weeks, wherein the subject has a moderate symptom state. Severe disease defined by an ESSPRI score of ^5, with low systemic disease activity defined by an ESSDAI score of <5,and in which a Diary for Analysis of the Patient-Reported Index of Sjögren's Syndrome (DASPRI) score is reduced in the subject after administration.

2. Method according to claim 1, characterized in that, prior to dosing every 4 weeks, the subject has been administered at least 3 loading doses of 1500 mg each.

3. Method, according to claim 2, characterized by at least 3 loading doses being administered in weeks 0, 2 and 4.

4. Method for treating Sjögren's syndrome (SS) in a subject in need thereof, characterized by comprising: administering a Tn3 framework, in which the framework Petition 870250087411, dated 09 / 26 / 2025, p.374 / 404 2 / 7 Tn3 comprises a specific CD40L monomeric subunit, wherein the specific CD40L monomeric subunit comprises seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein loop AB comprises SEQ ID NO: 11, loop BC comprises SEQ ID NO: 12, loop CD comprises SEQ ID NO: 13, loop DE comprises SEQ ID NO: 14, loop EF comprises SEQ ID NO: 15, and loop FG comprises SEQ ID NO: 16, wherein the Tn3 framework is administered at a dose of approximately 3000 mg once every 12 weeks, wherein the subject has moderate to severe symptom status defined by ESSPRI h score 5, with low systemic disease activity defined by ESSDAI score < 5, and in which a Diary for Analysis of the Patient-Reported Index of Sjogren's Syndrome (DASPRI) score is reduced in the subject after administration.

5. Method, according to claim 4, characterized in that, prior to dosing every 12 weeks, the subject has been administered at least 3 loading doses of 3000 mg each.

6. Method according to claim 5, characterized by at least 3 loading doses being administered in weeks 0, 4 and 12.

7. Method, according to any one of claims 1, 2, 3, 4, 5 or 6, characterized in that the salivary gland function in the subject is improved after administration of the Tn3 framework in about 3 weeks, 1 month, 2 months or 4 months after administration. Petition 870250087411, dated 09 / 26 / 2025, pp. 375 / 404 3 / 7 8. Method according to claim 7, characterized in that the function of the salivary glands is determined by fully stimulated salivary flow.

9. A method, according to any one of claims 1, 2, 3, 4, 5, 6, 7 or 8, characterized in that the ESSPRI score is reduced after administration.

10. Method, according to claim 9, characterized in that the ESSPRI score is reduced by at least about 1.5, 2, 3, 4 or 5 points.

11. A method according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, characterized in that the DASPRI score is reduced 2 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months or 6 months after administration.

12. Method, according to claim 11, characterized in that the DASPRI score is reduced by at least about 5, 10, 15 or 20 points.

13. Method, according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12, characterized in that administration of the Tn3 framework is effective in reducing a baseline score of tender and swollen joint counts of the subject after administration.

14. A method according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13, characterized in that administration of the Tn3 framework is effective in reducing a subject's baseline score on the Short Form Health Survey 36 (SF-36) after administration.

15. Method, according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14, characterized in that the administration of the Tn3 framework is effective in improving a subject's baseline score, wherein the baseline scores are selected from the group consisting of: Functional Fatigue Analysis in Chronic Disease Therapy (FACIT-Fatigue), PROMIS Fatigue Short Form 10a, Ocular Surface Disease Index (OSDI), EQ-5D-5L and Patient Global Impression of Severity (PGIS).

16. A method according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15, characterized in that administration of the Tn3 scaffold is effective in reducing a baseline level of inflammatory markers after administration, and wherein the markers are selected from the group consisting of: immunoglobulin, β-2 microglobulin, C-reactive protein and combinations thereof.

17. A method according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16, characterized in that administration of the Tn3 scaffold is effective in reducing a baseline level of a biomarker, and wherein the biomarker is selected from the group consisting of: plasma soluble CD40L, Ki67+CD27+ memory B cell, CD19, CD20, CD27, CD38, CD138, bright / elevated CD11c B cell, CD3, CD4, CD8, follicular helper T cell (Tfh), serum CXCL13, rheumatoid factor, anti-SSA autoantibodies, anti-Ro autoantibodies, anti-SSB autoantibodies, anti-La autoantibodies and combinations thereof.

18. Method, according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or 17, characterized in that the administration of the Tn3 framework is effective in reducing a baseline level of a disease symptom, and wherein the disease symptom is selected from the group consisting of: fatigue, dry mouth, dry eyes, vaginal dryness, pain and combinations thereof.

19. A method according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or 18, characterized in that the expression levels of genes, or levels of proteins encoded by the genes, associated with SS are reduced in a blood sample from the subject at week 48 after administration.

20. A method according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 or 19, characterized in that the levels of selected B cells from the group consist of: CD27+ memory B cells, marginal zone B cells, plasmablasts, plasma cells and combinations thereof, being reduced in a blood sample from the subject up to week 48 after administration.

21. A method according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20, characterized in that the subject is positive for anti-Ro autoantibodies, rheumatoid factor (RF), or both anti-Ro autoantibodies and RF.

22. Method, according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21, characterized in that the Tn3 scaffold is administered intravenously.

23. Method, according to any of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22, characterized in that the Tn3 framework Petition 870250087411, dated 09 / 26 / 2025, page 378 / 404 6 / 7 comprises two specific monomeric CD40L subunits connected in tandem.

24. Method according to claim 23, characterized in that the two specific monomeric subunits of CD40L each comprise SEQ ID NO:

3.

25. A method according to any one of claims 23 or 24, characterized by specific monomeric subunits of CD40L being connected by a linker.

26. A method according to any one of claims 23, 24 or 25, characterized in that at least one specific CD40L monomeric subunit is directly fused or conjugated to a polyethylene glycol (PEG).

27. A method according to any one of claims 23, 24, 25 or 26, characterized in that at least one specific CD40L monomeric subunit is fused or conjugated, by means of a ligand, to a polyethylene glycol (PEG).

28. Method according to claim 27, characterized in that the ligand comprises a peptide ligand.

29. Method according to claim 28, characterized in that the binder comprises SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 or SEQ ID NO:

10.

30. A method according to any one of claims 23, 24, 25, 26, 27, 28 or 29, characterized by at least one specific CD40L monomeric subunit being fused or conjugated to an albumin.

31. Method according to claim 30, characterized in that the albumin is human serum albumin (HSA).

32. Method according to claim 31, characterized in that HSA is a variant of HSA comprising SEQ ID NO:

4. Petition 870250087411, dated 09 / 26 / 2025, p. 379 / 404 7 / 7 33. Method, according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 or 32, characterized by the framework Tn3 comprising SEQ ID NO:

1.

34. Method, according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32 or 33, characterized in that the subject has a coexisting autoimmune indication.

35. Method, according to claim 34, characterized in that the coexisting autoimmune indication is rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or both RA and SLE.

36. Method, according to claim 34, characterized in that the coexisting autoimmune indication is rheumatoid arthritis.

37. Method, according to claim 34, characterized in that the coexisting autoimmune indication is systemic lupus erythematosus.

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