Compositions comprising brinp3 variants and methods of using the same for treatment of obesity, diabetes and liver disorders

Abstract

The disclosure relates to a composition comprising BRINP3 variants and methods of using the same for treatment of obesity, weight gain, diabetes, MASH, or MASLD in subjects in need thereof.

Description

DOCKET NO. STFD-012-PCT PCT APPLICATION COMPOSITIONS COMPRISING BRINP3 VARIANTS AND METHODS OF USING THE SAME FOR TREATMENT OF OBESITY, DIABETES AND LIVER DISORDERS CROSS REFERENCE TO RELATED APPLICATIONS

[0001] Thie application claims the benefit of U.S. Provisional Application No.63 / 572,179, which was filed March 30, 2024, is titled COMPOSITIONS COMPRISING BRINP3 VARIANTS AND METHODS OF USING THE SAME FOR TREATMENT OF OBESITY, DIABETES AND LIVER DISORDERS, and is incorporated herein by reference in its entirety. SEQUENCE LISTING

[0002] The electronic sequence listing filed herewith, titled “STFD-012-PCT_SL.xml,” created on March 31, 2025, and having a file size of 175,942 bytes is incorporated herein by reference in its entirety. FIELD

[0003] The disclosure relates to compositions and pharmaceutical compositions comprising BRINP3 and functional variants thereof. The disclosure also relates to methods of treatment of obesity, diabetes, MASH and MASLD in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a BRINP3 peptide or a functional variant thereof. BACKGROUND

[0004] Obesity is a chronic and multifactorial disease anticipated to impact over 25 % of the global population by 2035 [1]. Obesity significantly diminishes life expectancy by 5–10 years and increases mortality risk from diabetes, cardiovascular disease, and related mortality [2,3]. The discovery of genes involved in energy balance, which primarily modulate central regulation of food intake, underscores the potential for developing targeted therapeutic approaches [4]. Despite common lifestyle interventions, such as dietary modifications and increased physical activity, achieving sustained weight loss has until recently remained a challenge. The introduction of modified GLP-1 peptide analogs, such as liraglutide and semaglutide, has revolutionized obesity management by significantly reducing body weight in humans [5,6]. These peptide hormones, characterized by their small size (<100 amino acids),DOCKET NO. STFD-012-PCT PCT APPLICATION and low abundance, have demonstrated to be powerful regulators of food intake primarily through their action in the brain [7–9]. However, these interventions, similar to caloric restriction, have been associated with adverse effects, including muscle loss

[0010] . In clinical trials of semaglutide, a significant portion of weight reduction was attributed to the loss of lean mass [6]. This reduction is particularly concerning because it can lead to higher plasma glucose levels and elevate the risks of sarcopenia and frailty in older adults. Therefore, approaches such as combination therapies to counteract muscle loss have been explored

[0011] , but there is currently no approved treatment for weight-loss-induced muscle reduction or weight-loss strategies that do not result in muscle loss. SUMMARY OF EMBODIMENTS

[0005] In some embodiments the disclosure relates to an amino acid sequence comprising BRINP3, a functional variant thereof, or a pharmaceutically acceptable salt thereof. In some embodiments, the amino acid sequence comprises SEQ ID NO: 12, or a functional variant comprising at least about 75% sequence identity to SEQ ID NO:12, wherein X1 and X2 are independently selected from any amino acid, or a pharmaceutically acceptable salt thereof. In some embodiments, the amino acid sequence comprises SEQ ID NO: 9 or a functional variant comprising at least about 75% sequence identity to SEQ ID NO:9, wherein X1and X2are independently selected from any amino acid, or a pharmaceutically acceptable salt thereof. In some embodiments, the amino acid sequence comprises SEQ ID NO:10 or SEQ ID NO:11, or functional variants thereof comprising at least about 75% sequence identity to SEQ ID NO:10 or SEQ ID NO:11, or a pharmaceutically acceptable salt thereof. In some embodiments, the amino acid sequence is chosen from: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, or functional variants thereof comprising at least about 75% sequence identity to one or combination of: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8.

[0006] In some embodiments the disclosure relates to a composition comprising an amino acid sequence comprising BRINP3, a functional variant thereof, or a pharmaceutically acceptable salt thereof. In some embodiments, the amino acid sequence comprises SEQ ID NO: 12, or a functional variant comprising at least about 75% sequence identity to SEQ ID NO:12, wherein X1 and X2 are independently selected from any amino acid, or a pharmaceutically acceptable salt thereof. In some embodiments, the amino acid sequence comprises SEQ ID NO:DOCKET NO. STFD-012-PCT PCT APPLICATION 9 or a functional variant comprising at least about 75% sequence identity to SEQ ID NO:9, wherein X1and X2are independently selected from any amino acid, or a pharmaceutically acceptable salt thereof. In some embodiments, the amino acid sequence comprises SEQ ID NO:10 or SEQ ID NO:11, or functional variants thereof comprising at least about 75% sequence identity to SEQ ID NO:10 or SEQ ID NO:11, or a pharmaceutically acceptable salt thereof. In some embodiments, the amino acid sequence is chosen from: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, or functional variants thereof comprising at least about 75% sequence identity to one or combination of: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8.

[0007] In some embodiments the disclosure relates to a composition comprising composition comprising an amino acid sequence comprising a first and second domain, wherein the first domain is a BRINP3 domain and wherein the second domain is a GLP-1 domain. In some embodiments, the BRINP3 domain comprises SEQ ID NO: 12 or a functional variant comprising at least about 75% sequence identity to SEQ ID NO:12, wherein X1 and X2 are independently selected from any amino acid. In some embodiments, the BRINP3 domain comprises SEQ ID NO: 9 or a functional variant comprising at least about 75% sequence identity to SEQ ID NO:9, wherein X1 and X2 are independently selected from any amino acid. In some embodiments, the BRINP3 domain comprises SEQ ID NO:10, SEQ ID NO:11, or functional variants thereof comprising at least about 75% sequence identity to SEQ ID NO:10 or SEQ ID NO:11. In some embodiments, the BRINP3 domain comprising an amino acid is chosen from: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, or functional variants thereof comprising at least about 75% sequence identity to one or combination of: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8. In some embodiments, the first domain comprises SEQ ID NO:5 or a functional variant thereof comprising at least about 75% sequence identity to SEQ ID NO:5; and the second domain comprises SEQ ID NO:13 or a functional variant thereof comprising at least about at least about 75% sequence identity to SEQ ID NO:13.

[0008] In some embodiment, the disclosure relates to a pharmaceutical composition comprising: (i) a therapeutically effective amount (a) a composition comprising an amino acid sequence comprising BRINP3, a functional variant thereof, or a pharmaceutically acceptable salt thereof, (b) a composition comprising composition comprising an amino acid sequence comprising a first and second domain, wherein the first domain is a BRINP3 domain andDOCKET NO. STFD-012-PCT PCT APPLICATION wherein the second domain is a GLP-1 domain, or (c) an amino acid sequence comprising BRINP3, a functional variant thereof, or a pharmaceutically acceptable salt thereof.; and (ii) a pharmaceutically acceptable carrier. In some embodiments, the amino acid sequence comprises SEQ ID NO: 12, or a functional variant comprising at least about 75% sequence identity to SEQ ID NO:12, wherein X1 and X2 are independently selected from any amino acid, or a pharmaceutically acceptable salt thereof. In some embodiments, the amino acid sequence comprises SEQ ID NO: 9 or a functional variant comprising at least about 75% sequence identity to SEQ ID NO:9, wherein X1and X2are independently selected from any amino acid, or a pharmaceutically acceptable salt thereof. In some embodiments, the amino acid sequence comprises SEQ ID NO:10 or SEQ ID NO:11, or functional variants thereof comprising at least about 75% sequence identity to SEQ ID NO:10 or SEQ ID NO:11, or a pharmaceutically acceptable salt thereof. In some embodiments, the amino acid sequence is chosen from: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, or functional variants thereof comprising at least about 75% sequence identity to one or combination of: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8. In some embodiments, the BRINP3 domain comprises SEQ ID NO: 12 or a functional variant comprising at least about 75% sequence identity to SEQ ID NO:12, wherein X1 and X2 are independently selected from any amino acid. In some embodiments, the BRINP3 domain comprises SEQ ID NO: 9 or a functional variant comprising at least about 75% sequence identity to SEQ ID NO:9, wherein X1and X2are independently selected from any amino acid. In some embodiments, the BRINP3 domain comprises SEQ ID NO:10 or SEQ ID NO:11, or functional variants thereof comprising at least about 75% sequence identity to SEQ ID NO:10 or SEQ ID NO:11. In some embodiments, the BRINP3 domain comprising an amino acid is chosen from: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, or functional variants thereof comprising at least about 75% sequence identity to one or combination of: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8. In some embodiments, the first domain comprises SEQ ID NO:5 or a functional variant thereof comprising at least about 75% sequence identity to SEQ ID NO:5; and the second domain comprises SEQ ID NO:13 or a functional variant thereof comprising at least about at least about 75% sequence identity to SEQ ID NO:13.In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising the amino acid sequence chosen from: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ IDDOCKET NO. STFD-012-PCT PCT APPLICATION NO:7, SEQ ID NO:8, or functional variants thereof comprising at least about 75% sequence identity to one or combination of: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of an amino acid comprising at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO:1 or SEQ ID NO:5.

[0009] In some embodiments, the disclosure relates to a method of treating obesity, hyperglycemia, weight gain, diabetes, MASLD or MASH in a subject in need thereof. The method comprises administering to the subject (i) an amino acid sequence comprising BRINP3, a functional variant thereof, or a pharmaceutically acceptable salt thereof, (ii) a composition comprising an amino acid sequence comprising BRINP3, a functional variant thereof, or a pharmaceutically acceptable salt thereof, (iii) a composition comprising composition comprising an amino acid sequence comprising a first and second domain, wherein the first domain is a BRINP3 domain and wherein the second domain is a Glucagon-like peptide-1 (GLP-1) agonist domain, or (iv) a pharmaceutical composition comprising: (i) a therapeutically effective amount of (a) a composition comprising an amino acid sequence comprising BRINP3, a functional variant thereof, or a pharmaceutically acceptable salt thereof, (b) a composition comprising composition comprising an amino acid sequence comprising a first and second domain, wherein the first domain is a BRINP3 domain and wherein the second domain is a GLP-1 agonist domain, or (c) an amino acid sequence comprising BRINP3, a functional variant thereof, or a pharmaceutically acceptable salt thereof.; and (ii) a pharmaceutically acceptable carrier. In some embodiments, the amino acid sequence is as summarized above. In some embodiments the compositions are as summarized above. In some embodiments, the pharmaceutical composition is as summarized above. In some embodiments, the subject is a mammal. In some embodiments, the subject is a human. In some embodiments, the amino acid sequence, composition, or pharmaceutical composition is administered simultaneously with, before or after administration of a GLP-1 receptor modulator. In some embodiments, the amino acid sequence, composition, or pharmaceutical composition is administered as a dose of from about 0.1 milligrams to about 10,000 milligrams. In some embodiments, the amino acid sequence, composition, or pharmaceutical composition is administered as a dose of from about 0.1 milligrams per kilogram of the subject to about 1,000 milligrams per kilogram of the subject. In some embodiments, the amino acid sequence, composition, or pharmaceutical composition is administered as a dose of from about 0.1 milligrams per kilogram of the subject to about 1,000 milligrams per kilogram of the subject once a day or once a week.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0010] In some embodiments, the disclosure relates to a method of manufacturing any one of the amino acid sequences, compositions, or pharmaceutical compositions summarized above. The method comprises catalyzing a reaction between at least two amino acids in the amino acid sequence.

[0011] In some embodiments, the disclosure relates to a method of inducing phosphorylation of CREB in a cell. The method comprises exposing the cell to any of the amino acid sequences, compositions, or pharmaceutical compositions summarized above. In some embodiments, the step of exposing comprises exposing the cell to an amino acid sequence of Table 1 or functional variants thereof comprising at least about 75% sequence identity to SEQ ID: 1 through SEQ ID NO: 12. In some embodiments, the step of exposing is performed for a time period sufficient for any of the amino acid sequences, compositions, or pharmaceutical compositions summarized above. In some embodiments, the step of exposing is performed in vivo after administration any of the amino acid sequences, compositions, or pharmaceutical compositions summarized above to a subject. In some embodiments, the subject is a subject in need of a treatment for obesity or weight loss.

[0012] In some embodiments, the disclosure relates to a method of preventing obesity, weight gain, diabetes, MASH, or MASLD in a subject in need thereof. The method comprises administering to the subject any of the amino acid sequences, compositions, or pharmaceutical compositions summarized above. In some embodiments, the amino acid sequence, the composition, or the pharmaceutical composition is administered by oral adminstration, parenteral administration, sublingual administration, transdermal administration, rectal administration, transmucosal administration, topical administration, inhalation, buccal administration, intrapleural administration, intravenous administration, intraarterial administration, intraperitoneal administration, subcutaneous administration, intramuscular administration, intranasal administration, intrathecal administration, and intraarticular administration, or combinations thereof. In some embodiments, the subject is a mammal. In some embodiments, the subject is a human. In some embodiments, the amino acid sequence, the composition, or the pharmaceutical composition is administered simultaneously with, before or after administration of a GLP-1 modulator. In some embodiments, the amino acid sequence, the composition, or the pharmaceutical composition is administered as a dose of from about 0.1 milligrams to about 10,000 milligrams. In some embodiments, the amino acid sequence, the composition, or the pharmaceutical composition is administered as a dose of from about 0.1 milligrams per kilogram of the subject to about 1,000 milligrams per kilogram of the subject. In some embodiments, the amino acid sequence, the composition, or theDOCKET NO. STFD-012-PCT PCT APPLICATION pharmaceutical composition is administered as a dose of from about 0.1 milligrams per kilogram of the subject to about 1,000 milligrams per kilogram of the subject once a day or once a week.

[0013] In some embodiments, the disclosure relates to a method of treating diabetes in a subject in need thereof. The method comprises administering to the subject any of the amino acid sequences, compositions, or pharmaceutical compositions summarized above. In some embodiments, the subject is a mammal. In some embodiments, the subject is a human.

[0014] In some embodiments, the disclosure relates to a cell comprising any of the amino acid sequences, compositions, or pharmaceutical compositions summarized above.

[0015] In some embodiments, the disclosure relates to a method of suppressing appetite in a subject in need thereof. The method comprises administering to the subject any of the amino acid sequences, compositions, or pharmaceutical compositions summarized above. In some embodiments, the subject is a mammal. In some embodiments, the subject is a human. BRIEF DESCRIPTION OF DRAWINGS

[0016] FIGS. 1A–F illustrate. BRINP3, a secreted protein expressed in the brain and intestine, is associated with BMI. FIG. 1A shows a Manhattan plot of the GWAS variant associations with Body Mass Index (BMI). The x-axis shows the chromosome location of BRINP3, and the y-axis shows the -log of the P-value. Data obtained from Type 2 Diabetes Knowledge Portal (type2diabetesgenetics.org). BRINP3 Gene page. 2024 Feb 20; https: / / hugeamp.org / gene.html?gene=BRINP3 (RRID:SCR_003743). FIG. 1 B shows expression of BRINP genes by tissue as presented in the Human Protein Atlas. nTPM=Normalized transcripts per million. Tissues with an expression < 1 in all BRINP genes not shown. FIG. 1C shows percentage and expression level of Brinp3 and proconvertases in major cell subsets from adult mouse small intestine. Scaling is relative to each gene's expression across all cells in dot plot. FIGS.1D and 1E show percentage and expression level of Brinp3 and known prohormones in neuronal subsets from adult mouse small intestine (upper) and colon (lower) as reported in Drokhlyansky et al. Scaling as in E. FIG. 1F shows in-situ hybridization using probes for indicated genes on coronal sections of adult mouse brain. Pictures retrieved from Allen Mouse Brain Atlas.

[0017] FIGS.2A–2E illustrates that a 26-mer BRINP3-derived peptide (which may also be referred to as a BRINP3 peptide), BRP3, suppresses food intake in mice. FIG. 2A shows BRINP2 gene with the proconvertase cleavage sites KR / RK / KK / RR-X marked with * toDOCKET NO. STFD-012-PCT PCT APPLICATION delineate the six cleavage fragments from the parent protein BRINP3. SP = signal peptide. Peptide 5 is BRP3. FIG. 2B shows the chemical composition of BRP3. FIG. 2C shows AlphaFold prediction of the structures of BRINP3 and the cleaved BRP3 with hydrophobicity as marked by the scale bar in ChimeraX. FIG. 2D shows protein sequence analysis of BRP3 across monkey, chimpanzee, gorilla, human, rabbit, rat and mouse. Bolded amino acids represent natural variants that differ between species. FIG.2E shows accumulated food intake in male 6-week-old C57BL / 6 mice after a single I.P. injection of vehicle (saline) or 10 mg / kg BRP3 diluted in saline. Combined data from 3 independent experiments with N = 3 mice / group. Data are presented as S.E.M. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 by two-way Anova for multiple comparisons. Figure discloses SEQ ID NOS 110-113, 1, 114, 1, 1, 103, 115-116, 1, 117-118 and 104, respectively, in order of appearance.

[0018] FIGS. 3A–3I illustrate BRP3 reverses obesity and diabetes in diet-induced obese mice. FIGS. 3A–3E show representative images of mice (3A), total body weight (3B), body weight change (3C), accumulated food intake (3D), and daily food intake (3E) in mice during and after 14 days of treatment with vehicle or 10 mg / kg BRP3. N = 6 mice / group. FIGS.3F– 3G show glucose tolerance test (GTT) (3F) and insulin tolerance test (ITT) (3G) after 14 days of treatment with vehicle or 10 mg / kg BRP3. N = 6 mice / group. FIG.3H shows tissue weights after 14 days of treatment with vehicle or 10 mg / kg BRP3. N = 6 mice / group. FIG.3I showsl muscle force measurements in mice after 14 days of treatment with vehicle or 10 mg / kg BRP3. Representative pictures of N = 10 mice / group. Data are presented as S.E.M. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 by two-way Anova for multiple comparisons.

[0019] FIG.4 illustrates that BRP3 is endogenously circulating in human plasma. LC-MS (MS1 spectra) demonstrating the detection of endogenous BRP3 in human plasma at 34-35 minutes. Black = synthesized external BRP3 standard. Blue = endogenous BRP3 peptide. Figure discloses SEQ ID NO: 119.

[0020] FIGS. 5A–5C illustrate that BRP3 activates cFos expression and pCREB phosphorylation in neuronal cells. FIG.5A shows cfos expression in Neuro2 cells in response to indicated concentrations of BRP3 for 1 hour. Data are presented as S.E.M. N = 2 biological samples / group. FIGS.5B and 5C show Western blot analysis of pCREBS133, total CREB, and b-actin in U87MG (b) and Neuro2 (c) cells treated with 100 ug / ml BRP3 for 15, 30 and 60 minutes relative a vehicle-treated control (0 minutes). Shown are two representative experiments.

[0021] FIGS. 6A–6C illustrate a minimal sequence required for activity. FIG.6A shows a Western blot of pCREBS133 in Neuro2 cells after stimulation with BRP3 peptides for 15DOCKET NO. STFD-012-PCT PCT APPLICATION minutes at 100 ug / ml. Shown are full-length BRP3 (BRP3 1-26) followed by truncated versions. FIG.6B shows food intake suppression in C57BL / 6 mice using truncated versions of BRP3 after a single I.P. injection of 10 mg / kg peptides. N = 3 mice / group. FIG.6C shows food intake suppression in C57BL / 6 mice using BRP3 from different species after a single I.P. injection of 10 mg / kg peptides. N = 3 mice / group. Figure discloses SEQ ID NOS 1, 14-19, 5- 8, 20-29, 1, 1, and 103-105, respectively, in order of appearance.

[0022] FIG.7 illustrates alanine substitution results for BRP3.

[0023] FIG.8 illustrates gastric emptying results for vehicle, BRP3 and exendin-4.

[0024] FIG. 9 illustrates gastrointestinal transit time results after administration of saline, BRP3, semaglutide, and loperamide.

[0025] FIG. 10 illustrates changes in fat mass after administration with saline, BRP3, semaglutide, and semaglutide plus BRP3.

[0026] FIG. 11 illustrates percent changes in weight after administration of saline, BRP3, semaglutide, or semaglutide plus BRP3.

[0027] FIG. 12 illustrates food intake / mouse over time in light of administration with saline, BRP3, semaglutide, or semaglutide plus BRP3.

[0028] FIG. 13 illustrates food intake in light of administration with saline, BRP3, semaglutide, or semaglutide plus BRP3. DETAILED DESCRIPTION OF THE APPLICATION

[0029] Before the present amino acid sequences, compositions, pharmaceutical compositions and methods are described, it is to be understood that the present disclosure is not limited to the particular processes, compositions, or methodologies described, as these may vary. It is also to be understood that the terminology used in the description is for the purposes of describing the particular versions or embodiments only, and is not intended to limit the scope of the present disclosure. Various terms relating to the amino acid sequences, compositions, pharmaceutical compositions and methods and other aspects of the present embodiments are used throughout the specification and claims. Such terms are to be given their ordinary meaning in the art unless otherwise indicated. Other specifically defined terms are to be construed in a manner consistent with the definition provided herein. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the present disclosure, the amino acid sequences, compositions, pharmaceutical compositions and methods in some embodiments are now described. AllDOCKET NO. STFD-012-PCT PCT APPLICATION publications mentioned herein are incorporated by reference in their entireties, including patent applications, journal articles and gene accession numbers, and CAS registry identifiers. Nothing herein is to be construed as an admission that the present disclosure is not entitled to antedate such disclosure by virtue of prior disclosure. Definitions

[0030] As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the content clearly dictates otherwise.

[0031] The term “about” as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of ±20%, ±10%, ±5%, ±1%, or ±0.1% from the specified value, as such variations are appropriate to perform the disclosed methods.

[0032] The term “active state” refers to the conformation or set of conformations of a polypeptide that allows functional domain or domains of the polypeptide to associate or disassociate with another compound, macromolecule, or ligand. In some embodiments, the association or disassociation of the polypeptide with another compound, macromolecule, or ligand may propagate or inhibit a biologic signal.

[0033] The term “amino acid” refers to a molecule containing both an amino group and a carboxyl group bound to a carbon which is designated the α-carbon. Suitable amino acids herein include, without limitation, both the D- and L-isomers of the naturally-occurring amino acids, as well as non-naturally occurring amino acids prepared by organic synthesis (synthetic amino acids) or other metabolic routes. Amino acid, as used herein, also encompasses non- proteogenic amino acids, beta amino acids, homo-amino acids, beta-homo-amino acids, amino acids with modified side groups, N-methyl amino acids, alpha-methyl amino acids and D- amino acids. In some embodiments, a single “amino acid” might have multiple sidechain moieties, as available per an extended aliphatic or aromatic backbone scaffold. Unless the context specifically indicates otherwise, the term amino acid, as used herein, is intended to include amino acid analogs or derivatives.

[0034] The term “amino acid sequence” as used herein means a compound composed of at least two constituent amino acids connected by covalent bonds. In some embodiments, the connecting covalent bond is a peptide bond. The constituent amino acids may be from the group of the amino acids encoded by the genetic code and they may be natural amino acids which are not encoded by the genetic code, as well as synthetic amino acids. Natural amino acids which are not encoded by the genetic code are e.g., γ-carboxyglutamate, ornithine, phosphoserine, D-DOCKET NO. STFD-012-PCT PCT APPLICATION alanine and D-glutamine. Synthetic amino acids comprise amino acids manufactured by chemical synthesis, and in some embodiments are, for example, D-isomers of the amino acids encoded by the genetic code (for example, D-alanine and D-leucine), Aib (α-aminoisobutyric acid), Abu (α-aminobutyric acid), Tle (tert-butylglycine), β-alanine, 3-aminomethyl benzoic acid, and anthranilic acid.

[0035] A “non-essential” amino acid residue is a residue that can be altered from the wild- type sequence of an amino acid sequence without abolishing or substantially altering its essential biological or biochemical activity (e.g., receptor binding or activation). An “essential” amino acid residue is a residue that, when altered from the wild-type sequence of the polypeptide, results in abolishing or substantially abolishing the polypeptide’s essential biological or biochemical activity.

[0036] A “non-natural side chain” is a modified or synthetic chain of atoms joined by covalent bond to the α-carbon atom, β-carbon atom, or γ-carbon atom which does not make up the backbone of the polypeptide chain of amino acids. For example, the natural side chain, or R group, of alanine is a methyl group, and a non-natural side chain of alanine may include one or more deuterium in place of the natural hydrogen(s).

[0037] A “non-naturally encoded amino acid” refers to an amino acid that is not one of the 20 common amino acids or pyrolysine or selenocysteine. Other terms that may be used synonymously with the term “non-naturally encoded amino acid” are “non-natural amino acid,” “unnatural amino acid,” “non-naturally-occurring amino acid,” and variously hyphenated and non-hyphenated versions thereof. The term “non-naturally encoded amino acid” also includes, but is not limited to, amino acids that occur by modification (e.g., post- translational modifications) of a naturally encoded amino acid (including but not limited to, the 20 common amino acids or pyrolysine and seienocysteine) but are not themselves naturally incorporated into a growing polypeptide chain by the translation complex. Examples of non- naturally-occurring amino acids include, but are not limited to, N-acetylglucosaminyl-L -serine N acetylglucosaminyl-L-threonine and O phosphotyrosine.

[0038] An “amino terminus modification group” refers to any molecule that can be attached to the amino terminus of an amino acid sequence. Similarly, a “carboxy terminus modification group” refers to any molecule that can be attached to the carboxy terminus of an amino acid sequence. Terminus modification groups include, but are not limited to, various water soluble polymers, peptides or proteins such as serum albumin, immunoglobulin constant region portions such as Fc, or other moieties that increase serum half-life of peptides.DOCKET NO. STFD-012-PCT PCT APPLICATION Amidation is a terminus modification groups, including a carboxy terminus modification. In some embodiments, an amino acid sequence herein, an amino acid sequence in a composition herein, or an amino acid sequence in a pharmaceutical composition herein includes a carboxy- terminal amidation as a modification. The term “linkage” or “linker” refers to a structure that connects two or more additional structures. Examples of linkers include peptide linkers, protein linkers, PEG linkers, and combinations thereof. A "maleimide-PEG linker", as used herein, refers to a chemical moiety comprising a polyethylene glycol (PEG) polymer of the formula "-(O-CH2-CH2)n-" wherein "n" is from about 3 through about 24, and a derivatized maleimide functional group, wherein said linker may form a covalent attachment to an amino acid sequence disclosed herein through a thioether bond between a maleimide functional group and a cysteine residue in the antibody or an antigen-binding fragment, and / or or may form a covalent attachment to an N-formyl- methionine peptide through an amide bond to the epsilon amino side chain of the C-terminal lysine of a N-formyl-methionine peptide or an amide bond to the gamma carboxyl group of the C-terminal glutamic acid of a N-formyl-methionine peptide.. Hydrolytically stable linkages means that the linkages are substantially stable in water and do not react with water at useful pH values, including but not limited to, under physiological conditions for an extended period of time, perhaps even indefinitely. Hydrolytically unstable or degradable linkages mean that the linkages are degradable in water or in aqueous solutions, including for example, blood. Enzymatically unstable or degradable linkages mean that the linkage can be degraded by one or more enzymes. As understood in the art, PEG and related polymers may include degradable linkages in the polymer backbone or in the linker group between the polymer backbone and one or more of the terminal functional groups of the polymer molecule. For example, ester linkages formed by the reaction of PEG carboxy lie acids or activated PEG carboxy lie acids with alcohol groups on a biologically active agent generally hydrolyze under physiological conditions to release the agent. Other hydrolytically degradable linkages include, but are not limited to, carbonate linkages; imine linkages resulted from reaction of an amine and an aldehyde; phosphate ester linkages formed by reacting an alcohol with a phosphate group; hydrazone linkages which are reaction product of a hydrazide and an aldehyde; acetal linkages that are the reaction product of an aldehyde and an alcohol; orthoester linkages that are the reaction product of a formate and an alcohol; peptide linkages formed by an amine group, including but not limited to, at an end of a polymer such as PEG, and a carboxyl group of a peptide; and oligonucleotide linkages formed by a phosphoramidite group, including but notDOCKET NO. STFD-012-PCT PCT APPLICATION limited to, at the end of a polymer, and a 5' hydroxyl group of an oligonucleotide. In some embodiments, a linker herein is gamma-Gly or GABA.

[0039] The term “polypeptide” encompasses two or more naturally or non-naturally- occurring amino acids joined by a covalent bond (e.g., an amide bond). Polypeptides as described herein include full-length proteins (e.g., fully processed pro-proteins or full-length synthetic polypeptides) as well as shorter amino acid sequences (e.g., fragments of naturally- occurring proteins or synthetic polypeptide fragments).

[0040] A “conservative amino acid substitution” is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art. These families include amino acids with basic side chains (e.g., K, R, H), acidic side chains (e.g., D, E), uncharged polar side chains (e.g., G, N, Q, S, T, Y, C, H), nonpolar side chains (e.g., G, A, V, L, I, P, F, M, W), beta- branched side chains (e.g., T, V, I) and aromatic side chains (e.g., Y, F, W, H). Thus, a predicted nonessential amino acid residue in an amino acid sequence, for example, replaced with another amino acid residue from the same side chain family. Other examples of conserved amino acid substitutions are substitutions based on isosteric considerations (e.g., norleucine for methionine) or other properties (e.g., 2-thienylalanine for phenylalanine).

[0041] As used herein, the term “derived from” in the context of the relationship between a chemical structure or amino acid sequence and a related chemical structure or related amino acid sequence describes a chemical structure homologous or structurally related to a reference chemical structure, or a biological sequence (e.g., an amino acid sequence) based on but varying from a reference biological sequence (e.g., by amino acid change or chemical modification).

[0042] The term “functional variant thereof” refers to a peptide varying from the reference sequence but retaining biological activity compared to a peptide having the reference sequence. In some embodiments, the biological activity is measured by a functional assay disclosed herein or any functional assay in which, for example, the variant induces an increase in cfos expression or CREB phosphorylation or has a therapeutic effect when administered to a subject relative to any indication disclosed herein. In some embodiments, a “functional variant thereof” has at least about 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more sequence identity, or a sequence identify from about any two of 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%, or a sequence identity of about 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% to a stated reference sequence.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0043] “Variants” are intended to mean similar sequences, and any solvates, salts, or mutants of a wild-type or reference sequence upon which the variant is based. For nucleic acid molecules, a variant comprises a nucleic acid molecule having deletions (i.e., truncations) at the 5’ and / or 3’ end; deletion and / or addition of one or more nucleotides at one or more internal sites in the native polynucleotide and / or substitution of one or more nucleotides at one or more sites in the native polynucleotide. For amino acid sequences, the variant is any mutant sequence of a reference sequence including any one or combination of an amino acid sequence: that is a truncation mutant, that has at least one addition, that has at least one deletion mutation, that has at least one point mutation as compared to the sequence upon which the variant sequence is based. As used herein, a “native” nucleic acid molecule or polypeptide sequence comprises a naturally occurring or endogenous nucleotide sequence or amino acid sequence, respectively. For nucleic acid molecules, conservative variants include those sequences that, because of the degeneracy of the genetic code, encode the amino acid sequence of one of the polypeptides of the disclosure. Variant nucleic acid molecules and amino acid sequences also include synthetically derived nucleic acid molecules, such as those generated, for example, by using site-directed mutagenesis but which still encode a protein of the disclosure. Generally, variants of a particular nucleic acid molecule of the disclosure will have at least about 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% sequence identity to an amino acid sequence disclosed herein. Variants of a particular nucleic acid molecule of the disclosure (i.e., the reference DNA sequence) can also be evaluated by comparison of the percent sequence identity between the amino acid sequence encoded by a variant nucleic acid molecule and the amino acid sequence encoded by the reference nucleic acid molecule. Percent sequence identity between any two amino acid sequences can be calculated using sequence alignment programs and parameters described elsewhere herein. In some embodiments, the term “variant” amino acid sequence is intended to mean an amino acid sequence derived from the native amino acid sequence by deletion (so-called truncation) of one or more amino acids at the N-terminal and / or C-terminal end of the native amino acid sequence; deletion and / or addition of one or more amino acids at one or more internal sites in the native amino acid sequence; or substitution of one or more amino acids at one or more sites in the native amino acid sequence. Amino acid sequences encompassed by the present disclosure are biologically active, that is they are functional variants, as above, and continue to possess the desired biological activity of the native amino acid sequences as described herein. Biologically active variant is synonymous with functional variant herein. Such variants may result from, for example, genetic polymorphism or from human manipulation. In some embodiments, functional variants of anDOCKET NO. STFD-012-PCT PCT APPLICATION amino acid sequence of the disclosure will have at least about 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more sequence identity to the amino acid sequence for the native amino acid sequence as determined by sequence alignment programs and parameters described elsewhere herein. A biologically active variant of an amino acid sequence of the disclosure may differ from that amino acid sequence by from about 1 to about 10 amino acid residues, as few as about 1 to about 15, for example from about 6 to about 10, as few as about 5, as few as about 4, 3, 2, or even 1 amino acid residue. The amino acid sequences of the disclosure may be altered in various ways including amino acid substitutions, deletions, truncations, and insertions. Methods for such manipulations are generally known in the art. For example, amino acid sequence variants and fragments of the proteins or amino acid sequences can be prepared by mutations in the nucleic acid sequences that encode the proteins or amino acid sequences recombinantly.

[0044] Percent identity refers to the number of aligned positions between a sequence and a reference sequence where the matching characters (e.g., amino acids in proteins or nucleotides in nucleic acids) are identical divided by the length of the reference sequence, and where the quotient is then multiplied by one hundred. The “percent identity” of two polynucleotide or two amino acid sequences is determined by comparing the sequences using the GAP computer program (a part of the GCG Wisconsin Package, version 10.3 (Accelrys, San Diego, Calif.)) using its default parameters. “Identical” or “identity” as used herein in the context of two or more nucleic acids or amino acid sequences, may mean that the sequences have a specified percentage of residues that are the same over a specified region. The percentage may be calculated by optimally aligning the two sequences, comparing the two sequences over the specified region, determining the number of positions at which the identical residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the specified region, and multiplying the result by 100 to yield the percentage of sequence identity. In cases where the two sequences are of different lengths or the alignment produces one or more staggered ends and the specified region of comparison includes only a single sequence, the residues of single sequence are included in the denominator but not the numerator of the calculation. When comparing DNA and RNA, thymine (T) and uracil (U) may be considered equivalent. Identity may be performed manually or by using a computer sequence algorithm such as BLAST or BLAST 2.0. Briefly, the BLAST algorithm, which stands for Basic Local Alignment Search Tool is suitable for determining sequence similarity. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (ncbi.nlm.nih.gov). This algorithm involvesDOCKET NO. STFD-012-PCT PCT APPLICATION first identifying high scoring sequence pair (HSPs) by identifying short words of length Win the query sequence that either match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold (Altschul et al., supra). These initial neighborhood word hits act as seeds for initiating searches to find HSPs containing them. The word hits are extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Extension for the word hits in each direction are halted when: 1) the cumulative alignment score falls off by the quantity X from its maximum achieved value; 2) the cumulative score goes to zero or below, due to the accumulation of one or more negative- scoring residue alignments; or 3) the end of either sequence is reached. The Blast algorithm parameters W, T and X determine the sensitivity and speed of the alignment. The Blast program uses as defaults a word length (W) of 11, the BLOSUM62 scoring matrix (see Henikoff et al., Proc. Natl. Acad. Sci. USA, 1992, 89, 10915-10919, which is incorporated herein by reference in its entirety) alignments (B) of 50, expectation (E) of 10, M=5, N=4, and a comparison of both strands. The BLAST algorithm (Karlin et al., Proc. Natl. Acad. Sci. USA, 1993, 90, 5873- 5787, which is incorporated herein by reference in its entirety) and Gapped BLAST perform a statistical analysis of the similarity between two sequences. One measure of similarity provided by the BLAST algorithm is the smallest sum probability (P(N)), which provides an indication of the probability by which a match between two sequences would occur by chance. For example, a nucleic acid is considered similar to another if the smallest sum probability in comparison of the test nucleic acid to the other nucleic acid is less than about 1, less than about 0.1, less than about 0.01, and less than about 0.001. Two single-stranded polynucleotides are “the complement” of each other if their sequences can be aligned in an anti-parallel orientation such that every nucleotide in one polynucleotide is opposite its complementary nucleotide in the other polynucleotide, without the introduction of gaps, and without unpaired nucleotides at the 5’ or the 3’ end of either sequence. A polynucleotide is “complementary” to another polynucleotide if the two polynucleotides can hybridize to one another under moderately stringent conditions. Thus, a polynucleotide can be complementary to another polynucleotide without being its complement.

[0045] The term “derivative” as used herein in relation to an amino acid sequence means a chemically modified amino acid sequence or a variant thereof, wherein at least one substituent is not present in the unmodified amino acid sequence or a variant thereof; i.e., a peptide which has been covalently modified. Typical modifications are amides, carbohydrates, alkyl groups,DOCKET NO. STFD-012-PCT PCT APPLICATION acyl groups, esters and the like. The term “derivative” also encompasses a protein, peptide, or amino acid sequence including one or more non-naturally encoded amino acid.”

[0046] The term “excipient” as used herein means the chemical compounds which are normally added to pharmaceutical compositions; e.g., buffers, tonicity agents, preservatives and the like.

[0047] The term “pharmaceutical composition” as used herein means a product comprising an active amino acid disclosed herein or a salt thereof together with pharmaceutical excipients; e.g., a buffer, preservative, a tonicity modifier and / or a stabilizer. A pharmaceutical composition is also known in the art as a pharmaceutical formulation.

[0048] The term “salt” refers to acidic salts formed with inorganic and / or organic acids, as well as basic salts formed with inorganic and / or organic bases. Examples of these acids and bases are well known to those of ordinary skill in the art. Such acid addition salts will normally be pharmaceutically acceptable although salts of non-pharmaceutically acceptable acids may be of utility in the preparation and purification of the compound in question. Salts include those formed from hydrochloric, hydrobromic, sulphuric, phosphoric, citric, tartaric, lactic, pyruvic, acetic, succinic, fumaric, maleic, methanesulphonic and benzenesulphonic acids.

[0049] The term “subject” is used throughout the specification to describe an animal to whom treatment with an amino acid sequence, composition, or pharmaceutical composition herein is provided or administered. For treatment of those conditions which are specific for a specific subject, such as a human being, the term “patient” may be interchangeably used. In some instances in the description herein, the term “patient” will refer to human patients. In some embodiments, the subject may be a mammal to whom an amino acid sequence, composition, or pharmaceutical composition herein is provided or administered. In some embodiments, the subject may be a non-human animal to whom an amino acid sequence, composition, or pharmaceutical composition herein is provided or administered. In some embodiments, the subject is a domesticated animal, such as a horse, cow, pig, sheep, goat, dog, or cat.

[0050] The term “soluble” or “water soluble” refers to solubility that is higher than 1 / 100,000 (mg / ml). The solubility of a substance, or solute, is the maximum mass of that substance that can be dissolved completely in a specified mass of the solvent, such as water. “Practically insoluble” or “insoluble,” on the other hand, refers to an aqueous solubility that is 1 / 10,000 (mg / ml) or less. Water soluble or soluble substances include, for example, polyethylene glycol. In some embodiments, the polypeptide of the claimed disclosure may be bound by polyethylene glycol to better solubilize the composition comprising the peptide.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0051] The terms “treating” and “to treat”, mean to alleviate symptoms, eliminate the causation either on a temporary or permanent basis, or to prevent or slow the appearance of symptoms. The term “treatment” includes alleviation, elimination of causation (temporary or permanent) of, or prevention of symptoms and disorders associated with any condition. The treatment may be a pre-treatment as well as a treatment at the onset of symptoms.

[0052] “Effective amount” refers to an amount of an amino acid sequence, a composition, or pharmaceutical composition as described herein effective to achieve a particular biological result such as, but not limited to, biological results disclosed, described, or exemplified herein. Such results may include, but are not limited to, the effective reduction of symptoms associated with any of the disease states mentioned herein, as determined by any means suitable in the art. The effective amount of the composition may be dependent on any number of variables, including without limitation, the species, breed, size, height, weight, age, overall health of the subject, the type of formulation, the mode or manner or administration, the type and / or severity of the particular condition being treated, or the need to modulate the activity of the molecular pathway induced by association of the analog to its receptor. The appropriate effective amount can be routinely determined by those of skill in the art using routine optimization techniques and the skilled and informed judgment of the practitioner and other factors evident to those skilled in the art. A therapeutically effective dose of variants or derivatives described herein may provide partial or complete biological activity as compared to the biological activity induced by the wild-type or naturally occurring amino acid sequences upon which the variants or derivatives are derived. A therapeutically effective dose of the variants or derivatives described herein may provide a sustained biochemical or biological affect and / or an increased resistance to degradation when placed in solution as compared with the normal affect observed when the naturally occurring and fully processed and translated protein or peptide is administered to the same subject.

[0053] The term “fragment” refers to any variant of a naturally occurring amino acid disclosed herein that comprises at least 4 amino acids identical to the naturally occurring amino acid sequence upon which the variant is based. The term “functional fragment” refers to any fragment of any variant of a naturally occurring amino acid sequence disclosed herein that comprises at least 4 amino acids identical to the naturally occurring amino acid sequence upon which the variant is based and shares the function of the naturally occurring polypeptide upon which the variant is based. In some embodiments, the fragment comprises at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids common with the naturally occurring peptide. In some embodiments, the fragment is a variant comprises at least 4, 5, 6, 7, 8, 9, 10,DOCKET NO. STFD-012-PCT PCT APPLICATION 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids common with the naturally occurring peptide upon which the fragment is based or the as compared to the sequence upon which it is based, and the fragment is missing at least one amino acid residue as compared to the sequence upon which it is based.

[0054] A “GLP-1 domain” or “GLP-1 modulator” as used herein means a polypeptide or polypeptide-like molecule that acts as a glucagon-like peptide 1 modulator. In some embodiments, the GLP-1 modulator is an GLP-1 receptor agonist or a GLP-1 alpha receptor agonist.

[0055] As used herein, the terms “increase” and “decrease” mean, respectively, to cause a statistically significantly (i.e., p<0.15) increase or decrease of at least 1%, 2%, or 5%.

[0056] As used herein, the recitation of a numerical range for a variable is intended to convey that the embodiment may be practiced with the variable equal to any of the values within that range. Thus, for a variable which is inherently discrete, the variable is equal to any integer value within the numerical range, including the end-points of the range. Similarly, for a variable which is inherently continuous, the variable is equal to any real value within the numerical range, including the end-points of the range. As an example, and without limitation, a variable which is described as having values between 0 and 2 takes the values 0, 1 or 2 if the variable is inherently discrete, and takes the values 0.0, 0.1, 0.01, 0.001, 10–12,10-11,10-10,10- 9,10-8,10-7,10-6 ,10-5,10-4 or any other real values ≥0 and ≤2 if the variable is inherently continuous.

[0057] As used herein, unless specifically indicated otherwise, the word “or” is used in the inclusive sense of “and / or” and not the exclusive sense of “either / or.”

[0058] The term “biological activity” encompasses structural and functional properties of an amino acid sequence herein. Biological activity is, in some embodiments, inducing an increase in cfos expression or CREB phosphorylation. Biological activity is, in some embodiments, inducing insulin secretion, protects pancreatic beta cells, and inhibits glucagon secretion, gastric emptying and food intake which leads to weight loss. In some embodiments, biological activity is sensation of satiety, insulin secretion, and nutrient disposal. In some embodiments, the BRNP3 or variants thereof comprise biological activity but are free of a biological activity of inducing loss of muscle mass.

[0059] The terms “prodrug” or “prodrug derivative” mean a covalently-bonded derivative or carrier of the analog of an amino acid sequence herein that undergoes at least some biotransformation prior to exhibiting its pharmacological effect(s). In general, such prodrugs have metabolically cleavable groups and are rapidly transformed in vivo to yield theDOCKET NO. STFD-012-PCT PCT APPLICATION analog of the claimed disclosure, for example, by hydrolysis in blood, and generally include esters and amide analogs of the analogs. The prodrug is formulated with the objectives of improved chemical stability, improved patient acceptance and compliance, improved bioavailability, prolonged duration of action, improved organ selectivity, improved formulation (e.g., increased hydrosolubility), and / or decreased side effects (e.g., toxicity). In general, prodrugs themselves have weak or no biological activity and are stable under ordinary conditions. Prodrugs can be readily prepared from the analogs using methods known in the art, such as those described in A Textbook of Drug Design and Development, Krogsgaard-Larsen and H. Bundgaard (eds.), Gordon & Breach, 1991, particularly Chapter 5: “Design and Applications of Prodrugs”; Design of Prodrugs, H. Bundgaard (ed.), Elsevier, 1985; Prodrugs: Topical and Ocular Drug Delivery, K. B. Sloan (ed.), Marcel Dekker, 1998; Methods in Enzymology, K. Widder et al. (eds.), Vol.42, Academic Press, 1985, particularly pp.309-396; Burger’s Medicinal Chemistry and Drug Discovery, 5th Ed., M. Wolff (ed.), John Wiley & Sons, 1995, particularly Vol.1 and pp.172-178 and pp.949-982; Pro-Drugs as Novel Delivery Systems, T. Higuchi and V. Stella (eds.), Am. Chem. Soc., 1975; and Bioreversible Carriers in Drug Design, E. B. Roche (ed.), Elsevier, 1987, each of which is incorporated herein by reference in their entireties. In some embodiments, the composition comprises an amino acid sequence that is a prodrug that, when administered to the subject becomes biologically active sufficient to treat diabetes, obesity, weight gain, MASH, and / or MASLP.

[0060] In some embodiments, the disclosure relates to a composition or pharmaceutical composition comprising a pharmaceutically acceptable prodrug that, when administered to the subject becomes biologically active. The term “pharmaceutically acceptable prodrug” as used herein means a prodrug of an amino acid sequence herein that is, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit / risk ratio, and effective for their intended use, as well as the zwitterionic forms, where possible.

[0061] In some embodiments, an amino acid sequence or variant thereof is a pharmaceutically acceptable acid addition salt. The term “pharmaceutically acceptable acid addition salt” means those salts which retain the biological effectiveness and properties of the free bases and which are not biologically or otherwise undesirable, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, sulfamic acid, nitric acid, phosphoric acid, and the like, and organic acids such as acetic acid, trichloroacetic acid, trifluoroacetic acid, adipic acid, alginic acid, ascorbic acid, aspartic acid, benzenesulfonicDOCKET NO. STFD-012-PCT PCT APPLICATION acid, benzoic acid, 2-acetoxybenzoic acid, butyric acid, camphoric acid, camphorsulfonic acid, cinnamic acid, citric acid, digluconic acid, ethanesulfonic acid, glutamic acid, glycolic acid, glycerophosphoric acid, hemisulfic acid, heptanoic acid, hexanoic acid, formic acid, fumaric acid, 2-hydroxyethanesulfonic acid (isethionic acid), lactic acid, maleic acid, hydroxymaleic acid, malic acid, malonic acid, mandelic acid, mesitylenesulfonic acid, methanesulfonic acid, naphthalenesulfonic acid, nicotinic acid, 2-naphthalenesulfonic acid, oxalic acid, pamoic acid, pectinic acid, phenylacetic acid, 3-phenylpropionic acid, picric acid, pivalic acid, propionic acid, pyruvic acid, pyruvic acid, salicylic acid, stearic acid, succinic acid, sulfanilic acid, tartaric acid, p-toluenesulfonic acid, undecanoic acid, and the like. In some embodiments, the analog of the claimed disclosure is a pharmaceutically acceptable base addition salt. The term “pharmaceutically acceptable base addition salt” means those salts which retain the biological effectiveness and properties of the free acids and which are not biologically or otherwise undesirable, formed with inorganic bases such as ammonia or hydroxide, carbonate, or bicarbonate of ammonium or a metal cation such as sodium, potassium, lithium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, and the like. Suitable salts include ammonium, potassium, sodium, calcium, and magnesium salts. Salts derived from pharmaceutically-acceptable organic nontoxic bases include salts of primary, secondary, and tertiary amines, quaternary amine compounds, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion-exchange resins, such as methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, triethylamine, isopropylamine, tripropylamine, tributylamine, ethanolamine, diethanolamine, 2-dimethylaminoethanol, 2- diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, tetramethylammonium compounds, tetraethylammonium compounds, pyridine, N,N-dimethylaniline, N-methylpiperidine, N- methylmorpholine, dicyclohexylamine, dibenzylamine, N,N-dibenzylphenethylamine, 1- ephenamine, N,N’-dibenzylethylenediamine, polyamine resins, and the like. In some embodiments, the composition of the claimed disclosure comprises at least one organic nontoxic base chosen from isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine.

[0062] The term “solvate” means a physical association of a compound with one or more solvent molecules or a complex of variable stoichiometry formed by a solute (e.g., an amino acid sequence or variant and / or derivative thereof herein) and a solvent, for example, water, ethanol, or acetic acid. This physical association may involve varying degrees of ionicDOCKET NO. STFD-012-PCT PCT APPLICATION and covalent bonding, including hydrogen bonding. In certain instances, the solvate will be capable of isolation, for example, when one or more solvent molecules are incorporated in the crystal lattice of the crystalline solid. In general, the solvents selected do not interfere with the biological activity of the solute. Solvates encompasses both solution-phase and isolatable solvates. Representative solvates include hydrates, ethanolates, and methanolates.

[0063] The disclosure relates to amino acid sequences, nucleic acid sequences encoding the amino acid sequences and compositions comprising the same. In some embodiments, the compositions comprise one or more amino acid sequence of Table 1 or functional variants thereof. In some embodiments, the compositions comprise a nucleic acid sequence encoding one or more amino acid sequence of Table 1 or functional variants thereof. In some embodiments, the disclosure relates to a pharmaceutical composition comprising a therapeutically effective amount of one or more amino acid sequence of Table 1 or functional variants thereof. TABLE 1 Active Peptide Sequences YEQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO:1) YEQLEISMKQLFLKAQKIVHKLFSLS (SEQ ID NO:2) YEQLENSMKQLFLKAHRIVHKLFSLS (SEQ ID NO:3) YEQLETNMKQLFLKAQKIVHKLFSLS (SEQ ID NO:4) MKQLFLKAQKIVHKLFSLS (SEQ ID NO:5) KQLFLKAQKIVHKLFSLS (SEQ ID NO:6) QLFLKAQKIVHKLFSLS (SEQ ID NO:7) LFLKAQKIVHKLFSLS (SEQ ID NO:8) YEQLETNMKQLFLKAX1X2IVHKLFSLS (SEQ ID NO:9) wherein X1 is any amino acid and X2 is any amino acid YEQLEX1X2MKQLFLKAX3X4IVHKLFSLS (SEQ ID NO:10) wherein X1, X2, X3 and X4 are independently selected from any amino acid X1X2MKQLFLKAX3X4IVHKLFSLS (SEQ ID NO:11) wherein X1, X2, X3 and X4 are independently selected from any amino acid MKQLFLKAX1X2IVHKLFSLS (SEQ ID NO:12) wherein X1 is any amino acid and X2 is any amino acid. HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NO:13) EQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO:14) QLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO:15) LENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO:16) ENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO:17) NSMKQLFLKAQKIVHKLFSLS (SEQ ID NO:18)DOCKET NO. STFD-012-PCT PCT APPLICATION SMKQLFLKAQKIVHKLFSLS (SEQ ID NO:19) FLKAQKIVHKLFSLS (SEQ ID NO:20) LKAQKIVHKLFSLS (SEQ ID NO:21) KAQKIVHKLFSLS (SEQ ID NO:22) AQKIVHKLFSLS (SEQ ID NO:23) QKIVHKLFSLS (SEQ ID NO:24) KIVHKLFSLS (SEQ ID NO:25) IVHKLFSLS (SEQ ID NO:26) VHKLFSLS (SEQ ID NO:27) HKLFSLS (SEQ ID NO:28) KLFSLS (SEQ ID NO:29) LFSLS (SEQ ID NO:30) YEQLENSMKQLFLKAHRIVHKLFSLS (SEQ ID NO:31) YEQLEISMKQLFLKAQKIVHKLFSLS (SEQ ID NO:32) YEQLETNIKQLYLKAQKTIHKLFSLS (SEQ ID NO:33) GLP1 sequences 7-37 HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NO:34) 7-36 HAEGTFTSDVSSYLEGQAAKEFIAWLVKGR (SEQ ID NO:35) (Modifications: Arg-30 = C-terminal amide) Exendin-4 HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS (SEQ ID NO: 36) (Modifications: Ser-39 = C-terminal amide) GLP1 fusions can be added to any lysine (K) on the respective peptide. It can either be added directly via an amide bond, or using a linker* (gamma-Gly, or GABA) BRP_1-26 GLP17-37 C-terminal fusion YEQLENSMKQLFLKAQKIVHKLFSLS-linker*- HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NOS 37 and 45) BRP_1-26 GLP17-37 N-terminal fusion HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG-linker*- YEQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NOS 38 and 46) BRP_1-26 Liraglutide C-terminal fusionDOCKET NO. STFD-012-PCT PCT APPLICATION YEQLENSMKQLFLKAQKIVHKLFSLS-linker*- HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NOS 39 and 47) (Modifications: Lys-21 = Lys-(γ-Glu-palmitoyl)) BRP_1-26 Exendin-4 C-terminal fusion YEQLENSMKQLFLKAQKIVHKLFSLS - linker* - HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NOS 40 and 48) BRP_1-26 GLP17-37 fusion YEQLENSMKQLFLKAQKIVHKLFSLS -linker- HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NOS 41 and 49) Liraglutide HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NO: 42) (Modifications: Lys-20 = Lys-(γ-Glu-palmitoyl)) Oxyntomodulin HSQGTFTSDYSKYLDSRRAQDFVQWLMNTKRNKNNIA (SEQ ID NO: 43) H-His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala- Lys(AEEAc-AEEAc-γ-Glu-17-carboxyheptadecanoyl)-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg- Gly-Arg-Gly-OH (SEQ ID NO: 44) Further Active Peptide Sequences X1X2X3LENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 59) wherein X1, X2, andX3are independently selected from any amino acid X1X2X3X4X5X6X7X8X9X10X11X12LKAQKIVHKLFSLS (SEQ ID NO: 60) wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12are independently selected from any amino acid X1X2X3X4X5X6X7X8X9X10X11X12X13KAQKIVHKLFSLS (SEQ ID NO: 61) wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, and X13are independently selected from any amino acid X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15X16KIVHKLFSLS (SEQ ID NO: 62) wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16are independently selected from any amino acid X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15X16X17IVHKLFSLS (SEQ ID NO: 63) wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16,and X17are independently selected from any amino acid X1X2X3LX4X5X6MX7X8LFLKX9X10KX11X12X13KLFX14LX15(SEQ ID NO: 64) wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, and X15are independently selected from any amino acid X1X2X3LX4X5X6MKQLFLKAX7KIVHKLFSLS (SEQ ID NO: 65) wherein X1, X2, X3, X4, X5, and X6are independently selected from any amino acid YEQLENSMKQLFLKAQKX1X2X3KLFX4LX5 (SEQ ID NO: 66) wherein X1, X2, X3, X4, and X5are independently selected from any amino acidDOCKET NO. STFD-012-PCT PCT APPLICATION YEQLENSX1KQLFLKAQKX2X3X4KLFX5LX6(SEQ ID NO: 67) wherein X1, X2, X3, X4, X5, and X6are independently selected from any amino acid YEQLENSMKQX1FLKAQKX2X3X4KLFX5LX6(SEQ ID NO: 68) wherein X1, X2, X3, X4, X5, and X6are independently selected from any amino acid YEQLENSMKQLX1LKAQKX2X3X4KLFX5LX6(SEQ ID NO: 69) wherein X1, X2, X3, X4, X5, and X6are independently selected from any amino acid YEQLENSMKQLFX1KAQKX2X3X4KLFX5LX6(SEQ ID NO: 70) wherein X1, X2, X3, X4, X5, and X6are independently selected from any amino acid YEQLENSMKQLFLX1AQKX2X3X4KLFX5LX6(SEQ ID NO: 71) wherein X1, X2, X3, X4, X5, and X6are independently selected from any amino acid YEQLENSMKQLFLKAQX1X2X3X4KLFX5LX6(SEQ ID NO: 72) wherein X1, X2, X3, X4, X5, and X6are independently selected from any amino acid YEQLENSMKQLFLKAQKX1X2X3KLFX4X5X6(SEQ ID NO: 73) wherein X1, X2, X3, X4, X5, and X6are independently selected from any amino acid X2X3X4LX5X6X7X8X8X9X10X11X12X13X14X15KX16X17X18KLFX19X20X21(SEQ ID NO: 74) wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16,X17,X18, X19, X20, and X21are independently selected from any amino acid X1X2X3LX4X5X6MX7X8LFLKX9X10X11X12X13X14KLFX15LX16(SEQ ID NO: 75) wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16are independently selected from any amino acid BRP3 Hu 26 YEQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 76) KJS BRP3 A1 26 AEQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 77) KJS BRP3 A2 26 YAQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 78) KJS BRP3 A3 26 YEALENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 79) KJS BRP3 A4 26 YEQAENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 80) KJS BRP3 A5 26 YEQLANSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 81) KJS BRP3 A6 26 YEQLEASMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 82) KJS BRP3 A7 26 YEQLENAMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 83) KJS BRP3 A8 26 YEQLENSAKQLFLKAQKIVHKLFSLS (SEQ ID NO: 84) KJS BRP3 A9 26 YEQLENSMAQLFLKAQKIVHKLFSLS (SEQ ID NO: 85) KJS BRP3 A1026 YEQLENSMKALFLKAQKIVHKLFSLS (SEQ ID NO: 86) KJS BRP3 A1126 YEQLENSMKQAFLKAQKIVHKLFSLS (SEQ ID NO: 87) KJS BRP3 A1226 YEQLENSMKQLALKAQKIVHKLFSLS (SEQ ID NO: 88) KJS BRP3 A1326 YEQLENSMKQLFAKAQKIVHKLFSLS (SEQ ID NO: 89) KJS BRP3 A1426 YEQLENSMKQLFLAAQKIVHKLFSLS (SEQ ID NO: 90)DOCKET NO. STFD-012-PCT PCT APPLICATION KJS BRP3 A1526 YEQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 91) KJS BRP3 A1626 YEQLENSMKQLFLKAAKIVHKLFSLS (SEQ ID NO: 92) KJS BRP3 A1726 YEQLENSMKQLFLKAQAIVHKLFSLS (SEQ ID NO: 93) KJS BRP3 A1826 YEQLENSMKQLFLKAQKAVHKLFSLS (SEQ ID NO: 94) KJS BRP3 A1926 YEQLENSMKQLFLKAQKIAHKLFSLS (SEQ ID NO: 95) KJS BRP3 A2026 YEQLENSMKQLFLKAQKIVAKLFSLS (SEQ ID NO: 96) KJS BRP3 A2126 YEQLENSMKQLFLKAQKIVHALFSLS (SEQ ID NO: 97) KJS BRP3 A2226 YEQLENSMKQLFLKAQKIVHKAFSLS (SEQ ID NO: 98 KJS BRP3 A2326 YEQLENSMKQLFLKAQKIVHKLASLS (SEQ ID NO: 99) KJS BRP3 A2426 YEQLENSMKQLFLKAQKIVHKLFALS (SEQ ID NO: 100) KJS BRP3 A2526 YEQLENSMKQLFLKAQKIVHKLFSAS (SEQ ID NO: 101) KJS BRP3 A2626 YEQLENSMKQLFLKAQKIVHKLFSLA (SEQ ID NO: 102)

[0064] In some embodiments, the disclosure provides an amino acid sequence comprising BRINP3, a functional variant thereof, or a pharmaceutically acceptable salt or solvate thereof.

[0065] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 1), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:1.

[0066] In some embodiments, the amino acid sequence comprises YEQLEISMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 2), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:2.

[0067] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFLKAHRIVHKLFSLS (SEQ ID NO: 3), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:3.

[0068] In some embodiments, the amino acid sequence comprises MKQLFLKAQKIVHKLFSLS (SEQ ID NO: 5), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO:6. In some embodiments, the disclosure relates to an aminoDOCKET NO. STFD-012-PCT PCT APPLICATION acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:5.

[0069] In some embodiments, the amino acid sequence comprises KQLFLKAQKIVHKLFSLS (SEQ ID NO: 6), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO:6. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:6.

[0070] In some embodiments, the amino acid sequence comprises QLFLKAQKIVHKLFSLS (SEQ ID NO: 7), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 7. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:7.

[0071] In some embodiments, the amino acid sequence comprises LFLKAQKIVHKLFSLS (SEQ ID NO: 8), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO:8. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:8.

[0072] In some embodiments, the amino acid sequence comprises YEQLETNMKQLFLKAX1X2IVHKLFSLS (SEQ ID NO: 9), wherein X1 is any amino acid and X2is any amino acid, or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, X1and X2in SEQ ID NO: 9 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:9.

[0073] In some embodiments, the amino acid sequence comprises YEQLEX1X2MKQLFLKAX3X4IVHKLFSLS (SEQ ID NO: 10), wherein X1, X2, X3, and X4 are independently selected from any amino acid, or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:10. InDOCKET NO. STFD-012-PCT PCT APPLICATION some embodiments, X1, X2, X3, and X4 in SEQ ID NO: 10 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0074] In some embodiments, the amino acid sequence comprises X1X2MKQLFLKAX3X4IVHKLFSLS (SEQ ID NO: 11), wherein X1, X2, X3and X4are independently selected from any amino acid, or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:11. In some embodiments, X1, X2, X3, and X4 in SEQ ID NO: 11 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0075] In some embodiments, the amino acid sequence comprises MKQLFLKAX1X2IVHKLFSLS (SEQ ID NO: 12), wherein X1is any amino acid and X2is any amino acid, or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:12. In some embodiments, X1 and X2 in SEQ ID NO: 12 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0076] In some embodiments, the amino acid sequence comprises HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NO: 13), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:13.

[0077] In some embodiments, the amino acid sequence comprises HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NO: 13), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:13.

[0078] In some embodiments, the amino acid sequence comprises EQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 14), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or aboutDOCKET NO. STFD-012-PCT PCT APPLICATION 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:14.

[0079] In some embodiments, the amino acid sequence comprises QLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 15), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:15.

[0080] In some embodiments, the amino acid sequence comprises LENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 16), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:16.

[0081] In some embodiments, the amino acid sequence comprises ENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 17), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:17.

[0082] In some embodiments, the amino acid sequence comprises NSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 18), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:18.

[0083] In some embodiments, the amino acid sequence comprises SMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 19), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:19.

[0084] In some embodiments, the amino acid sequence comprises FLKAQKIVHKLFSLS (SEQ ID NO: 20), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:20.

[0085] In some embodiments, the amino acid sequence comprises LKAQKIVHKLFSLS (SEQ ID NO: 21), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%,DOCKET NO. STFD-012-PCT PCT APPLICATION 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:21.

[0086] In some embodiments, the amino acid sequence comprises KAQKIVHKLFSLS (SEQ ID NO: 22), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:22.

[0087] In some embodiments, the amino acid sequence comprises AQKIVHKLFSLS (SEQ ID NO: 23), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:23.

[0088] In some embodiments, the amino acid sequence comprises QKIVHKLFSLS (SEQ ID NO: 24), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:24.

[0089] In some embodiments, the amino acid sequence comprises KIVHKLFSLS (SEQ ID NO: 25), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:25.

[0090] In some embodiments, the amino acid sequence comprises IVHKLFSLS (SEQ ID NO: 26), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:26.

[0091] In some embodiments, the amino acid sequence comprises VHKLFSLS (SEQ ID NO: 27), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:27.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0092] In some embodiments, the amino acid sequence comprises HKLFSLS (SEQ ID NO: 28), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:28.

[0093] In some embodiments, the amino acid sequence comprises KLFSLS (SEQ ID NO: 29), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:29.

[0094] In some embodiments, the amino acid sequence comprises LFSLS (SEQ ID NO: 30), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:30.

[0095] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFLKAHRIVHKLFSLS (SEQ ID NO: 31), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:31.

[0096] In some embodiments, the amino acid sequence comprises YEQLEISMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 32), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:32.

[0097] In some embodiments, the amino acid sequence comprises YEQLETNIKQLYLKAQKTIHKLFSLS (SEQ ID NO: 33), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:33.

[0098] In some embodiments, the amino acid sequence comprises X1X2X3LENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 59), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 59. In some embodiments, the disclosure relates to anDOCKET NO. STFD-012-PCT PCT APPLICATION amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO: 59. In some embodiments, X1, X2, and X3are independently selected from any amino acid. In some embodiments, X1, X2, and X3 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, and X3 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, and X3are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, and X3 in SEQ ID NO: 59 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, and X3 in SEQ ID NO: 59 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0099] In some embodiments, the amino acid sequence comprises X1X2X3X4X5X6X7X8X9X10X11X12LKAQKIVHKLFSLS (SEQ ID NO: 60), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 60. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO: 60. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12are independently selected from any amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12in SEQ ID NO: 60 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12in SEQ ID NO: 60 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0100] In some embodiments, the amino acid sequence comprises X1X2X3X4X5X6X7X8X9X10X11X12X13KAQKIVHKLFSLS (SEQ ID NO: 61), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,DOCKET NO. STFD-012-PCT PCT APPLICATION 97%, 98% or about 99% sequence identity to SEQ ID NO: 61. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO: 61. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, and X13are independently selected from any amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, and X13 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, and X13are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, and X13 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, and X13in SEQ ID NO: 61 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, and X13 in SEQ ID NO: 61 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0101] In some embodiments, the amino acid sequence comprises X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15X16KIVHKLFSLS (SEQ ID NO: 62), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 62. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:62. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16in SEQ ID NO: 62 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16in SEQ ID NO: 62 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0102] In some embodiments, the amino acid sequence comprises X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15X16X17IVHKLFSLS (SEQ ID NO: 63), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 63. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO: 63. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, and X17 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16,and X17are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, and X17 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, and X17 in SEQ ID NO: 63 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, and X17 in SEQ ID NO: 63 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0103] In some embodiments, the amino acid sequence comprises X1X2X3LX4X5X6MX7X8LFLKX9X10KX11X12X13KLFX14LX15(SEQ ID NO: 64), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 64. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO: 64. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, and X15 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, and X15 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, and X15 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, and X15 in SEQ ID NO: 64 are chosen such that the amino acid sequence is free of the amino acidDOCKET NO. STFD-012-PCT PCT APPLICATION sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, and X15in SEQ ID NO: 64 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0104] In some embodiments, the amino acid sequence comprises X1X2X3LX4X5X6MKQLFLKAX7KIVHKLFSLS (SEQ ID NO: 65), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 65. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO: 65. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 65 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 65 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0105] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFLKAQKX1X2X3KLFX4LX5 (SEQ ID NO: 66), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 66. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO: 66. In some embodiments, X1, X2, X3, X4, and X5 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, and X5 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, and X5are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, and X5 in SEQ ID NO: 66 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, and X5 in SEQ ID NO: 66 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0106] In some embodiments, the amino acid sequence comprises YEQLENSX1KQLFLKAQKX2X3X4KLFX5LX6(SEQ ID NO: 67), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 67. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO: 67. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6in SEQ ID NO: 67 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6in SEQ ID NO: 67 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0107] In some embodiments, the amino acid sequence comprises YEQLENSMKQX1FLKAQKX2X3X4KLFX5LX6 (SEQ ID NO: 68), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 68. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO: 68. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6in SEQ ID NO: 68 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6in SEQ ID NO: 68 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0108] In some embodiments, the amino acid sequence comprises YEQLENSMKQLX1LKAQKX2X3X4KLFX5LX6 (SEQ ID NO: 69), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 69. In some embodiments, the disclosure relatesDOCKET NO. STFD-012-PCT PCT APPLICATION to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO: 69. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6in SEQ ID NO: 69 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6in SEQ ID NO: 69 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0109] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFX1KAQKX2X3X4KLFX5LX6 (SEQ ID NO: 70), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 70. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO: 70. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6in SEQ ID NO: 70 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6in SEQ ID NO: 70 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0110] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFLX1AQKX2X3X4KLFX5LX6 (SEQ ID NO: 71), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 71. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO: 71. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected fromDOCKET NO. STFD-012-PCT PCT APPLICATION any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6in SEQ ID NO: 71 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6in SEQ ID NO: 71 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0111] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFLKAQX1X2X3X4KLFX5LX6 (SEQ ID NO: 72), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 72. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO: 72. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6in SEQ ID NO: 72 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6in SEQ ID NO: 72 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0112] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFLKAQKX1X2X3KLFX4X5X6 (SEQ ID NO: 73), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 73. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO: 73. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6 in SEQ IDDOCKET NO. STFD-012-PCT PCT APPLICATION NO: 73 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6in SEQ ID NO: 73 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0113] In some embodiments, the amino acid sequence comprises X2X3X4LX5X6X7X8X8X9X10X11X12X13X14X15KX16X17X18KLFX19X20X21 (SEQ ID NO: 74), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 74. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO: 74. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16,X17,X18, X19, X20, and X21are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, X17, X18, X19, X20, and X21 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, X17, X18, X19, X20, and X21 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16,X17,X18, X19, X20, and X21in SEQ ID NO: 74 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16,X17,X18, X19, X20, and X21in SEQ ID NO: 74 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0114] In some embodiments, the amino acid sequence comprises X1X2X3LX4X5X6MX7X8LFLKX9X10X11X12X13X14KLFX15LX16(SEQ ID NO: 75), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 75. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO: 75. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16 are independently selectedDOCKET NO. STFD-012-PCT PCT APPLICATION from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16in SEQ ID NO: 75 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16in SEQ ID NO: 75 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0115] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 76), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 76.

[0116] In some embodiments, the amino acid sequence comprises AEQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 77), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 77.

[0117] In some embodiments, the amino acid sequence comprises YAQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 78), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 78.

[0118] In some embodiments, the amino acid sequence comprises YEALENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 79), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 79.

[0119] In some embodiments, the amino acid sequence comprises YEQAENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 80), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 80.

[0120] In some embodiments, the amino acid sequence comprises YEQLANSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 81), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 81.

[0121] In some embodiments, the amino acid sequence comprises YEQLEASMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 82), or functional variants thereofDOCKET NO. STFD-012-PCT PCT APPLICATION comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 82.

[0122] In some embodiments, the amino acid sequence comprises YEQLENAMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 83), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 83.

[0123] In some embodiments, the amino acid sequence comprises YEQLENSAKQLFLKAQKIVHKLFSLS (SEQ ID NO: 84), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 84.

[0124] In some embodiments, the amino acid sequence comprises YEQLENSMAQLFLKAQKIVHKLFSLS (SEQ ID NO: 85), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 85.

[0125] In some embodiments, the amino acid sequence comprises YEQLENSMKALFLKAQKIVHKLFSLS (SEQ ID NO: 86), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 86.

[0126] In some embodiments, the amino acid sequence comprises YEQLENSMKQAFLKAQKIVHKLFSLS (SEQ ID NO: 87), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 87.

[0127] In some embodiments, the amino acid sequence comprises YEQLENSMKQLALKAQKIVHKLFSLS (SEQ ID NO: 88), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 88.

[0128] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFAKAQKIVHKLFSLS (SEQ ID NO: 89), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 89.

[0129] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFLAAQKIVHKLFSLS (SEQ ID NO: 90), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 90.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0130] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 91), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 91.

[0131] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFLKAAKIVHKLFSLS (SEQ ID NO: 92), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 92.

[0132] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFLKAQAIVHKLFSLS (SEQ ID NO: 93), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 93.

[0133] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFLKAQKAVHKLFSLS (SEQ ID NO: 94), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 94.

[0134] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFLKAQKIAHKLFSLS (SEQ ID NO: 95), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 95.

[0135] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFLKAQKIVAKLFSLS (SEQ ID NO: 96), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 96.

[0136] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFLKAQKIVHALFSLS (SEQ ID NO: 97), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 97.

[0137] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFLKAQKIVHKAFSLS (SEQ ID NO: 98), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 98.

[0138] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFLKAQKIVHKLASLS (SEQ ID NO: 99), or functional variants thereofDOCKET NO. STFD-012-PCT PCT APPLICATION comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 99.

[0139] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFLKAQKIVHKLFALS (SEQ ID NO: 100), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 100.

[0140] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFLKAQKIVHKLFSAS (SEQ ID NO: 101), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 101.

[0141] In some embodiments, the amino acid sequence comprises YEQLENSMKQLFLKAQKIVHKLFSLA (SEQ ID NO: 102), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 102.

[0142] In some embodiments, the amino acid sequence comprises H-His-Aib-Glu-Gly- Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys(AEEAc-AEEAc-γ- Glu-17-carboxyheptadecanoyl)-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH (SEQ ID NO: 44) , or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:44.

[0143] In some embodiments, the amino acid sequence comprises SEQ ID NO: 12, a functional variant comprising at least about 75% sequence identity to SEQ ID NO:12, wherein X1 and X2 are independently selected from any amino acid, or a pharmaceutically acceptable salt thereof.

[0144] In some embodiments, the amino acid sequence comprises SEQ ID NO: 9 or a functional variant comprising at least about 75% sequence identity to SEQ ID NO:9, wherein X1 and X2 are independently selected from any amino acid, or a pharmaceutically acceptable salt thereof.

[0145] In some embodiments, the amino acid sequence comprises SEQ ID NO:10, SEQ ID NO:11, or functional variants thereof comprising at least about 75% sequence identity to SEQ ID NO:10 or SEQ ID NO:11, or a pharmaceutically acceptable salt thereof.

[0146] In some embodiments, the amino acid sequence is chosen from: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQDOCKET NO. STFD-012-PCT PCT APPLICATION ID NO:8, or functional variants thereof comprising at least about 75% sequence identity to one or combination of: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8.

[0147] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence herein. The disclosure also relates to a composition comprising BRINP3 or a variant of BRINP3, including solvates, salts or truncation mutants thereof comprising a first amino acid sequence that is no more than about 30 amino acids in length and comprises at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% 99%, or 100% sequence identity to one or a combination of: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13¸ SEQ ID NO: 14¸ SEQ ID NO: 15¸ SEQ ID NO: 16¸ SEQ ID NO: 17¸ SEQ ID NO: 18¸ SEQ ID NO: 19¸ SEQ ID NO: 20, SEQ ID NO: 21¸ SEQ ID NO:22¸ SEQ ID NO: 23¸ SEQ ID NO: 24¸ SEQ ID NO: 25¸ SEQ ID NO: 31¸ SEQ ID NO: 32¸ SEQ ID NO: 33, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, and SEQ ID NO: 102. In some embodiments, the amino acid comprises a first domain comprising BRINP3 or a variant of BRINP3, and a second domain comprising a second amino acid sequence that is a GLP-1 domain, or salt or solvate thereof. In some embodiments, the first domain is from about 20 to about 35 amino acids in length, and the second domain is from about 25 to about 35 amino acids in length.

[0148] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 1), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:1.

[0149] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLEISMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 2), orDOCKET NO. STFD-012-PCT PCT APPLICATION functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:2.

[0150] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAHRIVHKLFSLS (SEQ ID NO: 3), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:3.

[0151] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising MKQLFLKAQKIVHKLFSLS (SEQ ID NO: 5), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO:6. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:5.

[0152] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising KQLFLKAQKIVHKLFSLS (SEQ ID NO: 6), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO:6. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:6.

[0153] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising QLFLKAQKIVHKLFSLS (SEQ ID NO: 7), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 7. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:7.

[0154] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising LFLKAQKIVHKLFSLS (SEQ ID NO: 8), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO:8. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:8.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0155] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLETNMKQLFLKAX1X2IVHKLFSLS (SEQ ID NO: 9), wherein X1 is any amino acid and X2 is any amino acid, or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, X1 and X2 in SEQ ID NO: 9 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:9.

[0156] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLEX1X2MKQLFLKAX3X4IVHKLFSLS (SEQ ID NO: 10), wherein X1, X2, X3, and X4 are independently selected from any amino acid, or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:10. In some embodiments, X1, X2, X3, and X4 in SEQ ID NO: 10 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0157] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising X1X2MKQLFLKAX3X4IVHKLFSLS (SEQ ID NO: 11), wherein X1, X2, X3 and X4 are independently selected from any amino acid, or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:11. In some embodiments, X1, X2, X3, and X4 in SEQ ID NO: 11 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0158] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising MKQLFLKAX1X2IVHKLFSLS (SEQ ID NO: 12), wherein X1is any amino acid and X2 is any amino acid, or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:12. In some embodiments, X1 and X2 in SEQ ID NO: 12 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0159] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NO: 13), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:13.

[0160] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NO: 13), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:13.

[0161] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising EQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 14), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:14.

[0162] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising QLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 15), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:15.

[0163] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising LENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 16), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:16.

[0164] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising ENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 17), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to aDOCKET NO. STFD-012-PCT PCT APPLICATION composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:17.

[0165] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising NSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 18), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:18.

[0166] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising SMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 19), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:19.

[0167] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising FLKAQKIVHKLFSLS (SEQ ID NO: 20), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:20.

[0168] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising LKAQKIVHKLFSLS (SEQ ID NO: 21), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:21.

[0169] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising KAQKIVHKLFSLS (SEQ ID NO: 22), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:22.

[0170] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising AQKIVHKLFSLS (SEQ ID NO: 23), or functional variants thereofDOCKET NO. STFD-012-PCT PCT APPLICATION comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:23.

[0171] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising QKIVHKLFSLS (SEQ ID NO: 24), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:24.

[0172] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising KIVHKLFSLS (SEQ ID NO: 25), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:25.

[0173] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising IVHKLFSLS (SEQ ID NO: 26), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:26.

[0174] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising VHKLFSLS (SEQ ID NO: 27), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:27.

[0175] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising HKLFSLS (SEQ ID NO: 28), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:28.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0176] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising KLFSLS (SEQ ID NO: 29), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:29.

[0177] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising LFSLS (SEQ ID NO: 30), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:30.

[0178] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAHRIVHKLFSLS (SEQ ID NO: 31), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:31.

[0179] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLEISMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 32), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:32.

[0180] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLETNIKQLYLKAQKTIHKLFSLS (SEQ ID NO: 33), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:33.

[0181] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising X1X2X3LENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 59), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 59. In some embodiments, the disclosure relates to a composition comprising an amino acid sequenceDOCKET NO. STFD-012-PCT PCT APPLICATION comprising at least 75% sequence identity to SEQ ID NO: 59. In some embodiments, X1, X2, and X3are independently selected from any amino acid. In some embodiments, X1, X2, and X3are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, and X3are independently selected from any non-polar amino acid. In some embodiments, X1, X2, and X3 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, and X3in SEQ ID NO: 59 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, and X3in SEQ ID NO: 59 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0182] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising X1X2X3X4X5X6X7X8X9X10X11X12LKAQKIVHKLFSLS (SEQ ID NO: 60), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 60. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 60. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12are independently selected from any amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12in SEQ ID NO: 60 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12in SEQ ID NO: 60 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0183] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising X1X2X3X4X5X6X7X8X9X10X11X12X13KAQKIVHKLFSLS (SEQ ID NO: 61), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%,DOCKET NO. STFD-012-PCT PCT APPLICATION 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 61. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 61. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, and X13are independently selected from any amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, and X13 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, and X13are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, and X13 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, and X13 in SEQ ID NO: 61 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, and X13 in SEQ ID NO: 61 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0184] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15X16KIVHKLFSLS (SEQ ID NO: 62), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 62. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:62. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16in SEQ ID NO: 62 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16in SEQ ID NO: 62 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0185] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15X16X17IVHKLFSLS (SEQ ID NO: 63), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 63. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 63. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, and X17 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16,and X17are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, and X17 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, and X17 in SEQ ID NO: 63 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, and X17 in SEQ ID NO: 63 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0186] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising X1X2X3LX4X5X6MX7X8LFLKX9X10KX11X12X13KLFX14LX15(SEQ ID NO: 64), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 64. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 64. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, and X15 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, and X15 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, and X15 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, and X15 in SEQ ID NO: 64 are chosen such that the amino acid sequence is free of the amino acidDOCKET NO. STFD-012-PCT PCT APPLICATION sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, and X15in SEQ ID NO: 64 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0187] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising X1X2X3LX4X5X6MKQLFLKAX7KIVHKLFSLS (SEQ ID NO: 65), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 65. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 65. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 65 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 65 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0188] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKX1X2X3KLFX4LX5(SEQ ID NO: 66), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 66. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 66. In some embodiments, X1, X2, X3, X4, and X5 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, and X5 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, and X5are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, and X5 in SEQ ID NO: 66 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2,DOCKET NO. STFD-012-PCT PCT APPLICATION X3, X4, and X5 in SEQ ID NO: 66 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0189] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSX1KQLFLKAQKX2X3X4KLFX5LX6(SEQ ID NO: 67), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 67. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 67. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 67 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 67 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0190] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQX1FLKAQKX2X3X4KLFX5LX6 (SEQ ID NO: 68), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 68. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 68. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6in SEQ ID NO: 68 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6in SEQ ID NO: 68 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0191] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLX1LKAQKX2X3X4KLFX5LX6(SEQ ID NO: 69), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 69. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 69. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 69 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 69 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0192] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFX1KAQKX2X3X4KLFX5LX6 (SEQ ID NO: 70), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 70. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 70. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6in SEQ ID NO: 70 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6in SEQ ID NO: 70 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0193] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFLX1AQKX2X3X4KLFX5LX6 (SEQ ID NO: 71),DOCKET NO. STFD-012-PCT PCT APPLICATION or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 71. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 71. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 71 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 71 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0194] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQX1X2X3X4KLFX5LX6 (SEQ ID NO: 72), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 72. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 72. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6in SEQ ID NO: 72 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6in SEQ ID NO: 72 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0195] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKX1X2X3KLFX4X5X6 (SEQ ID NO: 73), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 73. In someDOCKET NO. STFD-012-PCT PCT APPLICATION embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 73. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 73 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 73 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0196] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising X2X3X4LX5X6X7X8X8X9X10X11X12X13X14X15KX16X17X18KLFX19X20X21 (SEQ ID NO: 74), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 74. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 74. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, X17, X18, X19, X20, and X21 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16,X17,X18, X19, X20, and X21are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16,X17,X18, X19, X20, and X21are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16,X17,X18, X19, X20, and X21in SEQ ID NO: 74 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16,X17,X18, X19, X20, and X21in SEQ ID NO: 74 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0197] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising X1X2X3LX4X5X6MX7X8LFLKX9X10X11X12X13X14KLFX15LX16(SEQ ID NO: 75), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 75. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 75. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16 in SEQ ID NO: 75 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16 in SEQ ID NO: 75 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0198] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 76), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 76.

[0199] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising AEQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 77), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 77.

[0200] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YAQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 78), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 78.

[0201] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEALENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 79), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 79.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0202] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQAENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 80), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 80.

[0203] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLANSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 81), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 81.

[0204] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLEASMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 82), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 82.

[0205] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENAMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 83), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 83.

[0206] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSAKQLFLKAQKIVHKLFSLS (SEQ ID NO: 84), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 84.

[0207] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMAQLFLKAQKIVHKLFSLS (SEQ ID NO: 85), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 85.

[0208] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKALFLKAQKIVHKLFSLS (SEQ ID NO: 86), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 86.

[0209] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQAFLKAQKIVHKLFSLS (SEQ ID NO: 87), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 87.

[0210] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLALKAQKIVHKLFSLS (SEQ ID NO: 88), orDOCKET NO. STFD-012-PCT PCT APPLICATION functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 88.

[0211] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFAKAQKIVHKLFSLS (SEQ ID NO: 89), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 89.

[0212] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFLAAQKIVHKLFSLS (SEQ ID NO: 90), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 90.

[0213] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 91), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 91.

[0214] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAAKIVHKLFSLS (SEQ ID NO: 92), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 92.

[0215] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQAIVHKLFSLS (SEQ ID NO: 93), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 93.

[0216] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKAVHKLFSLS (SEQ ID NO: 94), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 94.

[0217] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKIAHKLFSLS (SEQ ID NO: 95), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 95.

[0218] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKIVAKLFSLS (SEQ ID NO: 96), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 96.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0219] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKIVHALFSLS (SEQ ID NO: 97), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 97.

[0220] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKIVHKAFSLS (SEQ ID NO: 98), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 98.

[0221] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKIVHKLASLS (SEQ ID NO: 99), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 99.

[0222] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKIVHKLFALS (SEQ ID NO: 100), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 100.

[0223] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKIVHKLFSAS (SEQ ID NO: 101), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 101.

[0224] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKIVHKLFSLA (SEQ ID NO: 102), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 102.

[0225] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising H-His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu- Glu-Gly-Gln-Ala-Ala-Lys(AEEAc-AEEAc-γ-Glu-17-carboxyheptadecanoyl)-Glu-Phe-Ile- Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH (SEQ ID NO: 44) , or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:44.

[0226] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising SEQ ID NO: 12, a functional variant comprising at least about 75%DOCKET NO. STFD-012-PCT PCT APPLICATION sequence identity to SEQ ID NO:12, wherein X1 and X2 are independently selected from any amino acid, or a pharmaceutically acceptable salt thereof.

[0227] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising SEQ ID NO: 9 or a functional variant comprising at least about 75% sequence identity to SEQ ID NO:9, wherein X1 and X2 are independently selected from any amino acid, or a pharmaceutically acceptable salt thereof.

[0228] In some embodiments, the disclosure relates to a composition comprising one or a combination of an amino acid sequence comprising SEQ ID NO:10, SEQ ID NO:11, or functional variants thereof comprising at least about 75% sequence identity to SEQ ID NO:10 or SEQ ID NO:11, or a pharmaceutically acceptable salt thereof.

[0229] In some embodiments, the disclosure relates to a composition comprising an amino acid sequence comprising one or a combination of SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, or functional variants thereof comprising at least about 75% sequence identity to one or combination of: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8.

[0230] In some embodiments, the disclosure relates to a composition comprises an amino acid sequence comprising a first and second domain, wherein the first domain is a BRINP3 domain and wherein the second domain is a GLP-1 domain. In some embodiments, the first domain and the second domain are positioned in that order in the amino to carboxy orientation. In some embodiments, the amino acid sequence comprises one or a plurality of linkers positioned between the first and second domains. In some embodiments, the amino acid sequence comprises, in a an amino to carboxy orientation, the second domain and then the first domain.

[0231] In some embodiments, the amino acid sequence of the first domain is as described above for one of SEQ ID NOS: 1 through 33 and 59 through 102. In some embodiments, the amino acid sequence comprises a second domain comprising HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NO:34), or functional a variant thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO:34. In some embodiments, the amino acid sequence of the GLP-1 domain comprises an amino acid comprising at least 75% sequence identity to SEQ ID NO:34. In some embodiments, the amino acid sequence is HAEGTFTSDVSSYLEGQAAKEFIAWLVKGR (SEQ ID NO:35), or functional a variant thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%DOCKET NO. STFD-012-PCT PCT APPLICATION or about 99% sequence identity to SEQ ID NO:35. In some embodiments, the amino acid sequence of the GLP-1 domain comprises an amino acid comprising at least 75% sequence identity to SEQ ID NO:35. In some embodiments, the amino acid sequence is HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS (SEQ ID NO: 36), or functional a variant thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO:36. In some embodiments, the amino acid sequence of the GLP-1 domain comprises an amino acid comprising at least 75% sequence identity to SEQ ID NO:36. In some embodiments, the amino acid sequence is HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NO: 42), or functional variant thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 42. In some embodiments, the amino acid sequence of the GLP-1 domain comprises an amino acid comprising at least 75% sequence identity to SEQ ID NO:42. In some embodiments, the amino acid sequence is HSQGTFTSDYSKYLDSRRAQDFVQWLMNTKRNKNNIA (SEQ ID NO: 43), or functional a variant thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO:43. In some embodiments, the amino acid sequence of the GLP-1 domain comprises an amino acid comprising at least 75% sequence identity to SEQ ID NO:43.

[0232] In some embodiments, the amino acid sequence of the composition comprising an amino acid sequence comprising a first and second domain comprises YEQLENSMKQLFLKAQKIVHKLFSLS-linker*- HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NOS 37 and 45), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NOS 37 and 45. In some embodiments, the composition comprising an amino acid sequence comprising a first and second domain comprises an amino acid comprising at least 75% sequence identity to SEQ ID NOS 37 and 45. In some embodiments, the linker is gamma-Gly or GABA.

[0233] In some embodiments, the composition comprising an amino acid sequence comprising a first and second domain comprises HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG-linker*- YEQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NOS 38 and 46), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NOS 38 and 46. In some embodiments, the composition comprising an amino acid sequence comprising a first and second domainDOCKET NO. STFD-012-PCT PCT APPLICATION comprises an amino acid comprising at least 75% sequence identity to SEQ ID NOS 38 and 46. In some embodiments, the linker is gamma-Gly or GABA.

[0234] In some embodiments, the composition comprising an amino acid sequence comprising a first and second domain comprises YEQLENSMKQLFLKAQKIVHKLFSLS- linker*-HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NOS 39 and 47), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NOS 39 and 47. In some embodiments, the composition comprising an amino acid sequence comprising a first and second domain comprises an amino acid comprising at least 75% sequence identity to SEQ ID NOS 39 and 47. In some embodiments, Lys-20 is Lys-(γ-Glu-palmitoyl). In some embodiments, the linker is gamma-Gly or GABA.

[0235] In some embodiments, the composition comprising an amino acid sequence comprising a first and second domain comprises YEQLENSMKQLFLKAQKIVHKLFSLS- linker*-HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NOS 40 and 48), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NOS 40 and 48. In some embodiments, the composition comprising an amino acid sequence comprising a first and second domain comprises an amino acid comprising at least 75% sequence identity to SEQ ID NOS 40 and 48. In some embodiments, the linker is gamma-Gly or GABA.

[0236] In some embodiments, the composition comprising an amino acid sequence comprising a first and second domain comprises YEQLENSMKQLFLKAQKIVHKLFSLS- linker-HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NOS 41 and 49), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NOS 41 and 49. In some embodiments, the composition comprising an amino acid sequence comprising a first and second domain comprises an amino acid comprising at least 75% sequence identity to SEQ ID NOS 41 and 49. In some embodiments, the linker is gamma-Gly or GABA.

[0237] In some embodiments, the amino acid sequence of the GLP-1 domain comprises HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NO: 42), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO:42. In some embodiments, the amino acid sequence of the GLP-1 domain comprises an amino acid comprising at least 75% sequence identity to SEQ ID NO:42. In some embodiments, Lys-20 is Lys-(γ-Glu-palmitoyl). In some embodiments, the linker is gamma-Gly or GABA.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0238] In some embodiments, the amino acid sequence of the GLP-1 domain comprises HSQGTFTSDYSKYLDSRRAQDFVQWLMNTKRNKNNIA (SEQ ID NO: 43), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO:43. In some embodiments, the amino acid sequence of the GLP-1 domain comprises an amino acid comprising at least 75% sequence identity to SEQ ID NO:43. In some embodiments, Lys-20 is Lys-(γ-Glu-palmitoyl). In some embodiments, the linker is gamma-Gly or GABA.

[0239] In some embodiments, the amino acid sequence of the GLP-1 domain comprises tirzepatide or semaglutanide, or a functional variant or salt thereof. As used herein, “tirzepatide” means a GIP / GLP1 dual agonist peptide as described in US 9,474,780 and described by CAS Registry Number: 2023788-19-2 with a formula of: YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS, wherein X1is Aib; X2is Aib; K at position 20 is chemically modified through conjugation to the epsilon-amino group of the K side-chain with (2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(γGlu)1-CO-(CH2)18-CO2H; and the C-terminal amino acid is amidated as a C-terminal primary amide.

[0240] Compositions of the disclosure relate to amino acid sequences disclosed herein that optionally comprise a GLP-1 domain that comprises semaglutide, a functional variant thereof or a salt thereof. Semaglutide is an amino acid sequence comprising: H-His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala- Lys(AEEAc-AEEAc-γ-Glu-carboxyheptadecanoyl)-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly- Arg-Gly-OH or His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln- Ala-Ala-Lys(AEEAc-AEEAc-γ-Glu-carboxyheptadecanoyl)-Glu-Phe-Ile-Ala-Trp-Leu-Val- Arg-Gly-Arg-Gly, or a salt thereof.

[0241] The disclosure relates to a composition comprising an amino acid sequence In some embodiments, GLP1 fusions can be added to any lysine (K) on the respective peptide. It can either be added directly via an amide bond, or using a linker* (e.g., gamma-Gly, or GABA).

[0242] In some embodiments, the carboxy terminal (c-terminal) end of an amino acid sequence herein, the c-terminal end of an amino acid sequence in any composition or pharmaceutical composition disclosed herein, or a c-terminal end of an amino acid sequence in a pharmaceutical composition herein is modified with one or more chemical moieties. In some embodiments, the carboxy terminal end of the amino acid sequence is amidated. In some embodiments, one or more tyrosine an amino acid sequence herein, one or more tyrosine of an amino acid sequence in a composition herein, or one or more tyrosine of an amino acid sequence is sulfated in any of the compositions or pharmaceutical compositions disclosedDOCKET NO. STFD-012-PCT PCT APPLICATION herein. In some embodiments, the one or more tyrosine incudes tyrosine 1 in SEQ ID NO:1, tyrosine 1 in SEQ ID NO:2, tyrosine 1 in SEQ ID NO:3, tyrosine 1 in SEQ ID NO:4, tyrosine 1 in SEQ ID NO:9, tyrosine 1 in SEQ ID NO:10, tyrosine 1 in SEQ ID NO:31, tyrosine 1 in SEQ ID NO:32, tyrosine 1 in SEQ ID NO:33, tyrosine 1 in SEQ ID NO:37, tyrosine 1 in SEQ ID NO:39, tyrosine 1 in SEQ ID NO:40, and / or tyrosine 1 in SEQ ID NO:41. In some embodiments, the one or more tyrosine incudes tyrosines 1 and 12 in SEQ ID NO:33.

[0243] The amino acids of the composition and pharmaceutical compositions of the disclosure may also comprise one or a plurality of linkers. The disclosed peptides may be conjugated directly to an amino acid disclosed herein or a variant thereof. In other embodiments, the disclosed peptides may be conjugated indirectly to an amino acid sequence disclosed herein or a variant thereof via a linker. In some embodiments, one or more of the linkers has a selected linear length. Suitable selected lengths may include at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50 angstroms or longer, or a range bounded by any of these values (such as from about 5 to about 10 angstroms, from about 10 to about 20 angstroms, from about 15 to about 20 angstroms, from about 15 to about 25 angstroms, from about 20 to about 35 angstroms, from about 30 to about 40 angstroms, from about 35 to about 40 angstroms, from about 35 to about 50 angstroms, and from about 40-= to about 50 angstroms).

[0244] In some embodiments, the disclosed linkers have a spacer arm which may provide the linker with a selected length. For example, the disclosed linkers may have a formula represented as:Suitable spacer arms may comprise a polymeric moiety such as polyethylene glycol.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0245] In some embodiments, the linker has a formula selected from:

[0246] 24. In some embodiments, the linker comprises a malemide moiety and a PEG moiety and may be referred to as a "maleimide-PEG linker" which conjugates an N-formyl- CF3-methionine to an antibody, antibody fragment or salt thereof.

[0247] In some embodiments, the spacer arm comprises a peptide sequence of from about 1 to about 20 amino acids. In some embodiments, the spacer arm is a peptide sequence comprising amino acids selected from glycine, serine, and alanine (e.g., (G4S)m (SEQ ID NO: 50) where m is an integer selected from about 1 to about 5). In some embodiments, the disclosed linkers may comprise a polyethylene glycol moiety, for example, as a spacer arm or otherwise. In some embodiments, the linker comprises a polyethylene glycol (PEG) moiety (i.e., (-O-CH2-CH2)1-24).

[0248] In some embodiments, the disclosed linkers may comprise two or more PEG moieties that are split by a non-PEG moiety such as amino acid moieties. In some embodiments, the disclosed linkers comprise a split polyethylene glycol moiety represented as -((PEG)1-24)- (AA)1-2-((PEG)1-24)-, wherein AA is Glutamic acid bonded via gamma amino acylation or Lysine bonded via epsilon amino acylation.

[0249] In some embodiments, one or a plurality of linkers comprise about 0 to about 25, about 1 to about 25, about 2 to about 25, about 3 to about 25, about 4 to about 25, about 5 toDOCKET NO. STFD-012-PCT PCT APPLICATION about 25, about 6 to about 25, about 7 to about 25, about 8 to about 25, about 9 to about 25, about 10 to about 25, about 11 to about 25, about 12 to about 25, about 13 to about 25, about 14 to about 25, about 15 to about 25, about 16 to about 25, about 17 to about 25, about 18 to about 25, about 19 to about 25, about 20 to about 25, about 21 to about 25, about 22 to about 25, about 23 to about 25, about 24 to about 25 natural or non-natural nucleic acids in length. In some embodiments, each linker is about 0, 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 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25 natural or non-natural nucleic acids in length. In some embodiments, each linker is independently selectable from a linker that is about 0, 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 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25 natural or non-natural nucleic acids in length. In some embodiments, each linker is about 21 natural or non-natural nucleic acids in length.

[0250] In some embodiments, the length of one or plurality of linkers is the same. In some emobdiments, the length of each linker is different. For example, in some embodiments, the length of a first linker is about 0, 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 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25 natural or non-natural nucleic acids in length, and the length of a second linker is about 0, 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 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25 natural or non-natural nucleic acids in length, where the length of the first linker is different from the length of the second linker. Various configurations can be envisioned by the present disclosure, whereby the amino acid sequence of the disclosure comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more linkers wherein the linkers are of similar or different lengths.

[0251] In certain embodiments, one or more can be used together, in a nucleotide sequence that encodes a fusion peptide comprising a first domain that is BRINP3 or a variant thereof, a linker and a nucleotide sequence encoding a second domain. Accordingly, in some embodiments, the one or more linkers is independently selectable from about 0 to about 25 natural or non-natural nucleic acids in length, about 0 to about 25, about 1 to about 25, about 2 to about 25, about 3 to about 25, about 4 to about 25, about 5 to about 25, about 6 to about 25, about 7 to about 25, about 8 to about 25, about 9 to about 25, about 10 to about 25, about 11 toDOCKET NO. STFD-012-PCT PCT APPLICATION about 25, about 12 to about 25, about 13 to about 25, about 14 to about 25, about 15 to about 25, about 16 to about 25, about 17 to about 25, about 18 to about 25, about 19 to about 25, about 20 to about 25, about 21 to about 25, about 22 to about 25, about 23 to about 25, about 24 to about 25 natural or non-natural nucleic acids in length. In some embodiments, the second linker is independently selectable from about 0 to about 25, about 1 to about 25, about 2 to about 25, about 3 to about 25, about 4 to about 25, about 5 to about 25, about 6 to about 25, about 7 to about 25, about 8 to about 25, about 9 to about 25, about 10 to about 25, about 11 to about 25, about 12 to about 25, about 13 to about 25, about 14 to about 25, about 15 to about 25, about 16 to about 25, about 17 to about 25, about 18 to about 25, about 19 to about 25, about 20 to about 25, about 21 to about 25, about 22 to about 25, about 23 to about 25, about 24 to about 25 natural or non-natural nucleic acids in length. In some embodiments, the first linker is independently selectable from a linker that is about 0, 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 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25 natural or non-natural nucleic acids in length. In some embodiments, the second linker is independently selectable from a linker that is about 0, 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 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25 natural or non-natural nucleic acids in length.

[0252] In some embodiments, the formula representing the amino acid sequence of the disclosure (e.g. [BRINP3 domain]–[linker]–[second domain]) comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more linkers, wherein the BRINP3 domain comprises BRINP3 or a variant thereof. In some embodiments, the second domain comprises a GLP-1 receptor agonist or variant thereof. In some embodiments, the second domain comprises one amino acid sequence selected from: SEQ ID NO:36 through 44, or a functional variant thereof comprising at least about 75% sequence identity to SEQ ID NO:36 through 44. In some embodiments, the amino acid or composition comprising the same is free of non-natural amino acids.

[0253] In a further embodiment, the at least one linker comprises a furin protease cleavage site. Furin is a protease which resides in the trans-Golgi network of eukaryotic cells. Its function is to cleave proteins at a step just prior to their delivery to their final cellular destination. Furin recognizes a consensus amino acid sequence, RXRR, RXRK or KXKR (where X is any amino acid, Moehring et al., 1993, incorporated by reference in its entirety herein) and cuts proteins which contain these sequences when they reach the trans-GolgiDOCKET NO. STFD-012-PCT PCT APPLICATION network. Furin is a Ca2+-dependent serine endoprotease that cleaves protein precursors with a high specificity after the multiple basic motifs shown in Table 1 below.

[0254] In certain embodiments, the one or plurality of nucleic acid molecules encode or amino acid sequences comprise a furin-sensitive cleavage site selected from the sequence R-X- [R / K] -R, where R denotes arginine, X is any amino acid, and K is lysine. The "R / K" indicates that this amino acid may be either arginine or lysine. Table below discloses SEQ ID NOS 51-58, respectively, in order of appearance.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0255] The disclosure also relates to a composition comprising one or a plurality of nucleic acid sequences, wherein the nucleic acid sequence encodes a BRINP3 domain or a functional variant thereof. In some embodiments, the nucleic acid sequence encodes a BRINP3 functional variant comprising any one or more nucleic acid sequence encoding an amino acid sequence selected from SEQ ID NO:1 through SEQ ID NO:25, SEQ ID NO:31, SEQ ID NO, 32, SEQ ID NO: 33 and SEQ ID NO:34. In some embodiments, the nucleic acid sequence further encodes a linker. In some embodiments, the disclosure relates to a nucleic acid molecule comprising a nucleic acid sequence comprising a formula: [BRINP3 domain]–(linker)– or [BRINP3 domain]–(linker)–[second amino acid domain], wherein the “hyphen” is a peptide bond, a single covalent bond or series of amino acids that fuse the first and second domains into one contiguous amino acid sequence in an amino to carboxy terminal orientation. In some embodiments, the BRINP3 domain comprises peptide 5 of FIG.2A. In some embodiments, the BRINP3 domain comprises peptide 1 of FIG.2A. In some embodiments, the BRINP3 domain comprises peptide 2 of FIG.2A. In some embodiments, the BRINP3 domain comprises peptide 3 of FIG.2A. In some embodiments, the BRINP3 domain comprises peptide 4 of FIG.2A. In some embodiments, the BRINP3 domain comprises peptide 6 of FIG. 2A. In some embodiments, the BRINP3 domain comprises peptide 5 and any one or combination of: peptide 1, 2, 3, 4, or 6 of FIG. 2A. In some embodiments, the composition or pharmaceutical composition comprises peptide 5 of FIG. 2A but is free of any one or combination of peptide 1, 2, 3, 4, or 6 of FIG.2A.

[0256] In a still further aspect, the nucleic acid molecule described in any of the aspects and embodiments herein is a plasmid. In certain embodiments, an expression vector comprises the nucleic acid molecule described in any of the aspects and embodiments. In certain embodiments, the nucleic acid expression vector is a plasmid. The vector can be capable of expressing one or a plurality of amino acid sequences in the cell. The vector can be recombinant. The vector can comprise heterologous nucleic acid encoding the amino acids disclosed herein. The vector can be useful for transfecting cells with nucleic acid encoding BRINP3 or a BRINP3 variant disclosed herein optionally fused in a chimeric amino acid sequence to a second, biologically functional domain. In some embodiments, the disclosure relates to a cell comprising a nucleic acid molecule disclosed herein optionally cultured and maintained under conditions wherein expression of the amino acid domain or domains takes place. In some embodiments, the vector is capable of expressing one or a plurality of BRINP3 variants in the cell of a mammal in a quantity effective to stimulate a biological response in the mammal. In some embodiments, a cell comprising the nucleic acid molecule is capable ofDOCKET NO. STFD-012-PCT PCT APPLICATION expressing one or a plurality of amino acid sequences disclosed herein in the cell of a mammal in a quantity effective to isolate a quantity of amino acid. In some embodiments, the quantity of amino acid is predetermined for bioengineering processing to isolate from about 1 to about 10,000 grams of amino acid. In some embodiments, the quantity of amino acid is predetermined for bioengineering processing to isolate from about 1 to about 100,000 grams of amino acid.

[0257] The vector can comprise heterologous nucleic acid encoding a BRINP3 or BRINP3 variant and can further comprise an initiation codon, which can be upstream of the BRINP3 or BRINP3 variant coding sequence, and a stop codon, which can be downstream of the BRINP3 or BRINP3 variant coding sequence in a 5’ to 3’ orientation. The initiation and termination codon can be in frame with the BRINP3 or BRINP3 variant coding sequence. In some embodiments, the disclosure relates to a plasmid comprising a nucleic acid sequence encoding BRP3 or a functional variant thereof. In some embodiments, the functional variant of BRP3 is no more than 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40 amino acids in length and is free of peptide 1, 2, 3, 4, and / or 6 as depicted in FIG.2A.

[0258] The vector can also comprise a promoter that is operably linked to the expressible nucleic acid sequence encoding BRINP3 or a functional variant thereof. In some embodiments, the vector comprises a promoter that is operably linked to a nucleic acid sequence encoding BRINP3 or a functional variant thereof. The promoter operably linked to the BRINP3 or BRINP3 variant coding sequence can be a promoter from simian virus 40 (SV40), a mouse mammary tumor virus (MMTV) promoter, a human immunodeficiency virus (HIV) promoter such as the bovine immunodeficiency virus (BIV) long terminal repeat (LTR) promoter, a Moloney virus promoter, an avian leukosis virus (ALV) promoter, a cytomegalovirus (CMV) promoter such as the CMV immediate early promoter, Epstein Barr virus (EBV) promoter, or a Rous sarcoma virus (RSV) promoter. The promoter can also be a promoter from a human gene such as human actin, human myosin, human hemoglobin, human muscle creatine, or human metalothionein. The promoter can also be a tissue-specific promoter, such as a muscle or skin specific promoter, natural or synthetic. Examples of such promoters are described in US patent application publication no. US20040175727, the contents of which are incorporated herein in its entirety.

[0259] The vector can also comprise a polyadenylation signal, which can be downstream of the HA coding sequence. The polyadenylation signal can be a SV40 polyadenylation signal, LTR polyadenylation signal, bovine growth hormone (bGH) polyadenylation signal, human growth hormone (hGH) polyadenylation signal, or human beta-globin polyadenylation signal. The SV40 polyadenylation signal can be a polyadenylation signal from a pCEP4 vector (LifeDOCKET NO. STFD-012-PCT PCT APPLICATION Sciences, San Diego, Calif.). The vector can also comprise an enhancer upstream of the BRINP3 or BRINP3 variant coding. The enhancer can be necessary for DNA expression. The enhancer can be human actin, human myosin, human hemoglobin, human muscle creatine or a viral enhancer such as one from CMV, HA, RSV or EBV. Polynucleotide function enhances are described in U.S. Pat. Nos.5,593,972, 5,962,428, and WO94 / 016737, the contents of each are fully incorporated by reference.

[0260] The vector can also comprise a mammalian origin of replication in order to maintain the vector extrachromosomally and produce multiple copies of the vector in a cell. The disclosure relates to a cell comprising a nucleic acid sequence encoding a first amino acid domain comprising BRINP3 or a BRINP3 functional variant. In some embodiments, the disclosure relates to a cell comprising a nucleic acid molecule that is a plasmid comprising an expressible nucleic acid sequence, the nucleic acid sequence comprising a first amino acid domain that is BRINP3 or a BRINP3 functional variant. In some embodiments, the cell is a human cell, a mammalian cell, an insect cell or a prokaryotic cell. An isolated nucleic acid molecule encoding an amino acid sequences disclosed herein can be expressed by operably linking a promoter to one or more nucleic acid sequences encoding the amino acid domain. DNA fragments encompassing these regions can be obtained, e.g., by standard PCR amplification. Polynucleotides of the present disclosure can be expressed in a host cell after the sequences have been operably linked to an expression control sequence. The expression vectors are typically replicable in the host organisms either as episomes or as an integral part of the host chromosomal DNA. Expression vectors may contain selection markers, e.g., tetracycline, neomycin, and dihydrofolate reductase, to permit detection of those cells transformed with the desired DNA sequences. The vectors containing the polynucleotide sequences of interest (e.g., the polynucleotides encoding the polypeptides of the antibody and expression control sequences) can be transferred into the host cell by well-known methods which vary depending on the type of cellular host. Amino acid sequences of the disclosure can readily be produced in mammalian cells, of which non-limiting examples include CHO, NS0, HEK293 or COS cells. The host cells are cultured using techniques well known in the art. Mammalian expression of antibodies typically results in glycosylation. Glycosylation of amino acid sequences is typically either N-linked or O-linked. N-linked glycosylation refers to the attachment of a carbohydrate moiety to the side chain of an asparagine residue. O-linked glycosylationDOCKET NO. STFD-012-PCT PCT APPLICATION refers to the attachment of a sugar, for example N-acetylgalactosamine, galactose, or xylose to a hydroxyamino acid. Glycosylation sites can be modified to alter glycosylation (e.g., blocking or reducing glycosylation or altering the amino acid sequence to produce additional or diverse glycosylation). In some embodiments, the amino acid sequences of the disclosure are free of amino acid residues with glycosylation. Mammalian expression of amino acids disclosed herein can also result in the modification of N-terminal amino acids. For example, amino acid residues may be modified into pyro-glutamic acid. In some embodiments, the N-terminal amino acid is modified by an amidate or acyl group. In some embodiments, the C-terminal residue of a disclosed amino acid sequence is modified by an amidate or acyl group.

[0261] In some embodiments, the disclosure relates to a cell comprising a nucleic acid sequence encoding a first amino acid domain comprising BRINP3 or a BRINP3 functional variant modified by conjugation after expression. In some embodiments, the conjugate is formed by an enzymatically catalyzed glycomodification reaction, during which a modified glycosyl moiety [e.g., a glycosyl moiety modified with at least one poly(alkylene oxide) moiety] is covalently linked to the BRINP3 or a BRINP3 functional variant. Hence, in one example according to any of the above embodiments, the methods of the disclosure relate to a method of manufacturing BRINP3 or a BRINP3 functional variant comprising performing solid-state synthesis of the BRINP3 or a BRINP3 functional variant or recombinantly producing the BRINP3 or a BRINP3 functional variant in a cell. In some embodiments, the method further comprises: contacting the BRINP3 or a BRINP3 functional variant and a modified glycosyl donor species (e.g., a modified sugar nucleotide) having a glycosyl moiety covalently linked to a polymer (e.g., a poly(alkylene oxide) moiety), in the presence of an enzyme (e.g., a glycosyltransferase), for which the modified glycosyl donor species is a substrate, under conditions sufficient for the enzyme to catalyze the formation of a covalent bond between the glycosyl moiety that is linked to the polymer and the BRINP3 or a BRINP3 functional variant. In one example, the modified glycosyl moiety is a sialic acid (SA) moiety. In one example, the enzyme is a sialyltransferase. In another example, the polymer is PEG (e.g., m-PEG). GlycoPEGylation methods are art-recognized; see for example, WO 03 / 031464 to DeFrees et al. or WO 04 / 99231, the disclosures of which are incorporated herein by reference in their entirety. Compositions of the disclosure relate to a nucleic acid sequence that encodes a fusion protein comprising a first domain comprising an amino acid sequence disclosed herein fused to a second domain comprising an amino acid sequence known with GLP-1-like activityDOCKET NO. STFD-012-PCT PCT APPLICATION or GIP activity or both GLP-1 and GIP activity. In some embodiments, the fusion protein comprises a BRNP3 domain and a semaglutide domain.

[0262] Compositions and pharmaceutical compositions of the disclosure comprise an amino acid sequence (or nucleic acid sequence encoding the amino acid sequences disclosed herein), wherein the amino acid sequence is no more than about 30, 40, 50, 60, 70, 80, or 90 amino acids and wherein the amino acid sequence is free of full-length BRINP3. In some embodiments, the compositions or pharmaceutical compositions of the disclosure comprise an amino acid sequence free of peptide 1, peptide 2, peptide 3 peptide 4, and / or peptide 6 of Figure 2A.

[0263] In one example according to any of the above embodiments, the method of manufacturing comprises: recombinantly expressing the BRINP3 or a BRINP3 functional variant in a host cell, such as an insect cell, a mammalian cell (e.g., a CHO cell) or a fungal cell (e.g., yeast cell). In one example, the BRINP3 or a BRINP3 functional variant is expressed in an insect cell line (e.g., a Spodoptera frugiperda cell, e.g., Sf9). The BRINP3 or a BRINP3 functional variant may be further modified (e.g., through glycan remodeling) to include a substantially uniform (e.g., insect-specific) glycosylation pattern. The glycosylation pattern of the peptides can be elaborated, trimmed back or otherwise modified by methods utilizing enzymes. The methods of remodeling peptides using enzymes that transfer a sugar donor to an acceptor are discussed in detail in WO 03 / 031464 to De Frees et al. (published Apr.17, 2003); U.S. Patent Application 20040137557 (filed Nov. 5, 2002); U.S. Patent Application 20050143292 (filed Nov. 24, 2004) and WO 05 / 051327 (filed Nov. 24, 2004), each of which is incorporated herein by reference in its entirety.

[0264] Hence, in one embodiment, the method of manufacturing may further include: contacting the BRINP3 or a BRINP3 functional variant and a glycosyl donor molecule (e.g., a nucleotide sugar) in the presence of an enzyme for which the glycosyl donor molecule is a substrate, under conditions sufficient for the enzyme to form a covalent bond between a glycosyl moiety of the glycosyl donor molecule and the first polypeptide. The polypeptide used as a substrate in this reaction may be glycosylated or non-glycosylated. The enzyme may be a glycosyltransferase, such as a GlcNAc-transferase, a GalNAc-transferase, a Gal-transferase or a sialyltransferase.

[0265] Thus, in one example, the method of the disclosure includes: contacting a glycosylated or non-glycosylated BRINP3 or a BRINP3 functional variant and a nucleotide- N-acetylglucosamine (GlcNAc) or a nucleotide-N-acetylgalactosamine (GalNAc) molecule in the presence of a N-acetylglucosamine transferase (e.g., GnT1 or GnT2) or a N-DOCKET NO. STFD-012-PCT PCT APPLICATION acetylgalactosamine transferase, respectively. The reaction mixture may further include a nucleotide galactose (Gal) molecule, and a galactosyl transferase (e.g., GalT1). The components of the reaction mixture are contacted (e.g., in a single reaction vessel or sequentially) under conditions sufficient for the N-acetylglucosamine transferase and the galactosyl transferase to form a glycosylated first polypeptide having at least one glycan residue with a terminal -GlcNAc-Gal moiety or a -GalNAc-Gal moiety. That glycan residue is preferably mono-antennary with respect to the newly added -GlcNAc-Gal or -GalNAc-Gal moiety. In one embodiment, the -GlcNAc-Gal moiety is added to a mannose residue, which is part of a tri-mannosyl motif. In another embodiment, the -GalNAc-Gal moiety is added to a serine or threonine residue of the BRINP3 or a BRINP3 functional variant.

[0266] In some embodiments, the disclosure provides a method of making a composition that contains a BRINP3 amino acid disclosed herein or a BRINP3 functional variant, wherein the first amino acid domain comprising BRINP3 or BRINP3 variant includes a first number of poly(alkylene oxide) moieties covalently linked to an BRINP3 or BRINP3 variant. The method includes: (a) contacting a mixture containing the first amino acid domain comprising BRINP3 or BRINP3 variant with an anion exchange medium; (b) eluting the first amino acid domain comprising BRINP3 or BRINP3 variant from the anion exchange medium, forming a first eluate including the first amino acid domain comprising BRINP3 or BRINP3 variant; (c) contacting the first eluate with a hydrophobic interaction chromatography (HIC) medium; and (d) eluting the first amino acid domain comprising BRINP3 or BRINP3 variant from the hydrophobic interaction chromatography medium. The method may further include: (e) eluting the first amino acid domain comprising BRINP3 or BRINP3 variant from a cation exchange chromatography medium. In one example, step (e) is performed after step (d). In another example, step (e) is performed prior to step (c). The method may further include one or more dilution or diafiltration steps. In one example, diafiltration is used to concentrate and / or exchange the buffer in order to condition the sample for the next process step. For example, the eluate from the HIC step is concentrated and diafiltered into a new buffer system in order to prepare the sample for cation exchange chromatography.

[0267] In some embodiments according to this aspect, the mixture includes additional amino acid conjugates, from which the first amino acid domain comprising BRINP3 or BRINP3 variant is isolated. In an exemplary embodiment, the mixture includes a second conjugate having a second number of poly(alkylene oxide) moieties covalently linked to an BRINP3 or BRINP3 variant. In one embodiment, the first number and the second number are different, which means that the first amino acid domain comprising BRINP3 or BRINP3 variantDOCKET NO. STFD-012-PCT PCT APPLICATION and the second conjugate are glycoforms distinguished by the number of poly(alkylene oxide) moieties that are linked to each BRINP3 or BRINP3 variant. For example, the first amino acid domain comprising BRINP3 or BRINP3 variant includes 3 poly(alkylene oxide) moieties, while the second conjugate may include 0, 1, 2 or 4 poly(alkylene oxide) moieties. In one example, the method is useful to provide a composition including a first amino acid domain comprising BRINP3 or BRINP3 variant, wherein the concentration of the second conjugate in this composition is less than about 30%, less than about 25%, less than about 20%, less than about 15% and preferably less than about 10%, less than about 9%, less than about 8%, less than about 7%, less than about 6%, less than about 5%, less than about 4%, less than about 3%, less than about 2% or less than about 1%. In another embodiment, the mixture includes more than one glycoform of the first amino acid domain comprising BRINP3 or BRINP3 variant and the method provides a composition, in which the combined concentration of all glycoforms having a structure distinct from the structure of the first amino acid domain comprising BRINP3 or BRINP3 variant is less than about 30%, less than about 25%, less than about 20%, less than about 15% and preferably less than about 10%, less than about 9%, less than about 8%, less than about 7%, less than about 6%, less than about 5%, less than about 4%, less than about 3%, less than about 2% or less than about 1%.

[0268] The disclosure relates to a pharmaceutical compositions comprising one or a combination of amino acid sequences disclosed herein (such as a BRP3 peptide or functional variant thereof) and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of an amino acid sequence herein or pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition herein or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

[0269] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising the amino acid sequence chosen from: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, or functional variants thereof comprising at least about 75% sequence identity to one or combination of: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8.

[0270] In some embodiments, the pharmaceutical composition comprises the pharmaceutical composition comprises a therapeutically effective amount of an amino acidDOCKET NO. STFD-012-PCT PCT APPLICATION comprising at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO:1 or SEQ ID NO:5.

[0271] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 1), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:1.

[0272] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising a composition comprising an amino acid sequence comprising YEQLEISMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 2), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:2.

[0273] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAHRIVHKLFSLS (SEQ ID NO: 3), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:3.

[0274] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising composition comprising an amino acid sequence comprising MKQLFLKAQKIVHKLFSLS (SEQ ID NO: 5), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO:6. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:5.

[0275] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising KQLFLKAQKIVHKLFSLS (SEQ ID NO: 6), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequenceDOCKET NO. STFD-012-PCT PCT APPLICATION identity to SEQ ID NO:6. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:6.

[0276] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising QLFLKAQKIVHKLFSLS (SEQ ID NO: 7), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 7. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:7.

[0277] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising LFLKAQKIVHKLFSLS (SEQ ID NO: 8), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO:8. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:8.

[0278] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLETNMKQLFLKAX1X2IVHKLFSLS (SEQ ID NO: 9), wherein X1 is any amino acid and X2is any amino acid, or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, X1and X2in SEQ ID NO: 9 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:9.

[0279] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLEX1X2MKQLFLKAX3X4IVHKLFSLS (SEQ ID NO: 10), wherein X1, X2, X3, and X4are independently selected from any amino acid, or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising an amino acid comprising at least 75% sequence identity to SEQ ID NO:10. InDOCKET NO. STFD-012-PCT PCT APPLICATION some embodiments, X1, X2, X3, and X4 in SEQ ID NO: 10 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0280] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising X1X2MKQLFLKAX3X4IVHKLFSLS (SEQ ID NO: 11), wherein X1, X2, X3 and X4 are independently selected from any amino acid, or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:11. In some embodiments, X1, X2, X3, and X4in SEQ ID NO: 11 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0281] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising MKQLFLKAX1X2IVHKLFSLS (SEQ ID NO: 12), wherein X1 is any amino acid and X2 is any amino acid, or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:12. In some embodiments, X1 and X2 in SEQ ID NO: 12 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0282] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NO: 13), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:13.

[0283] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NO: 13), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical compositionDOCKET NO. STFD-012-PCT PCT APPLICATION comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:13.

[0284] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising EQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 14), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:14.

[0285] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising QLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 15), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:15.

[0286] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising LENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 16), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:16.

[0287] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising ENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 17), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising ng an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:17.

[0288] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising NSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 18), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99%DOCKET NO. STFD-012-PCT PCT APPLICATION sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:18.

[0289] I In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising SMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 19), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:19.

[0290] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising FLKAQKIVHKLFSLS (SEQ ID NO: 20), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:20.

[0291] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising LKAQKIVHKLFSLS (SEQ ID NO: 21), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:21.

[0292] I In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising KAQKIVHKLFSLS (SEQ ID NO: 22), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:22.

[0293] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising AQKIVHKLFSLS (SEQ ID NO: 23), or functional variants thereof comprising about 75%,DOCKET NO. STFD-012-PCT PCT APPLICATION 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:23.

[0294] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising QKIVHKLFSLS (SEQ ID NO: 24), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:24.

[0295] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising KIVHKLFSLS (SEQ ID NO: 25), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:25.

[0296] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising IVHKLFSLS (SEQ ID NO: 26), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:26.

[0297] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising VHKLFSLS (SEQ ID NO: 27), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:27.

[0298] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising HKLFSLSDOCKET NO. STFD-012-PCT PCT APPLICATION (SEQ ID NO: 28), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:28.

[0299] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising KLFSLS (SEQ ID NO: 29), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:29.

[0300] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising LFSLS (SEQ ID NO: 30), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:30.

[0301] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAHRIVHKLFSLS (SEQ ID NO: 31), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising ng an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:31.

[0302] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLEISMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 32), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:32.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0303] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLETNIKQLYLKAQKTIHKLFSLS (SEQ ID NO: 33), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:33.

[0304] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising X1X2X3LENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 59), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 59. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 59. In some embodiments, X1, X2, and X3 are independently selected from any amino acid. In some embodiments, X1, X2, and X3 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, and X3 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, and X3are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, and X3 in SEQ ID NO: 59 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, and X3in SEQ ID NO: 59 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0305] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising X1X2X3X4X5X6X7X8X9X10X11X12LKAQKIVHKLFSLS (SEQ ID NO: 60), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 60. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 60. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12are independently selected from any amino acid. In some embodiments, X1, X2, X3, X4, X5, X6,DOCKET NO. STFD-012-PCT PCT APPLICATION X7, X8, X9, X10, X11, and X12 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12 are independently selected from any non- polar amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12in SEQ ID NO: 60 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12in SEQ ID NO: 60 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0306] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising X1X2X3X4X5X6X7X8X9X10X11X12X13KAQKIVHKLFSLS (SEQ ID NO: 61), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 61. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 61. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, and X13are independently selected from any amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, and X13are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, and X13are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, and X13are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, and X13 in SEQ ID NO: 61 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, and X13 in SEQ ID NO: 61 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0307] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15X16KIVHKLFSLS (SEQ ID NO: 62), orDOCKET NO. STFD-012-PCT PCT APPLICATION functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 62. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:62. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16 in SEQ ID NO: 62 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16 in SEQ ID NO: 62 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0308] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15X16X17IVHKLFSLS (SEQ ID NO: 63), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 63. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 63. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, and X17 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, and X17 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, and X17 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, and X17 in SEQ ID NO: 63 are chosen such that the amino acid sequence is free of theDOCKET NO. STFD-012-PCT PCT APPLICATION amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16,and X17in SEQ ID NO: 63 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0309] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising X1X2X3LX4X5X6MX7X8LFLKX9X10KX11X12X13KLFX14LX15(SEQ ID NO: 64), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 64. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 64. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, and X15are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, and X15are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, and X15 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, and X15in SEQ ID NO: 64 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, and X15 in SEQ ID NO: 64 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0310] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising X1X2X3LX4X5X6MKQLFLKAX7KIVHKLFSLS (SEQ ID NO: 65), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 65. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 65. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from glycine,DOCKET NO. STFD-012-PCT PCT APPLICATION alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 65 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 65 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0311] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKX1X2X3KLFX4LX5 (SEQ ID NO: 66), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 66. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 66. In some embodiments, X1, X2, X3, X4, and X5are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, and X5 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, and X5 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, and X5 in SEQ ID NO: 66 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, and X5 in SEQ ID NO: 66 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0312] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSX1KQLFLKAQKX2X3X4KLFX5LX6 (SEQ ID NO: 67), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 67. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 67. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from glycine,DOCKET NO. STFD-012-PCT PCT APPLICATION alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 67 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 67 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0313] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQX1FLKAQKX2X3X4KLFX5LX6 (SEQ ID NO: 68), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 68. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 68. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 68 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 68 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0314] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQLX1LKAQKX2X3X4KLFX5LX6 (SEQ ID NO: 69), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 69. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 69. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from glycine,DOCKET NO. STFD-012-PCT PCT APPLICATION alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 69 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 69 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0315] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQLFX1KAQKX2X3X4KLFX5LX6 (SEQ ID NO: 70), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 70. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 70. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 70 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 70 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0316] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQLFLX1AQKX2X3X4KLFX5LX6 (SEQ ID NO: 71), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 71. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 71. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from glycine,DOCKET NO. STFD-012-PCT PCT APPLICATION alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 71 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 71 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0317] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQX1X2X3X4KLFX5LX6 (SEQ ID NO: 72), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 72. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 72. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 72 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 72 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0318] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKX1X2X3KLFX4X5X6 (SEQ ID NO: 73), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 73. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 73. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, and X6 are independently selected from glycine,DOCKET NO. STFD-012-PCT PCT APPLICATION alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 73 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, and X6 in SEQ ID NO: 73 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0319] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising X2X3X4LX5X6X7X8X8X9X10X11X12X13X14X15KX16X17X18KLFX19X20X21 (SEQ ID NO: 74), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 74. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO: 74. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, X17, X18, X19, X20, and X21 are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, X17, X18, X19, X20, and X21 are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16,X17,X18, X19, X20, and X21 are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16,X17,X18, X19, X20, and X21 in SEQ ID NO: 74 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, X17, X18, X19, X20, and X21 in SEQ ID NO: 74 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0320] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising X1X2X3LX4X5X6MX7X8LFLKX9X10X11X12X13X14KLFX15LX16 (SEQ ID NO: 75), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 75. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identityDOCKET NO. STFD-012-PCT PCT APPLICATION to SEQ ID NO: 75. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16are independently selected from any conservative amino acid substitute relative the respective amino acid residues of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16are independently selected from any non-polar amino acid. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16are independently selected from glycine, alanine, valine, leucine, or isoleucine. In some embodiments, including the foregoing regarding any amino acid, any conservative amino acid, any non-polar amino acid, and glycine, alanine, valine, leucine, or isoleucine, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16 in SEQ ID NO: 75 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1. In some embodiments, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, and X16in SEQ ID NO: 75 are chosen such that the amino acid sequence is free of the amino acid sequence of SEQ ID NO: 1.

[0321] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 76), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 76.

[0322] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising AEQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 77), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 77.

[0323] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YAQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 78), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 78.

[0324] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEALENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 79), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 79.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0325] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQAENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 80), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 80.

[0326] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLANSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 81), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 81.

[0327] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLEASMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 82), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 82.

[0328] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENAMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 83), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 83.

[0329] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSAKQLFLKAQKIVHKLFSLS (SEQ ID NO: 84), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 84.

[0330] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMAQLFLKAQKIVHKLFSLS (SEQ ID NO: 85), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 85.

[0331] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKALFLKAQKIVHKLFSLS (SEQ ID NO: 86), or functional variants thereofDOCKET NO. STFD-012-PCT PCT APPLICATION comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 86.

[0332] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQAFLKAQKIVHKLFSLS (SEQ ID NO: 87), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 87.

[0333] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQLALKAQKIVHKLFSLS (SEQ ID NO: 88), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 88.

[0334] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQLFAKAQKIVHKLFSLS (SEQ ID NO: 89), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 89.

[0335] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQLFLAAQKIVHKLFSLS (SEQ ID NO: 90), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 90.

[0336] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKIVHKLFSLS (SEQ ID NO: 91), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 91.

[0337] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising rising an amino acid sequence comprising YEQLENSMKQLFLKAAKIVHKLFSLS (SEQ ID NO: 92), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 92.

[0338] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprisingDOCKET NO. STFD-012-PCT PCT APPLICATION YEQLENSMKQLFLKAQAIVHKLFSLS (SEQ ID NO: 93), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 93.

[0339] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKAVHKLFSLS (SEQ ID NO: 94), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 94.

[0340] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKIAHKLFSLS (SEQ ID NO: 95), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 95.

[0341] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKIVAKLFSLS (SEQ ID NO: 96), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 96.

[0342] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKIVHALFSLS (SEQ ID NO: 97), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 97.

[0343] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKIVHKAFSLS (SEQ ID NO: 98), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 98.

[0344] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKIVHKLASLS (SEQ ID NO: 99), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 99.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0345] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKIVHKLFALS (SEQ ID NO: 100), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 100.

[0346] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKIVHKLFSAS (SEQ ID NO: 101), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 101.

[0347] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising YEQLENSMKQLFLKAQKIVHKLFSLA (SEQ ID NO: 102), or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity to SEQ ID NO: 102.

[0348] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising H-His-Aib- Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys(AEEAc- AEEAc-γ-Glu-17-carboxyheptadecanoyl)-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly- OH (SEQ ID NO: 44) , or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising at least 75% sequence identity to SEQ ID NO:44.

[0349] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising SEQ ID NO: 12, a functional variant comprising at least about 75% sequence identity to SEQ ID NO:12, wherein X1 and X2 are independently selected from any amino acid, or a pharmaceutically acceptable salt thereof.

[0350] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising SEQ ID NO: 9 or a functional variant comprising at least about 75% sequence identity to SEQ ID NO:9, wherein X1and X2are independently selected from any amino acid, or a pharmaceutically acceptable salt thereof.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0351] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising one or a combination of an amino acid sequence comprising SEQ ID NO:10, SEQ ID NO:11, or functional variants thereof comprising at least about 75% sequence identity to SEQ ID NO:10 or SEQ ID NO:11, or a pharmaceutically acceptable salt thereof.

[0352] In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising an amino acid sequence comprising one or a combination of SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, or functional variants thereof comprising at least about 75% sequence identity to one or combination of: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8.

[0353] In some embodiments, the pharmaceutical composition comprises an amino acid sequence comprising any of SEQ ID NO:2 – 75, but, if the sequence includes a formula with a variable amino acid residue such sequences are free of SEQ ID NO:1.

[0354] Another object of the disclosure is to provide a pharmaceutical composition comprising an amino acid sequence according to the disclosure which is present in a concentration from about 0.1 mg / ml to about 25 mg / ml, and which said formulation has a pH from about 3.0 to about 9.0. The pharmaceutical composition may further include a buffer system, preservative(s), tonicity agent(s), chelating agent(s), stabilizers and surfactants. In one embodiment of the disclosure the pharmaceutical formulation is an aqueous formulation, i.e. formulation comprising water. Such formulation is typically a solution or a suspension. In a further embodiment of the disclosure the pharmaceutical formulation is an aqueous solution. The term "aqueous formulation" is defined as a formulation comprising at least about 50%w / w water. Likewise, the term "aqueous solution" is defined as a solution comprising at least about 50% w / w water, and the term "aqueous suspension" is defined as a suspension comprising at least 50%w / w water. In some embodiments, the pharmaceutical composition is a freeze-dried formulation, whereto the physician or the patient adds solvents and / or diluents prior to use. In some embodiments, the pharmaceutical composition is a dried formulation (eg freeze-dried or spray-dried and / or lyophilized) ready for use without any prior dissolution.

[0355] In a further aspect the disclosure relates to a pharmaceutical formulation comprising an aqueous solution of a compound according to the present disclosure, and a buffer, wherein said compound is present in a concentration from 0.1 mg / ml or above, and wherein said formulation has a pH from about 3.0 to about 9.0.DOCKET NO. STFD-012-PCT PCT APPLICATION In another embodiment of the disclosure the pH of the formulation is from about 7.0 to about 9.5. In another embodiment of the disclosure the pH of the formulation is from about 3.0 to about 7.0. In another embodiment of the disclosure the pH of the formulation is from about 5.0 to about 7.5. In another embodiment of the disclosure the pH of the formulation is from about 7.5 to about 9.0. In another embodiment of the disclosure the pH of the formulation is from about 7.5 to about 8.5. In another embodiment of the disclosure the pH of the formulation is from about 6.0 to about 7.5. In another embodiment of the disclosure the pH of the formulation is from about 6.0 to about 7.0.

[0356] In a further embodiment of the disclosure the buffer is selected from the group consisting of sodium acetate, sodium carbonate, citrate, glycylglycine, histidine, glycine, lysine, arginine, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, and tris(hydroxymethyl) -aminomethan, bicine, tricine, malic acid, succinate, maleic acid, fumaric acid, tartaric acid, aspartic acid or mixtures thereof. Each one of these specific buffers constitutes an alternative embodiment of the disclosure.

[0357] In a further embodiments, pharmaceutical compositions of the disclosure further comprise a pharmaceutically acceptable preservative. In a further embodiment of the disclosure the preservative is selected from the group consisting of phenol, o-cresol, m-cresol, p-cresol, methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, 2-phenoxyethanol, butyl p- hydroxybenzoate, 2 -phenylethanol, benzyl alcohol, chlorobutanol, and thiomerosal, bronopol, benzoic acid, imidurea, chlorohexidine, sodium dehydroacetate, chlorocresol, ethyl p- hydroxybenzoate, benzethonium chloride, chlorphenesine (3p-chlorphenoxypropane-1,2-diol) or mixtures thereof. In some embodiments, the preservative is present in a concentration from about 0.1 mg / ml to about 20 mg / ml. In some embodiments, the preservative is present in a concentration from about 0.1 mg / ml to about 5 mg / ml. In a further embodiment of the disclosure the preservative is present in a concentration from about 5 mg / ml to about 10 mg / ml. In some embodiments, the preservative is present in a concentration from about 10 mg / ml to about 20 mg / ml. Each one of these specific condoms constitutes an alternative embodiment of the disclosure. The use of a preservative in pharmaceutical compositions is well-known to the skilled person. For convenience reference is made to Remington: The Science and Practice of Pharmacy, 19th edition, 1995.

[0358] In some embodiments, the pharmaceutical composition further comprises an isotonic agent. In a further embodiment of the disclosure the isotonic agent is selected from theDOCKET NO. STFD-012-PCT PCT APPLICATION group consisting of a salt (eg sodium chloride), a sugar or sugar alcohol, an amino acid (eg glycine, L-histidine, arginine, lysine, isoleucine, aspartic acid , tryptophan, threonine), an alditol (eg glycerol (glycerin), 1,2-propanediol (propyleneglycol), 1,3-propanediol, 1,3- butanediol) polyethyleneglycol (eg PEG400), or mixtures thereof. Any sugar such as mono-, di-, or polysaccharides, or water-soluble glucans, including for example fructose, glucose, mannose, sorbose, xylose, maltose, lactose, sucrose, trehalose, dextran, pullulan, dextrin, cyclodextrin, soluble starch , hydroxyethyl starch and carboxymethylcellulose-Na may be used. In one embodiment the sugar additive is sucrose. Sugar alcohol is defined as a C4 through C8 hydrocarbon having at least one -OH group and includes, for example, mannitol, sorbitol, inositol, galactitol, dulcitol, xylitol, and arabitol. In one embodiment the sugar alcohol additive is mannitol. The sugars or sugar alcohols mentioned above may be used individually or in combination. There is no fixed limit to the amount used, as long as the sugar or sugar alcohol is soluble in the liquid preparation and does not adversely effect the stabilizing effects achieved using the methods of the disclosure. In one embodiment, the sugar or sugar alcohol concentration is between about 1 mg / ml and about 150 mg / ml. In a further embodiment of the disclosure the isotonic agent is present in a concentration from about 1 mg / ml to about 50 mg / ml. In a further embodiment of the disclosure the isotonic agent is present in a concentration from about 1 mg / ml to about 7 mg / ml. In a further embodiment of the disclosure the isotonic agent is present in a concentration from about 8 mg / ml to about 24 mg / ml. In a further embodiment of the disclosure the isotonic agent is present in a concentration from about 25 mg / ml to about 50 mg / ml. Each one of these specific isotonic agents constitutes an alternative embodiment of the disclosure. The use of an isotonic agent in pharmaceutical compositions is well-known to the skilled person. For convenience reference is made to Remington: The Science and Practice of Pharmacy, 19th edition, 1995. The amino acid sequence or pharmaceutical composition doses of the disclosure include embodiments with concentrations of about 5 mg of amino acid / mL of solution in a liquid formulation. In some embodiments, the dose is about 10 mg / mL, about 15 mg / mL, about 20 mg / mL, about 25 mg / mL, about 30 mg / mL, about 40 mg / mL, and about 50 mg / mL. In some embodiments, compositions may be provided in a pre-filled syringe. Such pre-filled syringe may be useful for administering from about one half milliliter to 1 millimeter doses of such composition per subject per dose. The doses of some embodiments are administered subcutaneously. In some embodiments, the doses are typically administered using a pre-filled, disposable pen, reusable pen, or automatic pen injector. In some embodiments, the device is an automatic injection apparatus as claimed by U.S. Patent 8,734,394.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0359] In a further embodiment of the disclosure the formulation further comprises a chelating agent. In a further embodiment of the disclosure the chelating agent is selected from salts of ethylenediaminetetraacetic acid (EDTA), citric acid, and aspartic acid, and mixtures thereof. In a further embodiment of the disclosure the chelating agent is present in a concentration from 0.1 mg / ml to 5mg / ml. In a further embodiment of the disclosure the chelating agent is present in a concentration from 0.1 mg / ml to 2mg / ml. In a further embodiment of the disclosure the chelating agent is present in a concentration from 2mg / ml to 5mg / ml. Each one of these specific chelating agents constitutes an alternative embodiment of the disclosure. The use of a chelating agent in pharmaceutical compositions is well-known to the skilled person. For convenience reference is made to Remington: The Science and Practice of Pharmacy, 19th edition, 1995, which is incorporated by reference in its entirety.

[0360] In a further embodiment of the disclosure the formulation further comprises a stabilizer. The use of a stabilizer in pharmaceutical compositions is well-known to the skilled person. For convenience reference is made to Remington: The Science and Practice of Pharmacy, 19th edition, 1995.

[0361] According to some embodiments of the disclosure, the formulation may be supplied as part of a kit. In some embodiments, the kit comprises one or a plurality of amino acid sequences disclosed herein or a functional variant thereof, wherein the amino acid sequence comprise at least one domain comprising BRINP3 or a BRINP3 functional variant. In another embodiment, the kit comprises a pharmaceutically acceptable salt of an amino acid with a rehydration mixture. In another embodiment, the pharmaceutically acceptable salt of an amino acid sequence are in one container while the rehydration mixture is in a second container. The rehydration mixture may be supplied in dry form, to which water or other liquid solvent may be added to form a suspension or solution prior to administration. Rehydration mixtures are mixtures designed to solubilize a lyophilized, insoluble salt of the disclosure prior to administration of the composition to a subject takes at least one dose of a BRINP3 variant or BRINP3. In another embodiment, the kit comprises a pharmaceutically acceptable salt in orally available pill form.

[0362] The kit may contain two or more containers, packs, or dispensers together with instructions for preparation and administration. In some embodiments, the kit comprises at least one container comprising the pharmaceutical composition or compositions described herein and a second container comprising a means for delivery of the compositions such as a syringe . In some embodiments, the kit comprises a composition comprising an analog in solution orDOCKET NO. STFD-012-PCT PCT APPLICATION lyophilized or dried and accompanied by a rehydration mixture. In some embodiments, the analog and rehydration mixture may be in one or more additional containers.

[0363] The compositions included in the kit may be supplied in containers of any sort such that the shelf-life of the different components are preserved, and are not adsorbed or altered by the materials of the container. For example, suitable containers include simple bottles that may be fabricated from glass, organic polymers, such as polycarbonate, polystyrene, polypropylene, polyethylene, ceramic, metal or any other material typically employed to hold reagents or food; envelopes, that may consist of foil-lined interiors, such as aluminum or an alloy. Other containers include test tubes, vials, flasks, and syringes. The containers may have two compartments that are separated by a readily removable membrane that upon removal permits the components of the compositions to mix. Removable membranes may be glass, plastic, rubber, or other inert material.

[0364] Kits may also be supplied with instructional materials. Instructions may be printed on paper or other substrates, and / or may be supplied as an electronic-readable medium, such as a floppy disc, CD-ROM, DVD-ROM, zip disc, videotape, audio tape, or other readable memory storage device. Detailed instructions may not be physically associated with the kit; instead, a user may be directed to an internet web site specified by the manufacturer or distributor of the kit, or supplied as electronic mail.

[0365] In another embodiment, a packaged kit is provided that contains the pharmaceutical composition disclosed herein to be administered, i.e., a pharmaceutical formulation containing BRINP3 or BRINP3 functional variant disclosed herein, a container (e.g., a vial, a bottle, a pouch, an envelope, a can, a tube, an atomizer, an aerosol can, etc.), optionally sealed, for housing the formulation during storage and prior to use, and instructions for carrying out drug administration in a manner effective to enhance sexual desire and responsiveness. The instructions will typically be written instructions on a package insert, a label, and / or on other components of the kit.

[0366] The present kits will also typically include means for packaging the individual kit components, i.e., the pharmaceutical dosage forms, the administration device (if included), and the written instructions for use. Such packaging means may take the form of a cardboard or paper box, a plastic or foil pouch, etc.

[0367] The disclosure also relates to a kit comprising a nucleic acid molecule comprising a nucleic acid sequence encoding one or a plurality of BRINP3 amino acid sequences or functional variants thereof or those amino acids disclosed herein (including amino acidDOCKET NO. STFD-012-PCT PCT APPLICATION sequences comprising one, two or more domains). In some embodiments, the kit comprises a cell comprising the above-identified or disclosed nucleic acid molecules.

[0368] In some embodiments, the disclosure relates to a method of treating obesity, hyperglycemia, weight gain, or a liver disorder in a subject in need thereof. In some embodiments the liver disorder is Metabolic dysfunction-associated steatohepatitis (MASH) or Metabolic dysfunction–associated liver disease (MASLD). In some embodiments, the disclosure relates to a method of treating obesity, hyperglycemia, weight gain, diabetes or a liver disorder in a subject in need thereof. In some embodiments, the disclosure relates to a method of treating obesity, hyperglycemia, weight gain, diabetes or a liver disorder in a subject in need thereof without affecting or reducing skeletal or heart muscle mass. IN some embodiments, the disclosure relates to methods of treating diabetes, obesity, hyperglycemia, weight gain, or a liver disorder in a subject thereof without causing loss of lean mass, either through skeletal muscle mass or heart muscle mass. The method comprises administering to the subject an amino acid sequence herein, a composition herein, or a pharmaceutical composition herein. In some embodiments, the administration is by oral administration, parenteral administration, sublingual administration, transdermal administration, rectal administration, transmucosal administration, topical administration, inhalation, buccal administration, intrapleural administration, intravenous administration, intraarterial administration, intraperitoneal administration, subcutaneous administration, intramuscular administration, intranasal administration, intrathecal administration, and intraarticular administration, or combinations thereof. In some embodiments, the subject is a mammal. In some embodiments, the subject is a human. In some embodiments, the amino acid sequence, the composition, or the pharmaceutical composition is administered simultaneously with, before or after administration of a GLP-1 receptor modulator, such as a GLP-1 receptor agonist. In some embodiments, the amino acid sequence, the composition, or the pharmaceutical composition is administered as a dose of from about 0.1 milligrams to about 10,000 milligrams. In some embodiments, the composition, or the pharmaceutical composition is administered as a dose of from about 0.1 milligrams per kilogram of the subject to about 1,000 milligrams per kilogram of the subject. In some embodiments, the composition, or the pharmaceutical composition is administered as a dose of about 4 mg / kg in a human. In some embodiments, the composition, or the pharmaceutical composition is administered as a dose of about 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8.9.10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mg / kg. In some embodiments, the composition, or the pharmaceutical composition is administered as a dose in an amount between and two of 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8.9.10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20DOCKET NO. STFD-012-PCT PCT APPLICATION mg / kg. In an embodiment, the dose is delivered daily. In an embodiment, the dose is delivered once a day or once a week.

[0369] In some embodiment, the disclosure relates to a method of manufacturing any one of the amino acid sequences herein, any one of the compositions herein, or any one of the pharmaceutical compositions herein. In some embodiments, the method comprises catalyzing a reaction between at least two amino acids in the amino acid sequence. In some embodiments, the method comprises expressing a nucleic acid construct encoding the amino acid sequence. The expression in vitro in some embodiments. The expression comprises cloning the nucleic acid construct into a cell and expressing the nucleic acid construct therein in some embodiments. The nucleic acid construct in some embodiments includes a sequence encoding any one of the amino acid sequences herein or functional variants thereof comprising about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or about 99% sequence identity.

[0370] In some embodiment, the disclosure relates to a method of manufacturing any one of the amino acid sequences herein, any one of the compositions herein, or any one of the pharmaceutical compositions herein. The method may comprise synthesis of the amino acid sequence chemically. In some embodiments, the synthesis comprises synthesis of a resin bound Peptide. The synthesis of a resin bound peptide in some embodiments is as follows. Protected peptidyl resin would be synthesized according to the Fmoc strategy on an Applied Biosystems 433 peptide synthesizer in 0.25 mmol or 1.0 mmol scale using the manufacturer supplied FastMoc UV protocols which employ HBTU (2-(1H-Benzotriazol-1-yl-)-1,1,3,3 tetramethyluronium hexafluorophosphate) or HATU (O-(7-azabenzotriazol-1-yl)-1,1,3,3- tetramethyluronium hexafluorophosphate) mediated couplings in NMP (N-methyl pyrrolidone), and UV monitoring of the deprotection of the Fmoc protection group. The starting resin used for the synthesis of the amino acid sequence would be Rink-Amide resin and either Wang or chlorotrityl resin would be used for amino acid sequences with a carboxy C-terminal. The protected amino acid derivatives used would be standard Fmoc-amino acids (supplied from e.g., Anaspec, or Novabiochem) supplied in preweighed cartridges suitable for the ABI433A synthesizer with the exception of unnatural aminoacids such as Fmoc-Aib-OH (Fmoc- aminoisobutyric acid). The N terminal amino acid would be Boc protected at the alpha amino group (e.g. Boc-His(Boc)OH would be used for peptides with His at the N-terminal). The epsilon amino group of lysine in position 26 would either be protected with Mtt, Mmt, Dde, ivDde, or Boc, depending on the route for attachment of the albumin binding moiety and spacer. The synthesis of the peptides could in some cases be improved by the use of dipeptidesDOCKET NO. STFD-012-PCT PCT APPLICATION protected on the dipeptide amide bond with a group that can be cleaved under acidic conditions; for example, but not limited to, 2-Fmoc-oxy-4-methoxybenzyl or 2,4,6-trimethoxybenzyl. In cases where a serine or a threonine is present in the peptide, the use of pseudoproline dipeptides could be used (see e.g., catalogue from Novobiochem 2002 / 2003 or newer version, or W. R. Sampson (1999), J. Pep. Sci.5, 403.

[0371] Methods of the disclosure also include alternative methods of synthesizing the sequences by solid state synthesis. Solid state synthesis is generally known in the art. The method allows incorporation of non-natural amino acids into the amino acid disclosed herein. In some embodiments, non-ntrual amino acids include tyrosine analogs. Tyrosine analogs include, but are not limited to, para-substituted tyrosines, ortho-substituted tyrosines, and meta substituted tyrosines, where the substituted tyrosine comprises, including but not limited to, a keto group (including but not limited to, an acetyl group), a benzoyl group, an amino group, a hydrazine, an hydroxyamine, a thiol group, a carboxy group, an isopropyl group, a methyl group, a C6-C20straight chain or branched hydrocarbon, a saturated or unsaturated hydrocarbon, an O-methyl group, a polyether group, a nitro group, an alkynyl group or the like. In addition, multiply substituted aryl rings are also contemplated. Glutamine analogs may be suitable non-natural amino acids for incorporation. Analogs that may be suitable for use in the present disclosure include, but are not limited to, α. -hydroxy derivatives, cyclic derivatives, and amide substituted glutamine derivatives. Example phenylalanine analogs that may be suitable for use in the present disclosure include, but are not limited to, para-substituted phenylalanines, ortho-substituted phenyalanines, and meta-substituted phenylalanines, where the substituent comprises, including but not limited to, a hydroxy group, a methoxy group, a methyl group, an allyl group, an aldehyde, an azido, an iodo, a bromo, a keto group (including but not limited to, an acetyl group), a benzoyl, an alkynyl group, or the like. Specific examples of unnatural amino acids that may be suitable for use in the present disclosure include, but are not limited to, a p-acetyl-L-phenylalanine, an O-methyl-L-tyrosine, an L-3-(2- naphthyl)alanine, a 3-methyl-phenylalanine, an 0-4-allyl-L-tyrosine, a 4-propyl-L-tyrosine, a tri-O-acetyl-GlcNAcP-serine, an L-Dopa, a fluorinated phenylalanine, an isopropyl-L- phenylalanine, a p-azido-L-phenylalanine, a p-acyl-L-phenylalanine, a p-benzoyl-L- phenylalanine, an L-phosphoserine, a phosphonoserine, a phosphonotyrosine, a p-iodo- phenylalanine, a p-bromophenylalanine, a p-amino-L-phenylalanine, an isopropyl-L- phenylalanine, and a p-propargyloxy-phenylalanine, and the like. Examples of structures of a variety of unnatural amino acids that may be suitable for use in the present disclosure are provided in, for example, WO2002 / 085923 entitled "In vivo incorporation of unnatural aminoDOCKET NO. STFD-012-PCT PCT APPLICATION acids." See also Kiick et al., (2002). Incorporation of azides into recombinant proteins for chemoselective modification by the Staudinger ligation, PNAS 99:19-24, for additional methionine analogs. The chemical moieties via non-natural amino acids that can be incorporated into analogs offer a variety of advantages and manipulations of the protein. For example, the unique reactivity of a keto functional group allows selective modification of proteins with any of a number of hydrazine- or hydroxylamine-containing reagents in vitro and in vivo. A heavy atom unnatural amino acid, for example, can be useful for phasing X-ray structure data. The site-specific introduction of heavy atoms using unnatural amino acids also provides selectivity and flexibility in choosing positions for heavy atoms. In some embodiments, the composition or pharmaceutical compositions of the claimed disclosure comprises an analog of a polypeptide, wherein the variant amino acid sequence is based upon the fragments, polypeptides, and functional derivatives disclosed herein and wherein the analog comprises at least one or a plurality of unnatural amino acid or non-natural amino acid, wherein the non-natural amino is a photoreactive non-natural amino acid chosen from (including but not limited to, amino acids with benzophenone and arylazides (including but not limited to, phenylazide) side chains), for example, allow for efficient in vivo and in vitro photocrosslinking of protein. Examples of photoreactive unnatural amino acids include, but are not limited to, p-azido-phenylalanine and p-benzoyl-phenylalanine. The protein with the photoreactive unnatural amino acids can then be crosslinked at will by excitation of the photoreactive group-providing temporal control. In one example, the methyl group of an unnatural amino can be substituted with an isotopically labeled, including but not limited to, methyl group, as a probe of local structure and dynamics, including but not limited to, with the use of nuclear magnetic resonance and vibrational spectroscopy. Alkynyl or azido functional groups, for example, allow the selective modification of proteins with molecules through a {3+2} cycloaddition reaction. A non-natural amino acid incorporated into a polypeptide at the amino terminus can be composed of an R group that is any substituent other than one used in the twenty natural amino acids and a second reactive group different from the NH2group normally present in α-amino acids. A similar non-natural amino acid can be incorporated at the carboxyl terminus with a second reactive group different from the COOH group normally present in α-amino acids. Many of the unnatural amino acids suitable for use in the present disclosure are commercially available, e.g., from Sigma (USA) or Aldrich (Milwaukee, Wis., USA). Those that are not commercially available ar0 optionally synthesized as provided herein or as provided in various publications or using standard methods known to those of skill in the art. For organic synthesis techniques, see, e.g., Organic Chemistry by Fessendon andDOCKET NO. STFD-012-PCT PCT APPLICATION Fessendon, (1982, Second Edition, Willard Grant Press, Boston Mass.); Advanced Organic Chemistry by March (Third Edition, 1985, Wiley and Sons, New York); and Advanced Organic Chemistry by Carey and Sundberg (Third Edition, Parts A and B, 1990, Plenum Press, New York). Additional publications describing the synthesis of unnatural amino acids include, e.g., WO 2002 / 085923 entitled "In vivo incorporation of Unnatural Amino Acids;" Matsoukas et al., (1995) J. Med. Chem., 38, 4660-4669; King, F. E. & Kidd, D. A. A. (1949) A New Synthesis of Glutamine and of γ-Dipeptides of Glutamic Acid from Phthylated Intermediates. J. Chem. Soc, 3315-3319; Friedman, O. M. & Chattenji, R. (1959) Synthesis of Derivatives.

[0372] Amino acids of the disclosure may be generated by solid-phase peptide synthesis using a Fmoc / t-Bu strategy carried out on a Symphony automated peptide synthesizer (PTI Protein Technologies Inc.) starting from RAPP AM-Rink Amide resin and with couplings using 6 equivalents of amino acid activated with diisopropylcarbodiimide (DIC) and hydroxybenzotriazole (HOBt) (1:1:1 molar ratio) in dimethylformamide (DMF) for 90 min at 25° C.

[0373] Extended couplings (4h each) for Pro31, Trp25, G1n24, Va123, Phe22, Lys20, Gly4, Glu3 and Aib2 are necessary to improve the quality of the crude peptide. A Fmoc-Lys (Alloc)-OH building block is used for Lys20 coupling (orthogonal protecting group) to allow for site specific attachment of the fatty acid moiety later on in the synthetic process. The following conditions are used for the coupling of Fmoc-Ile-OH at position 12: Fmoc-Ile-OH (6 equiv), PyBOP (6 equiv), and DIEA (12 equiv) in DMF for 24 h at 25° C. The N-terminal residue is incorporated as Boc-Tyr(tBu)-OH using DIC-HOBt protocols as described above. After finishing the elongation of the peptide-resin described above, the Alloc protecting group present in Lys20 is removed using catalytic amounts of Pd(PPh3)4 in the presence of PhSiH3 as a scavenger. Additional coupling / deprotection cycles using a Fmoc / t-Bu strategy to extend the Lys20 side-chain involved Fmoc-NH-PEG2-CH2COOH (ChemPep Catalog#280102), Fmoc- Glu(OH)-OtBu (ChemPep Catalog#100703) and HOOC—(CH2)18-COOtBu. In all couplings, about 3 equivalents of the building block are used with PyBOP (3 equiv) and DIEA (6 equiv) in DMF for 4h at 25° C. Concomitant cleavage from the resin and side chain protecting group removal are carried out in a solution containing trifluoroacetic acid (TFA): triisopropylsilane: 1,2-ethanedithiol: water: thioanisole 90:4:2:2:2 (v / v) for 2 h at 25° C. followed by precipitation with cold ether. Crude peptide is purified to >99% purity (15-20% purified yield) by reversed- phase HPLC chromatography with water / acetonitrile (containing 0.05% v / v TFA) gradient on a C18 column, where suitable fractions are pooled and lyophilized.DOCKET NO. STFD-012-PCT PCT APPLICATION

[0374] In some embodiments, the disclosure relates to a method of inducing phosphorylation of CREB in a cell. In some embodiments, the method comprises exposing the cell to an amino acid sequence herein, a composition herein, or a pharmaceutical composition herein. In some embodiments, the step of exposing comprises exposing the cell to an amino acid sequence of Table 1 or functional variants thereof;. In some embodiments, the step of exposing comprises exposing the cell to an amino acid sequence comprising at least about 75% sequence identity to SEQ ID: 1 through SEQ ID NO: 12. In some embodiments, the step of exposing is performed for a time period sufficient for the amino acid sequence, the composition, or the pharmaceutical composition to catalyze the reaction of phosphate to CREB in the cell. In some embodiments, the step of exposing is performed in vivo after administration o...

Claims

DOCKET NO. STFD-012-PCT PCT APPLICATION CLAIMS 1. An amino acid sequence comprising BRINP3, a functional variant thereof, or a pharmaceutically acceptable salt thereof.

2. The amino acid sequence of claim 1 comprising SEQ ID NO: 12, a functional variant comprising at least about 75% sequence identity to SEQ ID NO:12, wherein X1and X2are independently selected from any amino acid, or a pharmaceutically acceptable salt thereof.

3. The amino acid sequence of claim 1 comprising SEQ ID NO: 9 or a functional variant comprising at least about 75% sequence identity to SEQ ID NO:9, wherein X1and X2are independently selected from any amino acid, or a pharmaceutically acceptable salt thereof.

4. The amino acid sequence of claim 1 comprising SEQ ID NO:10, SEQ ID NO:11, or functional variants thereof comprising at least about 75% sequence identity to SEQ ID NO:10 or SEQ ID NO:11, or a pharmaceutically acceptable salt thereof.

5. The amino acid sequence of claim 1, wherein the amino acid is chosen from: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, or functional variants thereof comprising at least about 75% sequence identity to one or combination of: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:

8.

6. A composition comprising the amino acid sequence of any of claims 1 through 5.

7. A composition comprising an amino acid sequence comprising a first and second domain, wherein the first domain is a BRINP3 domain and wherein the second domain is a GLP-1 domain.

8. The composition of claim 7, wherein the BRINP3 domain comprises SEQ ID NO: 12 or a functional variant comprising at least about 75% sequence identity to SEQ ID NO:12, wherein X1and X2are independently selected from any amino acid.DOCKET NO. STFD-012-PCT PCT APPLICATION 9. The composition of claim 7, wherein the BRINP3 domain comprises SEQ ID NO: 9 or a functional variant comprising at least about 75% sequence identity to SEQ ID NO:9, wherein X1and X2are independently selected from any amino acid.

10. The composition of claim 7, wherein the BRINP3 domain comprises SEQ ID NO:10, SEQ ID NO:11, or functional variants thereof comprising at least about 75% sequence identity to SEQ ID NO:10 or SEQ ID NO:

11.

11. The composition of claim 7, wherein the BRINP3 domain comprising an amino acid is chosen from: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, or functional variants thereof comprising at least about 75% sequence identity to one or combination of: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:

8.

12. The composition of claim 7, wherein the first domain comprises SEQ ID NO:5 or a functional variant thereof comprising at least about 75% sequence identity to SEQ ID NO:5; and the second domain comprises SEQ ID NO:13 or a functional variant thereof comprising at least about at least about 75% sequence identity to SEQ ID NO:

13.

13. A pharmaceutical composition comprising: (i) a therapeutically effective amount of the composition of claims 6 through 12 or the amino acid sequence of claims 1 through 5; and (ii) a pharmaceutically acceptable carrier.

14. The pharmaceutical composition of claim 13 wherein the pharmaceutical composition comprises a therapeutically effective amount of a composition comprising the amino acid sequence chosen from: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, or functional variants thereof comprising at least about 75% sequence identity to one or combination of: SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:

8.

15. The pharmaceutical composition of claim 13, wherein the pharmaceutical composition comprises a therapeutically effective amount of an amino acid comprising atDOCKET NO. STFD-012-PCT PCT APPLICATION least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO:1 or SEQ ID NO:

5.

16. A method of treating obesity, hyperglycemia, weight gain, diabetes, MASH, or MASLD in a subject in need thereof comprising administering to the subject an amino acid sequence of any of claims 1 through 5, 48 or 49, a composition of any of claims 6 through 12, or the pharmaceutical composition of any of claims 13 through 15 or 50.

17. The method of claim 16, wherein the amino acid or the pharmaceutical composition is administered by oral adminstration, parenteral administration, sublingual administration, transdermal administration, rectal administration, transmucosal administration, topical administration, inhalation, buccal administration, intrapleural administration, intravenous administration, intraarterial administration, intraperitoneal administration, subcutaneous administration, intramuscular administration, intranasal administration, intrathecal administration, and intraarticular administration, or combinations thereof.

18. The method of any of claims 16 through 17, wherein the subject is a mammal.

19. The method of any of claims 16 through 18, wherein the subject is a human.

20. The method of any of claims 16 through 19, wherein the amino acid sequence, the composition, or the pharmaceutical composition is administered simultaneously with, before or after administration of a GLP-1 modulator.

21. The method of any of claims 16 through 20, wherein the amino acid sequence, the composition, or the pharmaceutical composition is administered as a dose of from about 0.1 milligrams to about 10,000 milligrams.

22. The method of any of claims 16 through 21, wherein the amino acid sequence, the composition, or the pharmaceutical composition is administered as a dose of from about 0.1 milligrams per kilogram of the subject to about 1,000 milligrams per kilogram of the subject.

23. The method of claim 22, wherein the amino acid sequence, the composition, or the pharmaceutical composition is administered as a dose of from about 0.1 milligrams perDOCKET NO. STFD-012-PCT PCT APPLICATION kilogram of the subject to about 1,000 milligrams per kilogram of the subject once a day or once a week.

24. A method of manufacturing any one of the amino acid sequences of claims 1 through 5 or 48; or the compositions of claims 6 through 12 or 50, comprising catalyzing a reaction between at least two amino acids in the amino acid sequence.

25. A method of inducing phosphorylation of CREB in a cell comprising exposing the cell to an amino acid sequence of any of claims 1 through 5, an amino acid in the composition of any of claims 6 through 12; or exposing the cell to the pharmaceutical composition of any of claims 13 through 15.

26. The method of claim 25, wherein the step of exposing comprises exposing the cell to an amino acid sequence of Table 1 or functional variants thereof comprising at least about 75% sequence identity to SEQ ID: 1 through SEQ ID NO:

12.

27. The method of claims 25 or 26, wherein the step of exposing is performed for a time period sufficient for the amino acid sequence of any of claims 1 through 5 or the amino acid sequence in any of the compositions of claims 6 through 15 to catalyze the reaction of phosphate to CREB in the cell.

28. The method of any of claims 25 through 27, wherein the step of exposing is performed in vivo after administration of the amino acid sequence of any of claims 1 through 5 to a subject, administering an amino acid sequence in the composition of any of claims 6 through 12 to a subject; or administering the pharmaceutical composition of any of claims 13 through 15 to a subject.

29. The method of claims 28, wherein the subject is a subject in need of a treatment for obesity or weight loss.

30. A method of preventing obesity, weight gain, diabetes, MASH, MASLD in a subject in need thereof comprising administering to the subject an amino acid sequence of any of claims 1 through 5 or 50, or a pharmaceutically acceptable salt thereof, the composition ofDOCKET NO. STFD-012-PCT PCT APPLICATION any of claims 6–12 or a pharmaceutically acceptable salt thereof or the pharmaceutical composition of any of claims 13 through 15 or 50.

31. The method of claim 30, wherein the amino acid sequence, or the pharmaceutical composition is administered by oral adminstration, parenteral administration, sublingual administration, transdermal administration, rectal administration, transmucosal administration, topical administration, inhalation, buccal administration, intrapleural administration, intravenous administration, intraarterial administration, intraperitoneal administration, subcutaneous administration, intramuscular administration, intranasal administration, intrathecal administration, and intraarticular administration, or combinations thereof.

32. The method of any of claims 30 through 31, wherein the subject is a mammal.

33. The method of any of claims 30 through 32, wherein the subject is a human.

34. The method of any of claims 30 through 33, wherein amino acid sequence or the pharmaceutical composition is administered simultaneously with, before or after administration of a GLP-1 modulator.

35. The method of any of claims 30 through 34, wherein the amino acid sequence or the pharmaceutical composition is administered as a dose of from about 0.1 milligrams to about 10,000 milligrams.

36. The method of any of claims 30 through 35, wherein the amino acid sequence or the pharmaceutical composition is administered as a dose of from about 0.1 milligrams per kilogram of the subject to about 1,000 milligrams per kilogram of the subject.

37. The method of claim 36, wherein the amino acid sequence or the pharmaceutical composition is administered as a dose of from about 0.1 milligrams per kilogram of the subject to about 1,000 milligrams per kilogram of the subject once a day or once a week.

38. A method of treating diabetes in a subject in need thereof comprising administering to the subject an amino acid sequence of any of claims 1 through 5 or 48, the composition of any of claims 6 through 12; or the pharmaceutical composition of any of claims 13 through 15 or 50.DOCKET NO. STFD-012-PCT PCT APPLICATION 39. The method of claim 38, wherein the amino acid sequence, the composition, or the pharmaceutical composition is administered by oral adminstration, parenteral administration, sublingual administration, transdermal administration, rectal administration, transmucosal administration, topical administration, inhalation, buccal administration, intrapleural administration, intravenous administration, intraarterial administration, intraperitoneal administration, subcutaneous administration, intramuscular administration, intranasal administration, intrathecal administration, and intraarticular administration, or combinations thereof.

40. The method of any of claims 38 through 39, wherein the subject is a mammal.

41. The method of any of claims 38 through 40, wherein the subject is a human.

42. A cell comprising the amino acid sequence of any of claims 1 through 5 or the composition of any of claims 6 through 12.

43. A method of suppressing appetite or inducing weight loss in a subject in need thereof comprising administering to the subject an amino acid sequence of any of claims 1 through 5 and 48, the composition of any of claims 6 through 12; or the pharmaceutical composition of any of claims 13 through 15 or 50.

44. The method of claim 43, wherein the amino acid sequence, the composition or the pharmaceutical composition is administered by oral adminstration, parenteral administration, sublingual administration, transdermal administration, rectal administration, transmucosal administration, topical administration, inhalation, buccal administration, intrapleural administration, intravenous administration, intraarterial administration, intraperitoneal administration, subcutaneous administration, intramuscular administration, intranasal administration, intrathecal administration, and intraarticular administration, or combinations thereof.

45. The method of any of claims 43 through 44, wherein the subject is a mammal.

46. The method of any of claims 43 through 45, wherein the subject is a human.DOCKET NO. STFD-012-PCT PCT APPLICATION 47. The amino acid sequence of claim 2 further comprising an amidated modification on the carboxy terminal end of the peptide.

48. The amino acid sequence of claim 1 comprising SEQ ID NO: 75, a functional variant thereof comprising at least about 75% sequence identity to SEQ ID NO:75, or a pharmaceutically acceptable salt thereof, wherein the amino acid is free of SEQ ID NO:

1.

49. The amino acid of claim 48, wherein the amino acid sequence is SEQ ID NO:75 or a functional variant thereof comprising about 90% sequence identity to SEQ ID NO:75, or a pharmaceutically acceptable salt thereof.

50. A pharmaceutical composition comprising the amino acid of claim 48 or claim 49.

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