Combinations of Anti-GIP antibodies and incretins and uses thereof

Abstract

Provided for herein are anti-GIP antibodies, or antigen-binding fragments thereof. Conjugates of the anti-GIP antibodies, or antigen-binding fragments thereof, to biologically active peptides are also provided. Pharmaceutical compositions of the, anti-GIP antibodies, or antigen- binding fragments thereof, biologically active peptides, combinations thereof, or conjugates thereof are also provided. Methods of using the embodiments and compositions provided for herein are also provided.

Description

DOCKET NO: HEB-006WO PATENTCOMBINATIONS OF ANTI-GIP ANTIBODIES AND INCRETINS AND USES THEREOFRELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application Ser. No. 63 / 696,174 filed September 18, 2024, and U.S. Provisional Application Ser. No. 63 / 796,859 filed April 29, 2025, each of which are hereby incorporated by reference in their entirety.REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY

[0002] The instant application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. Said XML copy, created on September 17, 2025, is named “HEB-006WO_SL.xml” and is 163,224 bytes in size.FIELD

[0003] The present disclosure relates generally to anti-GIP antibodies and combinations with biologically active peptides for the treatment of diseases.BACKGROUND

[0004] Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood-glucose-dependent mechanism. Glucose-dependent insulinotropic polypeptide (GIP) and glucagon like polypeptide- 1 (GLP-l) are incretins also known as insulinotropic factors.

[0005] GIP, formerly known as gastric inhibitory polypeptide, is a single 42-amino acid peptide secreted from K-cells in the small intestine (duodenum and jejunum). Human GIP is derived from the processing of proGIP, a 153-amino acid precursor that is encoded by a gene localized to chromosome 17q. GIP secretion is induced by food ingestion GIP is an inhibiting hormone of the secretin family of hormones that, among other functions, stimulates insulin secretion. GIP has a1IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT number of physiological effects in tissues, including promotion of fat storage in adipocytes and promotion of pancreatic islet P-ccll function and glucosc-dcpcndcnt insulin secretion.

[0006] GLP-1 is a 31 -amino acid peptide derived from the proglucagon gene. It is secreted by intestinal L-cells and released in response to food ingestion to induce insulin secretion from pancreatic 0-cells. In addition to the incretin effects, GLP-1 also decreases glucagon secretion, delays gastric emptying and reduces caloric intake. GLP-1 exerts its effects by activation of the GLP-1 receptor (GLP-1R). The function of GLP-1 is limited by rapid degradation by the DPP-IV enzyme, resulting in a half-life of approximately 2 minutes. Treatment of obesity or other diseases characterized by fatty tissue buildup would benefit from an extension of the GLP-1 half-life. Long- lasting GLP-1 R agonists, such as exenatide, liraglutide, and dulaglutide, have been developed.

[0007] Although the signaling cascades involved in many metabolic disorders have been elucidated, effective treatments for these disorders remains elusive. There is an urgent need for new and innovative approaches to the treatment of metabolic disorders, especially given the health risk posed by not only the disorders themselves, but also by the common co-morbidities that increase the risk of overall negative outcomes. The present disclosure addresses these needs and others.BRIEF SUMMARY

[0008] In some embodiments, a method of treating a disease is provided, the method comprising administering an anti-glucose-dependent insulinotropic polypeptide (GIP) antibody, or an antigenbinding fragment thereof, and a biologically active peptide, wherein the biologically active peptide comprises a glucagon like peptide 1 receptor (GLP-1 R) agonist.

[0009] In some embodiments, the method comprises co-administering the anti-GIP antibody, or antigen-binding fragment thereof, and the biologically active peptide.

[0010] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, and the biologically active peptide are conjugated. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen binding fragment thereof, through a substituted cysteine residue in the IgG Fc region. In some embodiments, the IgG Fc is an IgGl Fc. In some embodiments, the IgGl Fc comprises one or more substitutions selected from D70C, E89C, V109C, Al 11C, A118C, S124C, A140C, E152C, S239C, V265C, E272C, K290C, Y300C, E345C,2IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTT359C, N390C, or S442C. In some embodiments, the CL comprises one or more substitutions selected from K149C or V205C.

[0011] In some embodiments, the GLP-1R agonist is liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 95% identical thereto.

[0012] In some embodiments, the anti-GIP antibody, or an antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a heavy chain complementarity domain 1 (HCDR1), a HCDR2, and a HCDR3 comprising amino acid sequences selected from: (a) SEQ ID NO: 15, SEQ ID NO: 26, and SEQ ID NO: 17, (b) SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, or (c) SEQ ID NO: 15, SEQ ID NO: 16, and SEQ ID NO: 17; and wherein the VL comprises a light chain complementarity domain 1 (LCDR1), a LCDR2, and a LCDR3 comprising amino acid sequences selected from: (d) SEQ ID NO: 27, SEQ ID NO: 28, and SEQ ID NO: 19, (e) SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, (f) SEQ ID NO: 18, SEQ ID NO: 5, and SEQ ID NO: 19, (g) SEQ ID NO: 27, SEQ ID NO: 31, and SEQ ID NO: 19, or (h) SEQ ID NO: 27, SEQ ID NO: 34, and SEQ ID NO: 19.3IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT

[0013] In some embodiments, the VH comprises an amino acid sequence having at least 90% identity to an amino acid sequence selected from SEQ ID NO: 29, SEQ ID NO: 13, SEQ ID NO: 24, SEQ ID NO: 32, or SEQ ID NO: 35. In some embodiments, the VL comprises an amino acid sequence having at least 90% identity to an amino acid sequence selected from SEQ ID NO: 30, SEQ ID NO: 14, SEQ ID NO: 25, SEQ ID NO: 33, or SEQ ID NO: 36.

[0014] In some embodiments, a method of treating a disease is provided, the method comprising administering an anti-glucose-dependent insulinotropic polypeptide (GIP) antibody, or an antigenbinding fragment thereof, and semaglutide. In some embodiments, the anti-GIP antibody and semaglutide are co-administered. In some embodiments, the anti-GIP antibody and semaglutide are co-formulated. In some embodiments, the semaglutide is conjugated to the anti-GIP antibody.

[0015] In some embodiments, a pharmaceutical composition is provided, the pharmaceutical composition comprising an anti-glucose-dependent insulinotropic polypeptide (GIP) antibody, or an antigen-binding fragment thereof, as provided for herein, and a biologically active peptide as provided for herein, wherein the biologically active peptide comprises a glucagon like peptide 1 receptor (GLP-1R) agonist.

[0016] In some embodiments, an apparatus for the delivery of a medicament is provided, the apparatus comprising a first chamber and a second chamber, wherein the first chamber comprises a pharmaceutical composition comprising a biologically active peptide and wherein the second chamber comprises a pharmaceutical composition comprising an anti-GIP antibody, or antigenbinding fragment thereof, wherein the biologically active peptide comprises a glucagon like peptide 1 receptor (GLP-1R) agonist.

[0017] In some embodiments, an apparatus for the delivery of a medicament is provided, the apparatus comprising a first chamber, wherein the first chamber comprises a pharmaceutical composition comprising an anti-GIP antibody, or antigen-binding fragment thereof, conjugated to a biologically active peptide, wherein the biologically active peptide comprises a glucagon like peptide 1 receptor (GLP-1R) agonist.

[0018] In some embodiments, a conjugate is provided, the conjugate comprising an anti-glucose- dependent insulinotropic polypeptide (GIP) antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, wherein the biologically active peptide comprises a glucagon like peptide 1 receptor (GLP-1R) agonist.4IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT

[0019] In some embodiments, a method of treating a disease is provided, the method comprising administering a conjugate as provided for herein.

[0020] In some embodiments, a pharmaceutical composition is provided, the composition comprising a conjugate as provided for herein.BRIEF DESCRIPTION OF FIGURES

[0021] FIG. 1 illustrates the results of a binding affinity assay between an anti-GIP antibody as provided for herein and rat GIP.

[0022] FIG. 2 illustrates the results of a binding affinity assay between an anti-GIP antibody as provided for herein and human GIP.

[0023] FIG. 3 illustrates the results of a binding affinity assay between an anti-GIP antibody as provided for herein and mouse GIP.

[0024] FIG. 4 illustrates the results of a binding affinity assay between an anti-GIP antibody as provided for herein and monkey GIP.

[0025] FIG. 5 illustrates the results of a GIP neutralization assay with antibody conjugates as provided for herein. Conjugation of the biologically active peptide to E272C of the antibody does not affect the ability of the antibody to bind GIP.

[0026] FIG. 6A and 6B illustrate the results of a GLP-1R activation assay with antibody conjugates as provided for herein. The biologically active peptide was conjugated at the recited HC or LC cysteine mutation sites. The order of the figure legend reflects the order of maximum luminescence at the highest conjugate concentration. FIG. 6A illustrates the results for LC- K149C-BrAc, HC-E272C-BrAc, HC-K290C-BrAc, LC-K149C-Mal, HC-S442C-BrAc, and HCR-188 (antibody alone control). FIG, 6B illustrates the results for LC-V205C-Mal, HC- S442C-Mal, HC-272C-Mal, Semaglutide, GLP-1, and HC-K290C-Mal.

[0027] FIG. 7 illustrates the results of a diet induced obesity (DIO) study in mice treated with various embodiments as provided for herein.

[0028] FIG. 8A-8D illustrate the results of a diet induced obesity (DIO) study in mice treated with various embodiments as provided for herein. FIG. 8A illustrates the results for 1 mg / kg treatment. FIG. 8B illustrates the results for 2 mg / kg treatment. FIG. 8C illustrates the results for 5 mg / kg treatment. FIG. 8D illustrates the results for 10 mg / kg treatment.5IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT

[0029] FIG. 9A and 9B illustrate the results of a DIO study in NHPs treated with various embodiments as provided for herein. FIG. 9A illustrates the mean % change in body weight (BW) for the various treatment groups. FIG. 9B illustrates the data of FIG. 9A adjusted for vehicle.

[0030] FIG. 10 illustrates the cumulative total energy intake (TEI) of each treatment group in a DIO study in NHPs treated with various embodiments as provided for herein.

[0031] FIG. HA and FIG. 11B illustrate the results of a single-dose pharmacokinetics study (SDPK) in DIO NHPs. FIG. HA illustrates the total change in body weight in the NHPs. FIG. 11B illustrates the TEI of each treatment group.DETAILED DESCRIPTION

[0032] Provided for herein are antibodies that bind glucose-dependent insulinotropic polypeptide (GIP) and methods of using the same. In some embodiments, the anti-GIP antibody is conjugated to a biologically active peptide. In some embodiments, the anti-GIP antibody is administered with a biologically active peptide. In some embodiments, the anti-GIP antibody is co-administered with a biologically active peptide.

[0033] Unless defined otherwise, all technical and scientific terms have the same meaning as is commonly understood by one of ordinary skill in the art to which the embodiments disclosed belongs.

[0034] As used herein, the terms “a” or “an” means that “at least one” or “one or more” unless the context clearly indicates otherwise.

[0035] As used herein, the term “about” means that the numerical value is approximate and small variations would not significantly affect the practice of the disclosed embodiments. Where a numerical limitation is used, unless indicated otherwise by the context, “about” means the numerical value can vary by ±10% and remain within the scope of the disclosed embodiments. Additionally, where a phrase recites “about x to y,” the term “about” modifies both x and y and can be used interchangeably with the phrase “about x to about y” unless context dictates differently.

[0036] As used herein, the term “individual” or “subject,” or “patient” used interchangeably, means any animal, including mammals, such as mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, or primates, such as humans.

[0037] As used herein, the terms “comprising” (and any form of comprising, such as “comprise”, “comprises”, and “comprised”), “having” (and any form of having, such as “have” and “has”),6IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT“including” (and any form of including, such as “includes” and “include”), or “containing” (and any form of containing, such as “contains” and “contain”), arc inclusive or open-ended and do not exclude additional, unrecited elements or method steps. Any step or composition that uses the transitional phrase of “comprise” or “comprising” can also be said to describe the same with the transitional phase of “consisting of’ or “consists.”

[0038] As used herein, the term “contacting” means bringing together of two elements in an in vitro system or an in vivo system. For example, “contacting” virus or vector described herein with an individual or patient or cell includes the administration of the virus to an individual or patient, such as a human, as well as, for example, introducing a compound into a sample containing a cellular or purified preparation containing the cell.

[0039] As used herein, the term “fused” or “linked” when used in reference to a protein having different domains or heterologous sequences or when used in reference to the joining of two polypeptides means that the protein domains are part of the same peptide chain that are connected to one another with either peptide bonds or other covalent bonding. The domains or section can be linked or fused directly to one another or another domain or peptide sequence can be between the two domains or sequences and such sequences would still be considered to be fused or linked to one another. In some embodiments, the various domains or proteins provided for herein are linked or fused directly to one another or a linker sequences, such as the glycine / serine sequences described herein link the two domains together.

[0040] A “disease” is a state of health of an animal wherein the animal cannot maintain homeostasis, and wherein if the disease is not ameliorated then the animal’s health continues to deteriorate. In contrast, a “disorder” in an animal is a state of health in which the animal is able to maintain homeostasis, but in which the animal’s state of health is less favorable than it would be in the absence of the disorder. Left untreated, a disorder does not necessarily cause a further decrease in the animal’s state of health.

[0041] “Effective amount” or “therapeutically effective amount” are used interchangeably herein, and refer to an amount of a compound, formulation, material, or composition, as described herein effective to achieve a particular biological result or provides a therapeutic or prophylactic benefit. Such results may include, but are not limited to an amount that when administered to a mammal, has the ability to decrease blood glucose, the ability to increase glucose tolerance, the ability to increase insulin sensitivity the ability to decrease body weight or reduce body weight gain; the7IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT ability to decrease fat mass or decrease inflammation in fat tissue; the ability to decrease fasting insulin levels; the ability to decrease circulating cholesterol levels; the ability to decrease circulating triglyceride levels; the ability to decrease liver steatosis or reduce triglyceride level in liver; the ability to decrease AST, ALT, and / or ALP levels. The skilled artisan would understand that the amount of the composition administered herein varies and can be readily determined based on a number of factors such as the disease or condition being treated, the age and health and physical condition of the mammal being treated, the severity of the disease, the particular compound being administered, and the like.

[0042] “Encoding” refers to the inherent property of specific sequences of nucleotides in a polynucleotide, such as a gene, a cDNA, or an mRNA, to serve as templates for synthesis of other polymers and macromolecules in biological processes having either a defined sequence of nucleotides (i.e., rRNA, tRNA and mRNA) or a defined sequence of amino acids and the biological properties resulting therefrom. Thus, a gene encodes a protein if transcription and translation of mRNA corresponding to that gene produces the protein in a cell or other biological system. Both the coding strand, the nucleotide sequence of which is identical to the mRNA sequence and is usually provided in sequence listings, and the non-coding strand, used as the template for transcription of a gene or cDNA, can be referred to as encoding the protein or other product of that gene or cDNA.

[0043] “Expression vector” refers to a vector comprising a recombinant polynucleotide comprising expression control sequences operatively linked to a nucleotide sequence to be expressed. An expression vector comprises sufficient cis-acting elements for expression; other elements for expression can be supplied by the host cell or in an in vitro expression system. Expression vectors include all those known in the art, such as cosmids, plasmids (e.g., naked or contained in liposomes) and viruses (e.g., Sendai viruses, lentiviruses, retroviruses, adenoviruses, and adeno-associated viruses) that incorporate the recombinant polynucleotide.

[0044] As used herein, the phrase “ex vivo” in reference to a cell being transduced, transfected or transformed ex vivo, refers to a cell being transduced, transfected or transformed outside of the subject, that is with the cells being removed from the subject before such cells are transduced, transfected or transformed.

[0045] “Identity” as used herein refers to the subunit sequence identity between two polymeric molecules such as between two nucleic acid or amino acid molecules, such as, between two8IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT polynucleotide or polypeptide molecules. When two amino acid sequences have the same residues at the same positions; e.g., if a position in each of two polypeptide molecules is occupied by an Arginine, then they are identical at that position. The identity or extent to which two amino acid or two nucleic acid sequences have the same residues at the same positions in an alignment is often expressed as a percentage. The identity between two amino acid or two nucleic acid sequences is a direct function of the number of matching or identical positions; e.g., if half of the positions in two sequences are identical, the two sequences are 50% identical; if 90% of the positions (e.g., 9 of 10), are matched or identical, the two amino acids sequences are 90% identical.

[0046] By "substantially identical" is meant a polypeptide or nucleic acid molecule exhibiting at least 50% identity to a reference amino acid sequence (for example, any one of the amino acid sequences described herein) or nucleic acid sequence (for example, any one of the nucleic acid sequences described herein). In some embodiments, such a sequence is at least 60%, 80% or 85%, or 90%, 95% or even 99% identical at the amino acid level or nucleic acid to the sequence used for comparison. Other percentages of identity in reference to specific sequences are described herein.

[0047] Sequence identity can be measured / determined using sequence analysis software (for example, Sequence Analysis Software Package of the Genetics Computer Group, University of Wisconsin Biotechnology Center, 1710 University Avenue, Madison, Wis. 53705, BLAST, BESTFIT, GAP, or PILEUP / PRETTYBOX programs). Such software matches identical or similar sequences by assigning degrees of homology to various substitutions, deletions, and / or other modifications. Conservative substitutions typically include substitutions within the following groups: glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid, asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine. In an exemplary approach to determining the degree of identity, a BLAST program may be used, with a probability score between e3 and el 00 indicating a closely related sequence. In some embodiments, sequence identity is determined by using BLAST with the default settings.

[0048] To the extent embodiments provided for herein, includes composition comprising various proteins, these proteins may, in some instances, comprise amino acid sequences that have sequence identity to the amino acid sequences disclosed herein. Therefore, in certain embodiments, depending on the particular sequence, the degree of sequence identity is preferably greater than 50% (e.g. 60%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%9IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT or more) to the SEQ ID NOs disclosed herein. In addition to these percentages, other percentages of identity arc provided for herein. Identity between polypeptides can be determined by the Smith- Waterman homology search algorithm as implemented in the MPSRCH program (Oxford Molecular), using an affine gap search with parameters gap open penalty - 12 and gap extension penalty = 1.

[0049] These proteins may, compared to the disclosed proteins, include one or more (e.g. 1, 2, 3,4, 5, 6, 7, 8, 9, 10, etc.) conservative amino acid replacements i.e. replacements of one amino acid with another which has a related side chain. Genetically-encoded amino acids are generally divided into four families: (1) acidic i.e. aspartate, glutamate; (2) basic i.e. lysine, arginine, histidine; (3) non polar i.e. alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan; and (4) uncharged polar i.e. glycine, asparagine, glutamine, cysteine, serine, threonine, tyrosine. Phenylalanine, tryptophan, and tyrosine are sometimes classified jointly as aromatic amino acids. In general, Substitution of single amino acids within these families does not have a major effect on the biological activity. The proteins may have one or more (e.g. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) single amino acid deletions relative to the disclosed protein sequences. The proteins may also include one or more (e.g. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) insertions (e.g. each of 1, 2, 3, 4 or 5 amino acids) relative to the disclosed protein sequences.

[0050] Synthetic, rare, or modified amino acid residues having known similar physiochemical properties to those of an above-described grouping can be used as a “conservative” substitute for a particular amino acid residue in a sequence. For example, a D-Arg residue may serve as a substitute for a typical L-Arg residue. It also can be the case that a particular substitution can be described in terms of two or more of the above described classes (e.g., a substitution with a small and hydrophobic residue means substituting one amino acid with a residue(s) that is found in both of the above-described classes or other synthetic, rare, or modified residues that are known in the art to have similar physiochemical properties to such residues meeting both definitions).

[0051] As used herein, the phrase “in vivo” in reference to a cell being transduced, transfected or transformed in vivo, refers to a cell being transduced, transfected or transformed in the subject without the cells being removed from the subject before such cells are transduced, transfected or transformed.

[0052] “Isolated” means altered or removed from the natural state. For example, a nucleic acid or a peptide naturally present in a living animal is not “isolated,” but the same nucleic acid or peptide10IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT partially or completely separated from the coexisting materials of its natural state is “isolated.” An isolated nucleic acid or protein can exist in substantially purified form, or can exist in a non-nativc environment such as, for example, a host cell.

[0053] By the term “modified” as used herein, is meant a changed state or structure of a molecule or cell as provided herein. Molecules may be modified in many ways, including chemically, structurally, and functionally, such as mutations, substitutions, insertions, or deletions (e.g. internal deletions truncations). Cells may be modified through the introduction of nucleic acids or the expression of heterologous proteins.

[0054] By the term “modulating,” as used herein, is meant mediating an increase or decrease in the level of a response in a subject compared with the level of a response in the subject in the absence of a treatment or compound, and / or compared with the level of a response in an otherwise identical but untreated subject. The term encompasses perturbing and / or affecting a native signal or response thereby mediating a beneficial therapeutic response in a subject, such as, a human.

[0055] Unless otherwise specified, a “nucleotide sequence encoding an amino acid sequence” includes all nucleotide sequences that are degenerate versions of each other and that encode the same amino acid sequence. The phrase nucleotide sequence that encodes a protein or an RNA may also include introns to the extent that the nucleotide sequence encoding the protein may in some version contain an intron(s).

[0056] The term “oligonucleotide” typically refers to short polynucleotides. It will be understood that when a nucleotide sequence is represented by a DNA sequence (i.e., A, T, C, G), this also provides the corresponding RNA sequence (i.e., A, U, C, G) in which “U” replaces “T.”

[0057] “ Parenteral” administration of a composition includes, e.g., subcutaneous (s.c.), intravenous (i.v.), intramuscular (i.m.), or intrasternal injection, or infusion techniques.

[0058] The term “polynucleotide” as used herein is defined as a chain of nucleotides. Furthermore, nucleic acids are polymers of nucleotides. Thus, the terms “nucleic acids” and “polynucleotides” as used herein are interchangeable. As used herein polynucleotides include, but are not limited to, all nucleic acid sequences which are obtained by any methods available in the art, including, without limitation, recombinant methods, i.e., the cloning of nucleic acid sequences from a recombinant library or a cell genome, using cloning technology and PCR, and the like, and by synthetic means.11IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT

[0059] As used herein, the terms “peptide,” “polypeptide,” and “protein” are used interchangeably, and refer to a compound comprised of a plurality of amino acid residues covalently linked by peptide bonds. As used herein, the term refers to both short chains, which also commonly are referred to in the art as peptides, oligopeptides and oligomers, for example, and to longer chains, which generally are referred to in the art as proteins, of which there are many types. “Polypeptides” include, for example, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, heterodimers, variants of polypeptides, modified polypeptides, derivatives, analogs, fusion proteins, among others. The polypeptides include natural peptides, recombinant peptides, synthetic peptides, or a combination thereof.

[0060] As used herein, the term “antibody” refers to a broad sense and includes immunoglobulin or antibody molecules including polyclonal antibodies, monoclonal antibodies including murine, human, humanized and chimeric monoclonal antibodies and antibody fragments, such as, but not limited to, single chain variable fragments (scFv).

[0061] A “non-naturally occurring amino acid” is a compound that has the same basic chemical structure as a naturally occurring amino acid, but is not incorporated into a growing polypeptide chain by the translation complex. “Non-naturally occurring amino acid” also includes, but is not limited to, amino acids that occur by modification (e.g., posttranslational modifications) of a naturally encoded amino acid (including but not limited to, the 20 common amino acids) but are not themselves naturally incorporated into a growing polypeptide chain by the translation complex. A non-limiting lists of examples of non-naturally occurring amino acids that can be inserted into a polypeptide sequence or substituted for a wild-type residue in polypeptide sequence include P- amino acids, homoamino acids, cyclic amino acids and amino acids with derivatized side chains. Examples include (in the L-form or D-form; abbreviated as in parentheses): citrulline (Cit), homocitrulline (hCit), Na-methylcitrulline (NMeCit), Na-methylhomocitrulline (Na-MeHoCit), ornithine (Orn), Na-Methylomi thine (Na-MeOm or NMeOm), sarcosine (Sai-), homolysine (hLys or hK), homoarginine (hArg or hR), homoglutamine (hQ), Na-methylarginine (NMeR), Na- methylleucine (Na-MeL or NMeL), N-methylhomolysine (NMeHoK), Na-methylglutamine (NMeQ), norleucine (Nle), norvaline (Nva), 1,2,3,4-tetrahydroisoquinoline (Tic), Octahydroindole-2-carboxylic acid (Oic), 3-(l-naphthyl)alanine (1-Nal), 3-(2-naphthyl)alanine (2-Nal), 1,2,3,4-tetrahydroisoquinoline (Tic), 2-indanylglycine (Igl), para- iodophenylalanine (pl- Phe), para-aminophenylalanine (4AmP or 4-Amino-Phe), 4-guanidino phenylalanine (Guf),12IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT glycyllysine (abbreviated “K(Ns-glycyl)” or “K(glycyl)” or “K(gly)”), nitrophenylalanine (nitrophc), aminophcnylalaninc (aminophc or Amino-Phc), bcnzylphcnylalaninc (bcnzylphc), y- carboxyglutamic acid (y-carboxyglu), hydroxyproline (hydroxypro), p-carboxyl-phenylalanine (Cpa), a-aminoadipic acid (Aad), Na-methyl valine (NMeVal), N-a-methyl leucine (NMeLeu), Na-methylnorleucine (NMeNle), cyclopentylglycine (Cpg), cyclohexylglycine (Chg), acetylarginine (acetylarg), a, P-diaminopropionoic acid (Dpr), a, y-diaminobutyric acid (Dab), diaminopropionic acid (Dap), cyclohexylalanine (Cha), 4-methyl-phenylalanine (MePhe), , P- diphenyl-alanine (BiPhA), aminobutyric acid (Abu), 4-phenyl- phenyl alanine (or biphenylalanine; 4Bip), a-amino-isobutyric acid (Aib), beta-alanine, beta-aminopropionic acid, piperidinic acid, aminocaprioic acid, aminoheptanoic acid, aminopimelic acid, desmosine, diaminopimelic acid, N- ethylglycine, N-ethylaspargine, hydroxy lysine, allo-hydroxylysine, isodesmosine, allo-isoleucine, N-methylglycine, N-methylisoleucine, N-methylvaline, 4-hydroxyproline (Hyp), y- carboxyglutamate, s-N,N,N-trimethyllysine, 8-N-acetyllysine, O-phosphoserine, N-acetylserine, N-formylmethionine, 3-methylhistidine, 5-hydroxylysine, co-methylarginine, 4-Amino-O-Phthalic Acid (4APA), and other similar amino acids, and derivatized forms of any of those specifically listed.

[0062] In general, antibodies are proteins or polypeptides that exhibit binding specificity to a specific antigen. Intact antibodies are heterotetrameric glycoproteins, composed of two identical light chains and two identical heavy chains. Typically, each light chain is linked to a heavy chain by one covalent disulfide bond, while the number of disulfide linkages varies between the heavy chains of different immunoglobulin isotypes. Each heavy and light chain also has regularly spaced intrachain disulfide bridges. Each heavy chain has at one end a variable domain (VH) followed by a number of constant domains. Each light chain has a variable domain at one end (VL) and a constant domain at its other end; the constant domain of the light chain is aligned with the first constant domain of the heavy chain and the light chain variable domain is aligned with the variable domain of the heavy chain. Antibody light chains of any vertebrate species can be assigned to one of two clearly distinct types, namely kappa and lambda, based on the amino acid sequences of their constant domains. Immunoglobulins can be assigned to five major classes, namely IgA, IgD, IgE, IgG and IgM, depending on the heavy chain constant domain amino acid sequence. IgA and IgG are further sub-classified as the isotypes IgAl, IgA2, IgGl, IgG2, IgG3 and IgG4.13IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT

[0063] As used herein, the term “antibody fragment” refers to an intact antibody, generally the antigen-binding or variable region of the intact antibody. Examples of antibody fragments include Fab, Fab', F(ab')2 and Fv fragments, diabodies, single chain antibody molecules and multispecific antibodies formed from at least two intact antibodies or fragments thereof.

[0064] As used herein, the term “antigen” refers to any molecule that has the ability to generate antibodies either directly or indirectly.

[0065] By the term “specifically binds,” as used herein with respect to an antibody, is meant an antibody which recognizes a specific antigen, but does not substantially recognize or bind other molecules in a sample. For example, an antibody that specifically binds to an antigen from one species may also bind to that antigen from one or more species. But, such cross-species reactivity does not itself alter the classification of an antibody as specific. In another example, an antibody that specifically binds to an antigen may also bind to different allelic forms of the antigen. However, such cross reactivity does not itself alter the classification of an antibody as specific. In some instances, the terms “specific binding” or “specifically binding,” can be used in reference to the interaction of an antibody, a protein, or a peptide with a second chemical species, to mean that the interaction is dependent upon the presence of a particular structure (e.g., an antigenic determinant or epitope) on the chemical species; for example, an antibody recognizes and binds to a specific protein structure rather than to proteins generally. If an antibody is specific for epitope “A”, the presence of a molecule containing epitope A (or free, unlabeled A), in a reaction containing labeled “A” and the antibody, will reduce the amount of labeled A bound to the antibody.

[0066] The term “epitope” is the portion of a molecule that is bound by an antigen-binding protein (for example, an antibody). The term includes any determinant capable of specifically binding to an antigen-binding protein, such as an antibody. An epitope can be contiguous or non-contiguous (discontinuous) (e.g., in a polypeptide, amino acid residues that are not contiguous to one another in the polypeptide sequence but that within in context of the molecule are bound by the antigenbinding protein). A conformational epitope is an epitope that exists within the conformation of an active protein but is not present in a denatured protein. In certain embodiments, epitopes may be mimetic in that they comprise a three dimensional structure that is similar to an epitope used to generate the antigen-binding protein, yet comprise none or only some of the amino acid residues found in that epitope used to generate the antigen-binding protein. Most often, epitopes reside on14IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT proteins, but in some instances may reside on other kinds of molecules, such as nucleic acids. Epitope determinants may include chemically active surface groupings of molecules such as amino acids, sugar side chains, phosphoryl or sulfonyl groups, and may have specific three dimensional structural characteristics, and / or specific charge characteristics. Generally, antigen-binding proteins specific for a particular’ target antigen will preferentially recognize an epitope on the target antigen in a complex mixture of proteins and / or macromolecules.

[0067] The term “subject” includes living organisms, including those in which an immune response can be elicited (e.g., mammals). A “subject” or “patient,” as used therein, may be a human or non-human mammal. Non-human mammals include, for example, livestock and pets, such as ovine, bovine, porcine, canine, non-human primates, feline and murine mammals. In some embodiments, the subject is human.

[0068] The term “therapeutic” as used herein means a treatment and / or prophylaxis. A therapeutic effect is obtained by suppression, remission, or eradication of a disease state.

[0069] The term “transfected” or “transformed” or “transduced” as used herein refers to a process by which exogenous nucleic acid is transferred or introduced into a cell. A “transfected” or “transformed” or “transduced” cell is one which has been transfected, transformed or transduced with exogenous nucleic acid. The cell includes the primary subject cell and its progeny. In some embodiments, the transfection, transformation, or transduction is performed or occurs in vivo.

[0070] To “treat” a disease as the term is used herein, means to reduce the frequency or severity of at least one sign or symptom of a disease or disorder experienced by a subject.

[0071] A “vector” is a composition of matter which comprises an isolated nucleic acid encoding a protein or a peptide. Numerous vectors are known in the art including, but not limited to, linear polynucleotides, plasmids, DNA, and RNA. Examples of viral vectors include, but are not limited to, Sendai viral vectors, adenoviral vectors, adeno-associated virus vectors, retroviral vectors, lentiviral vectors, and the like.

[0072] A “carrier” or “delivery vehicle” includes viral particles, viruses, polylysine compounds, and liposomes, which facilitate transfer of nucleic acid into cells. A carrier or delivery vehicle can also be used to deliver a protein or peptide to a cell.

[0073] Ranges: throughout this disclosure, various aspects of the embodiments can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation. Accordingly, the15IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the breadth of the range. Unless otherwise explicitly stated to the contrary, a range that is disclosed also includes the endpoints of the range.Antibodies

[0074] Disclosed herein are antibodies, or antigen-binding fragments thereof, or equivalents thereof, and methods of use thereof. In some embodiments, the antibody, or antigen-binding fragment thereof is a monoclonal antibody, or antigen-binding fragment thereof. In some embodiments, the antibody, or antigen-binding fragment thereof specifically binds to glucosedependent insulinotropic polypeptide (GIP). In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, selectively binds GIP.

[0075] Human GIP (UniProt: P09681) has the amino acid sequence of SEQ ID NO: 122, shown below.MVATKTFALLLLSLFLAVGLGEKKEGHFSALPSLPVGSHAKVSSPQPRGPRYAEGTFISDYSIA MDKIHQQDFVNWLLAQKGKKNDWKHNITQREARALELASQANRKEEEAVEPQSSPAKNPSDEDL LRDLLIQELLACLLDQTNLCRLRSR ( SEQ ID NO : 122 )

[0076] Full length GIP is processed prior to secretion resulting in a 42 amino acid circulating polypeptide. The processed form of human GIP has the amino acid sequence of SEQ ID NO: 123, shown below.YAEGTFISDYSIAMDKIHQQDFVNWLLAQKGKKNDWKHNITQ ( SEQ ID NO : 123 )

[0077] The gene sequence of GIP is highly conserved across species. The amino acid sequences of the processed forms of mouse (SEQ ID NO: 124), rat (SEQ ID NO: 125), and rhesus macaque (SEQ ID NO: 126) are provided below.16IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTYAEGTFISDYSIAMDKIRQQDFVNWLLAQRGKKSDWKHNITQ (SEQ ID NO : 124 )YAEGTFISDYSIAMDKIRQQDFVNWLLAQKGKKNDWKHNLTQ (SEQ ID NO : 125 )YAEGTFISDYSIAMDKIHQQDFVNWLLAQKGKKNDWKHNITQ (SEQ ID NO : 126 )

[0078] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, binds to an amino acid sequence of SEQ ID NO: 122. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, binds to secreted GIP and binds to an amino acid sequence of SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, or SEQ ID NO: 126. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, binds to an amino acid sequence of SEQ ID NO: 123. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, binds to an amino acid sequence of SEQ ID NO: 124. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, binds to an amino acid sequence of SEQ ID NO: 125. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, binds to an amino acid sequence of SEQ ID NO: 126.

[0079] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, does not substantially bind other native incretins or incretin analogues.

[0080] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, is monoclonal. In some embodiments, the monoclonal anti-GIP antibody, or antigen-binding fragment thereof, is a mouse, chimeric, humanized, or human monoclonal antibody or antigenbinding fragment thereof. In some embodiments, the monoclonal anti-GIP antibody, or antigenbinding fragment thereof, is a human monoclonal antibody or antigen-binding fragment thereof. In some embodiments, the monoclonal anti-GIP antibody, or antigen-binding fragment thereof, is a humanized monoclonal antibody or antigen-binding fragment thereof. In some embodiments, the monoclonal anti-GIP antibody, or antigen-binding fragment thereof, is a chimeric monoclonal antibody or antigen-binding fragment thereof. In some embodiments, the monoclonal anti-GIP antibody, or antigen-binding fragment thereof, is a mouse monoclonal antibody or antigen-binding fragment thereof.

[0081] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a CL, CHI, CH2, or CH3 region, or a combination thereof. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises an Fc region. The Fc region17IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT can be linked to the heavy or light chain of the antibody. In some embodiments, the Fc region is an IgG Fc. In some embodiments, the IgG is selected from IgGl, IgG2, IgG3, or IgG4. In some embodiments, the IgG Fc is an IgGl Fc. In some embodiments, the IgGl Fc comprises the amino acid sequence of SEQ ID NO: 127 below.ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFP AVLQSSGLYSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAP IE KTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK ( SEQ ID NO : 127 )

[0082] In some embodiments, the IgG Fc is IgG2 Fc. In some embodiments, the IgG2 Fc comprises the amino acid sequence of SEQ ID NO: 128 below.STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA VLQSSGLYSLSSWTVPSSSLGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPC PAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVQFNWYVDGVEV HNAKTKPREEQFNSTFRWSVLTWHQDWLNGKEYKCKVSNKGLPAP IEKTISK TKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK TTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG K ( SEQ ID NO : 128 )

[0083] In some embodiments, the IgG Fc is IgG4 Fc. In some embodiments, the IgG4 Fc comprises the amino acid sequence of SEQ ID NO: 129 below.STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA VLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSC PAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVE VHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTIS KAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSL GK ( SEQ ID NO : 129 )

[0084] In some embodiments, the Fc domain comprises mutations that render the Fc region “effectorless” and unable to bind Fc receptors. The mutations that render Fc regions effectorless are known in the art and any mutation or combination of mutations can be used. In some embodiments, the Fc domain comprises mutations that impair or inhibits recycling of the Fc. In some embodiments, the Fc domain comprises mutations that impair FcRn-mediated recycling of the Fc. In some embodiments, the Fc domain comprises a mutation, or a set of mutations, that impair binding of the Fc to an FcRn. In some embodiments, the Fc domain does not bind to an FcRn. In some embodiments, the Fc domain has reduced affinity to an FcRn. In some18IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT embodiments, the Fc domain comprising a mutation, or a set of mutations, that impairs binding of the Fc to an FcRn, exhibit better (i.c., more or enhanced) degradation as compared to an Fc domain not comprising the mutation, or set of mutations, that impairs its binding to the FcRn. In some embodiments, the Fc domain comprising a mutation, or a set of mutations, that impairs binding of the Fc to an FcRn, exhibit better lysosomal degradation as compared to an Fc domain not comprising the mutation, or set of mutations, that impairs its binding to the FcRn. In some embodiments, the Fc domain comprising a mutation, or a set of mutations, that impairs binding of the Fc to an FcRn, exhibit improved lysosomal degradation as compared to an Fc domain not comprising the mutation, or set of mutations, that impairs its binding to the FcRn. Without being bound to any particular theory, a Fc molecule that has improved lysosomal degradation will lead to the antigen being released from the Fc molecule through the lysosomal degradation pathway, and, therefore, improved antigen presentation on the surface of a cell, such as those cells provided herein. Therefore, in some embodiments, methods of providing antigen presentation on the surface of a cell are provided, wherein the antigen is linked or fused to a Fc that comprises a mutation that impairs the Fc’s binding to the FcRn. In some embodiments, the Fc domain comprises a mutation, or a set of mutations, selected from H310A, and / or G435A, wherein the mutation, or set of mutations impairs binding of the Fc to the FcRn. In some embodiments, the Fc region is an effectorless Fc region, and the Fc region does not bind, or has reduced affinity, to FcRn.

[0085] In some embodiments, the mutations in the Fc region, which is according to the known numbering system, are selected from the group consisting of: L234A, L235A, L234F, L235E, P329G, P329A, P331S, N297A, N297G, N297Q, G236A, A33OS, S239D, I332E, S267E, H268F, S324T, Y296W, T299A, V3O8P, H310A, R409K, Y435H, T307A, T309A, T309K, K322A, K326W, K334W, K326A, K334A, G237A, P238S, H268A, M252Y, S254T, T256E, M428L, N434S, or any combination thereof. In some embodiments, the Fc comprises a mutation apositions M242 and / or S254 and / or T256. In some embodiments, the Fc comprises M242Y and / or S254T and / or T256E mutations, which can be referred to as “YTE” mutations. In some embodiments, the Fc comprises a mutation at position M428 and / or N434. In some embodiments, the Fc comprises M428L and / or N434S mutations, which can be referred to as “LS” mutations. In some embodiments, the Fc comprises a mutation at L234 and / or L235 and / or G237. In some embodiments, the Fc comprises L234A and / or L235A mutations, which can be referred to as “LALA” mutations. In some embodiments, the Fc comprises L234A, L235A, and G237A19IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT mutations, which can be referred to as “LALAGA” or “AAA”. Tn some embodiments, the Fc comprises L234F, and L235E mutations, which can be referred to as “LAFE” mutations. In some embodiments, the Fc comprises L234A, L235A, and P329G mutations, which can be referred to as “LALAPG” mutations. In some embodiments, the Fc comprises L234A, L235A, P329G, and P331S mutations, which can be referred to as “LALAPGS” mutations. In some embodiments, the Fc comprises L234A, L235A, and P329S mutations, which can be referred to as “LALAPS” mutations. In some embodiments, the Fc comprises L234A, L235A, and P329A mutations, which can be referred to as “LALAPA” mutations. In some embodiments, the Fc comprises a N297A mutation. In some embodiments, the Fc mutations comprises a N297G mutation. In some embodiments, the Fc comprises a N297Q mutation. In some embodiments, the Fc comprises a P329G mutation. In some embodiments, the Fc comprises G236A, A330S, and P331S mutations, which can be referred to as “GASDALIE” mutations. In some embodiments, the Fc comprises S239D and I332E mutations, which can be referred to as “SIE” mutations. In some embodiments, the Fc comprises S267E, H268F, S324T, and I332E mutations, which can be referred to as “SEHFJSTIE” mutations. In some embodiments, the Fc comprises Y296W, T299A, and V3O8P mutations, which can be referred to as “YTEV” mutations. In some embodiments, the Fc comprises H310A, R409K, and Y435H mutations, which can be referred to as “HRY” mutations. In some embodiments, the Fc comprises T307A and T309A mutations, which can be referred to as “TATA” mutations. In some embodiments, the Fc comprises T307A and T309K mutations, which can be referred to as “TAKA” mutations. In some embodiments, the Fc comprises a K322A mutation. In some embodiments, the Fc comprises K326W and K334W mutations, which can be referred to as “WKWK” mutations. In some embodiments, the Fc comprises K326A and K334A mutations, which can be referred to as “AA” mutations. In some embodiments, the Fc comprises L234A, L235A, G237A, P238S, H268A, A33OS, and P331S mutations.

[0086] In some embodiments, the Fc comprises a H3I0A mutation. In some embodiments, the Fc comprises a H435A mutation. In some embodiments, the Fc comprises H310A and H435A mutations. In some embodiments, the Fc mutations comprise L234A, L235A, and H310A. In some embodiments, the Fc mutations comprise L234F, L235E, and H310A. In some embodiments, the Fc mutations comprise L234A, L235A, P329G, and H310A. In some embodiments, the Fc mutations comprise L234A, L235A, P329G, P331S, and H310A. In some embodiments, the Fc mutations comprise L234A, L235A, P329S, and H310A. In some embodiments, the Fc mutations20IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT comprise N297A, and H310A. In some embodiments, the Fc mutations comprise N297G, and H310A. In some embodiments, the Fc mutations comprise N297Q, and H310A. In some embodiments, the Fc mutations comprise P329G, and H310A. In some embodiments, the Fc mutations comprise G236A, A330S, P331S, and H310A. In some embodiments, the Fc mutations comprise S239D, I332E, and H310A. In some embodiments, the Fc mutations comprise S267E, H268F, S324T, I332E, and H310A. In some embodiments, the Fc mutations comprise Y296W, T299A, V3O8P, and H310A. In some embodiments, the Fc mutations comprise H310A, R409K, Y435H, and H310A. In some embodiments, the Fc mutations comprise T307A, T309A, and H310A. In some embodiments, the Fc mutations comprise T307A, T309K, and H310A. In some embodiments, the Fc mutations comprise K322A, and H310A. In some embodiments, the Fc mutations comprise K326W, K334W, and H310A. In some embodiments, the Fc mutations comprise K326A, K334A, and H310A. In some embodiments, the Fc mutations comprise L234A, L235A, and H435A. In some embodiments, the Fc mutations comprise L234F, L235E, and H435A. In some embodiments, the Fc mutations comprise L234A, L235A, P329G, and H435A. In some embodiments, the Fc mutations comprise L234A, L235A, P329G, P331S, and H435A. In some embodiments, the Fc mutations comprise L234A, L235A, P329S, and H435A. In some embodiments, the Fc mutations comprise N297A, and H435A. In some embodiments, the Fc mutations comprise N297G, and H435A. In some embodiments, the Fc mutations comprise N297Q, and H435A. In some embodiments, the Fc mutations comprise P329G, and H435A. In some embodiments, the Fc mutations comprise G236A, A330S, P331S, and H435A. In some embodiments, the Fc mutations comprise S239D, I332E, and H435A. In some embodiments, the Fc mutations comprise S267E, H268F, S324T, I332E, and H435A. In some embodiments, the Fc mutations comprise Y296W, T299A, V308P, and H435A. In some embodiments, the Fc mutations comprise H435A, R409K, Y435H, and H435A. In some embodiments, the Fc mutations comprise T307A, T309A, and H435A. In some embodiments, the Fc mutations comprise T307A, T309K, and H435A. In some embodiments, the Fc mutations comprise K322A, and H435A. In some embodiments, the Fc mutations comprise K326W, K334W, and H435A. In some embodiments, the Fc mutations comprise K326A, K334A, and H435A. In some embodiments, the Fc mutations comprise L234A, L235A, H310, and H435A. In some embodiments, the Fc mutations comprise L234F, L235E, H310, and H435A. In some embodiments, the Fc mutations comprise L234A, L235A, P329G, H310, and H435A. In some embodiments, the Fc mutations comprise L234A,21IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTL235A, P329G, P331S, H310, and H435A. In some embodiments, the Fc mutations comprise L234A, L235A, P329S, H310, and H435A. In some embodiments, the Fc mutations comprise N297A, H310, and H435A. In some embodiments, the Fc mutations comprise N297G, H310, and H435A. In some embodiments, the Fc mutations comprise N297Q, H310, and H435A. In some embodiments, the Fc mutations comprise P329G, H310, and H435A. In some embodiments, the Fc mutations comprise G236A, A330S, P331S, H310, and H435A. In some embodiments, the Fc mutations comprise S239D, I332E, H310, and H435A. In some embodiments, the Fc mutations comprise S267E, H268F, S324T, I332E, H310, and H435A. In some embodiments, the Fc mutations comprise Y296W, T299A, V308P, H310, and H435A. In some embodiments, the Fc mutations comprise H435A, R409K, Y435H, H310, and H435A. In some embodiments, the Fc mutations comprise T307A, T309A, H310, and H435A. In some embodiments, the Fc mutations comprise T307A, T309K, H310, and H435A. In some embodiments, the Fc mutations comprise K322A, H310, and H435A. In some embodiments, the Fc mutations comprise K326W, K334W, H310, and H435A. In some embodiments, the Fc mutations comprise K326A, K334A, H310, and H435A.

[0087] The mutations and positions of the Fc region, which can also be referred to as the Fc domain, are according to Kabat numbering.

[0088] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a heavy chain complementarity domain 1 (HCDR1), a HCDR2, and a HCDR3 and the VL comprises a light chain complementarity domain 1 (LCDR1) a LCDR2, and a LCDR3 as provided for in Table 1 below, which illustrates the CDR sequences based on Kabat numbering.TABLE 1: CDRs of Exemplary anti-GIP antibodies - Kabat numbering22IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT

[0089] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 as provided for in Table 2 below, which illustrates the CDR sequences based on Chothia numbering.TABLE 2: CDRs of Exemplary anti-GIP antibodies - Chothia numbering

[0090] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 as provided for in Table 3 below, which illustrates the CDR sequences based on IMGT numbering.TABLE 3: CDRs of Exemplary anti-GIP antibodies - IMGT numbering23IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT

[0091] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy or light chain CDR sequence as provided in the tables above. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy or light chain CDR sequence as provided in the tables above and binds to non-human primate GIP In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy or light chain CDR sequence as provided in the tables above and binds to human GIP.

[0092] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a light chain CDR having a sequence selected from SEQ ID NOs: 4-6, 18, 19, 27, 28, 31, or 34. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a light chain CDR having the amino acid sequence of SEQ ID NO: 4. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a light chain CDR having the amino acid sequence of SEQ ID NO: 5. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a light chain CDR having the amino acid sequence of SEQ ID NO: 6. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a light chain CDR having the amino acid sequence of SEQ ID NO: 18. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a light chain CDR having the amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a light chain CDR having the amino acid sequence of SEQ ID NO: 27. In some embodiments, the anti-GIP antibody, or antigenbinding fragment thereof, comprises a light chain CDR having the amino acid sequence of SEQ ID NO: 28. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a light chain CDR having the amino acid sequence of SEQ ID NO: 31. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a light chain CDR having the amino acid sequence of SEQ ID NO: 34. The CDRs referenced in the24IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT embodiments throughout the present disclosure are primarily of Kabat numbering system. However, any such Kabat CDR may be interchanged with the CDRs that arc characterized by different formats, such as Chothia and IMGT.

[0093] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a light chain variable region having a LCDR1, a LCDR2, and a LCDR3, wherein the LCDR1 has a sequence of SEQ ID NO: 4, the LCDR2 has a sequence of SEQ ID NO: 5, and the LCDR3 has a sequence of SEQ ID NO: 6. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a light chain variable region having a LCDR1, a LCDR2, and a LCDR3, wherein the LCDR1 has a sequence of SEQ ID NO: 12, the LCDR2 has a sequence of RT, and the LCDR3 has a sequence of SEQ ID NO: 6.

[0094] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a light chain variable region having a LCDR1, a LCDR2, and a LCDR3, wherein the LCDR1 has a sequence of SEQ ID NO: 18, the LCDR2 has a sequence of SEQ ID NO: 5, and the LCDR3 has a sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a light chain variable region having a LCDR1, a LCDR2, and a LCDR3, wherein the LCDR1 has a sequence of SEQ ID NO: 23, the LCDR2 has a sequence of RT, and the LCDR3 has a sequence of SEQ ID NO: 19.

[0095] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a light chain variable region having a LCDR1, a LCDR2, and a LCDR3, wherein the LCDR1 has a sequence of SEQ ID NO: 27, the LCDR2 has a sequence of SEQ ID NO: 28, and the LCDR3 has a sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a light chain variable region having a LCDR1, a LCDR2, and a LCDR3, wherein the LCDR1 has a sequence of SEQ ID NO: 23, the LCDR2 has a sequence of RT, and the LCDR3 has a sequence of SEQ ID NO: 19.

[0096] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a light chain variable region having a LCDR1, a LCDR2, and a LCDR3, wherein the LCDR1 has a sequence of SEQ ID NO: 27, the LCDR2 has a sequence of SEQ ID NO: 31, and the LCDR3 has a sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a light chain variable region having a LCDR1, a LCDR2, and a LCDR3, wherein the LCDR1 has a sequence of SEQ ID NO: 23, the LCDR2 has a sequence of RT, and the LCDR3 has a sequence of SEQ ID NO: 19.25IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT

[0097] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a light chain variable region having a LCDR1, a LCDR2, and a LCDR3, wherein the LCDR1 has a sequence of SEQ ID NO: 27, the LCDR2 has a sequence of SEQ ID NO: 34, and the LCDR3 has a sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a light chain variable region having a LCDR1, a LCDR2, and a LCDR3, wherein the LCDR1 has a sequence of SEQ ID NO: 23, the LCDR2 has a sequence of RT, and the LCDR3 has a sequence of SEQ ID NO: 19.

[0098] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy chain CDR having a sequence selected from SEQ ID NOs: 1-3, 15-17, or 26. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy chain CDR having the amino acid sequence of SEQ ID NO: 1. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy chain CDR having the amino acid sequence of SEQ ID NO: 2. In some embodiments, the anti-GIP antibody, or antigenbinding fragment thereof, comprises a heavy chain CDR having the amino acid sequence of SEQ ID NO: 3. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy chain CDR having the amino acid sequence of SEQ ID NO: 15. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy chain CDR having the amino acid sequence of SEQ ID NO: 16. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy chain CDR having the amino acid sequence of SEQ ID NO: 17. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy chain CDR having the amino acid sequence of SEQ ID NO: 26. The CDRs referenced in the embodiments throughout the present disclosure are primarily of Kabat numbering system. However, any such Kabat CDR may be interchanged with the CDRs that are characterized by different formats, such as Chothia and IMGT.

[0099] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy chain variable region having a HCDR1, a HCDR2, and a HCDR3, wherein the HCDR1 has a sequence of SEQ ID NO: 1, the HCDR2 has a sequence of SEQ ID NO: 2, and the HCDR3 has a sequence of SEQ ID NO: 3. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy chain variable region having a HCDR1, a HCDR2, and a HCDR3, wherein the HCDR1 has a sequence of SEQ ID NO: 7, the HCDR2 has a sequence of SEQ ID NO: 8, and the HCDR3 has a sequence of SEQ ID NO: 3. In some26IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy chain variable region having a HCDR1, a HCDR2, and a HCDR3, wherein the HCDR1 has a sequence of SEQ ID NO: 9, the HCDR2 has a sequence of SEQ ID NO: 10, and the HCDR3 has a sequence of SEQ ID NO: 11.

[0100] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy chain variable region having a HCDR1, a HCDR2, and a HCDR3, wherein the HCDR1 has a sequence of SEQ ID NO: 15, the HCDR2 has a sequence of SEQ ID NO: 16, and the HCDR3 has a sequence of SEQ ID NO: 17. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy chain variable region having a HCDR1, a HCDR2, and a HCDR3, wherein the HCDR1 has a sequence of SEQ ID NO: 20, the HCDR2 has a sequence of SEQ ID NO: 8, and the HCDR3 has a sequence of SEQ ID NO: 17. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy chain variable region having a HCDR1, a HCDR2, and a HCDR3, wherein the HCDR1 has a sequence of SEQ ID NO: 21, the HCDR2 has a sequence of SEQ ID NO: 10, and the HCDR3 has a sequence of SEQ ID NO: 22.

[0101] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy chain variable region having a HCDR1, a HCDR2, and a HCDR3, wherein the HCDR1 has a sequence of SEQ ID NO: 15, the HCDR2 has a sequence of SEQ ID NO: 26, and the HCDR3 has a sequence of SEQ ID NO: 17. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy chain variable region having a HCDR1, a HCDR2, and a HCDR3, wherein the HCDR1 has a sequence of SEQ ID NO: 20, the HCDR2 has a sequence of SEQ ID NO: 8, and the HCDR3 has a sequence of SEQ ID NO: 17. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy chain variable region having a HCDR1, a HCDR2, and a HCDR3, wherein the HCDR1 has a sequence of SEQ ID NO: 21, the HCDR2 has a sequence of SEQ ID NO: 10, and the HCDR3 has a sequence of SEQ ID NO: 22.

[0102] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises: (i) a light chain having any one of the foregoing recited combination of LCDR1, LCDR2, and LCDR3 sequences; and (ii) a heavy chain having any one of the foregoing recited combinations of HCDR1, HCDR2, and HCDR3 sequences.27IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT

[0103] The different CDR motifs can be combined in any combination, including those not depicted in the table above. For example, the following embodiments arc provided as non-limiting examples of such combinations.

[0104] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 4; the light chain CDR2 sequence has the amino acid sequence of sequence of SEQ ID NO: 5; and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 6; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 1, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 2, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 3; or variants of any of the foregoing.

[0105] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 4; the light chain CDR2 sequence has the amino acid sequence of sequence of SEQ ID NO: 5; and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 6; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 7, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 8, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 3; or variants of any of the foregoing.

[0106] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 12; the light chain CDR2 sequence has the amino acid sequence of sequence of RT; and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 6; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 9, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 10, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 11; or variants of any of the foregoing.28IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT

[0107] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 18; the light chain CDR2 sequence has the amino acid sequence of sequence of SEQ ID NO: 5; and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 15, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 16, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 17; or variants of any of the foregoing.

[0108] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 18; the light chain CDR2 sequence has the amino acid sequence of sequence of SEQ ID NO: 5; and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 20, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 8, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 17; or variants of any of the foregoing.

[0109] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 23; the light chain CDR2 sequence has the amino acid sequence of sequence of RT; and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 21, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 10, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 22; or variants of any of the foregoing.

[0110] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 27; the light chain CDR2 sequence has the amino acid sequence of sequence of SEQ ID NO: 28;29IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 15, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 26, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 17; or variants of any of the foregoing.

[0111] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 27; the light chain CDR2 sequence has the amino acid sequence of sequence of SEQ ID NO: 28; and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 20, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 8, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 17; or variants of any of the foregoing.

[0112] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 27; the light chain CDR2 sequence has the amino acid sequence of sequence of SEQ ID NO: 31; and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 15, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 26, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 17; or variants of any of the foregoing.

[0113] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 27; the light chain CDR2 sequence has the amino acid sequence of sequence of SEQ ID NO: 31; and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 20, the heavy chain30IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTCDR2 sequence has the amino acid sequence of SEQ ID NO: 8, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 17; or variants of any of the foregoing.

[0114] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 27; the light chain CDR2 sequence has the amino acid sequence of sequence of SEQ ID NO: 34; and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 15, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 26, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 17; or variants of any of the foregoing.

[0115] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 27; the light chain CDR2 sequence has the amino acid sequence of sequence of SEQ ID NO: 34; and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 20, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 8, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 17; or variants of any of the foregoing.

[0116] In some embodiments, the light chain variable region CDR1 is replaced with any of the other light chain CDR1 sequences. In some embodiments, the light chain variable region CDR2 is replaced with any of the other light chain CDR2 sequences. In some embodiments, the light chain variable region CDR3 is replaced with any of the other light chain CDR3 sequences. In some embodiments, the heavy chain variable region CDR1 is replaced with any of the other heavy chain CDR1 sequences. In some embodiments, the heavy chain variable region CDR2 is replaced with any of the other heavy chain CDR2 sequences. In some embodiments, the heavy chain variable region CDR3 is replaced with any of the other heavy chain CDR3 sequences.

[0117] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy chain variable region (VH) having one of the following sequences, or a variant thereof:31IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTTABLE 4: Sequences of the VH region of exemplary anti-GIP antibodies

[0118] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a light chain variable region (VL) having one of the following sequences, or a variant thereof:TABLE 5: Sequences of the VL region of exemplary anti-GIP antibodies32IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT

[0119] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH comprising an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 29, SEQ ID NO: 13, SEQ ID NO: 24, SEQ ID NO: 32, or SEQ ID NO: 35. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH comprising an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 29, SEQ ID NO: 13, SEQ ID NO: 24, SEQ ID NO: 32, or SEQ ID NO: 35. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 29, SEQ ID NO: 13, SEQ ID NO: 24, SEQ ID NO: 32, or SEQ ID NO: 35. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 29, SEQ ID NO: 13, SEQ ID NO: 24, SEQ ID NO: 32, or SEQ ID NO: 35. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH comprising an amino acid sequence having at least 98% identity to the amino acid sequence of SEQ ID NO: 29, SEQ ID NO: 13, SEQ ID NO: 24, SEQ ID NO: 32, or SEQ ID NO: 35. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH comprising an amino acid sequence of SEQ ID NO: 29, SEQ ID NO: 13, SEQ ID NO: 24, SEQ ID NO: 32, or SEQ ID NO: 35. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH comprising an amino acid sequence of SEQ ID NO: 29. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH comprising an amino acid sequence of SEQ ID NO: 13. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH comprising an amino acid sequence of SEQ ID NO: 24. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH comprising an amino acid sequence of SEQ ID NO: 32. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a Vn comprising an amino acid sequence of SEQ ID NO: 35.

[0120] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VL comprising an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 30, SEQ ID NO: 14, SEQ ID NO: 25, SEQ ID NO: 33, or SEQ ID NO: 36. In33IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VL comprising an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 30, SEQ ID NO: 14, SEQ ID NO: 25, SEQ ID NO: 33, or SEQ ID NO: 36. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VL comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 30, SEQ ID NO: 14, SEQ ID NO: 25, SEQ ID NO: 33, or SEQ ID NO: 36. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 30, SEQ ID NO: 14, SEQ ID NO: 25, SEQ ID NO: 33, or SEQ ID NO: 36. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VL comprising an amino acid sequence having at least 98% identity to the amino acid sequence of SEQ ID NO: 30, SEQ ID NO: 14, SEQ ID NO: 25, SEQ ID NO: 33, or SEQ ID NO: 36. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VL comprising an amino acid sequence of SEQ ID NO: 30, SEQ ID NO: 14, SEQ ID NO: 25, SEQ ID NO: 33, or SEQ ID NO: 36. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VL comprising an amino acid sequence of SEQ ID NO: 30. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VL comprising an amino acid sequence of SEQ ID NO: 14. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VL comprising an amino acid sequence of SEQ ID NO: 25. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VL comprising an amino acid sequence of SEQ ID NO: 33. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VL comprising an amino acid sequence of SEQ ID NO: 36.

[0121] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 13; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 14. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%,34IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 13; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 14; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 1, a HCDR2 having an amino acid sequence of SEQ ID NO: 2, and a HCDR3 having an amino acid sequence of SEQ ID NO: 3. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a Vn and a VL, wherein the Vn comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 13; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 14; provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 4, a LCDR2 having an amino acid sequence of SEQ ID NO: 5, and a LCDR3 having an amino acid sequence of SEQ ID NO: 6. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the Vucomprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 13; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 14; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 1, a HCDR2 having an amino acid sequence of SEQ ID NO: 2, and a HCDR3 having an amino acid sequence of SEQ ID NO: 3; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 4, a LCDR2 having an amino acid sequence of SEQ ID NO: 5, and a LCDR3 having an amino acid sequence of SEQ ID NO: 6. In some embodiments, the CDRs in the VH or VL are as set forth in the combinations provided for herein.

[0122] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the Vucomprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 13; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 14; provided that the Vu comprises a HCDR135IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT having an amino acid sequence of SEQ ID NO: 1 , wherein the HCDR1 comprises at most 1 conservative amino acid substitution, a HCDR2 having an amino acid sequence of SEQ ID NO: 2, wherein the HCDR2 comprises at most 1 conservative amino acid substitution, and a HCDR3 having an amino acid sequence of SEQ ID NO: 3 wherein the HCDR3 comprises at most 1 conservative amino acid substitution; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 4, wherein the LCDR1 comprises at most 1 conservative amino acid substitution, a LCDR2 having an amino acid sequence of SEQ ID NO: 5, wherein the LCDR2 comprises at most 1 conservative amino acid substitution, and a LCDR3 having an amino acid sequence of SEQ ID NO: 6, wherein the LCDR3 comprises at most 1 conservative amino acid substitution.

[0123] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 90%, identity to the amino acid sequence of SEQ ID NO: 13; and the VL comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 14; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 1, a HCDR2 having an amino acid sequence of SEQ ID NO: 2, and a HCDR3 having an amino acid sequence of SEQ ID NO: 3; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 4, a LCDR2 having an amino acid sequence of SEQ ID NO: 5, and a LCDR3 having an amino acid sequence of SEQ ID NO: 6. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 95%, identity to the amino acid sequence of SEQ ID NO: 13; and the VL comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 14; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 1, a HCDR2 having an amino acid sequence of SEQ ID NO: 2, and a HCDR3 having an amino acid sequence of SEQ ID NO: 3; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 4, a LCDR2 having an amino acid sequence of SEQ ID NO: 5, and a LCDR3 having an amino acid sequence of SEQ ID NO: 6. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 98%, identity to the amino acid sequence of SEQ ID NO: 13; and the VL comprises an amino acid sequence having at least 98% identity to the amino acid sequence of SEQ ID NO: 14; provided that the VH comprises a HCDR1 having an36IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT amino acid sequence of SEQ ID NO: 1 , a HCDR2 having an amino acid sequence of SEQ ID NO: 2, and a HCDR3 having an amino acid sequence of SEQ ID NO: 3; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 4, a LCDR2 having an amino acid sequence of SEQ ID NO: 5, and a LCDR3 having an amino acid sequence of SEQ ID NO: 6. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence of SEQ ID NO: 13 and the VL comprises an amino acid of SEQ ID NO: 14.

[0124] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 24; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 25. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 24; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 25; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, a HCDR2 having an amino acid sequence of SEQ ID NO: 16, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 24; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 25; provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 18, a LCDR2 having an amino acid sequence of SEQ ID NO: 5, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the Vncomprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid37IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT sequence of SEQ ID NO: 24; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 25; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, a HCDR2 having an amino acid sequence of SEQ ID NO: 16, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 18, a LCDR2 having an amino acid sequence of SEQ ID NO: 5, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19. In some embodiments, the CDRs in the VH or VL are as set forth in the combinations provided for herein.

[0125] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 24; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 25; provided that the Vu comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, wherein the HCDR1 comprises at most 1 conservative amino acid substitution, a HCDR2 having an amino acid sequence of SEQ ID NO: 16, wherein the HCDR2 comprises at most 1 conservative amino acid substitution, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17, wherein the HCDR3 comprises at most 1 conservative amino acid substitution; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 18, wherein the LCDR1 comprises at most 1 conservative amino acid substitution, a LCDR2 having an amino acid sequence of SEQ ID NO: 5, wherein the LCDR2 comprises at most 1 conservative amino acid substitution, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19, wherein the LCDR3 comprises at most 1 conservative amino acid substitution.

[0126] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 90%, identity to the amino acid sequence of SEQ ID NO: 24; and the VL comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 25; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, a HCDR2 having an amino acid sequence of SEQ ID NO: 16, and a HCDR3 having an amino acid sequence38IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT of SEQ ID NO: 17; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 18, a LCDR2 having an amino acid sequence of SEQ ID NO: 5, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 95%, identity to the amino acid sequence of SEQ ID NO: 24; and the VL comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 25; provided that the Vn comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, a HCDR2 having an amino acid sequence of SEQ ID NO: 16, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 18, a LCDR2 having an amino acid sequence of SEQ ID NO: 5, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 98%, identity to the amino acid sequence of SEQ ID NO: 24; and the VL comprises an amino acid sequence having at least 98% identity to the amino acid sequence of SEQ ID NO: 25; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, a HCDR2 having an amino acid sequence of SEQ ID NO: 16, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 18, a LCDR2 having an amino acid sequence of SEQ ID NO: 5, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence of SEQ ID NO: 24 and the VL comprises an amino acid sequence of SEQ ID NO: 25.

[0127] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 29; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 30. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 29; and the VL39IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 30; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, a HCDR2 having an amino acid sequence of SEQ ID NO: 26, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 29; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 30; provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 27, a LCDR2 having an amino acid sequence of SEQ ID NO: 28, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the Vncomprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 29; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 30; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, a HCDR2 having an amino acid sequence of SEQ ID NO: 26, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 27, a LCDR2 having an amino acid sequence of SEQ ID NO: 28, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19. In some embodiments, the CDRs in the VH or VL are as set forth in the combinations provided for herein.

[0128] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a Vn and a VL, wherein the Vncomprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 29; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 30; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, wherein the HCDR1 comprises at most 140IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT conservative amino acid substitution, a HCDR2 having an amino acid sequence of SEQ ID NO: 26, wherein the HCDR2 comprises at most 1 conservative amino acid substitution, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17, wherein the HCDR3 comprises at most 1 conservative amino acid substitution; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 27, wherein the LCDR1 comprises at most 1 conservative amino acid substitution, a LCDR2 having an amino acid sequence of SEQ ID NO: 28, wherein the LCDR2 comprises at most 1 conservative amino acid substitution, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19, wherein the LCDR3 comprises at most 1 conservative amino acid substitution.

[0129] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 29; and the VL comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 30; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, a HCDR2 having an amino acid sequence of SEQ ID NO: 26, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 27, a LCDR2 having an amino acid sequence of SEQ ID NO: 28, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 29; and the VL comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 30; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, a HCDR2 having an amino acid sequence of SEQ ID NO: 26, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 27, a LCDR2 having an amino acid sequence of SEQ ID NO: 28, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 98% identity to the amino acid sequence of SEQ ID NO: 29; and the VL comprises an amino acid sequence having at least 98% identity to the amino acid sequence of SEQ ID NO: 30; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, a HCDR2 having an amino acid sequence of SEQ ID41IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTNO: 26, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 27, a LCDR2 having an amino acid sequence of SEQ ID NO: 28, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence of SEQ ID NO: 29; and the VL comprises an amino acid sequence of SEQ ID NO: 30.

[0130] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 32; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 33. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 32; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 33; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, a HCDR2 having an amino acid sequence of SEQ ID NO: 26, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 32; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 33; provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 27, a LCDR2 having an amino acid sequence of SEQ ID NO: 31, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the Vucomprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 32; and the VL comprises an amino acid sequence having at least 85%,42IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 33; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, a HCDR2 having an amino acid sequence of SEQ ID NO: 26, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 27, a LCDR2 having an amino acid sequence of SEQ ID NO: 31, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19. In some embodiments, the CDRs in the Vn or VL are as set forth in the combinations provided for herein.

[0131] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 32; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 33; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, wherein the HCDR1 comprises at most 1 conservative amino acid substitution, a HCDR2 having an amino acid sequence of SEQ ID NO: 26, wherein the HCDR2 comprises at most 1 conservative amino acid substitution, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17, wherein the HCDR3 comprises at most 1 conservative amino acid substitution; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 27, wherein the LCDR1 comprises at most 1 conservative amino acid substitution, a LCDR2 having an amino acid sequence of SEQ ID NO: 31, wherein the LCDR2 comprises at most 1 conservative amino acid substitution, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19, wherein the LCDR3 comprises at most 1 conservative amino acid substitution.

[0132] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the Vn comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 32; and the VL comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 33; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, a HCDR2 having an amino acid sequence of SEQ ID NO: 26, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17; and provided that the VL comprises a LCDR1 having an amino acid sequence43IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT of SEQ ID NO: 27, a LCDR2 having an amino acid sequence of SEQ ID NO: 31 , and a LCDR3 having an amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 32; and the VL comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 33; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, a HCDR2 having an amino acid sequence of SEQ ID NO: 26, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 27, a LCDR2 having an amino acid sequence of SEQ ID NO: 31, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 98% identity to the amino acid sequence of SEQ ID NO: 32; and the VL comprises an amino acid sequence having at least 98% identity to the amino acid sequence of SEQ ID NO: 33; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, a HCDR2 having an amino acid sequence of SEQ ID NO: 26, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 27, a LCDR2 having an amino acid sequence of SEQ ID NO: 31, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence of SEQ ID NO: 32 and the VL comprises an amino acid sequence of SEQ ID NO: 33.

[0133] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 35; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 36. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 35; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%,44IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 36; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, a HCDR2 having an amino acid sequence of SEQ ID NO: 26, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 35; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 36; provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 27, a LCDR2 having an amino acid sequence of SEQ ID NO: 34, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the Vucomprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 35; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 36; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, a HCDR2 having an amino acid sequence of SEQ ID NO: 26, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 27, a LCDR2 having an amino acid sequence of SEQ ID NO: 34, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19. In some embodiments, the CDRs in the VH or VL are as set forth in the combinations provided for herein.

[0134] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the Vucomprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 35; and the VL comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 36; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, wherein the HCDR1 comprises at most 1 conservative amino acid substitution, a HCDR2 having an amino acid sequence of SEQ ID NO:45IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT26, wherein the HCDR2 comprises at most 1 conservative amino acid substitution, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17, wherein the HCDR3 comprises at most 1 conservative amino acid substitution; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 27, wherein the LCDR1 comprises at most 1 conservative amino acid substitution, a LCDR2 having an amino acid sequence of SEQ ID NO: 34, wherein the LCDR2 comprises at most 1 conservative amino acid substitution, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19, wherein the LCDR3 comprises at most 1 conservative amino acid substitution.

[0135] In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 35; and the VL comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 36; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, a HCDR2 having an amino acid sequence of SEQ ID NO: 26, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 27, a LCDR2 having an amino acid sequence of SEQ ID NO: 34, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a VH and a VL, wherein the VH comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 35; and the VL comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 36; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, a HCDR2 having an amino acid sequence of SEQ ID NO: 26, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17; and provided that the VL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 27, a LCDR2 having an amino acid sequence of SEQ ID NO: 34, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a Vn and a VL, wherein the VH comprises an amino acid sequence having at least 98% identity to the amino acid sequence of SEQ ID NO: 35; and the VL comprises an amino acid sequence having at least 98% identity to the amino acid sequence of SEQ ID NO: 36; provided that the VH comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 15, a HCDR2 having an amino acid sequence of SEQ ID NO: 26, and a HCDR3 having an amino acid sequence of SEQ ID NO: 17; and provided that the46IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTVL comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 27, a LCDR2 having an amino acid sequence of SEQ ID NO: 34, and a LCDR3 having an amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, comprises a Vu and a VL, wherein the Vu comprises an amino acid sequence of SEQ ID NO: 35 and the VL comprises an amino acid sequence of SEQ ID NO: 36.

[0136] In some embodiments, the anti-GIP antibody, or antigen binding fragment thereof, comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC comprise one of the following sequences, or a variant thereof:

[0137] In some embodiments, the anti-GIP antibody, or antigen binding fragment thereof, comprises a HC comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 37 and a LC comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 144. In some embodiments, the anti-GIP antibody, or antigen binding fragment thereof, comprises a HC comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 37 and a LC47IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 144. In some embodiments, the anti-GIP antibody, or antigen binding fragment thereof, comprises a HC comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 37 and a LC comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 144. In some embodiments, the anti-GIP antibody, or antigen binding fragment thereof, comprises a HC comprising an amino acid sequence having at least 98% identity to the amino acid sequence of SEQ ID NO: 37 and a LC comprising an amino acid sequence having at least 98% identity to the amino acid sequence of SEQ ID NO: 144. In some embodiments, the anti-GIP antibody, or antigen binding fragment thereof, comprises a HC comprising the amino acid sequence of SEQ ID NO: 37 and a LC comprising the amino acid sequence of SEQ ID NO: 144.

[0138] In some embodiments, the anti-GIP antibody, or antigen binding fragment thereof, comprises a HC comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 37 and a LC comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 144, provided that the HC comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 15, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 17, and provided that the LC comprising a LCDR1 comprising the amino acid sequence of SEQ ID NO: 27, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 28, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen binding fragment thereof, comprises a HC comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 37 and a LC comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 144, provided that the HC comprises an HCDRI comprising the amino acid sequence of SEQ ID NO: 15, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 17, and provided that the LC comprising a LCDR1 comprising the amino acid sequence of SEQ ID NO: 27, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 28, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen binding fragment thereof, comprises a HC comprising an amino acid sequence having at48IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT least 95% identity to the amino acid sequence of SEQ ID NO: 37 and a LC comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 144, provided that the HC comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 15, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 17, and provided that the LC comprising a LCDR1 comprising the amino acid sequence of SEQ ID NO: 27, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 28, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen binding fragment thereof, comprises a HC comprising an amino acid sequence having at least 98% identity to the amino acid sequence of SEQ ID NO: 37 and a LC comprising an amino acid sequence having at least 98% identity to the amino acid sequence of SEQ ID NO: 144, provided that the HC comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 15, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 17, and provided that the LC comprising a LCDR1 comprising the amino acid sequence of SEQ ID NO: 27, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 28, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-GIP antibody, or antigen binding fragment thereof, comprises a HC comprising the amino acid sequence of SEQ ID NO: 37 and a LC comprising the amino acid sequence of SEQ ID NO: 144.

[0139] In some embodiments, an anti-GIP antibody, or antigen-binding fragment thereof, as provided for herein, is conjugated to a biologically active peptide. In some embodiments, an anti- GIP antibody, or antigen-binding fragment thereof, as provided for herein, is not conjugated to a biologically active peptide. In some embodiments, an anti-GIP antibody, or antigen-binding fragment thereof, as provided for herein, is administered with a biologically active peptide. In some embodiments, an anti-GIP antibody, or antigen-binding fragment thereof, as provided for herein, is co-administered with a biologically active peptide. In some embodiments, an anti-GIP antibody, or antigen-binding fragment thereof, as provided for herein, is co-formulated with a biologically active peptide.

[0140] In some embodiments, the biologically active peptide comprises a glucagon like peptide 1 receptor (GLP-1R) agonist, a glucagon like peptide 2 receptor (GLP-2R) agonist, a glucagon49IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT receptor agonist. GLP-1R agonists are known in the art, and any such GLP-1R agonist is within the scope of the present disclosure. Non-limiting examples of GLP- 1R agonists include liraglutidc, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, and SEQ ID NO: 121. The sequences of SEQ ID NOs: 38-121 are as provided in Table 6 below:TABLE 6: Sequences of exemplary GLP-1R agonists50IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT51IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT52IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT53IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT54IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT55IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT

[0141] In some embodiments, the GLP-1R agonist is liraglutide. In some embodiments, the GLP- 1R agonist is albiglutide. In some embodiments, the GLP-1R agonist is taspoglutide. In some embodiments, the GLP-1R agonist is semaglutide. In some embodiments, the GLP-1R agonist is LY2428757. In some embodiments, the GLP-1R agonist is SEQ ID NO: 38. In some embodiments, the GLP-1R agonist is SEQ ID NO 39. In some embodiments, the GLP-1R agonist is SEQ ID NO: 40. In some embodiments, the GLP-1R agonist is SEQ ID NO: 41. In some embodiments, the GLP-1R agonist is SEQ ID NO 42. In some embodiments, the GLP-1R agonist is SEQ ID NO: 43. In some embodiments, the GLP-1R agonist is SEQ ID NO: 44. In some embodiments, the GLP-1R agonist is SEQ ID NO 45. In some embodiments, the GLP-1R agonist is SEQ ID NO: 46. In some embodiments, the GLP-1R agonist is SEQ ID NO: 47. In some embodiments, the GLP-1R agonist is SEQ ID NO 48. In some embodiments, the GLP-1R agonist is SEQ ID NO: 49. In some embodiments, the GLP-1R agonist is SEQ ID NO: 50. In some embodiments, the GLP-1R agonist is SEQ ID NO 51 . In some embodiments, the GLP-1R agonist is SEQ ID NO: 52. In some embodiments, the GLP-1R agonist is SEQ ID NO: 53. In some embodiments, the GLP-1R agonist is SEQ ID NO 54. In some embodiments, the GLP-1R agonist is SEQ ID NO: 55. In some embodiments, the GLP-1R agonist is SEQ ID NO: 56. In some embodiments, the GLP-1R agonist is SEQ ID NO 57. In some embodiments, the GLP-1R agonist is SEQ ID NO: 58. In some embodiments, the GLP-1R agonist is SEQ ID NO: 59. In some embodiments, the GLP-1R agonist is SEQ ID NO 60. In some embodiments, the GLP-1R agonist56IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT is SEQ ID NO: 61. In some embodiments, the GLP-1R agonist is SEQ ID NO: 62. In some embodiments, the GLP-1R agonist is SEQ ID NO: 63. In some embodiments, the GLP-1R agonist is SEQ ID NO: 64. In some embodiments, the GLP-1R agonist is SEQ ID NO: 65. In some embodiments, the GLP-1R agonist is SEQ ID NO: 66. In some embodiments, the GLP-1R agonist is SEQ ID NO: 67. In some embodiments, the GLP-1R agonist is SEQ ID NO: 68. In some embodiments, the GLP-1R agonist is SEQ ID NO: 69. In some embodiments, the GLP-1R agonist is SEQ ID NO: 70. In some embodiments, the GLP-1R agonist is SEQ ID NO: 71. In some embodiments, the GLP-1R agonist is SEQ ID NO: 72. In some embodiments, the GLP-1R agonist is SEQ ID NO: 73. In some embodiments, the GLP-1R agonist is SEQ ID NO: 74. In some embodiments, the GLP-1R agonist is SEQ ID NO: 75. In some embodiments, the GLP-1R agonist is SEQ ID NO: 76. In some embodiments, the GLP-1R agonist is SEQ ID NO: 77. In some embodiments, the GLP-1R agonist is SEQ ID NO: 78. In some embodiments, the GLP-1R agonist is SEQ ID NO: 79. In some embodiments, the GLP-1R agonist is SEQ ID NO: 80. In some embodiments, the GLP-1R agonist is SEQ ID NO: 81. In some embodiments, the GLP-1R agonist is SEQ ID NO: 82. In some embodiments, the GLP-1R agonist is SEQ ID NO: 83. In some embodiments, the GLP-1R agonist is SEQ ID NO: 84. In some embodiments, the GLP-1R agonist is SEQ ID NO: 85. In some embodiments, the GLP-1R agonist is SEQ ID NO: 86. In some embodiments, the GLP-1R agonist is SEQ ID NO: 87. In some embodiments, the GLP-1R agonist is SEQ ID NO: 88. In some embodiments, the GLP-1R agonist is SEQ ID NO: 89. In some embodiments, the GLP-1R agonist is SEQ ID NO: 90. In some embodiments, the GLP-1R agonist is SEQ ID NO: 91. In some embodiments, the GLP-1R agonist is SEQ ID NO: 92. In some embodiments, the GLP-1R agonist is SEQ ID NO: 93. In some embodiments, the GLP-1R agonist is SEQ ID NO: 94. In some embodiments, the GLP-1R agonist is SEQ ID NO: 95. In some embodiments, the GLP-1R agonist is SEQ ID NO: 96. In some embodiments, the GLP-1R agonist is SEQ ID NO: 97. In some embodiments, the GLP-1R agonist is SEQ ID NO: 98. In some embodiments, the GLP-1R agonist is SEQ ID NO: 99. In some embodiments, the GLP-1R agonist is SEQ ID NO: 100. In some embodiments, the GLP-1R agonist is SEQ ID NO: 101. In some embodiments, the GLP-1R agonist is SEQ ID NO: 102. In some embodiments, the GLP-1R agonist is SEQ ID NO: 103. In some embodiments, the GLP-1R agonist is SEQ ID NO: 104. In some embodiments, the GLP-1R agonist is SEQ ID NO: 105. In some embodiments, the GLP-1R agonist is SEQ ID NO: 106. In some embodiments, the GLP-1R agonist is SEQ ID NO: 107. In57IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT some embodiments, the GLP-1R agonist is SEQ TD NO: 108. In some embodiments, the GLP-1R agonist is SEQ ID NO: 109. In some embodiments, the GLP-1R agonist is SEQ ID NO: 110. In some embodiments, the GLP-1R agonist is SEQ ID NO: 111. In some embodiments, the GLP-1R agonist is SEQ ID NO: 112. In some embodiments, the GLP-1R agonist is SEQ ID NO: 113. In some embodiments, the GLP-1R agonist is SEQ ID NO: 114. In some embodiments, the GLP-1R agonist is SEQ ID NO: 115. In some embodiments, the GLP-1R agonist is SEQ ID NO: 116. In some embodiments, the GLP-1R agonist is SEQ ID NO: 117. In some embodiments, the GLP-1R agonist is SEQ ID NO: 118. In some embodiments, the GLP-1R agonist is SEQ ID NO: 119. In some embodiments, the GLP-1R agonist is SEQ ID NO: 120. In some embodiments, the GLP-1R agonist is SEQ ID NO: 121. In some embodiments, the GLP-1R agonist is at least 90 or 95% identical to any one of the foregoing peptides. In some embodiments, the GLP-1R agonist comprises any one of the foregoing peptides provided the peptide has 1, 2, or 3 substitutions or deletions as compared to the reference sequence. The reference sequence can be any of the foregoing peptides.

[0142] In some embodiments ,the GLP-1R agonist comprises a peptide having the following formula:Xi is absent or H; X2 is any amino acid (natural or unnatural), G, S, A, or V; X3 is E, D, or I; X4 is F or G; Xs is T; X« is F or any hydrophobic amino acid or a modified amino acid, such as those provided for herein at a similar position; X7 is T; Xs is S; X9 is E or D; X10 is L, V, Y, or any hydrophobic amino acid or a modified amino acid, such as those provided for herein at a similar position; Xu is S or V; X12 is K, R, or S; Xis is Q, I or Y; Xu is any modified amino acid, such as those provided for herein at a similar position, or L, M, or G; X15 is E; Xie is E, A, G, K, or any modified amino acid, such as those provided for herein at a similar position; X17 is K, E, Q, or any modified amino acid, such as those provided for herein at a similar position; Xis is A; X19 is A or V; X20 is K or R; X21 is E, K, or L; X22 is F; X23 is I; X24 is E or A, or any modified amino acid, such as those provided for herein at a similar position; X25 is F or W; X26 is L or any modified amino acid, such as those provided for herein at a similar position; X27 is K, R, I, or V, or any modified amino acid, such as those provided for herein at a similar position; X28 is Q, N, R, K; X29 is G, R, or absent; X30 is G, R, or absent; Xsi is P, G, K, or absent; X32 is S, K, or58IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT absent; X33 is S, K, or absent; X34 is G, E, or absent; X35 is A, I, or absent; Xse is P, I, or absent; X37 is P, S, or absent; X38 is P or absent; X39 is S, C, or absent; X40 is K, C, or absent. In some embodiments, X32-X40 are absent. In some embodiments, X31-X39 comprise the amino acid sequence of PSSGAPPPS and X40 is absent. In some embodiments, X31-X40 comprise the amino acid sequence of PSSGAPPPSK or PSSGAPPPCC.

[0143] In some embodiments, the GLP-1R agonist comprises a peptide means for agonizing GLP- 1R.

[0144] While certain embodiments herein refer to the biologically active peptide as a GLP-1R agonist, other biologically active peptides are also considered and are within the scope of the present disclosure. Non-limiting examples of additional biologically active peptides that are within the scope of the present disclosure include, but are not limited to, GLP-1 analogues, GIP, GIP analogues, and GLP-l / glucagon peptides.

[0145] The foregoing biologically active peptides are exemplary only and are not meant to be limiting in any way. Additional exemplary biologically active peptides may be found at least in WO2017 / 112824, WO2018 / 136440, US2021 / 0154318, US2022 / 0025059, US2025 / 0270196, U.S. Patent No. 10,294,303, U.S. Patent No. 10,905,772, and U.S. Patent No. 11,046,774, each of which are incorporated herein by reference in their entirety.Anti-GIP antibody: Biologically Active Peptide Conjugate

[0146] In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof. In some embodiments, the biologically active peptide is as provided for herein. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, is as provided for herein.

[0147] In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through a cysteine or non-canonical amino acid substitution at one or more conjugation sites. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through a cysteine substitution at one or more conjugation sites. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through a non-canonical amino acid substitution at one or more conjugation sites.59IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT

[0148] In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, within the CL, CHI, CH2, or CH3 region of the anti-GIP antibody, or antigen-binding fragment thereof, or any combination of the CL, CHI, CH2, or CH3 region of the anti-GIP antibody, or antigen-binding fragment thereof. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigenbinding fragment thereof, within the CL region of the anti-GIP antibody, or antigen-binding fragment thereof. In some embodiments, the biologically active peptide is conjugated to the anti- GIP antibody, or antigen-binding fragment thereof, within the CHI region of the anti-GIP antibody, or antigen-binding fragment thereof. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, within the CH2 region of the anti-GIP antibody, or antigen-binding fragment thereof. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, within the CH3 region of the anti-GIP antibody, or antigen-binding fragment thereof. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen -binding fragment thereof, within any combination of the CL, CHI, CH2, or CH3 region of the anti-GIP antibody, or antigen-binding fragment thereof.

[0149] In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, within the Fc region of the anti-GIP antibody, or antigen-binding fragment thereof. In some embodiments, the Fc region is an IgG Fc, as provided for herein. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, within the IgG region of the anti-GIP antibody, or antigen-binding fragment thereof. In some embodiments, the IgG region comprises one or more substitutions of a canonical amino acid to a cysteine. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through a substituted cysteine residue on the anti-GIP antibody, or antigen-binding fragment thereof.

[0150] In some embodiments, the IgG Fc is an IgGl Fc. In some embodiments, the IgGl Fc comprises one or more substitutions of a canonical amino acid to a cysteine at position 70, 89, 109, 111, 118, 124, 140, 152, 239, 265, 272, 290, 300, 345, 359, 390, 442, or any combination thereof, wherein the amino acid positions refer to the EU numbering of the Fc region. The EU numbering of residues in the Fc domain is according to the EU index, which is provided for herein and can be found in Kabat et al. (1991) Sequences of Proteins of Immunological Interest, National Institutes60IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT of Health, Bethesda, MD, and according to FIGs.3c-3f of U.S. Pat. App. Puh. No.2008 / 0248028. The “EU index” may also be referred to as “EU numbering”. Unless specified otherwise, the amino acid positions of canonical amino acid to cysteine mutations provided for herein are provided under the EU numbering system. In some embodiments, the IgGl Fc comprises a substitution of a canonical amino acid to a cysteine at position 70, 89, 109, 111, 118, 124, 140, 152, 239, 265, 272, 290, 300, 345, 359, 390, or 442. In some embodiments, the IgGl Fc comprises a substitution of a canonical amino acid to a cysteine at position 70. In some embodiments, the IgGl Fc comprises a substitution of a canonical amino acid to a cysteine at position 89. In some embodiments, the IgGl Fc comprises a substitution of a canonical amino acid to a cysteine at position 109. In some embodiments, the IgGl Fc comprises a substitution of a canonical amino acid to a cysteine at position 111. In some embodiments, the IgGl Fc comprises a substitution of a canonical amino acid to a cysteine at position 118. In some embodiments, the IgGl Fc comprises a substitution of a canonical amino acid to a cysteine at position 124. In some embodiments, the IgGl Fc comprises a substitution of a canonical amino acid to a cysteine at position 140. In some embodiments, the IgGl Fc comprises a substitution of a canonical amino acid to a cysteine at position 152. In some embodiments, the IgGl Fc comprises a substitution of a canonical amino acid to a cysteine at position 239. In some embodiments, the IgGl Fc comprises a substitution of a canonical amino acid to a cysteine at position 265. In some embodiments, the IgGl Fc comprises a substitution of a canonical amino acid to a cysteine at position 272. In some embodiments, the IgGl Fc comprises a substitution of a canonical amino acid to a cysteine at position 290. In some embodiments, the IgGl Fc comprises a substitution of a canonical amino acid to a cysteine at position 300. In some embodiments, the IgGl Fc comprises a substitution of a canonical amino acid to a cysteine at position 345. In some embodiments, the IgGl Fc comprises a substitution of a canonical amino acid to a cysteine at position or 359. In some embodiments, the IgGl Fc comprises a substitution of a canonical amino acid to a cysteine at position 390. In some embodiments, the IgGl Fc comprises a substitution of a canonical amino acid to a cysteine at position 442. In some embodiments, the IgGl Fc comprises more than one substitutions of a canonical amino acid to a cysteine at any combination of position 88, 99, 150, 152, 154, 156, 189, 377, 384, 421, 473, 487 and 526.

[0151] In some embodiments, the substitution of a canonical amino acid to a cysteine at position 70 comprises a D70C substitution. In some embodiments, the anti-GIP antibody, or antigen-61IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT binding fragment thereof, comprises an IgGl Fc domain, wherein the IgGl Fc comprises a D70C substitution. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through the D70C substitution.

[0152] In some embodiments, the substitution of a canonical amino acid to a cysteine at position 89 comprises a E89C substitution. In some embodiments, the anti-GIP antibody, or antigenbinding fragment thereof, comprises an IgGl Fc domain, wherein the IgGl Fc comprises a E89C substitution. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through the E89C substitution.

[0153] In some embodiments, the substitution of a canonical amino acid to a cysteine at position 109 comprises a V109C substitution. In some embodiments, the anti-GIP antibody, or antigenbinding fragment thereof, comprises an IgGl Fc domain, wherein the IgGl Fc comprises a V 109C substitution. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through the V109C substitution.3

[0154] In some embodiments, the substitution of a canonical amino acid to a cysteine at position 111 comprises a A111C substitution. In some embodiments, the anti-GIP antibody, or antigenbinding fragment thereof, comprises an IgGl Fc domain, wherein the IgGl Fc comprises a A111C substitution. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through the A111C substitution.

[0155] In some embodiments, the substitution of a canonical amino acid to a cysteine at position 118 comprises a A118C substitution. In some embodiments, the anti-GIP antibody, or antigenbinding fragment thereof, comprises an IgGl Fc domain, wherein the IgGl Fc comprises a A118C substitution. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through the A118C substitution.

[0156] In some embodiments, the substitution of a canonical amino acid to a cysteine at position 124 comprises a S124C substitution. In some embodiments, the anti-GIP antibody, or antigenbinding fragment thereof, comprises an IgGl Fc domain, wherein the IgGl Fc comprises a S124C substitution. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through the S124C substitution.

[0157] In some embodiments, the substitution of a canonical amino acid to a cysteine at position 140 comprises a A140C substitution. In some embodiments, the anti-GIP antibody, or antigenbinding fragment thereof, comprises an IgGl Fc domain, wherein the IgGl Fc comprises a A 140C62IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT substitution. Tn some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through the A140C substitution.

[0158] In some embodiments, the substitution of a canonical amino acid to a cysteine at position 152 comprises a E152C substitution. In some embodiments, the anti-GIP antibody, or antigenbinding fragment thereof, comprises an IgGl Fc domain, wherein the IgGl Fc comprises a E152C substitution. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through the E152C substitution.

[0159] In some embodiments, the substitution of a canonical amino acid to a cysteine at position 239 comprises a S239C substitution. In some embodiments, the anti-GIP antibody, or antigenbinding fragment thereof, comprises an IgGl Fc domain, wherein the IgGl Fc comprises a S239C substitution. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through the S239C substitution.

[0160] In some embodiments, the substitution of a canonical amino acid to a cysteine at position 265 comprises a V265C substitution. In some embodiments, the anti-GIP antibody, or antigenbinding fragment thereof, comprises an IgGl Fc domain, wherein the IgGl Fc comprises a V265C substitution. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through the V265C substitution.

[0161] In some embodiments, the substitution of a canonical amino acid to a cysteine at position 272 comprises a E272C substitution. In some embodiments, the anti-GIP antibody, or antigenbinding fragment thereof, comprises an IgGl Fc domain, wherein the IgGl Fc comprises a E272C substitution. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through the E272C substitution.

[0162] In some embodiments, the substitution of a canonical amino acid to a cysteine at position 290 comprises a K290C substitution. In some embodiments, the anti-GIP antibody, or antigenbinding fragment thereof, comprises an IgGl Fc domain, wherein the IgGl Fc comprises a K290C substitution. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through the K290C substitution.

[0163] In some embodiments, the substitution of a canonical amino acid to a cysteine at position 300 comprises a Y300C substitution. In some embodiments, the anti-GIP antibody, or antigenbinding fragment thereof, comprises an IgGl Fc domain, wherein the IgGl Fc comprises a Y300C63IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT substitution. Tn some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through the Y300C substitution.

[0164] In some embodiments, the substitution of a canonical amino acid to a cysteine at position 345 comprises a E345C substitution. In some embodiments, the anti-GIP antibody, or antigenbinding fragment thereof, comprises an IgGl Fc domain, wherein the IgGl Fc comprises a E345C substitution. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through the E345C substitution.

[0165] In some embodiments, the substitution of a canonical amino acid to a cysteine at position 359 comprises a T359C substitution. In some embodiments, the anti-GIP antibody, or antigenbinding fragment thereof, comprises an IgGl Fc domain, wherein the IgGl Fc comprises a T359C substitution. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through the T359C substitution.

[0166] In some embodiments, the substitution of a canonical amino acid to a cysteine at position 390 comprises a N390C substitution. In some embodiments, the anti-GIP antibody, or antigenbinding fragment thereof, comprises an IgGl Fc domain, wherein the IgGl Fc comprises a N390C substitution. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through the N390C substitution.

[0167] In some embodiments, the substitution of a canonical amino acid to a cysteine at position 442 comprises a S442C substitution. In some embodiments, the anti-GIP antibody, or antigenbinding fragment thereof, comprises an IgGl Fc domain, wherein the IgGl Fc comprises a S442C substitution. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through the S442C substitution.

[0168] In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, within the CL region of the anti-GIP antibody, or antigen-binding fragment thereof. In some embodiments, the CL region of the anti-GIP antibody, or antigen-binding fragment thereof comprises one or more substitutions of a canonical amino acid to a cysteine at position 149, 205, or any combination thereof, wherein the amino acid positions refer to the EU numbering. Unless specified otherwise, the amino acid positions of canonical amino acid to cysteine mutations provided for herein are provided under the EU numbering system. In some embodiments, the CL region of the anti-GIP antibody, or antigen-binding fragment thereof comprises a substitution of a canonical amino acid to a cysteine at position 149. In some64IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT embodiments, the CL region of the anti-GIP antibody, or antigen-binding fragment thereof comprises a substitution of a canonical amino acid to a cysteine at position 205.

[0169] In some embodiments, the substitution of a canonical amino acid to a cysteine at position 149 of the CL region comprises a K149C substitution. In some embodiments, the anti-GIP antibody, or antigen binding fragment thereof, comprises a CL wherein the CL comprises a K1 9C mutation. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen binding fragment thereof, through the K1 9C mutation.

[0170] In some embodiments, the substitution of a canonical amino acid to a cysteine at position 205 of the CL region comprises a V205C substitution. In some embodiments, the anti-GIP antibody, or antigen binding fragment thereof, comprises a CL wherein the CL comprises a V205C mutation. In some embodiments, the biologically active peptide is conjugated to the anti-GIP antibody, or antigen binding fragment thereof, through the V205C mutation.

[0171] In some embodiments, the anti-GIP antibody, or antigen binding fragment thereof, comprises one or more substitutions of a canonical amino acid to a cysteine in an IgGl Fc domain at a position as provided for herein and comprises one or more substitutions of a canonical amino acid to a cysteine in an CL at a position as provided for herein.

[0172] The conjugation site must be amenable to conjugation of an additional functional moiety (e.g. a biologically active peptide as provided for herein) by a defined conjugation chemistry through the side chain of an amino acid residue at the conjugation site. Achieving highly selective, site specific conjugation to the anti-GIP antibody, or antigen-binding fragment thereof, in accordance with the present disclosure, requires consideration of a diverse variety of design criteria. First, a conjugation or coupling chemistry must be defined or predetermined. Functional moieties, such as biologically active peptides, can be conjugated or coupled to the selected conjugation site of the anti-GIP antibody, or antigen-binding fragment thereof, through an assortment of different conjugation chemistries known in the art. For example, a maleimide activated conjugation partner targeting an accessible cysteine thiol on the anti-GIP antibody, or antigen-binding fragment thereof, is one embodiment, but numerous conjugation or coupling chemistries targeting the side chains of either canonical or non-canonical, e.g., unnatural amino acids in the anti-GIP antibody sequence, or the sequence of the anti-GIP antigen-binding fragment, are within the scope of the present disclosure.65IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT

[0173] Chemistries for the chemoselective conjugation include, but are not limited to, copper(I)- catalyzcd azidcalkync [3+2] dipolar cycloadditions, Staudingcr ligation, other acyl transfers processes (S- N; X->N), oximations, hydrazone bonding formation and other suitable organic chemistry reactions such as cross couplings using water-soluble palladium catalysts (E.g., Bong et al., Chemoselective Pd(0)-catalyzed peptide coupling in water, Organic Letters 3(16):2509-l 1 (2001); Dibowski et al., Bioconjugation of peptides by palladium-catalyzed C — C cross-coupling in water, Angew. Chem. Int. Ed. 37(4):476-78 (1998); DeVasher et al., Aqueous-phase, palladium- catalyzed cross-coupling of aryl bromides under mild conditions, using water-soluble, sterically demanding alkylphosphines, J. Org. Chem. 69:7919-27 (2004); Shaugnessy et al., J. Org. Chem, 2003, 68, 6767-6774; Prescher, J A and Bertozzi C R, Chemistry in living system, Nature Chemical Biology 1(1); 13-21 (2005)).

[0174] As mentioned above, in some embodiments, the conjugation (or covalent binding) to the anti-GIP antibody, or antigen-binding fragment thereof, is through the side chain of an amino acid residue at the conjugation site, for example, but not limited to, a cysteinyl residue. The amino acid residue, for example, a cysteinyl residue, at the internal conjugation site that is selected can be one that occupies the same amino acid residue position in a native Fc domain sequence, or the amino acid residue can be engineered into the Fc domain sequence by substitution or insertion.

[0175] Other examples of unnatural amino acid residues that can be particularly useful as the conjugation site include, but are not limited to, azido-containing amino acid residues, e.g., azidohomoalanine, p-azido-phenylalanine; keto-containing amino acid residues, e.g., p-acetyl- phenylalanine; alkyne-containing amino acid residues, e.g., p-ethynylphenylalanine, homopropargylglycine, p-(prop-2-ynyl)-tyrosine; alkene-containing amino acid residues e.g., homoallylglycine; aryl halide-containing amino acid residues e.g. p-iodophenylalanine, p- bromophenylalanine; and 1,2-aminothiol containing amino acid residues.

[0176] The non-canonical amino acid residues can be incorporated by amino acid substitution or insertion. Non-canonical amino acid residues can be incorporated into the peptide by chemical peptide synthesis rather than by synthesis in biological systems, such as recombinantly expressing cells, or alternatively the skilled artisan can employ known techniques of protein engineering that use recombinantly expressing cells. (See, e.g., Link et al., Non-canonical amino acids in protein engineering, Current Opinion in Biotechnology, 14(6):603-609 (2003); Schultz et al., In vivo incorporation of unnatural amino acids, U.S. Pat. No. 7,045,337).66IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT

[0177] The selection of the placement of the conjugation site in the overall anti-GIP antibody, or antigen-binding fragment thereof, is another important facet of selecting an internal conjugation site in accordance with the present disclosure. Any of the exposed amino acid residues on the anti- GIP antibody, or antigen-binding fragment thereof, can be potentially useful conjugation sites and can be mutated to cysteine or some other reactive amino acid for site- selective coupling, if not already present at the selected conjugation site of the anti-GIP antibody, or antigen-binding fragment thereof, protein sequence. While any of the exposed amino acid residues can be potentially useful, other factors must also be taken into consideration, such as potential steric constraints that may perturb the activity of the conjugated biologically active peptide or limit the reactivity of the engineered mutation.

[0178] Accordingly, in some embodiments, the biologically active peptide is conjugated directly to the anti-GIP antibody, or antigen-binding fragment thereof. In some embodiments, the conjugation site is at a substitution of a canonical amino acid for a cysteine or non-canonical amino acid, as provided for herein. In some embodiments, the conjugation site comprises a substitution at one or more of positions 70, 89, 109, 111, 118, 124, 140, 152, 239, 265, 272, 290, 300, 345, 359, 390, or 442 of an IgGl Fc domain as provided for herein or at one or more of positions 149 or 205 of a CL domain as provided for herein, or any combination thereof. In some embodiments, the conjugation is through a chemistry as provided for herein or an equivalent thereof.

[0179] In some embodiments, the biologically active peptide is conjugated indirectly to the anti- GIP antibody, or antigen-binding fragment thereof, such as through a linker moiety. In some embodiments, the linker is a polypeptide linker. Polypeptide linkers are known in the art, and any such linker is within the scope of the present disclosure. Nonlimiting examples of polypeptide linkers are provided in Table 7 below:TABLE 7: Sequences of exemplary polypeptide linkers67IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT

[0180] The foregoing linker peptides are exemplary only and are not meant to be limiting in any way. Additional exemplary linker peptides may be found at least in WO2025 / 184315 and US2025 / 0276080, each of which are incorporated herein by reference in their entirety.

[0181] In some embodiments, the polypeptide linker is located at the N-terminus of the biologically active peptide. In some embodiments, the polypeptide linker is located at the C- terminus of the biologically active peptide. In some embodiments, the polypeptide linker contains one or more additional amino acid residues to facilitate the conjugation of the polypeptide linker to the anti-GIP antibody, or antigen-binding fragment thereof. In some embodiments, the polypeptide linker is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through a chemistry as provided for herein or an equivalent thereof.

[0182] In some embodiments, a composition is provided, the composition comprising an anti-GIP antibody, or antigen binding fragment thereof, as provided for herein, conjugated or linked to a biologically active peptide, as provided for herein, wherein the biologically active peptide is conjugated or linked to the anti-GIP antibody, or antigen binding fragment thereof, at a residue on the antibody which reduces the potency of the biologically active peptide. In some embodiments, the reduced potency of the biologically active peptide is as compared to the same biologically active peptide which is not conjugated or linked to the anti-GIP antibody, or antigen binding fragment thereof. In some embodiments, the reduced potency of the biologically active peptide is as compared to the same biologically active peptide which is conjugated or linked to the anti-GIP antibody, or antigen binding fragment thereof, at another residue of the antibody or antigen binding68IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT fragment thereof. In some embodiments, the biologically active peptide is conjugated or linked to the anti-GIP antibody, or antigen binding fragment thereof, at a residue as provided for herein. In some embodiments, the biologically active peptide is conjugated or linked to the anti-GIP antibody, or antigen binding fragment thereof, at a substitution of a canonical amino acid to a cysteine, wherein the canonical amino acid substituted to a cysteine is as provided for herein. In some embodiments, the biologically active peptide is conjugated or linked to the anti-GIP antibody, or antigen binding fragment thereof in the Fc region of the antibody. In some embodiments, the Fc region is an IgGl Fc. In some embodiments, the IgGl Fc comprises one or more substitutions of a canonical amino acid to a cysteine at position 70, 89, 109, 111, 118, 124, 140, 152, 239, 265, 272, 290, 300, 345, 359, 390, 442, or any combination thereof, wherein the amino acid positions refer to the EU numbering of the Fc region. The EU numbering of residues in the Fc domain is according to the EU index, which is provided for herein. In some embodiments, the one substitutions of a canonical amino acid to a cysteine at position 70, 89, 109, 111, 118, 124, 140, 152, 239, 265, 272, 290, 300, 345, 359, 390, 442, or any combination thereof, comprises a D70C, E89C, V109C, A111C, A118C, S124C, A140C, E152C, S239C, V265C, E272C, K290C, Y300C, E345C, T359C, N390C, or S442C. In some embodiments, the biologically active peptide is conjugated or linked to the anti-GIP antibody, or antigen binding fragment thereof in the CL domain. In some embodiments, the CL region of the anti-GIP antibody, or antigen-binding fragment thereof comprises one or more substitutions of a canonical amino acid to a cysteine at position 149, 205, or any combination thereof, wherein the amino acid positions refer to the EU numbering. In some embodiments, the one substitutions of a canonical amino acid to a cysteine at position 149, 205, or any combination thereof comprise a K149C or V205C.

[0183] In some embodiments, the biologically active peptide is a GLP-1R agonist, such as a GLP- 1R agonist as provided for herein, linked to conjugated to the anti-GIP antibody via a peptide linker, such as a peptide linker as provided for herein, at a location in the antibody wherein the canonical amino acid has been substituted to a cysteine, such as at a position as provided for herein. In some non-limiting embodiments, the GLP-1R agonist comprises an amino acid sequence of SEQ ID NO: 116 and is conjugated to the anti-GIP antibody through a linker comprising the amino acid sequence of SEQ ID NO: 131 (n=3), wherein the linker sequence is at the C-terminus of the GLP-1R agonist sequence. In some embodiments, the linker sequence further comprises a C- terminal lysine. Accordingly, in some non-limiting embodiments, the GLP-1R agonist comprising69IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT a linker sequence comprises the amino acid sequence of HXEGTFTSDYSSYLEEQAAKEFIAWLVKGGG(GGGGS)3K (SEQ ID NO: 145, wherein X= 2- Aminoisobutyric acid). In some embodiments, the linker sequence may further be modified to comprise a C-terminal bromoacetyl group (BrAc). In some embodiments, the GLP-1R agonist comprising a linker sequence comprises the amino acid sequence of HXEGTFTSDYSSYLEEQAAKEFIAWLVKGGG(GGGGS)3K-[BrAc] (SEQ ID NO: 146, wherein X- 2-Aminoisobutyric acid).

[0184] Without being bound to any particular theory, the potency of a biologically active peptide may be modified by attaching it to a specific residue of the anti-GIP antibody, or antigen binding fragment thereof. The modified potency of the biologically active peptide may be different depending on which residue of the anti-GIP antibody, or antigen binding fragment thereof, the biologically active peptide is attached to. The modified potency may be beneficial, for example, in scenarios where a reduced potency helps to abrogate unwanted side effects of the biologically active peptide, wherein a reduced potency increases subject tolerability of the biologically active peptide and / or conjugate thereof, and / or wherein a reduced potency enhances the efficacy of the biologically active peptide conjugated to the anti-GIP antibody, or antigen binding fragment thereof.

[0185] In some embodiments, the biologically active peptide is appended to the anti-GIP antibody, or antigen binding fragment thereof, as a genetic fusion. In the context of the present disclosure, the term “genetic fusion” is defined as meaning that the anti-GIP antibody and biologically active peptide conjugate is produced recombinantly through the translation contiguous nucleic acid sequence. In some embodiments, the nucleic acid sequence encoding the biologically active peptide is located at the 5’ end of the nucleic acid sequence encoding the anti-GIP antibody, or antigen binding fragment thereof. In some embodiments, the nucleic acid sequence encoding the biologically active peptide is located at the 3’ end of the nucleic acid sequence encoding the anti- GIP antibody, or antigen binding fragment thereof. In some embodiments, the nucleic acid sequence encoding the biologically active peptide is located within the nucleic acid sequence encoding the anti-GIP antibody, or antigen binding fragment thereof in a manner such that the anti- GIP antibody, or antigen binding fragment thereof, still forms a functional molecule. Methods for the generation and expression of genetic fusions are known in the art, and any such method is70IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT within the scope of the present disclosure and may be used to produce the biologically active peptide: anti-GIP antibody, or antigen binding fragment thereof, fusion.Pharmaceutical Compositions

[0186] In some embodiments, a pharmaceutical composition is provided comprising an anti-GIP antibody, or an antigen-binding fragment thereof, and biologically active peptide. In some embodiments, the anti-GIP antibody is an antibody means for binding to the GIP ligand. In some embodiments, the anti-GIP antibody is an antibody means for binding to the GIP ligand and inhibiting its binding to its cognate receptor GIP1R.

[0187] In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 28, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is a GLP- 1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ71IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, or SEQ ID NO: 121, or a combination of any of the foregoing. In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 28, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is semaglutide.

[0188] In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 31, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is a GLP- 1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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 ID72IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTNO: 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 IDNO: 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, or SEQ ID NO: 121, or a combination of any of the foregoing. In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 31, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is semaglutide.

[0189] In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 34, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is a GLP- 1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44,SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ IDNO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55,SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID73IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTNO: 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, or SEQ ID NO: 121, or a combination of any of the foregoing. In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 34, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is semaglutide.

[0190] In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 16, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 18, a LCDR2 having the amino acid sequence of SEQ ID NO: 5, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID74IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTNO: 39, SEQ ID NO: 40, SEQ ID NO: 41 , SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44,SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ IDNO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55,SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ IDNO: 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 IDNO: 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 IDNO: 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 IDNO: 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, or SEQ ID NO: 121, or a combination of any of the foregoing. In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 16, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 18, a LCDR2 having the amino acid sequence of SEQ ID NO: 5, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is semaglutide.

[0191] In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 1, a HCDR2 having the amino acid sequence of SEQ ID NO: 2, and an HCDR3 having the amino acid sequence of SEQ75IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTID NO: 3, and wherein the VL comprises a LCDR 1 having the amino acid sequence of SEQ ID NO: 4, a LCDR2 having the amino acid sequence of SEQ ID NO: 5, and a LCDR3 having the amino acid sequence of SEQ ID NO: 6, and wherein the biologically active peptide a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44,SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ IDNO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55,SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ IDNO: 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 IDNO: 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 IDNO: 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 IDNO: 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, or SEQ ID NO: 121, or a combination of any of the foregoing. In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 1, a HCDR2 having the amino acid sequence of SEQ ID NO: 2, and an HCDR3 having the amino acid sequence of SEQ ID NO: 3, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 4, a LCDR2 having the amino acid sequence of SEQ ID NO: 5, and a LCDR3 having the amino acid sequence of SEQ ID NO: 6, and wherein the biologically active peptide is semaglutide.

[0192] In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically76IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 29, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 30, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, or SEQ ID NO: 121, or a combination of any of the foregoing. In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 29, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 30, and wherein the biologically active peptide is semaglutide.

[0193] In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the77IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTVH comprises an amino acid sequence of SEQ ID NO: 32, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 33, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ IDNO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50,SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ IDNO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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 IDNO: 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 IDNO: 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 IDNO: 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 IDNO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, or SEQ ID NO: 121, or a combination of any of the foregoing. In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 32, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 33, and wherein the biologically active peptide is semaglutide.

[0194] In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 35, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 36, and wherein the biologically active peptide a GLP-1R agonist,78IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, or SEQ ID NO: 121, or a combination of any of the foregoing. In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 35, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 36, and wherein the biologically active peptide is semaglutide.

[0195] In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 24, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 25, and wherein the biologically active peptide a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID79IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTNO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50,SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ IDNO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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 IDNO: 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 IDNO: 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 IDNO: 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 IDNO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, or SEQ ID NO: 121, or a combination of any of the foregoing. In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 24, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 25, and wherein the biologically active peptide is semaglutide.

[0196] In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 13, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 14, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39,SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ IDNO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50,SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID80IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTNO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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 IDNO: 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 IDNO: 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 IDNO: 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 IDNO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, or SEQ ID NO: 121, or a combination of any of the foregoing. In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 13, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 14, and wherein the biologically active peptide is semaglutide.

[0197] In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy chain (HC) and a light chain (LC), wherein the HC comprises an amino acid sequence of SEQ ID NO: 37, and wherein the LC comprises an amino acid sequence of SEQ ID NO: 144, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ IDNO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57,SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ IDNO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68,81IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTSEQ 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, or SEQ ID NO: 121, or a combination of any of the foregoing. In some embodiments, the pharmaceutical composition comprises an anti- GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a HC and a LC, wherein the HC comprises an amino acid sequence of SEQ ID NO: 37, and wherein the LC comprises an amino acid sequence of SEQ ID NO: 144, and wherein the biologically active peptide is semaglutide.

[0198] In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 28, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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: 65,82IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTSEQ 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto, or a combination of any of the foregoing. In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 28, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is semaglutide.

[0199] In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 31, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active83IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ IDNO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54,SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ IDNO: 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 IDNO: 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 IDNO: 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 IDNO: 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto, or a combination of any of the foregoing. In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 31, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is semaglutide.

[0200] In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding84IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 34, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ IDNO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54,SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ IDNO: 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 IDNO: 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 IDNO: 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 IDNO: 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto, or a combination of any of the foregoing. In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a85IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTLCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 34, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is semaglutide.

[0201] In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 16, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 18, a LCDR2 having the amino acid sequence of SEQ ID NO: 5, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto, or a combination of any of the foregoing. In some embodiments, the pharmaceutical composition86IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT comprises an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 16, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 18, a LCDR2 having the amino acid sequence of SEQ ID NO: 5, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is semaglutide.

[0202] In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 1, a HCDR2 having the amino acid sequence of SEQ ID NO: 2, and an HCDR3 having the amino acid sequence of SEQ ID NO: 3, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 4, a LCDR2 having the amino acid sequence of SEQ ID NO: 5, and a LCDR3 having the amino acid sequence of SEQ ID NO: 6, and wherein the biologically active peptide a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ87IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto, or a combination of any of the foregoing. In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 1, a HCDR2 having the amino acid sequence of SEQ ID NO: 2, and an HCDR3 having the amino acid sequence of SEQ ID NO: 3, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 4, a LCDR2 having the amino acid sequence of SEQ ID NO: 5, and a LCDR3 having the amino acid sequence of SEQ ID NO: 6, and wherein the biologically active peptide is semaglutide.

[0203] In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 29, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 30, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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 ID88IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTNO: 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto, or a combination of any of the foregoing. In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 29, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 30, and wherein the biologically active peptide is semaglutide.

[0204] In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 32, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 33, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49,SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ IDNO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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 IDNO: 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 IDNO: 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 ID89IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTNO: 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto, or a combination of any of the foregoing. In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 32, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 33, and wherein the biologically active peptide is semaglutide.

[0205] In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 35, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 36, and wherein the biologically active peptide a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49,SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ IDNO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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 IDNO: 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 IDNO: 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 ID90IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTNO: 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto, or a combination of any of the foregoing. In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 35, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 36, and wherein the biologically active peptide is semaglutide.

[0206] In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 24, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 25, and wherein the biologically active peptide a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49,SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ IDNO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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 IDNO: 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 IDNO: 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 ID91IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTNO: 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto, or a combination of any of the foregoing. In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 24, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 25, and wherein the biologically active peptide is semaglutide.

[0207] In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 13, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 14, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49,SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ IDNO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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 IDNO: 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 IDNO: 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 ID92IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTNO: 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto, or a combination of any of the foregoing. In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 13, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 14, and wherein the biologically active peptide is semaglutide.

[0208] In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy chain (HC) and a light chain (LC), wherein the HC comprises an amino acid sequence of SEQ ID NO: 37, and wherein the LC comprises an amino acid sequence of SEQ ID NO: 144, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ IDNO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56,SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ IDNO: 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 IDNO: 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 IDNO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89,93IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTSEQ 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto, or a combination of any of the foregoing. In some embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigenbinding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a HC and a LC, wherein the HC comprises an amino acid sequence of SEQ ID NO: 37, and wherein the LC comprises an amino acid sequence of SEQ ID NO: 144, and wherein the biologically active peptide is semaglutide.

[0209] In certain embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, and the biologically active peptide are conjugated. In some embodiments, the conjugation is as described herein. In certain embodiments, the pharmaceutical composition comprises an anti-GIP antibody, or antigen-binding fragment thereof, and the pharmaceutical composition is co-administered with a pharmaceutical composition comprising a biologically active peptide.

[0210] The compositions disclosed herein can comprise a pharmaceutical composition, and for example include a pharmaceutically acceptable carrier, and / or a pharmaceutical formulation.

[0211] The term “pharmaceutical formulation” refers to a preparation which is in such form as to permit the biological activity of an active ingredient contained therein to be effective, and which contains no additional components which are unacceptably toxic to a subject to which the formulation would be administered. A “pharmaceutically acceptable excipient” refers to an ingredient in a pharmaceutical formulation, other than an active ingredient, which is nontoxic to a subject. A pharmaceutically acceptable carrier includes, but is not limited to, a buffer, excipient, stabilizer, or preservative. In some aspects, the choice of carrier is determined in part by the particular cell and / or by the method of administration. Accordingly, there are a variety of suitable94IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT formulations. For example, the pharmaceutical composition can contain preservatives. Suitable preservatives may include, for example, mcthylparabcn, propylparaben, sodium benzoate, and benzalkonium chloride. In some aspects, a mixture of two or more preservatives is used. The preservative or mixtures thereof are typically present in an amount of about 0.0001% to about 2% by weight of the total composition. Carriers are described, e.g., by Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980). Pharmaceutically acceptable carriers are generally nontoxic to recipients at the dosages and concentrations employed, and include, but are not limited to: buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride; benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens such as methyl or propyl paraben; catechol; resorcinol; cyclohexanol; 3- pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counter-ions such as sodium; metal complexes (e.g. Zn-protein complexes); and / or non-ionic surfactants such as polyethylene glycol (PEG).

[0212] Buffering agents in some aspects are included in the compositions. Suitable buffering agents include, for example, citric acid, sodium citrate, phosphoric acid, potassium phosphate, and various other acids and salts. In some aspects, a mixture of two or more buffering agents is used. The buffering agent or mixtures thereof are typically present in an amount of about 0.001% to about 4% by weight of the total composition. Methods for preparing administrable pharmaceutical compositions are known. Exemplary methods are described in more detail in, for example, Remington: The Science and Practice of Pharmacy, Lippincott Williams & Wilkins; 21 st ed. (May 1, 2005).

[0213] The formulations can include aqueous solutions. The formulation or composition may also contain more than one active ingredient useful for the particular indication, disease, or condition being treated with the composition, preferably those with activities complementary to the composition, where the respective activities do not adversely affect one another. Such active ingredients are suitably present in combination in amounts that are effective for the purpose95IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT intended. Thus, in some embodiments, the pharmaceutical composition further includes other pharmaceutically active agents or drugs. The pharmaceutical composition in some embodiments contains the composition in amounts effective to treat or prevent the disease or condition, such as a therapeutically effective or prophylactically effective amount. Therapeutic or prophylactic efficacy in some embodiments is monitored by periodic assessment of treated subjects. The desired dosage can be delivered by a single bolus administration of the composition, by multiple bolus administrations of the composition, or by continuous infusion administration of the composition.

[0214] Formulations include those for oral, intravenous, intraperitoneal, subcutaneous, pulmonary, transdermal, intramuscular, intranasal, buccal, sublingual, or suppository administration. In some embodiments, the composition is administered parenterally. The term “parenteral,” as used herein, includes intravenous, intramuscular, subcutaneous, rectal, vaginal, and intraperitoneal administration. In some embodiments, the composition is administered to the subject using peripheral systemic delivery by intravenous, intraperitoneal, or subcutaneous injection. Compositions in some embodiments are provided as sterile liquid preparations, e.g., isotonic aqueous solutions, suspensions, emulsions, dispersions, or viscous compositions, which may in some aspects be buffered to a selected pH. Liquid preparations are normally easier to prepare than gels, other viscous compositions, and solid compositions. Additionally, liquid compositions are somewhat more convenient to administer, especially by injection. Viscous compositions, on the other hand, can be formulated within the appropriate viscosity range to provide longer contact periods with specific tissues. Liquid or viscous compositions can comprise carriers, which can be a solvent or dispersing medium containing, for example, water, saline, phosphate buffered saline, polyol (for example, glycerol, propylene glycol, liquid polyethylene glycol) and suitable mixtures thereof.

[0215] Sterile injectable solutions can be prepared by incorporating the composition in a solvent, such as in admixture with a suitable carrier, diluent, or excipient such as sterile water, physiological saline, glucose, dextrose, or the like. The compositions can contain auxiliary substances such as wetting, dispersing, or emulsifying agents (e.g., methylcellulose), pH buffering agents, gelling or viscosity enhancing additives, preservatives, flavoring agents, and / or colors, depending upon the route of administration and the preparation desired. Standard texts may in some aspects be consulted to prepare suitable preparations.96IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT

[0216] Various additives which enhance the stability and sterility of the compositions, including antimicrobial preservatives, antioxidants, chelating agents, and buffers, can be added. Prevention of the action of microorganisms can be ensured by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, and sorbic acid. Prolonged absorption of the injectable pharmaceutical form can be brought about by the use of agents delaying absorption, for example, aluminum monostearate and gelatin.

[0217] The formulations to be used for in vivo administration are generally sterile. Sterility may be readily accomplished, e.g., by filtration through sterile filtration membranes.Methods

[0218] In some embodiments, a method of treating disease is provided, the method comprising administering to a subject in need thereof a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, and a biologically active peptide. In some embodiments, the method of treating a disease comprises administering to a subject in need thereof a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient. In certain embodiments, the disease is a metabolic disorder. In certain embodiments, the disease is selected from the group consisting of, but not limited to, obesity, type 2 diabetes, coronary heart disease, lipodystrophy, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, Cushing’s syndrome, fatty liver disease, hyperphagia, Prader-Willi syndrome, metabolic syndrome, Kleine-Levin syndrome, Bardet-Biedl syndrome, Graves’ disease, cancer, Kluver-Bucy syndrome, Pick’s disease, Huntington’s chorea, Parkinson’s disease, hyperthyroidism, ischemic heart disease, stable angina pectoris, unstable angina, acute coronary syndrome, ST elevation myocardial infarction, and non-ST elevation myocardial infarction.

[0219] In some embodiments, the method comprises administering an anti-GIP antibody, or an antigen-binding fragment thereof, and a biologically active peptide, thereby treating the disease. In some embodiments, the anti-GIP antibody, or antigen-binding fragment thereof, is as provided for herein. In some embodiments, the biologically active peptide is as provided for herein. In some embodiments, the anti-GIP antibody, or an antigen-binding fragment thereof, is administered at a concentration sufficient to illicit the desired therapeutic effect. In some embodiments, the97IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT biologically active peptide is administered at a concentration sufficient to illicit the desired therapeutic effect.

[0220] In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 28, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, or SEQ ID NO: 121, or a combination of any of the foregoing. In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a98IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 28, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is semaglutide.

[0221] In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 31, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ99IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, or SEQ ID NO: 121, or a combination of any of the foregoing. In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 31, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is semaglutide.

[0222] In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 34, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44,SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ IDNO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55,SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ IDNO: 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 ID100IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTNO: 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 IDNO: 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 IDNO: 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, or SEQ ID NO: 121, or a combination of any of the foregoing. In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 34, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is semaglutide.

[0223] In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 16, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 18, a LCDR2 having the amino acid sequence of SEQ ID NO: 5, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID101IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTNO: 39, SEQ ID NO: 40, SEQ ID NO: 41 , SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, or SEQ ID NO: 121, or a combination of any of the foregoing. In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 16, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 18, a LCDR2 having the amino acid sequence of SEQ ID NO: 5, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is semaglutide.

[0224] In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH102IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 1 , a HCDR2 having the amino acid sequence of SEQ ID NO: 2, and an HCDR3 having the amino acid sequence of SEQ ID NO: 3, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 4, a LCDR2 having the amino acid sequence of SEQ ID NO: 5, and a LCDR3 having the amino acid sequence of SEQ ID NO: 6, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, or SEQ ID NO: 121, or a combination of any of the foregoing. In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 1, a HCDR2 having the amino acid sequence of SEQ ID NO: 2, and an HCDR3 having the amino acid sequence of SEQ ID NO: 3, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 4, a LCDR2 having the amino acid103IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT sequence of SEQ ID NO: 5, and a LCDR3 having the amino acid sequence of SEQ ID NO: 6, and wherein the biologically active peptide is scmaglutidc.

[0225] In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 29, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 30, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, or SEQ ID NO: 121, or a combination of any of the foregoing. In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigenbinding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 29, and wherein104IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT the VL comprises an amino acid sequence of SEQ ID NO: 30, and wherein the biologically active peptide is scmaglutidc.

[0226] In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 32, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 33, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ IDNO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50,SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ IDNO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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 IDNO: 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 IDNO: 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 IDNO: 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 IDNO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, or SEQ ID NO: 121, or a combination of any of the foregoing. In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigenbinding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 32, and wherein105IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT the VL comprises an amino acid sequence of SEQ ID NO: 33, and wherein the biologically active peptide is scmaglutidc.

[0227] In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 35, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 36, and wherein the biologically active peptide a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, or SEQ ID NO: 121, or a combination of any of the foregoing. In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigenbinding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 35, and wherein106IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT the VL comprises an amino acid sequence of SEQ ID NO: 36, and wherein the biologically active peptide is scmaglutidc.

[0228] In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 24, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 25, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ IDNO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50,SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ IDNO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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 IDNO: 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 IDNO: 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 IDNO: 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 IDNO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, or SEQ ID NO: 121, or a combination of any of the foregoing. In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigenbinding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 24, and wherein107IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT the VL comprises an amino acid sequence of SEQ ID NO: 25, and wherein the biologically active peptide is scmaglutidc.

[0229] In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 13, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 14, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ IDNO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50,SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ IDNO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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 IDNO: 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 IDNO: 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 IDNO: 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 IDNO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, or SEQ ID NO: 121, or a combination of any of the foregoing. In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigenbinding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 13, and wherein108IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT the VL comprises an amino acid sequence of SEQ ID NO: 14, and wherein the biologically active peptide is scmaglutidc.

[0230] In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a heavy chain (HC) and a light chain (LC), wherein the HC comprises an amino acid sequence of SEQ ID NO: 37, and wherein the LC comprises an amino acid sequence of SEQ ID NO: 144, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, or SEQ ID NO: 121, or a combination of any of the foregoing. In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a HC and a LC, wherein the HC comprises an amino acid sequence of SEQ ID NO: 37, and wherein the109IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTLC comprises an amino acid sequence of SEQ ID NO: 144, and wherein the biologically active peptide is scmaglutidc.

[0231] In some embodiments, the method of treating a disease in a subject in need thereof comprises the co-administration of the anti-GIP antibody, or an antigen-binding fragment thereof, and the biologically active peptide. In the context of the present disclosure, “co-administration” is understood to encompass any embodiments wherein the anti-GIP antibody, or an antigenbinding fragment thereof, and the biologically active peptide are administered during a time period wherein both the anti-GIP antibody, or an antigen-binding fragment thereof, and the biologically active peptide will be circulating within the subject simultaneously. For example, in some embodiments, the method of treating a disease in a subject in need thereof comprises the administration of a first pharmaceutical composition comprising the anti-GIP antibody, or an antigen-binding fragment thereof, and a pharmaceutically acceptable excipient and the administration of a second pharmaceutical composition comprising the biologically active peptide and a pharmaceutically acceptable excipient, wherein the first pharmaceutical composition and the second pharmaceutical composition are administered simultaneously. In some embodiments, the method of treating a disease in a subject in need thereof comprises the administration of a first pharmaceutical composition comprising the anti-GIP antibody, or an antigen-binding fragment thereof, and a pharmaceutically acceptable excipient and the administration of a second pharmaceutical composition comprising the biologically active peptide and a pharmaceutically acceptable excipient, wherein the first pharmaceutical composition is administered either immediately prior to or immediately after the second pharmaceutical composition. In some embodiments, the method of treating a disease in a subject in need thereof comprises the administration of a first pharmaceutical composition comprising the anti-GIP antibody, or an antigen-binding fragment thereof, and a pharmaceutically acceptable excipient and the administration of a second pharmaceutical composition comprising the biologically active peptide and a pharmaceutically acceptable excipient, wherein the first pharmaceutical composition is administered first and the second pharmaceutical composition is administered at a time period after the first pharmaceutical composition, such that the anti-GIP antibody, or an antigen-binding fragment thereof of the first pharmaceutical composition is still circulating within the subject at the time of administering the second pharmaceutical composition. In some embodiments, , the method of treating a disease in a subject in need thereof comprises the administration of a first110IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT pharmaceutical composition comprising the anti-GIP antibody, or an antigen-binding fragment thereof, and a pharmaceutically acceptable excipient and the administration of a second pharmaceutical composition comprising the biologically active peptide and a pharmaceutically acceptable excipient, wherein the second pharmaceutical composition is administered first and the first pharmaceutical composition is administered at a time period after the second pharmaceutical composition, such that the biologically active peptide of the second pharmaceutical composition is still circulating within the subject at the time of administering the first pharmaceutical composition.

[0232] In some embodiments, the anti-GIP antibody, or an antigen-binding fragment thereof, and the biologically active peptide are co-formulated. In the context of the present disclosure, “co- formulated” is understood to encompass any embodiments wherein the anti-GIP antibody, or an antigen-binding fragment thereof, and the biologically active peptide are simultaneously present in the same composition.

[0233] In some embodiments, the method comprises administering an anti-GIP antibody, or antigen binding fragment thereof, conjugated to a biologically active peptide. In some embodiments, the anti-GIP antibody, or antigen binding fragment thereof, is conjugated to the biologically active peptide as provided for herein.

[0234] In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 28, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54,111IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTSEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto, or a combination of any of the foregoing. In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti- GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 28, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is semaglutide.

[0235] In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a112IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTHCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 31, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto, or a combination of any of the foregoing. In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti- GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 31, and a113IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTLCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is scmaglutidc.

[0236] In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 34, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ IDNO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54,SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ IDNO: 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 IDNO: 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 IDNO: 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 IDNO: 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto, or a combination of any of the foregoing. In some embodiments, the method of treating a disease in a114IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT subject in need thereof comprises administering a pharmaceutical composition comprising an anti- GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 26, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 27, a LCDR2 having the amino acid sequence of SEQ ID NO: 34, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is semaglutide.

[0237] In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 16, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 18, a LCDR2 having the amino acid sequence of SEQ ID NO: 5, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ IDNO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54,SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ IDNO: 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 IDNO: 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 IDNO: 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 ID115IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTNO: 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto, or a combination of any of the foregoing. In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti- GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 15, a HCDR2 having the amino acid sequence of SEQ ID NO: 16, and an HCDR3 having the amino acid sequence of SEQ ID NO: 17, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 18, a LCDR2 having the amino acid sequence of SEQ ID NO: 5, and a LCDR3 having the amino acid sequence of SEQ ID NO: 19, and wherein the biologically active peptide is semaglutide.

[0238] In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 1, a HCDR2 having the amino acid sequence of SEQ ID NO: 2, and an HCDR3 having the amino acid sequence of SEQ ID NO: 3, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 4, a LCDR2 having the amino acid sequence of SEQ ID NO: 5, and a LCDR3 having the amino acid sequence of SEQ ID NO: 6, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID116IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTNO: 49, SEQ ID NO: 50, SEQ ID NO: 51 , SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto, or a combination of any of the foregoing. In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti- GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 1, a HCDR2 having the amino acid sequence of SEQ ID NO: 2, and an HCDR3 having the amino acid sequence of SEQ ID NO: 3, and wherein the VL comprises a LCDR1 having the amino acid sequence of SEQ ID NO: 4, a LCDR2 having the amino acid sequence of SEQ ID NO: 5, and a LCDR3 having the amino acid sequence of SEQ ID NO: 6, and wherein the biologically active peptide is semaglutide.

[0239] In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region117IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT(VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 29, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 30, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 95% identical thereto, or a combination of any of the foregoing. In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 29, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 30, and wherein the biologically active peptide is semaglutide.

[0240] In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding118IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 32, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 33, and wherein the biologically active peptide is a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 95% identical thereto, or a combination of any of the foregoing. In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 32, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 33, and wherein the biologically active peptide is semaglutide.

[0241] In some embodiments, the method of treating a disease in a subject in need thereof comprises administering a pharmaceutical composition comprising an anti-GIP antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, and a119IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT pharmaceutically acceptable excipient, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises an amino acid sequence of SEQ ID NO: 35, and wherein the VL comprises an amino acid sequence of SEQ ID NO: 36, and wherein the biologically active peptide a GLP-1R agonist, liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, S...

Claims

1. DOCKET NO: HEB-006WO PATENTWhat is Claimed:

1. A conjugate, comprising an anti-glucose-dependent insulinotropic polypeptide (GIP) antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, wherein the biologically active peptide comprises a glucagon like peptide 1 receptor (GLP-1R) agonist.

2. The conjugate of claim 1, wherein the anti-GIP antibody, or antigen-binding fragment thereof comprises a heavy chain (HC) comprising a variable heavy chain region (VH) and a light chain (LC) comprising a variable light chain region (VL), wherein the VH comprises a heavy chain complementarity domain 1 (HCDR1), a HCDR2, and a HCDR3 comprising amino acid sequences selected from: a. SEQ ID NO: 15, SEQ ID NO: 26, and SEQ ID NO: 17, b. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, c. SEQ ID NO: 15, SEQ ID NO: 16, and SEQ ID NO: 17, or and wherein the VL comprises a light chain complementarity domain 1 (LCDR1), a LCDR2, and a LCDR3 comprising amino acid sequences selected from: d. SEQ ID NO: 27, SEQ ID NO: 28, and SEQ ID NO: 19, e. SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, f. SEQ ID NO: 18, SEQ ID NO: 5, and SEQ ID NO: 19, g. SEQ ID NO: 27, SEQ ID NO: 31, and SEQ ID NO: 19, or h. SEQ ID NO: 27, SEQ ID NO: 34, and SEQ ID NO: 19.

3. The conjugate of claim 2, wherein the VH comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to an amino acid sequence selected from SEQ ID NO: 29, SEQ ID NO: 13, SEQ ID NO: 24, SEQ ID NO: 32, or SEQ ID NO: 35.

4. The conjugate of claim 2, wherein the VL comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to an amino181IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT acid sequence selected from SEQ ID NO: 30, SEQ ID NO: 14, SEQ ID NO: 25, SEQ ID NO: 33, or SEQ ID NO: 36.

5. The conjugate of claim 2, wherein the VH comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 29 and the VL comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 30, wherein the VH comprises a HCDR1 comprising an amino acid sequence of SEQ ID NO: 15, a HCDR2 comprising an amino acid sequence of SEQ ID NO: 26, and a HCDR3 comprising an amino acid sequence of SEQ ID NO: 17, and the VL comprises a LCDR1 comprising an amino acid sequence of SEQ ID NO: 27, a LCDR2 comprising an amino acid sequence of SEQ ID NO: 28, and a LCDR3 comprising an amino acid sequence of SEQ ID NO: 19.

6. The conjugate of claim 2, wherein the HC comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 37 and the LC comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 144.

7. The conjugate of claim 1, wherein the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through the substituted cysteine residue on the anti-GIP antibody.

8. The conjugate of claim 1, wherein the GLP-1R agonist is liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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:182IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT68, 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 95% identical thereto.

9. The conjugate of claim 8, wherein the GLP-1R agonist is SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 95% identical thereto.

10. The conjugate of claim 1, wherein the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, within a CL, CHI, CH2, or CH3 region of the anti-GIP antibody, or antigen-binding fragment thereof.

11. The conjugate of claim 1, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises an Fc region.

12. The conjugate of claim 11, wherein the Fc region is an IgG Fc, optionally wherein the IgG Fc is an IgGl, IgG2, IgG3, or IgG4 Fc.

13. The conjugate of claim 12, wherein IgG Fc comprises one or more substitutions of a canonical amino acid to a cysteine.

14. The conjugate of claim 13, wherein the biologically active peptide is conjugated to the anti-GIP antibody, or antigen-binding fragment thereof, through the substituted cysteine residue on the anti-GIP antibody.183IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT15. The conjugate of claim 12, wherein the IgG Fc is an IgGl Fc, and wherein the IgGl Fc comprises one or more substitutions of a canonical amino acid to a cysteine at position 70, 89, 109, 111, 118, 124, 140, 152, 239, 265, 272, 290, 300, 345, 359, 390, or 442.

16. The conjugate of claim 15, wherein the substitution of a canonical amino acid to a cysteine comprises a D70C, E89C, V109C, A111C, A118C, S124C, A140C, E152C, S239C, V265C, E272C, K290C, Y300C, E345C, T359C, N390C, or S442C mutation.

17. The conjugate of claim 10, wherein the CL domain comprises one or more substitutions of a canonical amino acid to a cysteine at position 149, 205, or any combination thereof.

18. The conjugate of claim 17, wherein the substitution of a canonical amino acid to a cysteine comprises a K149C or V205C substitution.

19. A conjugate comprising an anti-glucose-dependent insulinotropic polypeptide (GIP) antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide, wherein the biologically active peptide is conjugated to the anti-GIP antibody, or antigenbinding fragment thereof, through one or more substitutions of a canonical amino acid to a cysteine, wherein the one or more substitution of a canonical amino acid to a cysteine comprises a D70C, E89C, V109C, A111C, A118C, S124C, A140C, E152C, S239C, V265C, E272C, K290C, Y300C, E345C, T359C, N390C, or S442C mutation in a heavy chain of the antibody, and / or a K149C or V205C substitution in a light chain of the antibody, and wherein the biologically active peptide comprises a glucagon like peptide 1 receptor (GLP-1R) agonist.

20. A conjugate comprising an anti-glucose-dependent insulinotropic polypeptide (GIP) antibody, or an antigen-binding fragment thereof, conjugated to a biologically active peptide,184IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT wherein the biologically active peptide is conjugated to the anti-GIP antibody, or antigenbinding fragment thereof, through one or more substitutions of a canonical amino acid to a cysteine, wherein the one or more substitution of a canonical amino acid to a cysteine comprises an E272C, K290C, or S442C mutation in a heavy chain of the antibody, and / or a K149C or V205C substitution in a light chain of the antibody, and wherein the biologically active peptide comprises a glucagon like peptide 1 receptor (GLP-1R) agonist.

21. The conjugate of claim 19 or claim 20, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises a variable heavy chain region (VH) and comprises a variable light chain region (VL), wherein the VH comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 29 and the VL comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 30, wherein the VH comprises a HCDR1 comprising an amino acid sequence of SEQ ID NO: 15, a HCDR2 comprising an amino acid sequence of SEQ ID NO: 26, and a HCDR3 comprising an amino acid sequence of SEQ ID NO: 17, and the VL comprises a LCDR1 comprising an amino acid sequence of SEQ ID NO: 27, a LCDR2 comprising an amino acid sequence of SEQ ID NO: 28, and a LCDR3 comprising an amino acid sequence of SEQ ID NO: 19.

22. A pharmaceutical composition comprising the conjugate of any one of claims 1-21.

23. A composition comprising an anti-GIP antibody, or antigen binding fragment thereof, linked to a biologically active peptide, wherein the biologically active peptide is linked to the anti-GIP antibody, or antigen binding fragment thereof, at a residue on the antibody which reduces the potency of the biologically active peptide.

24. The composition of claim 23, wherein the biologically active peptide linked to the anti- GIP antibody, or antigen binding fragment thereof, has a reduced potency as compared to the185IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT biologically active peptide that is linked to the anti-GIP antibody, or antigen binding fragment thereof, at another residue of the antibody.

25. The composition of claim 23, wherein the biologically active peptide is linked to the anti- GIP antibody, or antigen-binding fragment thereof, within a CL, CHI, CH2, or CH3 region of the anti-GIP antibody, or antigen- binding fragment thereof.

26. The composition of claim 23, wherein the anti-GIP antibody, or antigen-binding fragment thereof, comprises an Fc region.

27. The composition of claim 26, wherein the Fc region is an IgG Fc, optionally wherein the IgG Fc is an IgGl, IgG2, IgG3, or IgG4 Fc.

28. The composition of claim 27, wherein IgG Fc comprises one or more substitutions of a canonical amino acid to a cysteine.

29. The composition of claim 28, wherein the biologically active peptide is linked to the anti- GIP antibody, or antigen-binding fragment thereof, through the substituted cysteine residue on the anti-GIP antibody.

30. The composition of claim 27, wherein the IgG Fc is an IgGl Fc, wherein the IgGl Fc comprises one or more substitutions of a canonical amino acid to a cysteine at position 70, 89, 109, 111, 118, 124, 140, 152, 239, 265, 272, 290, 300, 345, 359, 390, or 442.

31. The composition of claim 30, wherein the substitution of a canonical amino acid to a cysteine comprises a D70C, E89C, V109C, A111C, A118C, S124C, A140C, E152C, S239C, V265C, E272C, K290C, Y300C, E345C, T359C, N390C, or S442C mutation.

32. The composition of claim 25, wherein the CL domain comprises one or more substitutions of a canonical amino acid to a cysteine at position 149, 205, or any combination thereof.186IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT33. The composition of claim 32, wherein the substitution of a canonical amino acid to a cysteine comprises a K149C or V205C substitution.

34. The composition of claim 23, wherein the anti-GIP antibody, or antigen-binding fragment thereof comprises a heavy chain (HC) comprising a variable heavy chain region (VH) and a light chain (LC) comprising a variable light chain region (VL), wherein the VH comprises a heavy chain complementarity domain 1 (HCDR1), a HCDR2, and a HCDR3 comprising amino acid sequences selected from: a. SEQ ID NO: 15, SEQ ID NO: 26, and SEQ ID NO: 17, b. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, c. SEQ ID NO: 15, SEQ ID NO: 16, and SEQ ID NO: 17, or and wherein the VL comprises a light chain complementarity domain 1 (LCDR1), a LCDR2, and a LCDR3 comprising amino acid sequences selected from: d. SEQ ID NO: 27, SEQ ID NO: 28, and SEQ ID NO: 19, e. SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, f. SEQ ID NO: 18, SEQ ID NO: 5, and SEQ ID NO: 19, g. SEQ ID NO: 27, SEQ ID NO: 31, and SEQ ID NO: 19, or h. SEQ ID NO: 27, SEQ ID NO: 34, and SEQ ID NO: 19.

35. The composition of claim 34, wherein the VH comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to an amino acid sequence selected from SEQ ID NO: 29, SEQ ID NO: 13, SEQ ID NO: 24, SEQ ID NO: 32, or SEQ ID NO: 35.

36. The composition of claim 34, wherein the VL comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to an amino acid sequence selected from SEQ ID NO: 30, SEQ ID NO: 14, SEQ ID NO: 25, SEQ ID NO: 33, or SEQ ID NO: 36.187IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT37. The composition of claim 34, wherein the VH comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 29 and the VL comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 30, wherein the VH comprises a HCDR1 comprising an amino acid sequence of SEQ ID NO: 15, a HCDR2 comprising an amino acid sequence of SEQ ID NO: 26, and a HCDR3 comprising an amino acid sequence of SEQ ID NO: 17, and the VL comprises a LCDR1 comprising an amino acid sequence of SEQ ID NO: 27, a LCDR2 comprising an amino acid sequence of SEQ ID NO: 28, and a LCDR3 comprising an amino acid sequence of SEQ ID NO: 19.

38. The composition of claim 34, wherein the HC comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 37 and the LC comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 144.

39. The composition of claim 23, wherein the GLP-1R agonist is liraglutide, albiglutide, taspoglutide, semaglutide, LY2428757, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, 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, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106,188IPTS / 200128039.1DOCKET NO: HEB-006WO PATENTSEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111 , SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 95% identical thereto.

40. The composition of claim 39, wherein the GLP-1R agonist is SEQ ID NO: 145, or SEQ ID NO: 146, or a peptide that is 95% identical thereto.

41. A method of treating a disease or disorder in a patient in need thereof, the method comprising administering the conjugate of any one of claims 1-21, or a pharmaceutical composition comprising the same, to the patient, thereby treating the disease or disorder.

42. A method of treating a disease or disorder in patient in need thereof, the method comprising administering the composition of any one of claims 23-40 to the patient, thereby treating the disease or disorder.

43. The method of claim 41 or claim 42, wherein the disease or disorder is selected from obesity, type 2 diabetes, coronary heart disease, lipodystrophy, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, Cushing’s syndrome, fatty liver disease, hyperphagia, Prader-Willi syndrome, metabolic syndrome, Kleine-Levin syndrome, Bardet-Biedl syndrome, Graves’ disease, cancer, Kluver-Bucy syndrome, Pick’s disease, Huntington’s chorea, Parkinson’s disease, hyperthyroidism, ischemic heart disease, stable angina pectoris, unstable angina, acute coronary syndrome, ST elevation myocardial infarction, non-ST elevation myocardial infarction, or any combination thereof.

44. A method of treating a disease or disorder in a diabetic patient in need thereof, the method comprising administering to the diabetic patient the conjugate of any one of claims 1-21, or a pharmaceutical composition comprising the same, or the composition of any one of claims 23-40 to the patient, thereby treating the disease or disorder, wherein the disease or disorder is selected from coronary hear! disease, lipodystrophy, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, fatty liver disease, hyperphagia, metabolic syndrome, hyperthyroidism, ischemic heart disease, hypertension, stable angina189IPTS / 200128039.1DOCKET NO: HEB-006WO PATENT pectoris, unstable angina, acute coronary syndrome, ST elevation myocardial infarction, non-ST elevation myocardial infarction, or any combination thereof.

45. The method of claim 44, wherein the disease or disorder is treated and the patient simultaneously experiences significant weight loss or does not experience significant weight loss.

46. The method of claim 44, wherein the disease is obesity.

47. The method of claim 46, wherein administration of the conjugate, pharmaceutical composition thereof, or composition induces weight loss, thereby treating obesity.

48. A method for blunting or reducing cravings in a subject in need thereof, the method comprising administering to the patient the conjugate of any one of claims 1 -21 , or a pharmaceutical composition comprising the same, or the composition of any one of claims 23-40 to the patient, thereby blunting or reducing the cravings.

49. The method of claim 48, wherein the craving is a food craving or the craving is related to addictive behavior.190IPTS / 200128039.1

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