WO2023183898A1

WO2023183898A1 - Formulations for anti-cd47 antibodies

Info

Publication number: WO2023183898A1
Application number: PCT/US2023/064897
Authority: WO
Inventors: David C. Boisvert
Original assignee: Arch Oncology, Inc.
Priority date: 2022-03-24
Filing date: 2023-03-24
Publication date: 2023-09-28

Abstract

A composition comprising (i) a CD47 binding protein; (ii) a sodium acetate buffer, (iii) polysorbate 20 or polysorbate 80, (iv) sorbitol, and (v) arginine.

Description

FORMULATIONS FOR ANTI-CD47 ANTIBODIES CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority to U.S. Provisional No.63/323,352, filed March 24, 2022, which is incorporated herein by reference in its entirety. TECHNICAL FIELD [0002] The present disclosure generally relates to the field of compositions comprising CD47 binding proteins. Methods of using the compositions are also provided herein. SEQUENCE LISTING [0003] The contents of the electronic sequence listing (ARCO_016_01WO_SeqList_ST26.xml; Size: 147,268 bytes; and Date of Creation: March 17, 2023) are herein incorporated by reference in its entirety. BACKGROUND [0004] Drug substances are usually administered as part of a formulation in combination with one or more other agents. Such agents serve various functions, e.g., solubilization, dilution, thickening, stabilization, preservation, coloring, flavoring, etc. Due to the varying properties of active drug substances, dosage forms typically require pharmaceutical excipients that are uniquely tailored to the active drug substance being formulated to achieve advantageous physical and pharmaceutical properties. SUMMARY [0005] There remains a need in the art for formulations for CD47 binding proteins that would have the highest product stability. [0006] In one aspect, provided herein is composition comprising (i) a CD47 binding protein comprising: (a) a variable heavy chain (VH) comprising a variable heavy chain CDR1 (HCDR1) of SEQ ID NO:3; a variable heavy chain CDR2 (HCDR2) of SEQ ID NO:6; a variable heavy chain CDR3 (HCDR3) of SEQ ID NO:10; and (b) a variablx xight chain (VL) comprising a variable light chain CDR1 (LCDR1) of SEQ ID NO:14; a variable light chain CDR2 (LCDR2) of SEQ ID NO:17; a variable light chain CDR3 (LCDR3) of SEQ ID NO:18; (ii) a buffer; and (iii) a surfactant. In some embodiments, the VH comprises the sequence of SEQ ID NO:36, or a sequence at least 90% identical thereto. In some embodiments, the VL comprises the sequence of SEQ ID NO:52, or a sequence at least 90% identical thereto. In some embodiments, the binding protein is a monoclonal antibody. In some embodiments, the monoclonal antibody is humanized. In some embodiments, the monoclonal antibody is an IgG1, IgG2, IgG3, or IgG4. In some embodiments, the monoclonal antibody is an IgG4. In some embodiments, the buffer is a sodium acetate buffer or a histidine buffer. In some embodiments, the concentration of the buffer is in the range of from about 0.1 mM to about 500 mM. In some embodiments, the concentration of the buffer is about 50 mM. In some embodiments, the surfactant is polysorbate 20 or polysorbate 80. In some embodiments, the concentration of polysorbate 20 is from about 0.001% to about 0.1% (w/v). In some embodiments, the concentration of polysorbate 20 is about 0.006% (w/v). In some embodiments, the concentration of polysorbate 20 is about 0.06% (w/v). In some embodiments, the composition comprises at least one additional excipient. In some embodiments, the at least one additional excipient is a sugar alcohol. In some embodiments, the sugar alcohol is sorbitol, mannitol, xylitol, lactitol, or erythritol. In some embodiments, the sugar alcohol is sorbitol. In some embodiments, the concentration of the sugar alcohol is in the range of from about 1% to about 10% (w/v). In some embodiments, the concentration of the sugar alcohol is about 3% (w/v). In some embodiments, the concentration of the sugar alcohol is about 6% (w/v). In some embodiments, the composition comprises at least one amino acid. In some embodiments, the at least one amino acid is arginine. In some embodiments, the at least one amino acid is glycine. In some embodiments, the concentration of the amino acid is from about 10 mM to about 200 mM. In some embodiments, the concentration of the amino acid is xbout 40 mM, about 60 mM, about 80 mM, or about 125 mM. In some embodiments, the composition comprises at least one salt. In some embodiments, the at least one salt is sodium chloride. In some embodiments, the concentration of the salt is from about 10 mM to about 200 mM. In some embodiments, the concentration of the salt is about 50 mM or about 100 mM. In some embodiments, the concentration of the CD47 binding protein is in the range of from about 1 g/L to about 250 g/L. In some embodiments, the concentration of the CD47 binding protein is about 50 g/L. In some embodiments, the concentration of the CD47 binding protein is about 182 g/L. In some embodiments, the composition has a pH in the range of from about 5.0 to about 7.0. In some embodiments, the composition has a pH of about 5.2. In some embodiments, the composition has a pH of about 6.2. In some embodiments, the composition has a pH of about 6.8. [0007] In another aspect, provided herein is a composition comprising: (i) a CD47 binding protein comprising: (a) a variable heavy chain (VH) comprising a variable heavy chain CDR1 (HCDR1) of SEQ ID NO: 3; a variable heavy chain CDR2 (HCDR2) of SEQ ID NO: 6; a variable heavy chain CDR3 (HCDR3) of SEQ ID NO: 10; and (b) a variable light chain (VL) comprising a variable light chain CDR1 (LCDR1) of SEQ ID NO: 14; a variable light chain CDR2 (LCDR2) of SEQ ID NO: 17; a variable light chain CDR3 (LCDR3) of SEQ ID NO: 18; (ii) a sodium acetate buffer, (iii) polysorbate 20 or polysorbate 80, (iv) sorbitol, and (v) arginine. In some embodiments, the concentration of the sodium acetate buffer is in the range of from about 10 mM to about 100 mM, the concentration of the polysorbate 20 is in the range of from about 0.001% to about 0.1% (w/v), the concentration of the sorbitol is in the range of from about 1% to about 10% (w/v), and the concentration of the arginine is in the range of from about 10 mM to about 200 mM. In some embodiments, the concentration of the sodium acetate buffer is about 50 mM, the concentration of the polysorbate 20 is about 0.06% (w/v), the concentration of the sorbitol is about 6% (w/v), and the concentration of the arginine is about 60 mM. In some embodiments, the composition has a pH of from about 5.0 to about 7.0. In some embodiments, the composition has a pH of about 5.2. In some embodiments, the concentration of the CD47 binding protein is in the range of from about 1 g/L to about 200 g/L. In some embodiments, the concentration of CD47 binding protein is about 50 g/L. In some embodiments, the concentration of CD47 binding protein is about 182 g/L. In some embodiments, the composition is for intravenous administration. In some embodiments, the composition is for subcutaneous administration. In some embodiments, the subcutaneous administration mitigates or prevents thrombocytopenia. In some embodiments, the CD47 binding protein is substantially stable for at least 30 days at a temperature in the range of from about 2°C to about 8°C. In some embodiments, the composition slows or reduces the degradation of the CD47 binding protein as compared to an identical composition lacking the surfactant, when stored under the same conditions. In some embodiments, the composition is substantially resistant to the formation of particles upon agitation. In some embodiments, the composition is substantially resistant to the formation of particles following at least one freeze/thaw cycle. In some embodiments, the composition is substantially resistant to changes to the charge of the CD47 binding protein over time. [0008] In another aspect, provided herein is a method for treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of the composition disclosed herein. In some embodiments, the cancer is leukemia, lymphoma, ovarian cancer, breast cancer, endometrial cancer, colon cancer, rectal cancer, gastric cancer, bladder cancer, lung cancer, bronchial cancer, bone cancer, prostate cancer, pancreatic cancer, liver and bile duct cancer, esophageal cancer, renal cancer, thyroid cancer, head and neck cancer, testicular cancer, glioblastoma, astrocytoma, melanoma, myelodysplasia syndrome, or sarcoma. In some embodiments, the cancer is a solid tumor. In some embodiments, the cancer is multiple myeloma, gastric adenocarcinoma/ gastroesophageal adenocarcinoma, endometrial carcinoma, platinum-resistant ovarian cancer, or diffuse large b-cell lymphoma. In some embodiments, the composition is administered intravenously. In some embodiments, the composition is administered subcutaneously. In some embodiments, the subcutaneous administration mitigates or prevents thrombocytopenia. [0009] In yet another aspect, provided herein is use of the composition provided herein for treating cancer in a subject. In some embodiments, the cancer is multiple myeloma, gastric adenocarcinoma/ gastroesophageal adenocarcinoma, endometrial carcinoma, platinum- resistant ovarian cancer, or diffuse large b-cell lymphoma. In some embodiments, the composition is administered intravenously. In some embodiments, the composition is administered subcutaneously. In some embodiments, the subcutaneous administration mitigates or prevents thrombocytopenia. [0010] In yet another aspect, provided herein is use of the composition provided herein in the manufacture of a medicament for treating cancer in a subject. In some embodiments, provided herein is use the cancer is multiple myeloma, gastric adenocarcinoma/ gastroesophageal adenocarcinoma, endometrial carcinoma, platinum-resistant ovarian cancer, or diffuse large b-cell lymphoma. In some embodiments, the composition is administered intravenously. In some embodiments, the composition is administered subcutaneously. In some embodiments, the subcutaneous administration mitigates or prevents thrombocytopenia. [0011] In yet another aspect, provided herein is a kit for treating cancer in a subject in need thereof, the kit comprising the composition of disclosed herein contained in a vessel. In some embodiments, the kit further comprises instructions for using the composition. BRIEF DESCRIPTION OF FIGURES [0012] Fig.1 shows pH values of VLX9 formulations under various stress conditions. [0013] Fig.2 shows A280nm values of VLX9 formulations under various stress conditions. [0014] Fig.3 shows size exclusion chromatography (SEC) data for high molecular weight (HMW) species in the VLX9 formulations under various stress conditions. [0015] Fig. 4 shows SEC data for main peak species in the VLX9 formulations under various stress conditions. [0016] Fig. 5 shows SEC data for low molecular weight (LMW) species in the VLX9 formulations under various stress conditions. [0017] Fig. 6A – Fig. 6C shows design of experiments (DOE) models for area as a percentage of the main peak species (Fig. 6A), LMW species (Fig. 6B), and HMW species (Fig.6C). [0018] Fig.7 shows an exemplary capillary isoelectric focusing (cIEF) electropherogram. [0019] Fig.8A – Fig.8E show cIEF results for the acidic peak (Fig.8A), major peak 1 (Fig. 8B), major peak 2 (Fig. 8C), major peak 3 (Fig. 8D), and basic peak (Fig. 8E) in the VLX9 formulations under various stress conditions. [0020] Fig.9A – Fig.9E show the cIEF DOE models for the Acidic Peak (Fig.9A), Main Peak 1 (Fig.9B), Main Peak 2 (Fig.9C), Main Peak 3 (Fig.9D), and Basic Peak (Fig.9E). [0021] Fig. 10 shows LabChip results for reduced (LC+HC) VLX9 in the VLX9 formulations under various stress conditions. [0022] Fig. 11 shows LabChip results for non-reduced (intact IgG) VLX9 in the VLX9 formulations under various stress conditions. [0023] Fig.12A – Fig.12D shows microfluidic imaging (MFI) results for particles in four size ranges: 2 μm ≤ x < 5 μm (Fig.12A), 5 μm ≤ x < 10 μm (Fig. 12B), 10 μm ≤ x < 25 μm (Fig.12C); and ≥ 25 μm (Fig.12D) in the VLX9 formulations under various stress conditions. [0024] Fig.13A – Fig.13D show the MFI Week 8 stability DOE model for particles 2 μm ≤ x < 5 μm (Fig.13A), 5 μm ≤ x < 10 μm (Fig.13B), 10 μm ≤ x < 25 μm (Fig.13C), and 25 μm ≤ x (Fig.13D), respectively. [0025] Fig.14A – Fig.14D show the MFI Agitation stability DOE model for particles 2 μm ≤ x < 5 μm (Fig.14A), 5 μm ≤ x < 10 μm (Fig.14B), 10 μm ≤ x < 25 μm (Fig.14C), and 25 μm ≤ x (Fig.14D), respectively. [0026] Fig.15A – Fig. 15D show the MFI Freeze/Thaw stability DOE model for particles 2 μm ≤ x < 5 μm (Fig.15A), 5 μm ≤ x < 10 μm (Fig.15B), 10 μm ≤ x < 25 μm (Fig.15C), and 25 μm ≤ x (Fig.15D), respectively. [0027] Fig.16 shows ELISA binding results for VLX9 Formulation A1a. [0028] Fig.17 shows the DOE model of potency by ELISA. [0029] Fig. 18A – Fig. 18C show VLX9 related changes of RBC-related parameters in female cynomolgus monkeys. Fig.18A shows hemoglobin (HGB) concentrations (g/dL). Fig. 18B shows reticulocyte counts (thou/µL). Fig. 18C shows red cell distribution width (RDW) (%). [0030] Fig. 19 shows VLX9 related changes in monocyte counts in female cynomolgus monkeys. [0031] Fig. 20 shows VLX9 related changes in platelet counts in female cynomolgus monkeys. [0032] Fig.21 shows VLX9 related changes in albumin, globulin, total protein, and albumin to globulin ratio (AG) in female cynomolgus monkeys. [0033] Fig. 22 shows blood mean absolute immunophenotyping values for total T cells in female cynomolgus monkeys. [0034] Fig.23 shows blood mean absolute immunophenotyping values for T-helper cells in female cynomolgus monkeys. [0035] Fig.24 shows blood mean absolute immunophenotyping values for cytotoxic T cells in female cynomolgus monkeys. [0036] Fig. 25 shows blood mean absolute immunophenotyping values for total B cells in female cynomolgus monkeys. [0037] Fig. 26 shows blood mean absolute immunophenotyping values for total dendritic cells in female cynomolgus monkeys. [0038] Fig.27 shows blood mean absolute immunophenotyping values for total activated T cells in female cynomolgus monkeys. [0039] Fig. 28 shows blood mean absolute immunophenotyping values for activated cytotoxic T cells in female cynomolgus monkeys. [0040] Fig. 29 shows blood mean absolute immunophenotyping values for total Natural Killer (NK) cells in female cynomolgus monkeys. [0041] Fig.30 provides a summary of organ weight data at terminal euthanasia. [0042] Figs. 31A and 31B provide a summary of VLX9-realted microscopic findings at terminal euthanasia. [0043] Fig.32 provides a summary of analyzed toxicokinetic parameters of VLX9. DETAILED DESCRIPTION [0044] Disclosed herein are compositions comprising CD47 binding proteins and one or more agents for improving the physical and pharmaceutical properties of the compositions. Also provided herein are methods for treating diseases, such as cancers, autoimmune diseases, inflammatory diseases, ischemia. Further disclosed herein are kits for treating diseases. Definitions [0045] Unless otherwise defined herein, technical and scientific terms used in the present description have the meanings that are commonly understood by those of ordinary skill in the art. For purposes of interpreting this specification, the following description of terms will apply and whenever appropriate, terms used in the singular will also include the plural and vice versa unless the content clearly dictates otherwise. In the event that any description of a term set forth conflicts with any document incorporated herein by reference, the description of the term set forth below shall control. [0046] As used herein, the singular forms “a,” “an” and “the” include plural references unless the context clearly dictates otherwise. [0047] As used herein, the term “and/or” is used in this disclosure to either “and” or “or” unless indicated otherwise. [0048] As used herein, “about”, “approximately,” “substantially,” and “significantly” will be understood by persons of ordinary skill in the art and will vary to some extent on the context in which they are used. If there are uses of the term which are not clear to persons of ordinary skill in the art given the context in which it is used, “about” and “approximately” will mean up to plus or minus 10% of the particular term and “substantially” and “significantly” will mean more than plus or minus 10% of the particular term. [0049] The term “CD47”, “integrin-associated protein (IAP)”, “ovarian cancer antigen OA3”, “Rh-related antigen” and “MERG” are synonymous and may be used interchangeably. [0050] The term “antibody” refers to immunoglobulin molecules and immunologically active portions of immunoglobulin (Ig) molecules, i.e., molecules that contain an antigen binding site that specifically binds (immunoreacts with) an antigen. “Specifically binding” or “immuno reacting” with or against means that the antibody reacts with one or more antigenic determinants of the desired antigen and does not react with other polypeptides or binds at a much lower affinity (K_d > 10^-6). Antibodies include but are not limited to, polyclonal, monoclonal, chimeric, Fab fragments, Fab’ fragments, F(ab’)2 fragments, single chain Fv fragments, and one-armed antibodies. [0051] The term “monoclonal antibody” (mAb) refers to an antibody that is derived from a single copy or clone including, for example, any eukaryotic, prokaryotic, or phage clone, and not the method by which it is produced. mAbs of the present disclosure preferably exist in a homogeneous or substantially homogeneous population. Complete mAbs contain 2 heavy chains and 2 light chains. [0052] The term “antibody fragment” refers to a molecule other than an intact antibody that comprises a portion of an intact antibody that binds the antigen to which the intact antibody binds. Examples of antibody fragments include but are not limited to Fv, Fab, Fab’, Fab’-SH, F(ab’)2; diabodies; linear antibodies; single-chain antibody molecules (e.g., scFv); and multispecific antibodies formed from antibody fragments. [0053] The term “antigen-binding site” refers to the “Hypervariable regions”, “HVRs”, or “HVs”, and refer to the structurally hypervariable regions of antibody variable domains as defined by Chothia and Lesk (Chothia and Lesk, Mol. Biol.196:901-917, 1987). There are six HVRs, three in VH (H1, H2, H3) and three in VL (L1, L2, L3). We used herein complementarity-determining regions (CDRs) as defined by Kabat except in H-CDR1, which is extended to include H1. [0054] The term “epitope” refers to a specific arrangement of amino acids located on a peptide or protein to which an antibody or antibody fragment binds. Epitopes often consist of a chemically active surface grouping of molecules such as amino acids or sugar side chains, and have specific three dimensional structural characteristics as well as specific charge characteristics. Epitopes can be linear, i.e., involving binding to a single sequence of amino acids, or conformational, i.e., involving binding to two or more sequences of amino acids in various regions of the antigen that may not necessarily be contiguous in the linear sequence. [0055] The terms “specifically binds”, “bind specifically”, “specific binding”, and the like refer to the ability of a specific binding agent (such as an antibody) to bind to a target molecular species in preference to binding to other molecular species with which the specific binding agent and target molecular species are admixed. A specific binding agent is said specifically to recognize a target molecular species when it can bind specifically to that target. [0056] The term “binding affinity” refers to the strength of binding of one molecule to another at a site on the molecule. If a particular molecule will bind to or specifically associate with another particular molecule, these two molecules are said to exhibit binding affinity for each other. Binding affinity is related to the association constant and dissociation constant for a pair of molecules, but it is not critical to the methods herein that these constants be measured or determined. Rather, affinities as used herein to describe interactions between molecules of the described methods are generally apparent affinities (unless otherwise specified) observed in empirical studies, which can be used to compare the relative strength with which one molecule (e.g., an antibody or other specific binding partner) will bind two other molecules (e.g., two versions or variants of a peptide). The concepts of binding affinity, association constant, and dissociation constant are well known. [0057] The terms “humanized”, “humanization”, and the like, refer to grafting of the murine monoclonal antibody CDRs disclosed herein to human frameworks (FRs) and constant regions. Also encompassed by these terms are possible further modifications to the murine CDRs, and human FRs, by the methods disclosed in, for example, Kashmiri et al. (2005) Methods 36(1):25-34 and Hou et al. (2008) J. Biochem. 144(1):115-120, respectively, to improve various antibody properties. [0058] The term “humanized antibodies” refers to mAbs and antigen binding fragments thereof, that have binding and functional properties according to the disclosure similar to those disclosed herein, and that have FRs and constant regions that are substantially human or fully human surrounding CDRs derived from a non-human antibody. [0059] The term “sequence identity” means the percentage of identical nucleotide or amino acid residues at corresponding positions in two or more sequences when the sequences are aligned to maximize sequence matching, i.e., taking into account gaps and insertions. Identity can be readily calculated by known methods, including but not limited to those described in: Computational Molecular Biology, Lesk, A. M., ed., Oxford University Press, New York, 1988; Biocomputing: Informatics and Genome Projects, Smith, D. W., ed., Academic Press, New York, 1993; Computer Analysis of Sequence Data, Part I, Griffin, A. M., and Griffin, H. G., eds., Humana Press, New Jersey, 1994; Sequence Analysis in Molecular Biology, von Heinje, G., Academic Press, 1987; and Sequence Analysis Primer, Gribskov, M. and Devereux, J., eds., M Stockton Press, New York, 1991; and Carillo, H., and Lipman, D., SIAM J. Applied Math., 48: 1073 (1988). Methods to determine identity are designed to give the largest match between the sequences tested. Moreover, methods to determine identity are codified in publicly available computer programs. Optimal alignment of sequences for comparison can be conducted, for example, by the local homology algorithm of Smith & Waterman, by the homology alignment algorithms, by the search for similarity method or, by computerized implementations of these algorithms (GAP, BESTFIT, PASTA, and TFASTA in the GCG Wisconsin Package, available from Accelrys, Inc., San Diego, California, United States of America), or by visual inspection. See generally, Altschul, S. F. et al., J. Mol. Biol. 215: 403- 410 (1990) and Altschul et al. Nucl. Acids Res.25: 3389-3402 (1997). [0060] One example of an algorithm that is suitable for determining percent sequence identity and sequence similarity is the BLAST algorithm, which is described in (Altschul, S., et al., NCBI NLM NIH Bethesda, Md. 20894; and Altschul, S., et al., J. Mol. Biol. 215: 403-410 (1990). Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information. This algorithm involves first identifying high scoring sequence pairs (HSPs) by identifying short words of length in the query sequence, which either match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold. These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them. The word hits are then extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Cumulative scores are calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always; 0) and N (penalty score for mismatching residues; always; 0). For amino acid sequences, a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value, the cumulative score goes to zero or below due to the accumulation of one or more negative-scoring residue alignments, or the end of either sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses as defaults a word length (W) of 11, an expectation (E) of 10, a cutoff of 100, M = 5, N = -4, and a comparison of both strands. For amino acid sequences, the BLASTP program uses as defaults a word length (W) of 3, an expectation (E) of 10, and the BLOSUM62 scoring matrix. [0061] In addition to calculating percent sequence identity, the BLAST algorithm also performs a statistical analysis of the similarity between two sequences. One measure of similarity provided by the BLAST algorithm is the smallest sum probability (P(N)), which provides an indication of the probability by which a match between two nucleotide or amino acid sequences would occur by chance. For example, a test nucleic acid sequence is considered similar to a reference sequence if the smallest sum probability in a comparison of the test nucleic acid sequence to the reference nucleic acid sequence is in one embodiment less than about 0.1, in another embodiment less than about 0.01, and in still another embodiment less than about 0.001. [0062] The term “pharmaceutically acceptable” refers to being approved by a regulatory agency of the Federal or a state government or listed in United States Pharmacopeia, European Pharmacopeia or other generally recognized Pharmacopeia for use in animals, and more particularly in humans. [0063] The term “excipient” refers to a pharmaceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, solvent, or encapsulating material. Excipients include, for example, encapsulating materials or additives such as absorption accelerators, antioxidants, binders, buffers, carriers, coating agents, coloring agents, diluents, disintegrating agents, emulsifiers, extenders, fillers, flavoring agents, humectants, lubricants, perfumes, preservatives, propellants, releasing agents, sterilizing agents, sweeteners, solubilizers, wetting agents and mixtures thereof. The term “excipient” can also refer to a diluent, adjuvant (e.g., Freunds’ adjuvant (complete or incomplete) or vehicle. [0064] The term “effective amount” or “therapeutically effective amount” refers to the amount of binding molecule (e.g., an antibody) or pharmaceutical composition provided herein which is sufficient to result in the desired outcome. [0065] The term “administer” or “administration” refers to the act of injecting or otherwise physically delivering a substance as it exists outside the body into a patient, such as by mucosal, intradermal, intravenous, intramuscular delivery, and/or any other method of physical delivery disclosed herein or known in the art. [0066] The term “tumor” refers to all neoplastic cell growth and proliferation, whether malignant or benign, and all pre-cancerous and cancerous cells and tissues. The terms “cancer”, “cancerous”, and “tumor” are not mutually exclusive as used herein. [0067] The terms “cancer” and “cancerous” refer to or describe the physiological condition in mammals that is typically characterized by aberrant cell growth/proliferation. Examples of cancers include, but are not limited to, carcinoma, lymphoma (i.e., Hodgkin’s and non- Hodgkin’s lymphoma), blastoma, sarcoma, and leukemia. More particular examples of such cancers include squamous cell cancer, small-cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung, squamous carcinoma of the lung, cancer of the peritoneum, hepatocellular cancer, gastrointestinal cancer, pancreatic cancer, glioma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, breast cancer, colon cancer, colorectal cancer, endometrial or uterine carcinoma, salivary gland carcinoma, kidney cancer, liver cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma, leukemia and other lymphoproliferative disorders, and various types of head and neck cancer. [0068] The term “susceptible cancer” refers to a cancer, cells of which express CD47, and are responsive to treatment with an antibody or antigen binding fragment thereof, or competing antibody or antigen binding fragment thereof, of the present disclosure. [0069] The term “autoimmune disease” refers to when the body’s immune system turns against itself and mistakenly attacks healthy cells. [0070] The term “inflammatory disease” refers to a disease characterized by inflammation which is a fundamental pathologic process consisting of a dynamic complex of histologically apparent cytologic changes, cellular infiltration, and mediator release that occurs in the affected blood vessels and adjacent tissues in response to an injury or abnormal stimulation caused by a physical, chemical, or biologic agent, including the local reactions and resulting morphologic changes; the destruction or removal of the injurious material; and the responses that lead to repair and healing. [0071] The term “autoinflammatory disease” refers to a disease that results when the innate immune system causes inflammation for unknown reasons. [0072] The term “ischemia” refers to a vascular phenomenon in which a decrease in the blood supply to a bodily organ, tissue, or part is caused, for instance, by constriction or obstruction of one or more blood vessels. Ischemia sometimes results from vasoconstriction or thrombosis or embolism. Ischemia can lead to direct ischemic injury, tissue damage due to cell death caused by reduced oxygen supply. Ischemia can occur acutely, as during surgery, or from trauma to tissue incurred in accidents, injuries and war settings, or following harvest of organs intended for subsequent transplantation, for example. It can also occur sub-acutely, as found in atherosclerotic peripheral vascular disease, where progressive narrowing of blood vessels leads to inadequate blood flow to tissues and organs. When a tissue is subjected to ischemia, a sequence of chemical events is initiated that may ultimately lead to cellular dysfunction and necrosis. If ischemia is ended by the restoration of blood flow, a second series of injurious events ensue, producing additional injury. Thus, whenever there is a transient decrease or interruption of blood flow in a subject, the resultant injury involves two components--the direct injury occurring during the ischemic interval, and the indirect or reperfusion injury that follows. [0073] The term “reperfusion” refers to restoration of blood flow to tissue that is ischemic, due to decrease in blood flow. Reperfusion is a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. In addition to the immediate injury that occurs during deprivation of blood flow, “ischemic/reperfusion injury” involves tissue injury that occurs after blood flow is restored. Current understanding is that much of this injury is caused by chemical products, free radicals, and active biological agents released by the ischemic tissues. [0074] The term “treating” or “treat” or “treatment” refers to slowing, interrupting, arresting, controlling, stopping, reducing, or reversing the progression or severity of a sign, symptom, disorder, condition, or disease, but does not necessarily involve a total elimination of all disease-related signs, symptoms, conditions, or disorders. The term “treating” and the like refer to a therapeutic intervention that ameliorates a sign or symptom of a disease or pathological condition after it has begun to develop. [0075] The term “effective amount” refers to the amount or dose of an antibody compound of the present disclosure which, upon single or multiple dose administration to a patient or organ, provides the desired treatment or prevention. CD47 Binding Proteins [0076] In one aspect, disclosed herein are CD47 binding proteins. In some embodiments, the CD47 binding proteins are anti-CD47 antibodies. In some embodiments, the CD47 binding proteins are monoclonal antibodies, such as those disclosed in PCT/US2016/052383 and PCT/US2017/057716, the content of each of which is incorporated herein by reference in its entirety. [0077] A full-length antibody as it exists naturally is a “Y” shaped immunoglobulin (Ig) molecule comprising four polypeptide chains: two identical heavy (H) chains and two identical light (L) chains, interconnected by disulfide bonds. The amino terminal portion of each chain, termed the fragment antigen binding region (FAB), includes a variable region of about 100- 110 or more amino acids primarily responsible for antigen recognition via the complementarity determining regions (CDRs) contained therein. The carboxy-terminal portion of each chain defines a constant region (the “Fc” region) primarily responsible for effector function. [0078] The CDRs are interspersed with regions that are more conserved, termed frameworks (“FRs”). Amino acid sequences of many FRs are well known in the art. Each light chain variable region (LCVR) and heavy chain variable region (HCVR) is composed of 3 CDRs and 4 FRs, arranged from amino-terminus to carboxy-terminus in the following order: FRl, CDRl, FR2, CDR2, FR3, CDR3, FR4. The 3 CDRs of the light chain are referred to as “LCDRl, LCDR2, and LCDR3” and the 3 CDRs of the heavy chain are referred to as “HCDRl, HCDR2, and HCDR3.” The CDRs contain most of the residues which form specific interactions with the antigen. The numbering and positioning of CDR amino acid residues within the LCVR and HCVR regions are in accordance with the well-known Kabat numbering convention Kabat et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition. NIH Publication No. 91-3242. [0079] There are five types of mammalian immunoglobulin (Ig) heavy chains, denoted by the Greek letters α (alpha), δ (delta), ε (epsilon), γ (gamma), and μ (mu), which define the class or isotype of an antibody as IgA, IgD, IgE, IgG, or IgM, respectively. IgG antibodies can be further divided into subclasses, for example, IgGl, IgG2, IgG3, and IgG4. Each heavy chain type is characterized by a particular constant region with a sequence well known in the art. The constant region is identical in all antibodies of the same isotype, but differs in antibodies of different isotypes. Heavy chains γ, α, and δ have a constant region composed of three tandem immunoglobulin (Ig) domains, and a hinge region for added flexibility. Heavy chains μ and ε have a constant region composed of four Ig domains. The hinge region is a flexible amino acid stretch that links the Fc and Fab portions of an antibody. This region contains cysteine residues that can form disulfide bonds, connecting two heavy chains together. The variable region of the heavy chain differs in antibodies produced by different B cells, but is the same for all antibodies produced by a single B cell or B cell clone. The variable region of each heavy chain is approximately 110 amino acids long and is composed of a single Ig domain. [0080] In mammals, light chains are classified as kappa (κ) or lambda (λ), and are characterized by a particular constant region as known in the art. A light chain has two successive domains: one variable domain at the amino-terminal end, and one constant domain at the carboxy-terminal end. Each antibody contains two light chains that are always identical; only one type of light chain, κ or λ, is present per antibody in mammals. [0081] The Fc region, composed of two heavy chains that contribute three or four constant domains depending on the class of the antibody, plays a role in modulating immune cell activity. By binding to specific proteins, the Fc region ensures that each antibody generates an appropriate immune response for a given antigen. The Fc region also binds to various cell receptors, such as Fc receptors, and other immune molecules, such as complement proteins. By doing this, it mediates different physiological effects, including opsonization, cell lysis, and degranulation of mast cells, basophils and eosinophils. [0082] The monoclonal antibodies encompass antibodies in which a portion of the heavy and/or light chain is identical with, or homologous to, corresponding sequences in murine antibodies, in particular the murine CDRs, while the remainder of the chain(s) is (are) identical with, or homologous to, corresponding sequences in human antibodies. Other embodiments of the disclosure include antigen-binding fragments of these monoclonal antibodies that exhibit binding and biological properties similar or identical to the monoclonal antibodies. The antibodies of the present disclosure can comprise kappa or lambda light chain constant regions, and heavy chain IgA, IgD, IgE, IgG, or IgM constant regions, including those of IgG subclasses IgG1, IgG2, IgG3, and IgG4 and in some cases with various mutations to alter Fc receptor function. [0083] Fully human frameworks are those that are identical to a known human germline framework sequence. Human FR germline sequences can be obtained from the international ImMunoGeneTics (IMGT) database and from The Immunoglobulin FactsBook by Marie-Paule Lefranc and Gerard Lefranc, Academic Press, 2001, the contents of which are herein incorporated by reference in their entirety. The Immunoglobulin Facts Book is a compendium of the human germline immunoglobulin genes that are used to create the human antibody repertoire, and includes entries for 203 genes and 459 alleles, with a total of 837 displayed sequences. The individual entries comprise all the human immunoglobulin constant genes, and germline variable, diversity, and joining genes that have at least one functional or open reading frame allele, and which are localized in the three major loci. For example, germline light chain FRs can be selected from the group consisting of: IGKV3D-20, IGKV2-30, IGKV2-29, IGKV2-28, IGKV1-27, IGKV3-20, IGKV1-17, IGKV1-16, 1-6, IGKV1-5, IGKV1-12, IGKV1D-16, IGKV2D-28, IGKV2D-29, IGKV3-11, IGKV1-9, IGKV1-39, IGKV1D-39 and IGKV1D-33 and IGKJ1-5 and germline heavy chain FRs can be selected from the group consisting of: IGHV1-2, IGHV1-18, IGHV1-46, IGHV1-69, IGHV2-5, IGHV2-26, IGHV2- 70, IGHV1-3, IGHV1-8, IGHV3-9, IGHV3-11, IGHV3- 15, IGHV3-20, IGHV3-66, IGHV3- 72, IGHV3-74, IGHV4-31, IGHV3-21, IGHV3-23, IGHV3-30, IGHV3-48, IGHV4-39, IGHV4-59 and IGHV5-51 and IGHJ1-6. [0084] Substantially human FRs are those that have at least 80% sequence identity to a known human germline FR sequence. Preferably, the substantially human frameworks have at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity, to a framework sequences disclosed herein, or to a known human germline framework sequence. [0085] Several different methods can be used to generate humanized antibodies, which are disclosed herein. In one approach, the parent antibody compound CDRs are grafted into a human FR that has a high sequence identity with the parent antibody compound framework. The sequence identity of the new FR will generally be at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the sequence of the corresponding FR in the parent antibody compound. In the case of FRs having fewer than 100 amino acid residues, one, two, three, four, five, or more amino acid residues can be changed. This grafting may result in a reduction in binding affinity compared to that of the parent antibody. If this is the case, the FR can be back-mutated to the parent framework at certain positions based on specific criteria disclosed by Queen et al. (1991) Proc. Natl. Acad. Sci. USA 88:2869. Additional references describing methods useful to generate humanized variants based on homology and back mutations include as described in Olimpieri et al. Bioinformatics.2015 Feb 1;31(3):434-435 and U.S. Patents 4,816,397, 5,225,539, and 5,693,761; and the method of Winter and co-workers (Jones et al. (1986) Nature 321:522-525; Riechmann et al. (1988) Nature 332:323-327; and Verhoeyen et al. (1988) Science 239:1534- 1536. [0086] The identification of residues to consider for back-mutation can be carried out as described below. When an amino acid falls under the following category, the framework amino acid of the human germ-line sequence that is being used (the “acceptor FR”) is replaced by a framework amino acid from a framework of the parent antibody compound (the “donor FR”): (a) the amino acid in the human FR of the acceptor framework is unusual for human frameworks at that position, whereas the corresponding amino acid in the donor immunoglobulin is typical for human frameworks at that position; (b) the position of the amino acid is immediately adjacent to one of the CDRs; or (c) any side chain atom of a framework amino acid is within about 5-6 angstroms (center-to- center) of any atom of a CDR amino acid in a three dimensional immunoglobulin model. [0087] When each of the amino acids in the human FR of the acceptor framework and a corresponding amino acid in the donor framework is generally unusual for human frameworks at that position, such amino acid can be replaced by an amino acid typical for human frameworks at that position. This back-mutation criterion enables one to recover the activity of the parent antibody compound. [0088] Another approach to generating humanized antibodies exhibiting similar functional properties to the antibody compounds disclosed herein involves randomly mutating amino acids within the grafted CDRs without changing the framework, and screening the resultant molecules for binding affinity and other functional properties that are as good as, or better than, those of the parent antibody compounds. Single mutations can also be introduced at each amino acid position within each CDR, followed by assessing the effects of such mutations on binding affinity and other functional properties. Single mutations producing improved properties can be combined to assess their effects in combination with one another. [0089] Further, a combination of both of the foregoing approaches is possible. After CDR grafting, one can back-mutate specific FRs in addition to introducing amino acid changes in the CDRs. This methodology is described in Wu et al. (1999) J. Mol. Biol.294: 151-162. [0090] The monoclonal antibody or antigen-binding fragment thereof, or competing antibody disclosed herein can be of the human IgG1 isotype. [0091] The human IgGl constant region of the monoclonal antibody, antigen-binding fragment thereof, or competing antibody disclosed herein can be modified to alter antibody half-life. Antibody half-life is regulated in large part by Fc-dependent interactions with the neonatal Fc receptor (Roopenian and Alikesh, 2007). The human IgG1 constant region of the monoclonal antibody, antigen-binding fragment thereof, or competing antibody can be modified to increase half-life include, but are not limited to amino acid modifications N434A, T307A/E380A/N434A (Petkova et al., 2006, Yeung et al., 2009); M252Y/S254T/T256E (Dall’Acqua et al., 2006); T250Q/M428L (Hinton et al., 2006); and M428L/N434S (Zalevsky et al., 2010). [0092] As opposed to increasing half-life, there are some circumstances where decreased half-life would be desired, such as to reduce the possibility of adverse events associated with high Antibody-Dependent Cellular Cytotoxicity (ADCC) and Complement-Dependent Cytotoxicity (CDC) antibodies (Presta 2008). The human IgG1 constant region of the monoclonal antibody, antigen-binding fragment thereof, or competing antibody disclosed herein can be modified to decrease half-life and/or decrease endogenous IgG include, but are not limited to amino acid modifications I253A (Petkova et al., 2006); P257I/N434H, D376V/N434H (Datta-Mannan et al., 2007); and M252Y/S254T/T256E/H433K/N434F (Vaccaro et al., 2005). [0093] The human IgGl constant region of the monoclonal antibody, antigen-binding fragment thereof, or competing antibody disclosed herein can be modified to increase or decrease antibody effector functions. These antibody effector functions include, but are not limited to, Antibody-Dependent Cellular Cytotoxicity (ADCC), Complement-Dependent Cytotoxicity (CDC), Antibody-Dependent Cellular Phagocytosis (ADCP), C1q binding, and altered binding to Fc receptors. [0094] The human IgGl constant region of the monoclonal antibody, antigen-binding fragment thereof, or competing antibody disclosed herein can be modified to increase antibody effector function include, but are not limited to amino acid modifications S298A/E333A/K334 (Shields et al., 2001); S239D/I332E and S239D/A330L/I332E (Lazar et al., 2006); F234L/R292P/Y300L, F234L/R292P/Y300L/P393L, and F243L/R292P/Y300L/V305I/P396L (Stevenhagen et al., 2007); G236A, G236A/S239D/I332E, and G236A/S239D/A330L/I332E (Richards et al., 2008); K326A/E333A, K326A/E333S and K326W/E333S (Idusogie et al., 2001); S267E and S267E/L328F (Smith et al., 2012); H268F/S324T, S267E/H268F, S267E/S234T, and S267E/H268F/S324T (Moore et al., 2010); S298G/T299A (Sazinsky et al., 2008); E382V/M428I (Jung et al., 2010). [0095] The human IgGl constant region of the monoclonal antibody, antigen-binding fragment thereof, or competing antibody disclosed herein can be modified to decrease antibody effector function include, but are not limited to amino acid modifications N297A and N297Q (Bolt et al., 1993, Walker et al., 1989); L234A/L235A (Xu et al., 2000); K214T/E233P/L234V/L235A/G236-deleted/A327G/P331A/D356E/L358M (Ghevaert et al., 2008); C226S/C229S/E233P/L234V/L235A (McEarchern et al., 2007); S267E/L328F (Chu et al., 2008). [0096] The human IgG1 constant region of the monoclonal antibody, antigen-binding fragment thereof, or competing antibody disclosed herein can be modified to decrease antibody effector function include, but are not limited to amino acid modifications V234A/G237A (Cole et al., 1999); E233D, G237D, P238D, H268Q, H268D, P271G, V309L, A330S, A330R, P331S, H268Q/A330S/V309L/P331S, H268D/A330S/V309L/P331S, H268Q/A330R/V309L/P331S, H268D/A330R/V309L/P331S, E233D/A330R, E233D/A330S, E233D/P271G/A330R, E233D/P271G/A330S, G237D/H268D/P271G, G237D/H268Q/P271G, G237D/ P271G/A330R, G237D/ P271G/A330S, E233D/H268D/P271G/A330R, E233D/H268Q/P271G/A330R, E233D/H268D/P271G/A330S, E233D/H268Q/P271G/A330S, G237D/H268D/P271G/A330R, G237D/H268Q/P271G/A330R, G237D/H268D/P271G/A330S, G237D/H268Q/P271G/A330S, E233D/G237D/H268D/P271G/A330R, E233D/G237D/H268Q/P271G/A330R, E233D/G237D/H268D/P271G/A330S, E233D/G237D/H268Q/P271G/A330S, P238D/E233D/A330R, P238D/E233D/A330S, P238D/E233D/P271G/A330R, P238D/E233D/P271G/A330S, P238D/G237D/H268D/P271G, P238D/G237D/H268Q/P271G, P238D/G237D/ P271G/A330R, P238D/G237D/ P271G/A330S, P238D/E233D/H268D/P271G/A330R, P238D/E233D/H268Q/P271G/A330R, P238D/E233D/H268D/P271G/A330S, P238D/E233D/H268Q/P271G/A330S, P238D/G237D/H268D/P271G/A330R, P238D/G237D/H268Q/P271G/A330R, P238D/G237D/H268D/P271G/A330S, P238D/G237D/H268Q/P271G/A330S, P238D/E233D/G237D/H268D/P271G/A330R, P238D/E233D/G237D/H268Q/P271G/A330R, P238D/E233D/G237D/H268D/P271G/A330S, P238D/E233D/G237D/H268Q/P271G/A330S (An et al., 2009, Mimoto, 2013). [0097] The monoclonal antibody or antigen-binding fragment thereof, or competing antibody disclosed herein can be of the human IgG2 isotype. [0098] The human IgG2 constant region of the monoclonal antibody, antigen-binding fragment thereof, or competing antibody disclosed herein can be modified to increase or decrease antibody effector functions. These antibody effector functions include, but are not limited to, Antibody-Dependent Cellular Cytotoxicity (ADCC), Complement-Dependent Cytotoxicity (CDC), Antibody-Dependent Cellular Phagocytosis (ADCP), and C1q binding, and altered binding to Fc receptors. [0099] The human IgG2 constant region of the monoclonal antibody, antigen-binding fragment thereof, or competing antibody disclosed herein can be modified to increase antibody effector function include, but are not limited to the amino acid modification K326A/E333S (Idusogie et al., 2001). [0100] The human IgG2 constant region of the monoclonal antibody, antigen-binding fragment thereof, or competing antibody disclosed herein can be modified to decrease antibody effector function include, but are not limited to amino acid modifications V234A/G237A (Cole et al., 1999); E233D, G237D, P238D, H268Q, H268D, P271G, V309L, A330S, A330R, P331S, H268Q/A330S/V309L/P331S, H268D/A330S/V309L/P331S, H268Q/A330R/V309L/P331S, H268D/A330R/V309L/P331S, E233D/A330R, E233D/A330S, E233D/P271G/A330R, E233D/P271G/A330S, G237D/H268D/P271G, G237D/H268Q/P271G, G237D/ P271G/A330R, G237D/ P271G/A330S, E233D/H268D/P271G/A330R, E233D/H268Q/P271G/A330R, E233D/H268D/P271G/A330S, E233D/H268Q/P271G/A330S, G237D/H268D/P271G/A330R, G237D/H268Q/P271G/A330R, G237D/H268D/P271G/A330S, G237D/H268Q/P271G/A330S, E233D/G237D/H268D/P271G/A330R, E233D/G237D/H268Q/P271G/A330R, E233D/G237D/H268D/P271G/A330S, E233D/G237D/H268Q/P271G/A330S, P238D/E233D/A330R, P238D/E233D/A330S, P238D/E233D/P271G/A330R, P238D/E233D/P271G/A330S, P238D/G237D/H268D/P271G, P238D/G237D/H268Q/P271G, P238D/G237D/ P271G/A330R, P238D/G237D/ P271G/A330S, P238D/E233D/H268D/P271G/A330R, P238D/E233D/H268Q/P271G/A330R, P238D/E233D/H268D/P271G/A330S, P238D/E233D/H268Q/P271G/A330S, P238D/G237D/H268D/P271G/A330R, P238D/G237D/H268Q/P271G/A330R, P238D/G237D/H268D/P271G/A330S, P238D/G237D/H268Q/P271G/A330S, P238D/E233D/G237D/H268D/P271G/A330R, P238D/E233D/G237D/H268Q/P271G/A330R, P238D/E233D/G237D/H268D/P271G/A330S, P238D/E233D/G237D/H268Q/P271G/A330S (An et al., 2009, Mimoto, 2013). [0101] The Fc region of a human IgG2 of the monoclonal antibody, antigen-binding fragment thereof, or competing antibody disclosed herein can be modified to alter isoform and/or agonistic activity, include, but are not limited to amino acid modifications C127S (CH1 domain), C232S, C233S, C232S/C233S, C236S, and C239S (White et al., 2015, Lightle et al., 2010). [0102] The monoclonal antibody or antigen-binding fragment thereof, or competing antibody disclosed herein can be of the human IgG3 isotype. [0103] The human IgG3 constant region of the monoclonal antibody, or antigen binding fragment thereof, wherein said human IgG3 constant region of the monoclonal antibody, or antigen-binding fragment thereof can be modified at one or more amino acid(s) to increase antibody half-life, Antibody-Dependent Cellular Cytotoxicity (ADCC), Complement- Dependent Cytotoxicity (CDC), or apoptosis activity. [0104] The human IgG3 constant region of the monoclonal antibody, or antigen-binding fragment thereof, wherein said human IgG3 constant region of the monoclonal antibody, or antigen-binding fragment thereof can be modified at amino acid R435H to increase antibody half-life. [0105] The monoclonal antibody or antigen-binding fragment thereof, or competing antibody disclosed herein can be of the human IgG4 isotype. [0106] The human IgG4 constant region of the monoclonal antibody, antigen-binding fragment thereof, or competing antibody disclosed herein can be modified to decrease antibody effector functions. These antibody effector functions include, but are not limited to, Antibody- Dependent Cellular Cytotoxicity (ADCC) and Antibody-Dependent Cellular Phagocytosis (ADCP). [0107] The human IgG4 constant region of the monoclonal antibody, antigen-binding fragment thereof, or competing antibody disclosed herein can be modified to prevent Fab arm exchange and/or decrease antibody effector function include, but are not limited to amino acid modifications F234A/L235A (Alegre et al., 1994); S228P, L235E and S228P/L235E (Reddy et al., 2000). [0108] Applying the teachings of the present disclosure, a person skilled in the art can use common techniques, e.g., site-directed mutagenesis, to substitute amino acids within the presently disclosed CDR and FR sequences and thereby generate further variable region amino acid sequences derived from the present sequences. Up to all naturally occurring amino acids can be introduced at a specific substitution site. The methods disclosed herein can then be used to screen these additional variable region amino acid sequences to identify sequences having the indicated in vivo functions. In this way, further sequences suitable for preparing humanized antibodies and antigen-binding portions thereof in accordance with the present disclosure can be identified. Preferably, amino acid substitution within the frameworks is restricted to one, two, three, four, or five positions within any one or more of the four light chain and/or heavy chain FRs disclosed herein. Preferably, amino acid substitution within the CDRs is restricted to one, two, three, four, or five positions within any one or more of the three light chain and/or heavy chain CDRs. Combinations of the various changes within these FRs and CDRs described above are also possible. [0109] CDRs encompassed by the present disclosure include not only those specifically disclosed herein, but also CDR sequences having sequence identities of at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to a CDR sequence disclosed herein. Alternatively, CDRs encompassed by the present disclosure include not only those specifically disclosed herein, but also CDR sequences having 1, 2, 3, 4, or 5 amino acid changes at corresponding positions compared to CDR sequences disclosed herein. Such sequence identical, or amino acid modified, CDRs preferably bind to the antigen recognized by the intact antibody. [0110] Reviews of current methods for antibody engineering and improvement can be found, for example, in P. Chames, Ed., (2012) Antibody Engineering: Methods and Protocols, Second Edition (Methods in Molecular Biology, Book 907), Humana Press, ISBN-10: 1617799734; C. R. Wood, Ed., (2011) Antibody Drug Discovery (Molecular Medicine and Medicinal Chemistry, Book 4), Imperial College Press; R. Kontermann and S. Dubel, Eds., (2010) Antibody Engineering Volumes 1 and 2 (Springer Protocols), Second Edition; and W. Strohl and L. Strohl (2012) Therapeutic antibody engineering: Current and future advances driving the strongest growth area in the pharmaceutical industry, Woodhead Publishing. [0111] Methods for producing and purifying antibodies and antigen-binding fragments are well known in the art and can be found, for example, in Harlow and Lane (1988) Antibodies, A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, chapters 5-8 and 15. [0112] In some embodiments, the CD47 binding proteins comprise amino acid sequences disclosed herein. [0113] Light Chain CDRs

[0115] Murine Light Chain Variable Domains

T T T D

[0125] All combinations of 6 CDRs selected from the CDR sequence groups listed above are permissible. [0126] In some embodiments, the CD47 binding protein comprises a variable heavy chain (VH) comprising a variable heavy chain CDR1 (HCDR1) of SEQ ID NO:1; a variable heavy chain CDR2 (HCDR2) of SEQ ID NO:4; a variable heavy chain CDR3 (HCDR3) of SEQ ID NO:7. [0127] In some embodiments, the CD47 binding protein comprises a variable heavy chain (VH) comprising a variable heavy chain CDR1 (HCDR1) of SEQ ID NO:1; a variable heavy chain CDR2 (HCDR2) of SEQ ID NO:4; a variable heavy chain CDR3 (HCDR3) of SEQ ID NO:8. [0128] In some embodiments, the CD47 binding protein comprises a variable heavy chain (VH) comprising a variable heavy chain CDR1 (HCDR1) of SEQ ID NO:2; a variable heavy chain CDR2 (HCDR2) of SEQ ID NO:5; a variable heavy chain CDR3 (HCDR3) of SEQ ID NO:9. [0129] In some embodiments, the CD47 binding protein comprises a variable heavy chain (VH) comprising a variable heavy chain CDR1 (HCDR1) of SEQ ID NO:1; a variable heavy chain CDR2 (HCDR2) of SEQ ID NO:4; a variable heavy chain CDR3 (HCDR3) of SEQ ID NO:8. [0130] In some embodiments, the CD47 binding protein comprises a variable heavy chain (VH) comprising a variable heavy chain CDR1 (HCDR1) of SEQ ID NO:3; a variable heavy chain CDR2 (HCDR2) of SEQ ID NO:6; a variable heavy chain CDR3 (HCDR3) of SEQ ID NO:10. [0131] In some embodiments, the CD47 binding protein comprises a variable light chain CDR1 (LCDR1) of SEQ ID NO:11; a variable light chain CDR2 (LCDR2) of SEQ ID NO:15; a variable light chain CDR3 (LCDR3) of SEQ ID NO:18. [0132] In some embodiments, the CD47 binding protein comprises a variable light chain CDR1 (LCDR1) of SEQ ID NO:12; a variable light chain CDR2 (LCDR2) of SEQ ID NO:16; a variable light chain CDR3 (LCDR3) of SEQ ID NO:19. [0133] In some embodiments, the CD47 binding protein comprises a variable light chain CDR1 (LCDR1) of SEQ ID NO:13; a variable light chain CDR2 (LCDR2) of SEQ ID NO:16; a variable light chain CDR3 (LCDR3) of SEQ ID NO:19. [0134] In some embodiments, the CD47 binding protein comprises a variable light chain CDR1 (LCDR1) of SEQ ID NO:14; a variable light chain CDR2 (LCDR2) of SEQ ID NO:17; a variable light chain CDR3 (LCDR3) of SEQ ID NO:18. [0135] In some embodiments, the CD47 binding protein comprises a variable light chain CDR1 (LCDR1) of SEQ ID NO:14; a variable light chain CDR2 (LCDR2) of SEQ ID NO:17; a variable light chain CDR3 (LCDR3) of SEQ ID NO:20. [0136] In some embodiments, the CD47 binding protein comprises a variable heavy chain (VH) comprising a variable heavy chain CDR1 (HCDR1) of SEQ ID NO:3; a variable heavy chain CDR2 (HCDR2) of SEQ ID NO:6; a variable heavy chain CDR3 (HCDR3) of SEQ ID NO:10 and a variable light chain CDR1 (LCDR1) of SEQ ID NO:14; a variable light chain CDR2 (LCDR2) of SEQ ID NO:17; a variable light chain CDR3 (LCDR3) of SEQ ID NO:18. [0137] All combinations of a heavy chain variable domain and a light chain variable domain selected from the VH and VL sequences listed above are permissible. [0138] In some embodiments, the CD47 binding protein comprises a heavy chain variable domain having an amino acid sequence selected from the group consisting of the amino acid sequences of SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40 and amino acid sequences exhibiting at least 90%, 95%, 97%, 98%, or 99% sequence identity to one of the recited sequences. [0139] In some embodiments, the CD47 binding protein comprises a heavy chain variable domain having an amino acid sequence of SEQ ID NO:36. In some embodiments, the CD47 binding protein comprises a heavy chain variable domain having an amino acid sequence of at least 90% identical to SEQ ID NO:36. In some embodiments, the CD47 binding protein comprises a heavy chain variable domain having an amino acid sequence of at least 95% identical to SEQ ID NO:36. In some embodiments, the CD47 binding protein comprises a heavy chain variable domain having an amino acid sequence of at least 96% identical to SEQ ID NO:36. In some embodiments, the CD47 binding protein comprises a heavy chain variable domain having an amino acid sequence of at least 97% identical to SEQ ID NO:36. In some embodiments, the CD47 binding protein comprises a heavy chain variable domain having an amino acid sequence of at least 98% identical to SEQ ID NO:36. In some embodiments, the CD47 binding protein comprises a heavy chain variable domain having an amino acid sequence of at least 99% identical to SEQ ID NO:36. [0140] In some embodiments, the CD47 binding protein comprises a light chain variable domain having an amino acid sequence selected from the group consisting of: the amino acid sequences of SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52 and amino acid sequences exhibiting at least 90%, 95%, 97%, 98%, or 99% sequence identity to one of the recited sequences. [0141] In some embodiments, the CD47 binding protein comprises a light chain variable domain having an amino acid sequence of SEQ ID NO:52. In some embodiments, the CD47 binding protein comprises a light chain variable domain having an amino acid sequence of at least 90% identical to SEQ ID NO:52. In some embodiments, the CD47 binding protein comprises a light chain variable domain having an amino acid sequence of at least 95% identical to SEQ ID NO:52. In some embodiments, the CD47 binding protein comprises a light chain variable domain having an amino acid sequence of at least 96% identical to SEQ ID NO:52. In some embodiments, the CD47 binding protein comprises a light chain variable domain having an amino acid sequence of at least 97% identical to SEQ ID NO:52. In some embodiments, the CD47 binding protein comprises a light chain variable domain having an amino acid sequence of at least 98% identical to SEQ ID NO:52. In some embodiments, the CD47 binding protein comprises a light chain variable domain having an amino acid sequence of at least 99% identical to SEQ ID NO:52. [0142] In some embodiments, the CD47 binding protein comprises a combination of a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the combination is selected from the group consisting of: (i) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:21 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:41; (ii) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:23 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:43; (iii) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:34 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:49; (iv) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:36 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:52; (v) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:38 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:52; (vi) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:39 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:52; (vii) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:24 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:43; (viii) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:37 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:52; (ix) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:33 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:48; (x) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:26 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:44; (xi) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:27 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:44; and (xii) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:38 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:51; (xiii) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:39 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:51; (xiv) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:40 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:52; (xv) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:36 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:51; (xvi) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:29 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:47; (xvii) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:30 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:47; (xviii) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:31 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:47; (xix) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:32 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:47; (xx) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:33 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:47; (xxi) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:29 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:48; (xxii) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:30 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:48; (xxiii) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:31 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:48; (xxiv) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:32 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:48; (xxv) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:26 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:43; (xxvi) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:27 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:43; (xxvii) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:28 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:46; (xxviii)a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:35 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:50; (xxix) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:29 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:48; (xxx) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:30 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:48; (xxxi) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:31 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:48; (xxxii) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:32 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:48; (xxxiii)a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:37 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:51; and (xxxiv) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:40 and a light chain variable domain comprising the amino acid sequence SEQ ID NO:51. [0143] In some embodiments, the CD47 binding protein comprises a combination of a heavy chain variable domain and a light chain variable domain wherein the heavy chain variable domain comprises a VH sequence with at least 85% sequence identity, or at least 90% sequence identity, or at least 95% sequence identity, or at least 97%, 98% or 99% sequence identity, to the heavy chain amino acid sequences shown above in (i) to (xxxiv) and/or the light chain variable domain comprises a VL sequence with at least 85% sequence identity, or at least 90% sequence identity, or at least 95% sequence identity, or at least 97%, 98% or 99% sequence identity, to the light chain amino acid sequences shown above in (i) to (xxxiv). The specific VH and VL pairings or combinations in parts (i) through (xxxiv) may be preserved for anti- CD47 antibodies having VH and VL domain sequences with a particular percentage sequence identity to these reference sequences. [0144] For all embodiments wherein the heavy chain and/or light chain variable domains of the antibodies or antigen binding fragments are defined by a particular percentage sequence identity to a reference sequence, the VH and/or VL domains may retain identical CDR sequences to those present in the reference sequence such that the variation is present only within the framework regions. [0145] In some embodiments, the CD47 binding protein is a monoclonal antibody. In some embodiments, the anti-CD47 monoclonal antibody is humanized. In some embodiments, the anti-CD47 monoclonal antibody is an IgG. In some embodiments, the anti-CD47 monoclonal antibody is an IgG1. In some embodiments, the anti-CD47 monoclonal antibody is an IgG2. In some embodiments, the anti-CD47 monoclonal antibody is an IgG3. In some embodiments, the anti-CD47 monoclonal antibody is an IgG4. [0146] In some embodiments, the anti-CD47 monoclonal antibody comprises a human Fc IgG1 having an amino acid sequence of, or at least 90%, 95%, 97%, 98% or 99% sequence identity to, SEQ ID NO:53. In some embodiments, the anti-CD47 monoclonal antibody comprises a human Fc IgG1 having an amino acid sequence of, or at least 90%, 95%, 97%, 98% or 99% sequence identity to, SEQ ID NO:54. In some embodiments, the anti-CD47 monoclonal antibody comprises a human Fc IgG2 having an amino acid sequence of, or at least 90%, 95%, 97%, 98% or 99% sequence identity to, SEQ ID NO:55. In some embodiments, the anti-CD47 monoclonal antibody comprises a human Fc IgG3 having an amino acid sequence of, or at least 90%, 95%, 97%, 98% or 99% sequence identity to, SEQ ID NO:56. In some embodiments, the anti-CD47 monoclonal antibody comprises a human Fc IgG4 having an amino acid sequence of, or at least 90%, 95%, 97%, 98% or 99% sequence identity to, SEQ ID NO:57. In some embodiments, the anti-CD47 monoclonal antibody comprises a human Fc IgG4 having an amino acid sequence of, or at least 90%, 95%, 97%, 98% or 99% sequence identity to, SEQ ID NO:58. In some embodiments, the anti-CD47 monoclonal antibody comprises a human Fc IgG4 having an amino acid sequence of, or at least 90%, 95%, 97%, 98% or 99% sequence identity to, SEQ ID NO:59. In some embodiments, the anti-CD47 monoclonal antibody comprises a human Fc IgG4 having an amino acid sequence of, or at least 90%, 95%, 97%, 98% or 99% sequence identity to, SEQ ID NO:99. Compositions [0147] CD47 binding proteins provided herein can be formulated to achieve advantageous physical and pharmaceutical properties (e.g, stability). CD47 binding proteins provided herein can be formulated to be compatible with the intended method or route of administration. [0148] In one aspect, provided herein are compositions comprising a CD47 binding protein provided herein and one or more agents. In some embodiments, the CD47 binding protein and one or more agents are present in a therapeutically acceptable amount. In some embodiments, the one or more agents are pharmaceutically acceptable excipients. Examples of pharmaceutically acceptable excipients include buffers, such as phosphate, citrate, and other organic acids; antioxidants, including ascorbic acid; low molecular weight (e.g., fewer than about 10 amino acid residues) polypeptide; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers, such as polyvinylpyrrolidone; amino acids, such as L-histidine, glycine, glutamine, asparagine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates, including glucose, sucrose, trehalose dihydrate, mannose, or dextrins; chelating agents, such as EDTA; sugar alcohols, such as mannitol or sorbitol; salt-forming counterions, such as sodium; and/or nonionic surfactants, such as polysorbate 20, polysorbate 80, TWEEN™, polyethylene glycol (PEG), and PLURONICS™. Other examples of pharmaceutically acceptable excipients are described in Remington and Gennaro, Remington’s Pharmaceutical Sciences (18th ed.1990). [0149] In some embodiment, each component is “pharmaceutically acceptable” in the sense of being compatible with the other ingredients of a pharmaceutical formulation, and suitable for use in contact with the tissue or organ of humans and animals without excessive toxicity, irritation, allergic response, immunogenicity, or other problems or complications, commensurate with a reasonable benefit/risk ratio. See, e.g., Lippincott Williams & Wilkins: Philadelphia, PA, 2005; Handbook of Pharmaceutical Excipients, 6th ed.; Rowe et ah, Eds.; The Pharmaceutical Press and the American Pharmaceutical Association: 2009; Handbook of Pharmaceutical Additives, 3rd ed.; Ash and Ash Eds.; Gower Publishing Company: 2007; Pharmaceutical Preformulation and Formulation, 2nd ed.; Gibson Ed.; CRC Press LLC: Boca Raton, FL, 2009. In some embodiments, pharmaceutically acceptable excipients are nontoxic to the cell or mammal being exposed thereto at the dosages and concentrations employed. In some embodiments, a pharmaceutically acceptable excipient is an aqueous pH buffered solution. [0150] In some embodiments, excipients are sterile liquids, such as water and oils, including those of petroleum, animal, vegetable, or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil, and the like. Water is an exemplary excipient when a composition (e.g, a pharmaceutical composition) is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid excipients, particularly for injectable solutions. An excipient can also include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol, and the like. The composition, if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents. [0151] In some embodiments, the composition comprising (i) a CD47 binding protein comprising: (a) a variable heavy chain (VH) comprising a variable heavy chain CDR1 (HCDR1) of SEQ ID NO:3; a variable heavy chain CDR2 (HCDR2) of SEQ ID NO:6; a variable heavy chain CDR3 (HCDR3) of SEQ ID NO:10; and (b) a variable light chain (VL) comprising a variable light chain CDR1 (LCDR1) of SEQ ID NO:14; a variable light chain CDR2 (LCDR2) of SEQ ID NO:17; a variable light chain CDR3 (LCDR3) of SEQ ID NO:18; (ii) a buffer; and (iii) a surfactant. [0152] In some embodiments, the buffer is a sodium acetate buffer. In some embodiments, the buffer is a histidine buffer. In some embodiments, the concentration of the buffer is about 0.1 nM to about 500 nM. In some embodiments, the concentration of the buffer is at least about 0.1 nM. In some embodiments, the concentration of the buffer is at most about 500 nM. In some embodiments, the concentration of the buffer is about 0.1 nM to about 10 nM, about 0.1 nM to about 20 nM, about 0.1 nM to about 30 nM, about 0.1 nM to about 40 nM, about 0.1 nM to about 60 nM, about 0.1 nM to about 80 nM, about 0.1 nM to about 100 nM, about 0.1 nM to about 200 nM, about 0.1 nM to about 300 nM, about 0.1 nM to about 400 nM, about 0.1 nM to about 500 nM, about 10 nM to about 20 nM, about 10 nM to about 30 nM, about 10 nM to about 40 nM, about 10 nM to about 60 nM, about 10 nM to about 80 nM, about 10 nM to about 100 nM, about 10 nM to about 200 nM, about 10 nM to about 300 nM, about 10 nM to about 400 nM, about 10 nM to about 500 nM, about 20 nM to about 30 nM, about 20 nM to about 40 nM, about 20 nM to about 60 nM, about 20 nM to about 80 nM, about 20 nM to about 100 nM, about 20 nM to about 200 nM, about 20 nM to about 300 nM, about 20 nM to about 400 nM, about 20 nM to about 500 nM, about 30 nM to about 40 nM, about 30 nM to about 60 nM, about 30 nM to about 80 nM, about 30 nM to about 100 nM, about 30 nM to about 200 nM, about 30 nM to about 300 nM, about 30 nM to about 400 nM, about 30 nM to about 500 nM, about 40 nM to about 60 nM, about 40 nM to about 80 nM, about 40 nM to about 100 nM, about 40 nM to about 200 nM, about 40 nM to about 300 nM, about 40 nM to about 400 nM, about 40 nM to about 500 nM, about 60 nM to about 80 nM, about 60 nM to about 100 nM, about 60 nM to about 200 nM, about 60 nM to about 300 nM, about 60 nM to about 400 nM, about 60 nM to about 500 nM, about 80 nM to about 100 nM, about 80 nM to about 200 nM, about 80 nM to about 300 nM, about 80 nM to about 400 nM, about 80 nM to about 500 nM, about 100 nM to about 200 nM, about 100 nM to about 300 nM, about 100 nM to about 400 nM, about 100 nM to about 500 nM, about 200 nM to about 300 nM, about 200 nM to about 400 nM, about 200 nM to about 500 nM, about 300 nM to about 400 nM, about 300 nM to about 500 nM, or about 400 nM to about 500 nM. In some embodiments, the concentration of the buffer is about 0.1 nM, about 10 nM, about 20 nM, about 30 nM, about 40 nM, about 50 nM, about 60 nM, about 70 nM, about 80 nM, about 90 nM, about 100 nM, about 200 nM, about 300 nM, about 400 nM, or about 500 nM. In some embodiments, the concentration of the buffer is about 50nM. [0153] In some embodiments, the surfactant is polysorbate 20. In some embodiments, the concentration of polysorbate 20 is about 0.001% (w/v) to about 0.1% (w/v). In some embodiments, the concentration of polysorbate 20 is at least about 0.001% (w/v). In some embodiments, the concentration of polysorbate 20 is at most about 0.1% (w/v). In some embodiments, the concentration of polysorbate 20 is about 0.001% (w/v) to about 0.003% (w/v), about 0.001% (w/v) to about 0.005% (w/v), about 0.001% (w/v) to about 0.007% (w/v), about 0.001% (w/v) to about 0.009% (w/v), about 0.001% (w/v) to about 0.01% (w/v), about 0.001% (w/v) to about 0.03% (w/v), about 0.001% (w/v) to about 0.05% (w/v), about 0.001% (w/v) to about 0.07% (w/v), about 0.001% (w/v) to about 0.09% (w/v), about 0.001% (w/v) to about 0.1% (w/v), about 0.003% (w/v) to about 0.005% (w/v), about 0.003% (w/v) to about 0.007% (w/v), about 0.003% (w/v) to about 0.009% (w/v), about 0.003% (w/v) to about 0.01% (w/v), about 0.003% (w/v) to about 0.03% (w/v), about 0.003% (w/v) to about 0.05% (w/v), about 0.003% (w/v) to about 0.07% (w/v), about 0.003% (w/v) to about 0.09% (w/v), about 0.003% (w/v) to about 0.1% (w/v), about 0.005% (w/v) to about 0.007% (w/v), about 0.005% (w/v) to about 0.009% (w/v), about 0.005% (w/v) to about 0.01% (w/v), about 0.005% (w/v) to about 0.03% (w/v), about 0.005% (w/v) to about 0.05% (w/v), about 0.005% (w/v) to about 0.07% (w/v), about 0.005% (w/v) to about 0.09% (w/v), about 0.005% (w/v) to about 0.1% (w/v), about 0.007% (w/v) to about 0.009% (w/v), about 0.007% (w/v) to about 0.01% (w/v), about 0.007% (w/v) to about 0.03% (w/v), about 0.007% (w/v) to about 0.05% (w/v), about 0.007% (w/v) to about 0.07% (w/v), about 0.007% (w/v) to about 0.09% (w/v), about 0.007% (w/v) to about 0.1% (w/v), about 0.009% (w/v) to about 0.01% (w/v), about 0.009% (w/v) to about 0.03% (w/v), about 0.009% (w/v) to about 0.05% (w/v), about 0.009% (w/v) to about 0.07% (w/v), about 0.009% (w/v) to about 0.09% (w/v), about 0.009% (w/v) to about 0.1% (w/v), about 0.01% (w/v) to about 0.03% (w/v), about 0.01% (w/v) to about 0.05% (w/v), about 0.01% (w/v) to about 0.07% (w/v), about 0.01% (w/v) to about 0.09% (w/v), about 0.01% (w/v) to about 0.1% (w/v), about 0.03% (w/v) to about 0.05% (w/v), about 0.03% (w/v) to about 0.07% (w/v), about 0.03% (w/v) to about 0.09% (w/v), about 0.03% (w/v) to about 0.1% (w/v), about 0.05% (w/v) to about 0.07% (w/v), about 0.05% (w/v) to about 0.09% (w/v), about 0.05% (w/v) to about 0.1% (w/v), about 0.07% (w/v) to about 0.09% (w/v), about 0.07% (w/v) to about 0.1% (w/v), or about 0.09% (w/v) to about 0.1% (w/v). In some embodiments, the concentration of polysorbate 20 is about 0.001% (w/v), about 0.002% (w/v), about 0.003% (w/v), about 0.004% (w/v), about 0.005% (w/v), about 0.006% (w/v), about 0.007% (w/v), about 0.008% (w/v), about 0.009% (w/v), about 0.01% (w/v), about 0.02% (w/v), about 0.03% (w/v), about 0.04% (w/v), about 0.05% (w/v), about 0.06% (w/v), about 0.07% (w/v), about 0.08% (w/v), about 0.09% (w/v), or about 0.1% (w/v). In some embodiments, the concentration of polysorbate 20 is about 0.06% (w/v). In some embodiments, the concentration of polysorbate 20 is about 0.006% (w/v). [0154] In some embodiments, the surfactant is polysorbate 80. In some embodiments, the concentration of polysorbate 80 is about 0.001% (w/v) to about 0.1% (w/v). In some embodiments, the concentration of polysorbate 80 is at least about 0.001% (w/v). In some embodiments, the concentration of polysorbate 80 is at most about 0.1% (w/v). In some embodiments, the concentration of polysorbate 80 is about 0.001% (w/v) to about 0.003% (w/v), about 0.001% (w/v) to about 0.005% (w/v), about 0.001% (w/v) to about 0.007% (w/v), about 0.001% (w/v) to about 0.009% (w/v), about 0.001% (w/v) to about 0.01% (w/v), about 0.001% (w/v) to about 0.03% (w/v), about 0.001% (w/v) to about 0.05% (w/v), about 0.001% (w/v) to about 0.07% (w/v), about 0.001% (w/v) to about 0.09% (w/v), about 0.001% (w/v) to about 0.1% (w/v), about 0.003% (w/v) to about 0.005% (w/v), about 0.003% (w/v) to about 0.007% (w/v), about 0.003% (w/v) to about 0.009% (w/v), about 0.003% (w/v) to about 0.01% (w/v), about 0.003% (w/v) to about 0.03% (w/v), about 0.003% (w/v) to about 0.05% (w/v), about 0.003% (w/v) to about 0.07% (w/v), about 0.003% (w/v) to about 0.09% (w/v), about 0.003% (w/v) to about 0.1% (w/v), about 0.005% (w/v) to about 0.007% (w/v), about 0.005% (w/v) to about 0.009% (w/v), about 0.005% (w/v) to about 0.01% (w/v), about 0.005% (w/v) to about 0.03% (w/v), about 0.005% (w/v) to about 0.05% (w/v), about 0.005% (w/v) to about 0.07% (w/v), about 0.005% (w/v) to about 0.09% (w/v), about 0.005% (w/v) to about 0.1% (w/v), about 0.007% (w/v) to about 0.009% (w/v), about 0.007% (w/v) to about 0.01% (w/v), about 0.007% (w/v) to about 0.03% (w/v), about 0.007% (w/v) to about 0.05% (w/v), about 0.007% (w/v) to about 0.07% (w/v), about 0.007% (w/v) to about 0.09% (w/v), about 0.007% (w/v) to about 0.1% (w/v), about 0.009% (w/v) to about 0.01% (w/v), about 0.009% (w/v) to about 0.03% (w/v), about 0.009% (w/v) to about 0.05% (w/v), about 0.009% (w/v) to about 0.07% (w/v), about 0.009% (w/v) to about 0.09% (w/v), about 0.009% (w/v) to about 0.1% (w/v), about 0.01% (w/v) to about 0.03% (w/v), about 0.01% (w/v) to about 0.05% (w/v), about 0.01% (w/v) to about 0.07% (w/v), about 0.01% (w/v) to about 0.09% (w/v), about 0.01% (w/v) to about 0.1% (w/v), about 0.03% (w/v) to about 0.05% (w/v), about 0.03% (w/v) to about 0.07% (w/v), about 0.03% (w/v) to about 0.09% (w/v), about 0.03% (w/v) to about 0.1% (w/v), about 0.05% (w/v) to about 0.07% (w/v), about 0.05% (w/v) to about 0.09% (w/v), about 0.05% (w/v) to about 0.1% (w/v), about 0.07% (w/v) to about 0.09% (w/v), about 0.07% (w/v) to about 0.1% (w/v), or about 0.09% (w/v) to about 0.1% (w/v). In some embodiments, the concentration of polysorbate 80 is about 0.001% (w/v), about 0.002% (w/v), about 0.003% (w/v), about 0.004% (w/v), about 0.005% (w/v), about 0.006% (w/v), about 0.007% (w/v), about 0.008% (w/v), about 0.009% (w/v), about 0.01% (w/v), about 0.02% (w/v), about 0.03% (w/v), about 0.04% (w/v), about 0.05% (w/v), about 0.06% (w/v), about 0.07% (w/v), about 0.08% (w/v), about 0.09% (w/v), or about 0.1% (w/v). In some embodiments, the concentration of polysorbate 80 is about 0.06% (w/v). In some embodiments, the concentration of polysorbate 80 is about 0.006% (w/v). [0155] In some embodiments, the composition comprises at least one additional excipient. In some embodiments, the at least one additional excipient is a sugar alcohol. In some embodiments, the sugar alcohol is sorbitol. In some embodiments, the sugar alcohol is mannitol. In some embodiments, the sugar alcohol is xylitol. In some embodiments, the sugar alcohol is lactitol. In some embodiments, the sugar alcohol is erythritol. [0156] In some embodiments, the concentration of the sugar alcohol is about 0.1% (w/v) to about 20% (w/v). In some embodiments, the concentration of the sugar alcohol is about 1% (w/v) to about 10% (w/v). In some embodiments, the concentration of the sugar alcohol is at least about 0.1% (w/v). In some embodiments, the concentration of the sugar alcohol is at most about 20% (w/v). In some embodiments, the concentration of the sugar alcohol is about 0.1% (w/v) to about 1% (w/v), about 0.1% (w/v) to about 2% (w/v), about 0.1% (w/v) to about 3% (w/v), about 0.1% (w/v) to about 4% (w/v), about 0.1% (w/v) to about 5% (w/v), about 0.1% (w/v) to about 6% (w/v), about 0.1% (w/v) to about 7% (w/v), about 0.1% (w/v) to about 8% (w/v), about 0.1% (w/v) to about 9% (w/v), about 0.1% (w/v) to about 10% (w/v), about 0.1% (w/v) to about 20% (w/v), about 1% (w/v) to about 2% (w/v), about 1% (w/v) to about 3% (w/v), about 1% (w/v) to about 4% (w/v), about 1% (w/v) to about 5% (w/v), about 1% (w/v) to about 6% (w/v), about 1% (w/v) to about 7% (w/v), about 1% (w/v) to about 8% (w/v), about 1% (w/v) to about 9% (w/v), about 1% (w/v) to about 10% (w/v), about 1% (w/v) to about 20% (w/v), about 2% (w/v) to about 3% (w/v), about 2% (w/v) to about 4% (w/v), about 2% (w/v) to about 5% (w/v), about 2% (w/v) to about 6% (w/v), about 2% (w/v) to about 7% (w/v), about 2% (w/v) to about 8% (w/v), about 2% (w/v) to about 9% (w/v), about 2% (w/v) to about 10% (w/v), about 2% (w/v) to about 20% (w/v), about 3% (w/v) to about 4% (w/v), about 3% (w/v) to about 5% (w/v), about 3% (w/v) to about 6% (w/v), about 3% (w/v) to about 7% (w/v), about 3% (w/v) to about 8% (w/v), about 3% (w/v) to about 9% (w/v), about 3% (w/v) to about 10% (w/v), about 3% (w/v) to about 20% (w/v), about 4% (w/v) to about 5% (w/v), about 4% (w/v) to about 6% (w/v), about 4% (w/v) to about 7% (w/v), about 4% (w/v) to about 8% (w/v), about 4% (w/v) to about 9% (w/v), about 4% (w/v) to about 10% (w/v), about 4% (w/v) to about 20% (w/v), about 5% (w/v) to about 6% (w/v), about 5% (w/v) to about 7% (w/v), about 5% (w/v) to about 8% (w/v), about 5% (w/v) to about 9% (w/v), about 5% (w/v) to about 10% (w/v), about 5% (w/v) to about 20% (w/v), about 6% (w/v) to about 7% (w/v), about 6% (w/v) to about 8% (w/v), about 6% (w/v) to about 9% (w/v), about 6% (w/v) to about 10% (w/v), about 6% (w/v) to about 20% (w/v), about 7% (w/v) to about 8% (w/v), about 7% (w/v) to about 9% (w/v), about 7% (w/v) to about 10% (w/v), about 7% (w/v) to about 20% (w/v), about 8% (w/v) to about 9% (w/v), about 8% (w/v) to about 10% (w/v), about 8% (w/v) to about 20% (w/v), about 9% (w/v) to about 10% (w/v), about 9% (w/v) to about 20% (w/v), or about 10% (w/v) to about 20% (w/v). In some embodiments, the concentration of the sugar alcohol is about 0.1% (w/v), about 1% (w/v), about 2% (w/v), about 3% (w/v), about 4% (w/v), about 5% (w/v), about 6% (w/v), about 7% (w/v), about 8% (w/v), about 9% (w/v), about 10% (w/v), or about 20% (w/v). In some embodiments, the concentration of the sugar alcohol is about 3% (w/v). In some embodiments, the concentration of the sugar alcohol is about 6% (w/v). [0157] In some embodiments, the composition further comprises at least one amino acid. In some embodiments, the at least one amino acid is arginine. In some embodiments, the at least one amino acid is glycine. In some embodiments, the concentration of the amino acid is about 1 mM to about 200 mM. In some embodiments, the concentration of the amino acid is about 10 mM to about 200 mM. In some embodiments, the concentration of the amino acid is at least about 1 mM. In some embodiments, the concentration of the amino acid is at most about 200 mM. In some embodiments, the concentration of the amino acid is about 1 mM to about 10 mM, about 1 mM to about 30 mM, about 1 mM to about 50 mM, about 1 mM to about 70 mM, about 1 mM to about 90 mM, about 1 mM to about 100 mM, about 1 mM to about 120 mM, about 1 mM to about 140 mM, about 1 mM to about 160 mM, about 1 mM to about 180 mM, about 1 mM to about 200 mM, about 10 mM to about 30 mM, about 10 mM to about 50 mM, about 10 mM to about 70 mM, about 10 mM to about 90 mM, about 10 mM to about 100 mM, about 10 mM to about 120 mM, about 10 mM to about 140 mM, about 10 mM to about 160 mM, about 10 mM to about 180 mM, about 10 mM to about 200 mM, about 30 mM to about 50 mM, about 30 mM to about 70 mM, about 30 mM to about 90 mM, about 30 mM to about 100 mM, about 30 mM to about 120 mM, about 30 mM to about 140 mM, about 30 mM to about 160 mM, about 30 mM to about 180 mM, about 30 mM to about 200 mM, about 50 mM to about 70 mM, about 50 mM to about 90 mM, about 50 mM to about 100 mM, about 50 mM to about 120 mM, about 50 mM to about 140 mM, about 50 mM to about 160 mM, about 50 mM to about 180 mM, about 50 mM to about 200 mM, about 70 mM to about 90 mM, about 70 mM to about 100 mM, about 70 mM to about 120 mM, about 70 mM to about 140 mM, about 70 mM to about 160 mM, about 70 mM to about 180 mM, about 70 mM to about 200 mM, about 90 mM to about 100 mM, about 90 mM to about 120 mM, about 90 mM to about 140 mM, about 90 mM to about 160 mM, about 90 mM to about 180 mM, about 90 mM to about 200 mM, about 100 mM to about 120 mM, about 100 mM to about 140 mM, about 100 mM to about 160 mM, about 100 mM to about 180 mM, about 100 mM to about 200 mM, about 120 mM to about 140 mM, about 120 mM to about 160 mM, about 120 mM to about 180 mM, about 120 mM to about 200 mM, about 140 mM to about 160 mM, about 140 mM to about 180 mM, about 140 mM to about 200 mM, about 160 mM to about 180 mM, about 160 mM to about 200 mM, or about 180 mM to about 200 mM. In some embodiments, the concentration of the amino acid is about 1 mM, about 10 mM, about 20 mM, about 30 mM, about 40 mM, about 50 mM, about 60 mM, about 70 mM, about 80 mM, about 90 mM, about 100 mM, about 110 mM, about 120 mM, about 125 mM, about 130 mM, about 140 mM, about 150 mM, about 160 mM, about 170 mM, about 180 mM, about 190 mM, or about 200 mM. In some embodiments, the concentration of the amino acid is about 40 mM. In some embodiments, the concentration of the amino acid is about 60 mM. In some embodiments, the concentration of the amino acid is about 80 mM. In some embodiments, the concentration of the amino acid is about 125 mM. [0158] In some embodiments, the composition comprises at least one salt. In some embodiments, the at least one salt is sodium chloride. In some embodiments, the concentration of the salt is about 10 mM to about 200 mM. In some embodiments, the concentration of the salt is at least about 10 mM. In some embodiments, the concentration of the salt is at most about 200 mM. In some embodiments, the concentration of the salt is about 10 mM to about 20 mM, about 10 mM to about 40 mM, about 10 mM to about 60 mM, about 10 mM to about 80 mM, about 10 mM to about 100 mM, about 10 mM to about 120 mM, about 10 mM to about 140 mM, about 10 mM to about 160 mM, about 10 mM to about 180 mM, about 10 mM to about 200 mM, about 20 mM to about 40 mM, about 20 mM to about 60 mM, about 20 mM to about 80 mM, about 20 mM to about 100 mM, about 20 mM to about 120 mM, about 20 mM to about 140 mM, about 20 mM to about 160 mM, about 20 mM to about 180 mM, about 20 mM to about 200 mM, about 40 mM to about 60 mM, about 40 mM to about 80 mM, about 40 mM to about 100 mM, about 40 mM to about 120 mM, about 40 mM to about 140 mM, about 40 mM to about 160 mM, about 40 mM to about 180 mM, about 40 mM to about 200 mM, about 60 mM to about 80 mM, about 60 mM to about 100 mM, about 60 mM to about 120 mM, about 60 mM to about 140 mM, about 60 mM to about 160 mM, about 60 mM to about 180 mM, about 60 mM to about 200 mM, about 80 mM to about 100 mM, about 80 mM to about 120 mM, about 80 mM to about 140 mM, about 80 mM to about 160 mM, about 80 mM to about 180 mM, about 80 mM to about 200 mM, about 100 mM to about 120 mM, about 100 mM to about 140 mM, about 100 mM to about 160 mM, about 100 mM to about 180 mM, about 100 mM to about 200 mM, about 120 mM to about 140 mM, about 120 mM to about 160 mM, about 120 mM to about 180 mM, about 120 mM to about 200 mM, about 140 mM to about 160 mM, about 140 mM to about 180 mM, about 140 mM to about 200 mM, about 160 mM to about 180 mM, about 160 mM to about 200 mM, or about 180 mM to about 200 mM. In some embodiments, the concentration of the salt is about 10 mM, about 20 mM, about 30 mM, about 40 mM, about 50 mM, about 60 mM, about 70 mM, about 80 mM, about 90 mM, about 100 mM, about 110 mM, about 120 mM, about 130 mM, about 140 mM, about 150 mM, about 160 mM, about 170 mM, about 180 mM, about 190 mM, or about 200 mM. In some embodiments, the concentration of the salt is about 50 mM. In some embodiments, the concentration of the salt is about 100 mM. [0159] In some embodiments, the concentration of the CD47 binding protein is about 0.1 g/L to about 500 g/L. In some embodiments, the concentration of the CD47 binding protein is about 1 g/L to about 250 g/L. In some embodiments, the concentration of the CD47 binding protein is at least about 0.1 g/L. In some embodiments, the concentration of the CD47 binding protein is at most about 500 g/L. In some embodiments, the concentration of the CD47 binding protein is about 0.1 g/L to about 1 g/L, about 0.1 g/L to about 10 g/L, about 0.1 g/L to about 30 g/L, about 0.1 g/L to about 50 g/L, about 0.1 g/L to about 80 g/L, about 0.1 g/L to about 100 g/L, about 0.1 g/L to about 120 g/L, about 0.1 g/L to about 150 g/L, about 0.1 g/L to about 200 g/L, about 0.1 g/L to about 250 g/L, about 0.1 g/L to about 500 g/L, about 1 g/L to about 10 g/L, about 1 g/L to about 30 g/L, about 1 g/L to about 50 g/L, about 1 g/L to about 80 g/L, about 1 g/L to about 100 g/L, about 1 g/L to about 120 g/L, about 1 g/L to about 150 g/L, about 1 g/L to about 200 g/L, about 1 g/L to about 250 g/L, about 1 g/L to about 500 g/L, about 10 g/L to about 30 g/L, about 10 g/L to about 50 g/L, about 10 g/L to about 80 g/L, about 10 g/L to about 100 g/L, about 10 g/L to about 120 g/L, about 10 g/L to about 150 g/L, about 10 g/L to about 200 g/L, about 10 g/L to about 250 g/L, about 10 g/L to about 500 g/L, about 30 g/L to about 50 g/L, about 30 g/L to about 80 g/L, about 30 g/L to about 100 g/L, about 30 g/L to about 120 g/L, about 30 g/L to about 150 g/L, about 30 g/L to about 200 g/L, about 30 g/L to about 250 g/L, about 30 g/L to about 500 g/L, about 50 g/L to about 80 g/L, about 50 g/L to about 100 g/L, about 50 g/L to about 120 g/L, about 50 g/L to about 150 g/L, about 50 g/L to about 200 g/L, about 50 g/L to about 250 g/L, about 50 g/L to about 500 g/L, about 80 g/L to about 100 g/L, about 80 g/L to about 120 g/L, about 80 g/L to about 150 g/L, about 80 g/L to about 200 g/L, about 80 g/L to about 250 g/L, about 80 g/L to about 500 g/L, about 100 g/L to about 120 g/L, about 100 g/L to about 150 g/L, about 100 g/L to about 200 g/L, about 100 g/L to about 250 g/L, about 100 g/L to about 500 g/L, about 120 g/L to about 150 g/L, about 120 g/L to about 200 g/L, about 120 g/L to about 250 g/L, about 120 g/L to about 500 g/L, about 150 g/L to about 200 g/L, about 150 g/L to about 250 g/L, about 150 g/L to about 500 g/L, about 200 g/L to about 250 g/L, about 200 g/L to about 500 g/L, or about 250 g/L to about 500 g/L. In some embodiments, the concentration of the CD47 binding protein is about 0.1 g/L, about 1 g/L, about 10 g/L, about 20 g/L, about 30 g/L, about 40 g/L, about 50 g/L, about 60 g/L, about 70 g/L, about 80 g/L, about 90 g/L, about 100 g/L, about 110 g/L, about 120 g/L, about 130 g/L, about 140 g/L, about 150 g/L, about 160 g/L, about 170 g/L, about 180 g/L, about 182 g/L, about 190 g/L, about 200 g/L, about 250 g/L, or about 500 g/L. In some embodiments, the concentration of the CD47 binding protein is about 50 g/L. In some embodiments, the concentration of the CD47 binding protein is about 182 g/L. [0160] In some embodiments, the composition has a pH of about 5 to about 7. In some embodiments, the composition has a pH of at least about 5. In some embodiments, the composition has a pH of at most about 7. In some embodiments, the composition has a pH of about 5 to about 5.2, about 5 to about 5.4, about 5 to about 5.6, about 5 to about 5.8, about 5 to about 6, about 5 to about 6.2, about 5 to about 6.4, about 5 to about 6.6, about 5 to about 6.8, about 5 to about 7, about 5.2 to about 5.4, about 5.2 to about 5.6, about 5.2 to about 5.8, about 5.2 to about 6, about 5.2 to about 6.2, about 5.2 to about 6.4, about 5.2 to about 6.6, about 5.2 to about 6.8, about 5.2 to about 7, about 5.4 to about 5.6, about 5.4 to about 5.8, about 5.4 to about 6, about 5.4 to about 6.2, about 5.4 to about 6.4, about 5.4 to about 6.6, about 5.4 to about 6.8, about 5.4 to about 7, about 5.6 to about 5.8, about 5.6 to about 6, about 5.6 to about 6.2, about 5.6 to about 6.4, about 5.6 to about 6.6, about 5.6 to about 6.8, about 5.6 to about 7, about 5.8 to about 6, about 5.8 to about 6.2, about 5.8 to about 6.4, about 5.8 to about 6.6, about 5.8 to about 6.8, about 5.8 to about 7, about 6 to about 6.2, about 6 to about 6.4, about 6 to about 6.6, about 6 to about 6.8, about 6 to about 7, about 6.2 to about 6.4, about 6.2 to about 6.6, about 6.2 to about 6.8, about 6.2 to about 7, about 6.4 to about 6.6, about 6.4 to about 6.8, about 6.4 to about 7, about 6.6 to about 6.8, about 6.6 to about 7, or about 6.8 to about 7. In some embodiments, the composition has a pH of about 5, about 5.2, about 5.4, about 5.6, about 5.8, about 6, about 6.2, about 6.4, about 6.6, about 6.8, or about 7. In some embodiments, the composition has a pH of about 5.2. In some embodiments, the composition has a pH of about 6.2. In some embodiments, the composition has a pH of about 6.8. [0161] In some embodiments, the composition comprises: (i) a CD47 binding protein comprising: (a) a variable heavy chain (VH) comprising a variable heavy chain CDR1 (HCDR1) of SEQ ID NO: 3; a variable heavy chain CDR2 (HCDR2) of SEQ ID NO: 6; a variable heavy chain CDR3 (HCDR3) of SEQ ID NO: 10; and (b) a variable light chain (VL) comprising a variable light chain CDR1 (LCDR1) of SEQ ID NO: 14; a variable light chain CDR2 (LCDR2) of SEQ ID NO: 17; a variable light chain CDR3 (LCDR3) of SEQ ID NO: 18; (ii) a sodium acetate buffer, (iii) polysorbate 20 or polysorbate 80, (iv) sorbitol, and (v) arginine. [0162] In some embodiments, the composition comprises: (i) a CD47 binding protein comprising: (a) a variable heavy chain (VH) comprising a variable heavy chain CDR1 (HCDR1) of SEQ ID NO: 3; a variable heavy chain CDR2 (HCDR2) of SEQ ID NO: 6; a variable heavy chain CDR3 (HCDR3) of SEQ ID NO: 10; and (b) a variable light chain (VL) comprising a variable light chain CDR1 (LCDR1) of SEQ ID NO: 14; a variable light chain CDR2 (LCDR2) of SEQ ID NO: 17; a variable light chain CDR3 (LCDR3) of SEQ ID NO: 18; (ii) a sodium acetate buffer, (iii) polysorbate 20 or polysorbate 80, (iv) sorbitol, and (v) arginine, and the concentration of the sodium acetate buffer is in the range of from about 10 mM to about 100 mM, the concentration of the polysorbate 20 is in the range of from about 0.001% to about 0.1% (w/v), the concentration of the sorbitol is in the range of from about 1% to about 10% (w/v), and the concentration of the arginine is in the range of from about 10 mM to about 200 mM. [0163] In some embodiments, the composition comprises: (i) a CD47 binding protein comprising: (a) a variable heavy chain (VH) comprising a variable heavy chain CDR1 (HCDR1) of SEQ ID NO: 3; a variable heavy chain CDR2 (HCDR2) of SEQ ID NO: 6; a variable heavy chain CDR3 (HCDR3) of SEQ ID NO: 10; and (b) a variable light chain (VL) comprising a variable light chain CDR1 (LCDR1) of SEQ ID NO: 14; a variable light chain CDR2 (LCDR2) of SEQ ID NO: 17; a variable light chain CDR3 (LCDR3) of SEQ ID NO: 18; (ii) a sodium acetate buffer, (iii) polysorbate 20 or polysorbate 80, (iv) sorbitol, and (v) arginine, and the concentration of the sodium acetate buffer is about 50 mM, the concentration of the polysorbate 20 is about 0.06% (w/v), the concentration of the sorbitol is about 6% (w/v), and the concentration of the arginine is about 60 mM. [0164] In some embodiments, the composition comprises: (i) a CD47 binding protein comprising: (a) a variable heavy chain (VH) comprising a variable heavy chain CDR1 (HCDR1) of SEQ ID NO: 3; a variable heavy chain CDR2 (HCDR2) of SEQ ID NO: 6; a variable heavy chain CDR3 (HCDR3) of SEQ ID NO: 10; and (b) a variable light chain (VL) comprising a variable light chain CDR1 (LCDR1) of SEQ ID NO: 14; a variable light chain CDR2 (LCDR2) of SEQ ID NO: 17; a variable light chain CDR3 (LCDR3) of SEQ ID NO: 18; (ii) a sodium acetate buffer, (iii) polysorbate 20 or polysorbate 80, (iv) sorbitol, and (v) arginine, and the composition has a pH of from about 5.0 to about 7.0. [0165] In some embodiments, the composition comprises: (i) a CD47 binding protein comprising: (a) a variable heavy chain (VH) comprising a variable heavy chain CDR1 (HCDR1) of SEQ ID NO: 3; a variable heavy chain CDR2 (HCDR2) of SEQ ID NO: 6; a variable heavy chain CDR3 (HCDR3) of SEQ ID NO: 10; and (b) a variable light chain (VL) comprising a variable light chain CDR1 (LCDR1) of SEQ ID NO: 14; a variable light chain CDR2 (LCDR2) of SEQ ID NO: 17; a variable light chain CDR3 (LCDR3) of SEQ ID NO: 18; (ii) a sodium acetate buffer, (iii) polysorbate 20 or polysorbate 80, (iv) sorbitol, and (v) arginine, and the composition has a pH of about 5.2. [0166] In some embodiments, the composition comprises: (i) a CD47 binding protein comprising: (a) a variable heavy chain (VH) comprising a variable heavy chain CDR1 (HCDR1) of SEQ ID NO: 3; a variable heavy chain CDR2 (HCDR2) of SEQ ID NO: 6; a variable heavy chain CDR3 (HCDR3) of SEQ ID NO: 10; and (b) a variable light chain (VL) comprising a variable light chain CDR1 (LCDR1) of SEQ ID NO: 14; a variable light chain CDR2 (LCDR2) of SEQ ID NO: 17; a variable light chain CDR3 (LCDR3) of SEQ ID NO: 18; (ii) a sodium acetate buffer, (iii) polysorbate 20 or polysorbate 80, (iv) sorbitol, and (v) arginine, and the concentration of the CD47 binding protein is in the range of from about 1 g/L to about 200 g/L. [0167] In some embodiments, the composition comprises: (i) a CD47 binding protein comprising: (a) a variable heavy chain (VH) comprising a variable heavy chain CDR1 (HCDR1) of SEQ ID NO: 3; a variable heavy chain CDR2 (HCDR2) of SEQ ID NO: 6; a variable heavy chain CDR3 (HCDR3) of SEQ ID NO: 10; and (b) a variable light chain (VL) comprising a variable light chain CDR1 (LCDR1) of SEQ ID NO: 14; a variable light chain CDR2 (LCDR2) of SEQ ID NO: 17; a variable light chain CDR3 (LCDR3) of SEQ ID NO: 18; (ii) a sodium acetate buffer, (iii) polysorbate 20 or polysorbate 80, (iv) sorbitol, and (v) arginine, and the concentration of the CD47 binding protein is about 50 g/L. [0168] In some embodiments, the composition comprises: (i) a CD47 binding protein comprising: (a) a variable heavy chain (VH) comprising a variable heavy chain CDR1 (HCDR1) of SEQ ID NO: 3; a variable heavy chain CDR2 (HCDR2) of SEQ ID NO: 6; a variable heavy chain CDR3 (HCDR3) of SEQ ID NO: 10; and (b) a variable light chain (VL) comprising a variable light chain CDR1 (LCDR1) of SEQ ID NO: 14; a variable light chain CDR2 (LCDR2) of SEQ ID NO: 17; a variable light chain CDR3 (LCDR3) of SEQ ID NO: 18; (ii) a sodium acetate buffer, (iii) polysorbate 20 or polysorbate 80, (iv) sorbitol, and (v) arginine, and the concentration of the CD47 binding protein is about 182 g/L. [0169] In some embodiments, the composition comprises: (i) a CD47 binding protein comprising: (a) a variable heavy chain (VH) comprising a variable heavy chain CDR1 (HCDR1) of SEQ ID NO: 3; a variable heavy chain CDR2 (HCDR2) of SEQ ID NO: 6; a variable heavy chain CDR3 (HCDR3) of SEQ ID NO: 10; and (b) a variable light chain (VL) comprising a variable light chain CDR1 (LCDR1) of SEQ ID NO: 14; a variable light chain CDR2 (LCDR2) of SEQ ID NO: 17; a variable light chain CDR3 (LCDR3) of SEQ ID NO: 18; (ii) a sodium acetate buffer, (iii) polysorbate 20 or polysorbate 80, (iv) sorbitol, and (v) arginine, and the concentration of the sodium acetate buffer is about 50 mM, the concentration of the polysorbate 20 is about 0.06% (w/v), the concentration of the sorbitol is about 6% (w/v), the concentration of the arginine is about 60 mM, the composition has a pH of about 5.2, and the concentration of CD47 binding protein is about 50 g/L. [0170] In some embodiments, the composition comprises: (i) a CD47 binding protein comprising: (a) a variable heavy chain (VH) comprising a variable heavy chain CDR1 (HCDR1) of SEQ ID NO: 3; a variable heavy chain CDR2 (HCDR2) of SEQ ID NO: 6; a variable heavy chain CDR3 (HCDR3) of SEQ ID NO: 10; and (b) a variable light chain (VL) comprising a variable light chain CDR1 (LCDR1) of SEQ ID NO: 14; a variable light chain CDR2 (LCDR2) of SEQ ID NO: 17; a variable light chain CDR3 (LCDR3) of SEQ ID NO: 18; (ii) a sodium acetate buffer, (iii) polysorbate 20 or polysorbate 80, (iv) sorbitol, and (v) arginine, and the concentration of the sodium acetate buffer is about 50 mM, the concentration of the polysorbate 20 is about 0.06% (w/v), the concentration of the sorbitol is about 6% (w/v), the concentration of the arginine is about 60 mM, the composition has a pH of about 5.2, and the concentration of CD47 binding protein is about 182 g/L. [0171] In some embodiments, the CD47 binding protein is substantially stable for at least 10 days at a temperature in the range of from about 2°C to about 8°C. In some embodiments, the CD47 binding protein is substantially stable for at least 15 days at a temperature in the range of from about 2°C to about 8°C. In some embodiments, the CD47 binding protein is substantially stable for at least 20 days at a temperature in the range of from about 2°C to about 8°C. In some embodiments, the CD47 binding protein is substantially stable for at least 30 days at a temperature in the range of from about 2°C to about 8°C. In some embodiments, the CD47 binding protein is substantially stable for at least 40 days at a temperature in the range of from about 2°C to about 8°C. [0172] In some embodiments, the composition slows or reduces the degradation of the CD47 binding protein as compared to an identical composition lacking the surfactant, when stored under the same conditions. In some embodiments, the composition is substantially resistant to the formation of particles upon agitation. In some embodiments, the composition is substantially resistant to the formation of particles following at least one freeze/thaw cycle. In some embodiments, the composition is substantially resistant to changes to the charge of the CD47 binding protein over time. Methods of Treatment [0173] The compositions provided herein can be administered ex vivo or in vivo to a subject in order to practice treatment methods and uses provided herein. In some embodiments, provided herein is a method for treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of the composition provided herein. In some embodiments, provided herein is use of the composition provided herein for treating cancer in a subject. In some embodiments, provided herein is use of the composition provided herein in the manufacture of a medicament for treating cancer in a subject [0174] The composition comprising the CD47 binding protein disclosed herein can be used to treat hematologic cancers and solid tumors including, but not limited to, leukemias, including systemic mastocytosis, acute lymphocytic (lymphoblastic) leukemia (ALL), T cell – ALL, acute myeloid leukemia (AML), myelogenous leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), myeloproliferative disorder / neoplasm, monocytic cell leukemia, and plasma cell leukemia; multiple myeloma (MM); Waldenstrom’s Macroglobulinemia; lymphomas, including histiocytic lymphoma and T cell lymphoma, B cell lymphomas, including Hodgkin’s lymphoma and non-Hodgkin’s lymphoma, such as low grade/follicular non-Hodgkin’s lymphoma (NHL), cell lymphoma (FCC), mantle cell lymphoma (MCL), diffuse large cell lymphoma (DLCL), small lymphocytic (SL) NHL, intermediate grade/follicular NHL, intermediate grade diffuse NHL, high grade immunoblastic NHL, high grade lymphoblastic NHL, high grade small non-cleaved cell NHL, bulky disease NHL; solid tumors, including ovarian cancer, breast cancer, endometrial cancer, colon cancer (colorectal cancer), rectal cancer, bladder cancer, urothelial cancer, lung cancer (non-small cell lung cancer, adenocarcinoma of the lung, squamous cell carcinoma of the lung), bronchial cancer, bone cancer, prostate cancer, pancreatic cancer, gastric cancer, hepatocellular carcinoma (liver cancer, hepatoma), gall bladder cancer, bile duct cancer, esophageal cancer, renal cell carcinoma, thyroid cancer, squamous cell carcinoma of the head and neck (head and neck cancer), testicular cancer, cancer of the endocrine gland, cancer of the adrenal gland, cancer of the pituitary gland, cancer of the skin, cancer of soft tissues, cancer of blood vessels, cancer of brain, cancer of nerves, cancer of eyes, cancer of meninges, cancer of oropharynx, cancer of hypopharynx, cancer of cervix, and cancer of uterus, glioblastoma, meduloblastoma, astrocytoma, glioma, meningioma, gastrinoma, neuroblastoma, myelodysplastic syndrome, and sarcomas including, but not limited to, osteosarcoma, Ewing’s sarcoma, leiomyosarcoma, synovial sarcoma, alveolar soft part sarcoma, angiosarcoma, liposarcoma, fibrosarcoma, rhabdomyosarcoma, and chrondrosarcoma; and melanoma. In some embodiments, the cancer is leukemia, lymphoma, ovarian cancer, breast cancer, endometrial cancer, colon cancer, rectal cancer, gastric cancer, bladder cancer, lung cancer, bronchial cancer, bone cancer, prostate cancer, pancreatic cancer, liver and bile duct cancer, esophageal cancer, renal cancer, thyroid cancer, head and neck cancer, testicular cancer, glioblastoma, astrocytoma, melanoma, myelodysplasia syndrome, or sarcoma. In some embodiments, the cancer is a solid tumor. In some embodiments, the cancer is multiple myeloma, gastric adenocarcinoma/ gastroesophageal adenocarcinoma, endometrial carcinoma, platinum-resistant ovarian cancer, or diffuse large b- cell lymphoma. [0175] The composition comprising the CD47 binding protein disclosed herein can be used to treat a number of diseases and conditions in which ischemia-reperfusion injury (IRI) is a contributing feature, and to treat various autoimmune, autoinflammatory, inflammatory and cardiovascular diseases. These include: organ transplantation in which a mAb or antigen binding fragment thereof of the present invention is administered to the donor prior to organ harvest, to the harvested donor organ in the organ preservation solution, to the recipient patient, or to any combination thereof; skin grafting; surgical resections or tissue reconstruction in which such mAb or fragment is administered either locally by injection to the affected tissue or parenterally to the patient; reattachment of body parts; treatment of traumatic injury; pulmonary hypertension; pulmonary arterial hypertension; sickle cell disease (crisis); myocardial infarction; cerebrovascular disease; stroke; surgically-induced ischemia; acute kidney disease/kidney failure; any other condition in which IRI occurs and contributes to the pathogenesis of disease; autoimmune and inflammatory diseases, including arthritis, rheumatoid arthritis, multiple sclerosis, psoriasis, psoriatic arthritis, Crohn’s disease, inflammatory bowel disease, ulcerative colitis, lupus, systemic lupus erythematous, juvenile rheumatoid arthritis, juvenile idiopathic arthritis, Grave’s disease, Hashimoto’s thyroiditis, Addison’s disease, celiac disease, dermatomyositis, multiple sclerosis, myasthenia gravis, pernicious anemia, Sjogren syndrome, type I diabetes, vasculitis, uveitis and ankylosing spondylitis; autoinflammatory diseases, including familial Mediterrean fever, neonatal onset multisystem inflammatory disease, tumor necrosis factor (TNF) receptor-associated periodic syndrome, deficiency of the interleukin-1 receptor antagonist, Behcet’s disease; cardiovascular diseases, including coronary heart disease, coronary artery disease, atherosclerosis, myocardial infarction, heart failure, and left ventricular heart failure. [0176] The composition comprising the CD47 binding protein disclosed herein can be used to increase tissue perfusion in a subject in need of such treatment. Such subjects can be identified by diagnostic procedures indicating a need for increased tissue perfusion. In addition, the need for increased tissue perfusion may arise because the subject has had, is having, or will have, a surgery selected from integument surgery, soft tissue surgery, composite tissue surgery, skin graft surgery, resection of a solid organ, organ transplant surgery, or reattachment or an appendage or other body part. [0177] The composition comprising the CD47 binding protein disclosed herein can be combined with one or more therapeutic agent(s) for treating diseases disclosed herein. The one or more therapeutic agent(s) can be an antibody, a chemical small molecule, or biologic or a medical or surgical procedure which include, but are not limited to the following. [0178] Antibody and small molecule drugs that increase the immune response to cancer by modulating co-stimulatory or inhibitory interactions that influence the T cell response to tumor antigens, including inhibitors of immune checkpoints and modulators of co-stimulatory molecules, are also of particular interest in the context of the combination therapeutic methods encompassed herein and include, but are not limited to, other anti-CD47 antibodies. Administration of therapeutic agents that bind to the CD47 protein, for example, antibodies or small molecules that bind to CD47 and prevent interaction between CD47 and SIRPα, are administered to a patient, causing the clearance of cancer cells via phagocytosis. The therapeutic agent that binds to the CD47 protein is combined with a therapeutic agent such as an antibody, a chemical small molecule or biologic drug disclosed herein, directed against one or more additional cellular targets of CD70 (Cluster of Differentiation 70), CD200 (OX-2 membrane glycoprotein, Cluster of Differentiation 200), CD154 (Cluster of Differentiation 154, CD40L, CD40 ligand, Cluster of Differentiation 40 ligand), CD223 (Lymphocyte- activation gene 3, LAG3, Cluster of Differentiation 223), KIR (Killer-cell immunoglobulin- like receptors), GITR (TNFRSF18, glucocorticoid-induced TNFR-related protein, activation- inducible TNFR family receptor, AITR, Tumor necrosis factor receptor superfamily member 18), CD28 (Cluster of Differentiation 28), CD40 (Cluster of Differentiation 40, Bp50, CDW40, TNFRSF5, Tumor necrosis factor receptor superfamily member 5, p50), CD86 (B7-2, Cluster of Differentiation 86), CD160 (Cluster of Differentiation 160, BY55, NK1, NK28), CD258 (LIGHT, Cluster of Differentiation 258, Tumor necrosis factor ligand superfamily member 14, TNFSF14, HVEML, HVEM ligand, herpesvirus entry mediator ligand, LTg), CD270 (HVEM, Tumor necrosis factor receptor superfamily member 14, herpesvirus entry mediator, Cluster of Differentiation 270, LIGHTR, HVEA), CD275 (ICOSL, ICOS ligand, Inducible T-cell co- stimulator ligand, Cluster of Differentiation 275), CD276 (B7-H3, B7 homolog 3, Cluster of Differentiation 276), OX40L (OX40 Ligand), B7-H4 (B7 homolog 4, VTCN1, V-set domain- containing T-cell activation inhibitor 1), GITRL (Glucocorticoid-induced tumor necrosis factor receptor-ligand, glucocorticoid-induced TNFR-ligand), 4-1BBL (4-1BB ligand), CD3 (Cluster of Differentiation 3, T3D), CD25 (IL2Rα, Cluster of Differentiation 25, Interleukin-2 Receptor α chain, IL-2 Receptor α chain), CD48 (Cluster of Differentiation 48, B-lymphocyte activation marker, BLAST-1, signaling lymphocytic activation molecule 2, SLAMF2), CD66a (Ceacam- 1, Carcinoembryonic antigen-related cell adhesion molecule 1, biliary glycoprotein, BGP, BGP1, BGPI, Cluster of Differentiation 66a), CD80 (B7-1, Cluster of Differentiation 80), CD94 (Cluster of Differentiation 94), NKG2A (Natural killer group 2A, killer cell lectin-like receptor subfamily D member 1, KLRD1), CD96 (Cluster of Differentiation 96, TActILE, T cell activation increased late expression), CD112 (PVRL2, nectin, Poliovirus receptor-related 2, herpesvirus entry mediator B, HVEB, nectin-2, Cluster of Differentiation 112), CD115 (CSF1R, Colony stimulating factor 1 receptor, macrophage colony-stimulating factor receptor, M-CSFR, Cluster of Differentiation 115), CD205 (DEC-205, LY75, Lymphocyte antigen 75, Cluster of Differentiation 205), CD226 (DNAM1, Cluster of Differentiation 226, DNAX Accessory Molecule-1, PTA1, platelet and T cell activation antigen 1), CD244 (Cluster of Differentiation 244, Natural killer cell receptor 2B4), CD262 (DR5, TrailR2, TRAIL-R2, Tumor necrosis factor receptor superfamily member 10b, TNFRSF10B, Cluster of Differentiation 262, KILLER, TRICK2, TRICKB, ZTNFR9, TRICK2A, TRICK2B), CD284 (Toll-like Receptor-4, TLR4, Cluster of Differentiation 284), CD288 (Toll-like Receptor-8, TLR8, Cluster of Differentiation 288), TNFSF15 (Tumor necrosis factor superfamily member 15, Vascular endothelial growth inhibitor, VEGI, TL1A), TDO2 (Tryptophan 2,3-dioxygenase, TPH2, TRPO), IGF-1R (Type 1 Insulin-like Growth Factor), GD2 (Disialoganglioside 2), TMIGD2 (Transmembrane and immunoglobulin domain-containing protein 2), RGMB (RGM domain family, member B), VISTA (V-domain immunoglobulin-containing suppressor of T- cell activation, B7-H5, B7 homolog 5), BTNL2 (Butyrophilin-like protein 2), Btn (Butyrophilin family), TIGIT (T cell Immunoreceptor with Ig and ITIM domains, Vstm3, WUCAM), Siglecs (Sialic acid binding Ig-like lectins), Neurophilin, VEGFR (Vascular endothelial growth factor receptor), ILT family (LIRs, immunoglobulin-like transcript family, leukocyte immunoglobulin-like receptors), NKG families (Natural killer group families, C- type lectin transmembrane receptors), MICA (MHC class I polypeptide-related sequence A), TGFβ (Transforming growth factor β), STING pathway (Stimulator of interferon gene pathway), Arginase (Arginine amidinase, canavanase, L-arginase, arginine transamidinase), EGFRvIII (Epidermal growth factor receptor variant III), and HHLA2 (B7-H7, B7y, HERV– H LTR-associating protein 2, B7 homolog 7) , inhibitors of PD-1 (Programmed cell death protein 1, PD-1, CD279, Cluster of Differentiation 279), PD-L1 (B7-H1, B7 homolog 1, Programmed death-ligand 1, CD274, cluster of Differentiation 274), PD-L2 (B7-DC, Programmed cell death 1 ligand 2, PDCD1LG2, CD273, Cluster of Differentiation 273), CTLA-4 (Cytotoxic T-lymphocyte-associated protein 4, CD152, Cluster of Differentiation 152), BTLA (B- and T-lymphocyte attenuator, CD272, Cluster of Differentiation 272), Indoleamine 2,3-dioxygenase (IDO, IDO1), TIM3 (HAVCR2, Hepatitis A virus cellular receptor 2, T cell immunoglobulin mucin-3, KIM-3, Kidney injury molecule 3, TIMD-3, T cell immunoglobulin mucin-domain 3), A2A adenosine receptor (ADO receptor), CD39 (ectonucleoside triphosphate diphosphohydrolase-1, Cluster of Differentiation 39, ENTPD1), and CD73 (Ecto-5’-nucleotidase, 5’-nucleotidase, 5’-NT, Cluster of Differentiation 73), CD27 (Cluster of Differentiation 27), ICOS (CD278, Cluster of Differentiation 278, Inducible T-cell Co-stimulator), CD137 (4-1BB, Cluster of Differentiation 137, tumor necrosis factor receptor superfamily member 9, TNFRSF9), OX40 (CD134, Cluster of Differentiation 134), and TNFSF25 (Tumor necrosis factor receptor superfamily member 25), including antibodies, small molecules, and agonists, are also specifically contemplated herein. Additional agents include IL-10 (Interleukin-10, human cytokine synthesis inhibitory factor, CSIF) and Galectins. YERVOY^® (ipilimumab; Bristol-Meyers Squibb) is an example of an approved anti- CTLA-4 antibody. KEYTRUDA^® (pembrolizumab; Merck) and OPDIVO^® (nivolumab; Bristol-Meyers Squibb Company) are examples of approved anti-PD-1 antibodies. TECENTRIQ ^ (atezolizumab; Roche) is an example of an approved anti-PD-L1 antibody. [0179] For the treatment of autoimmune, autoinflammatory and inflammatory diseases, the combined therapeutic agents are: hydroxychloroquine, leflunomide, methotrexate, minocycline, sulfasalazine, abatacept, rituximab, tocilizumab, anti-TNF inhibitors or blockers (adalimumab, etanercept, infliximab, certolizumab pegol, golimumab), non-steroidal anti- inflammatory drugs, glucocorticoids, corticosteroids, intravenous immunoglobulin, anakinra, canakinumab, rilonacept, cyclophosphamide, mycophenolate mofetil, azathioprine, 6- mercaptopurine, belimumab, beta interferons, glatiramer acetate, dimethyl fumarate, fingolimod, teriflunomide, natalizumab, 5-aminosalicylic acid, mesalamine, cyclosporine, tacrolimus, pimecrolimus, vedolizumab, ustekinumab, secukinumab, ixekizumab, apremilast, budesonide and tofacitinib. [0180] For the treatment of atherosclerosis, the combined therapeutic agents or procedures are: medical procedures and/or surgery, including percutaneous coronary intervention (coronary angioplasty and stenting), coronary artery bypass grafting, and carotid endarterectomy; therapeutic agents, including angiotensin-converting enzyme (ACE) inhibitors (including ramipril, quinapril, captopril, and enalapril), calcium channel blockers (including amiodipine, nifedipine, verapamil, felodipine and diltiazem), angiotensin-receptor blockers (including eposartan, olmesarten, azilsartan, valsartan, telmisartan, losartan, candesartan, and irbesartan), the combination of ezetimibe and simvastatin, PCSK9 inhibitors (including alirocumab and evolocumab), anacetrapib, and HMG-CoA inhibitors (including atorvastatin, pravastatin, simvastatin, rosuvastatin, pitavastatin, lovastatin and fluvastatin). [0181] For the treatment of heart failure, the combined therapeutic agents are: ACE inhibitors, angiotensin receptor blockers, angiotensin receptor neprilsyn inhibitors (including the combination of sacubitril and valsartan), diuretics, digoxin, inotropes, beta blockers and aldosterone antagonists. [0182] For the treatment of pumonary hypertension the combined therapeutic agents are: sildenafil, tadalafil, ambrisentan, bosentan, macitentan, riociguat, treprostinil, epoprostenol, iloprost, and selexipag. [0183] The composition comprising the CD47 binding protein disclosed herein can be administered before, at the same time or after the combined therapeutic agents or medical or surgical procedures. [0184] The composition comprising the CD47 binding protein disclosed herein are administered in an effective amount to the subject. The precise effective amount for any particular subject will depend upon their size and health, the nature and extent of their condition, and the therapeutics or combination of therapeutics selected for administration. The effective amount for a given patient is determined by routine experimentation and is within the judgment of a clinician. Therapeutically effective amounts of the present antibody compounds can also comprise an amount in the range of from about 0.1 mg/kg to about 150 mg/kg, from about 0.1 mg/kg to about 100 mg/kg, from about 0.1 mg/kg to about 50 mg/kg, or from about 0.05 mg/kg to about 10 mg/kg per single dose administered to a harvested organ or to a patient. Known antibody-based pharmaceuticals provide guidance in this respect. For example, Herceptin™ is administered by intravenous infusion of a 21 mg/ml solution, with an initial loading dose of 4 mg/kg body weight and a weekly maintenance dose of 2 mg/kg body weight; Rituxan™ is administered weekly at 375 mg/m²; for example. [0185] A therapeutically effective amount for any individual patient can be determined by the health care provider by monitoring the effect of the antibody compounds on tumor regression, circulating tumor cells, tumor stem cells or anti-tumor responses. Analysis of the data obtained by these methods permits modification of the treatment regimen during therapy so that optimal amounts of antibody compounds of the present disclosure, whether employed alone or in combination with one another, or in combination with another therapeutic agent, or both, are administered, and so that the duration of treatment can be determined as well. In this way, the dosing/treatment regimen can be modified over the course of therapy so that the lowest amounts of antibody compounds used alone or in combination that exhibit satisfactory efficacy are administered, and so that administration of such compounds is continued only so long as is necessary to successfully treat the patient. Known antibody-based pharmaceuticals provide guidance relating to frequency of administration e.g., whether a pharmaceutical should be delivered daily, weekly, monthly, etc. Frequency and dosage may also depend on the severity of symptoms. [0186] The composition comprising the CD47 binding protein disclosed herein can be administered by a variety of routes including, but not limited to, oral, intravenous, intramuscular, intra-arterial, intramedullary, intraperitoneal, intrathecal, intraventricular, transdermal, transcutaneous, topical, subcutaneous, intratumoral, intranasal, enteral, sublingual, intravaginal, intravesiciular or rectal routes. The compositions can also be administered directly into a lesion such as a tumor. Hypo sprays may also be used to administer the pharmaceutical compositions. In some embodiments, the composition is for intravenous administration. In some embodiments, the composition is for subcutaneous administration. In some embodiments, the subcutaneous administration mitigates or prevents thrombocytopenia. [0187] Dosage treatment may be a single dose schedule or a multiple dose schedule. Typically, the compositions can be prepared as injectables, either as liquid solutions or suspensions. Solid forms suitable for solution in, or suspension in, liquid vehicles prior to injection can also be prepared. [0188] Veterinary applications include the treatment of companion/pet animals, such as cats and dogs; working animals, such as guide or service dogs, and horses; sport animals, such as horses and dogs; zoo animals, such as primates, cats such as lions and tigers, bears, etc.; and other valuable animals kept in captivity. Kits [0189] Further provided are kits, unit dosages, and articles of manufacture comprising any of the compositions disclosed herein. [0190] The kits of the present application are in suitable packaging. Suitable packaging includes, but is not limited to, vials, bottles, jars, flexible packaging (e.g., sealed Mylar or plastic bags), and the like. Kits may optionally provide additional components such as buffers and interpretative information. The present application thus also provides articles of manufacture, which include vials (such as sealed vials), bottles, jars, flexible packaging, and the like. [0191] The article of manufacture can comprise a container and a label or package insert on or associated with the container. Suitable containers include, for example, bottles, vials, syringes, etc. The containers may be formed from a variety of materials such as glass or plastic. [0192] Generally, the container holds a composition which is effective for treating a disease or disorder (such as cancer) disclosed herein, and may have a sterile access port (for example the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). The label or package insert indicates that the composition is used for treating the particular condition in an individual. The label or package insert will further comprise instructions for administering the composition to the individual. The label may indicate directions for reconstitution and/or use. The container holding the pharmaceutical composition may be a multi-use vial, which allows for repeat administrations (e.g. from 2-6 administrations) of the reconstituted formulation. Package insert refers to instructions customarily included in commercial packages of therapeutic products that contain information about the indications, usage, dosage, administration, contraindications and/or warnings concerning the use of such therapeutic products. Additionally, the article of manufacture may further comprise a second container comprising a pharmaceutically-acceptable buffer, such as bacteriostatic water for injection (BWFI), phosphate-buffered saline, Ringer’s solution and dextrose solution. It may further include other materials desirable from a commercial and user standpoint, including other buffers, diluents, filters, needles, and syringes. [0193] The kits or article of manufacture may include multiple unit doses of the pharmaceutical composition and instructions for use, packaged in quantities sufficient for storage and use in pharmacies, for example, hospital pharmacies and compounding pharmacies. [0194] In some embodiments, the kit is for treating cancer in a subject in need thereof, and the kit comprises the composition disclosed herein contained in a vessel. In some embodiments, the kit further comprises instructions for using the composition. EXAMPLES [0195] The following is a description of various methods and materials used in the studies. They are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how to make and use the present invention, and are not intended to limit the scope of what the inventors regard as their invention, nor are they intended to represent that the experiments below were performed and are all of the experiments that may be performed. It is to be understood that exemplary descriptions written in the present tense were not necessarily performed, but rather that the descriptions can be performed to generate the data and the like associated with the teachings of the present invention. Efforts have been made to ensure accuracy with respect to numbers used (e.g., amounts, percentages, etc.), but some experimental errors and deviations should be accounted for. Example 1: Formulation parameters [0196] Experiments were performed to identify a formulation for VLX9 with the highest product stability. Three buffers, each at different pH, and excipient combinations of Polysorbate 20, sorbitol, arginine, glycine, and NaCl, were evaluated. The stability of VLX9 under the stress conditions of agitation, freeze/thaw, and storage at temperatures that ranged from 2–8 °C to 40 °C were evaluated to identify the best formulation. This example describes the various formulation parameters that were tested for VLX9. The source material for the formulation study is described in Table 1. Table 1: pH stability VLX9 source material

[0197] The bulk drug substance (BDS) was concentrated and buffer-exchanged into each of the three buffers listed in Table 2. Table 2: Buffers

[0198] The VLX9 concentration was approximately 67 g/L in each buffer. Each VLX9 buffer (A1, A2, and A3) was spiked with Polysorbate 20 (PS20), sorbitol, arginine, glycine, or NaCl excipients to create each of the buffers listed in Table 3. Each formulated VLX9 was then adjusted to 50 g/L, filtered, and dispensed in 1 mL aliquots. Table 3: Study Excipients

[0199] The formulated materials were subjected to the stress and storage conditions in Table 4. The time zero (T0) control samples were collected at the initiation of each condition. At the specified intervals, the stressed or stored samples were collected. Table 4: Stress and Storage Conditions

[0200] Samples were analyzed for each of the following parameters: osmolality, appearance, pH, A280nm, SEC-HPLC, capillary isoelectric focusing (cIEF), LabChip electrophoresis, microfluidic imaging (MFI), and antigen binding. Example 2: Osmolality of VLX9 formulations [0201] The osmolality of each prepared solution was evaluated according to the testing requirements of the United States Pharmacopeia (USP) Physical Tests, Chapter <785> Osmolality and Osmolarity. A 290 mmol/kg check standard was used to monitor result validity. Each sample was measured in triplicate and reported as the average of the three values. The osmolality results for each formulation are provided in Table 5 below. Table 5: Formulation osmolality

Example 3: Appearance of VLX9 formulations [0202] Appearance of each formulation was assayed by first transferring a 1 mL sample into an appearance vial. The sample was held near a controlled light source for observation. The vial was gently agitated under observation to determine if the appearance changed. Appearance was verified against black and white backgrounds. Clarity was assessed as “clear”, “turbid”, or “slightly turbid”. Color, physical state, and foreign particles were documented. All control samples (T0) were clear, colorless liquids and essentially particle-free (Table 6). The conditions tested that contained PS20, either 0.006% or 0.06%, were generally clear and had low particles. The exception was Condition A1d at Week 4 (Table 7). At T0 and Week 8 (Table 8), this condition was clear. The MFI results for this condition described in Example 8 are consistent with other conditions with PS20, suggesting this A1d result maybe be due to subjective human error. Table 6: Appearance – Agitation and Freeze/Thaw

Table 7: Appearance – Week 4 Storage

Table 8: Appearance – Week 8 Storage

Example 4: pH of VLX9 formulations [0203] The pH of each sample was analyzed in triplicate and reported as the average of the three values. The pH values of the sample aliquots were within the assay variability at the start and end of each condition or time interval (Fig. 1). Therefore, the pH was not considered stability indicating. Example 5: A280nm of VLX9 formulations [0204] The VLX9 concentration was determined by measuring sample absorbance in triplicate at 280 nm by SoloVPE (C Technologies, Inc). Absorbance was corrected with absorbance at 320 nm to avoid potential light scattering interference from aggregates or particles. SoloVPE uses an absorbance vs. pathlength plot to determine a slope value for quantitation of sample concentrations. For each stress condition, the sample concentrations did not change or had minimal changes within the method variability from the T0 sample (Fig.2). The A280nm results were not stability-indicating and not used to determine a final formulation. Example 6: SEC-HPLC analysis of VLX9 formulations [0205] The SEC-HPLC parameters are outlined in Table 9. The SEC analysis was considered in two parts: formation of high molecular weight species (HMWS) and formation of low-molecular weight species (LMWS). Fig.3 shows the HMWS results; Fig.4 shows the main peak results; Fig.5 shows the LMWS results. Table 9: SEC parameters

[0206] Agitation and freeze/thaw had a minimal impact on HMWS formation. Of the formulations, Formulations A1 and A2 were least impacted. At 2–8 °C and 25 °C storage, Formulations A1c, A2a, and A2e showed a slight increase in HMWS (< 1%). The other formulation samples remained unchanged after incubation. The percent of the HMWS for the heated sample was the highest (1.09–2.16%) and A1c the highest of all (2.16%). After incubation at elevated temperature, Formulation A1a, all A2 formulations, and A3b showed minimal change in HMWS. [0207] The LMWS was elevated for all eight-week samples by ~0.5% to ~2%. It was further determined that the elevated levels of LMWS across the formulations were caused by a deteriorated column used for testing. Selected Week 10 at 25 °C samples were re-tested and the LMWS levels were similar to previous timepoints. A reference standard was used for system suitability for better control of the method for future development. The relative percent of LMWS was not stability-indicating. [0208] Design of experiments (DOE) models describe the effects of the formulation components and storage conditions on the stability of AO-176, such as the impact to the area as a percentage of the main peak, LMWS, and HMWS, respectively. These models were used to determine the effects of a particular formulation factor (i.e., pH, temperature, salt concentrations) on the amounts of each species present in the formulation over time. Week 8 was excluded from the DOE model. Week 10 data for conditions A1a, A1d, and A2d were included in the DOE model along with time zero and Week 4 data. High temperature decreased the main peak area over time (Fig. 6A). The LMWS area increased over time but decreased with higher temperature (Fig.6B). Higher NaCl concentrations and higher temperature resulted in more HMWS over time (Fig.6C). Example 7: Capillary isoelectric focusing (cIEF) analysis of VLX9 formulations [0209] Capillary isoelectric focusing (cIEF) is a high-resolution analytical technique that allows the separation of protein/peptide mixtures, protein glycoforms, and other charge variants, based on their isoelectric point (pI). The cIEF parameters are outlined in Table 10. Five species as shown in Fig.7 (an example VLX9 electropherogram that indicates the location of each species) were monitored by cIEF: Acidic (Fig.8A), Major Species 1 (Fig.8B), Major Species 2 (Fig.8C), Major Species 3 (Fig.8D), and Basic Species (Fig.8E). The same trend in all cIEF species was observed across the 13 formulations. The results were used for the selection of an optimal formulation but were referred to as supportive data. Table 10: cEIF Method Parameters

[0210] cIEF DOE models were generated for the for the Acidic Peak (Fig.9A), Main Peak 1 (Fig.9B), Main Peak 2 (Fig.9C), Main Peak 3 (Fig. 9D), and Basic Peak (Fig.9E). Lower pH and lower temperature prevented the formation of the Acidic Peak, Main Peak 1, Main Peak 2, and Main Peak 3. Main Peak 1 appeared to change into Main Peak 2 and Main Peak 3. Lower pH and Lower temperature were also beneficial to the protein stability and prevented degradation of the Basic Peak. Example 8: LabChip analysis of VLX9 formulations [0211] LabChip GX assays are based on traditional SDS gel electrophoresis principles that have been transferred to a chip format. Reduced and non-reduced samples were electrophoresed in separation channels by size. The LabChip results, reduced (LC+HC) and non-reduced (intact IgG), are shown in Fig.10 and Fig.11, respectively. [0212] Agitation and freeze/thaw cycles did not impact the percent light chain (LC) and heavy chain (HC; reduced) or the percent intact antibody (Non-reduced) in the sample. Intact antibody values (non-reduced) were within assay variability across timepoints and conditions. However, the percent of total light and heavy chains did decrease (up to 30%) with extended and elevated temperature storage for most formulations. The selected samples with decreased percentages (LC+HC) in LabChip testing were tested by CE-SDS (Reduced) and no fragments of the molecule were observed, suggesting the LabChip results for those samples were atypical and the method may not suitable for this molecule. In summary, the LabChip method was not stability-indicating. Example 9: Microfluidic imaging (MFI) analysis of VLX9 formulations [0213] Proteins can form sub-visible particles in response to stressed conditions, such as heat, freeze/thaw cycles, and agitation. An optimal formulation can stabilize a biologic drug substance against stressed conditions and protect the drug substance from the formation of particles. MFI was used to evaluate particle counts at four size ranges: 2 μm ≤ x < 5 μm (Fig. 12A), 5 μm ≤ x < 10 μm (Fig.12B), 10 μm ≤ x < 25 μm (Fig.12C); and ≥ 25 μm (Fig.12D). [0214] For MFI analysis, all standards and samples were prepared in a hood that had been wiped down with IPA and lint-free wipes. The 5 μm and 10 μm polystyrene size standards for the System Suitability were prepared with WFI water that had been 0.2 μm filtered. The 5 μm standard was used for the System Suitability. The 10 μm standard was used to ensure that the MFI was in focus and counting beads correctly. Before starting the MFI method, the flow cell was flushed several times with WFI water. A flow cell integrity check was performed to look at the background noise of the flow cell. The system verification was performed whenever a flow cell was replaced. All samples were equilibrated to ambient temperature prior to mixing and pooling. The sample was pooled from no less than three containers and read once. Values were reported in “Particles per mL” to the nearest whole number for the size ranges 2 ≤ x < 5 μm, 5 ≤ x < 10 μm, 10 ≤ x < 25 μm, and 25 ≤ x μm. To avoid counting the same particle multiples times, edge particles, stuck particles, and slow-moving particles were ignored on the software. [0215] Formulations A1c, A1e, A2a, A2c, and A3c, without PS20, had significantly more particles in all sizes (Fig. 12A), including the same controls (T0), and were not considered further. The appearance results for these formulations had also indicated a cloudy appearance. Formulations A1a and A3a generated the fewest particles of each size range after stress and storage. [0216] The MFI DOE models showed that PS20 greatly decreased the number of particles; higher sorbitol and arginine concentrations decreased particles; agitation had little effect on protein stability in the presence of PS20, and freeze/thaw had little effect on protein stability in the presence of PS20. Fig. 13A, Fig. 13B, Fig. 13C, and Fig. 13D show the MFI Week 8 stability DOE model for particles 2 μm ≤ x < 5 μm, 5 μm ≤ x < 10 μm, 10 μm ≤ x < 25 μm, and 25 μm ≤ x, respectively. Fig. 14A, Fig. 14B, Fig. 14C, and Fig. 14D show the MFI Agitation stability DOE model for particles 2 μm ≤ x < 5 μm, 5 μm ≤ x < 10 μm, 10 μm ≤ x < 25 μm, and 25 μm ≤ x, respectively. Fig.15A, Fig.15B, Fig.15C, and Fig.15D show the MFI Freeze/Thaw stability DOE model for particles 2 μm ≤ x < 5 μm, 5 μm ≤ x < 10 μm, 10 μm ≤ x < 25 μm, and 25 μm ≤ x, respectively. These data demonstrate that the presence of PS20 was a critical factor in maintaining the stability of the VLX9 formulations, mitigating particle formation and the effects of agitation and freeze thaw on the VLX9 formulations. Example 10: ELISA analysis of VLX9 formulations [0217] The binding of VLX9 to human CD47 was quantified by ELISA. The method uses the binding of VLX9 to determine the relative potency (%) of VLX9. High-binding ELISA plates were coated with 100 μL/well of recombinant Human His-CD47 (coating antigen) at 0.5 μg/mL in PBS by storage at 2–8 °C overnight. The following day, the coated ELISA plates were washed with PBST, pH 7.5 (Wash Buffer 1) via a plate washer. A volume of 250 μL/well of blocking buffer was applied and then the ELISA plates were incubated at ambient temperature on a plate shaker at ~ 400 rpm for 1 hr. During the blocking incubation, the VLX9 reference standard and sample curves were prepared with assay buffer. The standard and sample curves for each plate were prepared at a starting concentration of 30 μg/mL, and then diluted three-fold across the dilution plates. [0218] Following 1 hr of incubation, the coated/blocked ELISA plates were washed with PBST, pH 6.0 (Wash Buffer 2).100 μL/well of standard, sample, or assay buffer (blank) was added to the washed plate and then incubated at ambient temperature on a plate shaker at ~ 400 rpm for 1 hr. Following incubation, the ELISA plates were washed with PBST, pH 6.0 (Wash Buffer 2). The detection antibody (Anti-Human IgG (heavy and light), horse radish peroxidase) was diluted 1:15000 with assay buffer, and then 100 μL/well was added to the ELISA plates. The ELISA plates were incubated at ambient temperature on a plate shaker at ~ 400 rpm for 1 hr. After 1 hr incubation, the ELISA plates were washed with PBST, pH 6.0 (Wash Buffer 2). To the plate, 100 μL/well of QuantaBlu Working Solution was added and the plate incubated at ambient temperature on a plate shaker at ~ 400 rpm for 9 min. The reaction was stopped by the addition of 100 μL of QuantaBlu Stop Solution to each well. The ELISA plates were read at 315–340 nm for excitation, 370–470 nm for emission with 85 gain on BioTek plate reader. The results were generated and analyzed using Gen5 software and applying a parallel line analysis to determine the EC50 and relative potency (%). [0219] Based on the results from appearance (Example 3), SEC (Example 5), and MFI (Example 8), Formulation A1a was identified as an exemplary formulation for this product. Therefore, an ELISA binding assay was performed for this formulation as a measure of potency. Fig.16 shows the binding results. [0220] Freeze/thaw cycling stress resulted in an apparent 28.6% increase in potency from the control T(0) timepoint. Agitation stress resulted in an apparent reduced potency of 13.5% from the time zero timepoint. The difference measured for freeze/thaw and agitation may be due to assay error. Storage at 2–8 °C and 25 °C for four weeks had minimal impact to the relative potency of the VLX9. After eight weeks, the potency was 4.4% less potent than time zero timepoint at 2–8 °C and was 12.9% less potent than the time zero timepoint at 25 °C. The impact of heat stress (40 °C) after four weeks of storage was 16.7% decrease in potency relative to the time zero timepoint. Therefore, it appears incubation at higher temperature results in a loss of potency. Overall, Formulation A1a retained its binding activity after being subjected to stress conditions, except when subjected to agitation or prolonged exposure to 40 °C storage. Fig. 17 shows the DOE model of potency by ELISA and that the protein will decrease in potency faster at higher temperatures. Agitation and freeze/thaw data was not included as part of this model analysis. Example 11: Selection of VLX9 Formulation [0221] Based on the data described above, the following parameters in the selection of a particular VLX9 formulation for further study were noted as important factors: (a) Polysorbate 20 decreased particles and prevented the formation of particles upon agitation and freeze/thaw as measured by MFI. (b) Lower pH and lower temperature prevented aggregation as measured by SEC and changes to the protein charge as measured by cIEF. (c) Higher sorbitol and higher arginine concentrations decreased the number of particles as measured by MFI. [0222] A280 was not a stability indicating method for the conditions tested and resulted in an unexpected and unexplained increase over time. Similarly, visual inspection did not appear to be a reliable stability-indicating method, although appearance observations were generally well correlated with particle formation determined by MFI. [0223] With the data from appearance, SEC, and MFI and supported by A280nm, LabChip and cIEF analyses, Formulation A1a, comprised of 50 mM sodium acetate, 0.006% Polysorbate 20, 6% sorbitol, 60 mM arginine, pH 5.2, was identified as the best formulation for reducing particle formation and maintaining stability during stress (e.g., agitation, heat, freeze-thaw, See Example 8). In particular, the addition of Polysorbate 20 prevented the formation of particles across a variety of size ranges and maintained stability during agitation and freeze-thaw stress. See Examples 3 and 8. PS20 concentrations between 0.006% and 0.06% were sufficient to confer these benefits. The PS20 concentration was increased to 0.06% in the final formulation to reduce the risk that multiple stages of filtration would reduce PS20 levels below 0.006% in order to maintain the protective effects observed with PS20. Example 12: Toxicokinetic profile of VLX9 [0224] The objective of this study was to evaluate the tolerability and toxicokinetic profile of VLX9 when administered once weekly for 5 consecutive weeks (5 doses) via a 1-hour intravenous infusion to female cynomolgus monkeys. In addition, 3 groups were dosed once with either a single 1-hour intravenous infusion or a single subcutaneous bolus injection for toxicokinetic assessment. The study design is provided in Table 11. Groups 1 through 4 were dosed on Days 1, 8, 15, 22, and 29 and scheduled for a terminal necropsy on Day 36. Groups 5, 6, and 7 were dosed once on Day 1 and transferred to the CRL colony on Day 36. Table 11: Experimental Design

[0225] VLX9 and vehicle control formulations were administered by 1-hour intravenous infusion once weekly, for 5 consecutive weeks (Days 1, 8, 15, 22 and 29) to Groups 1 through 4. Groups 5, 6 and 7 were dosed once by subcutaneous injection (Group 5) or 1-hour intravenous infusion (Groups 6 and 7) on Day 1 to compare intravenous and subcutaneous routes of administration. [0226] The following parameters and end points were evaluated in this study: clinical signs, body weights, body weight gains, clinical pathology parameters (hematology, coagulation, serum chemistry, and urinalysis), peripheral blood immunophenotyping, complement analysis, cytokine analysis, toxicokinetic parameters, anti-drug antibody analysis, gross necropsy findings, organ weights, and histopathologic examinations. A summary of the various parameters analyzed are provided in Table 12 and Table 13. Table 12: Study parameters

Table 13: Toxicokinetic Parameters

[0227] All animals survived to the scheduled necropsy. No VLX9-related clinical findings were noted. No effects were noted on body weights or body weight changes. All clinical observations in the VLX9-treated groups were noted with similar incidence in the control group, were limited to single animals, were not noted in a dose-related manner, and/or were common findings for laboratory monkeys of this age and breed. [0228] Body weights were unaffected by VLX9 administration. From Days -1 to 7, a mean body weight loss of 0.03 kg was noted for females in the 10 mg/kg/dose SC and IV single dose groups and the 1 mg/kg/dose IV single dose group, which was statistically significant when compared to a mean body weight loss of 0.20 kg in the control group over the same time period. However, this was attributed to biological variation. [0229] Administration of VLX9 resulted in non-adverse VLX9 alterations in hematology, including in the blood smears and serum chemistry. There was no evidence of agglutination, and there were no changes in coagulation and urinalysis parameters. The changes noted in the clinical pathology parameters were considered to be non-adverse based on magnitude and lack of clinical signs. Red blood cell parameters [0230] VLX9-related changes in hematology and blood smears were of minimal to moderate magnitude and consisted of transient decreased red blood cell mass and increased reticulocyte count (with increased polychromasia, macrocytosis, and anisocytosis) and red cell distribution width (RDW) that were noted in all groups particularly at the earlier time points. The decreased red blood cell mass persisted through Day 14 in the 10 mg/kg/dose IV group, through Day 31 in the 50 and 100 mg/kg/dose IV groups and through Day 11 in the 10 mg/kg/dose (single dose) IV and SC groups. The changes in red blood cell mass were accompanied by the presence of minimal to mild numbers of spherocytes in all groups, except in the 1 mg/kg/dose (single dose) IV group. These changes in red blood cell mass with the presence of spherocytes were considered to be related to the pharmacology of VLX9. [0231] VLX9-related alterations in the red blood cell-related parameters consisted of non- adverse decreased red blood cell mass and increased reticulocyte count and red cell distribution width (RDW), as shown in Fig.18A-Fig.18C. Overall, the red blood cell parameters showed a transient decrease that trended or reversed back to baseline by the end of the study and did not recur upon subsequent dosing. These changes were considered to be non-adverse based on magnitude and lack of related clinical signs. VLX9 binds minimally to CD47 on monkey red blood cells and in previous studies, a mild and transient decrease in red blood cell mass was also observed and was not considered to be adverse. [0232] Non-adverse, minimal to moderate and transient decrease in red blood cell mass was noted in dose groups administered VLX9. Specifically, VLX9-related minimally to moderately decreased red blood cell mass represented by hemoglobin in Fig.18A was noted in the 10, 50, and 100 mg/kg/dose IV groups from Day 3 to 14. In the 10 mg/kg/dose IV group, this change continued through Day 14; while in the 50 and 100 mg/kg/dose IV groups, this change continued through Day 31; however, the change lacked a clear dose response, was noted particularly for hemoglobin, and often in a single animal in the group. In the 10 mg/kg/dose (single dose) SC group and 1 and 10 mg/kg/dose (single dose) IV groups, minimally to mildly decreased red blood cell mass was noted initially at Day 3, which continued in the 10 mg/kg/dose (single dose) IV and SC groups through Day 11. No adverse clinical signs were associated with the transient decrease in red blood cell mass. [0233] VLX9-related non-adverse increased reticulocyte count indicative of increased erythropoiesis (regenerative response) was observed shortly after the onset of the transient decreased red blood cell mass. Specifically, minimally to moderately increased reticulocyte count was noted in the 10, 50, and 100 mg/kg/dose IV groups from Day 7 to 28 and 50 and 100 mg/kg/dose IV groups at Day 31. Mildly to moderately increased reticulocyte count was also noted in the 10 mg/kg/dose (single dose) SC group and 1 and 10 mg/kg/dose (single dose) IV groups at Days 7 and 9, which continued increased in the 10 mg/kg/dose (single dose) IV and SC groups at Days 11 and 14 and in the 10 mg/kg/dose (single dose) SC group at Day 17. The increased reticulocyte count correlated with the histopathology finding of increased hematopoiesis, including erythroid precursors noted in the bone marrow. [0234] Additional VLX9-related changes in red blood cell parameters related to the increased reticulocyte counts, included minimally to moderately increased RDW in the 10, 50, and 100 mg/kg/dose IV groups and 10 mg/kg/dose (single dose) IV and SC groups at Days 7 to 28. [0235] Increased red blood cell mass was noted in the 1 and 10 mg/kg/dose (single dose) IV groups from Day 17 through 36 with decreased reticulocyte count noted in the 10 mg/kg/dose (single dose) SC group and/or 1 and 10 mg/kg/dose (single dose) IV groups at Days 28, 31, and/or 36 when compared to the concurrent control group. These changes were not considered to be related to VLX9 administration and was likely attributed to different blood collections scheduled for control animals because the reticulocyte values were within the acclimation period range in these groups. [0236] The transiently decreased red blood cell mass and increased reticulocyte count, with minimal numbers of spherocytes (see Section 8.4.3.) was considered to be related to the pharmacology of VLX9 (i.e. CD47 normally expressed on the red blood cell membrane, activating clearance of the red blood cells by macrophages). White Blood Cell-Related Parameters [0237] Other changes in hematology included transient increased monocyte counts (potentially VLX9-related, See Fig. 19) and/or the presence of band neutrophils and Dohle bodies in all groups at Day 7. [0238] A potentially VLX9-related, minimally increased monocyte count was noted on Day 7 in the 10, 50, and 100 mg/kg/dose IV groups, the 1 and 10 mg/kg/dose (single dose) IV groups, and the 10 mg/kg/dose (single dose) SC group. This change was considered to be potentially related to VLX9 administration based on the dose response pattern, concurrent evidence of inflammation noted in these groups (presence of band neutrophils and Dohle bodies see Section 8.4.3 and the fact that individual values of some animals in these groups were above the range of acclimation period values. Of note, the monocyte counts in the control group animals at Days 7 and 9 were decreased compared to respective acclimation period values and to the historical control (Range: 0.12-0.64 thousand/μL), which was most likely attributed to the fact that the differential cell count in these animals was performed manually. The decreased monocyte count in the control group at Day 9 resulted in statistically significant increased monocyte count in some treated groups at this time point, which was considered to be unlikely related to VLX9 administration because all individual values were within the range of acclimation period and/or there was no dose response or no other findings indicative of inflammation, at this time point. [0239] In addition to the potentially VLX9-related effect on monocytes, a mildly to moderately decreased neutrophil count was noted in the 50 mg/kg/dose IV group on Day 3 (Female Nos.3501 and 3503) and Days 14 through 21 (Female No.3503); the 100 mg/kg /dose IV group at Day 17 (Female Nos. 4501 and 4502); and the 10 mg/kg/dose (single dose) IV group at Day 11 (Female No.6501). This change was of an uncertain relationship with VLX9 administration because it was transient (did not maintain over time when subsequent doses were administered), of low incidence and lacked a clear dose response pattern. [0240] VLX9-related transient decreased platelet count was noted in most groups only at Day 3 and returned to levels similar or higher than the control or acclimation period values at Day 7, except in a single animal in the 50 mg/kg/day IV group, in which the platelet count was moderately decreased again at Days 14, 17, and 24, returning to acclimation period or control range at Days 31 and 36. The increased platelet count was potentially a response to both the decreased platelet count noted at Day 3 and to the regenerative response (increased reticulocyte count) noted at these time points. The changes in the platelet count was considered to be non- adverse based on magnitude and lack of related clinical signs. See Fig.20. [0241] Other differences in the hematology parameters, including those determined to be statistically significant were considered to be due to biological variation and not related to the administration of VLX9. Serum Chemistry [0242] VLX9-related changes in serum chemistry resulted in minimally to mildly decreased mean albumin and albumin to globulin ratio (AG) in the 50 and 100 mg/kg/dose IV groups and minimally to moderately increased globulin with increased total protein in the 10, 50, and /or 100 mg/kg/dose IV groups. See Fig.21. The increased globulin was at least partially attributed to the intravenous administration of the monoclonal antibody VLX9. Other differences in the serum chemistry parameters, including those determined to be statistically significant were considered to be due to biological variation and not related to the administration of VLX9. Peripheral blood immunophenotyping [0243] When compared to pretreatment/pre-dose values, the only immunophenotyping (flow cytometry) change suggestive of an VLX9 related effect was the notable lowering in the absolute counts of B cells at the 100 mg/kg/dose IV group. The percent differences (lowering) in B cell counts when compared to pretreatment values were approximately 37.6% and 39.8% on Days 15 and 36 respectively. The relationship of other changes observed in the high dose group (100 mg/kg/dose IV) for total T cells, T helper cells, T cytotoxic cells and B cells (50 mg/kg/dose IV group) to VLX9 was unclear. The significance of these findings is also unclear in these subsets since similar changes were observed in the control group for total T cells, T helper cells, T cytotoxic cells and B cells. Many of these changes were within the historical control reference ranges for animals in similar age groups, showed a similar change in controls (either by percent change or absolute counts), and/or did not show a clear dose response. Therefore, these changes have an unclear relationship to treatment. [0244] Compared to the control group, there were statistically significant higher mean percentage values of total T and T helper cells in the 1 mg/kg/dose (single dose) IV group (Group 7). However, these values were not considered VLX9-related, because the values observed in these phenotypes after dosing were similar to the pretreatment values. [0245] The following changes discussed below were not statistically significant and were generally within the range of historical control data, but were nonetheless notably different when compared to each group’s own pretreatment values and suggestive of a potential VLX9- related effect. Compared to pretreatment values (i.e. when compared to each group’s baseline value on Day -6), the following notable changes were observed. [0246] Moderate lowering in the mean absolute counts of total T cells (Fig. 22), T helper (Fig.23), and T cytotoxic cells (Fig.24) was observed in the 100 mg/kg/dose IV group (Group 4) on Days 15 and 36. When compared to each group’s concurrent pretreatment Day -6 value, the percentage differences observed on Days 15 and 36 were approximately 40.2% and 50.3%, respectively, for total T cells, 35.0% and 51.9%, respectively, for T helper cells, and 44.7% and 47.4%, respectively, for T cytotoxic cells. Importantly, these are within the range of natural variations seen from animal to animal, since a similar magnitude of variation was observed in the control group. Animals in the control group showed a decrease up to 40.5% in total T cells, 27.9% in T helper cells, and 50.8% in T cytotoxic cells. The historical control reference range for absolute cell counts for female Cynomolgus monkeys between 154-187 weeks of age ranged from 1.6-4.8 for total T cells, 1.2-2.9 for T helper cells, and finally 0.4–1.8 thousand/μL for T cytotoxic cells. The changes observed in the treatment arms are mostly within the historical control range and showed a similar percent change and absolute cell count to the control group on Day 36. An exception to this was T helper cells in the 100 mg/kg/dose IV group (Group 4), which had a mean absolute count of 0.88 thousand/μL on Day 36. However, this is not suggestive of a VLX9 related effect since the mean absolute counts of T helper cells observed in the control group on Day 36 was 0.80 thousand/μL, which is lower than the values observed in the 100 mg/kg/dose IV treatment group. Because of these reasons, it is unclear whether the changes in Total T cells, T helper cells, or T cytotoxic cells were a true treatment- related effect. [0247] Moderate lowering in the mean absolute counts of B cells was observed in the 50 mg/kg/dose IV group (Group 3) on Day 36, and in the 100 mg/kg/dose IV group (Group 4) on Days 15, and 36 (Fig. 25). When compared to concurrent pretreatment day values, the percentage differences observed on Day 15 for the 100 mg/kg/dose IV group was approximately 37.6%. The percentage differences observed on Day 36 were approximately 43.8% and 39.8%, respectively, for 50 and 100 mg/kg/dose IV groups. Controls also showed a minimal to mild decrease in B cells of 20.7 % and 31.0%, respectively on Day 15 and Day 36 which are comparable to the changes observed at 50 and 100 mg/kg/dose IV group. The historical control reference range for B cells in female monkeys in this age group ranged from 0.7-1.9 thousand/μL. The values observed in different dose groups were in general within the historical control range, except for the 100 mg/kg/dose IV group which had mean absolute values of 0.58 and 0.56 thousand/μL on Day 15 and 36 respectively which were slightly below that range. Hence, the lowering of B cells at the 100 mg/kg/dose IV group is suggestive of a possible effect of VLX9. However, the moderate lowering in the mean absolute counts of B cells in the 50 mg/kg/dose IV groups on Day 36 could not be attributed to a true treatment related effect because the mean absolute count of 0.68 thousand/μL observed in this group was similar to the values observed in the concurrent control group at 0.80 thousand/μL. In addition, this value was within the historical control reference range of 0.7-1.9 thousands/μL. [0248] Moderate lowering in the mean absolute counts of dendritic cells was observed in the 100 mg/kg/dose IV group (Group 4) and moderate to marked higher mean absolute counts were observed in the 10 mg/kg/dose IV group (Group 2) on Days 15 and 36 (Fig. 26). When compared to concurrent pretreatment day values, the percentage differences observed on Days 15 and 36 were 33.3% and 51.7%, respectively, for the 100 mg/kg/dose IV group, and 40.6% and 88.4 %, respectively, for the 10 mg/kg/dose IV group. However, no notable changes were observed in the 50 mg/kg/dose IV group (Group 3). A mild decrease of 34.9% was seen in the control group on Day 36. Historical control data is not available for dendritic cells. In addition, due to the low counts observed in this cell subset any small changes due to natural or random variations would be reflected as a percentage difference with a larger magnitude. [0249] Markedly higher mean absolute counts of total activated T cells (Fig. 27 - 10 mg/kg/dose IV group (Group 2) on Day 36), activated T cytotoxic cells (Fig. 28 - 10 mg/kg/dose IV group (Group 2) on Day 36, and the 1 mg/kg/dose (single dose) IV group (Group 7) on Days 15 and 36), and NK cells (Fig. 29 - Days 15 and 36 in the 10 and 50 mg/kg/dose groups (Groups 2 and 3, respectively), and 10 mg/kg/dose (single dose) IV and 10 mg/kg/dose (single dose) SC groups (Groups 5 and 6, respectively) on Days 15 and 36) were observed. However, these changes were not considered VLX9-related because similar magnitude of changes were also observed in the control group and or the low dose group. In addition, due to the extremely low counts observed in these cell subsets any small changes happening due to natural or random variations will be reflected as a change with a larger magnitude. [0250] Taken together, these data indicate that there are no significant adverse effects on peripheral blood cell populations associated with the use of VLX9 in vivo. Organ Weights [0251] Organ weight changes included an increase in spleen weight (absolute, % of body weight and, % of brain weight) that correlated histologically with increased mild to moderate increased cellularity of the red pulp and less frequently increased cellularity of the white pulp (See Fig. 30 and Fig. 31). VLX9 related microscopic findings included increased hematopoiesis in the femur bone marrow that was mild at 10 mg/kg/dose and severe at 50 and 100 mg/kg/dose. Additionally, within the spleen there was mild to moderate increased cellularity of the red pulp and mild increased cellularity of the white pulp. These microscopic findings within the bone marrow and spleen were considered non-adverse and are reflective of a regenerative response (Fig.31A). [0252] Additional microscopic findings included minimally increased severity of interstitial mononuclear infiltrates in the lung and kidney of treated animals compared to control animals and presence of minimal perivascular mononuclear infiltrates within the brain observed in treated animals only (Fig.31B). The mononuclear infiltrates within the brain were within the historical control data range, therefore unlikely to be treatment related. Additionally, mononuclear infiltrates in these tissues are commonly described background findings in cynomolgus monkeys. The increased severity of mononuclear infiltrates in treated animals (groups 3 & 4 for lung and group 3 for kidney), however, were slightly outside the historical control data range, therefore, it is unclear if there is also an effect related to the administration of VLX9 in the kidney and lung. [0253] These data indicate that there are no adverse effects on organ weights or cellular infiltrates associated with the use of VLX9 in vivo. Cytokine and Complement Analysis [0254] While no clinical signs indicative of cytokine release or complement activation were evident during the 5-week toxicology and toxicokinetic study, samples from several of the monkeys collected during the study had elevated levels of cytokines and SC5b-9, defined as any serum analyte concentration higher than that of the highest vehicle control and at least 3- fold or greater than the pre-study baseline level for the individual animal. This method was employed due to the general lack of non-human primate reference ranges for these analytes in the literature. It should be noted that post-infusion/injection IL-6 levels in all vehicle control animals were increased relative to pre-dose levels, which would suggest that changes in IL-6 levels for most samples may be associated with procedure rather than VLX9. Toxicokinetic Evaluations [0255] Single or repeated 1-hour IV infusion of VLX9 to female monkeys resulted in systemic exposure to VLX9 on all evaluation days (Fig.32). Following a 1-hour IV infusion, exposure to VLX9, in terms of AUC(0-168) and Cmax, increased with dose in a greater than dose-proportional manner from 10 to 100 mg/kg/dose. Following IV infusion, mean Cl was generally low and volume distribution at steady state (Vss) was small. There was no clear trend in differences related to dose or evaluation day. This resulted in a T1/2 that ranged from approximately 40 to 90 hours. A single SC injection of VLX9 to female monkeys resulted in systemic exposure to VLX9 on Day 1. When comparing the single SC injection with the single 1-hour IV infusion at 10 mg/kg/dose, AUC (0-168) and Cmax were approximately 1.4- and 4.8-fold higher in the IV infusion group, respectively. Following a single SC injection, T1/2 was 50.1 hours. In monkeys that received a single IV infusion of VLX9 at 10 mg/kg SC (Group 5), 10 mg/kg IV infusion (Group 6), or 1 mg/kg IV infusion (Group 7), all animals were found to have a positive anti-drug antibody (ADA) status on Day 36. In monkeys that received an IV infusion of VLX9 at 10, 50, or 100 mg/kg/dose (Group 2, Group 3, and Group 4) on Day 1, Day 8, Day 15, Day 22 and Day 29, 5 of 12 monkeys were confirmed as having a positive ADA status on Day 29 and Day 36. In the 10 mg/kg group, all monkeys were confirmed positive on both days. At 50 and 100 mg/kg/dose VLX9, there was a single monkey in each dose group (Animal No.3503 and Animal No.4502, respectively) had a confirmed positive ADA response on Day 29 and Day 36. A marked increase in clearance and subsequent decrease in exposure was noted at 10 mg/kg/dose, but no notable impact of a positive ADA status was noted at 50 or 100 mg/kg/dose. There was no accumulation noted in the repeated IV infusion groups with ratios of 0.197, 1.22, and 1.41 for 10, 50, and 100 mg/kg/dose, respectively. Anti-drug Antibody (ADA) Analysis [0256] Positive ADA results were obtained for 21 of 54 samples, including 3/3 samples at 10 mg/kg IV (Group 2) and 1/3 samples at 50 and 100 mg/kg IV (Groups 3 and 4) on Day 29 and 3/3 samples at 10 mg/kg IV (Group 2), 1/3 samples at 50 and 100 mg/kg IV (Groups 3 and 4), and 3/3 samples at 10 mg/kg SC and IV (Groups 5 and 6) and 1 mg/kg IV (Group 7) on Day 36. In addition, 2 pre-dose samples were confirmed positive. Conclusions [0257] Based on the results of this study, intravenous administration of VLX9 to cynomolgus monkeys at dosage levels of 10, 50, and 100 mg/kg/dose, once weekly for 5 weeks, was well tolerated at all dosages with no VLX9-associated clinical signs. VLX9-related effects included non-adverse, transient, and reversible decreases in red blood cell mass, increased reticulocytes (with increased polychromasia, macrocytosis, and anisocytosis) and RDW, minimal to mild decreases in mean albumin, minimal to moderate increases in globulin, increased total protein, an increase in spleen weights with non-adverse increased hematopoiesis and mild to moderate increased cellularity of the red pulp of the spleen. There was no evidence of agglutination in this study. Based on the absence of overt toxicity, the no-observed-adverse effect level (NOAEL) was considered to be 100 mg/kg/day. This dosage corresponded to mean AUC0-168hr values of 180,000,000 and 253,000,000 ng•hr/mL and mean Cmax values of 3,380,000 and 3,570,000 ng/mL for females on Day 1 and 29, respectively. * * * * * [0258] It will be appreciated by those skilled in the art that changes could be made to the embodiments described above without departing from the broad inventive concept thereof. It is understood, therefore, that this invention is not limited to the some embodiments disclosed, but it is intended to cover modifications within the spirit and scope of the present invention as defined by the present description. [0259] Various publications, articles and patents are cited or described in the background and throughout the specification; each of these references is herein incorporated by reference in its entirety. Discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is for the purpose of providing context for the invention. Such discussion is not an admission that any or all of these matters form part of the prior art with respect to any inventions disclosed or claimed.

Claims

CLAIMS What is claimed: 1. A composition comprising: (i) a CD47 binding protein comprising: (a) a variable heavy chain (VH) comprising a variable heavy chain CDR1 (HCDR1) of SEQ ID NO:3; a variable heavy chain CDR2 (HCDR2) of SEQ ID NO:6; a variable heavy chain CDR3 (HCDR3) of SEQ ID NO:10; and (b) a variable light chain (VL) comprising a variable light chain CDR1 (LCDR1) of SEQ ID NO:14; a variable light chain CDR2 (LCDR2) of SEQ ID NO:17; a variable light chain CDR3 (LCDR3) of SEQ ID NO:18; (ii) a buffer; and (iii) a surfactant.

2. The composition of claim 1, wherein the VH comprises the sequence of SEQ ID NO:36, or a sequence at least 90% identical thereto.

3. The composition of claim 1, wherein the VL comprises the sequence of SEQ ID NO:52, or a sequence at least 90% identical thereto.

4. The composition of any one of claims 1-3, wherein the binding protein is a monoclonal antibody.

5. The composition of claim 4, wherein the monoclonal antibody is humanized.

6. The composition of claim 4, wherein the monoclonal antibody is an IgG1, IgG2, IgG3, or IgG4.

7. The composition of claim 4, wherein the monoclonal antibody is an IgG4.

8. The composition of any one of claims 1-7, wherein the buffer is a sodium acetate buffer or a histidine buffer.

9. The composition of any one of claims 1-8, wherein the concentration of the buffer is in the range of from about 0.1 mM to about 500 mM.

10. The composition of claim 9, wherein the concentration of the buffer is about 50 mM.

11. The composition of any one of claims 1-10, wherein the surfactant is polysorbate 20 or polysorbate 80.

12. The composition of claim 11, wherein the concentration of polysorbate 20 is from about 0.001% to about 0.1% (w/v).

13. The composition of claim 12, wherein the concentration of polysorbate 20 is about 0.006% (w/v).

14. The composition of claim 12, wherein the concentration of polysorbate 20 is about 0.06% (w/v).

15. The composition of any one of claims 1-14, wherein the composition comprises at least one additional excipient.

16. The composition of claim 15, wherein the at least one additional excipient is a sugar alcohol.

17. The composition of claim 16, wherein the sugar alcohol is sorbitol, mannitol, xylitol, lactitol, or erythritol.

18. The composition of claim 16, wherein the sugar alcohol is sorbitol.

19. The composition of any one of claims 16-18, wherein the concentration of the sugar alcohol is in the range of from about 1% to about 10% (w/v).

20. The composition of claim 19, wherein the concentration of the sugar alcohol is about 3% (w/v).

21. The composition of claim 19, wherein the concentration of the sugar alcohol is about 6% (w/v).

22. The composition of any one of claims 1-21, wherein the composition comprises at least one amino acid.

23. The composition of claim 22, wherein the at least one amino acid is arginine.

24. The composition of claim 22, wherein the at least one amino acid is glycine.

25. The composition of any one of claims 22-24, wherein the concentration of the amino acid is from about 10 mM to about 200 mM.

26. The composition of claim 25, wherein the concentration of the amino acid is about 40 mM, about 60 mM, about 80 mM, or about 125 mM.

27. The composition of any one of claims 1-26, wherein the composition comprises at least one salt.

28. The composition of claim 27, wherein the at least one salt is sodium chloride.

29. The composition of any one of claims 27-28, wherein the concentration of the salt is from about 10 mM to about 200 mM.

30. The composition of claim 29, wherein the concentration of the salt is about 50 mM or about 100 mM.

31. The composition of any one of claims 1-30, wherein the concentration of the CD47 binding protein is in the range of from about 1 g/L to about 250 g/L.

32. The composition of claim 31, wherein the concentration of the CD47 binding protein is about 50 g/L.

33. The composition of claim 31, wherein the concentration of the CD47 binding protein is about 182 g/L.

34. The composition of any one of claims 1-33, wherein the composition has a pH in the range of from about 5.0 to about 7.0.

35. The composition of claim 34, wherein the composition has a pH of about 5.2.

36. The composition of claim 34, wherein the composition has a pH of about 6.2.

37. The composition of claim 34, wherein the composition has a pH of about 6.8.

38. A composition comprising: (i) a CD47 binding protein comprising: (a) a variable heavy chain (VH) comprising a variable heavy chain CDR1 (HCDR1) of SEQ ID NO: 3; a variable heavy chain CDR2 (HCDR2) of SEQ ID NO: 6; a variable heavy chain CDR3 (HCDR3) of SEQ ID NO: 10; and (b) a variable light chain (VL) comprising a variable light chain CDR1 (LCDR1) of SEQ ID NO: 14; a variable light chain CDR2 (LCDR2) of SEQ ID NO: 17; a variable light chain CDR3 (LCDR3) of SEQ ID NO: 18; (ii) a sodium acetate buffer, (iii) polysorbate 20 or polysorbate 80, (iv) sorbitol, and (v) arginine.

39. The composition of claim 38, wherein the concentration of the sodium acetate buffer is in the range of from about 10 mM to about 100 mM, the concentration of the polysorbate 20 is in the range of from about 0.001% to about 0.1% (w/v), the concentration of the sorbitol is in the range of from about 1% to about 10% (w/v), and the concentration of the arginine is in the range of from about 10 mM to about 200 mM.

40. The composition of claim 39, wherein the concentration of the sodium acetate buffer is about 50 mM, the concentration of the polysorbate 20 is about 0.06% (w/v), the concentration of the sorbitol is about 6% (w/v), and the concentration of the arginine is about 60 mM.

41. The composition of any one of claims 38-40, wherein the composition has a pH of from about 5.0 to about 7.0.

42. The composition of claim 41, wherein the composition has a pH of about 5.2.

43. The composition of any one of claims 38-42, wherein the concentration of the CD47 binding protein is in the range of from about 1 g/L to about 200 g/L.

44. The composition of claim 43, wherein the concentration of CD47 binding protein is about 50 g/L.

45. The composition of claim 43, wherein the concentration of CD47 binding protein is about 182 g/L.

46. The composition of any one of claims 1-45, wherein the composition is for intravenous administration.

47. The composition of any one of claims 1-45, wherein the composition is for subcutaneous administration.

48. The composition of claim 46, wherein subcutaneous administration mitigates or prevents thrombocytopenia.

49. The composition of any one of claims 1-48, wherein the CD47 binding protein is substantially stable for at least 30 days at a temperature in the range of from about 2°C to about 8°C.

50. The composition of any one of claims 1-48, wherein the composition slows or reduces the degradation of the CD47 binding protein as compared to an identical composition lacking the surfactant, when stored under the same conditions.

51. The composition of claim any one of claims 1-48, wherein the composition is substantially resistant to the formation of particles upon agitation.

52. The composition of any one of claims 1-48, wherein the composition is substantially resistant to the formation of particles following at least one freeze/thaw cycle.

53. The composition of any one of claims 1-48, wherein the composition is substantially resistant to changes to the charge of the CD47 binding protein over time.

54. A method for treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of the composition of any one of claims 1-53.

55. The method of claim 54, wherein the cancer is leukemia, lymphoma, ovarian cancer, breast cancer, endometrial cancer, colon cancer, rectal cancer, gastric cancer, bladder cancer, lung cancer, bronchial cancer, bone cancer, prostate cancer, pancreatic cancer, liver and bile duct cancer, esophageal cancer, renal cancer, thyroid cancer, head and neck cancer, testicular cancer, glioblastoma, astrocytoma, melanoma, myelodysplasia syndrome, or sarcoma.

56. The method of claim 54, wherein the cancer is a solid tumor.

57. The method of claim 54, wherein the cancer is multiple myeloma, gastric adenocarcinoma/ gastroesophageal adenocarcinoma, endometrial carcinoma, platinum- resistant ovarian cancer, or diffuse large b-cell lymphoma.

58. The method of any one of claims 54-57, wherein the composition is administered intravenously.

59. The method of any one of claims 54-57, wherein the composition is administered subcutaneously.

60. The method of claim 59, wherein the subcutaneous administration mitigates or prevents thrombocytopenia.

61. Use of the composition of any one of claims 1-53 for treating cancer in a subject.

62. The use of claim 61, wherein the cancer is multiple myeloma, gastric adenocarcinoma/ gastroesophageal adenocarcinoma, endometrial carcinoma, platinum-resistant ovarian cancer, or diffuse large b-cell lymphoma.

63. The use of claim 61 or 62, wherein the composition is administered intravenously.

64. The use of claim 61 or 62, wherein the composition is administered subcutaneously.

65. The use of claim 64, wherein the subcutaneous administration mitigates or prevents thrombocytopenia.

66. Use of the composition of any one of claims 1-53 in the manufacture of a medicament for treating cancer in a subject.

67. The use of claim 66, wherein the cancer is multiple myeloma, gastric adenocarcinoma/ gastroesophageal adenocarcinoma, endometrial carcinoma, platinum-resistant ovarian cancer, or diffuse large b-cell lymphoma.

68. The use of claim 66 or 67, wherein the composition is administered intravenously.

69. The use of claim 66 or 67, wherein the composition is administered subcutaneously.

70. The use of claim 69, wherein the subcutaneous administration mitigates or prevents thrombocytopenia.

71. A kit for treating cancer in a subject in need thereof, the kit comprising the composition of any one of claims 1-53 contained in a vessel.

72. The kit of claim 71, wherein the kit further comprises instructions for using the composition.