THE USE OF LOW MOLECULAR WEIGHT POLYVINYLPYRROLIDONE (PVP) TO REDUCE THE VISCOSITY OF HIGH-CONCENTRATION PROTEIN FORMULATIONS

Abstract

The present invention relates to a method for reducing the viscosity of a pharmaceutical formulation comprising a therapeutic protein at a concentration, wherein the concentration is at least 70 mg / mL, characterized in that it comprises combining the therapeutic protein with a concentration of viscosity-reducing polyvinylpyrrolidone (PVP), thereby producing a reduced viscosity formulation comprising the therapeutic protein at said concentration, wherein the PVP has an average molecular weight of 2,000 Da to 25,000 Da.

Description

THE USE OF LOW MOLECULAR WEIGHT POLYVINYLPYRROLIDONE (PVP) TO REDUCE THE VISCOSITY OF HIGH-CONCENTRATION PROTEIN FORMULATIONS CROSS REFERENCE TO RELATED APPLICATION This application claims the benefit of U.S. Provisional Application No. 262 / 837,647, filed on April 23, 2019, which is incorporated herein by reference. FIELD OF INVENTION The subject matter presented relates to the field(s) of pharmaceutical formulations. Specifically, the subject matter presented relates to high-concentration therapeutic protein formulations and compositions and methods for reducing their viscosity using polyvinylpyrrolidone (PVP). BACKGROUND Pharmaceutically active proteins, such as antibodies, are frequently formulated as liquid solutions, particularly for parenteral injection. For products intended for subcutaneous administration, for example, for self-administration, formulations with delivery volumes greater than 1–2 milliliters are often poorly tolerated. In such cases, highly concentrated protein formulations can achieve the convenient smaller dose volume. The requirements for a high dose and small delivery volume mean that the therapeutic protein can reach concentrations of more than 100 mg / ml, or even higher. Highly concentrated protein formulations can present many challenges in the manufacture and administration of protein therapies. One challenge posed by some highly concentrated protein formulations is increased viscosity. High-viscosity formulations are difficult to handle during manufacturing, even in the bulk and fill phases. High-viscosity formulations are also difficult to draw into a syringe and inject, making administration to the patient difficult and unpleasant. There is a need in the pharmaceutical industry to identify compounds that are useful for reducing the viscosity of highly concentrated protein formulations, to develop methods for reducing the viscosity of such formulations, and to provide pharmaceutical formulations with reduced viscosity. SUMMARY In the first aspect, compositions comprising a concentration of a therapeutic protein and polyvinylpyrrolidone (PVP) are disclosed in this document, wherein the viscosity of the composition comprising the PVP is lower than that of a composition comprising the same concentration of the therapeutic protein, but the PVP is absent. Secondly, this document discloses compositions comprising a concentration of a therapeutic protein and PVP, where the viscosity of the composition is less than or equal to 80 cP. The viscosity may be, for example, 70, 40, or 20 cP. In both the first and second aspects, the viscosity of the composition can be read at 25 °C and reported at a shear rate of 1000 rpm, using, for example, a TA Instruments AR-G2 cone and plate rheometer from New Castle, Delaware (USA). The concentration of the therapeutic protein is greater than 70 mg / ml, such as from approximately 140 mg / ml to approximately 250 mg / ml, including, for example, approximately 145, 160, 198, 200, 238, and 249 mg / ml. The PVP may be present at a concentration of approximately 0.3% to approximately 10%, such as approximately 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, and 10%, and increments in between.The stability of the therapeutic protein is approximately the same as that of a control lacking PVP. Stability can be assessed by the presence of at least one selected fragment from the group consisting of high-molecular-weight species, low-molecular-weight species, dimers, and oligomers of the therapeutic protein. In some sub-aspects, the therapeutic protein comprises at least one complementarity-determining region (CDR) and may be, for example, an antibody, such as a monoclonal antibody (mAb). Additionally, the therapeutic protein comprising at least one CDR may be an antigen-binding fragment or an antibody derivative. The antigen-binding fragment may be one selected fragment from the group consisting of a Fab' fragment, an F'(ab)2 fragment, and an Fv fragment.In the case of an antibody derivative, the derivative may be selected from the group consisting of a humanized antibody, a chimeric antibody, a multispecific antibody, a maxibody, a BiTE® molecule, a single-stranded antibody, a diabody, and a peptibody. The PVP has a K value of 12–17, such as 12 or 17. The PVP may have a weight-average molecular weight of 11,000 Da or less, such as from approximately 2,000 Da to approximately 25,000 Da, or from approximately 2,000 Da to approximately 3,000 Da. The composition may be formulated for administration to a patient. The formulation may have a pH between approximately 4.0 and approximately 8.0, such as from approximately 4.6 to approximately 5.4. Additionally, the composition may comprise arginine, such as N-acetyl arginine (at a concentration of, for example, 10 mM), or an arginine salt, such as arginine monohydrochloride (Arg HCI), arginine glutamate, or arginine acetate.In the case of Arg HCI, the Arg. HCI may be present at approximately 67 mM. In a sub-aspect, where the composition comprises Arg HCI, PVP may be present at approximately 1%. In a sub-aspect of these first and second aspects, methods for preparing a lyophilized powder are disclosed in this document, comprising the step of lyophilizing the composition of the first or second aspect. In a third aspect, this document discloses methods for reducing the viscosity of a pharmaceutical formulation comprising a therapeutic protein, including the step of combining the therapeutic protein with a viscosity-reducing concentration of PVP. The viscosity of the composition manufactured using the methods in this third aspect is less than or equal to 80 cP. The viscosity may be, for example, 70, 40, or 20 cP. In this third aspect, the viscosity of the compositions manufactured using the methods described in this aspect can be read at 25 °C and reported at a shear rate of 1000 rpm, using, for example, an AR-G2 cone and plate rheometer from TA Instruments of New Castle, Delaware (USA). The concentration of the therapeutic protein is greater than 70 mg / ml, such as from approximately 140 mg / ml to approximately 250 mg / ml, including, for example, approximately 145, 160, 198, 200, 238, and 249 mg / ml. The PVP may be present at a concentration of approximately 0.3% to approximately 10%, such as approximately 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, and 10%, and increments in between.The stability of the therapeutic protein is approximately the same as that of a control lacking PVP. Stability can be assessed by the presence of at least one selected fragment from the group consisting of high-molecular-weight species, low-molecular-weight species, dimers, and oligomers of the therapeutic protein. In some sub-aspects, the therapeutic protein comprises at least one complementarity-determining region (CDR) and may be, for example, an antibody, such as a monoclonal antibody (mAb). Additionally, the therapeutic protein comprising at least one CDR may be an antigen-binding fragment or an antibody derivative. The antigen-binding fragment may be one selected fragment from the group consisting of a Fab' fragment, an F'(ab)2 fragment, and an Fv fragment.In the case of an antibody derivative, the derivative may be selected from the group consisting of a humanized antibody, a chimeric antibody, a multispecific antibody, a maxibody, a BiTE® molecule, a single-stranded antibody, a diabody, and a peptibody. The PVP has a K value of 12–17, such as 12 or 17. The PVP may have a weight-average molecular weight of 11,000 Da or less, such as from approximately 2,000 Da to approximately 25,000 Da, or from approximately 2,000 Da to approximately 3,000 Da. The composition may be formulated for administration to a patient. The formulation may have a pH between approximately 4.0 and approximately 8.0, such as from approximately 4.6 to approximately 5.4. Additionally, the composition may comprise arginine, such as N-acetyl arginine (at a concentration of, for example, 10 mM), or an arginine salt, such as arginine monohydrochloride (Arg HCI), arginine glutamate, or arginine acetate.In the case of Arg HCl, the Arg HCl may be present at approximately 67 mM. In a sub-aspect, where the composition comprises Arg HCl, PVP may be present at approximately 1%. In a fourth aspect, this document discloses lyophilized powders comprising a therapeutic protein and PVP, wherein the PVP is present at a weight:weight concentration effective for reducing viscosity after reconstitution with a diluent. In related sub-aspects, the PVP is present at a concentration of between approximately 100 pg / mg of therapeutic protein and approximately 1 mg / mg of therapeutic protein. For example, the PVP is present at a concentration of between approximately 200 pg / mg and approximately 500 pg / mg of therapeutic protein at approximately 1 mg / mg of therapeutic protein before reconstitution with a diluent. The viscosity of the compositions when the lyophilized powder is reconstituted with a diluent of this fourth aspect is less than or equal to 80 cP. The viscosity may be, for example, in cP, 70, 40 or 20. In this fourth aspect, for compositions where the lyophilized powder is reconstituted with a diluent, the viscosity can be read at 25 °C and reported at a shear rate of 1000 rpm, using, for example, a TA Instruments AR-G2 cone and plate rheometer from New Castle, Delaware (USA). The concentration of the therapeutic protein is greater than 70 mg / ml, such as from approximately 140 mg / ml to approximately 250 mg / ml, including, for example, approximately 145, 160, 198, 200, 238, and 249 mg / ml. The PVP may be present at a concentration of approximately 0.3% to approximately 10%, such as approximately 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, and 10%, and increments in between.The stability of the therapeutic protein is approximately the same as compared to a control lacking PVP; stability can be assessed by the presence of at least one selected from the group consisting of high-molecular-weight species, low-molecular-weight species, dimers, and oligomers of the therapeutic protein. In some sub-aspects, the therapeutic protein comprises at least one complementarity-determining region (CDR) and may be, for example, an antibody, such as a monoclonal antibody (mAb). Additionally, the therapeutic protein comprising at least one CDR may be an antigen-binding fragment or an antibody derivative. The antigen-binding fragment may be one selected from the group consisting of a Fab' fragment, an F'(ab)2 fragment, and an Fv fragment. In the case of an antibody derivative, the derivative may be selected from the group consisting of a humanized antibody or an antibody. 7Q / 7Ln / L7nZ / E / YI¡ chimeric, a multispecific antibody, a maxibody, a BiTE® molecule, a single-stranded antibody, a diabody, and a peptibody. The PVP has a K value of 12-17, such as 12 or 17. The PVP may have a weight-average molecular weight of 11,000 Da or less, such as from approximately 2,000 Da to approximately 25,000 Da or from approximately 2,000 Da to approximately 3,000 Da. The composition may be formulated for delivery to a patient. The formulation may have a pH from approximately 4.0 to approximately 8.0, such as from approximately 4.6 to approximately 5.4. Additionally, the composition may include arginine, such as N-acetylarginine (at a concentration of, for example, 10 mM), or an arginine salt, such as arginine monohydrochloride (Arg HCl), arginine glutamate, or arginine acetate. In the case of Arg HCl, the Arg HCl may be present at approximately 67 mM.In one sub-aspect, where the composition comprises Arg HCI, PVP may be present at approximately 1%. In another aspect, this document provides methods for reconstituting a lyophilized powder of the fourth aspect, comprising the step of adding a sterile aqueous diluent. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows a graph of the viscosity (in centipoises (cP)) of a monoclonal antibody (mAb) lgG2, mAb1, at a concentration of 200 mg / ml in the presence of polyvinylpyrrolidone (PVP) K12. Figure 2 shows a graph of the effect of PVP K12 on the viscosity of mAb2 solutions, a therapeutic lgG1 mAb, at a concentration of 198 mg / ml. Figure 3 shows a graph of the effect of PVP K12 on the viscosity of mAb3 solutions, a therapeutic lgG1 mAb, at a concentration of 238 mg / ml. Figure 4 shows a graph of the effect of PVP K12 on the viscosity of mAb4 solutions, a therapeutic lgG1 mAb, at a concentration of 249 mg / ml. Figure 5 shows a graph of the effect of PVP K12 concentrations on the viscosity of mAb1 at a concentration of 145 mg / ml. Figure 6 shows a graph comparing the effects of PVP viscosity having two different molecular weights on solutions having a high concentration (160 mg / ml) of mAb1. Figure 7 shows a graph of the appearance of high molecular weight (HMW) species, low molecular weight (LMW) species, and oligomers and dimers of a high concentration of mAb (mAb 1,3, 4 and 5) in the presence of PVP K12. 7Q / 7Ln / L7n7 / E / Yli DETAILED DESCRIPTION High-concentration protein formulations often face challenges due to their high viscosity. These formulations are difficult to handle during manufacturing, including bulk and fill stages. They are also difficult to draw into a syringe and inject, often requiring the use of larger gauge (larger diameter) needles, which can be unpleasant (e.g., uncomfortable or even painful) for the patient. This document discloses compositions and methods that take advantage of a surprising observation: the addition of low-molecular-weight polyvinylpyrrolidone (PVP) can reduce the viscosity of viscous therapeutic formulations. PVP is not commercially available as a viscosity-reducing agent; in fact, some are sold as thickening agents (e.g., PVP K90; (2014)). PVP is sold under various brand names, including Kollidon® (BASF), which is a brand name for a line of pharmaceutical-grade PVP. For example, PVP K12 and PVP K17 are low molecular weight grades that are non-toxic and acceptable for use in parenteral formulations. Both PVP K12 and PVP K17 are marketed as lyophilizing agents that stabilize the micromolecular structure in lyophilized products and injectables; as dispersing agents for parenteral suspensions; and as complexing agents and dissolution enhancers, which form hydrogen bonds with compounds of complementary structures to improve dissolution (2014). This document discloses methods and compositions that take advantage of the surprising results showing that PVP can reduce the viscosity of high-concentration therapeutic protein compositions, such as those containing antibodies (such as monoclonal antibodies (mAbs) and antigen-binding fragments thereof, as well as derivatives and analogues thereof). In some cases, PVP is combined with arginine (such as an arginine salt, such as arginine hydrochloride, Arg-HCl) to further decrease viscosity, a surprising result that suggests that PVP and arginine act in a complementary manner. Based on the results described in the Examples, PVP K12 is a preferred (but not the only useful) PVP for reducing the viscosity of high concentrations of therapeutic proteins. For example, PVP K12 can be used at concentrations of 5% or less; PVP K12 can be used in combination with other excipients. Interestingly, when PVP K12 and arginine-HCl are combined, a synergistic effect on viscosity reduction is observed, exhibiting inherently low viscosity and a low contribution to the solution's osmolality at the concentrations tested. PVP K12 does not appear to stimulate the precipitation of therapeutic proteins or induce any detrimental effects. 7Q / 7 ίΠ / ίZΠZ / Β / ΥΙ significant on the stability of proteins at low concentrations that have been shown to significantly reduce viscosity. Components of compositions and methods The following sections discuss PVP (and Arg-HCl), as well as appropriate therapeutic proteins, viscosity, formulation preparation, pharmaceutical compositions, storage, and kits. Further definitions can be found after the Examples. Polyvinylpyrrolidone (PVP) Polyvinylpyrrolidone (PVP), also known as povidone, is a synthetic polymer vehicle often used to disperse and suspend drugs. It has multiple uses, including as a binder for tablets and capsules, as a film former for ophthalmic solutions, to help flavor liquids and chewable tablets, and as an adhesive for transdermal systems. Polyvinylpyrrolidone refers to a molecule that has the formula (CeHgNOjn, and has the structure of formula (1): 7Q / 7Ln / L7n7 / E / Yli (1) PVP, also known as povidone, polypovidone, polyvidonum, poly(N-vinyl-2-pyrrolidinone), poly(N-vinylbutyrolactam), poly(1-vinyl-2-pyrrolidinone), 1-vinyl-2-pyrrolidinone homopolymer, and poly[1-(2-oxo-1-pyrrolidinyl)ethylene], is a highly polar, water-soluble, amphoteric polymer (polyamide). Purified PVP occurs as a white or slightly off-white powder. PVP is often described using a k-value (Fikentscher K-value), which refers to the K-value viscosity of the PVP. Higher K-values ​​indicate higher K-value viscosities. Commercially available PVP comes in a variety of viscosity grades according to its K-value; for example, PVP K15, K30, K60, and K90. See also Table 1. The Fikentscher value of the K value of the viscosity characteristics represents a viscosity index related to molecular weight and is calculated using Fikentscher's formula (2) with a relative viscosity measured with a capillary viscometer at 25 °C: Κ= (1.5 log ηΓθι -1) / (0.15+0.003c)+ (300c log qfei + (c+1.5clog ηΓθι)2)1 / 2 / (0.15c+0.003c2) (2) in which Orel: Relative viscosity of an aqueous PVP solution with respect to water; c: PVP content (% w / w) in an aqueous PVP solution Since PVP is a polymer, its molecular weight can be determined by at least three different methods {Bühler, 2005 n.e12}: 1. Weight average, expressed as Mw, in which the individual weights of the molecules are determined, such as by light scattering (Table 1). 2. Number average, expressed as Mn, and determined by methods that measure the number of molecules, such as osmometry. This value is rarely determined or used for PVP. 3. Average viscosity, expressed as Mv, and determined by measuring viscosity. The value can be calculated directly from the relative viscosity, the intrinsic viscosity, or the K value (Table 1). Polymers consist of molecules with a range of molecular weights with, in the ideal case, a Gaussian distribution {Bühler, 2005 n.212}. Kollidon® is a pharmaceutical-grade PVP marketed by BASF Corporation (Florham Park, NJ). Table 1 shows the molecular weight value for the different grades of Kollidon. PVP can be found in the form of monomers, dimers and polymers, and mixtures thereof. Table 1 Examples of commercial pharmaceutical PVP (weight average molecular weight determined by light scattering (Mw); average viscosity values ​​calculated from the range of K values ​​(Mv) and nominal K value (Mv) as provided in (Bühler, 2005 n.212) Kollidon Quality Value (Daltons)* Mw Mv Value (range) Theoretical Value) Mv (K Kollidon 12 2,000-3,000 2,600-5,500 3,900 Kollidon 12 PF 2,000-3,000 2,600-5,500 3,900 Kollidon 17 PF 7,000-11,000 7,100-11,000 9,300 Kollidon 25 28,000-34,000 19,300-31,100 25,700 Kollidon 30 44,000-54,000 31,700-51,400 42,500 Kollidon 90 F 1,000,000-1,500,000 790,000-1,350,000 1,100,000 * As determined after 1980 {Bühler, 2005 n.e12} Therefore, this document provides methods for stabilizing or reducing the viscosity of protein formulations (pharmaceutical formulations / pharmaceutical compositions) by adding PVP and, in some cases, Arg-HCl, in an amount effective for viscosity reduction. Furthermore, reduced viscosity formulations of therapeutic proteins, including antibodies (such as monoclonal antibodies (mAbs) and antigen-binding fragments thereof), containing effective amounts or concentrations of PVP and, in some cases, Arg-HCl, are provided. Additionally, methods for screening one or more formulations, each containing different concentrations of PVP (with and without Arg-HCl), are contemplated herein to identify suitable or optimum concentrations for viscosity reduction.Methods are also provided for preparing a freeze-dried powder from the disclosed reduced viscosity solution formulations, and methods for reconstituting such freeze-dried powders by adding a (sterile) diluent. Therefore, pharmaceutical formulations containing biologically active (therapeutic) polypeptides and viscosity-reducing concentrations of PVP or a combination of PVP and Arg-HCl are provided. The viscosity reduction is at least approximately 5–90% compared to control formulations (e.g., those lacking PVP and / or Arg-HCl). For example, the viscosity reduction may range from approximately 10% to approximately 80%. In other cases, the viscosity reduction is at least approximately 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, or 85%, or more. An expert in the field can experimentally determine the concentration and quality of PVP (with or without Arg-HCl) to reduce viscosity. In some examples, the PVP may have a concentration of approximately 0.3–10%, such as (in %) approximately 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, or 10, and any intermediate increments. The weight average molecular weight (Mw) of PVP, in Daltons, can be approximately 2,000-25,000, such as 2,000, 2500, 3,000, 3500, 4,000, 4500, 5,000, 5500, 6,000, 6500, 7,000, 7500, 8,000, 8500, 9,000, 9500, 10,000, 10,500, 11,000, 12,000, 13,000, 14,000, 15,000, 16,000, 17,000, 18,000, 19,000, 20,000, 21,000. 22,000, 23,000, 24,000, 25,000, and any intermediate increments. In some embodiments, PVP has a weight-average molecular weight, in Daltons, of less than or equal to 11,000. In other embodiments, PVP has a weight-average molecular weight that is less than or equal to 25,000 Da. In some embodiments, PVP has a weight-average molecular weight, in Daltons, of less than or equal to 20,000. In other embodiments, PVP has a weight-average molecular weight that is less than or equal to 15,000 Da. In some embodiments, PVP has a molecular weight In some embodiments, PVP has a weight-average molecular weight, in Daltons, of less than or equal to 11,000. In other embodiments, PVP has a weight-average molecular weight that is less than or equal to 10,000 Da. In some embodiments, PVP has a weight-average molecular weight, in Daltons, of less than or equal to 11,000. In other embodiments, PVP has a weight-average molecular weight that is less than or equal to 10,000 Da. In still other embodiments, PVP has a weight-average molecular weight that is less than or equal to 9,000. In other embodiments, PVP has a weight-average molecular weight that is equal to or less than 8,000 Da. In still other embodiments, PVP has a weight-average molecular weight that is equal to or less than 7,000 Da. In further embodiments, PVP has a weight-average molecular weight of less than or equal to 6,000 Da. In further embodiments, PVP has a weight-average molecular weight of less than or equal to 5,000 Da.In further embodiments, PVP has a weight-average molecular weight of less than or equal to 6,000 Da. In further embodiments, PVP has a weight-average molecular weight of less than or equal to 3,000 Da. And in some other embodiments, PVP has a weight-average molecular weight of less than or equal to 2,000 Da. Expressed as average molecular weight viscosity values, Mv, calculated from the K value, of the PVP, in Daltons, can be approximately 2600-25,000, such as approximately 2600 to approximately 5500 (K12) (including Mv calculated from the theoretical K value of 3900) and approximately 7100 to approximately 11,000 (K17) (including Mv calculated from the theoretical K value of 9300), as well as approximately 11,000 to approximately 25,000. For example, the average viscosity value for molecular weight can be 2600, 2700, 2800, 2900, 3000, 3100, 3200, 3300, 3400, 3500, 3600, 3700, 3800, 3900, 4000, 4100, 4200, 4300, 4400, 4500, 4600, 4700, 4800, 4900, 5000, 5100, 5200, 5300, 5400, 5500, 6000, 7000, 7100, 7500, 8000, 8500, 9000, 9500, 10,000, 10,500, 11,000, 12,000, 13,000, 14,000, 15,000, 16,000, 17,000, 18,000, 19,000, 20,000, 21,000, 22,000, 23,000, 24,000, 25,000, and any intermediate increases.In some embodiments, PVP has a weight-average molecular weight, in Daltons, of less than or equal to 11,000. In other embodiments, PVP has a weight-average molecular weight that is less than or equal to 25,000 Da. In some embodiments, PVP has a weight-average molecular weight, in Daltons, of less than or equal to 20,000. In other embodiments, PVP has a weight-average molecular weight that is less than or equal to 15,000 Da. In some embodiments, PVP has a weight-average molecular weight, in Daltons, of less than or equal to 11,000. In other embodiments, PVP has a weight-average molecular weight that is less than or equal to 10,000 Da. In still other embodiments, PVP has a weight-average molecular weight that is less than or equal to 9,000. In other embodiments, PVP has a weight-average molecular weight equal to or less than 8,000 Da. In still other embodiments, PVP has a weight-average molecular weight equal to or less than 7,000 Da.In further embodiments, PVP has a weight-average molecular weight of less than or equal to 6,000 Da. In further embodiments, PVP has a weight-average molecular weight of less than or equal to 5,000 Da. In further embodiments, PVP has a weight-average molecular weight of less than or equal to 6,000 Da. In further embodiments, PVP has a weight-average molecular weight of less than or equal to 3,000 Da. And in some other embodiments, PVP has a weight-average molecular weight of less than or equal to 2,600 Da. In some embodiments, arginine is present. In some embodiments, arginine is present as an arginine salt. In some embodiments, the arginine salt is Arg-HCl. In such embodiments, the concentration of Arg-HCl can vary from approximately 0.1 mM to approximately 100 mM, including, for example, (in mM) approximately 0.1, 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 and 100 in intermediate increments; The concentration of Arg-HCI can also be, in mM, 110, 120, 125, 130, 140, 150, 160, 170, 175, 180, 190 and 200; and intermediate increments. The arginine salt may also be Arg acetate or Arg glutamate and is present at a concentration of approximately 25 mM to approximately 150 mM, such as approximately 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145 or approximately 150 ml / l.With or without an arginine salt, N-acetyl arginine may also be present at a concentration of approximately 25 mM to approximately 230 mM, such as approximately 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210, 215, 220, 225 or approximately 230 mM and an increase in between. Therapeutic polypeptides The illustrative protein concentrations in the formulation may vary from approximately 70 mg / ml to approximately 300 mg / ml, approximately 120 mg / ml to approximately 270 mg / ml, approximately 140 mg / ml to approximately 255 mg / ml, approximately 140 mg / ml to approximately 240 mg / ml, or approximately 140 mg / ml to approximately 220 mg / ml, or alternatively from approximately 190 mg / ml to approximately 210 mg / ml. The protein concentration depends on the end use of the pharmaceutical formulation and can be easily determined by someone skilled in the art. The protein concentrations specifically considered are at least approximately 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 7Q / 7Ln / L7n7 / E / Yli 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292 293, 294, 295, 296, 297, 298, 299 and 300 mg / ml. Viscosity and other characteristics of formulations containing PVP In one aspect, the disclosed pharmaceutical formulations (with PVP and with or without ArgHCl) have a viscosity level of less than approximately 80 centipoise (cP) measured at room temperature (i.e., 25°C). In certain embodiments, the pharmaceutical formulation has a viscosity level of less than approximately 80 cP to less than approximately 1 cP, such as 80 cP, 70 cP, approximately 60 cP, approximately 50 cP, approximately 40 cP, approximately 30 cP, approximately 25 cP, approximately 20 cP, approximately 18 cP, approximately 15 cP, approximately 12 cP, approximately 10 cP; approximately 8 cP, approximately 6 cP, approximately 4 cP; approximately 2 cP; or approximately 1 cP. In one respect, a pharmaceutical formulation is considered stable as measured by at least one stability assay, such as an assay that examines the biophysical or biochemical characteristics of the therapeutic protein (such as an antibody) over time. A stable pharmaceutical formulation, or stable formulation, refers to a pharmaceutical formulation comprising a therapeutic protein that exhibits limited increase in aggregation and / or reduced loss of biological activity of no more than 5–10% when stored at approximately -30°C (or colder) to approximately 5°C to approximately 40°C for at least one month, or two months, or three months, or six months, or one year, or two years, or five years, or longer compared to a control formulation sample.The stability of the formulation can be determined using any number of conventional assays, including size exclusion HPLC (SEC-HPLC), cation exchange HPLC (CEX-HPLC), light obscuration detection of subvisible particles (HIAC), and / or visual inspection. Generally, the warmer the storage temperature, the shorter the shelf life of the formulation. The stability of a pharmaceutical formulation can also be assessed using visual evaluation. Visual evaluation is a qualitative method used to describe the visible physical characteristics of a sample. The sample is viewed against a black and / or white background in an inspection booth, depending on the characteristic being evaluated (e.g., color, clarity, presence of particles or foreign matter). Samples are also viewed in comparison to an opalescent reference standard and color reference standards. In the case of visual evaluation, a stable pharmaceutical formulation does not exhibit significant changes in color, clarity, presence of particles, or foreign matter compared to a control sample. The formulations can have any pH that is both appropriate for the therapeutic polypeptide to maintain its activity and acceptable stability, and suitable for administration to a patient. For example, the pH can be from approximately 4.0 to approximately 8.0, such as approximately 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, and 8.0. In some cases, the pH range is approximately 4.6 to approximately 5.4 Formulation and components of the pharmaceutical composition Pharmaceutical compositions, suitable for administration to a patient, can be prepared not only with PVP (and in some cases, with arginine, such as Arg HCI), but are formulated with other components. The acceptable pharmaceutical components are preferably non-toxic to patients at the dosages and concentrations used. Pharmaceutical compositions may include agents to modify, maintain, or preserve, for example, pH, osmolarity, viscosity, clarity, color, isotonicity, odor, sterility, stability, dissolution or release rate, adsorption, or penetration of the composition. In general, excipients can be classified based on the mechanisms by which they stabilize proteins against various chemical and physical stresses. Some excipients alleviate the effects of a specific stress or regulate a particular susceptibility of a specific polypeptide. Other excipients more generally affect the physical and covalent stabilities of proteins. Common excipients in liquid and lyophilized protein formulations are shown in Table A (see also (Kamerzell et al 2011). Table A Examples of excipient components for polypeptide formulations ίΠ / ί7Π7 / E / YΥ Component Function Examples Buffers Maintain the pH of the solution Mediate specific interactions between buffer ions and polypeptides Citrate, Succinate, Acetate, Glutamate, Aspartate, Histidine, Phosphate, Tris, Glycine Sugars v Stabilizing polypeptides Sucrose derivatives, carbohydrates Tonic agents Trehalose, Sorbitol, Mannitol, Glucose, Lactose, Cyclodextrin Component Function Examples 5 Stabilizers Act as carriers for inhaled drugs (e.g., lactose) Provide dextrose solutions during IV administration Enhance product bulk and prevent bursting Mannitol, glycine 10 v bulking agents Provide structural strength to the lyophilized cake Osmolytes Stabilization against environmental stress (temperature, dehydration) Sucrose, Trehalose, Sorbitol, Amino acids Mediate specific interactions with polypeptides Glycine, Proline, Glutamate, Glycerol, Urea Histidine, Arginine, Glycine, Proline, Lysine, Methionine, Polypeptides v Provide antioxidant activity (e.g., His, Met) Buffer, tone Act as competitive inhibitors of polypeptide adsorption mixtures of amino acids (e.g., Glu / Arg) HSA, PVA, PVP, PLGA, PEG, 20 polymers gelatin, dextran,25-Hydroxyethyl Antioxidants Provide bulking agents for lyophilization Act as drug delivery vehicles Prevention of oxidative damage to starch, HEC, CMC Reducing agents, 30 polypeptides Metal ion binders (if a metal is included as a cofactor or is required for protease activity) Oxygen scavengers, Free radical scavengers, Chelating agents (e.g., EDTA, EGTA, DTPA), Ethanol Ions Free radical scavengers Polypeptide cofactors Magnesium, Zinc metals Coordination complexes (suspensions), Component Function Examples Ligands Conformation stabilizers Metals, ligands, amino acids, specific natural against stress-induced unfolding Provide conformational flexibility polyanions Surfactants Act as competitive inhibitors of polypeptide adsorption Act as competitive inhibitors of polypeptide surface denaturation Provide liposomes as drug delivery vehicles Inhibit aggregation during lyophilization Act as reducers of lyophilized product reconstitution times Polysorbate 20, Polysorbate 80, Poloxamer 188, anionic surfactants (e.g., sulfonates and sulfosuccinates), cationic surfactants, zwitterionic surfactants Salts Tonicity agents Stabilizing or destabilizing agents for polypeptides, especially anions NaCl, KCl, NaSO4 Preservatives Protect against microbial growth Benzyl alcohol, m-cresol, Phenol Other excipients are known in the art (e.g., see Powell et al., 1998). Skilled practitioners can determine the appropriate amount or range of excipients to include in any given formulation to achieve a biopharmaceutical composition that promotes stability. For example, the amount and type of salt to be included in the biopharmaceutical composition can be selected based on the desired osmolality (i.e., isotonic, hypotonic, or hypertonic) of the final solution, as well as the amounts and osmolality of other components to be included in the formulation. Preparation of polypeptide formulations The pharmaceutical formulations disclosed herein may be prepared by either of the two procedures designated as Procedures 1 and 2. Procedure 1 comprises: a. dialyze or concentrate a solution of a therapeutic protein; b. dialyze or concentrate a solution of selected excipients or provide a dry mixture of selected excipients; c. Add the excipient solution or dry mixture of excipients to the protein solution at a selected pH to achieve a desired final excipient concentration, a desired final protein concentration, and a desired final pH. d. The UF / DF ultrafiltration / diafiltration procedure exchanges the buffer and concentrates the protein simultaneously. Procedure 2 comprises: a. dialyze a solution of a therapeutic protein; b. dialyze a solution of selected excipients or provide a dry mixture of selected excipients; c. add the excipient solution or dry mixture of excipients to the dialyzed protein solution at a selected pH and a desired excipient concentration, and d. Concentrate the solution resulting from step c to a desired final protein concentration and desired final pH In procedure 1, the pH of the concentrated protein to achieve the desired final pH can vary from approximately 4 to approximately 8. In procedure 2, the pH of the concentrated protein solution to achieve the desired final pH can vary from approximately 4 to approximately 8. When a particular excipient is reported in a formulation by, for example, percent (%) w / v, those skilled in the art recognize that the equivalent molar concentration of that excipient is also considered. The formulations can be lyophilized for subsequent resuspension with an appropriate diluent; often, liquid formulations are modified to incorporate a cryoprotectant and a bulking agent; acetates are replaced by glutamates or phosphates to reduce volatility. Storage and kits Once formulated, the pharmaceutical formulation can be stored in sterile vials as a solution, suspension, gel, emulsion, solid, or as a dehydrated or lyophilized powder. Such formulations can be stored in a ready-to-use form or in a form (e.g., lyophilized) that is reconstituted before administration. In some cases, therapeutic polypeptide formulations can be stored in containers, such as suitable storage bags (e.g., those manufactured by Sartorius (Göttingen, Germany)) or polycarbonate carboys. Once formulated, the pharmaceutical formulation can also be stored in pre-filled syringes (JPCs; such as 2.25 mL JPCs) as a ready-to-use solution or suspension, as well as in glass vials (such as 5 mL glass vials). In certain embodiments, kits are provided for producing a single-dose delivery unit. In certain embodiments, the kit may contain both a first container with a dry protein and a second container with an aqueous formulation. In certain embodiments, kits are included that contain pre-filled syringes with one or more chambers (e.g., liquid syringes and lyo-syringes). ACHIEVEMENTS Embodiment 1: A composition comprising a concentration of a therapeutic protein and polyvinylpyrrolidone (PVP), wherein the viscosity of the composition comprising the PVP is lower than that of a composition comprising the same concentration of the therapeutic protein, but the PVP is absent. Realization 2: A composition comprising a concentration of a therapeutic protein and PVP, wherein the viscosity of the composition is less than or equal to 80 cP. Realization 3: The composition of realization 2, wherein the viscosity of the composition is less than or equal to 70 cP. Realization 4: The composition of realization 2, wherein the viscosity of the composition is less than or equal to 40 cP. Realization 5: The composition of realization 2, wherein the viscosity of the composition is less than or equal to 20 cP. Embodiment 6: The composition of embodiment 1 or 2, wherein the viscosity of the composition is read at 25 °C and reported at a shear rate of 1000 / s. Embodiment 7: The composition of embodiment 6, wherein viscosity is measured using an AR-G2 cone and plate rheometer from TA Instruments of New Castle, Delaware (USA). Realization 8: The composition of realization 1 or 2, wherein the concentration of the therapeutic protein is greater than 70 mg / ml. Realization 9: The composition of realization 8, wherein the concentration of the therapeutic protein is greater than or equal to approximately 140 mg / ml to approximately 250 mg / ml. Realization 10: The composition of realization 9, wherein the concentration of the therapeutic protein, in mg / ml, is selected from the group consisting of approximately 145, 160, 198, 200, 238, and 249. Realization 11: The composition of realization 1 or 2, wherein PVP is present at a concentration of approximately 0.3% to approximately 10%. ZQ / ZLn / LZnZ / E / Yli Realization 12: The composition of realization 11, wherein PVP is present at a concentration selected from the group consisting of approximately 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, and 10%, and increments in between. Realization 13: The composition of realization 1 or 2, wherein the stability of the therapeutic protein is approximately the same compared to a control lacking PVP. Realization 14: The composition of realization 13, wherein stability is evaluated by the presence of at least one selected from the group consisting of high molecular weight species, low molecular weight species, dimers, and oligomers. Realization 15: The composition of realization 1 or 2, wherein the therapeutic protein comprises at least one complementarity-determining region (CDR). Realization 16: The composition of realization 15, wherein the therapeutic protein is an antibody. Realization 17: The composition of realization 16, wherein the antibody is a monoclonal antibody (mAb). Realization 18: The composition of realization 17, wherein the antibody is an antigen-binding fragment or antibody derivative. Realization 19: The composition of realization 18, wherein the antigen-binding fragment is selected from the group consisting of a Fab' fragment, an F'(ab)2 fragment, and an Fv fragment. Embodiment 20: The composition of embodiment 18, wherein the antibody derivative is selected from the group consisting of a humanized antibody, a chimeric antibody, a multispecific antibody, a maxibody, a BiTE® molecule, a single-stranded antibody, a diabody, and a peptibody. Realization 21: The composition of realization 1 or 2, where the PVP has a K value of 12-17, such as 12 or 17. Realization 22: The composition of realization 1 or 2, wherein the PVP has a weight average molecular weight of 11,000 Da or less. Realization 23: The composition of realization 23, wherein PVP has a weight average molecular weight of approximately 2,000 Da to approximately 25,000 Da. Realization 24: The composition of realization 24, wherein PVP has a weight average molecular weight of approximately 2,000 Da to approximately 3,000 Da. Realization 25: The composition of realization 1 or 2, wherein the composition is formulated for delivery to a patient. Realization 26: The composition of realization 1 or 2, having a pH between approximately 4.0 and approximately 8.0. 7Q / 7Ln / L7n7 / E / Yli Realization 27: The composition of realization 26, which has a pH of approximately 4.6 to approximately 5.4. Realization 28: The composition of realization 1 or 2, which further comprises arginine. Realization 29: The composition of realization 28, wherein arginine is N-acetyl arginine. Realization 30: The composition of realization 29, wherein N-acetylarginine is present at approximately 10 mM. Realization 31: The composition of realization 28, wherein the arginine is an arginine salt. Realization 32: The composition of realization 31, wherein the arginine is arginine monohydrochloride (Arg HCI), arginine glutamate, or arginine acetate. Realization 33: The composition of realization 32, wherein Arg HCI is present at approximately 67 mM. Realization 34: The composition of realization 33, where PVP is present at approximately 1%. Embodiment 35: A method for preparing a freeze-dried powder comprising the step of freeze-drying the composition of embodiments 1 or 2. Implementation 36: A method for reducing the viscosity of a pharmaceutical formulation comprising a therapeutic protein, comprising the step of combining the therapeutic protein with a viscosity-reducing concentration of PVP. 7Q / 7Ln / L7n7 / E / Yli Realization 37: The method of realization 36, composition is less than or equal to 80 cP. Realization 38: The method of realization 36, composition is less than or equal to 70 cP. Realization 39: The method of realization 36, composition is less than or equal to 40 cP. Realization 40: The method of realization 36, composition is less than or equal to 20 cP. Implementation 41: The method of implementation 36, wherein the viscosity of the composition is read at 25 °C and reported at a shear rate of 1000 / s. Realization 42: The method of realization 42, wherein viscosity is measured using an AR-G2 cone and plate rheometer from TA Instruments of New Castle, Delaware (USA). Realization 43: The method of realization 36, where the concentration of the therapeutic protein is greater than 70 mg / ml. Realization 44: The method of realization 43, wherein the concentration of the therapeutic protein is greater than or equal to approximately 140 mg / ml to approximately 250 mg / ml. Realization 45: The method of realization 44, wherein the concentration of the therapeutic protein, in mg / ml, is selected from the group consisting of approximately 145, 160, 198, 200, 238, and 249. Realization 46: The method of realization 36, wherein PVP is present at a concentration of approximately 0.3% to approximately 10%. Realization 47: The method of realization 46, wherein the PVP is present at a concentration selected from the group consisting of approximately 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, and 10%, and increments between these. Realization 48: The method of realization 36, wherein the stability of the therapeutic protein is approximately the same compared to a control lacking PVP. Realization 49: The method of realization 48, wherein stability is evaluated by the presence of at least one selected from the group consisting of high molecular weight species, low molecular weight species, dimers, and oligomers. Realization 50: The method of realization 36, wherein the therapeutic protein comprises at least one complementarity-determining region (CDR). Realization 51: The method of realization 50, wherein the therapeutic protein is an antibody. Realization 52: The method of realization 51, wherein the antibody is a monoclonal antibody (mAb). Realization 53: The method of realization 51, wherein the antibody is an antigen-binding fragment or antibody derivative. Realization 54: The method of realization 53, wherein the antigen-binding fragment is selected from the group consisting of a Fab' fragment, an F'(ab)2 fragment, and an Fv fragment. Realization 55: The method of realization 53, wherein the antibody derivative is selected from the group consisting of a humanized antibody, a chimeric antibody, a multispecific antibody, a maxibody, a BiTE® molecule, a single-stranded antibody, a diabody, and a peptibody. Realization 56: The method of realization 36, where the PVP has a K value of 1217, such as 12 or 17. Realization 57: The method of realization 36, wherein the PVP has a weight average molecular weight of 11,000 Da or less. Realization 58: The method of realization 57, wherein PVP has a weight average molecular weight of approximately 2,000 Da to approximately 25,000 Da. ZQ / ZLn / LZnZ / E / Yli Realization 59: The method of realization 58, wherein PVP has a weight average molecular weight of approximately 2,000 Da to approximately 3,000 Da. Realization 60: The composition of realization 36, wherein the composition is formulated for delivery to a patient. Realization 61: The method of realization 36, wherein the composition has a pH between approximately 4.0 and approximately 8.0 after reconstitution with a diluent. Realization 62: The method of realization 61, wherein the composition has a pH of approximately 4.6 to approximately 5.4. Realization 63: The method of realization 33, wherein the composition further comprises arginine. Realization 64: The method of realization 64, wherein arginine is N-acetylarginine. Realization 65: The method of realization 65, wherein N-acetylarginine is present at approximately 10 mM. Realization 66: The method of realization 63, wherein arginine is an arginine salt. Realization 67: The method of realization 66, wherein the arginine is arginine monohydrochloride (Arg HCI), arginine glutamate, or arginine acetate. Realization 68: The method of realization 67, wherein Arg HCI is present at approximately 67 mM. Realization 69: The method of realization 68, where the PVP is present at approximately 1%. Implementation 70: A lyophilized powder comprising a therapeutic protein and PVP, wherein the PVP is present at a weight:weight concentration effective to reduce viscosity after reconstitution with a diluent. Realization 71: The lyophilized powder of realization 70, wherein PVP is present at a concentration of between approximately 100 pg / mg of therapeutic protein and approximately 1 mg / mg of therapeutic protein. Embodiment 72: The lyophilized powder of embodiment 71, wherein the PVP is present at a concentration of between approximately 200 pg / mg and approximately 500 pg / mg of therapeutic protein to approximately 1 mg / mg of therapeutic protein before reconstitution with a diluent. Embodiment 73: The lyophilized powder of embodiment 71, wherein the viscosity of the method is less than or equal to 80 cP after reconstitution with a diluent. Embodiment 74: The lyophilized powder of embodiment 71, wherein the viscosity of the method is less than or equal to 70 cP after reconstitution with a diluent. Embodiment 75: The lyophilized powder of embodiment 71, wherein the viscosity of the method is less than or equal to 40 cP after reconstitution with a diluent. Embodiment 76: The lyophilized powder of embodiment 71, wherein the viscosity of the method is less than or equal to 20 cP after reconstitution with a diluent. Embodiment 77: The lyophilized powder of embodiment 71, wherein the viscosity of the method is read at 25 °C and reported at a shear rate of 1000 / s after reconstitution with a diluent. Embodiment 78: The freeze-dried powder of embodiment 71, wherein the viscosity is measured using an AR-G2 cone and plate rheometer from TA Instruments of New Castle, Delaware (USA). Embodiment 79: The lyophilized powder of embodiment 70, wherein the PVP is present at a concentration of approximately 0.3% to approximately 10% after reconstitution with a diluent. Embodiment 80: The lyophilized powder of embodiment 79, wherein the PVP is present at a concentration selected from the group consisting of approximately 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9% and 10%, and increments between these after reconstitution with a diluent. Realization 81: The lyophilized powder of realization 70, wherein the therapeutic protein comprises at least one complementarity-determining region (CDR). Realization 82: The lyophilized powder of realization 81, wherein the therapeutic protein is an antibody. Realization 83: The lyophilized powder of realization 82, wherein the antibody is a monoclonal antibody (mAb). Realization 84: The lyophilized powder of realization 82, wherein the antibody is an antigen-binding fragment or antibody derivative. Realization 85: The lyophilized powder of realization 84, wherein the antigen-binding fragment is selected from the group consisting of a Fab' fragment, an F'(ab)2 fragment, and an Fv fragment. Embodiment 86: The lyophilized powder of embodiment 85, wherein the antibody derivative is selected from the group consisting of a humanized antibody, a chimeric antibody, a multispecific antibody, a maxibody, a BiTE® molecule, a single-stranded antibody, a diabody, and a peptibody. Realization 87: The freeze-dried powder of embodiment 70, wherein the PVP has a K value of 12-17, such as 12 or 17. Realization 88: The freeze-dried powder of embodiment 70, wherein the PVP has a weight average molecular weight of 11,000 Da or less. 7Q / 7Ln / L7n7 / E / Yli Embodiment 89: The freeze-dried powder of embodiment 88, wherein the PVP has a weight average molecular weight of approximately 2,000 Da to approximately 25,000 Da. Realization 90: The freeze-dried powder of embodiment 89, wherein the PVP has a weight average molecular weight of approximately 2,000 Da to approximately 3,000 Da. Realization 91: The lyophilized powder of realization 70, wherein the method is formulated for delivery to a patient after reconstitution with a diluent. Realization 92: The lyophilized powder of embodiment 70, having a pH between approximately 4.0 and approximately 8.0 after reconstitution with a diluent. Realization 93: The freeze-dried powder of embodiment 92, having a pH of approximately 4.6 to approximately 5.4. Embodiment 94: The lyophilized powder of embodiment 70, further comprising arginine. Realization 95: The lyophilized powder of embodiment 94, wherein the arginine is N-acetyl arginine. Embodiment 96: The lyophilized powder of embodiment 95, wherein N-acetylarginine is present at approximately 10 mM. Embodiment 97: The freeze-dried powder of embodiment 94, wherein the arginine is an arginine salt. Embodiment 98: The lyophilized powder of embodiment 97, wherein the arginine is arginine monohydrochloride (Arg HCI), arginine glutamate, or arginine acetate. Embodiment 99: The lyophilized powder of embodiment 98, wherein arginine hydrochloride is present at approximately 67 mM. Realization 100: The freeze-dried powder of realization 99, wherein PVP is present at approximately 1%. Embodiment 101: A method for reconstituting a lyophilized powder of embodiment 70, comprising the step of adding a sterile aqueous diluent. The following examples are provided for illustrative purposes only and are not set forth to limit disclosure or claims in any way. EXAMPLES Example 1: PVP K12 as a viscosity-reducing excipient (with and without arginine-HCl) in a high concentration solution of mAb (mAb1) To evaluate the impact of PVP K12 on the viscosity of a high concentration of a therapeutic mAb (lgG2), mAb1. mAb1 was dialyzed against 15 mM sodium acetate, pH 5.2. After dialysis, mAb1 was concentrated to 220 mg / mL using 10K Amicon® Ultra molecular weight cut-off (MWCO) centrifuge filters (Millipore Sigma; Burlington, MA). Stock solutions of concentrated excipient (PVP K12 (BASF Corp. (based in Ludwigshafen, Germany) and arginine HCl) were then added. ZQ / ZLn / LZnZ / E / Yli (Sigma-Aldrich; St. Louis, MO) was added to this material at 10% by volume, diluting the concentration of mAb1 to 200 mg / mL. The viscosity of each sample was measured using an AR-G2 cone-and-plate rheometer (TA Instruments; Newcastle, DE) at 25 °C, with data reported at a shear rate of 1000 rpm. The data in Fig. 1 show that the addition of 1% and 3% PVP K12 resulted in a substantial decrease in the viscosity of the mAb1 formulation. The amount of reduction for 3% PVP K12 is comparable to the level observed with the addition of 67 mM arginine HCl (Arg-HCl), which was used for comparison. The combination of 1% PVP K12 with 67 mM arginine HCI unexpectedly showed an additional reduction in viscosity compared to formulations containing a single excipient. Example 2: PVP K12 as a viscosity-reducing excipient (with and without arginine-HCl) in a high concentration solution of mAb (mAb2) An experiment was conducted to evaluate the impact of PVP K12 on the viscosity of a high concentration of a therapeutic mAb, mAb2 (lgG1). mAb2 was dialyzed against 10 mM sodium acetate pH 5.2 containing 10 mM N-acetylarginine (NAR). After dialysis, mAb2 was concentrated to 220 mg / ml using MWCO 10K Amicon Ultra centrifuge filters. Concentrated excipient stock solutions were then added to this material at 10% by volume, diluting the mAb2 concentration to 198 mg / ml. Sample viscosities were measured using an AR-G2 cone-plate rheometer at 25 °C, with data reported at a shear rate of 1000 s. The data in Fig. 2 show that the addition of PVP K12 at 0.3%, 1% and 3% (in the presence of 10 mM NAR) resulted in a decrease in the viscosity of the mAb2 formulation, with the 3% PVP formulation having the lowest viscosity among the three PVP concentrations analyzed.The amount of reduction for 3% PVP K12 was comparable to the level observed with the addition of 67 mM Arginine HCl, which was included for comparison. The combination of 1% PVP K12 with 67 mM Arginine HCl unexpectedly showed an additional reduction in viscosity compared to formulations containing only one excipient. Example 3: PVP K12 as a viscosity-reducing excipient (with and without arginine-HCl) in a high concentration solution of mAb (mAb3) An experiment was conducted to evaluate the impact of PVP K12 on the viscosity of a high concentration of a therapeutic mAb, mAb3 (1gG1). mAb3 was dialyzed against 15 mM sodium acetate, pH 5.2. After dialysis, mAb3 was concentrated to 265 mg / ml using MWCO 10K Amicon Ultra centrifuge filters. Concentrated excipient stock solutions were then added to this material at 10% by volume, diluting the mAb3 concentration to 238 mg / ml. Sample viscosities were measured using an AR-G2 cone-plate rheometer at 25 °C, with data reported at a shear rate of 1000 rpm. Data in Fig. 3. The reference source was not found, showing that the addition of PVP K12 at 0.3%, 1% and 3% resulted in a decrease in the viscosity of the mAb3 formulation, with the PVP K12 formulation at 1% having the lowest viscosity among the three PVP concentrations analyzed.The combination of 1% PVP K12 with 67 mM Arginine HCI unexpectedly showed an additional reduction in viscosity compared to formulations containing a single excipient. Example 4: PVP K12 as a viscosity-reducing excipient (with and without arginine-HCl) in a high concentration solution of mAb (mAb4) An experiment was conducted to evaluate the impact of PVP K12 on the viscosity of a therapeutic mAb, mAb4 (lgG1). mAb4 was dialyzed against 15 mM sodium acetate, pH 5.2. After dialysis, mAb3 was concentrated to 277 mg / ml using MWCO 10K Amicon Ultra centrifuge filters. Concentrated excipient stock solutions were then added to this material at 10% by volume, diluting the mAb4 concentration to 249 mg / ml. Sample viscosities were measured using an ARG2 cone-plate rheometer at 25 °C, with data reported at a shear rate of 1000 rpm. The data in Fig. 4 show that the addition of PVP K12 at 0.3%, 1% and 3% resulted in a decrease in the viscosity of the mAb4 formulation, with the 1% PVP formulation having the lowest viscosity among the three PVP concentrations analyzed.The amount of reduction for 1% PVP K12 was comparable to the level observed with the addition of 67 mM Arginine HCl, which was included for comparison. The combination of 1% PVP K12 with 67 mM Arginine HCl unexpectedly showed an additional reduction in viscosity compared to formulations containing only one excipient. Example 5: Effect of different concentrations of PVP K12 in high concentration solutions of mAb (mAb1) An experiment was conducted to evaluate the effect of different concentrations of PVP K12 on the viscosity reduction of the mAb1 formulation. mAb1 was dialyzed against 15 mM sodium acetate, pH 5.2, and concentrated to 181 mg / ml using MWCO 10K Amicon Ultra centrifuge filters. A 50% (w / v) PVP K12 solution was then added to the concentrated protein solutions to generate a PVP concentration range up to 10%. The final mAb concentration was 145 mg / ml. Sample viscosities were measured using an AR-G2 plate cone rheometer at 25 °C, with data reported at a shear rate of 1000 rpm. The data in Figure 5 show that as the PVP K12 concentration increases, the viscosity reduction begins to decrease when the PVP K12 concentration is > 3%. The minimum viscosity was achieved with PVP K12 between 5% and 10%, with an increase in viscosity with PVP K12 between 7.5% and 10%. Example 6: Comparison of the effects on viscosity using PVP of varying molecular weights in a high concentration mAb solution (mAb1) An experiment was conducted to compare the effects of PVP of varying molecular weights on the viscosity of mAb1 formulations. mAb1 was dialyzed against 15 mM sodium acetate, pH 5.2. After dialysis, mAb1 was concentrated to 178 mg / ml using Amicon Ultra MWCO10K centrifuge filters. Concentrated stock solutions of PVP K12 (MW: 2,000–3,000 Da) and PVP K17 (MW: 7,000–11,000 Da) (all from BASF Corp.) were then added to this material at 10% by volume, diluting the mAb1 concentration to 160 mg / ml. Sample viscosities were measured using an AR-G2 cone-plate rheometer at 25 °C, with data reported at a shear rate of 1000 rpm. The data in Fig. 6 show that PVP K12, which has a lower average molecular weight compared to PVP K17, was a more effective viscosity-reducing excipient than PVP K17 at equivalent concentrations. Example 7: mAb stability in formulations comprising PVP K12 An experiment was conducted to evaluate the effect of 2% PVP K12 on the stability of several mAbs. The mAbs (including mAb5, an lgG2) were dialyzed against 15 mM sodium acetate, pH 5.2. After dialysis, PVP K12 was added to a final concentration of 2%. The mAb concentrations were adjusted to 100 mg / ml, and the samples were incubated at 40 °C for 2 weeks before analysis by size exclusion high-performance liquid chromatography (SE-HPLC). Figure 7 shows a plot of the SE-HPLC % area for various degradation products for mAb samples with 2% PVP K12 compared to controls with added water. These results indicate that 2% PVP K12 did not have a significant impact on mAb stability. This observation suggests that viscosity-reducing effects can be applied without inducing any significant increase in aggregation or shearing. DEFINITIONS Viscosity is the resistance of a liquid to flow and can be measured in units of centipoise (cP) or millipascal-seconds (mPa-s), where 1 cP = 1 mPa-s, at a given shear rate. Viscosity can be measured using a viscometer, for example, a Brookfield Engineering Dial-Reading Viscometer, Model LVT (AMETEK Brookfield; Middleboro, MA), and an AR-G2 Plate and Cone Rheometer (TA Instruments; New Castle, DE). In some cases, viscosity is measured at 25 °C and reported at a shear rate of 1000 rpm. Viscosity can be measured using any other method and in any other unit known in the art (e.g., absolute, kinematic, or dynamic viscosity), it being understood that the percentage reduction in viscosity provided by the use of the excipients described in the invention is what is important.Regardless of the method used to determine viscosity, the percentage reduction in viscosity in excipient formulations versus. 7Q / 7Ln / L7n7 / E / Yli control formulations will remain approximately the same at a given shear rate. An effective viscosity-reducing quantity or concentration (a viscosity-reducing amount) of an excipient means that the viscosity of the formulation in its final form for administration (whether a solution or a powder, after reconstitution with the desired amount of diluent) is at least 5% lower than the viscosity of an appropriate control formulation, such as water, buffer, other known viscosity-reducing agents such as salt, etc., and the control formulations exemplified herein. Furthermore, excipient-free control formulations may be used even if they cannot be implemented as a therapeutic formulation due to hypotonicity, for example. Similarly, a reduced viscosity formulation is a formulation that exhibits reduced viscosity compared to a control formulation. A pharmaceutical formulation or pharmaceutical composition is a sterile composition of a pharmaceutically active drug, such as a biologically active protein, that is suitable for parenteral administration (including, but not limited to, intravenous, intramuscular, subcutaneous, aerosolized, intrapulmonary, intranasal, or intrathecal) to a patient in need and includes only pharmaceutically acceptable excipients, diluents, and other additives deemed safe by the Food and Drug Administration or other national regulatory agencies. Pharmaceutical formulations include liquid solutions, such as aqueous solutions, that can be administered directly, and lyophilized powders that can be reconstituted into solutions by adding a diluent prior to administration.Specifically excluded from the scope of the expression pharmaceutical formulation are compositions for topical administration to patients, compositions for oral ingestion, and compositions for parenteral nutrition. Shelf life refers to the storage period during which an active ingredient, such as a therapeutic protein, in a pharmaceutical formulation, undergoes minimal degradation (e.g., no more than approximately 5% to 10% degradation) when the pharmaceutical formulation is stored under specific storage conditions, e.g., 2–8 °C. Techniques for assessing degradation vary depending on the identity of the protein in the pharmaceutical formulation.Illustrative techniques include size exclusion chromatography (SEC)-HPLC to detect, for example, aggregation; reversed-phase (RP)-HPLC to detect, for example, protein fragmentation; ion-exchange spectroscopy-HPLC to detect, for example, changes in protein charge; mass spectrometry; fluorescence spectroscopy; circular dichroism (CD) spectroscopy; Fourier transform infrared (FT-IR) spectroscopy; and Raman spectroscopy to detect protein conformational changes. All of these techniques can be used individually or in combination to assess protein degradation in the pharmaceutical formulation and determine the shelf life of that formulation. Pharmaceutical formulations preferably exhibit increases in degradation (e.g., fragmentation, aggregation, or unfolding) of no more than approximately 5–10% over two years when stored at 2–8 °C. High molecular weight species, or HMW species, in the context of a pharmaceutical formulation containing a therapeutic polypeptide, means therapeutic proteins that are larger than the original therapeutic polypeptide, as determined by accepted assays. HMW species include therapeutic polypeptide oligomers and therapeutic polypeptide aggregates. Low molecular weight species, or LMW species, in the context of a pharmaceutical formulation containing a therapeutic polypeptide, means polypeptides that are smaller than the original therapeutic polypeptide, as determined by accepted assays. LMW species include fragments of the therapeutic polypeptide. A stable pharmaceutical formulation, or a pharmaceutical formulation is stable, refers to a pharmaceutical formulation that exhibits limited aggregation increase and / or reduced loss of biological activity of no more than 5% when stored at approximately -30°C (or colder) to approximately 5°C to approximately 40°C for at least 1 month, or 2 months, or 3 months, or 6 months, or 1 year, or 2 years, or 5 years, or longer, compared to a control formulation sample. A person skilled in the art can determine the stability of the formulation using any number of conventional assays, including size exclusion HPLC (SEC-HPLC), cation exchange HPLC (CEX-HPLC), light obscuration detection of subvisible particles (HIAC), and / or visual inspection. Generally, the warmer the storage temperature, the shorter the shelf life of the formulation. The techniques for assessing degradation vary depending on the identity of the protein in the pharmaceutical formulation. Illustrative techniques include size exclusion chromatography (SEC)-HPLC to detect, for example, aggregation; reversed-phase (RP) HPLC to detect, for example, protein fragmentation; ion-exchange HPLC to detect, for example, changes in protein charge; mass spectrometry; fluorescence spectroscopy; circular dichroism (CD) spectroscopy; Fourier transform infrared (FT-IR) spectroscopy; and Raman spectroscopy to detect protein conformational changes. All of these techniques can be used individually or in combination to assess protein degradation in the pharmaceutical formulation and determine its shelf life.The pharmaceutical formulations disclosed herein normally exhibit increases of no more than approximately 2% to 5% in degradation (e.g., fragmentation, aggregation, or unfolding) over two years when stored at 2-8°C. Lyophilization, freeze-dried, and cryo-drying refer to a process in which the material to be dried is first frozen, and then the ice or frozen solvent is removed by sublimation in a vacuum environment. An excipient may be included in pre-lyophilized formulations to enhance the stability of the freeze-dried product during storage. A diluent is a substance that aids in the formulation and / or administration of an active agent and / or its absorption by a patient and may be included in disclosed compositions without causing a significant adverse effect in the patient. An example of a diluent is water, preferably sterile and purified. Arginine salt means a salt of arginine. Examples include arginine monohydrochloride (Arg HCl), arginine acetate (Arg acetate), and arginine glutamate (Arg glutamate). N-acetyl arginine (NAR) means the molecule of formula 1. (1) A polypeptide, also known as a protein, is used interchangeably. Illustrative polypeptides include antibodies, peptibodies, immunoglobulin-like proteins, non-antibody proteins, and non-immunoglobulin-like proteins. The inclusion of naturally occurring protein analogues in the formulations of the present invention is contemplated, including polypeptides with modified glycosylation and non-glycosylated polypeptides. A protein analogue is a sequence of amino acids that has insertions, deletions, or substitutions with respect to the precursor sequence, while still substantially maintaining the biological activity of the original sequence, as determined using biological assays known to a person skilled in the art.Naturally occurring polypeptide derivatives or analogues that have been chemically modified, for example, to link water-soluble polymers (e.g., pegylated), radionuclides, or other diagnostic, targeting, or therapeutic fractions. A "therapeutic protein" is a protein (or therapeutic polypeptide, the terms are used interchangeably) that has at least one therapeutic (beneficial) effect for a patient. Therapeutic proteins include antibodies and related molecules. An antibody, or immunoglobulin, refers to a tetrameric glycoprotein consisting of two heavy chains and two light chains, each comprising a variable (V) domain and a constant (C) domain. Heavy chains and light chains refer to substantially full-length canonical immunoglobulin light and heavy chains; the variable (VL and VC) domains of the heavy and light chains constitute the V region of the antibody and contribute to antigen binding and specificity. Antibodies include monoclonal antibodies, polyclonal antibodies, chimeric antibodies, human antibodies, and humanized antibodies. Light chains can be classified as kappa and lambda light chains. Heavy chains are typically classified as mu, delta, gamma, alpha, or epsilon and define the antibody isotype as IgM, IgD, IgG, IgA, and IgE, respectively.IgG has several subclasses, including IgG1, IgG2, IgG3, and IgG4. IgM has subclasses including IgG1 and IgG2. IgA is similarly subdivided into subclasses including IgA1 and IgG2. In full-length light and heavy chains, the variable and constant regions are typically linked by a J region of approximately 12 or more amino acids, with the heavy chain also including a D region of approximately 10 more amino acids. The variable regions of each light / heavy chain pair typically form the antigen-binding site. A monoclonal antibody refers to an antibody obtained from a substantially homogeneous antibody population; that is, the individual antibodies within the population are identical except for possible naturally occurring mutations that may be present in trace amounts. Antibody variants include antibody fragments and antibody-like proteins with structural changes to canonical tetrameric antibodies. Typical antibody variants include V regions with a change in the constant regions or, alternatively, the addition of V regions to constant regions, optionally in a non-canonical manner. Examples include multispecific antibodies (e.g., bispecific antibodies, trispecific antibodies), antibody fragments that can bind to an antigen (e.g., Fab', F'(ab)2, Fv, single-stranded antibodies, diabodies), recombinant peptides, and biparatopic compounds comprising the above, provided they exhibit the desired biological activity. Multispecific antibodies target more than one antigen or epitope. For example, a bispecific, double-specific, or bifunctional antibody is a hybrid antibody with two distinct antigen-binding sites. Bispecific antibodies can be produced using a variety of methods, including fusion hybridomas or the ίΠ / ί7Π7 / Β / ΥΙ junction of Fab fragments (Kostelny et al., 1992; Songsivilai and Lachmann, 1990; Wu and Demarest, 2018). The two binding sites of a bispecific antibody each bind to a different epitope. Similarly, trispecific antibodies have three binding sites and bind to three different epitopes. Several methods for manufacturing trispecific antibodies are known and under development (Wu and Demarest, 2018; Wu et al., 2018). DARTs (short for dual-affinity re-targeting molecules) are also examples of a multi-specific antibody. BiTE® Molecules: In some cases, a therapeutic protein is a bi-specific T-cell engager (BiTE). A BiTE molecule is a bi-specific antibody construct or a bi-specific fusion protein comprising two antibody-binding domains (or targeting regions) joined together. One arm of the molecule is engineered to bind to a protein found on the surface of cytotoxic T cells, and the other arm is engineered to bind to a specific protein found primarily on the tumor cell. When both targets are coupled, the BiTE molecule bridges the gap between the cytotoxic T cell and the tumor cell, enabling the T cell to recognize and attack the tumor cell by infusing it with toxic molecules.The tumor-binding arm of the molecule can be modified to create different BiTE antibody constructs that target different cancer types. The term "binding domain" in a BiTE molecule refers to a domain that specifically binds to, interacts with, or recognizes a given target epitope or target site on target molecules (antigens). The structure and function of the first binding domain (which recognizes the tumor cell antigen), and preferably also the structure and / or function of the second binding domain (cytotoxic T lymphocyte antigen), are based on the structure and / or function of an antibody, for example, a whole immunoglobulin molecule. For instance, the BiTE molecule comprises a first binding domain characterized by the presence of three light-chain CDRs (i.e., CDR1, CDR2, and CDR3 of the VL region) and three heavy-chain CDRs (i.e., CDR1, CDR2, and CDR3 of the VH region).The second binding domain preferably further comprises the minimum structural requirements of an antibody that enable binding to the target. More preferably, the second binding domain comprises at least three light chain CDRs (i.e., CDR1, CDR2, and CDR3 of the VL region) and / or three heavy chain CDRs (i.e., CDR1, CDR2, and CDR3 of the VH region). The first and / or second binding domain is envisaged to be produced or obtainable by library screening or phage presentation methods rather than by grafting CDR sequences from a pre-existing (monoclonal) antibody onto a scaffold. A binding domain can typically comprise a light chain variable (VL) region of an antibody and a variable region. 7Q / 7Ln / L7n7 / E / Yli heavy chain (VH) of an antibody; however, it does not have to comprise both. Fd fragments, for example, have two VH regions and often retain some of the antigen-binding function of the intact antigen-binding domain. Examples of (modified) antigen-binding antibody fragments include (1) a Fab fragment, a monovalent fragment having the VL, VH, CL, and CH1 domains; (2) an F(ab')2 fragment, a bivalent fragment having two Fab fragments joined by a disulfide bridge in the hinge region; (3) an Fd fragment having both VH and CH1 domains; (4) an Fv fragment having the VL and VH domains from a single antibody arm; (5) a dAb fragment (Ward et al., 1989), having a VH domain. (6) an isolated complementarity determining region (CDR) and (7) a single-stranded Fv (scFv), the latter being preferred (e.g., obtained from an scFV library). Antibody fragments include antigen-binding portions of the antibody, including, for example, Fab, Fab', F(ab')2, Fv, antibody domain (dAb), complementarity-determining region (CDR) fragments, CDR-grafted antibodies, single-stranded antibodies (scFv), maxibodies (scFv-Fc), single-stranded antibody fragments, chimeric antibodies, diabodies, tribodies, tetrabodies, minibody, linear antibody; recombinant chelating antibody, a tribody or bibody, an intrabody, a nanobody, a small modular immunopharmaceutical agent (SMIP).an antigen-binding domain immunoglobulin fusion protein, single-domain antibodies (including a camelized antibody), an antibody containing VHH, or a variant or derivative thereof, and polypeptides containing at least a portion of an immunoglobulin that is sufficient to confer polypeptide-specific antigen binding, such as one, two, three, four, five, or six CDR sequences, provided that the antibody retains the desired binding activity. REFERENCES 2014. Kollidon(R) - The Original. In BASF, ed. BASF: BASF Ausubel FM. 1987. Current protocols in molecular biology. Brooklyn, NY Media, Pa.: Greene Pub. Associates; J. Wiley, order fulfillment. 2 volumes (loose leaves) pp. Kamerzell TJ, Esfandiary R, Joshi SB, Middaugh CR, Volkin DB. 2011. Proteinexcipient interactions: mechanisms and biophysical characterization applied to protein formulation development. Adv Drug Deliv Rev 63:1118-59 Kostelny SA, Colé MS, Tso JY. 1992. Formation of a bispecific antibody by the use of leucine zippers. J Immunol 148:1547-53 Powell MF, Nguyen T, Baloian L. 1998. Compendium of excipients for parenteral formulations. PDA J Pharm Sel Technol 52: 238-311 Sambrook J, Russell DW. 2001. Molecular cloning: a laboratory manual. Coid Spring Harbor, N.Y.: Coid Spring Harbor Laboratory Press. Songsivilai S, Lachmann PJ. 1990. Bispecific antibody: a tool for diagnosis and treatment of disease. Clin Exp Immunol 79: 315-21 Ward ES, Gussow D, Griffiths AD, Jones PT, Winter G. 1989. Binding activities of a repertoire of single ¡mmunoglobulin variable domains secreted from Escherichia col!. Nature 341:544-6 Wu X, Demarest SJ. 2018. Building blocks for bispecific and trispecific antibodies. Métodos Wu X, Yuan R, Bacica M, Demarest SJ. 2018. Generation of orthogonal Fabbased trispecific antibody formats. Protein Eng Des Sel 31: 249-56 Unless the context requires otherwise, singular terms shall include plurals and plural terms shall include singular. In general, the tissue and cell culture techniques, molecular biology, immunology, microbiology, genetics and protein and nucleic acid chemistry, and hybridization, and the nomenclatures used in connection therewith, described herein, are well known and commonly used in the art. The methods and techniques of the present invention are generally carried out in accordance with conventional methods well known in the art and as described in various general and more specific references cited and discussed throughout this specification, unless otherwise indicated. See, for example, Ausubel et al. (1987 et seq.) and Sambrook et al. (2001) (Ausubel 1987, Sambrook and Russell 2001).Enzymatic reactions and purification techniques are performed according to the manufacturer's specifications, as is customary in the art, or as described herein. The terminology used in relation to laboratory procedures and techniques in analytical chemistry, synthetic organic chemistry, and medicinal and pharmaceutical chemistry, as described herein, is well known and commonly used in the art. Conventional techniques may be used for chemical synthesis, chemical analysis, pharmaceutical preparation, formulation, and dispensing, and patient treatment. All patents and other publications identified are expressly incorporated herein in their entirety by reference to describe and disclose, for example, the methodologies described in such publications, which could be used in connection with the foregoing. NOVELTY OF THE INVENTION Having described the present invention as above, it is considered novel and, therefore, the contents contained in the following are claimed as property:

Claims

1. A composition comprising a concentration of a therapeutic protein and polyvinylpyrrolidone (PVP), wherein the viscosity of the composition comprising the PVP is lower than that of a composition comprising the same concentration of the therapeutic protein, but the PVP is absent.

2. A composition comprising a concentration of a therapeutic protein and PVP, wherein the viscosity of the composition is less than or equal to 80 cP.

3. The composition of claim 2, wherein the viscosity of the composition is less than or equal to 70 cP.

4. The composition of claim 2, wherein the viscosity of the composition is less than or equal to 40 cP.

5. The composition of claim 2, wherein the viscosity of the composition is less than or equal to 20 cP.

6. The composition of claim 1 or 2, wherein the viscosity of the composition is read at 25 °C and reported at a shear rate of 1000 / s.

7. The composition of claim 6, wherein the viscosity is measured using an AR-G2 cone and plate rheometer from TA Instruments of New Castle, Delaware (USA).

8. The composition of claim 1 or 2, wherein the concentration of the therapeutic protein is greater than 70 mg / ml.

9. The composition of claim 8, wherein the concentration of the therapeutic protein is greater than or equal to approximately 140 mg / ml to approximately 250 mg / ml.

10. The composition of claim 9, wherein the concentration of the therapeutic protein, in mg / ml, is selected from the group consisting of approximately 145, 160, 198, 200, 238 and 249.

11. The composition of claim 1 or 2, wherein the PVP is present at a concentration of approximately 0.3% to approximately 10%.

12. The composition of claim 11, wherein the PVP is present at a concentration selected from the group consisting of approximately 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9% and 10%, and increments therein.

13. The composition of claim 1 or 2, wherein the stability of the therapeutic protein is approximately the same compared to a control lacking PVP. Ln / L7R7 / E / Yli 14. The composition of claim 13, wherein stability is evaluated by the presence of at least one selected from the group consisting of high molecular weight species, low molecular weight species, dimers, and oligomers.

15. The composition of claim 1 or 2, wherein the therapeutic protein comprises at least one complementarity-determining region (CDR).

16. The composition of claim 15, wherein the therapeutic protein is an antibody.

17. The composition of claim 16, wherein the antibody is a monoclonal antibody (mAb).

18. The composition of claim 17, wherein the antibody is an antigen-binding fragment or antibody derivative.

19. The composition of claim 18, wherein the antigen-binding fragment is selected from the group consisting of a Fab' fragment, an F'(ab)2 fragment, and an Fv fragment.

20. The composition of claim 18, wherein the antibody derivative is selected from the group consisting of a humanized antibody, a chimeric antibody, a multispecific antibody, a maxibody, a BiTE® molecule, a single-stranded antibody, a diabody, and a peptibody.

21. The composition of claim 1 or 2, wherein the PVP has a K value of 12-17, such as 12 or 17.

22. The composition of claim 1 or 2, wherein the PVP has a weight average molecular weight of 11,000 Da or less.

23. The composition of claim 23, wherein the PVP has a weight average molecular weight of approximately 2,000 Da to approximately 25,000 Da.

24. The composition of claim 24, wherein the PVP has a weight average molecular weight of approximately 2,000 Da to approximately 3,000 Da.

25. The composition of claim 1 or 2, wherein the composition is formulated for delivery to a patient.

26. The composition of claim 1 or 2, having a pH between approximately 4.0 and approximately 8.

0.

27. The composition of claim 26, having a pH of approximately 4.6 to approximately 5.

4.

28. The composition of claim 1 or 2, further comprising arginine.

29. The composition of claim 28, wherein the arginine is N-acetyl arginine.

30. The composition of claim 29, wherein N-acetyl arginine is present at approximately 10 mM. iΠ / i7Π7 / E / YI 31. The composition of claim 28, wherein the arginine is an arginine salt.

32. The composition of claim 31, wherein the arginine is arginine monohydrochloride (Arg HCI), arginine glutamate, or arginine acetate.

33. The composition of claim 32, wherein Arg HCI is present at approximately 67 mM.

34. The composition of claim 33, wherein PVP is present at approximately 1%.

35. A method for preparing a freeze-dried powder comprising the step of freeze-drying the composition of claim 1 or 2.

36. A method for reducing the viscosity of a pharmaceutical formulation comprising a therapeutic protein, comprising the step of combining the therapeutic protein with a viscosity-reducing concentration of PVP.

37. The method of claim 36, wherein the viscosity of the composition is less than or equal to 80 cP.

38. The method of claim 36, wherein the viscosity of the composition is less than or equal to 70 cP.

39. The method of claim 36, wherein the viscosity of the composition is less than or equal to 40 cP.

40. The method of claim 36, wherein the viscosity of the composition is less than or equal to 20 cP.

41. The method of claim 36, wherein the viscosity of the composition is read at 25 °C and reported at a shear rate of 1000 / s.

42. The method of claim 42, wherein the viscosity is measured using an AR-G2 cone and plate rheometer from TA Instruments of New Castle, Delaware (USA).

43. The method of claim 36, wherein the concentration of the therapeutic protein is greater than 70 mg / ml.

44. The method of claim 43, wherein the concentration of the therapeutic protein is greater than or equal to approximately 140 mg / ml to approximately 250 mg / ml.

45. The method of claim 44, wherein the concentration of the therapeutic protein, in mg / ml, is selected from the group consisting of approximately 145, 160, 198, 200, 238 and 249.

46. ​​The method of claim 36, wherein the PVP is present at a concentration of approximately 0.3% to approximately 10%. iΠ / i7Π7 / B / YI 47. The method of claim 46, wherein the PVP is present at a concentration selected from the group consisting of approximately 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9% and 10%, and increments therein.

48. The method of claim 36, wherein the stability of the therapeutic protein is approximately the same compared to a control lacking PVP.

49. The method of claim 48, wherein stability is evaluated by the presence of at least one selected from the group consisting of high molecular weight species, low molecular weight species, dimers, and oligomers.

50. The method of claim 36, wherein the therapeutic protein comprises at least one complementarity-determining region (CDR).

51. The method of claim 50, wherein the therapeutic protein is an antibody.

52. The method of claim 51, wherein the antibody is a monoclonal antibody (mAb).

53. The method of claim 51, wherein the antibody is an antigen-binding fragment or antibody derivative.

54. The method of claim 53, wherein the antigen-binding fragment is selected from the group consisting of a Fab' fragment, an F'(ab)2 fragment, and an Fv fragment.

55. The method of claim 53, wherein the antibody derivative is selected from the group consisting of a humanized antibody, a chimeric antibody, a multispecific antibody, a maxibody, a BiTE® molecule, a single-stranded antibody, a diabody, and a peptibody.

56. The method of claim 36, wherein the PVP has a K value of 12-17, such as 12 or 17.

57. The method of claim 36, wherein the PVP has a weight average molecular weight of 11,000 Da or less.

58. The method of claim 57, wherein the PVP has a weight average molecular weight of approximately 2,000 Da to approximately 25,000 Da.

59. The method of claim 58, wherein the PVP has a weight average molecular weight of approximately 2,000 Da to approximately 3,000 Da.

60. The method of claim 36, wherein the composition is formulated for delivery to a patient.

61. The method of claim 36, wherein the composition has a pH between approximately 4.0 and approximately 8.0 after reconstitution with a diluent. 7Q / 7 ίΠ / ί7Π7 / Β / ΥΙ 62. The method of claim 61, wherein the composition has a pH of approximately 4.6 to approximately 5.

4.

63. The method of claim 33, wherein the composition further comprises arginine.

64. The method of claim 64, wherein the arginine is N-acetyl arginine.

65. The method of claim 65, wherein N-acetyl arginine is present at approximately 10 mM.

66. The method of claim 63, wherein the arginine is an arginine salt.

67. The method of claim 66, wherein the arginine is arginine monohydrochloride (Arg HCI), arginine glutamate, or arginine acetate.

68. The method of claim 67, wherein Arg HCI is present at approximately 67 mM.

69. The method of claim 68, wherein the PVP is present at approximately 1%.

70. A lyophilized powder comprising a therapeutic protein and PVP, wherein the PVP is present at a weight:weight concentration effective to reduce viscosity after reconstitution with a diluent.

71. The freeze-dried powder of claim 70, wherein the PVP is present at a concentration of between approximately 100 pg / mg of therapeutic protein and approximately 1 mg / mg of therapeutic protein.

72. The lyophilized powder of claim 71, wherein the PVP is present at a concentration of between approximately 200 pg / mg and approximately 500 pg / mg of therapeutic protein to approximately 1 mg / mg of therapeutic protein before reconstitution with a diluent.

73. The freeze-dried powder of claim 71, wherein the viscosity of the method is less than or equal to 80 cP after reconstitution with a diluent.

74. The freeze-dried powder of claim 71, wherein the viscosity of the method is less than or equal to 70 cP after reconstitution with a diluent.

75. The freeze-dried powder of claim 71, wherein the viscosity of the method is less than or equal to 40 cP after reconstitution with a diluent.

76. The freeze-dried powder of claim 71, wherein the viscosity of the method is less than or equal to 20 cP after reconstitution with a diluent.

77. The freeze-dried powder of claim 71, wherein the viscosity of the method is read at 25 °C and reported at a shear rate of 1000 / s after reconstitution with a diluent. iΠ / i7Π7 / B / YI 78. The freeze-dried powder of claim 71, wherein the viscosity is measured using an AR-G2 cone and plate rheometer from TA Instruments of New Castle, Delaware (USA).

79. The freeze-dried powder of claim 70, wherein the PVP is present at a concentration of approximately 0.3% to approximately 10% after reconstitution with a diluent.

80. The freeze-dried powder of claim 79, wherein the PVP is present at a concentration selected from the group consisting of approximately 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9% and 10%, and increments between these after reconstitution with a diluent.

81. The freeze-dried powder of claim 70, wherein the therapeutic protein comprises at least one complementarity-determining region (CDR).

82. The lyophilized powder of claim 81, wherein the therapeutic protein is an antibody.

83. The lyophilized powder of claim 82, wherein the antibody is a monoclonal antibody (mAb).

84. The lyophilized powder of claim 82, wherein the antibody is an antigen-binding fragment or antibody derivative.

85. The lyophilized powder of claim 84, wherein the antigen-binding fragment is selected from the group consisting of a Fab' fragment, an F'(ab)2 fragment, and an Fv fragment.

86. The lyophilized powder of claim 85, wherein the antibody derivative is selected from the group consisting of a humanized antibody, a chimeric antibody, a multispecific antibody, a maxibody, a BiTE® molecule, a single-stranded antibody, a diabody, and a peptibody.

87. The freeze-dried powder of claim 70, wherein the PVP has a K value of 12-17, such as 12 or 17.

88. The freeze-dried powder of claim 70, wherein the PVP has a weight average molecular weight of 11,000 Da or less.

89. The freeze-dried powder of claim 88, wherein the PVP has a weight average molecular weight of approximately 2,000 Da to approximately 25,000 Da.

90. The freeze-dried powder of claim 89, wherein the PVP has a weight average molecular weight of approximately 2,000 Da to approximately 3,000 Da.

91. The lyophilized powder of claim 70, wherein the method is formulated for administration to a patient after reconstitution with a diluent. 7Q / 7Ln / L7n7 / E / Yli 92. The freeze-dried powder of claim 70, having a pH between approximately 4.0 and approximately 8.0 after reconstitution with a diluent.

93. The freeze-dried powder of claim 92, having a pH of approximately 4.6 to approximately 5.

4.

94. The freeze-dried powder of claim 70, further comprising arginine.

95. The freeze-dried powder of claim 94, wherein the arginine is N-acetyl arginine.

96. The freeze-dried powder of claim 95, wherein N-acetyl arginine is present at approximately 10 mM.

97. The freeze-dried powder of claim 94, wherein the arginine is an arginine salt.

98. The freeze-dried powder of claim 97, wherein the arginine is arginine monohydrochloride (Arg HCI), arginine glutamate, or arginine acetate.

99. The freeze-dried powder of claim 98, wherein arginine hydrochloride is present at approximately 67 mM.

100. The freeze-dried powder of claim 99, wherein the PVP is present in approximately 1%.

101. A method for reconstituting a lyophilized powder of claim 70, comprising the step of adding a sterile aqueous diluent. ZQ / ZLn / LZnZ / E / Yli